Glutamates

BL-001 demonstrated a favorable safety and tolerability profile in healthy volunteers that supports dosing up to 10-fold higher than the efficacious dose level in animal models Dose dependent strain kinetics of BL-001 observed The U.S. Food and Drug Administration (FDA) grants Rare Pediatric Disease Designation to BL-001 for Dravet syndrome SAN DIEGO, Aug. 17, 2023 /PRNewswire/ -- Bloom Science, Inc., a clinical-stage, central nervous system (CNS) company focused on discovering and developing breakthrough therapeutics that target the Gut-Brain Axis for neurological diseases, today announced positive results from its Phase 1 clinical study in healthy volunteers that demonstrate a favorable safety, tolerability and strain kinetics profile of BL-001, an orally-delivered Live Biotherapeutic Product (LBP). Bloom is developing BL-001 for both Dravet syndrome and amyotrophic lateral sclerosis (ALS). Bloom also announced today that BL-001 received Rare Pediatric Disease Designation from FDA for Dravet syndrome. "Dravet syndrome is a rare and devastating form of childhood epilepsy in which there is an unmet need for patients whose seizures remain difficult to control and who experience significant side effects with current medications," said Paolo Baroldi, PhD, MD, Chief Medical Officer of Bloom Science. "BL-001 shows promise as a novel treatment option that can change lives. With these results we plan to proceed into Phase 2 clinical development with doses we expect to be within the therapeutic window in both Dravet syndrome and ALS." Summary of Key BL-001 Phase 1 Study Results: BL-001 demonstrated a favorable safety profile and was well tolerated with no Serious Adverse Events (SAEs) across all four dose cohorts Favorable strain kinetics were observed with BL-001 component strains increasing in a dose dependent manner All treatment-related Adverse Events (AEs) were mild with the exception of one subject in the highest dose who experienced moderate fatigue that resolved without intervention and they continued on treatment In the highest dose cohort of BL-001, the most common treatment-related adverse event (AE) was decreased appetite (3/6 subjects) with no other treatment-related AEs occurring in more than a single individual All treatment-related AEs were transient, with the exception of decreased appetite which persisted until the follow-up period for two subjects, and all treatment-related AEs resolved without intervention No AEs led to study drug withdrawal and all participants completed the study There were no clinically significant ECG abnormalities reported in any individual across all treatment cohorts "By taking a breakthrough approach to therapeutic development via the Gut-Brain Axis, we believe Bloom has the potential to develop completely novel, transformational treatments with superior safety and efficacy profiles that can have a significant impact on the lives of the patients suffering from rare diseases," said Christopher Reyes, PhD, founder and CEO of Bloom Science. "This milestone builds on many years of groundbreaking work that validate Bloom's IrisRx platform and ability to select strains optimized for both safety and activity." Based on the preclinical profile together with these Phase 1 results, Bloom intends to advance BL-001 into Phase 2 studies in both Dravet syndrome and ALS patients in 2024. About Phase 1 Clinical Trial of BL-001 in Healthy Volunteers The Phase 1 study of BL-001 was a randomized, double-blind, placebo-controlled, single-center, multiple ascending dose study in healthy volunteers (NCT05818306). The primary objective of the study was to investigate the safety and tolerability of BL-001 in healthy volunteers for 28 consecutive days. In the study, BL-001 or placebo was administered to 32 healthy adult participants (BL-001 n=24; placebo n =8) across four dose cohorts. About BL-001 BL-001 is a first-in-class, orally delivered, Live Biotherapeutic Product (LBP) being developed by Bloom Science for the treatment of multiple neurological diseases, including Dravet syndrome and ALS. BL-001 was first designed to replicate the antiepileptic effect of the Ketogenic Diet to modulate gamma aminobutyric acid (GABA) and other key bioenergetic pathways. BL-001 contains two rationally selected human gut microbes that have been shown in both cell-based assays and animal studies to eliminate hyper-excitatory activity, increase GABA in the hippocampus and significantly reduce or eliminate both seizure frequency and duration. BL-001 also aims to address the underlying oxidative stress, a critical factor in the progression of ALS, to potentially slow or halt disease progression. BL-001 has been shown to attenuate motor-neuron loss, increase lifespan and motor coordination in preclinical ALS studies. About Bloom Science Bloom Science is a clinical-stage, central nervous system (CNS) company, trailblazing a path to transformative, novel therapeutics for patients with rare and complex neurological disorders. Bloom's proprietary discovery platform, IrisRx™ enables a fundamentally different approach to developing medicines by harnessing our expanding insight into the Gut-Brain Axis to design and develop therapeutics that target novel biology with superior safety profiles. The IrisRx™ platform unlocks the potential for developing multi-functional therapeutics from the most common cell type in the human body, gut commensal microbes, while also utilizing an expanding proprietary knowledge base to advance therapeutic candidates based on synthetic biology. Bloom Science is advancing a deep pipeline of programs, including Dravet syndrome, other rare epilepsies, Amyotrophic Lateral Sclerosis (ALS), and other neurodegenerative and cognitive disorders. For more information, visit: Forward-Looking Statement This press release may contain "forward-looking statements," including statements by Dr. Reyes or other persons on Bloom Science's behalf and statements regarding Bloom Science's expectations about any of the following: (i) the safety, efficacy and clinical progress of our various clinical programs, including our BL-001 program; (ii) the status of clinical trials (including activities at clinical trial sites); (iii) the data generated by ongoing and planned clinical trials, and the ability to use that data for the design and initiation of further clinical trials; and (iv) the therapeutic value, development, and commercial potential of Bloom Science Live Biotherapeutic Products. The words "believes," "anticipates," "plans," "expects" and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although Bloom Science believes such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. Bloom Science disclaims any obligation or undertaking to update or revise any forward-looking statements, other than as required by law. SOURCE Bloom Science

- Taldefgrobep alfa, a myostatin-targeting biologic investigational agent, in Phase 3 development to increase muscle mass for Spinal Muscular Atrophy patients now granted Fast Track in addition to previously receiving Orphan Drug Designation in the US Biohaven Ltd. (NYSE: BHVN; "Biohaven") announced today that it received Fast Track designation from the U.S. Food and Drug Administration (FDA) for taldefgrobep alfa, a novel anti-myostatin adnectin, for the treatment of spinal muscular atrophy (SMA). Fast Track designation enables important new drugs to reach patients earlier by facilitating more frequent communications with the FDA and expeditious review of a drug which treats a serious condition and fills an unmet medical need. Biohaven previously received orphan drug designation from the FDA for taldefgrobep in the treatment of SMA. SMA is a rare, progressively debilitating motor neuron disease in which development and growth of muscle mass are compromised, resulting in progressive weakness and muscle atrophy, reduced motor function, impaired quality of life and often death. Inhibition of myostatin, a naturally occurring protein that limits skeletal muscle growth, an important process in healthy muscular development, is a potential therapeutic target for SMA. Taldefgrobep has the potential to be a novel therapy to be used in combination with disease modifying therapies to enhance muscle function by blocking myostatin activity. Taldefgrobep's novelty in a field of myostatin inhibitors is based on its mechanism of action. It binds to myostatin to both lower overall myostatin levels and also function as a receptor antagonist, thereby blocking myostatin signaling in skeletal muscles. Lindsey Lee Lair, M.D., M.B.A., F.A.A.N, Vice President, Clinical Development, Biohaven commented, "We are very pleased the FDA granted Fast Track designation for taldefgrobep alfa for the treatment of SMA. Children and adults living with SMA experience significant muscle weakness and functional impairments affecting their quality of life daily, and a substantial unmet medical need persists. We are excited about the potential for taldefgrobep alfa to improve the lives of patients and families affected by SMA." Karen Chen, Ph.D., CEO, SMA Foundation, added, "Fast Track designation from the FDA underscores the high unmet medical need in SMA and supports the need for additional novel combination therapies in children and adults living with this progressive neurologic disease. The SMA Foundation is heavily investing in supporting the development of additional muscle and neuromuscular regenerative medicine therapies that provide functional benefits to patients. We are happy to see the commitment of health authorities to rapidly advance the development of new therapies" As a leader in innovative trials addressing neurodegenerative diseases, Biohaven is currently enrolling a Phase 3 clinical trial of taldefgrobep in SMA: A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants with Spinal Muscular Atrophy (RESILIENT) (NCT05337553). About Taldefgrobep alfa Taldefgrobep alfa (also known as BHV2000) is a modified adnectin designed to specifically bind to myostatin (GDF-8). Taldefgrobep is a fully human anti-myostatin recombinant protein that lowers free myostatin and acts as an Activin 2b receptor antagonist with the myostatin-taldefgrobep complex. Adnectins are an established proprietary protein therapeutic class based on human fibronectin, an extracellular protein that is naturally abundant in human serum. About Spinal Muscular Atrophy (SMA) Spinal muscular atrophy (SMA) is a rare genetic neurodegenerative disorder characterized by the loss of motor neurons, atrophy of the voluntary muscles of the limbs and trunk and progressive muscle weakness that is often fatal and typically diagnosed in young children. The underlying pathology of SMA is caused by insufficient production of the SMN (survival of motor neuron) protein, essential for the survival of motor neurons, and is encoded by two genes, SMN1 and SMN2. In the U.S., SMA affects approximately 1 in 11,000 births, and about 1 in every 50 Americans is a genetic carrier. About Biohaven Biohaven is a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies for people with debilitating neurological and neuropsychiatric diseases, including rare disorders. Biohaven is advancing a pipeline of best-in-class therapies for diseases with little or no treatment options, leveraging its proven drug development capabilities and proprietary platforms, including Kv7 ion channel modulation for epilepsy and neuronal hyperexcitability; glutamate modulation for obsessive-compulsive disorder and spinocerebellar ataxia and myostatin inhibition for neuromuscular diseases. Biohaven's portfolio of early- and late-stage product candidates also includes discovery research programs focused on TRPM3 channel activation for neuropathic pain and CD-38 antibody recruiting, bispecific molecules for multiple myeloma. More information about Biohaven is available at www.biohaven.com. Forward-looking Statements This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "believe", "may" and "will" and similar expressions, are intended to identify forward-looking statements. These forward-looking statements involve substantial risks and uncertainties, including statements that are based on the current expectations and assumptions of Biohaven's management about taldefgrobep alfa as treatment for patients with neuromuscular disease. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates are not guarantees of future performance or results and involve substantial risks and uncertainties. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this new release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Biohaven Contact: Jennifer Porcelli Vice President, Investor Relations [email protected] 201-248-0741 Mike Beyer Sam Brown Inc. [email protected] 312-961-2502 SOURCE BIOHAVEN LTD

NEW HAVEN, Conn., Sept. 29, 2022 /PRNewswire/ -- Biohaven Pharmaceutical Holding Company Ltd. ( NYSE: BHVN) today announced results from a focused analysis of treatment with verdiperstat in the HEALEY ALS Platform Trial in amyotrophic lateral sclerosis (ALS). The HEALEY ALS Platform Trial, the first-ever platform trial in ALS, is designed as an adaptive trial to evaluate multiple investigational treatments simultaneously, thus accelerating the development of effective and breakthrough treatments for people living with ALS. Verdiperstat did not statistically differentiate from placebo on the prespecified primary efficacy outcome, disease progression measured by the ALS Functional Rating Scale-Revised and survival, nor the key secondary efficacy measures during the 24-week study period. Initial analysis of safety data was consistent with the overall profile of verdiperstat from prior clinical trial experience. Additional analyses are ongoing, and complete study results will be presented at an upcoming scientific meeting. Irfan Qureshi, M.D., Senior Vice President of Neurology at Biohaven, stated, "We are incredibly grateful to our collaborators at the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, HEALEY ALS Platform Trial study investigators, and the ALS community – especially people with ALS and their families –– who made the trial possible. While we are disappointed that verdiperstat did not demonstrate efficacy for ALS, Biohaven remains committed to developing treatments for people who suffer from neurodegenerative diseases." About ALS ALS is a progressive, life-threatening, and rare neuromuscular disease that affects approximately 30,000 people in the United States. The median age of onset is 55 years and average survival is 3-5 years after onset of first symptoms. ALS is characterized by the loss of motor neurons in the brain, brainstem, and spinal cord that leads to progressive muscle weakness and difficulties in speaking, swallowing, and breathing. There are currently limited treatment options and no cure for ALS. About Biohaven Biohaven is a global commercial-stage biopharmaceutical company with a portfolio of innovative, best-in-class therapies to improve the lives of patients with debilitating neurological and neuropsychiatric diseases, including rare disorders. Biohaven's Neuroinnovation™ portfolio includes FDA-approved Nurtec ® ODT (rimegepant) for the acute and preventive treatment of migraine (EMA-approved as Vydura™ (rimegepant) for the acute treatment of migraine with or without aura, and prophylaxis of episodic migraine in adults who have at least four migraine attacks per month) and a broad pipeline of late-stage product candidates across five distinct mechanistic platforms: CGRP receptor antagonism for the acute and preventive treatment of migraine; glutamate modulation for obsessive-compulsive disorder and spinocerebellar ataxia; and MPO inhibition for amyotrophic lateral sclerosis; Kv7 Ion Channel Activators (Kv7) for focal epilepsy and neuronal hyperexcitability, and myostatin inhibition for neuromuscular diseases. More information about Biohaven is available at www.biohavenpharma.com.