RIPK1 x TNF-α

Courtesy of JHVEPhoto/GettyImages The FDA is busy accepting drug applications, granting specialty designations and approving drugs for market. Here's a look at this week's FDA activity. Daewoong Pharmaceutical Co. announced that the FDA cleared its Investigational New Drug (IND) application to launch a Phase I trial of DWP213388 for autoimmune diseases. The drug is a dual-target inhibitor for both B and T cells, inhibiting BTK and Interleukin-2-inducible T-cell Kinase (ITK). Novavax submitted an application to the FDA for an Emergency Use Authorization (EUA) for its COVID-19 vaccine as a booster in adults 18 and older. An original EUA was granted in July for the vaccine as a two-dose initial series. Preceptis Medical said the FDA cleared its Hummingbird Tympanostomy Tube System (TTS) for office-based pediatric ear tube procedures. The new label allows for in-office procedures in all children six months and older. NovelMed Therapeutics received clearance from the FDA to initiate an efficacy trial of NM8074 in patients with C3G, a rare disease characterized by the deposition of Cd/C3b on kidney cells, proteinuria, and reduced eGFR. The drug is a monoclonal antibody that binds Bb with picomolar affinity and exhibits dual specificity. VySpine reported the FDA granted 510(k) clearance for its VyPlate Anterior Cervical Plate System, which is indicated for stabilization of the anterior cervical spine from C2 to C7, employing unicortical screw fixation at the anterior face of the vertebral bodies. AstraZeneca and Merck announced the FDA accepted and granted priority review for their supplemental New Drug Application (sNDA) for Lynparza in combination with abiraterone and prednisone or prednisolone for adults with metastatic castration-resistant prostate cancer. There is a PDUFA date in the fourth quarter of this year. The FDA finalized a ruling that hearing aids can be sold over the counter to patients with mild to moderate hearing impairment. No physician prescription or device fitting is required. It only applies to patients 18 years and older. Bluebird bio announced the FDA approved Zynteglo (betibeglogene autotemcel) for adults and children with beta-thalassemia who require regular RBC transfusions. The therapy is a cell-based gene therapy. Thermo Fisher Scientific received clearance of ImmunoCAP Specific IgE Allergen Components for wheat and sesame allergies for in vitro diagnostic use. These are advanced blood tests to help ID wheat and sesame allergies. AVAVA reported that the FDA granted 510(k) clearance for treating benign pigmented skin lesions, including hyperpigmentation. The technology approved is an AI enabled, precise 3D laser treatment. Samsung Bioepis and Organon & Co. announced the FDA approved the citrate-free, high-concentration formulation of Hadlime (adalimumab-bwwd), a biosimilar to AbbVie's Humira (adalimumab). AUM Biosciences' AUM601 received Orphan Drug Designation from the FDA for solid tumors with the NTRK fusion gene. AUM601 is a highly selective, oral small molecule that inhibits the pan-TRK (TRKA, TRKB, and TRKC), but also resistance mutations of TRKs by blocking the activity of tyrosine kinases. Spectral Medical's wholly-owned subsidiary Dialco Medical's Investigational Device Exemption (IDE) received approval by the FDA for up to 10 new clinical sites in its pivotal Tigris trial. Curis announced the FDA lifted the partial clinical hold on the TakeAim Lymphoma Phase I/II trial of emavusertib. The company now expects preliminary data in 2023. Zavation Medical Products received FDA 510K clearance of Varisync, a cervical intervertebral body fusion device. GenFleet Therapeutics received a greenlight from the FDA for its Phase II trial of GFH312 for patients with peripheral artery disease and intermittent claudication. GFH312 is a RIPK1 inhibitor and blocks the process of TNF-alpha-induced necroptosis. Bayer announced the FDA approved an sNDA that extends the duration of use for its intrauterine device (IUD) Mirena (levonorgestrel-releasing intrauterine system) 52 mg by one more year. This will make it available to prevent pregnancy for up to eight years. Axsome Therapeutics announced the FDA approved its Auvelty (dextromethorphan HBr-bupropion HCl) for major depressive disorder (MDD) in adults. Calyptus Pharmaceuticals received FDA approval for its Abbreviated NDA (ANDA) for an AP-rated generic version of Cetrotide to Calyptus' partner, Akorn Operating Company. The FDA also granted its Competitive Generic Therapy (CGT) designation. Cetrotide is used to treat infertility. IMPACT Therapeutics' fixed-dose combination of Senaparib (PARP inhibitor) and temozolomide (TMZ) for adults with small cell lung cancer received Orphan Drug Designation from the FDA.

Courtesy of JHVEPhoto/GettyImages The FDA is busy accepting drug applications, granting specialty designations and approving drugs for market. Here’s a look at this week’s FDA activity. Courtesy of JHVEPhoto/GettyImages The FDA is busy accepting drug applications, granting specialty designations and approving drugs for market. Here’s a look at this week’s FDA activity. Daewoong Pharmaceutical Co. announced that the FDA cleared its Investigational New Drug (IND) application to launch a Phase I trial of DWP213388 for autoimmune diseases. The drug is a dual-target inhibitor for both B and T cells, inhibiting BTK and Interleukin-2-inducible T-cell Kinase (ITK). Novavax submitted an application to the FDA for an Emergency Use Authorization (EUA) for its COVID-19 vaccine as a booster in adults 18 and older. An original EUA was granted in July for the vaccine as a two-dose initial series. Preceptis Medical said the FDA cleared its Hummingbird Tympanostomy Tube System (TTS) for office-based pediatric ear tube procedures. The new label allows for in-office procedures in all children six months and older. NovelMed Therapeutics received clearance from the FDA to initiate an efficacy trial of NM8074 in patients with C3G, a rare disease characterized by the deposition of Cd/C3b on kidney cells, proteinuria, and reduced eGFR. The drug is a monoclonal antibody that binds Bb with picomolar affinity and exhibits dual specificity. VySpine reported the FDA granted 510(k) clearance for its VyPlate Anterior Cervical Plate System, which is indicated for stabilization of the anterior cervical spine from C2 to C7, employing unicortical screw fixation at the anterior face of the vertebral bodies. AstraZeneca and Merck announced the FDA accepted and granted priority review for their supplemental New Drug Application (sNDA) for Lynparza in combination with abiraterone and prednisone or prednisolone for adults with metastatic castration-resistant prostate cancer. There is a PDUFA date in the fourth quarter of this year. The FDA finalized a ruling that hearing aids can be sold over the counter to patients with mild to moderate hearing impairment. No physician prescription or device fitting is required. It only applies to patients 18 years and older. Bluebird bio announced the FDA approved Zynteglo (betibeglogene autotemcel) for adults and children with beta-thalassemia who require regular RBC transfusions. The therapy is a cell-based gene therapy. Thermo Fisher Scientific received clearance of ImmunoCAP Specific IgE Allergen Components for wheat and sesame allergies for in vitro diagnostic use. These are advanced blood tests to help ID wheat and sesame allergies. AVAVA reported that the FDA granted 510(k) clearance for treating benign pigmented skin lesions, including hyperpigmentation. The technology approved is an AI enabled, precise 3D laser treatment. Samsung Bioepis and Organon & Co. announced the FDA approved the citrate-free, high-concentration formulation of Hadlima (adalimumab-bwwd), a biosimilar to AbbVie’s Humira (adalimumab). AUM Biosciences’ AUM601 received Orphan Drug Designation from the FDA for solid tumors with the NTRK fusion gene. AUM601 is a highly selective, oral small molecule that inhibits the pan-TRK (TRKA, TRKB, and TRKC), but also resistance mutations of TRKs by blocking the activity of tyrosine kinases. Spectral Medical’s wholly-owned subsidiary Dialco Medical’s Investigational Device Exemption (IDE) received approval by the FDA for up to 10 new clinical sites in its pivotal Tigris trial. Curis announced the FDA lifted the partial clinical hold on the TakeAim Lymphoma Phase I/II trial of emavusertib. The company now expects preliminary data in 2023. Zavation Medical Products received FDA 510K clearance of Varisync, a cervical intervertebral body fusion device. GenFleet Therapeutics received a greenlight from the FDA for its Phase II trial of GFH312 for patients with peripheral artery disease and intermittent claudication. GFH312 is a RIPK1 inhibitor and blocks the process of TNF-alpha-induced necroptosis. Bayer announced the FDA approved an sNDA that extends the duration of use for its intrauterine device (IUD) Mirena (levonorgestrel-releasing intrauterine system) 52 mg by one more year. This will make it available to prevent pregnancy for up to eight years. Axsome Therapeutics announced the FDA approved its Auvelty (dextromethorphan HBr-bupropion HCl) for major depressive disorder (MDD) in adults. Calyptus Pharmaceuticals received FDA approval for its Abbreviated NDA (ANDA) for an AP-rated generic version of Cetrotide to Calyptus’ partner, Akorn Operating Company . The FDA also granted its Competitive Generic Therapy (CGT) designation. Cetrotide is used to treat infertility. IMPACT Therapeutics’ fixed-dose combination of Senaparib (PARP inhibitor) and temozolomide (TMZ) for adults with small cell lung cancer received Orphan Drug Designation from the FDA.

SHANGHAI, Aug. 18, 2022 /PRNewswire/ -- GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced US Food and Drug Administration (FDA) has approved the clinical trial application for GFH312 in a randomized, double-blinded, placebo-controlled phase II monotherapy study. The trial will be conducted in patients with peripheral artery disease and with intermittent claudication at 15 research centers, including University of Colorado Anschutz Medical Campus. GenFleet completed the phase I study of GFH312 in Australia with data to be published in relevant international medical conference later this year. According to research, there are estimated over 200 million people worldwide living with peripheral artery disease (PAD) with prevalence ranging as high as 20% in populations aged 70 years or over. Most patients are either asymptomatic or have intermittent claudication (IC), but all with an increased risk for myocardial infarction, stroke and vascular-related mortality. There is a significant unmet medical need for PAD, given that currently no anti-inflammatory treatments have been approved globally. RIPK1 exhibits dual immunomodulatory effects and is a key regulator of multiple immune pathways. Many scientific publications have indicated that RIPK1-mediated inflammatory response plays a crucial part in the occurrence and development of PAD with IC. Preclinical data demonstrated GFH312 is able to inhibit RIPK1 kinase activity in human cells, down-regulate RIPK1 phosphorylation in animal models and curb the inflammatory response of animals' nervous system. "The data from completed phase I trial in Australia demonstrated excellent safety profile and desirable PK & PD properties of GFH312. GFH312 is GenFleet's first Phase 2-ready product in non-oncology indications. We wish to further confirm the safety and therapeutic effectiveness of GFH312 in the trial." said Dr. Yu Wang, Chief Medical Officer of GenFleet Therapeutics. "GenFleet has launched a series of initiatives in global clinical development and strategic partnership this year. GFH312 is GenFleet's first program entering into clinical trial in Australia, and now we are thrilled to see this program moving into phase II study in the US. This is a significant milestone for the company's multi-regional clinical development. To date, no RIPK1 inhibitor has been approved for therapeutic use and we look forward to bringing more innovative therapies to benefit patients worldwide." said Dr. Jiong Lan, Co-founder and Chief Executive Officer of GenFleet Therapeutics. The primary objective of this study is to evaluate the effect of GFH312 on symptomatic functional capacity among PAD patients with IC after 12 weeks of treatment. The study will also assess the safety, tolerability and pharmacokinetics of GFH312 and explore the beneficial impact of GFH312 on the quality of PAD patients' life. Moreover, GenFleet is planning to start a double-blinded, randomized, placebo-controlled phase I study in China to support further phase II study in China for other potential indications. References: 1. Peripheral Arterial Disease in Women: an Overview of Risk Factor Profile, Clinical Features, and Outcomes, Curr Atheroscler Rep, 2018 2. A national study of the prevalence and risk factors associated with peripheral arterial disease from China: The China Hypertension Survey 2012-2015, Int J Cardio, 2019 3. Epidemiology, diagnosis and classification of peripheral artery disease (PAD), Nova Science Pub Inc, 2016 About peripheral arterial disease and intermittent claudication Peripheral arterial disease (PAD) is a chronic disease in which plaque builds up in the arteries and leads to stenosis or even complete occlusion. Narrowed vessels would reduce blood flow to the arms or legs and cause intermittent claudication and other cardiovascular symptoms. According to research, PAD affects almost 27 million people in US and Europe; in China, PAD prevalence amounts to 6% among people above 35 years old and PAD-affected population is calculated to exceed 40 million. At present, antiplatelet drugs, vasodilators, or drugs for prevention and treatment of venous thrombosis and systemic circulation embolism are commonly prescribed to relieve PAD symptoms. As a common symptom in vascular and neurological diseases, intermittent claudication (IC) is mainly caused by local ischemia and induces microvascular obstruction, leg weakness and intermittent walking difficulty. The symptoms can be alleviated in varying degrees and durations after stopping lower limb movement. About RIPK1 and GFH312 As a subtype of receptor interacting protein kinase family, RIPK1 is a central regulator of multiple immune signaling pathways. Widely expressed in human cells, the serine/threonine kinase of RIPK1 is most abundant in fat, endothelial and perivascular cell clusters and also discovered in immune cell clusters (dendritic cells, macrophages and T cells). Small-molecule RIPK1 inhibitors are expected to show efficacy for treating autoinflammatory and autoimmune diseases (including psoriasis, rheumatoid arthritis, ulcerative colitis, etc.). In vitro experiments demonstrate that GFH312 blocks the process of TNF-α-induced necroptosis. It's observed in a variety of animal models that GFH312 can reduce inflammation and resist necroptosis; besides, low dosage of GFH312 can decrease the death risk caused by acute systemic inflammation and significantly improve the action capability of experimental animals. The phase I clinical trial data confirm the safety and tolerance of GFH312. SOURCE GenFleet Therapeutics