Core Insights - Voyager Therapeutics announced eight presentations at the ASGCT annual meeting, focusing on advancements in gene therapies for neurological diseases, particularly Alzheimer's disease [1][2] Group 1: Gene Therapy Developments - The company highlighted its TRACER capsids, which have shown the ability to transduce 43%-98% of neurons and 87%-99% of astrocytes in non-human primates after a single intravenous dose [2] - The tau silencing gene therapy VY1706 demonstrated up to 73% knockdown of tau mRNA in non-human primates following a single intravenous dose of 1.3e13 vg/kg [2][6] - Presentations will include data on anti-amyloid gene therapy and enhancements to capsids aimed at immune evasion to broaden patient eligibility [2][6] Group 2: Presentation Details - Oral presentations will cover various topics, including the intravenous delivery of VY1706 and its effects on tau levels in the central nervous system [7] - Other presentations will focus on the discovery of AAV9-derived capsids that evade neutralizing antibodies and machine-learning applications for capsid screening [7][8] Group 3: Company Overview - Voyager Therapeutics is dedicated to leveraging human genetics to treat neurological diseases, with a pipeline that includes programs for Alzheimer's disease, Friedreich's ataxia, and Parkinson's disease [9] - The TRACER platform has enabled the development of novel capsids for gene therapy, enhancing the potential for high brain penetration following intravenous dosing [9][8]

Core Insights - Voyager Therapeutics is advancing two preclinical programs targeting tau for Alzheimer's disease treatment, specifically the tau silencing gene therapy VY1706 and the anti-tau antibody VY7523 [1][2] Group 1: VY1706 Tau Silencing Gene Therapy - A single intravenous (IV) administration of VY1706 resulted in a dose-dependent reduction of tau mRNA by 44% to 73% and tau protein by 27% to 55% in a non-human primate study, with effects sustained for up to three months [4] - The therapy demonstrated broad distribution across brain regions affected by Alzheimer's disease, including the hippocampus and frontal cortex, while liver targeting was reduced by approximately 30-fold compared to wild type AAV9 [4][8] - VY1706 is currently in Investigational New Drug (IND)-enabling studies, with an IND filing anticipated in 2026 [4][8] Group 2: VY7523 Anti-Tau Antibody - Preclinical data indicate that the murine version of VY7523 selectively binds to pathological tau tangles and effectively reduces tau spread in a P301S mouse model [5][9] - VY7523 has shown approximately 70% inhibition of pathological tau spread in preclinical studies and is currently being evaluated in a multiple ascending dose trial for early Alzheimer's disease patients [9] - Initial tau positron emission tomography (PET) imaging data for VY7523 is expected in the second half of 2026 [5][9] Group 3: Upcoming Events and Presentations - Voyager will present data on both therapies at the AD/PD™ 2025 conference in Vienna from April 1-5, 2025, and will host a live webcast on April 7, 2025, to recap key findings [1][7] - Dr. Toby Ferguson, Chief Medical Officer, will participate in two panels discussing anti-tau therapies and drug development challenges at the conference [6]

Core Viewpoint - Bragar Eagel & Squire, P.C. is investigating potential claims against four companies: Dave, Inc., Red Cat Holdings, Inc., Perpetua Resources Corp., and Voyager Therapeutics, Inc. for possible violations of federal securities laws and other unlawful business practices [1] Company Summaries Dave, Inc. (NASDAQ: DAVE) - The Justice Department and FTC announced a civil enforcement action against Dave, Inc. and its CEO Jason Wilk for alleged violations of the FTC Act and ROSCA, claiming misleading advertising regarding cash advances, hidden fees, and recurring monthly fees without a cancellation mechanism [2] - Following the announcement, Dave shares opened at $84.00 on December 31, 2024, reflecting a drop of over 10% from the previous day [3] Red Cat Holdings, Inc. (NASDAQ: RCAT) - Kerrisdale Capital published a report alleging that Red Cat overstated the revenue potential of its U.S. Army SRR drone contract and lacks the production capacity to fulfill its promises, raising concerns about executive departures and insider transactions [4] - As a result, Red Cat's stock price fell by $2.36 per share, or 21.63%, closing at $8.55 per share on January 17, 2025 [4] Perpetua Resources Corp. (NASDAQ: PPTA) - The investigation focuses on whether Perpetua issued false or misleading statements and failed to disclose pertinent information. The company released an updated cash flow model for the Stibnite Gold Project, indicating increased capital expenditures and costs, but improved economic metrics due to rising commodity prices [5] - Following this news, shares of Perpetua fell by 22.3% on February 14, 2025 [5] Voyager Therapeutics, Inc. (NASDAQ: VYGR) - Voyager announced it would assess alternate payloads for its gene therapy program for ALS, stating that emerging preclinical data indicated issues with the siRNA payload component of VY9323, which does not meet their standards [6] - Consequently, Voyager's stock price dropped by $1.11 per share, or 20.86%, closing at $4.21 per share on February 11, 2025 [6]

Financial Data and Key Metrics Changes - The company reported $332 million in cash as of the end of 2024, with $8.2 billion in potential future milestone payments expected from partnerships, indicating a strong financial position [9][10]. - Developmental milestones amount to $2.9 billion, with total potential milestone payments exceeding $8 billion, providing significant upside to the company's cash runway guidance extending to mid-2027 [28][30]. Business Line Data and Key Metrics Changes - The SOD1 silencing gene therapy program has moved back into the research stage due to the payload not meeting target profiles, while the VY1706 tau silencing gene therapy has advanced into IND-enabling studies [14][15]. - The company is seeing promising results from non-human primate studies, with 50% to 73% knockdown of tau messenger RNA across the brain [16][111]. Market Data and Key Metrics Changes - The anti-tau antibody, VY7523, has shown favorable results in a single ascending dose study, with no serious adverse events reported and a CSF to serum ratio of 0.3%, consistent with other approved monoclonal antibodies for Alzheimer's treatment [17][126]. - The company is closely monitoring third-party data from competitors in the anti-tau space, which could influence its own programs and strategies [101][105]. Company Strategy and Development Direction - Voyager Therapeutics is focused on building a multimodal neuro-therapeutics company, emphasizing gene therapy as a key component of its pipeline, particularly targeting tau in Alzheimer's disease [8][11]. - The company is open to additional partnerships to enhance its pipeline and revenue streams, indicating a proactive approach to business development [10][134]. Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the potential of its tau-targeting programs, highlighting the importance of genetically validated targets in severe diseases with high unmet needs [12][18]. - The company acknowledges the competitive landscape in the tau space and is prepared to adapt its strategies based on emerging data from both its own studies and those of competitors [144]. Other Important Information - The company is exploring the applicability of its ALPL-based non-viral shuttle for various diseases, with ongoing assessments of its potential to transport proteins, antibodies, and oligonucleotides across the blood-brain barrier [37][81]. - The management emphasized the importance of understanding the mechanisms of action for both antibody and knockdown approaches in treating Alzheimer's disease, indicating a comprehensive strategy to address the complexities of the disease [140][144]. Q&A Session Summary Question: Insights on upcoming data at ADPD - Management anticipates data from bepranemab regarding exposure PD relationships and the necessary decrease in tau spreading for clinical relevance [22][24]. Question: Upcoming milestones from partnered programs - The company confirmed that developmental milestones are not included in the current cash runway guidance, representing additional upside potential [30]. Question: Details on tau gene silencing IND - The main requirement before filing the IND is completing the GLP tox study and ensuring a therapeutic window [35]. Question: Applications of the ALPL shuttle - The ALPL shuttle is being evaluated for its ability to transport various modalities across the blood-brain barrier, with ongoing assessments of its effectiveness [37][81]. Question: Differences between tau silencing and antibody approaches - The knockdown approach is believed to provide broader tau knockdown and may be more effective in certain patient populations compared to antibody therapies [48][141]. Question: Cash runway and investment strategy - The company plans to balance investments in internal programs with potential licensing opportunities, remaining open to various partnership structures [132][134].

Financial Data and Key Metrics Changes - The company reported $332 million in cash as of the end of 2024, with $8.2 billion in potential future milestone payments expected to contribute significantly to the bottom line [9][10]. - Developmental milestones amount to $2.9 billion, with total potential milestones exceeding $8 billion, providing a significant upside to the mid-2027 cash runway guidance [28][30]. Business Line Data and Key Metrics Changes - The SOD1 silencing gene therapy program has moved back into the research stage due to the payload not meeting target profiles, while the VY1706 tau silencing gene therapy has advanced into IND-enabling studies [14][15]. - The anti-tau antibody, VY7523, showed promising results in a single ascending dose study, with no serious adverse events reported and a CSF to serum ratio of 0.3% [16][17]. Market Data and Key Metrics Changes - The company is focusing on the tau target in Alzheimer's disease, which is viewed as critical, with multiple upcoming data readouts expected to generate excitement in the market [8][18]. - The recent data from UCB's bepranemab indicated that an anti-tau antibody can impact tau accumulation in the human brain, although it did not meet its primary endpoint [17][18]. Company Strategy and Development Direction - The company aims to build a multimodal neuro-therapeutics platform, emphasizing gene therapy as a key component of its pipeline [11][12]. - Partnerships have been a significant source of non-dilutive revenue, and the company remains open to additional business opportunities [10][11]. Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the potential of their IV-delivered AAV capsids to efficiently deliver therapies across the blood-brain barrier, which is critical for treating CNS diseases [13][18]. - The management acknowledged the challenges in the gene therapy field but emphasized the importance of focusing on genetically validated targets in severe diseases with high unmet needs [11][12]. Other Important Information - The company is preparing to share data from its non-human primate studies, which showed a 50% to 73% knockdown of tau mRNA across the brain [16][17]. - The company is also exploring the applicability of its ALPL-based non-viral shuttle for various diseases, including spinal cord and cerebral cortex conditions [37][39]. Q&A Session Summary Question: Insights on upcoming data at ADPD - Management anticipates data from bepranemab regarding exposure PD relationships and the necessary decrease in tau spreading for clinical relevance [22][24]. Question: Upcoming milestones from partnered programs - The company has $2.9 billion in developmental milestones, with additional upside to the mid-2027 cash runway guidance [28][30]. Question: Details on tau gene silencing IND - The main requirement is completing the GLP tox study and ensuring a therapeutic window [35]. Question: Applications of the ALPL shuttle - The ALPL shuttle is being assessed for various diseases, with potential for transporting proteins, antibodies, and oligonucleotides [37][39]. Question: Differences between tau silencing and antibody approaches - The knockdown approach may allow for broader tau knockdown and is administered via IV, which could be more beneficial for patients [45][46]. Question: Proof of concept for SOD1 gene silencing - The next opportunities for capsid proof of concept lie with the Friedreich's ataxia and GBA programs, which are partnered with Neurocrine [52][53]. Question: Comparison of ALPL shuttle to other shuttles - The ALPL shuttle may have advantages over TfR-based shuttles, particularly regarding safety and distribution [149][150]. Question: Future indications for tau silencing program - The company intends to focus on Alzheimer's disease first, given the extensive knowledge of its natural history and measurement techniques [114][118].

Group 1 - Voyager Therapeutics reported a quarterly loss of $0.59 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.35, and a significant decline from earnings of $1.25 per share a year ago, indicating an earnings surprise of -68.57% [1] - The company posted revenues of $6.28 million for the quarter ended December 2024, missing the Zacks Consensus Estimate by 68.81%, and a sharp decline from year-ago revenues of $90.06 million [2] - Voyager Therapeutics shares have declined approximately 26.5% since the beginning of the year, contrasting with the S&P 500's decline of -4.5% [3] Group 2 - The earnings outlook for Voyager Therapeutics is mixed, with the current consensus EPS estimate for the coming quarter at -$0.37 on revenues of $18.69 million, and for the current fiscal year at -$1.59 on revenues of $88.9 million [7] - The Medical - Biomedical and Genetics industry, to which Voyager Therapeutics belongs, is currently ranked in the top 29% of over 250 Zacks industries, suggesting a favorable industry outlook [8]

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].

Core Insights - Voyager Therapeutics has made significant advancements in its anti-tau programs targeting Alzheimer's disease, with VY7523 in clinical trials and VY1706 in IND-enabling studies [2] - The company generated approximately $80 million in non-dilutive funding in 2024, which is expected to support operations through mid-2027 [2] - Collaboration revenues decreased significantly in Q4 2024 and for the full year compared to 2023, primarily due to reduced revenue from Neurocrine and Novartis agreements [5][8] Financial Results - Collaboration revenue for Q4 2024 was $6.3 million, down from $90.1 million in Q4 2023; total collaboration revenue for 2024 was $80.0 million compared to $250.0 million in 2023 [5][18] - Net loss for Q4 2024 was $34.5 million, compared to a net income of $56.4 million in Q4 2023; the full year net loss was $65.0 million versus a net income of $132.3 million in 2023 [14][19] - Research and development expenses increased to $35.6 million in Q4 2024 from $25.8 million in Q4 2023, with total R&D expenses for 2024 at $127.4 million compared to $92.2 million in 2023 [14][19] Upcoming Milestones - VY1706 is expected to file for IND in 2026, with additional data to be presented at the ADPD conference in April 2025 [6][7] - Initial tau PET imaging data for VY7523 is anticipated in the second half of 2026 [6] - IND filings for partnered gene therapies related to GBA1 Parkinson's and Friedreich's ataxia are expected in 2025 [7] Cash Position - As of December 31, 2024, Voyager had cash, cash equivalents, and marketable securities totaling $332.4 million, an increase from $230.9 million in 2023 [14][19] - The company's cash runway is projected to extend into mid-2027, not including potential milestone payments from existing partnerships [9][14]

Financial Performance - Voyager's collaboration revenue for Q4 2024 was $6.3 million, a decrease of 93% from $90.1 million in Q4 2023, and total collaboration revenue for the year was $80.0 million, down from $250.0 million in 2023[8][18]. - The net loss for Q4 2024 was $34.5 million, compared to a net income of $56.4 million in Q4 2023, and the net loss for the full year was $65.0 million, down from a net income of $132.3 million in 2023[8][18]. - Voyager's total operating expenses for Q4 2024 were $44.6 million, compared to $36.0 million in Q4 2023, reflecting increased program-related spending[8][18]. - GAAP collaboration revenue for Q4 2024 was $6.278 million, compared to $90.061 million in Q4 2023[22]. - Net collaboration revenue decreased to $4.385 million in Q4 2024 from $87.009 million in Q4 2023[22]. - For the year ended December 31, 2024, GAAP collaboration revenue totaled $250.008 million, compared to $80.001 million in 2023[22]. - Yearly net collaboration revenue increased to $71.538 million in 2024 from $239.913 million in 2023[22]. Research and Development - Research and development expenses increased to $35.6 million in Q4 2024 from $25.8 million in Q4 2023, and for the full year, R&D expenses rose to $127.4 million from $92.2 million in 2023[8][18]. - Total research and development expenses increased to $35.583 million in Q4 2024 from $25.756 million in Q4 2023[22]. - Net research and development expenses rose to $33.690 million in Q4 2024, up from $22.704 million in Q4 2023[22]. - Reimbursable research and development services incurred in Q4 2024 were $1.893 million, down from $3.052 million in Q4 2023[22]. - Total research and development expenses for the year 2024 were $127.368 million, significantly higher than $92.172 million in 2023[22]. - Reimbursable research and development services for the year 2024 amounted to $8.463 million, compared to $10.095 million in 2023[22]. Cash Position and Funding - Voyager's cash, cash equivalents, and marketable securities as of December 31, 2024, were $332.4 million, up from $230.9 million in 2023, providing a runway into mid-2027[8][18]. - Voyager generated approximately $80 million in non-dilutive funding in 2024, supporting its advancing pipeline and cash position[2][8]. - The company is no longer advancing the VY9323 candidate for SOD1 ALS, which has contributed to extending the cash runway into mid-2027[4][5][8]. Product Development - The tau silencing gene therapy VY1706 reduced tau mRNA levels by 50% to 73% in a non-human primate study, with additional data expected to be presented at the ADPD conference in April 2025[3][8]. - The anti-tau antibody VY7523 showed an acceptable safety profile in a Phase 1 trial, with initial tau PET imaging data expected in H2 2026[3][8]. - The company is anticipating IND filings in 2025 for partnered gene therapies targeting GBA1 Parkinson's and Friedreich's ataxia[8][9]. Collaboration Agreements - The company has collaboration agreements with Neurocrine and Novartis for preclinical development activities, impacting revenue and expenses[22].

Company Overview - Voyager Therapeutics, Inc. is a biotechnology company focused on advancing neurogenetic medicines aimed at curing neurological diseases [3] - The company's pipeline includes programs targeting Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and other central nervous system diseases [3] - Voyager utilizes its TRACER™ AAV capsid discovery platform to develop novel capsids for high brain penetration of genetic medicines [3] Upcoming Financial Results - Voyager Therapeutics will report its fourth quarter 2024 financial and operating results after market close on March 11, 2025 [1] - A conference call and webcast will follow at 4:30 p.m. ET on the same day [1] Investor Information - A live webcast of the conference call will be available on the Investors section of the Voyager website [2] - A replay of the call will be accessible approximately two hours after its completion and will remain available for at least 30 days [2]