Business Overview and History

Voyager Therapeutics, Inc. (VYGR) is a biotechnology company dedicated to leveraging the power of human genetics to modify the course of and ultimately cure neurological diseases. The company's diverse pipeline of gene therapy, antibody, and non-viral therapeutic programs targets some of the most challenging central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Friedreich's ataxia.

Voyager Therapeutics was incorporated in June 2013 with the mission of developing transformative treatments for neurological diseases. The company's initial focus was on advancing its proprietary adeno-associated virus (AAV) gene therapy platform, which utilizes engineered AAV capsids, known as TRACER Capsids, to enable targeted delivery of therapeutic payloads across the blood-brain barrier.

Throughout its history, Voyager has worked to advance its proprietary platforms, including its TRACER capsid discovery platform for AAV gene therapies and its non-viral therapeutics platform. The company has used these platforms to develop a pipeline of gene therapy, antibody, and non-viral therapy programs targeting neurological diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Friedreich's ataxia, among others.

In its early years, Voyager Therapeutics established partnerships and collaborations to advance its proprietary platforms and pipeline. In 2015, the company entered into a collaboration agreement with Sanofi Genzyme to research, develop, and commercialize certain of Voyager's AAV gene therapy products. However, this collaboration was later terminated in 2019.

Voyager faced some early challenges with its VY-AADC program for Parkinson's disease. In 2021, Neurocrine terminated the collaboration specifically for this program after the RESTORE-1 Phase 2 clinical trial did not meet its primary endpoint. Despite this setback, Voyager was able to regain the worldwide rights to the VY-AADC program.

Undeterred, Voyager pivoted its focus to other promising therapeutic areas, particularly Alzheimer's disease and rare neurological disorders. In 2019, the company formed a collaboration with Neurocrine Biosciences to develop gene therapy products for Friedreich's ataxia and two undisclosed CNS targets. This partnership was expanded in 2023 to include a GBA1 gene therapy program for Parkinson's disease and other GBA1-mediated diseases.

Voyager has also forged partnerships with Novartis and Alexion (now part of AstraZeneca) to leverage its TRACER Capsid technology for the development of gene therapies targeting spinal muscular atrophy, Huntington's disease, and a rare neurological disease. These collaborations have provided Voyager with significant non-dilutive funding, including upfront payments, milestone payments, and reimbursement for research and development expenses.

Financial Performance and Liquidity

As of December 31, 2024, Voyager reported cash, cash equivalents, and marketable securities of $332.4 million, which the company expects will be sufficient to fund its operations into mid-2027. This strong cash position is bolstered by the potential for up to $8.2 billion in future milestone payments from its collaborations.

For the full year 2024, Voyager reported total revenue of $80.0 million, primarily from its strategic partnerships. The company incurred a net loss of $65.0 million, with research and development expenses of $127.4 million and general and administrative expenses of $35.9 million. Voyager's net cash used in operating activities was $15.3 million for the year, with free cash flow of -$18.8 million.

In the fourth quarter of 2024, Voyager reported revenue of $6.3 million and a net loss of $34.5 million. The decrease in revenue and net income compared to the prior year was primarily due to the timing of milestone achievements and recognition of collaboration revenue.

Voyager's financial position remains solid, with a debt-to-equity ratio of 0.146 as of December 31, 2024. The company had cash and cash equivalents of $71.4 million, and both its current ratio and quick ratio stood at 5.56, indicating strong short-term liquidity.

It's worth noting that Voyager Therapeutics is primarily focused on the U.S. market and does not have significant international operations. The company's revenue is primarily derived from its ongoing collaborations and licensing agreements with partners such as Neurocrine, Novartis, and Alexion. For the year ended December 31, 2024, the company recognized $49.7 million from the 2023 Neurocrine Collaboration Agreement, $15 million from the Novartis Amendment, $10.4 million from the 2019 Neurocrine Collaboration Agreement, and $4.9 million from the 2023 Novartis Collaboration Agreement.

Pipeline and Key Programs

Voyager's pipeline consists of four wholly-owned programs and 13 partnered programs, spanning multiple therapeutic modalities and neurological diseases.

Alzheimer's Disease:

Voyager's two lead wholly-owned programs in Alzheimer's disease are: 1. VY7523, an anti-tau antibody: The company recently completed a successful single-ascending dose (SAD) study in healthy volunteers, demonstrating a favorable safety and pharmacokinetic profile. Voyager has now initiated a multiple-ascending dose (MAD) study in early Alzheimer's patients, with initial tau PET imaging data expected in the second half of 2026. The murine version of VY7523 reduced tau spread by more than 60% in preclinical studies.

2. VY1706, a tau silencing gene therapy: In November 2024, Voyager selected VY1706 as the development candidate for its tau silencing program. Preclinical data in non-human primates showed 50-73% reductions in tau mRNA levels across the cerebral cortex with a single intravenous dose. Voyager plans to file an investigational new drug (IND) application for VY1706 in 2026.

Rare Neurological Disorders: Voyager's rare disease pipeline includes:

• Friedreich's ataxia: The company's Friedreich's ataxia program, VY-FXN01, is being developed in collaboration with Neurocrine Biosciences. Neurocrine is expected to file an IND for this program in 2025.
• Parkinson's disease with GBA1 mutations: Voyager is also collaborating with Neurocrine on a GBA1 gene therapy program for Parkinson's disease and other GBA1-mediated diseases. Neurocrine plans to file an IND for this program in 2025 as well.
• Huntington's disease: Voyager is working with Novartis on the development of a TRACER Capsid-based gene therapy for Huntington's disease.

In addition to these advanced programs, Voyager is exploring earlier-stage opportunities in amyotrophic lateral sclerosis (ALS) and other CNS indications. The company's proprietary pipeline also includes early research initiatives to develop a vectorized anti-amyloid antibody for Alzheimer's disease and a vectorized superoxide dismutase 1 (SOD1) knockdown gene therapy for SOD1 amyotrophic lateral sclerosis.

Partnerships and Collaborations

Voyager's strategic partnerships have been a crucial source of non-dilutive funding and have allowed the company to advance its pipeline while minimizing its own investment. The partnerships with Neurocrine, Novartis, and Alexion (now AstraZeneca) have provided Voyager with over $500 million in upfront payments, milestone payments, and reimbursement for research and development expenses to date.

Looking ahead, Voyager has the potential to earn up to $8.2 billion in future milestone payments from its collaborations, in addition to royalties on any approved products. These partnerships have also enabled the company to leverage its TRACER Capsid technology and accelerate the development of gene therapy candidates for a broader range of neurological diseases.

Voyager is advancing seven gene therapy programs with Neurocrine Biosciences, including a glucosylceramidase beta 1 (GBA1) gene therapy program for Parkinson's disease and other GBA1-mediated diseases, as well as a frataxin (FXN) gene therapy program for Friedreich's ataxia. Development candidates were selected for three of these programs in 2024, resulting in milestone payments to Voyager.

The company has also partnered with Novartis on TRACER Capsid-based gene therapies for spinal muscular atrophy and Huntington's disease. Additionally, Voyager has licensed TRACER Capsids to Novartis for three undisclosed central nervous system targets and to Alexion for one undisclosed rare neurological disease target.

Risks and Challenges

As with any biotechnology company, Voyager faces several risks and challenges that could impact its future success:

1. Clinical development risks: The company's product candidates, particularly in the early stages of development, may fail to demonstrate the desired safety and efficacy profiles in clinical trials, leading to delays or termination of development programs.

2. Regulatory hurdles: Obtaining regulatory approvals for gene therapies and other novel therapeutic modalities can be a complex and time-consuming process, with no guarantee of success.

3. Manufacturing and supply chain challenges: Voyager's reliance on third-party manufacturers and suppliers could expose the company to disruptions in the production and delivery of its product candidates.

4. Competition: Voyager operates in a highly competitive landscape, with other biotechnology and pharmaceutical companies developing their own gene therapies, antibodies, and non-viral approaches for neurological disorders.

5. Financing and capital requirements: As Voyager continues to advance its pipeline and expand its research and development efforts, the company may need to raise additional capital through equity or debt financing, which could be dilutive to existing shareholders.

Despite these risks, Voyager's diverse pipeline, innovative platforms, and strategic partnerships position the company well to tackle some of the most challenging neurological diseases. The company's focus on genetically validated targets, coupled with its expertise in CNS-targeted delivery, suggests a promising future for Voyager Therapeutics.

Future Outlook

Voyager Therapeutics' strategy is to leverage its expertise in blood-brain barrier crossing and neuropharmacology to address the delivery challenges that have constrained the neurology discipline. The company's diverse pipeline of gene therapy, antibody, and non-viral therapeutic programs, along with its collaborations, provide multiple avenues for potential value creation.

With $332 million in cash as of the end of 2024 and a cash runway expected to extend past mid-2027, Voyager is well-positioned to advance its pipeline and pursue its strategic objectives. The potential for $8.2 billion in future milestone payments from partnerships, including $2.9 billion in development milestones, represents significant upside potential for the company.

As Voyager continues to progress its wholly-owned programs and collaborate with industry leaders, investors and stakeholders will be closely watching for key clinical milestones, particularly the initial tau PET imaging data from the VY7523 multiple-ascending dose study expected in the second half of 2026 and the planned IND filing for VY1706 in 2026. The success of these programs could potentially transform the treatment landscape for Alzheimer's disease and other neurological disorders, positioning Voyager as a leader in the field of neurogenetic medicines.