ATXN3

Spinocerebellar Ataxia (SCA) is a rare, genetic, life-threatening neurodegenerative disease with no available treatment. Troriluzole demonstrated a 50-70% slowing of SCA disease progression on the primary and secondary outcome measures at the 3-year endpoint in a real-world evidence (RWE) study. Troriluzole has a well-established safety profile and if approved, would be the first and only FDA-approved treatment for SCA; subject to receipt of FDA approval, Biohaven is prepared to commercialize troriluzole for SCA in the US in 2025. NEW HAVEN, Conn. , Feb. 11, 2025 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), today announced that the US Food and Drug Administration (FDA) has accepted for review the Company's New Drug Application (NDA) for troriluzole for the treatment of adult patients with spinocerebellar ataxia (SCA) and has granted Priority Review. This designation is assigned to applications for drugs that would offer a significant improvement over other available treatments for a given disorder or would provide a treatment option where none exists. In the case of SCA, a rare, genetic, neurodegenerative disease, troriluzole would be the first and only FDA-approved treatment for this life-threatening disorder. The FDA's decision regarding the NDA is expected within 6 months of filing (during 3Q2025). Based on FDA Priority Review timelines and if ultimately approved, Biohaven is prepared to commercialize troriluzole for SCA in the US in 2025. Melissa Beiner , M.D., SCA Clinical Development Lead at Biohaven , commented, "Our NDA filing is the culmination of over 8 years of clinical research and represents an important collaboration across the SCA community. The troriluzole NDA reflects rigorous scientific collaborations between advocacy groups, patients and their families, clinical experts in SCA and Biohaven . The FDA decision to grant Priority Review demonstrates the extremely high unmet need in this rare neurodegenerative disease. Time is of the essence for patients with SCA, who are suffering relentless and irreversible functional decline including impairments in coordination and balance leading to falls, loss of ambulation, and difficulties with vision, speech and swallowing." Dr. Beiner added, "The robust clinical data presented in the NDA demonstrate sustained and compelling treatment benefit in SCA patients treated with troriluzole, a once-daily, oral pill. We look forward to working closely with the FDA throughout the review process to bring the very first treatment to patients and families suffering from SCA." The NDA submission was based, in part, on positive topline results from Study BHV4157-206-RWE (NCT06529146), in which troriluzole 200 mg dosed orally in patients with SCA met the study's primary endpoint of change from baseline on the functional Scale for the Assessment and Rating of Ataxia (f-SARA), in all SCA genotypes, at 3 years compared to an external control arm. Troriluzole showed statistically significant superiority across 9 consecutive, prespecified primary and secondary endpoints with highly consistent, sustained, robust and clinically meaningful treatment effects. SCA patients treated with troriluzole showed a 50-70% slower rate of decline, representing 1.5-2.2 years delay in disease progression, over the 3-year study period (Figures 1-3 and Table 1). The NDA also includes confirmatory and supportive data from Studies BHV4157-201 and BHV4157-206, the first large, multi-center registrational trials in SCA. Notably, these data include disease stabilization in the SCA3 genotype (Figure 4) and a reduction in falls in all SCA genotypes (Figure 5), both compared to placebo over 48 weeks in Study BHV4157-206. Jeremy Schmahmann , M.D., Professor of Neurology at Harvard Medical School and Founding Director of the Ataxia Center and the Martha and Robert Fogelman Endowed Chair in Ataxia and Cerebellar Neurology at Massachusetts General Hospital commented, "The FDA acceptance for review of this NDA represents a critical milestone for SCA patients. Since the discovery of the first gene for SCA in 1993, patients and families affected by SCA have watched generation after generation suffer severe, progressive disability and premature death with no treatment options. The need for an intervention that can slow disease progression and help patients maintain their independence is urgent. The delay in disease decline shown in the real-world evidence study is a watershed in the history of the SCAs. This is what patients have been waiting for. It is what the doctors who have been powerless, have been waiting for. Additionally, the importance of troriluzole's effects on reducing falls in this patient population cannot be overstated. I applaud the FDA for recognizing this urgency by granting a Priority Review and look forward to using troriluzole in the clinic if approved." Biohaven's troriluzole clinical development program in SCA collected data over 8 years, including a robust long-term safety profile, and was the first industry trial conducted in SCA. The external control arms used in Biohaven's BHV4157-206-RWE Study were provided from objective, third-party data gathered from two independent natural history cohorts: one in the United States and one in Europe (EUROSCA Natural History Study). The National Ataxia Foundation (NAF) sponsored the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA) that served as the basis for the US natural history cohort. The data from the CRC-SCA is managed by the University of South Florida Health Informatics Institute . A total of 35 clinical sites provided data in the US and European natural history cohorts that served as the external controls in BHV4157-206-RWE. As per instructions from FDA on the real-world evidence study design and statistical analysis plan, the external control arm was determined using a Propensity Score Matching (PSM) method to ensure that untreated subjects from the comparator natural history cohort were rigorously matched to treated subjects from the troriluzole arm of Study BHV4157-206. PSM was used on all prognostic, demographic, and baseline characteristics known to be associated with disease progression in SCA, including baseline f-SARA, age, sex, age at symptom onset, genotype, and trinucleotide repeat length (by genotype). Andrew Rosen , Chief Executive Officer of the National Ataxia Foundation (NAF), stated, " Biohaven's SCA program reflects years of dedicated clinical research and collaboration with leading world experts and advocacy groups to advance the ataxia field. We are proud that our multi-year effort to fund and support the Clinical Research Consortium for the Study of Cerebellar Ataxia played such a critical role in providing the external control arm of Biohaven's study. The goal of CRC-SCA is to improve our understanding of SCA disease progression and to promote the development of disease-modifying therapies for SCA." Mr. Rosen added, "On behalf of patients and families, who have watched generations of family members succumb to this devastating disease and have been waiting for decades for a treatment that could slow disease progression, I thank the FDA for not only accepting this NDA for review, but recognizing the need for urgency for our community in the form of a Priority Review." Biohaven previously received both Fast-Track and Orphan Drug Designation (ODD) from the FDA, and ODD from the European Medicines Agency , where a troriluzole MAA is currently under review. An expanded access protocol (EAP) is currently enrolling patients with SCA who are eligible. EAPs are designed to give early access to potential therapies before they are approved by the FDA. More information about can be found at https://clinicaltrials.gov/study/NCT06034886. About Spinocerebellar Ataxia (SCA)Spinocerebellar ataxia is a group of dominantly inherited neurodegenerative disorders characterized by progressive loss of voluntary motor control and atrophy of the cerebellum and brainstem. SCA affects approximately 15,000 people in the United States and 24,000 in Europe and the United Kingdom . Patients experience significant morbidity, including impaired gait leading to falls, loss of ambulation and progression to a wheelchair, inability to communicate due to speech impairment, difficulty swallowing, and premature death. While signs and symptoms can appear anytime from childhood to late adulthood, SCA typically presents in early adulthood and progresses over a number of years. Currently, there are no FDA-approved treatments and no cure for SCA. About TroriluzoleTroriluzole is a new chemical entity (NCE) and third-generation novel prodrug that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. The primary mode of action of troriluzole is reducing synaptic levels of glutamate. Troriluzole increases glutamate uptake from the synapse, by augmenting the expression and function of excitatory amino acid transporters located on glial cells that play a key role in clearing glutamate from the synapse. The glutamate modulating activity of troriluzole addresses the widely documented glutamate deregulation that underlies neurodegeneration and Purkinje cell dysfunction in patients with SCA. Troriluzole also has the potential to be developed in a number of other diseases associated with excessive glutamate. More information about troriluzole can be found at the Biohaven's website: https://www.biohaven.com/pipeline/clinical-programs/glutamate/. About Biohaven Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience, and oncology. The company is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's extensive clinical and preclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; extracellular protein degradation for immunological diseases; TRPM3 antagonism for migraine and neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory disorders; glutamate modulation for OCD and SCA ; myostatin inhibition for neuromuscular and metabolic diseases, including SMA and obesity; antibody recruiting bispecific molecules and antibody drug conjugates for cancer. For more information, visit www.biohaven.com. Forward-looking StatementsThis news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, , including the potential approval and commercialization of troriluzole for SCA, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates; the potential for Biohaven's product candidates to be first approved therapies; and the effectiveness and safety of Biohaven's product candidates. 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 news 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. Investor Contact: Jennifer Porcelli Vice President, Investor Relationsjennifer.porcelli@biohavenpharma.com+1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. mikebeyer@sambrown.com+1 (312) 961-2502 View original content to download multimedia:https://www.prnewswire.com/news-releases/biohaven-announces-fda-acceptance-and-priority-review-of-troriluzole-new-drug-application-for-the-treatment-of-spinocerebellar-ataxia-302373056.html SOURCE Biohaven Ltd.

PASADENA, Calif.--( BUSINESS WIRE )--Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that the global licensing and collaboration agreement with Sarepta Therapeutics (NASDAQ: SRPT) announced on November 26, 2024, has now closed. Closing of the transaction was subject to the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 and other customary conditions. Summary Financial Terms Upon closing, Arrowhead receives a $500 million upfront payment and $325 million through the purchase by Sarepta of Arrowhead common stock priced at $27.25 per share. Arrowhead will also receive $250 million to be paid in annual installments of $50 million over 5 years. Arrowhead also has the potential to receive $300 million in near-term payments associated with the continued enrollment of certain cohorts of a Phase 1/2 study of ARO-DM1, which Arrowhead is on track to achieve during the next 12 months. Arrowhead is eligible to receive development milestone payments of between $110 million and $410 million per program and sales milestone payments of between $500 million and $700 million per program. Arrowhead is also eligible to receive tiered royalties on commercial sales up to the low double digits. Summary of Programs under License and Collaboration Agreement Clinical Stage ARO-DUX4, which is designed to target the gene that encodes the DUX4 protein as a potential treatment for patients with facioscapulohumeral muscular dystrophy type 1, currently dosing patients in a Phase 1/2 clinical study. ARO-DM1, which is designed to reduce expression of the dystrophia myotonica protein kinase (DMPK) gene in skeletal muscle as a potential treatment for patients with type 1 myotonic dystrophy, currently dosing patients in a Phase 1/2 clinical study. ARO-MMP7, which is designed to reduce expression of matrix metalloproteinase 7 (MMP7) in the lung as a potential treatment for idiopathic pulmonary fibrosis, currently dosing patients in a Phase 1/2 clinical study. ARO-ATXN2, which is designed to silence expression of the toxic ATXN2 protein in the CNS as a potential treatment for spinocerebellar ataxia 2 (SCA2), currently in a Phase 1/2 study that is open for enrollment. Preclinical Stage ARO-HTT for patients Huntington’s disease expected to be CTA-ready in 2025 ARO-ATXN1 for patients with spinocerebellar ataxia 1 (SCA1) expected to be CTA-ready in 2026 ARO-ATXN3 for patients with spinocerebellar ataxia 3 (SCA3) expected to be CTA-ready in 2026 Discovery During the five-year term, Sarepta can propose up to six new CNS or muscle targets for which Arrowhead will perform discovery and preclinical development. Sarepta would then receive an exclusive license to those programs and be responsible for clinical development and commercialization. Drug Manufacturing Under the agreement, Arrowhead will manufacture clinical drug supply for all programs arising out of the license and collaboration, and commercial drug product for the four programs currently in clinical trials. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit www.arrowheadpharma.com , or follow us on X (formerly Twitter) at @ArrowheadPharma , LinkedIn , Facebook , and Instagram . To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts . Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” “continue,” “target,” “forecast” or “continue” or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc.

WOODBRIDGE, Conn.--( BUSINESS WIRE )--Cure Rare Disease (CRD) announced it has been awarded a $5.69 million grant from the California Institute for Regenerative Medicine (CIRM) to advance the development of an antisense oligonucleotide therapy for spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disorder with no current treatment. Cure Rare Disease launched its SCA3 program in 2021 to develop an antisense oligonucleotide (ASO) therapy, with initial funding support provided by Gregory Klassen, a patient living with SCA3. In 2022 and 2023, in collaboration with Leiden University Medical Center and the Cure Rare Disease team, several in vivo studies were conducted in a disease mouse model, demonstrating functional improvement. A clinical candidate was identified through non-GLP toxicology studies conducted with Charles River Labs. In 2024, a Type B pre-IND meeting with the Food and Drug Administration (FDA) provided regulatory guidance ahead of manufacturing scale-up and clinical trial design. With CIRM funding support, Cure Rare Disease will complete manufacturing scale-up, conduct IND-enabling toxicology studies and submit an investigational new drug (IND) application to initiate early clinical trials. The trials will be led by Principal Investigator Dr. Susan Perlman at UCLA. "This program is a powerful example of what can be achieved when patients, organizations, researchers and governing bodies come together with a shared mission. From Greg Klassen’s initial support to our collaborations with leading scientists and clinicians, industry partners and regulatory guidance from the FDA, the development of a therapy for SCA3 has been a truly unified effort,” said Cure Rare Disease CEO and founder Richard Horgan. “We are incredibly appreciative of CIRM’s support in helping us take this program into the clinic, proving that rare disease treatments can be brought to patients through our model of collective dedication and innovation." About SCA3 Spinocerebellar ataxia type 3 (SCA3) is a rare neuromuscular disease with a prevalence of one to five in 100,000 people. It is the most common form of spinocerebellar ataxia. The disease is caused by mutations in the ATXN3 gene, which codes for the enzyme ataxin-3. Ataxin-3 is found throughout the body and helps destroy and remove damaged proteins. SCA3 results from a mutation that causes a toxic accumulation of trinucleotide repeats. About Cure Rare Disease (CRD) Cure Rare Disease (CRD) is a nonprofit biotechnology company focused on developing genetic medicines for rare and ultra-rare diseases. CRD is committed to accelerating the development of treatments for individuals with rare diseases through a patient-centric approach to research and development. The company's programs include gene therapy and antisense oligonucleotide (ASO) treatments for a range of rare diseases. For more information, visit www.cureraredisease.org . About the California Institute for Regenerative Medicine (CIRM) The California Institute for Regenerative Medicine (CIRM) is a funding agency established by Californians to accelerate regenerative medicine research and deliver treatments for patients with unmet medical needs. Established in 2004 through the passage of Proposition 71, CIRM was initially funded with $3 billion from the state of California to support ongoing research. In 2020, Proposition 14 provided an additional $5.5 billion to continue the agency’s work. CIRM has funded billions in stem cell and genetic research, as well as development programs. Through its research, infrastructure and education programs, CIRM aims to transform regenerative medicine, stimulate economic growth and improve the lives of diverse communities throughout the state. For more information, visit www.cirm.ca.gov .