Charcot-Marie-Tooth disease type 2S

WASHINGTON, Jan. 23, 2024 /PRNewswire/ -- Vanda Pharmaceuticals, Inc. (Vanda) (Nasdaq: VNDA) today announced that the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application to evaluate VCA-894A for the treatment of a patient with Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S), caused by cryptic splice site variants within the IGHMBP2 gene. CMT2S is a rare subtype of Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy for which there is no available treatment. CMT2S is characterized by slowly progressive distal muscle weakness and atrophy, affecting the upper and lower limbs in a child's first decade of life, leaving patients with decreased reflexes and sensory impairment1,2 The estimated overall prevalence of CMT is 1 in 2,500 individuals, with varying clinical features dependent on the various genetic variants of CMT.1,2 The prevalence of the CMT2S variant is estimated to be less than 1 in 1,000,000 worldwide.3 "This is an important milestone in the pursuit of personalized medicine, which has the potential to enable the development of treatments tailored to one's genetic variants, in this case specifically for a patient with CMT2S causing genetic mutations," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. VCA-894A is a novel antisense oligonucleotide (ASO) with a mechanism of action that specifically targets a cryptic splice site variant within immunoglobulin mu-binding protein 2 (IGHMBP2). Mutations within IGHMBP2 play a pivotal role in the manifestation of CMT2S, likely due to alpha-motor neuron loss, and consequently peripheral nervous system deterioration.4 ASOs have the capacity to modulate gene expression, allowing for the personalized treatment of rare diseases. Delivery of ASOs to the central nervous system has been previously successful in several ASO programs, with a broad applicability in addressing a number of neurodegenerative and neuromuscular disorders.5 References Cottenie, E., et al. (2014). Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. American journal of human genetics, 95(5), 590–601. Nam, S. H., & Choi, B-O. (2019). Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes." Precision and Future Medicine, 3(2), 43–68. (2023). Charcot-Marie-Tooth disease type 2S. Orpha.net. Rzepnikowska, W., & Kochański, A. (2021). Models for IGHMBP2-associated diseases: an overview and a roadmap for the future. Neuromuscular disorders: NMD, 31(12), 1266–1278. Crooke, S. T., Liang, X. H., Baker, B. F., & Crooke, R. M. (2021). Antisense technology: A review. The Journal of biological chemistry, 296, 100416. About Vanda Pharmaceuticals Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit and follow us on Twitter @vandapharma. About VCA-894A VCA-894A is a 2'-O-methoxyethyl (MOE) phosphorothioate oligonucleotide sodium salt. VCA-894A specifically targets a cryptic splice site variant within IGHMBP2, which causes CMT2S. ASOs may have broad applicability in addressing a number of disorders, from nervous system treatments to systemic treatments. CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS Various statements in this press release, including, but not limited to statements regarding the estimated prevalence of CMT and CMT2S and the development of individualized treatments, are "forward-looking statements" under the securities laws. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, the accuracy of the reporting and diagnosis of CMT and CMT2S cases and the ability to successfully complete the clinical development of, and obtain regulatory approval for, VCA-894A in the treatment of CMT2S. Therefore, no assurance can be given that the results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Forward-looking statements in this press release should be evaluated together with the various risks and uncertainties that affect Vanda's business and market, particularly those identified in the "Cautionary Note Regarding Forward-Looking Statements", "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's most recent Annual Report on Form 10-K, as updated by Vanda's subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the U.S. Securities and Exchange Commission, which are available at . All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this press release is provided only as of the date of this press release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 pr@vandapharma.com Company Codes: NASDAQ-NMS:VNDA

WASHINGTON, June 1, 2023 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for VCA-894A for the treatment of Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S), caused by cryptic splice site variants within IGHMBP2. CMT2S is a rare subtype of Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy for which there is no available treatment. The estimated prevalence of CMT is 1 in 2,500 individuals, with varying clinical features dependent on the various genetic variants of CMT.1,2 The prevalence of CMT2S is estimated to be less than 1 in 1,000,000 worldwide.3 Onset of CMT2S begins in early childhood.2 CMT2S is characterized by slowly progressive distal muscle weakness and atrophy, affecting the upper and lower limbs in a child's first decade of life, leaving patients with decreased reflexes and sensory impairment.1,2 Because CMT2S is a progressive disease, most patients become wheelchair bound. "This designation is an important milestone, which we believe may enable the development of individualized treatments tailored to one's genetic variants for patients with CMT2S," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. VCA-894A is a novel antisense oligonucleotide (ASO) with a mechanism of action that specifically targets a cryptic splice site variant within immunoglobulin mu-binding protein 2 (IGHMBP2). Mutations within IGHMBP2 play a pivotal role in the manifestation of CMT2S, likely due to alpha-motor neuron loss, and consequently peripheral nervous system deterioration.4 ASOs have the capacity to modulate gene expression, allowing for the personalized treatment of rare diseases. Delivery of ASOs to the central nervous system has been previously successful in several ASO programs, with a broad applicability in addressing a number of neurodegenerative and neuromuscular disorders.5 Orphan Drug Designation is granted by the FDA to investigational therapies addressing rare medical conditions and provides benefits to drug developers. References Cottenie, E., et al. (2014). Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. American journal of human genetics, 95(5), 590–601. Nam, S. H., & Choi, B-O. (2019). Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes." Precision and Future Medicine, 3(2), 43–68. (2023). Charcot-Marie-Tooth disease type 2S. Orpha.net. Rzepnikowska, W., & Kochański, A. (2021). Models for IGHMBP2-associated diseases: an overview and a roadmap for the future. Neuromuscular disorders: NMD, 31(12), 1266–1278. Crooke, S. T., Liang, X. H., Baker, B. F., & Crooke, R. M. (2021). Antisense technology: A review. The Journal of biological chemistry, 296, 100416. About Vanda Pharmaceuticals Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit and follow us on Twitter @vandapharma. About VCA-894A VCA-894A is a 2'-O-methoxyethyl (MOE) phosphorothioate oligonucleotide sodium salt. VCA-894A specifically targets a cryptic splice site variant within IGHMBP2, which causes CMT2S. ASOs may have broad applicability in addressing a number of disorders, from nervous system treatments to systemic treatments. CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS Various statements in this press release, including, but not limited to statements regarding the estimated prevalence of CMT and CMT2S and the development of individualized treatments, are "forward-looking statements" under the securities laws. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, the accuracy of the reporting and diagnosis of CMT and CMT2S cases and the ability to successfully complete the clinical development of, and obtain regulatory approval for, VCA-894A in the treatment of CMT2S. Therefore, no assurance can be given that the results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Forward-looking statements in this press release should be evaluated together with the various risks and uncertainties that affect Vanda's business and market, particularly those identified in the "Cautionary Note Regarding Forward-Looking Statements", "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's most recent Annual Report on Form 10-K, as updated by Vanda's subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the U.S. Securities and Exchange Commission, which are available at . All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this press release is provided only as of the date of this press release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] Elizabeth Van Every Head of Corporate Affairs Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] SOURCE Vanda Pharmaceuticals Inc.

CAMBRIDGE, MA and LOWELL, MA, USA I January 04, 2023 I Biogen Inc. (Nasdaq: BIIB) and Alcyone Therapeutics (Alcyone) have entered into a license and collaboration agreement to develop Alcyone’s ThecaFlex DRx™ System, an implantable medical device intended for subcutaneous delivery of antisense oligonucleotide (ASO) therapies into the intrathecal space. Through this agreement, Biogen aims to leverage the ThecaFlex DRx™ System with a goal of improving the patient treatment experience and accessibility for a broader population of people suffering from neurological disorders, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). The ThecaFlex DRx™ System has the potential to be the first implantable device designed to enable routine subcutaneous administration of ASO therapies to the cerebrospinal fluid. The ThecaFlex DRx™ System has received a CE Mark in Europe. In addition, it has also received Breakthrough Device Designation from the U.S. Food and Drug Administration (FDA) and will require further clinical studies before it can be submitted to the FDA for review. “We are continually listening to the neuromuscular disease community and whenever possible, adapting our work to meet their evolving needs for treatment and patient care,” said Priya Singhal, Interim Head of R&D at Biogen. “Biogen looks forward to working with Alcyone to explore the potential of this device, which we believe will provide greater flexibility to people with spinal muscular atrophy and other neurological disorders as well as their doctors in making the right treatment decisions.” “Alcyone designed the ThecaFlex DRx™ System to be a therapeutic delivery alternative for patients with a chronic neurological condition whose current treatment requires repeat lumbar puncture,” said PJ Anand, Chief Executive Officer of Alcyone. "This agreement underscores Alcyone’s expertise in cerebrospinal fluid delivery technology which we believe will lead to an improved treatment experience for some people living with neurological conditions and their caregivers. We consider Biogen, a global leader, an ideal collaborator toward this mutual goal.” Under the terms of the agreement, Biogen will make an upfront payment of $10 million to Alcyone for an exclusive global license to the ThecaFlex DRx™ System in SMA and ALS as well as a co-exclusive global license in an unnamed indication. Should certain development and commercial milestones be achieved, Alcyone will be eligible to receive up to $41 million in potential milestone payments. The deal also provides flexibility to expand the collaboration as additional ASO therapies progress through Biogen’s pipeline. Biogen and Alcyone will jointly collaborate on clinical development of the ThecaFlex DRx™ System for ASO therapies, and Alcyone will be solely responsible for its manufacture and commercialization. The ThecaFlex DRx™ System will initially be evaluated with SPINRAZA® (nusinersen) in SMA, which will inform pathways for Biogen's broader portfolio of investigational ASO therapies. About The ThecaFlex DRx™ System The ThecaFlex DRx™ System (ThecaFlex), a technology within Alcyone’s Falcon™ Delivery Platform, is an implantable intrathecal (IT) catheter, catheter fixation device, and subcutaneous port system designed to provide access to the cerebrospinal fluid (CSF) for the infusion of therapy by IT bolus administration. Lumbar puncture (LP), commonly known as a spinal tap, is the current standard of care approach to delivering therapeutics into the CSF. ThecaFlex is designed to be an alternative to LP, especially for people with challenging anatomy or for those who require multiple anesthesia and radiation exposures for repeat LPs. The ThecaFlex DRx™ System has received CE Mark in Europe and Breakthrough Device Designation from the U.S. Food and Drug Administration (FDA). ThecaFlex is not approved by the FDA. For more information, visit www.alcyonetx.com . About SPINRAZA ® (nusinersen) SPINRAZA is approved to treat infants, children and adults with spinal muscular atrophy (SMA) and is approved in more than 60 countries. As a foundation of care in SMA, more than 13,000 individuals have been treated with SPINRAZA worldwide. 1 SPINRAZA is an antisense oligonucleotide (ASO) that targets the root cause of SMA by continuously increasing the amount of full-length survival motor neuron (SMN) protein produced in the body. 2 It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts. 2 SPINRAZA has demonstrated sustained efficacy across ages and SMA types with a well-established safety profile based on data in patients treated up to 8 years, combined with unsurpassed real-world experience. 3 The nusinersen clinical development program encompasses more than 10 clinical studies, which have included more than 460 individuals across a broad spectrum of patient populations, including two randomized controlled studies (ENDEAR and CHERISH). The ongoing SHINE and NURTURE open-label extension studies are evaluating the long-term impact of SPINRAZA. The most common adverse events observed in clinical studies were respiratory infection, fever, constipation, headache, vomiting and back pain. Laboratory tests can monitor for renal toxicity and coagulation abnormalities, including acute severe low platelet counts, which have been observed after administration of some ASOs. Biogen licensed the global rights to develop, manufacture and commercialize SPINRAZA from Ionis Pharmaceuticals, Inc. (Nasdaq: IONS). Please click here for Important Safety Information and full Prescribing Information for SPINRAZA in the U.S., or visit your respective country’s product website. About Biogen As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and developed the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing one of the industry’s most diversified pipelines in neuroscience that will transform the standard of care for patients in several areas of high unmet need. We routinely post information that may be important to investors on our website at www.biogen.com . Follow us on social media - Twitter , LinkedIn , Facebook , YouTube . About Alcyone Therapeutics Alcyone Therapeutics is a biotechnology company pioneering next-generation precision gene-based therapies for complex neurological conditions. The company integrates innovation in neuroscience, precision dosing platforms, and manufacturing capabilities to deliver transformative therapies to patients. Alcyone leverages the synergy between Falcon™, the Company’s proprietary intrathecal precision dosing and biodistribution platform that incorporates deep knowledge of cerebral spinal fluid (CSF) dynamics, computational modeling, and bioengineering, and novel gene-based therapeutics platforms developed at the Abigail Wexner Research Institute at Nationwide Children’s Hospital (AWRI). This comprehensive approach allows for the optimization of central nervous system (CNS) dosing and delivery to better target the pathophysiology and anatomy specific to various neurological diseases. Alcyone’s lead programs utilize X chromosome reactivation for X-linked disorders and targets the treatment of Rett syndrome, and gene replacement for the treatment of IGHMBP2-related disorders including spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot Marie Tooth disease type 2S (CMT2S). For more information, visit www.alcyonetx.com . References: SOURCE: Biogen