VYGR

• Pipeline includes 4 wholly owned and 13 partnered programs, with clinical data generated and more expected. • Excited about two wholly owned tau-targeted programs and CNS delivery platforms (TRACER capsid for IV-delivered CNS gene therapies and ALPL-based non-viral shuttle). • Partnerships have provided non-dilutive revenue, with $332 million in cash as of end 2024 and $8.2 billion in potential milestones. • SOD1 silencing gene therapy program moved back to research due to payload issue; VY1706 tau silencing gene therapy advanced to IND-enabling studies. • VY7523 anti-tau antibody had positive single ascending dose study, initiated multiple ascending dose study; external readouts in tau space (e.g., bepranemab, Merck) to watch for at conferences like ADPD, AAIC, etc.

• Cash runway extending into mid-2027. • Anticipation of upcoming data releases from external programs at conferences to build excitement for tau-related advancements. • Forward-looking on potential milestones from partnerships and progress in internal programs.

No detailed financial performance by product segments provided in the transcript.

• Forward-looking statements are subject to risks and uncertainties, with actual results possibly differing materially from expectations. • Risks associated with gene therapy development, including uncertainties in clinical trial outcomes and safety profiles. • Uncertainties in achieving expected clinical and commercial success for programs, especially in competitive gene therapy space.

Q: Any additional color on external readouts at ADPD related to tau?

A: Hoping to see data from bepranemab on exposure PD relationship, PK/PD, and more on tau spreading and subgroups. Also, other companies' anti-tau data like [ASI]'s fluid-based biomarkers.

Q: Details on what's needed before VY1706 IND filing?

A: Complete GLP tox study and ensure therapeutic window based on non-human primate data showing 50%-73% tau mRNA knockdown.

Q: Application of ALPL shuttle?

A: Broadly applicable across various diseases, targets, transporting proteins, antibodies, and potentially oligonucleotides; aims to improve CNS delivery of drugs.

Q: Differences between tau silencing and antibody approaches?

A: Tau silencing uses IV injection with second-gen TRACER capsids for broader bio-distribution; antibodies have different mechanisms, with tau silencing potentially offering advantages in bio-distribution and ease of administration.

Q: How to establish human proof of concept for capsids?

A: Through partnered programs with Neurocrine (Friedreich’s ataxia and GBA) where biomarker measurement (e.g., protection levels, enzyme/substrate levels) can indicate capsid efficacy.

Q: Preclinical data on ALPL shuttle later this year?

A: Expect to show in vivo data, compare to TFR-based shuttles, and potentially show multiple payloads to assess plug-and-play nature.

Q: Confidence SOD1 ALS program neuro tox not capsid-related?

A: Timing of adverse events (delay after capsid clearance) and lack of adverse events with same capsid in other constructs indicate payload, not capsid, is the issue.

Q: Utility of vector distribution data at ADPD?

A: At ADPD, will present data on delivery to brain and peripheral tissues, discussing important locations and on/off target delivery.