Invivyd (IVVD) Study Update summary

Program Overview and Rationale

• VYD2311 is being developed as a vaccine-alternative monoclonal antibody for COVID-19 prophylaxis, aiming to provide enhanced and durable immune protection against SARS-CoV-2 and potentially other pathogens.

• Antibody innovation targets highly conserved, stable epitopes on the spike protein RBD for broad and lasting efficacy despite viral evolution.

• VYD2311 is engineered for improved potency, half-life, and patient-friendly intramuscular administration, with minimal structural changes to maximize safety and efficacy.

• The platform's antibodies have maintained high potency against evolving COVID variants, with VYD2311 showing a flat potency profile over time.

• The program addresses unmet needs due to declining vaccine uptake and public mistrust, offering an alternative with potentially superior safety and efficacy.

Clinical Study Design and Objectives

• The REVOLUTION program includes completed Phase 1/2, pivotal Phase 3 DECLARATION, and LIBERTY vaccine comparison studies.

• Phase 1/2 tested suprapharmacologic doses up to 4,500 mg, confirming safety, tolerability, pharmacokinetics, and immunogenicity in healthy participants.

• DECLARATION is a randomized, triple-blind, placebo-controlled Phase 3 trial in adults and adolescents (≥12 years, ≥40 kg), with three arms (single-dose, multi-dose, placebo), enrolling ~600 subjects per arm, targeting a 70%-90% reduction in symptomatic COVID over 90 days.

• LIBERTY Phase 3 trial compares safety, tolerability, and co-administration of VYD2311 with mRNA COVID vaccines in 210 participants.

• Future studies may include pediatric safety, long-term efficacy, head-to-head efficacy with mRNA vaccines, and Long COVID prevention.

Efficacy, Safety, and Dosing Insights

• VYD2311 at 250 mg IM is expected to provide robust protection, with multi-dose regimens offering incremental benefit for higher titers.

• Protection is projected to remain above 50% for up to one year, surpassing current vaccine durability estimates.

• Safety profile is favorable, with low rates of adverse events, mild or moderate injection/infusion reactions, and tolerability similar to placebo at low doses.

• No deaths, serious adverse events, hypersensitivity, or severe treatment-emergent adverse events were observed in Phase 1/2.

• Manufacturing at the 250 mg dose is feasible and scalable for broad population use.