Rapastinel

Funding rounds this week saw money flow into innovative drug discovery and delivery platforms, cancer imaging and RNA synthesis, while pharma powerhouse Pfizer wrapped up two high-value neuro deals. EnPlusOne’s Enzyme-Based RNA Synthesis Platform Earns $12M Seed With $12 million in seed financing, biotech startup EnPlusOne Biosciences Inc. launched last week with its cutting-edge enzymatic RNA synthesis platform ezRNA. The funding round was led by Northpond Ventures; Breakout Ventures, Coatue and angel investors participated. The culmination of more than six years of development, the ezRNA synthesis platform uses enzymes to generate RNA oligonucleotides and can incorporate a wide variety of nucleotide modifications. EnPlusOne will use the seed proceeds to further develop and scale ezRNA and expand its team. The young company is led by Daniel Wiegand, its chief executive officer. Dr. Jonathan Rittichier, Ph.D., is its chief scientific officer, while Dan Ahlstedt is the chief operating officer. All three spun EnPlusOne from the Wyss Institute for Biologically Inspired Engineering at Harvard University. Wiegand and Rittichier are the company’s technical founders. Unique Approach to Drug Discovery Scores Cellarity $121M in Series C Cambridge, MA-based Cellarity made $121 million in its recent Series C financing round, the company announced Tuesday. It plans to use the proceeds to strengthen its platform, expand its talent base and drive its programs to the clinic. Cellarity’s approach goes beyond individual molecular targets and focuses on the entire cell to identify factors influencing the transition to a diseased state. Deep learning models combined with high-dimensional transcriptomic data allow Cellarity to design medicines targeting a disease’s cellular structure, which could lead to treatments for previously undruggable targets. The funding round was led by venture capital firm and Cellarity founder Flagship Pioneering. Four new investors also threw their support behind Cellarity, including Hanwha Impact Partners and Kyowa Kirin Co. Ltd. Since Cellarity was founded in 2017, it has already raised $274 million. Voyager Earns $10M from Pfizer’s License Option for its Next-Generation AAV Capsid On Tuesday, pharma giant Pfizer exercised its license option to Voyager Therapeutics’ novel AAV capsid, triggering a $10 million payment to the latter. According to a company spokesperson, Voyager will use these proceeds to further develop its proprietary TRACER discovery platform and ongoing pipeline programs. The exercise option is part of a licensing agreement between Voyager and Pfizer, inked October last year, which entailed a $30 million upfront payment for the capsid program that could be used to deliver potential gene therapies for a still undisclosed rare neurologic disorder. Voyager remains eligible for up to $290 million in milestones and tiered royalties. The company is banking on an external partnership strategy to help it advance its technology and pipeline. “Voyager also announced in March 2023 a license option agreement with Novartis under which Novartis may exercise options to license TRACER generated AAV capsids for potential use with three undisclosed CNS targets and options to access capsids for two additional rare disease targets to be agreed on in the future,” the spokesperson told BioSpace. Series B Pumps $21.5M Into Vergent’s Fluorescent Tumor Imaging Agent With its Series B round of financing closing Tuesday, Vergent Bioscience posted proceeds of $21.5 million, which the company will use to further advance the clinical development of VGT-309, its tumor-targeted fluorescent imaging agent. Delivered via a short infusion a couple of hours before surgery, VGT-309 contains a molecule that covalently bonds to cathepsins, a group of proteins known to be over-expressed in a wide variety of solid tumors, including lung cancer. This action allows surgeons to spot previously undetectable or hard-to-visualize tumor tissues during minimally invasive or robotic surgeries. Orlando Health Ventures led Vergent’s Series B. The Minneapolis, MN-based company earned new investors during this round, including Rex Health Ventures, Windham Venture Partners and Intuitive Surgical, Inc. Pfizer Completes $11.6 Billion Biohaven Buyout First revealed in May, Pfizer announced Monday that it had completed its migraine leader Biohaven Pharmaceuticals acquisition in a deal valued at $11.6 billion. The industry giant bought all outstanding shares of Biohaven at $148.50 per share. Biohaven is now a wholly-owned subsidiary of Pfizer. As a result of the buyout, Pfizer now holds the rights to Nurtec ODT (rimegepant), for the treatment of migraines in adults, with or without auras, and for the prevention of episodic migraine. The deal also gives Pfizer Zavegepant, an intranasal spray under review by the FDA for acute migraine relief. The regulatory body is set to arrive at a decision early next year. The acquisition also grants Pfizer a portfolio of pre-clinical calcitonin gene-related peptide receptor antagonists. Drug Discovery Technologies Win Alloy $42M in Series D Biotech ecosystem company Alloy Therapeutics counted $42 million in earnings during its recent Series D financing round. The proceeds will be used to bolster the company’s pre-competitive drug discovery technologies in new biologic modalities, as well as support new partnership models to foster innovation in the drug discovery community. Launched in 2017, Alloy initially provided human antibody mouse discovery capabilities using a suite of transgenic mouse strains. With its Series C in March 2021, the company was able to extend its discovery technologies and services into T cell receptors and genetic medicines. Monday’s Series D will also help Alloy expand its offerings across its six modalities, including peptides and cell therapies. The Series D was led by existing investors 8VC and Mubadala Capital. Returning supporters, Thiel Capital, Founders Fund and Presight Capital, and other unnamed funds, participated. After Stealth Exit, Gate Counts $25M in Financing Precision medicine biotech Gate Neurosciences announced last week that it had earned a total of $25 million in funding from a cadre of life science-focused investors, including ThornApple Capital, Innoviva, Biocrossroads and Luson Bioventures, among others. Alongside its financing, the company touted a new peer-reviewed publication highlighting the novel mechanism and pharmacology of its lead program Zelquistinel. The paper shows that a single dose of the molecule can modulate NMDA receptors and enhance synaptic plasticity in specific brain regions, which leads to a rapid and durable antidepressant effect. Gate launched in 2019 and emerged from stealth in August. The company has previously acquired the Zelquistinel, Apimostinel and Rapastinel depression programs from pharma giant AbbVie, and has recently earned exclusive rights to Eli Lilly’s preclinical mGlu2/3 receptor antagonists for sleep disorders.

Sept. 29, 2022 12:00 UTC New publication highlights novel and differentiated NMDA receptor mechanism, and rapid and long-lasting antidepressant activity with lead clinical program, Zelquistinel Supports further development of Zelquistinel in a Phase 2 confirmatory study in Major Depressive Disorder, with expected initiation in early 2023 Company highlights business update, recent and upcoming clinical milestones, and additions to advisory network, after emerging from stealth last month INDIANAPOLIS--(BUSINESS WIRE)-- Gate Neurosciences, Inc. today announced the results of research, published in the International Journal of Neuropsychopharmacology, supporting the mechanism of action and clinical foundation of Zelquistinel – the company’s lead oral program in Phase 2 development – as a rapid-acting, long-lasting and safe antidepressant. Publication highlights robust preclinical pro novel mechanism for lead Phase 2 clinical program, Zelquistinel The peer-reviewed manuscript spotlights Zelquistinel’s novel mechanism and pharmacology by which it elicits rapid and long-lasting antidepressant effects. Zelquistinel was shown to positively modulate NMDA receptors (NMDARs) and enhance synaptic plasticity in the hippocampus and medial prefrontal cortex. A single dose of the molecule demonstrated a dose-dependent antidepressant-like response within one hour of administration that was sustained for more than 7 days. The studies highlighted in the publication build upon a robust underlying translational data package and predictive dose model that is consistent across Gate’s class of NMDAR modulators. Zelquistinel’s potential as an oral pill was confirmed by its high bioavailability and brain exposure, and also shows 1000-fold greater potency and a longer plasma half-life compared to its precursor molecule Rapastinel (GLYX-13). In terms of safety, Zelquistinel lacked the sedative, ataxic, and motor impairment effects that are typically observed with NMDAR antagonists and notably, it reversed NMDAR antagonist side effects upon co-administration. These data highlight Zelquistinel’s novel, potent, and highly differentiated mechanism of action with potential for a significantly improved safety pro to other NMDAR-targeted antidepressants in development for depressive disorders. “Zelquistinel’s mechanism of action represents a novel pharmacological approach which may help address patient needs in the treatment of depression,” said Maurizio Fava M.D., Psychiatrist-in-Chief at Massachusetts General Hospital, and a key advisor to Gate Neurosciences. “The upcoming Phase 2 study seeks to navigate the known challenges of conducting trials in psychiatry to confirm efficacy in Major Depressive Disorder.” Business Update Since its inception in 2019, Gate Neurosciences has assembled and advanced a clinical-stage pipeline of next-generation central nervous system therapies, as previously highlighted when the company emerged from stealth-mode in August 2022. Alongside the previously detailed Zelquistinel, Apimostinel and Rapastinel programs acquired from AbbVie, the company has also acquired exclusive rights to preclinical mGlu2/3 receptor antagonists from Eli Lilly which it is currently developing for sleep disorders, and is advancing a preclinical-stage Insulin Growth Factor 2 Receptor (IGF2R) program for cognitive disorders in collaboration with Northwestern University. Recent Milestones Completed financings totaling $25M from life science-focused investors, including Innoviva, Luson Bioventures, Biocrossroads, and ThornApple Capital, among others. Appointed new Board of Directors member Sarah Schlesinger M.D., a leading clinical investigator and chair of the Institutional Review Board at Rockefeller University, and member of the Board of Directors of Innoviva, Inc. Successfully advanced Investigational New Drug (IND) Applications for lead clinical programs. Initiated a Phase 1b clinical study exploring human target engagement biomarkers with 2nd generation injectable NMDAR program Apimostinel, in development for acute severe depression. Established extensive scientific and clinical advisor network, including leading psychiatrists across top institutions in the US. Hosted an R&D Day event at the 2022 ASCP Annual Meeting: “Update on NMDAR Modulators for Depressive Disorders.” Published in several peer-reviewed journals highlighting novel NMDAR mechanism and antidepressant activity of lead programs. The full list of publication can be found at gateneuro.com/publications. Upcoming Milestones First patient dosed in a single- and repeat-dose Phase 1b safety and EEG (electroencephalography) target engagement biomarker study of Apimostinel in 40 healthy volunteers in Q4 2022 with topline readouts expected in Q1 2023. Initiation of a confirmatory Phase 2 study of Zelquistinel in subjects with major depressive disorder (MDD) in early 2023, with topline readout expected mid-2024. Advancement of Rapastinel (GLYX-13) into investigator-led studies in collaboration with multiple leading research hospitals, under the FDA’s Expanded Access Program, beginning in 2023. Key Additions to Advisory Network Gate Neurosciences has continued expanding its network of 20+ scientific and clinical advisors from top psychiatry institutions across the US, who are providing encouraging perspectives on the company’s NMDA receptor modulator portfolio. Recent key additions include Maurizio Fava, M.D., Psychiatrist-in-Chief at Massachusetts General Hospital, and Thomas Laughren, M.D., Former Director for the Division of Psychiatry Products at the FDA. NMDAR Modulator Portfolio: Data Highlights & Mechanistic Understanding The core scientific focus of Gate’s pipeline is addressing synaptic dysfunction, the hallmark disease biology of many cognitive and psychiatric disorders, by enhancing synaptic plasticity and normalizing brain signaling. NMDARs play an essential role in synaptic plasticity and are the targets of an emerging class of rapid-acting antidepressants. Considerable recent progress has been made, along with a suite of publications, clarifying the underlying mechanisms various NMDAR-targeted molecules. Gate Neurosciences’ lead programs are highly differentiated from other NMDAR-targeted antidepressants by acting through positive modulation instead of antagonism. Gate’s molecules positively modulate NMDAR activity on glutamatergic neurons to enhance synaptic plasticity and elicit antidepressant activity. In contrast, antagonists act through NMDARs located on GABA interneurons, causing a profound ‘burst’ of neurotransmitters and accompanying dissociative side effects, before indirectly stimulating downstream effects on synaptic plasticity. Gate’s novel approach represents a more direct mechanism for enhancing natural neuronal plasticity processes, with the potential for a significantly improved safety profile. Recent literature highlighting Gate’s novel mechanism can be found on its website. Key data highlights from the company’s lead NMDAR programs include: Zelquistinel: 3rd generation oral NMDAR modulator Development as a rapid, durable, and well-tolerated chronic oral therapy to address more than 17 million Americans with MDD Supported by a robust, de-risking translational data package across ~350 patients, including consistent target engagement and EEG biomarkers, safety, and clinical antidepressant efficacy A Phase 2a exploratory dose-finding study in MDD (n=251) showed that Zelquistinel 10mg delivered once-weekly was generally safe and well-tolerated, and demonstrated statistically significant differences from placebo on MADRS change from baseline at multiple timepoints over the study Apimostinel: 2nd generation IV NMDAR modulator Development as an acute injectable procedure for the rapid reduction of depressive symptoms in millions of Americans with acute depressive episodes Molecule is 1000-fold more potent than precursor compound Rapastinel, and is the most potent compound in Gate’s class of NMDAR modulators A Phase 2a proof-of-concept study in MDD (n=151) showed that a single dose of Apimostinel 10mg was generally safe and well-tolerated with no ketamine-like side effects, and demonstrated a 5.4-point difference from placebo on HDRS-17 change from baseline at 24-hours (p=0.0034) and a 74% response rate (p=0.0067), among the largest seen to-date within the class of rapid antidepressants Early Stage Research and Development Highlights Company continues to advance preclinical programs towards IND milestones in 2023 GATE-102: oral mGlu2/3 receptor antagonist for hypersomnia GATE-301: IGFBP2 mimetic for neurodegenerative and neurodevelopmental disorders GATE-252: 4th generation oral NMDAR modulator for cognitive disorders Company established cutting-edge research operations at Northwestern University’s Falk Center for Molecular Therapeutics led by Dr. Joseph Moskal Ph.D., the original inventor of Gate’s NMDAR platform Collaborating with leading research institutions with access to world-class laboratory facilities, equipment, and capabilities Advancing development of objective biomarkers for mood disorders, including novel methods to identify and predict patient responder subsets Advancing early research into growth-factor signaling and other novel drug targets of interest that enhance neuronal function and synaptic plasticity “We are excited about the momentum Gate Neurosciences has gathered heading into the remainder of the year, along with our upcoming clinical milestones for our lead programs,” said Mike McCully, President & CEO of Gate Neurosciences. “I believe our next-generation portfolio has true transformative potential for patients suffering from neuropsychiatric and cognitive disorders.” About Gate Neurosciences Gate Neurosciences is a precision medicine biotechnology company focused on advancing next-generation CNS treatments that address growing needs in mental health. The company is developing a portfolio of novel mechanisms of action that enhance synaptic function to address neuropsychiatric and neurocognitive diseases, including major depressive disorder (MDD). Using learnings from extensive clinical, preclinical, and translational data and a better understanding of CNS development challenges, the company is advancing its clinical pipeline using evidence-driven, precision psychiatry approaches.