Winston Pharmaceuticals Dolorac Nasal Solution Phase 3

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Thousand Oaks, CA, United States

Amgen is an American multinational biopharmaceutical company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotechnology firm. In 2013, the company's largest selling product lines were NeulastaMimpara, Nplate, Vectibix, Prolia and XGEVA. Wikipedia.

Clinical Trial
Register: EUDRA | Status: Ongoing | Type: Interventional | Phase 3 | Year: 2021

Main objective of the trial: To assess the efficacy of ABP 938 compared to aflibercept. Secondary objectives of the trial: To assess the safety and immunogenicity of ABP 938 compared to aflibercept Principal inclusion criteria: 1. 1. Subjects or their legally authorized representative must sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) before any study-specific procedures 2. Men or women ≥ 50 years old 3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by central imaging vendor before randomization) 4. Active, treatment naïve subfoveal CNV lesions secondary to neovascular (wet) AMD including juxtafoveal lesions that affect the fovea as confirmed with SD-OCT, FA and/or FP in the study eye (confirmed by central imaging vendor before randomization) 5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye (confirmed by central imaging vendor before randomization) 7. Central retinal thickness (CRT) of ≥ 270 µm in the study eye as measured by the machine, calculated average thickness in the ETDRS central 1 mm subfield (CST) by SD-OCT at screening (confirmed by central imaging vendor before randomization) Principal exclusion criteria: 1. Total lesion size > 12 disc areas (30.5 mm2, including blood, scars, and neovascularization) in the study eye (confirmed by central imaging vendor before randomization) 2. Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye (confirmed by central imaging vendor before randomization) 3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by central imaging vendor before randomization) 4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye (confirmed by central imaging vendor before randomization) 5. History of any vitreous hemorrhage within 4 weeks before randomization in the study eye 6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye (confirmed by central imaging vendor before randomization with the exception of the refractive error and axial length which is to be assessed by the investigator) 7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye 8. History of retinal detachment in the study eye 9. Any history of macular hole of stage 2 and above in the study eye 10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane (confirmed by central imaging vendor before randomization) 11. Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection 12. Prior trabeculectomy or other filtration surgery in the study eye 13. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye 14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 15. Previous therapeutic radiation in the region of the study eye 16. History of corneal transplant or corneal dystrophy in the study eye 17. Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye 18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety 19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD (confirmed by central imaging vendor before randomization) 20. Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization 21. Active scleritis or episcleritis or presence of scleromalacia 22. Active extraocular infection or history of extraocular infections as follows: a. any active infection for which systemic anti-infectives were used within 4 weeks before randomization b. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject 23. Acute coronary event or stroke within 3 months before randomization 24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease 25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 26. Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor [VEGF] therapy) in the study eye, except dietary supplements or vitamins 27. Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 6 months before randomization, except dietary supplements or vitamins 28. Prior systemic anti-VEGF treatment as follows: a. Investigational or approved anti-VEGF therapy systemically within 3 months before randomization b. Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at any time Primary endpoints: Change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 8

Clinical Trial
Register: EUDRA | Status: Ongoing | Type: Interventional | Phase 3 | Year: 2021

Main objective of the trial: To assess the efficacy of ABP 938 compared to aflibercept. Secondary objectives of the trial: To assess the safety and immunogenicity of ABP 938 compared to aflibercept Principal inclusion criteria: 1. Subjects must sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) before any study-specific procedures 2. Men or women ≥ 50 years old 3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by central imaging vendor before randomization) 4. Active, treatment naïve CNV lesions secondary to neovascular (wet) AMD as confirmed with SD-OCT, FA and FP in the study eye (confirmed by central imaging vendor before randomization) 5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye (confirmed by central imaging vendor before randomization) 7. Central retinal thickness (CRT) of ≥ 300 µm in the study eye as determined by SD-OCT at screening (confirmed by central imaging vendor before randomization) Principal exclusion criteria: 1. Total lesion size > 9 disc areas (22.86 mm2, including blood, scars, and neovascularization) in the study eye (confirmed by central imaging vendor before randomization) 2. Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye (confirmed by central imaging vendor before randomization) 3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by central imaging vendor before randomization) 4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye (confirmed by central imaging vendor before randomization) 5. History of any vitreous hemorrhage within 4 weeks before randomization in the study eye 6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye (confirmed by central imaging vendor before randomization with the exception of the refractive error and axial length which is to be assessed by the investigator) 7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye 8. History of retinal detachment in the study eye 9. Any history of macular hole of stage 2 and above in the study eye 10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane (confirmed by central imaging vendor before randomization) 11. Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection 12. Prior trabeculectomy or other filtration surgery in the study eye 13. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye 14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 15. Previous therapeutic radiation in the region of the study eye 16. History of corneal transplant or corneal dystrophy in the study eye 17. Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye 18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety 19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD (confirmed by central imaging vendor before randomization) 20. Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization 21. Active scleritis or episcleritis or presence of scleromalacia 22. Active extraocular infection or history of extraocular infections as follows: a. any active infection for which systemic anti-infectives were used within 4 weeks before randomization b. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject 23. Acute coronary event or stroke within 3 months before randomization 24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease 25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 26. Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor [VEGF] therapy) in the study eye, except dietary supplements or vitamins 27. Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 6 months before randomization, except dietary supplements or vitamins 28. Prior systemic anti-VEGF treatment as follows: a. Investigational or approved anti-VEGF therapy systemically within 3 months before randomization b. Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at any time Primary endpoints: Change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 8

Clinical Trial
Register: EUDRA | Status: Ongoing | Type: Interventional | Phase 3 | Year: 2021

Main objective of the trial: To assess the efficacy of ABP 938 compared to aflibercept. Secondary objectives of the trial: To assess the safety and immunogenicity of ABP 938 compared to aflibercept Principal inclusion criteria: 1. Subjects must sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) before any study-specific procedures 2. Men or women ≥ 50 years old 3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by central imaging vendor before randomization) 4. Active, treatment naïve CNV lesions secondary to neovascular (wet) AMD as confirmed with SD-OCT, FA and FP in the study eye (confirmed by central imaging vendor before randomization) 5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye (confirmed by central imaging vendor before randomization) 7. Central retinal thickness (CRT) of ≥ 300 µm in the study eye as determined by SD-OCT at screening (confirmed by central imaging vendor before randomization) Principal exclusion criteria: 1. Total lesion size > 9 disc areas (22.86 mm2, including blood, scars, and neovascularization) in the study eye (confirmed by central imaging vendor before randomization) 2. Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye (confirmed by central imaging vendor before randomization) 3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by central imaging vendor before randomization) 4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye (confirmed by central imaging vendor before randomization) 5. History of any vitreous hemorrhage within 4 weeks before randomization in the study eye 6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye (confirmed by central imaging vendor before randomization with the exception of the refractive error and axial length which is to be assessed by the investigator) 7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye 8. History of retinal detachment in the study eye 9. Any history of macular hole of stage 2 and above in the study eye 10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane (confirmed by central imaging vendor before randomization) 11. Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection 12. Prior trabeculectomy or other filtration surgery in the study eye 13. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye 14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 15. Previous therapeutic radiation in the region of the study eye 16. History of corneal transplant or corneal dystrophy in the study eye 17. Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye 18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety 19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD (confirmed by central imaging vendor before randomization) 20. Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization 21. Active scleritis or episcleritis or presence of scleromalacia 22. Active extraocular infection or history of extraocular infections as follows: a. any active infection for which systemic anti-infectives were used within 4 weeks before randomization b. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject 23. Acute coronary event or stroke within 3 months before randomization 24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease 25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 26. Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor [VEGF] therapy) in the study eye, except dietary supplements or vitamins 27. Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 6 months before randomization, except dietary supplements or vitamins 28. Prior systemic anti-VEGF treatment as follows: a. Investigational or approved anti-VEGF therapy systemically within 3 months before randomization b. Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at any time Primary endpoints: Change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 8

Clinical Trial
Register: EUDRA | Status: Ongoing | Type: Interventional | Phase 3 | Year: 2021

Main objective of the trial: To assess the efficacy of ABP 938 compared to aflibercept. Secondary objectives of the trial: To assess the safety and immunogenicity of ABP 938 compared to aflibercept Principal inclusion criteria: 1. Subjects must sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) before any study-specific procedures 2. Men or women ≥ 50 years old 3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by central imaging vendor before randomization) 4. Active, treatment naïve CNV lesions secondary to neovascular (wet) AMD as confirmed with SD-OCT, FA and FP in the study eye (confirmed by central imaging vendor before randomization) 5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye (confirmed by central imaging vendor before randomization) 7. Central retinal thickness (CRT) of ≥ 300 µm in the study eye as determined by SD-OCT at screening (confirmed by central imaging vendor before randomization) Principal exclusion criteria: 1. Total lesion size > 9 disc areas (22.86 mm2, including blood, scars, and neovascularization) in the study eye (confirmed by central imaging vendor before randomization) 2. Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye (confirmed by central imaging vendor before randomization) 3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by central imaging vendor before randomization) 4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye (confirmed by central imaging vendor before randomization) 5. History of any vitreous hemorrhage within 4 weeks before randomization in the study eye 6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye (confirmed by central imaging vendor before randomization with the exception of the refractive error and axial length which is to be assessed by the investigator) 7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye 8. History of retinal detachment in the study eye 9. Any history of macular hole of stage 2 and above in the study eye 10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane (confirmed by central imaging vendor before randomization) 11. Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection 12. Prior trabeculectomy or other filtration surgery in the study eye 13. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye 14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 15. Previous therapeutic radiation in the region of the study eye 16. History of corneal transplant or corneal dystrophy in the study eye 17. Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye 18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety 19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD (confirmed by central imaging vendor before randomization) 20. Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization 21. Active scleritis or episcleritis or presence of scleromalacia 22. Active extraocular infection or history of extraocular infections as follows: a. any active infection for which systemic anti-infectives were used within 4 weeks before randomization b. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject 23. Acute coronary event or stroke within 3 months before randomization 24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease 25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 26. Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor [VEGF] therapy) in the study eye, except dietary supplements or vitamins 27. Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 6 months before randomization, except dietary supplements or vitamins 28. Prior systemic anti-VEGF treatment as follows: a. Investigational or approved anti-VEGF therapy systemically within 3 months before randomization b. Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at any time Primary endpoints: Change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 8

Clinical Trial
Register: EUDRA | Status: Ongoing | Type: Interventional | Phase 3 | Year: 2021

Main objective of the trial: To assess the efficacy of ABP 938 compared to aflibercept. Secondary objectives of the trial: To assess the safety and immunogenicity of ABP 938 compared to aflibercept Principal inclusion criteria: 1. Subjects must sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) before any study-specific procedures 2. Men or women ≥ 50 years old 3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by central imaging vendor before randomization) 4. Active, treatment naïve CNV lesions secondary to neovascular (wet) AMD as confirmed with SD-OCT, FA and FP in the study eye (confirmed by central imaging vendor before randomization) 5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye (confirmed by central imaging vendor before randomization) 7. Central retinal thickness (CRT) of ≥ 300 µm in the study eye as determined by SD-OCT at screening (confirmed by central imaging vendor before randomization) Principal exclusion criteria: 1. Total lesion size > 9 disc areas (22.86 mm2, including blood, scars, and neovascularization) in the study eye (confirmed by central imaging vendor before randomization) 2. Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye (confirmed by central imaging vendor before randomization) 3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by central imaging vendor before randomization) 4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye (confirmed by central imaging vendor before randomization) 5. History of any vitreous hemorrhage within 4 weeks before randomization in the study eye 6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye (confirmed by central imaging vendor before randomization with the exception of the refractive error and axial length which is to be assessed by the investigator) 7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye 8. History of retinal detachment in the study eye 9. Any history of macular hole of stage 2 and above in the study eye 10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane (confirmed by central imaging vendor before randomization) 11. Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection 12. Prior trabeculectomy or other filtration surgery in the study eye 13. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye 14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 15. Previous therapeutic radiation in the region of the study eye 16. History of corneal transplant or corneal dystrophy in the study eye 17. Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye 18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety 19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD (confirmed by central imaging vendor before randomization) 20. Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization 21. Active scleritis or episcleritis or presence of scleromalacia 22. Active extraocular infection or history of extraocular infections as follows: a. any active infection for which systemic anti-infectives were used within 4 weeks before randomization b. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject 23. Acute coronary event or stroke within 3 months before randomization 24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease 25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 26. Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor [VEGF] therapy) in the study eye, except dietary supplements or vitamins 27. Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 6 months before randomization, except dietary supplements or vitamins 28. Prior systemic anti-VEGF treatment as follows: a. Investigational or approved anti-VEGF therapy systemically within 3 months before randomization b. Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at any time Primary endpoints: Change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 8

News: GlobeNewswire, Research Analysis And Reports
Site: globenewswire.com

Dublin, Oct. 20, 2020 (GLOBE NEWSWIRE) -- The "Global Dermatological Therapeutics Market 2019-2028" report has been added to ResearchAndMarkets.com's offering. According to the publisher, the global dermatological therapeutics market is expected to display a positive market trend over the forecast period of 2019-2028, exhibiting a CAGR of 7.90%. Skin disease is one of the major factors responsible for the growing global disease burden, affecting millions of people around the world. This is expected to lead to an increase in the adoption of dermatological treatments, which, in turn, will propel the studied market growth. Also, the rise in awareness regarding disease origin and progression is creating opportunities for market growth. Dermatological therapies are used to treat different types of skin conditions and disorders. But despite this, there are certain major side-effects associated with anti-infectives, corticosteroids, retinoids, and every other drug class, which are quite prominent than others. This is majorly hampering the growth of the dermatological therapeutics market. Furthermore, unawareness about dermatological diagnosis is another factor challenging this market's growth. The Middle East and Africa, Latin America, Europe, the Asia-Pacific, and North America together envelop the global dermatological therapeutics market. North America leads the global market for dermatological therapeutics market, accounting for the largest share. The growth of this market is attributable to the expanding rate of occurrence of pores and skin diseases among people in the region. The United States is the greatest commercial center for dermatology drugs, followed by Canada. The rise in the demand for dermatological services in North America is driven by the rise in incidence of skin cancer, particularly melanoma. Another major factor fuelling the demand for these services is the increase in the geriatric population in the region. Thus, the increased demand for dermatological services is augmenting the growth of the North American dermatological therapeutics market. The notable players in this market include Merck & Co, Glaxosmithkline Plc, Abbvie Inc, Pfizer Inc, Amgen Inc, Leo Pharma A/S, Almirall, Allergan, Bausch Health Companies Inc, Galderma, Novartis AG, AGI Dermatics, and Johnson & Johnson. Novartis AG is a globally popular pharmaceutical company, with a major presence in diverse biopharmaceutical segments. One of its products in the dermatology segment, Cosentyx, is a prescription medicine used for treating adults with moderate to severe plaque psoriasis. The company has operations across Europe, North America, Latin America, the Asia-Pacific, and the Middle East and Africa. Novartis reported revenues worth $53,166 million for the fiscal year ended December 2018 (FY2018), which was an increase of 6% over the preceding year. Key Topics Covered: 1. Global Dermatological Therapeutics Market - Summary 2. Industry Outlook 2.1. Market Definition 2.2. Key Insights 2.2.1. Asia-Pacific is Most Encouraging Regional Market 2.2.2. China is Leading Overall Market 2.2.3. Advancements in Biologics 2.2.4. Atopic Dermatitis is Anticipated to Grow at Highest CAGR 2.3. Porter's Five Forces Analysis 2.3.1. Threat of New Entrants 2.3.2. Threat of Substitute 2.3.3. Bargaining Power of Suppliers 2.3.4. Bargaining Power of Buyers 2.3.5. Threat of Competitive Rivalry 2.4. Impact of COVID-19 - Dermatological Therapeutics 2.5. Market Attractiveness Index 2.6. Vendor Scorecard 2.7. Market Drivers 2.7.1. Increasing Burden of Dermatological Diseases 2.8. Market Restraints 2.8.1. Grave Side-Effects for Certain Classes of Therapeutic Drugs 2.9. Market Opportunities 2.9.1. Rise in Awareness Levels of Disease Origin and Progression 2.10. Market Challenges 2.10.1. Unawareness Towards Dermatological Diagnosis 3. Global Dermatological Therapeutics Market Outlook - by Drug Class 3.1. Anti-Infectives 3.2. Corticosteroids 3.3. Anti-Acne 3.4. Calcineurin Inhibitors 3.5. Retinoids 3.6. Other Drug Classes 4. Global Dermatological Therapeutics Market Outlook - by Application 4.1. Alopecia 4.2. Herpes 4.3. Psoriasis 4.4. Rosacea 4.5. Atopic Dermatitis 4.6. Acne Vulgaris 4.7. Other Applications 5. Global Dermatological Therapeutics Market - Regional Outlook 5.1. North America 5.1.1. Market by Drug Class 5.1.2. Market by Application 5.1.3. Country Analysis 5.1.3.1. United States 5.1.3.2. Canada 5.2. Europe 5.2.1. Market by Drug Class 5.2.2. Market by Application 5.2.3. Country Analysis 5.2.3.1. United Kingdom 5.2.3.2. Germany 5.2.3.3. France 5.2.3.4. Spain 5.2.3.5. Italy 5.2.3.6. Russia 5.2.3.7. Rest of Europe 5.3. Asia-Pacific 5.3.1. Market by Drug Class 5.3.2. Market by Application 5.3.3. Country Analysis 5.3.3.1. China 5.3.3.2. Japan 5.3.3.3. India 5.3.3.4. South Korea 5.3.3.5. Asean Countries 5.3.3.6. Australia & New Zealand 5.3.3.7. Rest of Asia-Pacific 5.4. Latin America 5.4.1. Market by Drug Class 5.4.2. Market by Application 5.4.3. Country Analysis 5.4.3.1. Brazil 5.4.3.2. Mexico 5.4.3.3. Rest of Latin America 5.5. Middle East and Africa 5.5.1. Market by Drug Class 5.5.2. Market by Application 5.5.3. Country Analysis 5.5.3.1. United Arab Emirates 5.5.3.2. Turkey 5.5.3.3. Saudi Arabia 5.5.3.4. South Africa 5.5.3.5. Rest of Middle East & Africa 6. Competitive Landscape 6.1. Abbvie Inc 6.2. Allergan 6.3. Almirall 6.4. Amgen Inc 6.5. Bausch Health Companies Inc 6.6. Galderma 6.7. GlaxoSmithKline plc 6.8. Johnson & Johnson 6.9. Novartis Ag 6.10. Pfizer Inc 6.11. AGI Dermatics 6.12. Leo Pharma A/S 6.13. Merck & Co 7. Methodology & Scope 7.1. Research Scope & Deliverables 7.2. Sources of Data 7.3. Research Methodology For more information about this report visit https://www.researchandmarkets.com/r/kokwn5 Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research. CONTACT: ResearchAndMarkets.com Laura Wood, Senior Press Manager press@researchandmarkets.com For E.S.T Office Hours Call 1-917-300-0470 For U.S./CAN Toll Free Call 1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

Clinical Trial
Register: EUDRA | Status: Ongoing | Type: Interventional | Phase 3 | Year: 2021

Main objective of the trial: To assess the efficacy of ABP 938 compared to aflibercept. Secondary objectives of the trial: To assess the safety and immunogenicity of ABP 938 compared to aflibercept Principal inclusion criteria: 1. Subjects or their legally authorized representative must sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) before any study-specific procedures 2. Men or women ≥ 50 years old 3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by central imaging vendor before randomization) 4. Active, treatment naïve subfoveal CNV lesions secondary to neovascular (wet) AMD including juxtafoveal lesions that affect the fovea as confirmed with SD-OCT, FA and/or FP in the study eye (confirmed by central imaging vendor before randomization) 5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye (confirmed by central imaging vendor before randomization) 7. Central retinal thickness (CRT) of ≥ 270 µm in the study eye as measured by the machine calculated average thickness in the ETDRS central 1 mm subfield (CST) by SD-OCT at screening (confirmed by central imaging vendor before randomization) Principal exclusion criteria: 1. Total lesion size > 12 disc areas (30.5 mm2, including blood, scars, and neovascularization) in the study eye (confirmed by central imaging vendor before randomization) 2. Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye (confirmed by central imaging vendor before randomization) 3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by central imaging vendor before randomization) 4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye (confirmed by central imaging vendor before randomization) 5. History of any vitreous hemorrhage within 4 weeks before randomization in the study eye 6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye (confirmed by central imaging vendor before randomization with the exception of the refractive error and axial length which is to be assessed by the investigator) 7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye 8. History of retinal detachment in the study eye 9. Any history of macular hole of stage 2 and above in the study eye 10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane (confirmed by central imaging vendor before randomization) in the study eye 11. Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection 12. Prior trabeculectomy or other filtration surgery in the study eye 13. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye 14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 15. Previous therapeutic radiation in the region of the study eye 16. History of corneal transplant or corneal dystrophy in the study eye 17. Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye 18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety 19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD (confirmed by central imaging vendor before randomization) 20. Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization 21. Active scleritis or episcleritis or presence of scleromalacia 22. Active extraocular infection or history of extraocular infections as follows: a. any active infection for which systemic anti-infectives were used within 4 weeks before randomization b. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject 23. Acute coronary event or stroke within 3 months before randomization 24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease 25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 26. Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor [VEGF] therapy) in the study eye, except dietary supplements or vitamins 27. Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 30 days before randomization, except dietary supplements or vitamins ...more in protocol... Primary endpoints: Change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 8

News: GlobeNewswire, Research Analysis And Reports
Site: globenewswire.com

Dublin, Oct. 30, 2019 (GLOBE NEWSWIRE) -- The "Frontier Pharma - Small Cell Lung Cancer: Diverse First-in-Class Pipeline Shows Promise of Targeted Therapies to Treat Aggressive Disease" report has been added to ResearchAndMarkets.com's offering. Initially considered a curable disease due to substantial sensitivity to chemotherapy, small cell lung cancer (SCLC) remains a fatal disease with a poor outcome, with the majority of patients surviving one year or less after diagnosis. Unlike non-small cell lung cancer (NSCLC), in which major advances in treatment have been made following the approval of numerous targeted therapies, the field of SCLC has seen little advancement, and the standard of care (SOC) for several decades has been platinum-etoposide chemotherapy. Limited tumor tissue for translational research, poor understanding of the mechanisms underlying disease biology, and therapeutic resistance are major factors impeding the discovery of effective drugs, including targeted therapies in SCLC, proving a major clinical need for patients. To date, there have been three targeted therapies approved to treat SCLC, Bristol-Myers Squibb's Opdivo (nivolumab), Roche's Tecentriq (atezolizumab), and Merck & Co.'s Keytruda (pembrolizumab) which were approved by the FDA in August 2018, March 2019 and June 2019, respectively. The recent approval of targeted and immuno-therapies for SCLC will generate a new maintenance setting following chemotherapy in SCLC. Following the approval of these new agents, relapsed/refractory patients are expected to have significantly improved therapeutic options. The increased prescription of branded therapies in treatment-nave and advanced patients will be the primary impetus driving the substantial growth in the SCLC market. Scope There are 165 pipeline programs in active development for SCLC. What proportion of these products are first-in-class? How does first-in-class innovation vary by development stage and molecular target class? Which molecular target classes are prominently represented in the first-in-class SCLC pipeline? Which first-in-class targets have been identified as most promising for the treatment of SCLC? How does the distribution of target classes differ in terms of development stage? Across the SCLC landscape, there are 118 active companies. Which companies have formed partnerships? Which companies have first-in-class assets in development with no prior deal involvement? Reasons to Buy Understand the current disease landscape with an overview of etiology, pathophysiology, disease classification and staging systems and epidemiology. Visualize the composition of the SCLC market in terms of dominant molecule types and molecular targets. Analyze and compare the SCLC pipeline and stratify by stage of development, molecule type, and molecular target. Assess the therapeutic potential of first-in-class targets. Using a proprietary matrix, first-in-class programs have been assessed and ranked according to their clinical potential. Promising first-in-class targets have been reviewed in greater detail. Recognize commercial opportunities by identifying first-in-class pipeline programs for SCLC that have not yet been involved in licensing or co-development deals, and by analyzing company strategies in prior deals through case studies of key deals for first-in-class SCLC programs. Companies Mentioned Bristol-Myers Squibb Merck & Co. Roche Key Topics Covered 1 Table of Contents 1.1 List of Tables 1.2 List of Figures 2 Small Cell Lung Cancer: Executive Summary 2.1 Pipeline Holds Some Potential for the Approval of More Targeted Therapies 2.2 High Levels of First-in-Class Innovation 2.3 Need for Disease-Modifying Pharmacotherapies 3 Introduction 3.1 Catalyst 3.2 Related Reports 3.3 Upcoming Related Reports 4 Disease Overview 4.1 Etiology and Pathophysiology 4.2 Classification or Staging Systems 4.3 Sustained Innovation in SCLC 4.4 Epidemiology for SCLC 4.5 Overview for Marketed Products 5 Assessment of Pipeline Product Innovation 5.1 Overview 5.2 Pipeline by Stage of Development and Molecule Type 5.3 Pipeline by Molecular Target 5.4 Comparative Distribution of Programs Between SCLC Market and Pipeline by Therapeutic Target Family 5.5 Comparative Distribution of First-in-Class and Non-First-in-Class Pipeline Programs by Molecular Target Class 5.5.1 Percentage Distribution of First-in-Class and Non-First-in-Class Pipeline Programs 5.6 Ratio of First-in-Class Programs to First-in-Class Molecular Targets Within the Pipeline 6 First-in-Class Molecular Target Evaluation 6.1 Overview 6.2 Pipeline Programs Targeting GTPase KRAS 6.3 Pipeline Programs Targeting Interleukin 2 Receptor Beta and Gamma 6.4 Pipeline Programs Targeting Heat Shock Protein 6.5 Pipeline Programs Targeting Serine/Threonine Protein Kinase AKT (AKT1, AKT2, AKT3) 6.6 Pipeline Programs Targeting Hepatitis A Virus Cellular Receptor 6.7 Pipeline Programs Targeting Serine/Threonine-Protein Kinase ATR 6.8 Pipeline Programs Targeting Protein Phosphatase 2A 6.9 Pipeline Programs Targeting Histone-lysine N-methyltransferase EZH2 6.10 Pipeline Programs Targeting Lymphocyte Activation Gene 3 Protein 7 Key Players and Deals 7.1 Overview 7.1.1 Allogene Therapeutics Enters into Licensing Agreement with Cellectis 7.1.2 Amgen and MD Anderson Enter Two Collaboration Agreements Across Various Cancer Types 7.1.3 MabVax Therapeutics Enters into Research Agreement with Memorial Sloan Kettering Cancer Center List of Tables Table 1: Definitions Used in TNM Classification and Clinical Staging System in Lung Cancer Table 2: AJCC Staging of Lung Cancer Table 3: SCLC Diagnosed Prevalent Cases (N), Thousands, 2014-2024 List of Figures Figure 1: SCLC, Global Market by Molecular Target and Molecule Type, 2019 Figure 2: SCLC, Global, Pipeline by Stage of Development and Molecule Type, 2019 Figure 3: SCLC, Global, Pipeline by Molecular Target and Stage of Development, 2019 Figure 4: SCLC, Global, Distribution of Pipeline and Marketed Products by Molecular Target Class, 2019 Figure 5: SCLC, Global, Distribution of Pipeline Products by First-in-Class Status and Molecular Target Class, 2019 Figure 6: SCLC, Global, Percentage Distribution of First-in-Class and Non-First-in-Class Products by Stage of Development and Molecular Target Class, 2019 Figure 7: SCLC, Global, Ratio of First-in-Class and Non-First-in-Class Products to First-in-Class Targets by Stage of Development and Molecular Target Class, 2019 For more information about this report visit https://www.researchandmarkets.com/r/4c6vb4 Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research. CONTACT: ResearchAndMarkets.com Laura Wood, Senior Press Manager press@researchandmarkets.com For E.S.T Office Hours Call 1-917-300-0470 For U.S./CAN Toll Free Call 1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

News: Business Wire Health, Pharmaceutical News
Site: www.businesswire.com

DUBLIN--(BUSINESS WIRE)--The "Global Osteoporosis Drugs Market By Route of Administration, By Drug Class, By Region, Industry Analysis and Forecast, 2020-2026" report has been added to ResearchAndMarkets.com's offering. The Global Osteoporosis Drugs Market size is expected to reach $10.9 billion by 2026, rising at a market growth of 4.4% CAGR during the forecast period. The condition may lead to severe fractures, which may have harmful effects on the health of the patient. Nevertheless, the condition requires treatment, including the use of osteoporosis medications. Many of the drugs on the market include selective estrogen inhibitor modulator (SERM) bisphosphonates, parathyroid hormone treatment, calcitonin, and RANK ligand inhibitors. These drugs are administered through different routes in the body, like orally or intravenously. International Osteoporosis Foundation reports that about 200 million people worldwide suffer from osteoporosis disorder. Currently, it is believed that about 200 million people globally suffer from this illness. About 30% of the postmenopausal people have osteoporosis in the US and Europe. According to the National Institute of Health, about 53 million people in the US are either suffering from osteoporosis or at elevated risk due to low bone density. The rising consumer base for osteoporosis disorders means steady demand development over the projected period. Bisphosphonates are a type of drug used to reduce deterioration of the bone structure and to treat osteoporosis and related diseases. These are the most widely used medications used for the treatment of osteoporosis. They are called bisphosphonates because they have two groups of PO(OH) phosphonates. They are sometimes called diphosphonates (bis-or di-+phosphonates). Data shows that they reduce the likelihood of fracture in postmenopausal women with osteoporosis. The market research report covers the analysis of key stake holders of the market. Key companies profiled in the report include Amgen, Inc., F. Hoffmann-La Roche Ltd., GlaxoSmithKline PLC (GSK), Merck & Co., Inc., Novartis AG, Pfizer, Inc., Sun Pharmaceutical Industries Ltd., Teva Pharmaceuticals Industries Ltd., Allergan PLC, and Eli Lilly and Company. Strategies Deployed in the Market 2019-Apr: Amgen and UCB announced that the U.S. Food and Drug Administration (FDA) approved EVENITY (romosozumab-aqqg) for the treatment of osteoporosis in postmenopausal women at high risk for fracture. EVENITY is the first and only bone builder with a unique dual effect that both increases bone formation and to a lesser extent reduces bone resorption (or bone loss) to rapidly reduce the risk of fracture. 2018-May: Amgen got the U.S. Food and Drug Administration (FDA) approval for the use of Prolia (denosumab) for the treatment of glucocorticoid-induced osteoporosis (GIOP) in men and women at high risk of fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. 2017-Oct: Novartis signed an agreement with Daewoong Pharmaceutical. Under this agreement, the latter company has acquired marketing and commercial rights for an osteoporosis drug from Sandoz, Novartis' generic division. By acquiring these rights, Daewoong strengthened its product lineup and secure a steady cash-flow. 2016-Sep: Amgen extended its collaboration with Dr. Reddy's Laboratories Ltd. Following the expansion, Dr. Reddy was aimed to market and distribute three of Amgen's medicines in India in the therapy areas of oncology and osteoporosis. 2016-Jun: Amgen came into partnership with Zuellig Pharma following which the latter company helps the former company in driving growth of products and therapies in multiple markets across Asia. Zuellig was aimed to support Amgen with a range of services including Commercialization, Regulatory Services and Distribution. The partnership includes the commercialization of Amgen's oncology therapeutics Neupogen, Neulastim, Vectibix, and XGEVA, and Amgen's osteoporosis medicine Prolia, in nine Asian markets. Key Topics Covered Chapter 1. Market Scope & Methodology 1.1 Market Definition 1.2 Objectives 1.3 Market Scope 1.4 Segmentation 1.4.1 Global Osteoporosis Drugs Market, by Route of Administration 1.4.2 Global Osteoporosis Drugs Market, by Drug Class 1.4.3 Global Osteoporosis Drugs Market, by Geography 1.5 Methodology for the Research Chapter 2. Market Overview 2.1 Introduction 2.1.1 Overview 2.1.2 Market Composition and Scenario 2.2 Key Factors Impacting the Market 2.2.1 Market Drivers 2.2.2 Market Restraints Chapter 3. Global Osteoporosis Drugs Market by Route of Administration 3.1 Global Oral Market by Region 3.2 Global Injectable Market by Region 3.3 Global Other Route of Administration Market by Region Chapter 4. Global Osteoporosis Drugs Market by Drug Class 4.1 Global Bisphosphonates Market by Region 4.2 Global Rank Ligand Inhibitors Market by Region 4.3 Global Parathyroid Hormone Therapy Market by Region 4.4 Global Calcitonin Market by Region 4.5 Global Selective Estrogen Inhibitors Modulator (SERM) Market by Region 4.6 Global Other Drug Class Market by Region Chapter 5. Global Osteoporosis Drugs Market by Region 5.1 North America Osteoporosis Drugs Market 5.2 Europe Osteoporosis Drugs Market 5.3 Asia-Pacific Osteoporosis Drugs Market 5.4 LAMEA Osteoporosis Drugs Market Chapter 6. Company Profiles 6.1 Amgen, Inc. 6.2 F. Hoffmann-La Roche Ltd. 6.3 GlaxoSmithKline PLC (GSK) 6.4 Merck & Co. Inc. 6.5 Novartis AG 6.6 Pfizer, Inc. 6.7 Sun Pharmaceutical Industries Ltd. 6.8 Teva Pharmaceutical Industries Ltd. 6.9 Allergan PLC 6.1 Eli Lilly and Company For more information about this report visit https://www.researchandmarkets.com/r/fcfg69

Patent
Amgen Inc. | Date: 2017-12-13

The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A, X, R^(2), R^(2), R^(3), R^(4), R^(5), R^(6), and R^(7 )of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimers Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions. 1. A compound of Formula I 2. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein the compound of Formula I is a compound of Formula II 3. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein the compound of Formula I is a compound of Formula III 4. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein A is N. 5. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein A is CH. 6. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein A is CR ^(4). 7. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein X is NR ^(1). 8. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein R ^(1 )is methyl. 9. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein X is C(R ^(1)R ^(1)). 10. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein R ^(1 )and R ^(1) independently are H or methyl. 11. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein R ^(1 )and R ^(1) are methyl. 12. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein one of R ^(1 )and R ^(1) and one of R ^(2 )and R ^(2) together optionally form a CH _(2)CH _(2) group bridging the two carbon atoms to which R ^(1), R ^(1), R ^(2 )and R ^(2) are attached, wherein the other of R ^(1 )and R ^(1) and the other of R ^(2 )and R ^(2) independently are H or C _(1-4)alkyl, wherein the C _(1-4)alkyl is optionally substituted with 1 to 3 fluoro substituents. 13. The compound of claim 12, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein the compound is a compound of Formula IV 14. The compound of claim 13, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein R ^(1) is CH _(2)F and R ^(2) is H. 15. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein R ^(2 )and R ^(2) independently are H, F, or methyl. 16. (canceled) 17. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein R ^(2 )and R ^(2) with the carbon atom to which R ^(2 )and R ^(2) are attached optionally form a C _(3)carbocycle. 18. (canceled) 19. (canceled) 20. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein R ^(3 )is methyl, CH _(2)F, or CHF _(2). 21. (canceled) 22. (canceled) 23. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein R ^(4 )is F. 24. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein one of R ^(6 )and R ^(7 )is F or H and the other of R ^(6 )and R ^(7 )is tetrahydropyranyl, tetrahydofuranyl, thiophenyl, thiazolyl, phenyl, pyridyl, pyrazinyl, 2,3-dihydrobenzo[b][1,4]dioxinyl, 2,3-dihydro-[1,4]dioxino[2,3-c]pyridyl, [1,3]dioxolo[4,5-c]pyridyl, 3,4-dihydro-2H-pyrano[2,3-c]pyridyl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridyl, 6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidinyl, isoquinolinyl, or pyrido[3,4-b]pyrazinyl, and wherein said other of R ^(6 )and R ^(7 )is optionally substituted. 25. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein one of R ^(6 )and R ^(7 )is F or H and the other of R ^(6 )and R ^(7 )is optionally substituted with 1 or 2 substituents independently selected from F, Cl, Br, OH, CN, methyl, trifluoromethyl, cyclopropyl, cyclopropylethynyl, methoxy, trifluoromethoxy, ethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-methoxyethoxy, propoxy, 2,2,3,3-tetrafluoropropoxy, 3,3,3-trifluoropropoxy, propan-1-ol-2-oxy, 2-propanoloxy, 2-cyano-2-methyl-propoxy, oxetan-3-ylmethoxy, (1-methoxypropan-2-yl)oxy, 2-methoxypropoxy, allyloxy, 2-propynyloxy, 2-butynyloxy, 3-butyn-2-yloxy, 2-butyn-4-ol-oxy, 4-fluoro-2-butynoxy, pent-1-yn-3-yloxy, pent-3-yn-2-yloxy, hex-4-yn-3-yloxy, hex-3-yn-2-yloxy, OCH _(2)C(O)OC _(2)H _(5), cyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, phenoxy, benzyloxy, or OC _(1)-2alkyl-heteroaryl, wherein the heteroaryl is optionally substituted with one or two methyl groups or the heteroaryl is optionally substituted with one bromo. 26. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein one of R ^(6 )and R ^(7 )is F or H and the other of R ^(6 )and R ^(7 )is 27. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein one of R ^(6 )and R ^(7 )is F or H and the other of R ^(6 )and R ^(7 )is tetrahydropyranyl, phenyl, pyridyl, pyrazinyl, or 6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidinyl, and wherein the other of R ^(6 )and R ^(7 )is optionally substituted. 28. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein one of R ^(6 )and R ^(7 )is F or H and the other of R ^(6 )and R ^(7 )is optionally substituted with 1 or 2 substituents independently selected from OH, CN, methyl, trifluoromethyl, cyclopropylethynyl, trifluoromethoxy, ethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-methoxyethoxy, propoxy, 2,2,3,3-tetrafluoropropoxy, 3,3,3-trifluoropropoxy, propan-1-ol-2-oxy, 2-propanoloxy, 2-cyano-2-methyl-propoxy, (1-methoxypropan-2-yl)oxy, 2-methoxypropoxy, allyloxy, 2-propynyloxy, 2-butynyloxy, 3-butyn-2-yloxy, 2-butyn-4-ol-oxy, 4-fluoro-2-butynoxy, (S)-pent-1-yn-3-yloxy, (S)-pent-3-yn-2-yloxy, hex-4-yn-3-yloxy, OCH _(2)C(O)OC _(2)H _(5), cyclopropylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, benzyloxy, or OCH _(2)-(5-membered-heteroaryl), wherein the 5-membered-heteroaryl is optionally substituted with one or two methyl groups or the heteroaryl is optionally substituted with one bromo. 29. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein one of R ^(6 )and R ^(7 )is F or H and the other of R ^(6 )and R ^(7 )is 30.33.- 33. (canceled) 34. The compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, wherein R^(5 )is H; and R^(6 )is F. 35. (canceled) 36. The compound of claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, selected from (R,Z)-9-amino-7-(5-(2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-7-methyl-5-thia-8-azaspiro[3.5]non-8-ene 5,5-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; 6-((Z)-2-(3-((1S,2R,5R)-4-amino-5-(fluoromethyl)-2-methyl-8,8-dioxido-8-thia-3-azabicyclo[3.2.1]oct-3-en-2-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-6-(2-(3-(9-amino-7-methyl-5,5-dioxido-5-thia-8-azaspiro[3.5]non-8-en-7-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-3-amino-5-(5-(2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4,5-difluorophenyl)-1-fluorovinyl)nicotinonitrile; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(tetrahydro-2H-pyran-4-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-6-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-5-amino-3-(5-(2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(oxazol-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-(cyclopropylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-((5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-methoxypyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-ethoxypyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (1R,4R,5S)-4-(5-((Z)-2-(5-(allyloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2-amino-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(oxetan-3-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-6-(2-(3-(6-amino-5,8-dimethyl-4,4-dioxido-4-thia-5,7-diazaspiro[2.5]oct-6-en-8-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(oxazol-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-methoxyethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(((S)-1-methoxypropan-2-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-(cyclobutylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-fluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-(2,2-difluoroethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-propoxypyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-((2-methoxypropoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-propyn-1-yloxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (8R)-8-(5-((Z)-2-(5-chloro-2-pyrazinyl)-2-fluoroethenyl)-2-fluorophenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-hydroxypyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(3,3,3-trifluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(cyclopropylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(cyclopentylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(cyclobutylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-5-(2-(3-(6-amino-5,8-dimethyl-4,4-dioxido-4-thia-5,7-diazaspiro[2.5]oct-6-en-8-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-9-amino-7-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-7-methyl-5-thia-8-azaspiro[3.5]non-8-ene 5,5-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(cyclohexylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,E)-3-amino-5-(5-(2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-((5-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazin-2-yl)oxy)-2,2-dimethylpropanenitrile; (R,Z)-5-amino-3-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-(5-(2-(5-(2-(1H-imidazol-1-yl)ethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-amino-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(2-(4-bromo-1H-pyrazol-1-yl)ethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-(5-(2-(5-(2-(1H-pyrazol-1-yl)ethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-amino-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-((5-methyl-3-isoxazolyl)methoxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,2-trifluoroethoxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (R)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(((S)-1-methoxypropan-2-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(oxazol-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide hydrochloride; (R,Z)-3-amino-5-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-((5-methyl-1,3-oxazol-2-yl)methoxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (R,Z)-5-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile; (R)-3-amino-5-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-methoxypropoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-((5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(cyclobutylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-((5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((R)-pent-1-yn-3-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((S)-pent-1-yn-3-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(oxetan-3-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-6-(2-(3-(3-amino-2,5,6,6-tetramethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-5-(2-(3-(3-amino-2,5,6,6-tetramethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile; (R,Z)-3-amino-5-(5-(2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5,6,6-tetramethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-2,5,6,6-tetramethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5,6,6-tetramethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5,6,6-tetramethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (S,Z)-6-(2-(3-(5-amino-3-(fluoromethyl)-6,6-dimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (S,Z)-5-amino-3-(5-(2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (S,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,2-difluoro-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-6-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4,5-difluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-5-amino-3-(5-(2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (S,Z)-5-amino-3-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (S)-5-amino-3-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-6-(2-(5-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-6-fluoropyridin-3-yl)-1-fluorovinyl)nicotinonitrile; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((R)-hex-4-yn-3-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((S)-hex-4-yn-3-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (2R,3R)-5-amino-2-fluoro-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (2S,3R)-5-amino-2-fluoro-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-2,2-difluoro-3-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2,3-difluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(cyclopropylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((R)-pent-3-yn-2-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((S)-pent-3-yn-2-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(benzyloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(pyridin-4-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-phenoxypyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-4-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)benzonitrile; (2S,3R)-5-amino-3-(5-((Z)-2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-2-fluoro-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (2R,3R)-5-amino-3-(5-((Z)-2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-2-fluoro-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-2,2-difluoro-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((R)-hex-3-yn-2-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((S)-hex-3-yn-2-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-(((S)-1-hydroxypropan-2-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((S)-2-hydroxypropoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(thiazol-4-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((3-methylisoxazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-chloro-4-hydroxypyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((5-methylisoxazol-3-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(oxazol-4-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; 6-((Z)-2-(3-((5R)-3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluoroethenyl)-4-fluoro-3-pyridinecarbonitrile; (R,Z)-5-(5-(2-(5-(allyloxy)pyrazin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-3-amino-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(pyrimidin-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((5-methyl-1,2,4-oxadiazol-3-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-chloro-4-methoxypyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-2-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)-5-chloroisonicotinonitrile; (R,Z)-3-amino-5-(5-(2-(5-chloro-4-fluoropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-Amino-5-(5-(2-(6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-((R)-6-methyl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-((S)-7-methyl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((4-methylthiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-((2,5-dimethyloxazol-4-yl)methoxy)pyrazin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (5R)-5-(5-((Z)-2-(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-yl)-2-fluoroethenyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; (5R)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-fluoro-2-pyridinyl)ethenyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; (5R)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-methoxy-2-pyrazinyl)ethenyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; (5R)-5-(5-((Z)-2-(3-chloro-5-(trifluoromethyl)-2-pyridinyl)-2-fluoroethenyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; (R,Z)-ethyl 2-((5-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4,5-difluorophenyl)-1-fluorovinyl)pyrazin-2-yl)oxy)acetate; (5R)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(trifluoromethyl)-2-pyridinyl)ethenyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; 6-((Z)-2-(3-((5R)-3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluoroethenyl)-5-methyl-3-pyridinecarbonitrile; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((5-methyloxazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(cyclopropylethynyl)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((1-methyl-1H-imidazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (5R)-5-(2-fluoro-5-((Z)-2-fluoro-2-(pyrido[3,4-b]pyrazin-7-yl)ethenyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(cyclopropylethynyl)pyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-((4-hydroxybut-2-yn-1-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; 2-((Z)-2-(3-((5R)-3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluoroethenyl)-1,3-thiazole-5-carbonitrile; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-((4-fluorobut-2-yn-1-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (5R)-5-(5-((Z)-2-(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-6-yl)-2-fluoroethenyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; 5-((Z)-2-(3-((5R)-3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluoroethenyl)-2-thiophenecarbonitrile; (5R)-5-(5-((Z)-2-([1,3]dioxolo[4,5-c]pyridin-6-yl)-2-fluoroethenyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(trifluoromethoxy)pyridin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (5R)-5-(2-fluoro-5-((Z)-2-fluoro-2-(3-isoquinolinyl)ethenyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; (5R)-5-(5-((Z)-2-(6-chloro-3-isoquinolinyl)-2-fluoroethenyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; 6-((Z)-2-(4-((4aS,7aS)-3-amino-2,2-dimethyl-1,1-dioxido-4a,5,7,7a-tetrahydro-2H-furo[3,4-b][1,4]thiazin-4a-yl)-3-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-fluoropyridin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-methoxypyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(trifluoromethyl)pyridin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-cyclopropylpyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; 2-((Z)-2-(3-((5R)-3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluoroethenyl)-1,3-thiazole-4-carbonitrile; (R,Z)-6-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)-5-chloronicotinonitrile; (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)-5-chloronicotinonitrile; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-fluoropyridin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-methoxypyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(trifluoromethyl)pyridin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-6-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)-5-methylnicotinonitrile; (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4,5-difluorophenyl)-1-fluorovinyl)-5-methylnicotinonitrile; (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4,5-difluorophenyl)-1-fluorovinyl)-5-chloronicotinonitrile; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(tetrahydrofuran-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((E)-2-fluoro-2-(tetrahydrofuran-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; or (R,E)-5-amino-3-(5-(4-chlorostyryl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide. 37. The compound of claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, selected from (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; 6-((Z)-2-(3-((1S,2R,5R)-4-amino-5-(fluoromethyl)-2-methyl-8,8-dioxido-8-thia-3-azabicyclo[3.2.1]oct-3-en-2-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-6-(2-(3-(9-amino-7-methyl-5,5-dioxido-5-thia-8-azaspiro[3.5]non-8-en-7-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4,5-difluorophenyl)-1-fluorovinyl)nicotinonitrile; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(tetrahydro-2H-pyran-4-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-6-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(oxazol-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-(cyclopropylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-((5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-methoxypyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-ethoxypyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (1R,4R,5S)-4-(5-((Z)-2-(5-(allyloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2-amino-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-6-(2-(3-(6-amino-5,8-dimethyl-4,4-dioxido-4-thia-5,7-diazaspiro[2.5]oct-6-en-8-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(oxazol-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-methoxyethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(((S)-1-methoxypropan-2-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-(cyclobutylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-fluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-(2,2-difluoroethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-propoxypyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-methoxypropoxy)pyrazin-2-yl)vinyl)phenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (1R,4R,5S)-2-amino-4-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(fluoromethyl)-4-methyl-8-thia-3-azabicyclo[3.2.1]oct-2-ene 8,8-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-propyn-1-yloxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (8R)-8-(5-((Z)-2-(5-chloro-2-pyrazinyl)-2-fluoroethenyl)-2-fluorophenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-hydroxypyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(3,3,3-trifluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(cyclopropylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(cyclopentylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(cyclobutylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-5-(2-(3-(6-amino-5,8-dimethyl-4,4-dioxido-4-thia-5,7-diazaspiro[2.5]oct-6-en-8-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-9-amino-7-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-7-methyl-5-thia-8-azaspiro[3.5]non-8-ene 5,5-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(cyclohexylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-((5-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazin-2-yl)oxy)-2,2-dimethylpropanenitrile; (R,Z)-5-amino-3-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(2-(4-bromo-1H-pyrazol-1-yl)ethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-(5-(2-(5-(2-(1H-pyrazol-1-yl)ethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-amino-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-5-amino-3-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-((5-methyl-3-isoxazolyl)methoxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,2-trifluoroethoxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (R)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(((S)-1-methoxypropan-2-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(oxazol-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide hydrochloride; (R,Z)-3-amino-5-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (8R)-8-(2-fluoro-5-((Z)-2-fluoro-2-(5-((5-methyl-1,3-oxazol-2-yl)methoxy)-2-pyrazinyl)ethenyl)phenyl)-5,8-dimethyl-4-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine 4,4-dioxide; (R,Z)-5-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile; (R)-3-amino-5-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-methoxypropoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-((5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-((5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((S)-pent-1-yn-3-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(oxetan-3-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-6-(2-(3-(3-amino-2,5,6,6-tetramethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-5-(2-(3-(3-amino-2,5,6,6-tetramethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile; (R,Z)-3-amino-5-(5-(2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5,6,6-tetramethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-2,5,6,6-tetramethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5,6,6-tetramethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5,6,6-tetramethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (S,Z)-6-(2-(3-(5-amino-3-(fluoromethyl)-6,6-dimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (S,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-6-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4,5-difluorophenyl)-1-fluorovinyl)nicotinonitrile; (S,Z)-5-amino-3-(5-(2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (S)-5-amino-3-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-6-(2-(5-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-6-fluoropyridin-3-yl)-1-fluorovinyl)nicotinonitrile; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((R)-hex-4-yn-3-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((S)-hex-4-yn-3-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (2R,3R)-5-amino-2-fluoro-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (2S,3R)-5-amino-2-fluoro-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-2,2-difluoro-3-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2,3-difluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(cyclopropylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(5-(benzyloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-4-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)benzonitrile; (2S,3R)-5-amino-3-(5-((Z)-2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-2-fluoro-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (2R,3R)-5-amino-3-(5-((Z)-2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-2-fluoro-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(5-(2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-2,2-difluoro-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-(((S)-1-hydroxypropan-2-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R)-5-amino-3-(2-fluoro-5-((Z)-2-fluoro-2-(5-((S)-2-hydroxypropoxy)pyrazin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(thiazol-4-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((3-methylisoxazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((5-methylisoxazol-3-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(oxazol-4-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; 6-((Z)-2-(3-((5R)-3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluoroethenyl)-4-fluoro-3-pyridinecarbonitrile; (R,Z)-5-(5-(2-(5-(allyloxy)pyrazin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-3-amino-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(pyrimidin-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((5-methyl-1,2,4-oxadiazol-3-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-2-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)-5-chloroisonicotinonitrile; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-Amino-5-(5-(2-(6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-((R)-6-methyl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-((S)-7-methyl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((4-methylthiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-((2,5-dimethyloxazol-4-yl)methoxy)pyrazin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (5R)-5-(5-((Z)-2-(3-chloro-5-(trifluoromethyl)-2-pyridinyl)-2-fluoroethenyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; (R,Z)-ethyl 2-((5-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4,5-difluorophenyl)-1-fluorovinyl)pyrazin-2-yl)oxy)acetate; (5R)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(trifluoromethyl)-2-pyridinyl)ethenyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; 6-((Z)-2-(3-((5R)-3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluoroethenyl)-5-methyl-3-pyridinecarbonitrile; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((5-methyloxazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(cyclopropylethynyl)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-((1-methyl-1H-imidazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(5-(cyclopropylethynyl)pyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-((4-hydroxybut-2-yn-1-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; 2-((Z)-2-(3-((5R)-3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluoroethenyl)-1,3-thiazole-5-carbonitrile; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-((4-fluorobut-2-yn-1-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (5R)-5-(5-((Z)-2-([1,3]dioxolo[4,5-c]pyridin-6-yl)-2-fluoroethenyl)-2-fluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-amine 1,1-dioxide; (R,Z)-3-amino-5-(2-fluoro-5-(2-fluoro-2-(5-(trifluoromethoxy)pyridin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; 6-((Z)-2-(4-((4aS,7aS)-3-amino-2,2-dimethyl-1,1-dioxido-4a,5,7,7a-tetrahydro-2H-furo[3,4-b][1,4]thiazin-4a-yl)-3-fluorophenyl)-1-fluorovinyl)nicotinonitrile; (R,Z)-5-amino-3-(5-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-5-amino-3-(2-fluoro-5-(2-fluoro-2-(5-(trifluoromethyl)pyridin-2-yl)vinyl)phenyl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide; (R,Z)-6-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)-5-chloronicotinonitrile; (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-1-fluorovinyl)-5-chloronicotinonitrile; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-methoxypyrazin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(5-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-3-amino-5-(2,3-difluoro-5-(2-fluoro-2-(5-(trifluoromethyl)pyridin-2-yl)vinyl)phenyl)-2,5-dimethyl-5,6-dihydro-2H-1,2,4-thiadiazine 1,1-dioxide; (R,Z)-6-(2-(3-(5-amino-3,6,6-trimethyl-1,1-dioxido-3,6-dihydro-2H-1,4-thiazin-3-yl)-4-fluorophenyl)-1-fluorovinyl)-5-methylnicotinonitrile; (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4,5-difluorophenyl)-1-fluorovinyl)-5-methylnicotinonitrile; or (R,Z)-6-(2-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4,5-difluorophenyl)-1-fluorovinyl)-5-chloronicotinonitrile. 38. The compound of claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, selected from 39.52.- 52. (canceled) 53. A pharmaceutical composition comprising the compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer, and a pharmaceutically acceptable excipient. 54.62.- 62. (canceled) 63. A method of reducing beta amyloid peptide levels in the cerebral spinal fluid of a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer. 64. A method of treating Alzheimers disease, cognitive impairment or a combination thereof in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer. 65. A method of treating a neurological disorder selected from mild cognitive impairment, Downs syndrome, hereditary cerebral hemorrhage with Dutch-type amyloidosis, cerebral amyloid angiopathy, degenerative dementia, dementia associated with Parkinsons disease, dementia associated with supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimers disease, or a combination thereof in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer. 66. A method of reducing the formation of plaque on the brain of a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to claim 1, or a tautomer, or a pharmaceutically acceptable salt of said compound or tautomer.

Clinical Trial
Register: EUDRA | Status: Ongoing | Type: Interventional | Phase 3 | Year: 2021

Main objective of the trial: To assess the efficacy of ABP 938 compared to aflibercept. Evaluar la eficacia de ABP 938 en comparación con aflibercept. Secondary objectives of the trial: To assess the safety and immunogenicity of ABP 938 compared to aflibercept Evaluar la seguridad y la inmunogenia de ABP 938 en comparación con aflibercept. Principal inclusion criteria: 1. Subjects must sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) before any study-specific procedures 2. Men or women ≥ 50 years old 3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by central imaging vendor before randomization) 4. Active, treatment naïve CNV lesions secondary to neovascular (wet) AMD as confirmed with SD-OCT, FA and FP in the study eye (confirmed by central imaging vendor before randomization) 5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye (confirmed by central imaging vendor before randomization) 7. Central retinal thickness (CRT) of ≥ 300 µm in the study eye as determined by SD-OCT at screening (confirmed by central imaging vendor before randomization) 1. Los sujetos deberán firmar el documento de consentimiento informado aprobado por el Comité de Ética (ICF) antes de la práctica de cualquier procedimiento del estudio 2. Hombres o mujeres de edad ≥ 50 años 3. Diagnóstico de AMD neovascular (húmeda) en el ojo en estudio (confirmada por el servicio centralizado de diagnóstico por imagen antes de la aleatorización) 4. Lesiones de CNV activas, no tratadas previamente, secundarias a AMD neovascular (húmeda), confirmadas por SD-OCT, FA y FP en el ojo en estudio (confirmadas por el servicio centralizado de diagnóstico por imagen antes de la aleatorización) 5. BCVA entre 73 y 34 letras, ambos extremos incluidos, en el ojo en estudio utilizando los optotipos ETDRS. 6. Presencia de líquido intra y/o subretiniano, identificado por SD-OCT, atribuible a CNV activa en el ojo en estudio (confirmada por el servicio centralizado de diagnóstico por imagen antes de la aleatorización) 7. Grosor central de la retina ≥ 300 μm en el ojo en estudio, determinado por SD-OCT en la selección (confirmado por el servicio centralizado de diagnóstico por imagen antes de la aleatorización) Principal exclusion criteria: 1. Total lesion size > 9 disc areas (22.86 mm2, including blood, scars, and neovascularization) in the study eye (confirmed by central imaging vendor before randomization) 2. Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye (confirmed by central imaging vendor before randomization) 3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by central imaging vendor before randomization) 4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye (confirmed by central imaging vendor before randomization) 5. History of any vitreous hemorrhage within 4 weeks before randomization in the study eye 6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye (confirmed by central imaging vendor before randomization with the exception of the refractive error and axial length which is to be assessed by the investigator) 7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye 8. History of retinal detachment in the study eye 9. Any history of macular hole of stage 2 and above in the study eye 10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane (confirmed by central imaging vendor before randomization) 11. Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection 12. Prior trabeculectomy or other filtration surgery in the study eye 13. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye 14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 15. Previous therapeutic radiation in the region of the study eye 16. History of corneal transplant or corneal dystrophy in the study eye 17. Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye 18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety 19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD (confirmed by central imaging vendor before randomization) 20. Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization 21. Active scleritis or episcleritis or presence of scleromalacia 22. Active extraocular infection or history of extraocular infections as follows: a. any active infection for which systemic anti-infectives were used within 4 weeks before randomization b. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject 23. Acute coronary event or stroke within 3 months before randomization 24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease 25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 26. Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor [VEGF] therapy) in the study eye, except dietary supplements or vitamins 27. Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 6 months before randomization, except dietary supplements or vitamins 28. Prior systemic anti-VEGF treatment as follows: a. Investigational or approved anti-VEGF therapy systemically within 3 months before randomization b. Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at any time 1. Tamaño total de la lesión > 9 áreas papilares (22,86 mm2, incluyendo sangre, cicatrices y neovascularización) en el ojo en estudio (confirmado por el servicio centralizado de diagnóstico por imagen antes de la aleatorización). 2. Área de CNV activa (componentes clásicos más ocultos) que supone < 50% del área lesional total en el ojo en estudio (confirmada por el servicio centralizado de diagnóstico por imagen antes de la aleatorización). 3. Cicatriz, fibrosis o atrofia que afecta al centro de la fóvea del ojo en estudio (confirmada por el servicio centralizado de diagnóstico por imagen antes de la aleatorización). 4. Presencia de desgarros o roturas del epitelio pigmentario de retina que afectan a la mácula del ojo en estudio (confirmada por el servicio centralizado de diagnóstico por imagen antes de la aleatorización). 5. Antecedentes de hemorragia vítrea en el ojo en estudio en el plazo de las 4 semanas anteriores a la aleatorización 6. Presencia de otras causas de CNV, tales como miopía patológica (equivalente esférico de 8 o más dioptrías negativas o longitud axial de 25 mm o más), síndrome de histoplasmosis ocular, estrías angioides, ruptura coroidea o coroiditis multifocal en el ojo en estudio (confirmadas por el servicio centralizado de diagnóstico por imagen antes de la aleatorización, con la excepción del error refractivo y la longitud axial, que deben evaluarse por el investigador). 7. Vitrectomía o cirugía láser previas de la mácula (incluida la terapia fotodinámica o la fotocoagulación focal con láser) en el ojo en estudio 8. Antecedente de desprendimiento de retina en el ojo en estudio. 9. Antecedente de agujero macular en estadio 2 y superior en el ojo en estudio 10. Toda patología macular que pueda limitar la visión, por ejemplo, tracción vitreomacular o membrana epirretiniana significativa (confirmadas por el servicio centralizado de diagnóstico por imagen antes de la aleatorización) 11. Cirugía intraocular o periocular en el ojo en estudio en el plazo de los 3 meses anteriores a la aleatorización, excepto la cirugía palpebral, que no podrá haber tenido lugar en el plazo de las 4 semanas anteriores a la aleatorización y siempre que no sea probable que pueda interferir con la inyección. 12. Trabeculectomia u otra cirugía de filtración previas en el ojo en estudio 13. Glaucoma no controlado (definido como presión intraocular [IOP] ≥ 25 mmHg a pesar del tratamiento con medicación antiglaucoma) en el ojo en estudio 14. Afaquia o seudoafaquia con ausencia completa de la cápsula posterior (salvo si se debiera a capsulotomía posterior mediante yttrium aluminum garnet [YAG]) en el ojo en estudio 15. Radioterapia previa en la región del ojo en estudio 16. Antecedentes de trasplante de córnea o distrofia corneal en el ojo en estudio 17. Opacificación importante de medios, incluida catarata, que pudiera interferir con la agudeza visual o con la evaluación de la seguridad, en el ojo en estudio 18. Todo proceso intraocular concomitante distinto de la AMD neovascular (húmeda) en el ojo en estudio que, en opinión del investigador, pueda precisar la programación de intervención médica o quirúrgica durante el estudio o que aumente el riesgo para el sujeto más allá de lo previsible como consecuencia de los procedimientos estándar de la inyección intraocular o que pueda interferir de cualquier otra forma con el procedimiento de inyección o con la evaluación de la eficacia o la seguridad 19. Antecedente o evidencia clínica de uveitis, retinopatía diabética, edema macular diabético o cualquier otra enfermedad vascular que afecte a la retina distinta de la AMD neovascular (húmeda) (confirmado por el servicio centralizado de diagnóstico por imagen antes de la aleatorización) 20. Inflamación intraocular activa o infección ocular o periocular activa o de sospecha, en el plazo de las 2 semanas anteriores a la aleatorización. 21. Escleritis o episcleritis activas o presencia de escleromalacia 22. Infección extraocular activa o antecedente de infección extraocular, tal como: a. toda infección activa para la que se hayan utilizado antiinfecciosos sistémicos en el plazo de las 4 semanas anteriores a la aleatorización b. infección recurrente o crónica u otra infección activa que, en opinión del investigador, pudiera hacer que la participación en el estudio fuera nociva para el sujeto. 23. Accidente coronario o cerebrovascular agudos en el plazo de los 3 meses anteriores a la aleatorización. 24. Enfermedad sistémica clínicamente importante no controlada, como diabetes mellitus, hipertensión, enfermedad cardiovascular -incluida la insuficiencia cardiaca moderada osevera (clase III/IV de la New York Heart Association), enfermedad renal o hepática No hay suficiente espacio para incluir todo. Por favor, refieran al documento "Resumen del protocolo del ensayo en español" para ver la lista completa. Primary endpoints: Change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 8 Variación frente al basal en la mejor agudeza visual con corrección (best corrected visual acuity, BCVA), medida mediante el número de letras de los optotipos del Early Treatment Diabetic Retinopathy Study (ETDRS) en la semana 8

News: GlobeNewswire, Health
Site: globenewswire.com

Intra-articular (IA) Delivery of AMB-05X Demonstrates Proof-of-Concept in TGCT With A Rapid Onset of Tumor Reduction in All Patients Within Six Weeks Interim AMB-05X Data Support Potential for Best-in-Class Therapy for Treatment of TGCT REDWOOD CITY, Calif., Oct. 20, 2021 (GLOBE NEWSWIRE) -- AmMax Bio, Inc. ("AmMax"), a private clinical-stage biotech company developing novel treatments with AMB-05X, its proprietary anti-CSF1R monoclonal antibody platform, today announced positive interim data from a Phase 2 study of AMB-05X for the treatment of tenosynovial giant cell tumor (TGCT). "We are very excited to report these positive interim results of AMB-05X for the treatment of TGCT", said Larry Hsu, Ph.D., Chief Executive Officer of AmMax Bio. "We have sought to match our highly potent and selective monoclonal antibody with an optimal local delivery route for superior efficacy and safety, that delivers best-in-class clinical benefits for patients suffering from TGCT. What we have seen so far supports that AMB-05X could dramatically impact the current treatment paradigm, with an unparalleled fast onset of response after only 6 weeks and no significant adverse events. We are working closely with our investigators in Europe and the U.S. to complete our Phase 2 program and prepare for a pivotal trial." The Phase 2 trial is designed as a 12-week adaptive, multi-center, open-label, proof-of-concept study to evaluate the safety, efficacy and pharmacokinetics of intra-articular injections of AMB-05X in patients with TGCT of the knee – the predominant joint affected by this sarcoma. (ClinicalTrials.gov Identifier: NCT04731675). Key study outcomes include overall response rate (ORR) via magnetic resonance imaging (MRI), improvements in pain, stiffness, range-of-motion, quality-of-life, pharmacokinetics measures and safety. Interim (6-Week) Results At Week 6 (after 3 doses), a preliminary analysis showed that all 5 enrolled patients exhibited early evidence of clinical benefit, including tumor reduction based on RECIST criteria and improvements across clinically meaningful patient-reported functional outcomes including reduction of pain and stiffness, improvements in quality-of-life measures, and increased range-of-motion of the affected joint. Patient tolerability data for AMB-05X was favorable with no serious adverse events (AEs) and few non-serious Grade 1 or 2 AEs. Detailed data from the study will be presented at a future scientific conference. "These interim data are very positive and align with the favorable patient responses we've observed during study visits," stated Hans Gelderblom, M.D., Ph.D., Chair of Medical Oncology at the Leiden University Medical Center in the Netherlands and Principal Investigator of the study. "Improvements in both clinical and radiologic outcomes, coupled with reduced systemic safety risks, suggest that AMB-05X could emerge as an important new therapy for this indication." "While surgery is the primary option for most patients with TGCT, the challenges associated with tumor recurrence, post-op recovery, and pain management could be better served by adding optimal pharmacologic options to the treatment mix", said Michiel van de Sande, M.D., Professor of Orthopedic Oncology, at the Leiden University Medical Center in the Netherlands. "As a locally-administered, non-surgical treatment, AMB-05X could offer an optimal balance of safety and efficacy as a meaningful treatment option." About TGCT Tenosynovial Giant Cell Tumor (TGCT), with a worldwide incidence of over 300,000, is a serious and debilitating locally aggressive tumor in which patients can experience severe pain, disability, and diminished quality of life. Surgical resection is the primary standard of care for TGCT, but carries significant risk to patients, including complications, prolonged postoperative care, infections, and frequent relapse. A safe and efficacious pharmacological therapy remains a significant unmet need. AmMax is uniquely positioned to address this need in treating TGCT by leveraging the target selectivity of AMB-05X and its enhanced safety profile, while creating a sizable commercial opportunity from improved patient care. About AMB-05X A potent monoclonal antibody against CSF1R, AMB-05X represents a therapeutic platform targeting serious macrophage-driven inflammatory, fibrotic and neovascular diseases. CSF1R, via its binding to two regulatory cytokines, CSF1 and IL-34, is critically involved in the regulation of macrophages and related cells in multiple biological processes across many organ systems, making it an attractive target with broad therapeutic applications. About AmMax Bio Inc. AmMax was founded in March 2020 to develop therapies under an exclusive worldwide license from Amgen, Inc. that leverages the diverse and critical roles played by the colony stimulating factor 1 receptor (CSF1R) signaling pathway for macrophage-driven diseases in multiple organ systems. AmMax is enrolling patients in Phase 2 clinical programs for tenosynovial giant cell tumor (TGCT) and has achieved nonclinical proof-of-concept in both neovascular age-related macular degeneration (nAMD) and idiopathic pulmonary fibrosis (IPF). For more information, please visit the company's website at www.AmMaxBio.com . Contact

News: GlobeNewswire, Market Research Reports
Site: globenewswire.com

New York, Oct. 21, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Cholesterol Lowering Drug Market Research Report by Class of Drug - Global Forecast to 2025 - Cumulative Impact of COVID-19" - https://www.reportlinker.com/p05913822/?utm_source=GNW The Global Cholesterol Lowering Drug Market is expected to grow from USD 16,298.41 Million in 2019 to USD 24,822.40 Million by the end of 2025 at a Compound Annual Growth Rate (CAGR) of 7.26%. Market Segmentation & Coverage: This research report categorizes the Cholesterol Lowering Drug to forecast the revenues and analyze the trends in each of the following sub-markets: Based on Class of Drug, the Cholesterol Lowering Drug Market studied across Cholesterol Absorption Inhibitors, Fibrates, Fixed-Dose Combinations, Ion Exchange Resins, Novel Cholesterol-Lowering Drugs, PCSK9 Inhibitors, and Statins. Based on Geography, the Cholesterol Lowering Drug Market studied across Americas, Asia-Pacific, and Europe, Middle East & Africa. The Americas region surveyed across Argentina, Brazil, Canada, Mexico, and United States. The Asia-Pacific region surveyed across Australia, China, India, Indonesia, Japan, Malaysia, Philippines, South Korea, and Thailand. The Europe, Middle East & Africa region surveyed across France, Germany, Italy, Netherlands, Qatar, Russia, Saudi Arabia, South Africa, Spain, United Arab Emirates, and United Kingdom. Company Usability Profiles: The report deeply explores the recent significant developments by the leading vendors and innovation profiles in the Global Cholesterol Lowering Drug Market including AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Kowa Company, Ltd., Merck and Co., Novartis, Pfizer, and Sanofi. FPNV Positioning Matrix: The FPNV Positioning Matrix evaluates and categorizes the vendors in the Cholesterol Lowering Drug Market on the basis of Business Strategy (Business Growth, Industry Coverage, Financial Viability, and Channel Support) and Product Satisfaction (Value for Money, Ease of Use, Product Features, and Customer Support) that aids businesses in better decision making and understanding the competitive landscape. Competitive Strategic Window: The Competitive Strategic Window analyses the competitive landscape in terms of markets, applications, and geographies. The Competitive Strategic Window helps the vendor define an alignment or fit between their capabilities and opportunities for future growth prospects. During a forecast period, it defines the optimal or favorable fit for the vendors to adopt successive merger and acquisition strategies, geography expansion, research & development, and new product introduction strategies to execute further business expansion and growth. Cumulative Impact of COVID-19: COVID-19 is an incomparable global public health emergency that has affected almost every industry, so for and, the long-term effects projected to impact the industry growth during the forecast period. Our ongoing research amplifies our research framework to ensure the inclusion of underlaying COVID-19 issues and potential paths forward. The report is delivering insights on COVID-19 considering the changes in consumer behavior and demand, purchasing patterns, re-routing of the supply chain, dynamics of current market forces, and the significant interventions of governments. The updated study provides insights, analysis, estimations, and forecast, considering the COVID-19 impact on the market. The report provides insights on the following pointers: 1. Market Penetration: Provides comprehensive information on the market offered by the key players 2. Market Development: Provides in-depth information about lucrative emerging markets and analyzes the markets 3. Market Diversification: Provides detailed information about new product launches, untapped geographies, recent developments, and investments 4. Competitive Assessment & Intelligence: Provides an exhaustive assessment of market shares, strategies, products, and manufacturing capabilities of the leading players 5. Product Development & Innovation: Provides intelligent insights on future technologies, R&D activities, and new product developments The report answers questions such as: 1. What is the market size and forecast of the Global Cholesterol Lowering Drug Market? 2. What are the inhibiting factors and impact of COVID-19 shaping the Global Cholesterol Lowering Drug Market during the forecast period? 3. Which are the products/segments/applications/areas to invest in over the forecast period in the Global Cholesterol Lowering Drug Market? 4. What is the competitive strategic window for opportunities in the Global Cholesterol Lowering Drug Market? 5. What are the technology trends and regulatory frameworks in the Global Cholesterol Lowering Drug Market? 6. What are the modes and strategic moves considered suitable for entering the Global Cholesterol Lowering Drug Market? Read the full report: https://www.reportlinker.com/p05913822/?utm_source=GNW About Reportlinker ReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place. __________________________ Clare: clare@reportlinker.com US: (339)-368-6001 Intl: +1 339-368-6001

News: GlobeNewswire, Industry News on Consumer Services
Site: globenewswire.com

New York, Oct. 14, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Colorectal Cancer Drugs Market Research Report by Class - Global Forecast to 2025 - Cumulative Impact of COVID-19" - https://www.reportlinker.com/p05913894/?utm_source=GNW 33 Million in 2019 to USD 11,484.91 Million by the end of 2025 at a Compound Annual Growth Rate (CAGR) of 3.94%. Market Segmentation & Coverage: This research report categorizes the Colorectal Cancer Drugs to forecast the revenues and analyze the trends in each of the following sub-markets: Based on Class, the Colorectal Cancer Drugs Market studied across Chemotherapy and Immunotherapy. Based on Geography, the Colorectal Cancer Drugs Market studied across Americas, Asia-Pacific, and Europe, Middle East & Africa. The Americas region surveyed across Argentina, Brazil, Canada, Mexico, and United States. The Asia-Pacific region surveyed across Australia, China, India, Indonesia, Japan, Malaysia, Philippines, South Korea, and Thailand. The Europe, Middle East & Africa region surveyed across France, Germany, Italy, Netherlands, Qatar, Russia, Saudi Arabia, South Africa, Spain, United Arab Emirates, and United Kingdom. Company Usability Profiles: The report deeply explores the recent significant developments by the leading vendors and innovation profiles in the Global Colorectal Cancer Drugs Market including AbbVie Inc., Amgen, Astellas Pharma Inc., Bayer, Bristol-Myers Squibb, Eli Lilly, Merck & Co., Inc., Novartis AG, Pfizer Inc., Roche, and Sanofi. FPNV Positioning Matrix: The FPNV Positioning Matrix evaluates and categorizes the vendors in the Colorectal Cancer Drugs Market on the basis of Business Strategy (Business Growth, Industry Coverage, Financial Viability, and Channel Support) and Product Satisfaction (Value for Money, Ease of Use, Product Features, and Customer Support) that aids businesses in better decision making and understanding the competitive landscape. Competitive Strategic Window: The Competitive Strategic Window analyses the competitive landscape in terms of markets, applications, and geographies. The Competitive Strategic Window helps the vendor define an alignment or fit between their capabilities and opportunities for future growth prospects. During a forecast period, it defines the optimal or favorable fit for the vendors to adopt successive merger and acquisition strategies, geography expansion, research & development, and new product introduction strategies to execute further business expansion and growth. Cumulative Impact of COVID-19: COVID-19 is an incomparable global public health emergency that has affected almost every industry, so for and, the long-term effects projected to impact the industry growth during the forecast period. Our ongoing research amplifies our research framework to ensure the inclusion of underlaying COVID-19 issues and potential paths forward. The report is delivering insights on COVID-19 considering the changes in consumer behavior and demand, purchasing patterns, re-routing of the supply chain, dynamics of current market forces, and the significant interventions of governments. The updated study provides insights, analysis, estimations, and forecast, considering the COVID-19 impact on the market. The report provides insights on the following pointers: 1. Market Penetration: Provides comprehensive information on the market offered by the key players 2. Market Development: Provides in-depth information about lucrative emerging markets and analyzes the markets 3. Market Diversification: Provides detailed information about new product launches, untapped geographies, recent developments, and investments 4. Competitive Assessment & Intelligence: Provides an exhaustive assessment of market shares, strategies, products, and manufacturing capabilities of the leading players 5. Product Development & Innovation: Provides intelligent insights on future technologies, R&D activities, and new product developments The report answers questions such as: 1. What is the market size and forecast of the Global Colorectal Cancer Drugs Market? 2. What are the inhibiting factors and impact of COVID-19 shaping the Global Colorectal Cancer Drugs Market during the forecast period? 3. Which are the products/segments/applications/areas to invest in over the forecast period in the Global Colorectal Cancer Drugs Market? 4. What is the competitive strategic window for opportunities in the Global Colorectal Cancer Drugs Market? 5. What are the technology trends and regulatory frameworks in the Global Colorectal Cancer Drugs Market? 6. What are the modes and strategic moves considered suitable for entering the Global Colorectal Cancer Drugs Market? Read the full report: https://www.reportlinker.com/p05913894/?utm_source=GNW About Reportlinker ReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place. __________________________ Clare: clare@reportlinker.com US: (339)-368-6001 Intl: +1 339-368-6001

News: Industry Today
Site: industrytoday.co.uk

Published Fri, Oct 1st 2021 The Global Rheumatoid Arthritis Drugs Market is expected to gain market growth in the forecast period of 2020 to 2027. Posted via Industry Today. Follow us on Twitter @IndustryToday Global Rheumatoid Arthritis Drugs Market Synopsis: According to the world class Rheumatoid Arthritis Drugs Market report, the leading players are focusing more on offering products at rational prices to gain a competitive advantage over the other players in the Healthcare industry. The main objective of this exploratory study is to provide a clear picture and a better understanding of the Market to the suppliers, manufacturers, and distributors. With an excellent Rheumatoid Arthritis Drugs Market report businesses can create a unique space in the global industry and get identified as the most consistent and dedicated growth partner for Market research, strategy formulation and sustainable development of organization. The readers can gain deep insights into this Market that can enable them to formulate and develop critical strategies for the further expansion of their businesses. The wide ranging Rheumatoid Arthritis Drugs Market report helps the firm in exploring new uses and new Markets for its existing products and thereby increasing the demand for its products. Under the Market forecasts section, the report offers accurate Market by Market opportunities for the Healthcare industry, its segments and sub-segments, product type, application and characteristics and all regions considered for the study. The first class Rheumatoid Arthritis Drugs business report offers sustainable forward looking growth programs to ensure success which is imperative for organizations. Get Sample Report + All Related Graphs & Charts @ https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-rheumatoid-arthritis-drugs-market . According to the market report analysis, Rheumatoid Arthritis is a chronic inflammatory disorder that can affect many body joints. In sever cases rheumatoid arthritis can damage various body part such as skin, lungs, heart, eyes and blood vessels. It is an auto-immune disorder and affects lining of the joints which causes painful swelling and causes joint deformity. Some of most important key factors driving the growth of the Global Rheumatoid Arthritis Drugs Market are rising prevalence of joint disorders worldwide and emerging markets, growing cases of arthritis and other joint disorders, increased acceptance of biopharmaceuticals, surge in geriatric population especially males, and continuous advancement in technology for the diagnosis & treatment. Global Rheumatoid Arthritis Drugs Market Segmentation: Based on the Drugs, the rheumatoid arthritis drugs market is segmented into nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, disease-modifying antirheumatic drugs (DMARDs), janus kinase (JAK) inhibitors, biologic agents, others. Based on the Route of Administration, the rheumatoid arthritis drugs market is segmented into oral, parenteral, topical, others. Based on the End-Users, the rheumatoid arthritis drugs market is segmented into hospitals, specialty clinics, others Regional analysis, North America accounts the largest market share due to increased prevalence of rheumatoid arthritis, and technological advancements in early diagnosis of the disease. Europe is considered second largest market for rheumatoid arthritis drugs due to increase obesity and metabolic diseases & other joint related disorders in the region. APAC is expected to account for the largest market share over coming years for the rheumatoid arthritis drugs market. Access Complete Report @ https://www.databridgemarketresearch.com/reports/global-rheumatoid-arthritis-drugs-market . Global Key Players: Pfizer Inc Fresenius Kabi USA Vintage Labs Abbvie Inc. Novartis AG Amgen Inc Boehringer Ingelheim International GmbH Samsung Bioepis. Merck & Co Inc. Sun Pharmaceutical Industries Ltd. Teva Pharmaceuticals Industries Ltd. Casper Pharma GlaxoSmithKline Plc Johnsons & Johnsons Services Limited Report contents include 1 Analysis of the Rheumatoid Arthritis Drugs Market including revenues, future growth, market outlook 2 Historical data and forecast 3 Regional analysis including growth estimates 4 Analyses the end user markets including growth estimates 5 Profiles on Rheumatoid Arthritis Drugs including products, sales/revenues, and market position 6 Rheumatoid Arthritis Drugs Market structure, market drivers and restraints Get a TOC of "Global Rheumatoid Arthritis Drugs Market Report 2021" @ https://www.databridgemarketresearch.com/toc/?dbmr=global-rheumatoid-arthritis-drugs-market . Global Rheumatoid Arthritis Drugs Market: Table of Contents 1 Report Overview 2021-2027 2 Global Growth Trends 2021-2027 3 Competition Landscape by Key Players 4 Global Rheumatoid Arthritis Drugs Market Analysis by Regions 5 Global Rheumatoid Arthritis Drugs Market Analysis by Type 6 Global Rheumatoid Arthritis Drugs Market Analysis by Applications 7 Global Rheumatoid Arthritis Drugs Market Analysis by End-User 8 Key Companies Profiled 9 Global Rheumatoid Arthritis Drugs Market Manufacturers Cost Analysis 10 Marketing Channel, Distributors, and Customers 11 Market Dynamics 12 Global Rheumatoid Arthritis Drugs Market Forecasts 2021-2027 13 Research Findings and Conclusion 14 Methodology and Data Source About Data Bridge Market Research: Data Bridge set forth itself as an unconventional and neoteric Market research and consulting firm with unparalleled level of resilience and integrated approaches. We are determined to unearth the best market opportunities and foster efficient information for your business to thrive in the market. Data Bridge endeavors to provide appropriate solutions to the complex business challenges and initiates an effortless decision-making process. Contact us: Data Bridge Market Research US: +1 888 387 2818 UK: +44 208 089 1725 Hong Kong: +852 8192 7475 Email: Corporatesales@databridgemarketresearch.com

News: PR Newswire, Health
Site: www.prnewswire.com

DUBLIN, Oct. 30, 2018 /PRNewswire/ -- The "Migraine Drugs Market Analysis Report By Therapeutic Class (Triptans, CGRP-based Therapies, Ditans, Neurotoxins, NSAIDs), By Treatment, By Route of Administration, And Segment Forecasts, 2018 - 2025" report has been added to ResearchAndMarkets.com's offering. The global migraine drugs market size is expected to be valued at USD 7.7 billion by 2025, exhibiting an 18% CAGR during the forecast period. The market is largely driven by factors such as rise in disease prevalence, development of novel therapies, lifestyle changes, and hormonal medications. Over the past five years, the global migraine drugs market has been relatively stagnant, with the market mainly dominated by usage of generic triptans and other off-label drugs. Majority of the currently prescribed drugs for both acute and preventative treatment are associated with poor efficacy and an unfavorable side-effect profile. Launch of Amgen/Novartis' CGRP mAb Aimovig is the first step toward revolutionizing the treatment paradigm of migraine prevention. For drug manufacturers likely to enter the market by 2019, such as Eli Lilly, Teva Pharma, and Alder BioPharma, pricing will be a key differentiating factor as all CGRP-based therapies have a similar efficacy and safety profile. Key Findings Germany leads the European market, driven by rising disease prevalence, novel drug launches, and increase in R&D activities leads the European market, driven by rising disease prevalence, novel drug launches, and increase in R&D activities The acute migraine treatment market will be supported by rapid uptake of novel drug classes such as CGRP receptor antagonists and ditans currently under active investigation in multiple Phase II/III trials Biohaven's rimegepant is expected to face competition from Allergan's ubrogepant, which has shown superior efficacy in Phase III trials compared to rimegepant Eli Lilly's Phase III 5-HT1F receptor agonist Lasmiditan is expected to be a novel first-line non triptan acute treatment option for patients in whom triptans are contradicted Approximately 20% of patients seeking preventive treatment for migraine do not respond to available generic medications. Several biologics and small molecules drugs are undergoing active development to target high unmet needs in the preventive treatment segment Drugs with novel targets in early-phase development include AOBiome Therapeutics' AOB-203 (antibacterial), Winston Pharma's Dolorac (histamine H1 receptor antagonists), NeuroAxons' NXN-188 (combination of NOS inhibitor and a triptan), and Biohaven's BHV-3500 (gepant). These novel agents are under evaluation for both episodic and chronic migraine in multiple Phase I/II trials Key Topics Covered Chapter 1 Report Scope 1.1 Treatment Scope 1.2 Therapeutic Class Scope 1.3 Mode of Administration Scope 1.4 Country Scope 1.5 Estimates and Forecast Timeline Chapter 2 Methodology 2.1 Research Methodology 2.2 Information or Data Analysis 2.3 Market Formulation & Validation 2.4 List of Sources 2.5 List of Abbreviations Chapter 3 Executive Summary Chapter 4 Disease Primer and Epidemiology 4.1 Disease Primer 4.2 Epidemiology Chapter 5 Global Migraine Market Overview 5.1 Introduction and Market Overview 5.2 Market, by Treatment 5.3 Market, by Therapeutic Class 5.4 Market Size and Forecast by Country (2017 - 2025) 5.5 Market Share Distribution, by Company (2017 - 2025) 5.6 Market Dynamics and Brand Strategies 5.7 Patent Expiry Schedule 5.8 Migraine Drugs Market: Drivers and Restraints 5.9 M&A, Deal Landscape (2014 - 2018 YTD) 5.10 Emerging Markets 5.11 Pricing & Reimbursement 5.12 SWOT Chapter 6 Migraine Drugs Market: Pipeline Intelligence 6.1 Pipeline Landscape 6.2 Key R&D Trends 6.3 Pipeline Landscape 6.4 Clinical Profiles of Disruptive Drugs Chapter 7 Company Profiles 7.1 Allergan 7.2 Amgen 7.3 Pfizer 7.4 GlaxoSmithKline 7.5 Eli Lilly 7.6 Teva Pharma Chapter 8 Market Outlook 8.1 Winners and Losers 8.2 Emerging Companies/New Technology Platforms 8.3 What the Future Holds For more information about this report visit https://www.researchandmarkets.com/research/5gcnjg/worldwide?w=5 Media Contact: Research and Markets Laura Wood, Senior Manager press@researchandmarkets.com For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 SOURCE Research and Markets Related Links http://www.researchandmarkets.com

News: GlobeNewswire, News from Georgia
Site: globenewswire.com

BOGART, Ga., Oct. 05, 2021 (GLOBE NEWSWIRE) -- Lanier Biotherapeutics Inc., ("Lanier" or the "Company"), a developer of first-in-class antibodies targeting retina, dermatology, and Type 2 Inflammatory specialty diseases, today announced that it has entered into a license agreement (the "Agreement") with Alloy Therapeutics ("Alloy"), a privately held drug discovery company. Alloy will acquire the AbeoMouse™ and Direct Selection of Hybridomas (DiSH™) antibody discovery technologies, which were originally developed by Abeome Corporation, Inc. ("Abeome"), one of Lanier's two predecessor companies. Upon closing of the Agreement, Alloy will license to Lanier certain rights to AbeoMouse™ and Alloy's ATX-Gx™ platform of proprietary transgenic mouse strains. "We are pleased to enter into this mutually beneficial Agreement, which provides both companies with access to enabling antibody discovery technologies while augmenting our development pipeline and further strengthening our balance sheet," said Kirby Alton, Lanier's Chairman. Lanier was recently formed by combining the businesses of Abeome and Biophtha Inc., with bridge funding from investors, including founders Kirby Alton, PhD, former Senior Vice President of Development at Amgen; and Daniel White, MBA, former CEO of Clearside Biomedical. Messrs. Alton and White are joined by Lanier's other two founders, Martin Simonetti, MS, MBA and Chris McLeod, MS, to form Lanier's experienced leadership team: President, CEO & Director, Daniel White, is an accomplished entrepreneur and visionary in the biotech and pharmaceutical space. As the founder and CEO of Clearside Biomedical, he led the company from early private financing through its initial public offering and brings a wealth of biomedical development and successful fundraising experience. Chairman, Kirby Alton, reprises his role of Chairman of Abeome, and brings deep product development expertise gained as one of Amgen's original scientists. Director, Martin Simonetti, has significant Amgen and Genentech experience; an immense track record of leadership and growth across several biotechnology enterprises; and has led successful financings in both private and capital markets. Director, Chris McLeod, is an experienced biotechnology executive with vast expertise in growth companies and strategic collaborations. He is a former Executive Vice President of CuraGen and President of 454 Life Sciences; and is the current managing partner of Elm Street Ventures. Lanier is developing a portfolio of 11 first-in-class therapeutic antibodies for specialty disease across four major verticals: Multi-functional Retina, Type 2 Inflammation, Dermatology, and ImmunoOncology. "With a robust portfolio of 11 first-in-class, proprietary therapeutic antibodies, we are eager to progress toward the clinic with our two lead candidates: one targeting retinal disease using our multifunction anti VEGF inhibitor and the second using the most advanced and proprietary anti IL25 to treat Type 2 Inflammatory diseases," said Daniel White, President and CEO of Lanier. "Lanier has initiated a fund raise to launch these two programs that hold promise for improving treatment to provide a better life for patients." Multi-functional Retina Lanier's LNR 653.1 is a proprietary bifunctional antibody being developed for the treatment of retinal neovascularization diseases (wet age-related macular degeneration, diabetic macular edema and retinal vein occlusion. LNR 653.1 is designed to combine the anti-vascular endothelial growth factor (VEGF) effect of aflibercept (marketed as Eylea by Regeneron) with the anti-inflammatory and anti-apoptotic effects similar to that of secukinumab (marketed as Cosentyx by Novartis). Preclinical data suggest that LNR 653.1 is safe, with efficacy similar or superior to aflibercept. Lanier is currently conducting pre-formulation experiments and non-clinical functional testing, with plans to initiate investigational new drug ("IND")-enabling studies of LNR 653.1 in 2022. Type 2 Inflammation LNR 125.38 is a monoclonal antibody that inhibits the upstream cytokine IL-25. By reducing, or even eliminating the effects of downstream allergic and antiviral cytokines, LNR 125.38 targets Type 2 Inflammation, which is implicated in different atopic, allergic and inflammatory diseases. Lanier is prioritizing the development of LNR 125.38 across a broad range of potential treatments of moderate to severe asthma that is classified as either high or low eosinophil challenge by allergy or rhinovirus; chronic sinusitis with nasal polyps; and eosinophil esophagitis and gastritis. Preclinical data have demonstrated that LNR 125.38 significantly reduces Type 2 (downstream) cytokines and inflammatory cells in allergic mouse and rhinovirus-induced asthma exacerbations. Lanier is currently conducting pre-formulation experiments and non-clinical functional testing, with plans to initiate IND-enabling studies of LNR 125.38 in the second half of 2022. Dermatology Lanier is developing LNR 653.1 for the treatment of psoriasis, where functional testing has demonstrated potency and efficacy comparable to secukinumab and ixekizumab (marketed as Taltz by Eli Lilly). The Company is also developing LNR 125.38 for the treatment of chronic urticaria and atopic dermatitis. ImmunoOncology MT-6402 is an engineered toxin body manufactured by Molecular Templates, Inc., which contains a PDL-1 inhibitor previously licensed by it from Lanier's extensive library of proprietary checkpoint inhibitors. In July, Molecular Templates dosed the first subject in a Phase 1 study evaluating MT-6402 in patients with PD-L1-positive solid tumors and expects to provide an update on the study by the end of this year. About Alloy Therapeutics Alloy Therapeutics is a biotechnology ecosystem company empowering the global scientific community to make better medicines together. Through a community of partners, Alloy democratizes access to tools, technologies, services, and company creation capabilities that are foundational for discovering and developing therapeutic biologics. The company facilitates affordable, non-exclusive access to the entire drug discovery community from academic scientists, small and medium biotech, to the largest biopharma. Alloy's lead offering, the ATX-Gx™ platform, is a human therapeutic antibody discovery platform consisting of a growing suite of proprietary transgenic mice strains. Founded in 2017 and privately funded by visionary investors, Alloy is headquartered in Boston, MA with European labs in Cambridge, UK. As a reflection of Alloy's relentless commitment to the scientific community, Alloy reinvests 100% of its revenue in innovation and access to innovation. About AbeoMouse™ AbeoMouse™ is a novel transgenic antibody discovery platform that generates mature B-cells with high surface immunoglobulin (Ig) expression, allowing for the direct selection and cloning of antigen-specific B-cells. AbeoMouse™ over-expresses immunoglobulin co-receptors alpha (Ig- / CD79a), beta (Ig- / CD79b) and interleukin 6 (IL6) genes, such that immunized animals produce a 45-fold increase in surface Ig positive antibody secreting cells and an accelerated immune response. About DiSH™ DiSH™ technology enables the rapid selection and cloning of antigen-specific hybridomas. Using fluorescence activated cell sorting (FACS) or magnetic separation, desired hybridomas can be labelled and subsequently isolated from among a pool of hundreds of thousands of cells, in a matter of hours. About Lanier Biotherapeutics Lanier Biotherapeutics was founded by combining the businesses of Biophtha and Abeome, to further develop an existing first-in-class biologics portfolio for specialty disease, with the ultimate goal of improving the way we survive, age, and live. Lanier targets four major verticals: Multi-functional Retina, Type 2 Inflammation, Dermatology, and ImmunoOncology. Lanier's lead developments programs include LNR 653.1, a fully humanized anti-VEGF / IL-17A multifunctional antibody for the treatment of retinal neovascularization diseases and LNR 125.36, a fully humanized anti-IL-25 monoclonal antibody for the treatment of Type 2 Inflammatory diseases. For more information, please visit www.lanierbio.com. Contact: Stephen Kilmer Lanier Biotherapeutics Inc. Investor & Public Relations (646) 274-3580 stephen@kilmerlucas.com

News: PR Newswire
Site: www.prnewswire.com

BOSTON, Oct. 16, 2019 /PRNewswire/ -- Below is the September 2019 Monthly Update for the Liberty All-Star Equity Fund. (NYSE: USA) Liberty All-Star Equity Fund Ticker: USA Monthly Update, September, 2019 Investment Approach: Fund Style: Large-Cap Core Fund Strategy: Combines three value-style and two growth-style investment managers. Those selected demonstrate a consistent investment philosophy, decision making process, continuity of key people and above-average long-term results compared to managers with similar styles. Investment Managers: Value Managers: Aristotle Capital Management, LLC Macquarie Investment Management Pzena Investment Management, LLC Growth Managers: Sustainable Growth Advisers, LP TCW Investment Management Company Top 20 Holdings at Month-End (31.0% of equity portfolio) 1 PayPal Holdings, Inc. 2.2% 2 Visa, Inc. 2.1% 3 Adobe, Inc. 2.0% 4 Amazon.com, Inc. 2.0% 5 Alphabet, Inc. 2.0% 6 Microsoft Corp. 1.9% 7 salesforce.com, Inc. 1.6% 8 Facebook, Inc. 1.5% 9 Halliburton Co. 1.5% 10 American International Group, Inc. 1.5% 11 Mondelez International, Inc. 1.5% 12 Abbott Laboratories 1.5% 13 Danaher Corp. 1.4% 14 Equinix, Inc. 1.4% 15 Bank of America Corp. 1.3% 16 Capital One Financial Corp. 1.3% 17 Home Depot, Inc. 1.2% 18 American Tower Corp. 1.1% 19 Lowe's Cos., Inc. 1.0% 20 Amgen, Inc. 1.0% Holdings are subject to change. Monthly Performance: Performance NAV Market Price Discount Beginning of month value $6.40 $6.13 -4.2% End of month value $6.51 $6.40 -1.7% Performance for month 1.72% 4.40% Performance year-to-date 19.64% 28.77% Net Assets at Month-End ($millions) Total $1,347.1 Equities $1,318.3 Percent Invested 97.9% Sector Breakdown (% of equity portfolio)* Information Technology 20.9% Financials 17.0% Health Care 14.9% Consumer Discretionary 12.6% Industrials 8.7% Energy 6.3% Communication Services 6.1% Consumer Staples 6.0% Real Estate 3.8% Materials 2.7% Utilities 1.0% Total Market Value 100.0% *Based on Standard & Poor's and MSCI Barra Global Industry Classification Standard (GICS). New Holdings Trade Desk, Inc. Workday, Inc., Class A Holdings Liquidated National Fuel Gas Co. Walt Disney Co. The net asset value (NAV) of a closed-end fund is the market value of the underlying investments (i.e., stocks and bonds) in the Fund's portfolio, minus liabilities, divided by the total number of Fund shares outstanding. However, the Fund also has a market price; the value at which it trades on an exchange. If the market price is above the NAV the Fund is trading at a premium. If the market price is below the NAV the Fund is trading at a discount. Performance returns for the Fund are total returns, which includes dividends, and are net of management fees and other Fund expenses. Returns are calculated assuming that a shareholder reinvested all distributions. Past performance cannot predict future investment results. Performance will fluctuate with changes in market conditions. Current performance may be lower or higher than the performance data shown. Performance information shown does not reflect the deduction of taxes that shareholders would pay on Fund distributions or the sale of Fund shares. Shareholders must be willing to tolerate significant fluctuations in the value of their investment. An investment in the Fund involves risk, including loss of principal. All data is as of September 30, 2019 unless otherwise noted. Liberty All-Star® Equity Fund www.all-starfunds.com SOURCE Liberty All-Star Equity Fund

News: GlobeNewswire, Industry News on Industrials
Site: globenewswire.com

Dublin, Oct. 22, 2021 (GLOBE NEWSWIRE) -- The "Asthma Therapeutics Market: Global Industry Trends, Share, Size, Growth, Opportunity and Forecast 2021-2026" report has been added to ResearchAndMarkets.com's offering. The global asthma therapeutics market reached a value of US$ 17.6 Billion in 2020. Looking forward, the market is expected to reach a value of US$ 19.13 Billion by 2026, expanding at a CAGR of 1.60% during 2021-2026. Keeping in mind the uncertainties of COVID-19, the analyst is continuously tracking and evaluating the direct as well as the indirect influence of the pandemic. These insights are included in the report as a major market contributor. Asthma therapeutics refer to various pharmaceutical drugs that are used for the treatment of asthma. Asthma is usually triggered by indoor and outdoor causative agents, including pollution, allergens and dust. These therapeutics are usually bronchodilators and anti-inflammatory drugs, which include corticosteroids, long-acting beta-agonists (LABA), methylxanthine, immunomodulators and leukotriene modifiers. A number of combination therapy drugs are also used that can be inhaled, injected, or orally administered. These drugs expand the passageway into the lungs and enable the movement of air to improve breathing. They also aid in clearing mucus from the lungs that gets coughed out with ease. Global Asthma Therapeutics Market Trends and Drivers The increasing prevalence of asthma and other respiratory disorders, along with improvements in the diagnostic technologies, is one of the key factors driving the growth of the market. Furthermore, rising awareness among the masses regarding the availability of effective asthma therapeutics is also providing driving the market growth. For instance, asthmatic patients are primarily treated with inhaled corticosteroids and patients with advanced conditions or persistent asthma are treated with target-specific drugs. There is also an extensive demand for monoclonal antibodies (mAbs) that block immunoglobulin E and specific cytokines. The development of combination therapies for the treatment of respiratory diseases is acting as another growth-inducing factor. Increasing healthcare expenditures, extensive research, and development (R&D) activities in the field of medical sciences and improvements in the healthcare infrastructure are some of the other factors that are expected to drive the market further. Key Market Segmentation The analyst provides an analysis of the key trends in each sub-segment of the global asthma therapeutics market, along with forecasts at the global, regional and country level from 2021-2026. The report has categorized the market based on drug class, product type, treatment type, route of administration and region. Breakup by Drug Class Anti-Inflammatory Drugs Bronchodilators Combination Therapies Breakup by Product Type Inhalers Dry Powder Inhalers Metered Dose Inhalers Soft Mist Inhalers Nebulizers Pneumatic Nebulizers Ultrasonic Nebulizers Mesh Nebulizers Breakup by Treatment Type Quick-Relief Medications Long-Term Asthma Control Medications Breakup by Route of Administration Inhalation Oral Parenteral Breakup by Region North America United States Canada Asia Pacific China Japan India South Korea Australia Indonesia Others Europe Germany France United Kingdom Italy Spain Russia Others Latin America Brazil Mexico Others Middle East and Africa Competitive Landscape The report has also analysed the competitive landscape of the market with some of the key players being AstraZeneca, Abbott, Amgen Inc., Biogen Inc., Boehringer Ingelheim GmbH, F. Hoffmann-La Roche AG, GlaxoSmithKline plc., Merck & Co. Inc., Novartis AG, Sunovion Pharmaceuticals Inc. (Dainippon Sumitomo Pharma Co. Ltd.) and Teva Pharmaceutical Industries Ltd. Key Topics Covered: 1 Preface 2 Scope and Methodology 3 Executive Summary 4 Introduction 4.1 Overview 4.2 Key Industry Trends 5 Global Asthma Therapeutics Market 5.1 Market Overview 5.2 Market Performance 5.3 Impact of COVID-19 5.4 Market Forecast 6 Market Breakup by Drug Class 6.1 Anti-Inflammatory Drugs 6.1.1 Market Trends 6.1.2 Market Forecast 6.2 Bronchodilators 6.2.1 Market Trends 6.2.2 Market Forecast 6.3 Combination Therapies 6.3.1 Market Trends 6.3.2 Market Forecast 7 Market Breakup by Product Type 7.1 Inhalers 7.1.1 Market Trends 7.1.2 Major Types 7.1.2.1 Dry Powder Inhalers 7.1.2.2 Metered Dose Inhalers 7.1.2.3 Soft Mist Inhalers 7.1.3 Market Forecast 7.2 Nebulizers 7.2.1 Market Trends 7.2.2 Major Types 7.2.2.1 Pneumatic Nebulizers 7.2.2.2 Ultrasonic Nebulizers 7.2.2.3 Mesh Nebulizers 7.2.3 Market Forecast 8 Market Breakup by Treatment Type 8.1 Quick-Relief Medications 8.1.1 Market Trends 8.1.2 Market Forecast 8.2 Long-Term Asthma Control Medications 8.2.1 Market Trends 8.2.2 Market Forecast 9 Market Breakup by Route of Administration 9.1 Inhalation 9.1.1 Market Trends 9.1.2 Market Forecast 9.2 Oral 9.2.1 Market Trends 9.2.2 Market Forecast 9.3 Parenteral 9.3.1 Market Trends 9.3.2 Market Forecast 10 Market Breakup by Region 11 SWOT Analysis 12 Value Chain Analysis 13 Porters Five Forces Analysis 14 Price Analysis 15 Competitive Landscape 15.1 Market Structure 15.2 Key Players 15.3 Profiles of Key Players 15.3.1 AstraZeneca 15.3.1.1 Company Overview 15.3.1.2 Product Portfolio 15.3.1.3 Financials 15.3.1.4 SWOT Analysis 15.3.2 Abbott 15.3.2.1 Company Overview 15.3.2.2 Product Portfolio 15.3.2.3 Financials 15.3.2.4 SWOT Analysis 15.3.3 Amgen Inc. 15.3.3.1 Company Overview 15.3.3.2 Product Portfolio 15.3.3.3 Financials 15.3.3.4 SWOT Analysis 15.3.4 Biogen Inc. 15.3.4.1 Company Overview 15.3.4.2 Product Portfolio 15.3.4.3 Financials 15.3.4.4 SWOT Analysis 15.3.5 Boehringer Ingelheim GmbH 15.3.5.1 Company Overview 15.3.5.2 Product Portfolio 15.3.6 F. Hoffmann-La Roche AG 15.3.6.1 Company Overview 15.3.6.2 Product Portfolio 15.3.6.3 SWOT Analysis 15.3.7 GlaxoSmithKline PLC. 15.3.7.1 Company Overview 15.3.7.2 Product Portfolio 15.3.7.3 Financials 15.3.7.4 SWOT Analysis 15.3.8 Merck & Co. Inc. 15.3.8.1 Company Overview 15.3.8.2 Product Portfolio 15.3.8.3 Financials 15.3.8.4 SWOT Analysis 15.3.9 Novartis AG 15.3.9.1 Company Overview 15.3.9.2 Product Portfolio 15.3.9.3 Financials 15.3.9.4 SWOT Analysis 15.3.10 Sunovion Pharmaceuticals Inc. (Dainippon Sumitomo Pharma Co. Ltd.) 15.3.10.1 Company Overview 15.3.10.2 Product Portfolio 15.3.10.3 SWOT Analysis 15.3.11 Teva Pharmaceutical Industries Ltd. 15.3.11.1 Company Overview 15.3.11.2 Product Portfolio 15.3.11.3 Financials 15.3.11.4 SWOT Analysis For more information about this report visit https://www.researchandmarkets.com/r/9xahsc

News: GlobeNewswire, Industry News on Consumer Services
Site: globenewswire.com

New York, Oct. 14, 2019 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Global Migraine Drugs Industry" - https://www.reportlinker.com/p05817938/?utm_source=GNW 6%. The shifting dynamics supporting this growth makes it critical for businesses in this space to keep abreast of the changing pulse of the market. Poised to reach over US$4.8 Billion by the year 2025, Acute Treatment will bring in healthy gains adding significant momentum to global growth. - Representing the developed world, the United States will maintain a 16% growth momentum. Within Europe, which continues to remain an important element in the world economy, Germany will add over US$162.6 Million to the region's size and clout in the next 5 to 6 years. Over US$135.5 Million worth of projected demand in the region will come from Rest of Europe markets. In Japan, Acute Treatment will reach a market size of US$237.4 Million by the close of the analysis period. As the world's second largest economy and the new game changer in global markets, China exhibits the potential to grow at 23% over the next couple of years and add approximately US$1.1 Billion in terms of addressable opportunity for the picking by aspiring businesses and their astute leaders. Presented in visually rich graphics are these and many more need-to-know quantitative data important in ensuring quality of strategy decisions, be it entry into new markets or allocation of resources within a portfolio. Several macroeconomic factors and internal market forces will shape growth and development of demand patterns in emerging countries in Asia-Pacific, Latin America and the Middle East. All research viewpoints presented are based on validated engagements from influencers in the market, whose opinions supersede all other research methodologies. - Competitors identified in this market include among others, Allergan PLC; Amgen, Inc.; Biohaven Pharmaceutical Holding Company Ltd.; Eli Lilly and Company; GlaxoSmithKline PLC; Johnson & Johnson; Pfizer, Inc.; Teva Pharmaceutical Industries Ltd. Read the full report: https://www.reportlinker.com/p05817938/?utm_source=GNW I. INTRODUCTION, METHODOLOGY & REPORT SCOPE II. EXECUTIVE SUMMARY 1. MARKET OVERVIEW Global Competitor Market Shares Migraine Drugs Competitor Market Share Scenario Worldwide (in %): 2019 & 2028 2. FOCUS ON SELECT PLAYERS 3. MARKET TRENDS & DRIVERS 4. GLOBAL MARKET PERSPECTIVE Table 1: Migraine Drugs Global Market Estimates and Forecasts in US$ Thousand by Region/Country: 2018-2025 Table 2: Migraine Drugs Global Retrospective Market Scenario in US$ Thousand by Region/Country: 2009-2017 Table 3: Migraine Drugs Market Share Shift across Key Geographies Worldwide: 2009 VS 2019 VS 2025 Table 4: Acute Treatment (Treatment) World Market by Region/Country in US$ Thousand: 2018 to 2025 Table 5: Acute Treatment (Treatment) Historic Market Analysis by Region/Country in US$ Thousand: 2009 to 2017 Table 6: Acute Treatment (Treatment) Market Share Breakdown of Worldwide Sales by Region/Country: 2009 VS 2019 VS 2025 Table 7: Preventive Treatment (Treatment) Potential Growth Markets Worldwide in US$ Thousand: 2018 to 2025 Table 8: Preventive Treatment (Treatment) Historic Market Perspective by Region/Country in US$ Thousand: 2009 to 2017 Table 9: Preventive Treatment (Treatment) Market Sales Breakdown by Region/Country in Percentage: 2009 VS 2019 VS 2025 Table 10: Triptans (Therapeutic Class) Geographic Market Spread Worldwide in US$ Thousand: 2018 to 2025 Table 11: Triptans (Therapeutic Class) Region Wise Breakdown of Global Historic Demand in US$ Thousand: 2009 to 2017 Table 12: Triptans (Therapeutic Class) Market Share Distribution in Percentage by Region/Country: 2009 VS 2019 VS 2025 Table 13: Acetylcholine Inhibitors/Neurotoxins (Therapeutic Class) World Market Estimates and Forecasts by Region/Country in US$ Thousand: 2018 to 2025 Table 14: Acetylcholine Inhibitors/Neurotoxins (Therapeutic Class) Market Historic Review by Region/Country in US$ Thousand: 2009 to 2017 Table 15: Acetylcholine Inhibitors/Neurotoxins (Therapeutic Class) Market Share Breakdown by Region/Country: 2009 VS 2019 VS 2025 Table 16: Ergot Alkaloids (Therapeutic Class) World Market by Region/Country in US$ Thousand: 2018 to 2025 Table 17: Ergot Alkaloids (Therapeutic Class) Historic Market Analysis by Region/Country in US$ Thousand: 2009 to 2017 Table 18: Ergot Alkaloids (Therapeutic Class) Market Share Distribution in Percentage by Region/Country: 2009 VS 2019 VS 2025 Table 19: NSAIDs (Therapeutic Class) World Market Estimates and Forecasts in US$ Thousand by Region/Country: 2018 to 2025 Table 20: NSAIDs (Therapeutic Class) Market Worldwide Historic Review by Region/Country in US$ Thousand: 2009 to 2017 Table 21: NSAIDs (Therapeutic Class) Market Percentage Share Distribution by Region/Country: 2009 VS 2019 VS 2025 Table 22: Other Therapeutic Classes (Therapeutic Class) Market Opportunity Analysis Worldwide in US$ Thousand by Region/Country: 2018 to 2025 Table 23: Other Therapeutic Classes (Therapeutic Class) Global Historic Demand in US$ Thousand by Region/Country: 2009 to 2017 Table 24: Other Therapeutic Classes (Therapeutic Class) Market Share Distribution in Percentage by Region/Country: 2009 VS 2019 VS 2025 Table 25: Oral (Route of Administration) World Market by Region/Country in US$ Thousand: 2018 to 2025 Table 26: Oral (Route of Administration) Historic Market Analysis by Region/Country in US$ Thousand: 2009 to 2017 Table 27: Oral (Route of Administration) Market Share Breakdown of Worldwide Sales by Region/Country: 2009 VS 2019 VS 2025 Table 28: Injectables (Route of Administration) Potential Growth Markets Worldwide in US$ Thousand: 2018 to 2025 Table 29: Injectables (Route of Administration) Historic Market Perspective by Region/Country in US$ Thousand: 2009 to 2017 Table 30: Injectables (Route of Administration) Market Sales Breakdown by Region/Country in Percentage: 2009 VS 2019 VS 2025 Table 31: Other Route of Administrations (Route of Administration) Geographic Market Spread Worldwide in US$ Thousand: 2018 to 2025 Table 32: Other Route of Administrations (Route of Administration) Region Wise Breakdown of Global Historic Demand in US$ Thousand: 2009 to 2017 Table 33: Other Route of Administrations (Route of Administration) Market Share Distribution in Percentage by Region/Country: 2009 VS 2019 VS 2025 III. MARKET ANALYSIS GEOGRAPHIC MARKET ANALYSIS UNITED STATES Market Facts & Figures US Migraine Drugs Market Share (in %) by Company: 2019 & 2025 Table 34: United States Migraine Drugs Market Estimates and Projections in US$ Thousand by Treatment: 2018 to 2025 Table 35: Migraine Drugs Market in the United States by Treatment: A Historic Review in US$ Thousand for 2009-2017 Table 36: United States Migraine Drugs Market Share Breakdown by Treatment: 2009 VS 2019 VS 2025 Table 37: United States Migraine Drugs Market Estimates and Projections in US$ Thousand by Therapeutic Class: 2018 to 2025 Table 38: Migraine Drugs Market in the United States by Therapeutic Class: A Historic Review in US$ Thousand for 2009-2017 Table 39: United States Migraine Drugs Market Share Breakdown by Therapeutic Class: 2009 VS 2019 VS 2025 Table 40: United States Migraine Drugs Market Estimates and Projections in US$ Thousand by Route of Administration: 2018 to 2025 Table 41: Migraine Drugs Market in the United States by Route of Administration: A Historic Review in US$ Thousand for 2009-2017 Table 42: United States Migraine Drugs Market Share Breakdown by Route of Administration: 2009 VS 2019 VS 2025 CANADA Table 43: Canadian Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Treatment: 2018 to 2025 Table 44: Canadian Migraine Drugs Historic Market Review by Treatment in US$ Thousand: 2009-2017 Table 45: Migraine Drugs Market in Canada: Percentage Share Breakdown of Sales by Treatment for 2009, 2019, and 2025 Table 46: Canadian Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Therapeutic Class: 2018 to 2025 Table 47: Canadian Migraine Drugs Historic Market Review by Therapeutic Class in US$ Thousand: 2009-2017 Table 48: Migraine Drugs Market in Canada: Percentage Share Breakdown of Sales by Therapeutic Class for 2009, 2019, and 2025 Table 49: Canadian Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Route of Administration: 2018 to 2025 Table 50: Canadian Migraine Drugs Historic Market Review by Route of Administration in US$ Thousand: 2009-2017 Table 51: Migraine Drugs Market in Canada: Percentage Share Breakdown of Sales by Route of Administration for 2009, 2019, and 2025 JAPAN Table 52: Japanese Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Treatment for the Period 2018-2025 Table 53: Migraine Drugs Market in Japan: Historic Sales Analysis in US$ Thousand by Treatment for the Period 2009-2017 Table 54: Japanese Migraine Drugs Market Share Analysis by Treatment: 2009 VS 2019 VS 2025 Table 55: Japanese Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 56: Migraine Drugs Market in Japan: Historic Sales Analysis in US$ Thousand by Therapeutic Class for the Period 2009-2017 Table 57: Japanese Migraine Drugs Market Share Analysis by Therapeutic Class: 2009 VS 2019 VS 2025 Table 58: Japanese Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Route of Administration for the Period 2018-2025 Table 59: Migraine Drugs Market in Japan: Historic Sales Analysis in US$ Thousand by Route of Administration for the Period 2009-2017 Table 60: Japanese Migraine Drugs Market Share Analysis by Route of Administration: 2009 VS 2019 VS 2025 CHINA Table 61: Chinese Migraine Drugs Market Growth Prospects in US$ Thousand by Treatment for the Period 2018-2025 Table 62: Migraine Drugs Historic Market Analysis in China in US$ Thousand by Treatment: 2009-2017 Table 63: Chinese Migraine Drugs Market by Treatment: Percentage Breakdown of Sales for 2009, 2019, and 2025 Table 64: Chinese Migraine Drugs Market Growth Prospects in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 65: Migraine Drugs Historic Market Analysis in China in US$ Thousand by Therapeutic Class: 2009-2017 Table 66: Chinese Migraine Drugs Market by Therapeutic Class: Percentage Breakdown of Sales for 2009, 2019, and 2025 Table 67: Chinese Migraine Drugs Market Growth Prospects in US$ Thousand by Route of Administration for the Period 2018-2025 Table 68: Migraine Drugs Historic Market Analysis in China in US$ Thousand by Route of Administration: 2009-2017 Table 69: Chinese Migraine Drugs Market by Route of Administration: Percentage Breakdown of Sales for 2009, 2019, and 2025 EUROPE Market Facts & Figures European Migraine Drugs Market: Competitor Market Share Scenario (in %) for 2019 & 2025 Table 70: European Migraine Drugs Market Demand Scenario in US$ Thousand by Region/Country: 2018-2025 Table 71: Migraine Drugs Market in Europe: A Historic Market Perspective in US$ Thousand by Region/Country for the Period 2009-2017 Table 72: European Migraine Drugs Market Share Shift by Region/Country: 2009 VS 2019 VS 2025 Table 73: European Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Treatment: 2018-2025 Table 74: Migraine Drugs Market in Europe in US$ Thousand by Treatment: A Historic Review for the Period 2009-2017 Table 75: European Migraine Drugs Market Share Breakdown by Treatment: 2009 VS 2019 VS 2025 Table 76: European Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Therapeutic Class: 2018-2025 Table 77: Migraine Drugs Market in Europe in US$ Thousand by Therapeutic Class: A Historic Review for the Period 2009-2017 Table 78: European Migraine Drugs Market Share Breakdown by Therapeutic Class: 2009 VS 2019 VS 2025 Table 79: European Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Route of Administration: 2018-2025 Table 80: Migraine Drugs Market in Europe in US$ Thousand by Route of Administration: A Historic Review for the Period 2009-2017 Table 81: European Migraine Drugs Market Share Breakdown by Route of Administration: 2009 VS 2019 VS 2025 FRANCE Table 82: Migraine Drugs Market in France by Treatment: Estimates and Projections in US$ Thousand for the Period 2018-2025 Table 83: French Migraine Drugs Historic Market Scenario in US$ Thousand by Treatment: 2009-2017 Table 84: French Migraine Drugs Market Share Analysis by Treatment: 2009 VS 2019 VS 2025 Table 85: Migraine Drugs Market in France by Therapeutic Class: Estimates and Projections in US$ Thousand for the Period 2018-2025 Table 86: French Migraine Drugs Historic Market Scenario in US$ Thousand by Therapeutic Class: 2009-2017 Table 87: French Migraine Drugs Market Share Analysis by Therapeutic Class: 2009 VS 2019 VS 2025 Table 88: Migraine Drugs Market in France by Route of Administration: Estimates and Projections in US$ Thousand for the Period 2018-2025 Table 89: French Migraine Drugs Historic Market Scenario in US$ Thousand by Route of Administration: 2009-2017 Table 90: French Migraine Drugs Market Share Analysis by Route of Administration: 2009 VS 2019 VS 2025 GERMANY Table 91: Migraine Drugs Market in Germany: Recent Past, Current and Future Analysis in US$ Thousand by Treatment for the Period 2018-2025 Table 92: German Migraine Drugs Historic Market Analysis in US$ Thousand by Treatment: 2009-2017 Table 93: German Migraine Drugs Market Share Breakdown by Treatment: 2009 VS 2019 VS 2025 Table 94: Migraine Drugs Market in Germany: Recent Past, Current and Future Analysis in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 95: German Migraine Drugs Historic Market Analysis in US$ Thousand by Therapeutic Class: 2009-2017 Table 96: German Migraine Drugs Market Share Breakdown by Therapeutic Class: 2009 VS 2019 VS 2025 Table 97: Migraine Drugs Market in Germany: Recent Past, Current and Future Analysis in US$ Thousand by Route of Administration for the Period 2018-2025 Table 98: German Migraine Drugs Historic Market Analysis in US$ Thousand by Route of Administration: 2009-2017 Table 99: German Migraine Drugs Market Share Breakdown by Route of Administration: 2009 VS 2019 VS 2025 ITALY Table 100: Italian Migraine Drugs Market Growth Prospects in US$ Thousand by Treatment for the Period 2018-2025 Table 101: Migraine Drugs Historic Market Analysis in Italy in US$ Thousand by Treatment: 2009-2017 Table 102: Italian Migraine Drugs Market by Treatment: Percentage Breakdown of Sales for 2009, 2019, and 2025 Table 103: Italian Migraine Drugs Market Growth Prospects in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 104: Migraine Drugs Historic Market Analysis in Italy in US$ Thousand by Therapeutic Class: 2009-2017 Table 105: Italian Migraine Drugs Market by Therapeutic Class: Percentage Breakdown of Sales for 2009, 2019, and 2025 Table 106: Italian Migraine Drugs Market Growth Prospects in US$ Thousand by Route of Administration for the Period 2018-2025 Table 107: Migraine Drugs Historic Market Analysis in Italy in US$ Thousand by Route of Administration: 2009-2017 Table 108: Italian Migraine Drugs Market by Route of Administration: Percentage Breakdown of Sales for 2009, 2019, and 2025 UNITED KINGDOM Table 109: United Kingdom Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Treatment for the Period 2018-2025 Table 110: Migraine Drugs Market in the United Kingdom: Historic Sales Analysis in US$ Thousand by Treatment for the Period 2009-2017 Table 111: United Kingdom Migraine Drugs Market Share Analysis by Treatment: 2009 VS 2019 VS 2025 Table 112: United Kingdom Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 113: Migraine Drugs Market in the United Kingdom: Historic Sales Analysis in US$ Thousand by Therapeutic Class for the Period 2009-2017 Table 114: United Kingdom Migraine Drugs Market Share Analysis by Therapeutic Class: 2009 VS 2019 VS 2025 Table 115: United Kingdom Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Route of Administration for the Period 2018-2025 Table 116: Migraine Drugs Market in the United Kingdom: Historic Sales Analysis in US$ Thousand by Route of Administration for the Period 2009-2017 Table 117: United Kingdom Migraine Drugs Market Share Analysis by Route of Administration: 2009 VS 2019 VS 2025 SPAIN Table 118: Spanish Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Treatment: 2018 to 2025 Table 119: Spanish Migraine Drugs Historic Market Review by Treatment in US$ Thousand: 2009-2017 Table 120: Migraine Drugs Market in Spain: Percentage Share Breakdown of Sales by Treatment for 2009, 2019, and 2025 Table 121: Spanish Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Therapeutic Class: 2018 to 2025 Table 122: Spanish Migraine Drugs Historic Market Review by Therapeutic Class in US$ Thousand: 2009-2017 Table 123: Migraine Drugs Market in Spain: Percentage Share Breakdown of Sales by Therapeutic Class for 2009, 2019, and 2025 Table 124: Spanish Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Route of Administration: 2018 to 2025 Table 125: Spanish Migraine Drugs Historic Market Review by Route of Administration in US$ Thousand: 2009-2017 Table 126: Migraine Drugs Market in Spain: Percentage Share Breakdown of Sales by Route of Administration for 2009, 2019, and 2025 RUSSIA Table 127: Russian Migraine Drugs Market Estimates and Projections in US$ Thousand by Treatment: 2018 to 2025 Table 128: Migraine Drugs Market in Russia by Treatment: A Historic Review in US$ Thousand for 2009-2017 Table 129: Russian Migraine Drugs Market Share Breakdown by Treatment: 2009 VS 2019 VS 2025 Table 130: Russian Migraine Drugs Market Estimates and Projections in US$ Thousand by Therapeutic Class: 2018 to 2025 Table 131: Migraine Drugs Market in Russia by Therapeutic Class: A Historic Review in US$ Thousand for 2009-2017 Table 132: Russian Migraine Drugs Market Share Breakdown by Therapeutic Class: 2009 VS 2019 VS 2025 Table 133: Russian Migraine Drugs Market Estimates and Projections in US$ Thousand by Route of Administration: 2018 to 2025 Table 134: Migraine Drugs Market in Russia by Route of Administration: A Historic Review in US$ Thousand for 2009-2017 Table 135: Russian Migraine Drugs Market Share Breakdown by Route of Administration: 2009 VS 2019 VS 2025 REST OF EUROPE Table 136: Rest of Europe Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Treatment: 2018-2025 Table 137: Migraine Drugs Market in Rest of Europe in US$ Thousand by Treatment: A Historic Review for the Period 2009-2017 Table 138: Rest of Europe Migraine Drugs Market Share Breakdown by Treatment: 2009 VS 2019 VS 2025 Table 139: Rest of Europe Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Therapeutic Class: 2018-2025 Table 140: Migraine Drugs Market in Rest of Europe in US$ Thousand by Therapeutic Class: A Historic Review for the Period 2009-2017 Table 141: Rest of Europe Migraine Drugs Market Share Breakdown by Therapeutic Class: 2009 VS 2019 VS 2025 Table 142: Rest of Europe Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Route of Administration: 2018-2025 Table 143: Migraine Drugs Market in Rest of Europe in US$ Thousand by Route of Administration: A Historic Review for the Period 2009-2017 Table 144: Rest of Europe Migraine Drugs Market Share Breakdown by Route of Administration: 2009 VS 2019 VS 2025 ASIA-PACIFIC Table 145: Asia-Pacific Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Region/Country: 2018-2025 Table 146: Migraine Drugs Market in Asia-Pacific: Historic Market Analysis in US$ Thousand by Region/Country for the Period 2009-2017 Table 147: Asia-Pacific Migraine Drugs Market Share Analysis by Region/Country: 2009 VS 2019 VS 2025 Table 148: Migraine Drugs Market in Asia-Pacific by Treatment: Estimates and Projections in US$ Thousand for the Period 2018-2025 Table 149: Asia-Pacific Migraine Drugs Historic Market Scenario in US$ Thousand by Treatment: 2009-2017 Table 150: Asia-Pacific Migraine Drugs Market Share Analysis by Treatment: 2009 VS 2019 VS 2025 Table 151: Migraine Drugs Market in Asia-Pacific by Therapeutic Class: Estimates and Projections in US$ Thousand for the Period 2018-2025 Table 152: Asia-Pacific Migraine Drugs Historic Market Scenario in US$ Thousand by Therapeutic Class: 2009-2017 Table 153: Asia-Pacific Migraine Drugs Market Share Analysis by Therapeutic Class: 2009 VS 2019 VS 2025 Table 154: Migraine Drugs Market in Asia-Pacific by Route of Administration: Estimates and Projections in US$ Thousand for the Period 2018-2025 Table 155: Asia-Pacific Migraine Drugs Historic Market Scenario in US$ Thousand by Route of Administration: 2009-2017 Table 156: Asia-Pacific Migraine Drugs Market Share Analysis by Route of Administration: 2009 VS 2019 VS 2025 AUSTRALIA Table 157: Migraine Drugs Market in Australia: Recent Past, Current and Future Analysis in US$ Thousand by Treatment for the Period 2018-2025 Table 158: Australian Migraine Drugs Historic Market Analysis in US$ Thousand by Treatment: 2009-2017 Table 159: Australian Migraine Drugs Market Share Breakdown by Treatment: 2009 VS 2019 VS 2025 Table 160: Migraine Drugs Market in Australia: Recent Past, Current and Future Analysis in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 161: Australian Migraine Drugs Historic Market Analysis in US$ Thousand by Therapeutic Class: 2009-2017 Table 162: Australian Migraine Drugs Market Share Breakdown by Therapeutic Class: 2009 VS 2019 VS 2025 Table 163: Migraine Drugs Market in Australia: Recent Past, Current and Future Analysis in US$ Thousand by Route of Administration for the Period 2018-2025 Table 164: Australian Migraine Drugs Historic Market Analysis in US$ Thousand by Route of Administration: 2009-2017 Table 165: Australian Migraine Drugs Market Share Breakdown by Route of Administration: 2009 VS 2019 VS 2025 INDIA Table 166: Indian Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Treatment: 2018 to 2025 Table 167: Indian Migraine Drugs Historic Market Review by Treatment in US$ Thousand: 2009-2017 Table 168: Migraine Drugs Market in India: Percentage Share Breakdown of Sales by Treatment for 2009, 2019, and 2025 Table 169: Indian Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Therapeutic Class: 2018 to 2025 Table 170: Indian Migraine Drugs Historic Market Review by Therapeutic Class in US$ Thousand: 2009-2017 Table 171: Migraine Drugs Market in India: Percentage Share Breakdown of Sales by Therapeutic Class for 2009, 2019, and 2025 Table 172: Indian Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Route of Administration: 2018 to 2025 Table 173: Indian Migraine Drugs Historic Market Review by Route of Administration in US$ Thousand: 2009-2017 Table 174: Migraine Drugs Market in India: Percentage Share Breakdown of Sales by Route of Administration for 2009, 2019, and 2025 SOUTH KOREA Table 175: Migraine Drugs Market in South Korea: Recent Past, Current and Future Analysis in US$ Thousand by Treatment for the Period 2018-2025 Table 176: South Korean Migraine Drugs Historic Market Analysis in US$ Thousand by Treatment: 2009-2017 Table 177: Migraine Drugs Market Share Distribution in South Korea by Treatment: 2009 VS 2019 VS 2025 Table 178: Migraine Drugs Market in South Korea: Recent Past, Current and Future Analysis in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 179: South Korean Migraine Drugs Historic Market Analysis in US$ Thousand by Therapeutic Class: 2009-2017 Table 180: Migraine Drugs Market Share Distribution in South Korea by Therapeutic Class: 2009 VS 2019 VS 2025 Table 181: Migraine Drugs Market in South Korea: Recent Past, Current and Future Analysis in US$ Thousand by Route of Administration for the Period 2018-2025 Table 182: South Korean Migraine Drugs Historic Market Analysis in US$ Thousand by Route of Administration: 2009-2017 Table 183: Migraine Drugs Market Share Distribution in South Korea by Route of Administration: 2009 VS 2019 VS 2025 REST OF ASIA-PACIFIC Table 184: Rest of Asia-Pacific Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Treatment for the Period 2018-2025 Table 185: Migraine Drugs Market in Rest of Asia-Pacific: Historic Sales Analysis in US$ Thousand by Treatment for the Period 2009-2017 Table 186: Rest of Asia-Pacific Migraine Drugs Market Share Analysis by Treatment: 2009 VS 2019 VS 2025 Table 187: Rest of Asia-Pacific Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 188: Migraine Drugs Market in Rest of Asia-Pacific: Historic Sales Analysis in US$ Thousand by Therapeutic Class for the Period 2009-2017 Table 189: Rest of Asia-Pacific Migraine Drugs Market Share Analysis by Therapeutic Class: 2009 VS 2019 VS 2025 Table 190: Rest of Asia-Pacific Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Route of Administration for the Period 2018-2025 Table 191: Migraine Drugs Market in Rest of Asia-Pacific: Historic Sales Analysis in US$ Thousand by Route of Administration for the Period 2009-2017 Table 192: Rest of Asia-Pacific Migraine Drugs Market Share Analysis by Route of Administration: 2009 VS 2019 VS 2025 LATIN AMERICA Table 193: Latin American Migraine Drugs Market Trends by Region/Country in US$ Thousand: 2018-2025 Table 194: Migraine Drugs Market in Latin America in US$ Thousand by Region/Country: A Historic Perspective for the Period 2009-2017 Table 195: Latin American Migraine Drugs Market Percentage Breakdown of Sales by Region/Country: 2009, 2019, and 2025 Table 196: Latin American Migraine Drugs Market Growth Prospects in US$ Thousand by Treatment for the Period 2018-2025 Table 197: Migraine Drugs Historic Market Analysis in Latin America in US$ Thousand by Treatment: 2009-2017 Table 198: Latin American Migraine Drugs Market by Treatment: Percentage Breakdown of Sales for 2009, 2019, and 2025 Table 199: Latin American Migraine Drugs Market Growth Prospects in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 200: Migraine Drugs Historic Market Analysis in Latin America in US$ Thousand by Therapeutic Class: 2009-2017 Table 201: Latin American Migraine Drugs Market by Therapeutic Class: Percentage Breakdown of Sales for 2009, 2019, and 2025 Table 202: Latin American Migraine Drugs Market Growth Prospects in US$ Thousand by Route of Administration for the Period 2018-2025 Table 203: Migraine Drugs Historic Market Analysis in Latin America in US$ Thousand by Route of Administration: 2009-2017 Table 204: Latin American Migraine Drugs Market by Route of Administration: Percentage Breakdown of Sales for 2009, 2019, and 2025 ARGENTINA Table 205: Argentinean Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Treatment: 2018-2025 Table 206: Migraine Drugs Market in Argentina in US$ Thousand by Treatment: A Historic Review for the Period 2009-2017 Table 207: Argentinean Migraine Drugs Market Share Breakdown by Treatment: 2009 VS 2019 VS 2025 Table 208: Argentinean Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Therapeutic Class: 2018-2025 Table 209: Migraine Drugs Market in Argentina in US$ Thousand by Therapeutic Class: A Historic Review for the Period 2009-2017 Table 210: Argentinean Migraine Drugs Market Share Breakdown by Therapeutic Class: 2009 VS 2019 VS 2025 Table 211: Argentinean Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Route of Administration: 2018-2025 Table 212: Migraine Drugs Market in Argentina in US$ Thousand by Route of Administration: A Historic Review for the Period 2009-2017 Table 213: Argentinean Migraine Drugs Market Share Breakdown by Route of Administration: 2009 VS 2019 VS 2025 BRAZIL Table 214: Migraine Drugs Market in Brazil by Treatment: Estimates and Projections in US$ Thousand for the Period 2018-2025 Table 215: Brazilian Migraine Drugs Historic Market Scenario in US$ Thousand by Treatment: 2009-2017 Table 216: Brazilian Migraine Drugs Market Share Analysis by Treatment: 2009 VS 2019 VS 2025 Table 217: Migraine Drugs Market in Brazil by Therapeutic Class: Estimates and Projections in US$ Thousand for the Period 2018-2025 Table 218: Brazilian Migraine Drugs Historic Market Scenario in US$ Thousand by Therapeutic Class: 2009-2017 Table 219: Brazilian Migraine Drugs Market Share Analysis by Therapeutic Class: 2009 VS 2019 VS 2025 Table 220: Migraine Drugs Market in Brazil by Route of Administration: Estimates and Projections in US$ Thousand for the Period 2018-2025 Table 221: Brazilian Migraine Drugs Historic Market Scenario in US$ Thousand by Route of Administration: 2009-2017 Table 222: Brazilian Migraine Drugs Market Share Analysis by Route of Administration: 2009 VS 2019 VS 2025 MEXICO Table 223: Migraine Drugs Market in Mexico: Recent Past, Current and Future Analysis in US$ Thousand by Treatment for the Period 2018-2025 Table 224: Mexican Migraine Drugs Historic Market Analysis in US$ Thousand by Treatment: 2009-2017 Table 225: Mexican Migraine Drugs Market Share Breakdown by Treatment: 2009 VS 2019 VS 2025 Table 226: Migraine Drugs Market in Mexico: Recent Past, Current and Future Analysis in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 227: Mexican Migraine Drugs Historic Market Analysis in US$ Thousand by Therapeutic Class: 2009-2017 Table 228: Mexican Migraine Drugs Market Share Breakdown by Therapeutic Class: 2009 VS 2019 VS 2025 Table 229: Migraine Drugs Market in Mexico: Recent Past, Current and Future Analysis in US$ Thousand by Route of Administration for the Period 2018-2025 Table 230: Mexican Migraine Drugs Historic Market Analysis in US$ Thousand by Route of Administration: 2009-2017 Table 231: Mexican Migraine Drugs Market Share Breakdown by Route of Administration: 2009 VS 2019 VS 2025 REST OF LATIN AMERICA Table 232: Rest of Latin America Migraine Drugs Market Estimates and Projections in US$ Thousand by Treatment: 2018 to 2025 Table 233: Migraine Drugs Market in Rest of Latin America by Treatment: A Historic Review in US$ Thousand for 2009-2017 Table 234: Rest of Latin America Migraine Drugs Market Share Breakdown by Treatment: 2009 VS 2019 VS 2025 Table 235: Rest of Latin America Migraine Drugs Market Estimates and Projections in US$ Thousand by Therapeutic Class: 2018 to 2025 Table 236: Migraine Drugs Market in Rest of Latin America by Therapeutic Class: A Historic Review in US$ Thousand for 2009-2017 Table 237: Rest of Latin America Migraine Drugs Market Share Breakdown by Therapeutic Class: 2009 VS 2019 VS 2025 Table 238: Rest of Latin America Migraine Drugs Market Estimates and Projections in US$ Thousand by Route of Administration: 2018 to 2025 Table 239: Migraine Drugs Market in Rest of Latin America by Route of Administration: A Historic Review in US$ Thousand for 2009-2017 Table 240: Rest of Latin America Migraine Drugs Market Share Breakdown by Route of Administration: 2009 VS 2019 VS 2025 MIDDLE EAST Table 241: The Middle East Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Region/Country: 2018-2025 Table 242: Migraine Drugs Market in the Middle East by Region/Country in US$ Thousand: 2009-2017 Table 243: The Middle East Migraine Drugs Market Share Breakdown by Region/Country: 2009, 2019, and 2025 Table 244: The Middle East Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Treatment: 2018 to 2025 Table 245: The Middle East Migraine Drugs Historic Market by Treatment in US$ Thousand: 2009-2017 Table 246: Migraine Drugs Market in the Middle East: Percentage Share Breakdown of Sales by Treatment for 2009, 2019, and 2025 Table 247: The Middle East Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Therapeutic Class: 2018 to 2025 Table 248: The Middle East Migraine Drugs Historic Market by Therapeutic Class in US$ Thousand: 2009-2017 Table 249: Migraine Drugs Market in the Middle East: Percentage Share Breakdown of Sales by Therapeutic Class for 2009, 2019, and 2025 Table 250: The Middle East Migraine Drugs Market Estimates and Forecasts in US$ Thousand by Route of Administration: 2018 to 2025 Table 251: The Middle East Migraine Drugs Historic Market by Route of Administration in US$ Thousand: 2009-2017 Table 252: Migraine Drugs Market in the Middle East: Percentage Share Breakdown of Sales by Route of Administration for 2009, 2019, and 2025 IRAN Table 253: Iranian Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Treatment for the Period 2018-2025 Table 254: Migraine Drugs Market in Iran: Historic Sales Analysis in US$ Thousand by Treatment for the Period 2009-2017 Table 255: Iranian Migraine Drugs Market Share Analysis by Treatment: 2009 VS 2019 VS 2025 Table 256: Iranian Market for Migraine Drugs: Annual Sales Estimates and Projections in US$ Thousand by Therapeutic Class for the Period 2018-2025 Table 257: Migraine Drugs Market in Iran: Historic Sales Analysis in US$ Thousand by Therapeutic Class for the Period 2009-2017 Table 258: Iranian Migraine Drugs Market Share Analysis by Therapeutic Class: 2009 VS 2019 VS 2025 Please contact our Customer Support Center to get the complete Table of Contents Read the full report: https://www.reportlinker.com/p05817938/?utm_source=GNW About Reportlinker ReportLinker is an award-winning market research solution. 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Winston Pharmaceuticals Dolorac Nasal Solution Phase 3

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Winston Pharmaceuticals Dolorac Nasal Solution Phase 3

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