C1S

Top-line results from gMG MaGic trial anticipated in 2H 2025 Building a neuromuscular franchise with DNTH103 through additional planned Phase 2 trials in Multifocal Motor Neuropathy (MMN) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) DNTH103 is a potential best-in-class, potent classical pathway inhibitor planned for self-administration as a low volume, subcutaneous injection once every two weeks Feb. 26, 2024 -- Dianthus Therapeutics, Inc. (Nasdaq: DNTH), a clinical-stage biotechnology company dedicated to advancing the next generation of antibody complement therapeutics to treat severe autoimmune diseases, today announced the initiation of the Phase 2 MaGic trial of DNTH103 in patients with generalized Myasthenia Gravis. The initiation follows U.S. Food and Drug Administration (FDA) clearance of the Phase 2 Investigational New Drug (IND) application for DNTH103. Top-line results from this trial are anticipated in the second half of 2025. “Following our encouraging Phase 1 data demonstrating a 60-day half-life and potent, specific classical pathway inhibition, we are excited to rapidly advance DNTH103, our investigational active C1s inhibitor, into a Phase 2 study in generalized Myasthenia Gravis,” said Simrat Randhawa, M.D., Chief Medical Officer of Dianthus Therapeutics. “DNTH103 provides a unique approach to complement inhibition in gMG, which could result in a more convenient and safer alternative for patients versus current options.” The MaGic trial is a global, randomized, double-blind, placebo-controlled Phase 2 study in up to 60 patients with generalized Myasthenia Gravis who are acetylcholine receptor (AchR) antibody positive. Following an initial loading dose, DNTH103 will be administered every two weeks (Q2W) via subcutaneous (S.C.) injection. The S.C. treatment duration will initially be 12 weeks with a 52-week open label extension. The primary endpoint of the study is safety and tolerability. Secondary endpoints include Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) and Quantitative Myasthenia Gravis (QMG) score assessments. Initial top-line results from this trial are anticipated to be available in the second half of 2025. “For patients with AchR-positive gMG, inappropriate activation of the complement classical pathway is a major driver of disease pathology and therefore patient symptoms,” said Mazen M. Dimachkie, M.D., Professor of Neurology and Director of Neuromuscular Division at the University of Kansas Medical Center. “I am excited to collaborate with Dianthus to evaluate this investigational, highly specific classical pathway inhibitor that could fill the need for a more convenient and safe complement inhibitor for my gMG patients.” DNTH103 is an investigational, clinical-stage, potent monoclonal antibody engineered to selectively target the classical pathway by inhibiting only the active form of the C1s protein, a clinically validated complement target. DNTH103 is enhanced with YTE half-life extension technology designed to enable a more convenient subcutaneous, self-administered injection dosed as infrequently as once every two weeks. Additionally, selective inhibition of the classical complement pathway may lower patient risk of infection from encapsulated bacteria by preserving immune activity of the lectin and alternative pathways. As the classical pathway plays a significant role in disease pathology, DNTH103 has the potential to be a best-in-class pipeline-in-a-product across a range of autoimmune disorders with high unmet need. Dianthus has initiated a Phase 2 trial in generalized Myasthenia Gravis and plans to initiate additional Phase 2 trials in other neuromuscular indications, including Multifocal Motor Neuropathy and Chronic Inflammatory Demyelinating Polyneuropathy, in 2024. Dianthus Therapeutics is a clinical-stage biotechnology company dedicated to designing and delivering novel, best-in-class monoclonal antibodies with improved selectivity and potency. Based in New York City and Waltham, Mass., Dianthus is comprised of an experienced team of biotech and pharma executives who are leading the development of next-generation antibody complement therapeutics, aiming to deliver transformative medicines for people living with severe autoimmune and inflammatory diseases. Dianthus has initiated a Phase 2 trial of DNTH103, a potential best-in-class active C1s inhibitor, in generalized Myasthenia Gravis and plans to initiate additional Phase 2 trials in other neuromuscular indications, including Multifocal Motor Neuropathy and Chronic Inflammatory Demyelinating Polyneuropathy, in 2024. The content above comes from the network. if any infringement, please contact us to modify.

Pictured: a physician looks at a brain scan on a computer screen/iStock, gorodenkoff With a plethora of promising candidates moving through clinical trials, there are several upcoming data readouts of interest in both the neurodegenerative and neuropsychiatric spaces. Targeting amyotrophic lateral sclerosis (ALS), major depressive disorder, Huntington’s disease and many other worthy indications, here are six mid- to late-stage data readouts for candidates you’ll want to have on your radar. 1. Sanofi and Denali’s SAR443820/DNL788 Amyotrophic lateral sclerosis In the ALS space, Sanofi is expected to announce topline results from the Phase II HIMALAYA trial of SAR443820/DNL788, which it is developing with partner Denali Therapeutics, according to a Denali press release. SAR443820/DNL788 is a small molecule inhibitor of RIPK1, a critical signaling protein in a canonical inflammatory and cell death pathway, according to Denali. Increased RIPK1 activity in the central nervous system is thought to drive neuroinflammation and cell death, contributing to neurodegeneration. Part A of the double-blinded, randomized, placebo-controlled HIMALAYA trial, which has completed enrolling all 305 participants, involves evaluating patients’ change from baseline on the ALS Functional Rating Scale-Revised (ALSFRS-R), a tool used to determine disease progression. The primary outcome for Part B of the HIMALAYA program, the open-label extension, is the combined assessment of the function and survival (CAFS) score. SAR443820/DNL788 holds the FDA’s Fast Track designation for the treatment of ALS. Sanofi and Denali are also developing SAR443820/DNL788 for multiple sclerosis, for which it is being tested in the Phase II K2 study. 2. Intra-Cellular Therapies’ Lumateperone Major depressive disorder According to Graig Suvannavejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, major depressive disorder (MDD) is an area to watch this year. “There are several readouts in major depressive disorder,” he told BioSpace. Among those, he highlighted anticipated Phase III datasets for Intra-Cellular Therapies’ Caplyta (lumateperone). Intra-Cellular’s lead asset, lumateperone won approval in 2019 for schizophrenia and received a label expansion in December 2021 for depressive episodes associated with bipolar disorder. Now the company is seeking a third indication, MDD, and expects data from two Phase III studies during the first half of 2024. Lumateperone, an oral antipsychotic medication, is currently being assessed in a three-part Phase III program for MDD. Studies 501, 502 and 505 are testing the drug in adult patients who are having inadequate response to an approved antidepressant. The primary endpoint for these studies is change in Montgomery Asberg Depression Rating Scale (MADRS) total score after six weeks, while a key secondary endpoint is change in CGI-S score over the same period of time. The company anticipates topline data from Study 501 in the first quarter of 2024 and for Study 502 in Q2, according to a January corporate presentation. In another Phase III trial, reported in March 2023, lumateperone eased the burden of depressive episodes in patients with MDD or bipolar depression with mixed features. Suvannavejh said these data, along with lumateperone’s approval for depressive episodes associated with bipolar disorder, “gives us a level of confidence” in the drug. 3. Annexon Biosciences’ ANX005 Guillain-Barré syndrome Brisbane, Calif.–based Annexon Biosciences is expecting pivotal data from a Phase III trial of its lead candidate ANX005, being developed for Guillain-Barré syndrome (GBS), during the first six months of 2024. There are no FDA-approved treatments for GBS, a potentially fatal, serious autoimmune condition of the nervous system that can cause paralysis, neurodegeneration and cognitive impairment, according to an Annexon press release outlining expected 2024 milestones. GBS is caused by an autoantibody attack on the peripheral nerves, triggering the complement cascade (C1q). ANX005 is designed to inhibit C1s along with the entire complement pathway. It has received both Fast Track and Orphan Drug designations from the FDA in this indication. A Phase III study testing the efficacy, safety, pharmacokinetics and pharmacodynamics of ANX005, an investigational monoclonal antibody, completed enrollment in 2023 and is on track to read out data before July, Annexon noted in the press release. In a Phase Ib trial, ANX005 “showed rapid and consistent improvement in muscle strength” and “improvement in neuronal damage and clinical function in patients with GBS,” according to Annexon. 4. Wave Life Sciences’ WVE-003 Huntington’s disease One of the most intractable neurodegenerative illnesses, Huntington’s disease continues to stump biopharma, but companies aren’t giving up. One of these is Cambridge, Mass.–based Wave Life Sciences, which is testing an antisense therapy, WVE-003, in the Phase Ib/IIa SELECT-HD trial. Wave anticipates sharing data from the 30 mg multi-dose cohort of this study with extended follow-up, along with all single-dose data, in the second quarter of 2024, according to a company press release outlining 2024 milestones. Huntington’s disease is caused by a CAG repeat in the first exon of the huntingtin (HTT) gene. This mutation causes brain cells to die, leading to a host of progressive cognitive, psychiatric and movement symptoms, including an involuntary jerking or writhing movement, also known as chorea. WVE-003 is designed to preferentially lower mutant HTT (mHTT) protein levels by targeting a single nucleotide polymorphism called SNP3 that appears on the mHTT transcript, Wave CEO Paul Bolno told BioSpace in a previous interview. An estimated 40% of adults with Huntington’s carry SNP3 in association with the Huntington’s mutation, Bolno said. Wave presented data in September 2022 from SELECT-HD showing early indications of decreases in mHTT in the cerebrospinal fluid. Wildtype HTT [wtHTT]—the good type of huntingtin protein—was preserved at both doses, the company reported. A recently posted preclinical study reinforced the importance of wtHTT-sparing biology and that the protein’s preservation is also “important in delaying the progression of the disease,” Bolno told BioSpace last week. “These data will be the first repeat-dose assessment of wildtype [huntingtin] preservation with mutant huntingtin knockdown.” For Wave, the anticipated results also have implications for an existing collaboration agreement with Takeda, which has the option to co-develop and co-commercialize WVE-003. Per the press release, these data are expected to inform Takeda’s decision on whether or not to opt in. However, under the terms of the agreement, Wave retains control of development and regulatory approval in either case, Bolno noted. So the company is more focused on whether the program “goes the distance in terms of delivering a medicine to patients,” he said. 5 and 6. Praxis Precision Medicines’ PRAX-562 and PRAX-628 Epilepsy Two key anticipated data readouts in the epilepsy space come from Praxis Precision Medicines. First, topline results from the Phase IIa PPR study of PRAX-628 in patients with photo-paroxysmal response (PPR) epilepsy are expected in the first quarter of this year. Positive preliminary analysis of the study’s 15-mg cohort “exceeds expectations” in terms of drug activity, according to a Praxis clinical portfolio update. The new data are expected to be released following completion of the 45-mg cohort. PRAX-628, which targets focal epilepsy, is a next-generation, functionally selective small molecule targeting the hyperexcitable state of sodium-channels in the brain. Initial data show the candidate “has a good tolerability profile, a potentially wide therapeutic index” and the ability to reach efficacious concentrations within 24 hours, according to Praxis. Also expected during the first half of 2024 are results from the Phase II EMBOLD study testing PRAX-562, a unique sodium channel modulator, in pediatric patients with SCN2A and SCN8A developmental epilepsies. PRAX-628 and PRAX-562 are both based on Praxis’ Cerebrum small molecule platform, which leverages a “deep understanding of neuronal excitability and neuronal networks,” according to Praxis’ website. Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.

ANX005 Phase 3 Pivotal Data in Guillain-Barré Syndrome (GBS) On Track for First Half of 2024; Potential to be First Approved Treatment for GBS Patients in the U.S. ANX007 Global Pivotal Program in Geographic Atrophy (GA) to Initiate Mid-2024; First Pivotal Trial Using Vision Preservation as Primary Outcome Measure in GA Clinical Proof-of-Concept Study of ANX1502 First-in-Kind Oral Small Molecule Inhibitor of the Classical Pathway to Initiate in First Half of 2024 Recent Successful $125 Million Financing Extends Operating Runway into Second Quarter 2026 Jan. 07, 2024 -- Annexon, Inc. (Nasdaq: ANNX), a clinical-stage biopharmaceutical company developing a new class of complement-based medicines for people living with devastating inflammatory-related diseases, today outlined its strategic priorities for 2024 with late-stage clinical milestones, including ANX005 for Guillain-Barré syndrome (GBS), ANX007 for geographic atrophy (GA) and its first-in-kind oral small molecule complement inhibitor, ANX1502, for a range of autoimmune indications. “Our distinct classical complement portfolio has been built over 10 years of research focused on stopping C1q-driven inflammation activated on diseased tissue in complement-mediated diseases of the body, brain and eye. The robust and consistent functional outcome data generated by our flagship and next wave programs has reinforced our founding thesis of stopping the classical complement disease process where it starts,” said Douglas Love, president and CEO of Annexon. “This is a pivotal time for Annexon, with registration programs for our two lead candidates, numerous late- and mid-stage clinical catalysts expected across our portfolio, and a strong balance sheet to fuel our priority programs to meaningful inflection points. We are proud of what we’ve accomplished over our decade-long history and are excited by the potential to achieve our goal of bringing transformative therapies to millions of patients with debilitating autoimmune, ophthalmic and neurodegenerative diseases.” Annexon is sharply focused on mid- to late-stage development of three value-driving programs: GBS is a serious autoimmune condition of the nervous system that can lead to sudden paralysis and even death in otherwise healthy individuals. GBS impacts more than 12,000 people annually in the U.S. and Europe, and there are currently no approved therapies for GBS in the U.S. Annexon is conducting a randomized, double-blind, placebo-controlled, multi-center Phase 3 clinical trial (N=241) designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ANX005 in patients with GBS. The study completed enrollment in 2023 and the company is on-track to report Phase 3 data in the first half of 2024. ANX005 was granted orphan drug designation by the EMA for the treatment of GBS based on a meta-analysis of past studies with ANX005 and intravenous immunoglobulin (IVIg). In a completed proof-of-concept, placebo-controlled Phase 1b trial, ANX005 showed rapid and consistent improvement in muscle strength that translated into observable gains in health status, including a reduction in the need of mechanical ventilation, as well as improvement in neuronal damage and clinical function in patients with GBS. GA is an advanced form of dry age-related macular degeneration (AMD), an eye disease that is the leading cause of vision loss in the elderly, that affects an estimated eight million people globally. In the randomized, multi-center, double-masked, sham-controlled Phase 2 ARCHER clinical trial, ANX007 was the first and only program to show statistically significant and consistent protection against vision loss in a broad population of patients with GA. Annexon plans to initiate ARCHER II, a global, sham-controlled Phase 3 clinical trial in patients with GA in mid-2024. ARCHER II is designed to confirm the results from the Phase 2 ARCHER trial, and potentially expedite the path to regulatory approval in Europe. Annexon also plans to initiate the ARROW clinical trial, an injection-controlled head-to-head study against SYFOVRE® (pegcetacoplan injection) in late 2024. ARROW has the potential to underscore ANX007’s unique mechanism of action and provide critical differentiation on visual function. ANX007 is the first therapeutic candidate for the treatment of GA to receive PRIME designation in the EU, which provides early and proactive support to developers of promising medicines that may offer a major therapeutic advantage over existing treatments or benefit to patients without treatment options. ANX1502 is a potential first-in-kind oral small molecule inhibitor of the classical complement pathway that targets the active form of C1s, an enzyme associated with C1q. In the Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy volunteers, ANX1502 was generally well-tolerated, achieved target levels of active drug and showed supportive impact on a pharmacodynamic biomarker of complement activity that support its clinical advancement. Annexon plans to advance a tablet formulation of ANX1502 into a proof-of-concept trial designed to assess pharmacodynamics and efficacy in patients with cold agglutinin disease (CAD) in the first half of 2024. Following the successful completion of the proof-of-concept study, Annexon intends to evaluate ANX1502 in additional serious complement-mediated autoimmune diseases with the aim of providing efficacy with enhanced dosing flexibility and convenience for long-term treatment of chronic autoimmune conditions. Mr. Love will present an overview of Annexon and outline the company’s pipeline updates at the 42nd Annual J.P. Morgan Healthcare Conference on Wednesday, January 10, 2023, at 2:15 p.m. PT in San Francisco. A live webcast of the event can be accessed under the ‘Events & Presentations’ section on the Investors page at www.annexonbio.com. A replay of the webcast will be archived on the Annexon website for 30 days following the presentation. Annexon Biosciences (Nasdaq: ANNX) is a clinical-stage biopharmaceutical company utilizing a distinct scientific approach to stop C1q and all inflammatory aspects of classical complement pathway activation before it starts. As the only company solely focused on targeting C1q, Annexon is developing a fit-for-purpose pipeline of therapeutics designed to provide meaningful benefits across multiple diseases of the body, brain and eye. With proof-of concept data in both Guillain-Barré syndrome and geographic atrophy, Annexon is rigorously advancing its mid-to late-stage clinical trials to bring their potential treatments to patients as quickly as possible. To learn more visit annexonbio.com. The content above comes from the network. if any infringement, please contact us to modify.