• Alignment follows Type C meeting for VYD2311 as previously disclosed
• BLA pathway for VYD2311 to be supported by a single, Phase 2/3 randomized, double-blind, placebo-controlled trial with a primary endpoint of reduction in symptomatic COVID-19, resembling CANOPY Cohort B
• Company’s target product profile is low-dose, intramuscular, scalable, low-cost, long-lasting, protective option for target populations, including adults and adolescents (12 years+; 40kg+) and, subject to FDA alignment, pediatrics (aged 0 to 12 years)
• Anticipate compact trial (12-week primary endpoint analysis) evaluating prevention of COVID-19 largely among ordinary Americans, enabling rapid enrollment
• Planned head-to-head safety evaluation with COVID-19 vaccine, pending regulatory alignment
• Quantities of VYD2311 potential commercial launch product available

 Invivyd, Inc. announced it has received and is aligned with advice from the U.S. Food and Drug Administration (FDA) on a compact and, therefore, rapid pathway to potential Biologics License Application (BLA) approval for Invivyd’s novel monoclonal antibody (mAb) candidate VYD2311, for the prevention of COVID-19.   As part of a recent Type C meeting, FDA advised that a single, Phase 2/3 randomized, double-blind, placebo-controlled trial evaluating mAb efficacy from a relatively modest number of RT-PCR -confirmed symptomatic COVID-19 disease events could support a BLA submission for VYD2311 for the prevention of COVID-19 in a broad population of Americans (12 years of age and older, weighing at least 40kg), including immunocompromised people, subject to agreement on safety database size and pending full protocol review.

“We believe monoclonal antibodies such as VYD2311 can serve as a powerful alternative to vaccines for COVID-19 prevention, and represent an important potential paradigm shift to move American medicine beyond the real and perceived limitations of COVID-19 vaccines. Amidst declining public trust in vaccines, we want to offer Americans a new, non-vaccine choice,” said Marc Elia, Chairman of Invivyd’s Board of Directors. “COVID-19 monoclonal antibody medicines work alongside natural human immunity without needing to activate the immune system, and, if we can make them widely available, we believe mAbs represent the natural next step beyond vaccination to keep people safe and well, if approved, in the face of pervasive COVID-19.”

FDA advice and background statements to Invivyd cited observations on Invivyd’s efficient execution of its Phase 3 randomized clinical trial of pemivibart for the prevention of COVID-19 (CANOPY), the antiviral durability of pemivibart, and the strong protection demonstrated by pemivibart among ordinary Americans in CANOPY Cohort B, while recognizing that Invivyd antibodies stem from a common molecular lineage.   Multiple such Invivyd antibodies have undergone successful randomized, placebo-controlled clinical trials, including efficacy assessment in contemporary Americans. In agreement with FDA advice, Invivyd plans to study two doses of VYD2311 to assess any differences in resulting levels of protection or differences in safety, with a goal to unlock further choice for Americans in need of COVID-19 protection.

“We are grateful for the FDA’s clear and constructive feedback, which provides a well-defined path forward for our COVID-19 development program. We believe the FDA’s feedback underscores the shared urgency to advance innovative solutions for prevention of COVID-19,” said Rachael Gerlach, Ph.D., Vice President, Regulatory Affairs at Invivyd. “Combined with Invivyd’s unique discovery platform, this alignment is a critical step in bringing forward a potentially important, medically attractive and patient-friendly alternative to COVID vaccination, providing protective monoclonal antibodies, if approved, to any American who wishes protection, whether immune compromised, at high risk for severe disease, or just interested in not getting sick.”

The FDA provided advice for pursuit of a traditional BLA pathway for the prevention of COVID-19 caused by SARS-CoV-2 in adults and adolescents weighing at least 40 kg, recommending a Phase 2/3 randomized, double-blind, placebo-controlled trial with a primary endpoint of RT-PCR-confirmed symptomatic COVID-19, with a timepoint for measuring the primary endpoint coinciding with the expected duration of protection, anticipated as 12 weeks (3 months), and the potential for selection of an additional, longer duration timepoint, which Invivyd anticipates as 24 weeks (6 months).

Invivyd’s analysis of CANOPY clinical trial data and Cox Proportional Hazards modeling, combined with biophysical properties of VYD2311, suggest likely robust, long-term protection from symptomatic COVID-19 due to high potency and observed long half-life of ~76 days, following a relatively low dose of VYD2311 via intramuscular route of administration. Invivyd’s most recent analysis aligns well with multiple similar analyses spanning the majority of SARS-CoV-2 virus variation since emerging as a global human disease in 2020, lending confidence to dose selection and anticipated clinical benefit. In addition, as COVID-19 monoclonal antibodies represent additional immune support and do not require engagement of the human immune system with associated inflammation symptoms (reactogenicity), Invivyd anticipates, pending regulatory alignment, a clinical trial cohort exploring randomized, active-controlled safety and tolerability of VYD2311 compared to vaccination.

“Our completed first-in-human study of VYD2311 demonstrated high SARS-CoV-2 antiviral titers and an attractive safety profile at very high doses, well beyond doses we contemplate going forward with in development. We look forward to opening a U.S. IND and moving as quickly as possible to finalize a pivotal clinical trial design with the FDA,” said Mark Wingertzahn, Ph.D., Senior Vice President, Clinical Development at Invivyd, “If successful, we have the potential to change practice and provide consumers and central health authorities with an attractive alternative to COVID-19 vaccination. We anticipate sharing our plans as soon as possible once we finalize them with FDA.”

Invivyd has quantities of VYD2311 clinical supply and potential commercial launch product available.