Voyager Therapeutics(VYGR) - 2023 Q4 - Annual Report

Part I Business Voyager Therapeutics is a biotechnology company focused on developing neurogenetic medicines for diseases like Alzheimer's, ALS, and Parkinson's - The company's core strategy is to leverage its TRACER™ AAV capsid discovery platform to develop genetic medicines for neurological diseases with high brain penetration after intravenous dosing[25] - Voyager's pipeline includes both wholly-owned assets and programs advanced in collaboration with partners like Neurocrine, Novartis, and Alexion[25][27] Pipeline Overview (as of Q1 2024) | Category | Program | Indication | Partner | Stage | | :--- | :--- | :--- | :--- | :--- | | Wholly-Owned | Anti-tau Antibody (VY-TAU01) | Alzheimer's Disease | - | IND-Enabling | | | SOD1 Silencing Gene Therapy | ALS | - | IND-Enabling | | | Tau Silencing Gene Therapy | Alzheimer's Disease | - | Late Research | | | Anti-Aβ Gene Therapy | Alzheimer's Disease | - | Early Research | | Partnership Reimbursed | FXN Gene Therapy | Friedreich's Ataxia | Neurocrine | IND-Enabling | | | GBA1 Gene Therapy | Parkinson's/Other | Neurocrine | Late Research | | | Five Gene Therapy Programs | Undisclosed | Neurocrine | Undisclosed | | | Huntington's Gene Therapy | Huntington's Disease | Novartis | Undisclosed | | Capsid Licenses | Gene Therapy | Rare Neurological Disease | Alexion | - | | | Three Gene Therapy Programs | SMA + CNS Diseases | Novartis | - | | | Gene Therapy | Prion Disease | Sangamo | - | Vision, Mission, and Strategy The company's vision is to provide transformative treatments for neurological diseases, focusing on advancing its CNS pipeline and maximizing asset value - Strategic initiatives include advancing the CNS pipeline to establish proof-of-concept, initiating new research programs in gene therapy, and maximizing value from both proprietary and partnered assets[33] Our Platforms Voyager's core technology is the TRACER™ platform, discovering AAV capsids for effective blood-brain barrier penetration and gene therapy delivery - The TRACER™ platform uses directed evolution to rapidly discover AAV capsids with robust BBB penetration and enhanced CNS tropism in multiple species, including non-human primates[34] - The company possesses expertise in non-viral delivery, including monoclonal antibodies and leveraging identified receptors for TRACER capsids to potentially shuttle non-viral genetic medicines across the BBB[36][37] Wholly-Owned Programs Voyager's wholly-owned pipeline includes anti-tau and SOD1 silencing programs, with IND submissions planned for Alzheimer's and ALS - The lead anti-tau antibody candidate, VY-TAU01, targets the C-terminus of the tau protein and is planned for an IND submission to the FDA in the first half of 2024[41][44] - The SOD1 silencing gene therapy program for ALS selected a lead development candidate in Q4 2023 and targets an IND submission in mid-2025[48] - The tau silencing gene therapy program for AD was prioritized in Q1 2024, with an IND submission anticipated in 2026[52] Collaboration Programs and Licensing Agreements Voyager maintains high-value collaborations with Neurocrine, Novartis, and Alexion, generating revenue from licensing and development agreements - The Friedreich's Ataxia (FA) program with Neurocrine selected a development candidate in Q1 2024, with first-in-human trials expected in 2025, and Voyager has a 40% co-commercialization option in the U.S[32][58] - The GBA1 gene therapy program for Parkinson's disease with Neurocrine is in preclinical development, and Voyager has a 50% co-commercialization option in the U.S[32][62] Key Collaboration Financial Terms | Partner | Agreement Date | Upfront/Option Fees | Potential Milestones (Dev/Reg/Comm) | Royalties | | :--- | :--- | :--- | :--- | :--- | | Novartis | Dec 2023 | $80M upfront + $20M equity | Up to $1.2B | High single-digit to low double-digit | | Novartis | Mar 2022 | $54M upfront + $25M option exercise | Varies per target | Mid- to high-single-digit | | Neurocrine | Jan 2023 | ~$136M upfront + ~$39M equity | Up to $1.5B (GBA1) + $825M (Discovery) | Mid-single to 20% | | Neurocrine | Jan 2019 | $115M upfront + $50M equity | Up to $1.1B (aggregate cap) | Mid-single to high-teens | | Alexion (Pfizer) | Oct 2021 | $30M upfront + $10M option exercise | Up to $290M + sales milestones | Mid- to high-single-digit | Competition Voyager faces intense competition in neurogenetic medicine, particularly for its anti-tau programs, ALS therapy, and TRACER capsid platform - The anti-tau and tau silencing programs for AD compete with therapies from major players like Lundbeck, Roche, Eisai, and an antisense program from Ionis/Biogen[163] - The TRACER discovery platform competes with other companies developing novel AAV capsids, including 4D Molecular Therapeutics, Affinia Therapeutics, and Capsida Biotherapeutics[164] Manufacturing The company uses a proprietary HEK 293 manufacturing process and relies on third-party cGMP contractors for clinical and commercial production - Voyager has developed a proprietary HEK 293 transient transfection manufacturing process for scalable AAV production[169] - The company contracts with third parties for clinical and commercial scale cGMP manufacturing and does not currently plan to build its own large-scale facilities[172] Intellectual Property Voyager's IP strategy involves patenting its TRACER platform, novel capsids, and therapeutic programs, alongside in-licensed technologies - The company owns at least 79 patents and 422 pending applications, and co-owns at least 12 patents and 42 pending applications in the U.S. and foreign jurisdictions[175] - Key patent families cover the TRACER discovery platform, specific capsid variants identified by the platform, vectorized antibodies, and therapeutic approaches for Tauopathies, ALS, Friedreich's Ataxia, GBA1, and Huntington's Disease[176][177][178][179][180][182] - Voyager has in-licensed key intellectual property, including RNAi constructs and AAV capsids from the University of Massachusetts[195][196] Government Regulation Voyager's products are subject to extensive FDA regulation as biologics, requiring rigorous preclinical and clinical development for approval - Gene therapy and antibody products are regulated as biologics by the FDA's Center for Biologics Evaluation and Research (CBER)[204][230] - The development process involves preclinical testing, submitting an IND, and conducting Phase 1, 2, and 3 clinical trials to demonstrate safety and efficacy before filing a BLA for marketing approval[205] - The company is subject to healthcare reform measures, such as the Inflation Reduction Act (IRA), which could impact drug pricing and reimbursement through mechanisms like Medicare price negotiations[282] Risk Factors The company faces significant risks including historical losses, funding needs, high development failure rates, reliance on collaborations, and intense competition - The company has a history of significant losses and expects to continue incurring them, requiring it to raise additional capital which may not be available on acceptable terms[297][307] - All revenue to date has been derived from collaborations with Neurocrine, Novartis, Alexion, and others, and termination of these agreements would significantly harm the business[409] - AAV gene therapy is a novel technology with a complex and uncertain regulatory approval process, and product candidates may fail to demonstrate safety and efficacy in clinical trials[319][338] - The company faces significant competition from better-funded companies, and its TRACER platform and therapeutic programs may be rendered obsolete by more advanced or effective therapies[394] Unresolved Staff Comments The company reports no unresolved staff comments from the SEC - The company reports no material pending legal proceedings as of December 31, 2023[622] Cybersecurity The company manages cybersecurity risks with board oversight and has identified no material threats to its business operations - The Audit Committee provides board-level oversight of cybersecurity risk, receiving updates from management twice a year[618] - The company has not identified any known cybersecurity risks that are reasonably likely to have a material effect on its business, operations, or financial condition[618] Properties The company leases corporate headquarters and laboratory space in Lexington and Cambridge, Massachusetts - The company leases approximately 26,148 sq. ft. in Cambridge, MA (expiring 2026) and 93,449 sq. ft. in Lexington, MA (expiring 2031)[292] Legal Proceedings As of December 31, 2023, the company was not a party to any material pending legal proceedings - The company reports no material pending legal proceedings as of December 31, 2023[622] Part II Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities The company's common stock trades on Nasdaq, has approximately 12 record holders, and does not anticipate paying cash dividends - Common stock trades on the Nasdaq Global Select Market under the symbol "VYGR"[625] - The company has never paid cash dividends and does not plan to in the foreseeable future[627] Management's Discussion and Analysis of Financial Condition and Results of Operations Voyager reported a net income of $132.3 million in 2023, driven by increased collaboration revenue, and expects its cash runway to extend into 2027 Results of Operations (Years ended December 31) | (in thousands) | 2023 | 2022 | Change | | :--- | :--- | :--- | :--- | | Collaboration revenue | $250,008 | $40,907 | $209,101 | | Research and development | $92,172 | $60,764 | $31,408 | | General and administrative | $35,822 | $30,980 | $4,842 | | Total operating expenses | $127,994 | $91,744 | $36,250 | | Net income (loss) | $132,330 | $(46,408) | $178,738 | - The significant increase in collaboration revenue in 2023 was primarily due to recognizing $79.0 million from the 2022 Novartis Agreement, $80.0 million from the 2023 Novartis Agreement, and $80.8 million from the 2023 Neurocrine Agreement[659] - As of December 31, 2023, the company had $230.9 million in cash, cash equivalents, and marketable securities, and with subsequent financing, the company projects its cash runway extends into 2027[664] Quantitative and Qualitative Disclosures about Market Risk The company's primary market risk is interest rate sensitivity on its investments, with no material impact expected from rate changes or inflation - The primary market risk is interest rate sensitivity on its portfolio of cash, cash equivalents, and marketable securities[692] - The company does not believe that a 100 basis point change in interest rates or inflation would have a material effect on its financial condition or results of operations[694][696] Financial Statements and Supplementary Data This section presents the company's audited consolidated financial statements for 2023, including balance sheets, statements of operations, and cash flows Consolidated Balance Sheets As of December 31, 2023, total assets increased to $351.3 million, driven by cash and marketable securities, with a corresponding rise in equity Consolidated Balance Sheet Summary (as of December 31) | (in thousands) | 2023 | 2022 | | :--- | :--- | :--- | | Cash, cash equivalents, and marketable securities | $230,875 | $118,848 | | Total Assets | $351,281 | $159,356 | | Deferred revenue (current & non-current) | $75,240 | $65,827 | | Total Liabilities | $114,961 | $100,336 | | Total Stockholders' Equity | $236,320 | $59,020 | Consolidated Statements of Operations and Comprehensive Income (Loss) For 2023, the company reported a net income of $132.3 million, a significant turnaround from 2022, primarily due to higher collaboration revenue Consolidated Statement of Operations Summary (Years ended December 31) | (in thousands, except per share data) | 2023 | 2022 | | :--- | :--- | :--- | | Collaboration revenue | $250,008 | $40,907 | | Total operating expenses | $127,994 | $91,744 | | Net income (loss) | $132,330 | $(46,408) | | Net income (loss) per share, basic | $3.08 | $(1.21) | Consolidated Statements of Cash Flows In 2023, net cash provided by operating activities was $77.9 million, leading to a net decrease in cash due to investing activities Consolidated Statement of Cash Flows Summary (Years ended December 31) | (in thousands) | 2023 | 2022 | | :--- | :--- | :--- | | Net cash provided by (used in) operating activities | $77,919 | $(12,509) | | Net cash (used in) provided by investing activities | $(141,643) | $(7,339) | | Net cash provided by financing activities | $33,645 | $1,110 | | Net (decrease) increase in cash, cash equivalents, and restricted cash | $(30,079) | $(18,738) | Controls and Procedures Management concluded that the company's disclosure controls and internal control over financial reporting were effective as of December 31, 2023 - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2023[700] - Based on the COSO framework, management concluded that internal control over financial reporting was effective as of December 31, 2023[705] Other Information No directors or officers adopted or terminated Rule 10b5-1 trading arrangements during Q4 2023 - No directors or officers adopted or terminated a Rule 10b5-1 trading plan during the quarter ended December 31, 2023[707] Part III Directors, Executive Officers, Corporate Governance, Compensation, and Principal Accountant Fees Information required for Items 10 through 14, covering directors, executive officers, corporate governance, executive compensation, security ownership, related transactions, director independence, and principal accountant fees and services, is incorporated by reference from the company's definitive Proxy Statement for its 2024 Annual Meeting of Stockholders - Information for Items 10, 11, 12, 13, and 14 is incorporated by reference from the forthcoming 2024 Proxy Statement[710][711][712][713][714] Part IV Exhibits and Financial Statement Schedules This section lists the exhibits and financial statement schedules filed as part of the Annual Report on Form 10-K