Voyager Therapeutics(VYGR) - 2024 Q4 - Annual Report

Neurological Disease Programs - The company is advancing a proprietary pipeline focused on neurological diseases, particularly Alzheimer's disease (AD), with two key programs targeting tau: VY7523 (anti-tau antibody) and VY1706 (tau silencing gene therapy) [28]. - VY7523 is currently in a Phase 1 multiple ascending dose clinical trial, with initial tau PET imaging data expected in the second half of 2026; preclinical studies showed over 70% reduction in tau spread [28][41]. - VY1706 demonstrated 50% to 73% reductions in tau mRNA levels in non-human primate studies, with an IND application anticipated in 2026 [28][45]. - The SOD1 silencing gene therapy program for ALS is in preclinical development, with the company assessing alternate payloads for optimal product profile [47]. - The Friedreich's Ataxia Program, VY-FXN01, is currently in preclinical development, with an IND filing expected in 2025 [54]. - The GBA1 Gene Replacement Program for Parkinson's disease is also in preclinical development, with an IND filing anticipated in 2025 [58]. - Parkinson's disease affects about 1 million patients in the United States and over 10 million patients globally, with GBA1 mutations increasing the risk by approximately 20-fold [55]. - Preclinical studies showed significant improvement in efficacy biomarkers in mouse models for the GBA1 program, with sustained expression for three or more months post-IV administration [57]. Collaborations and Partnerships - The company has partnered with Neurocrine on seven gene therapy programs, with milestone payments exceeding $500 million to date and potential earnings of up to$8.2 billion in milestone payments across its partnered portfolio [29]. - The Novartis Collaboration Agreement was established on December 28, 2023, to develop AAV gene therapy products for Huntington's disease [60]. - Under the Novartis Collaboration Agreement, Novartis will assume sole responsibility for the development and commercialization of gene therapy products after the first IND application filing [61]. - The collaboration includes a governance structure managed by a Joint Steering Committee to oversee the development of both the Novartis SMA and HD Programs [63]. - Neurocrine is responsible for all costs incurred in preclinical development activities for each 2023 Neurocrine Program, except for one preclinical study where costs are shared [91]. - The company has the option to co-develop and co-commercialize products in the GBA1 Program, sharing costs and profits equally with Neurocrine [92]. - Neurocrine made an upfront payment of approximately $136.0 million and an equity purchase of 4,395,588 shares for approximately$39.0 million in February 2023 [98]. - The 2023 Collaboration Agreement prohibits either party from developing competitive gene therapy products directed to targets under the agreement during its term [103]. Financial Aspects and Milestones - Novartis made an upfront payment of $80.0 million under the 2023 Collaboration Agreement and is eligible for up to$200.0 million in milestone payments for the SMA Program and $225.0 million for the HD Program [74]. - The company is eligible for up to$125.0 million in milestone payments for the first Novartis Initial Licensed Product and $130.0 million for the first Novartis Direct Licensed Product [84]. - The agreement allows for a maximum of four potential development candidates at any given time during the 2023 Discovery Period [96]. - Aggregate development milestone payments from Neurocrine can reach up to$195.0 million for the FA Program and $130.0 million for each of the two 2019 Discovery Programs [119]. - The Alexion Agreement includes an upfront payment of$30.0 million and an additional fee of $10.0 million for option exercise prior to the transfer of rights to Alexion [134]. - The company is eligible for up to$115.0 million in milestone payments for the first Alexion Licensed CNS Product to achieve specified milestones [134]. Intellectual Property - The company owns at least 421 pending patent applications and has 113 patents issued in the United States and foreign jurisdictions, indicating a strong intellectual property position [153]. - The company has 10 pending patent families directed to antibodies to tau, with patents expected to commence expiration in 2037, and some later applications extending to 2045 [154]. - The company owns eight pending patent families with 27 applications directed to AAVs encoding GBA1 for treating Parkinson's disease, with patents expected to commence expiration in 2041 [158]. - The company has seven pending patent families and 22 issued patents directed to targeting SOD1 for the treatment of ALS, with patents expected to commence expiration in 2035 [161]. - The company has a non-viral therapeutics patent family with six pending applications, expected to commence expiration in 2044 [166]. - The company has three patent families with 52 issued patents directed to vector genome engineering, with patents expected to commence expiration in 2035, 2037, and 2038 [169]. Regulatory Environment - The FDA requires substantial time and financial resources for the regulatory approval process of biological products, which includes multiple phases of clinical trials [185][186]. - Human clinical trials are conducted in three phases, with Phase 3 trials providing evidence for regulatory approval based on safety and efficacy [196][201]. - The FDA may require post-marketing studies to assess the safety and effectiveness of approved product candidates, with non-compliance potentially leading to withdrawal of approval [204]. - The FDA has established guidelines for gene therapy products, including long-term follow-up studies for potential adverse effects, typically recommending monitoring for up to five years [214]. - The FDA aims to review BLAs within ten months for standard reviews and six months for priority reviews, although actual review times may vary [222].