Invivyd Updates VYD2311 REVOLUTION Trials, Modestly Upsizes Study, Unveils Measles mAb VMS-063

Key Points

• Invivyd modestly upsized its pivotal DECLARATION trial for VYD2311 (adding roughly 500 subjects) after a pre-specified interim sample-size re-estimation as pooled blinded COVID-19 event rates approached target levels, a conservative step intended to reduce the risk of underpowering while the company prepares toward a potential BLA.
• The company plans to initiate the LIBERTY study to evaluate comparative and combination safety/immunology of a monoclonal antibody with an mRNA vaccine, and has FDA alignment on a pediatric DRUMMER plan featuring parallel cohorts (including infants 0–2) to support a pediatric BLA if DECLARATION is successful.
• Invivyd unveiled VMS-063, a potentially first‑in‑class measles monoclonal antibody showing highly potent neutralization in preclinical assays, and has begun preclinical development while engaging public health and regulatory authorities on likely prophylactic and treatment use cases for vulnerable populations.

Invivyd NASDAQ: IVVD provided updates on its REVOLUTION program for COVID-19 monoclonal antibody candidate VYD2311 and announced the discovery and early development work for a measles monoclonal antibody candidate, VMS-063, during a conference call led by board chairman Marc Elia alongside Chief Scientific Officer Dr. Robert Allen and Chief Medical Officer Dr. Michael Mina.

Company frames monoclonal antibodies as an alternative to vaccines for vulnerable populations

Elia argued that SARS-CoV-2 continues to transmit broadly in the U.S., with periodic waves that contribute to “lifespan-shortening” damage. He said Invivyd’s goal is to develop monoclonal antibodies that could serve as a more durable and immediate form of protection than vaccination, describing antibodies as “immediate, equitable, non-inflammatory or reactogenic,” and “free of spike protein,” which he characterized as “an important inflammatory and fundamentally toxic antigen.”

Elia also pointed to Invivyd’s currently authorized COVID-19 antibody, pemivibart (PEMGARDA), as proof of concept for “durably drug[ging] an evolving target,” and said VYD2311 is intended for broader use with “dramatically lower access barriers” than PEMGARDA.

DECLARATION pivotal study: event rates and a modest sample size increase

Elia said the company’s DECLARATION pivotal trial for VYD2311 is designed with the U.S. Food and Drug Administration to assess safety and efficacy versus placebo, with two active arms (single-dose and multi-dose). The primary endpoint is reduction in PCR-confirmed symptomatic COVID-19 compared with placebo—an approach he said is consistent with Invivyd’s prior randomized trials.

He emphasized the importance of “attack rate,” or community infection levels, for powering infectious disease prevention trials. Elia said that around the midpoint of the base trial conduct, pooled blinded confirmed COVID-19 clinical event rates are approaching the company’s target level, which he said provides confidence in statistical powering.

Invivyd also completed a pre-specified interim sample size re-estimation and “upsized our study to a modest extent,” which Elia described as a conservative step intended to reduce the risk of underpowering. In Q&A, he said the incremental enrollment (referencing an added 500 subjects) is expected to be “credibly measured in weeks,” while cautioning that timing is difficult to promise with precision.

Elia also said the company is preparing to evaluate the clinical profile of VYD2311 later this year and to begin commercial preparation toward an anticipated biologics license application (BLA) filing and potential approval, while acknowledging uncertainty around future event accumulation and ultimate powering.

Additional REVOLUTION studies: LIBERTY and pediatric plan alignment

Beyond DECLARATION, Elia said Invivyd is on track to initiate the LIBERTY study “shortly.” He described LIBERTY as a companion study intended to assess comparative and combination safety and immunology between a monoclonal antibody and an mRNA vaccine—work he said could help regulators and clinicians advise vulnerable patients who may use both approaches.

Elia also said the company has achieved alignment with the FDA on a pediatric study plan aimed at enabling a BLA for VYD2311 in children ages 0–11. He noted that while Invivyd proposed an age cohort de-escalation approach, the agency recommended a parallel group design that includes infants ages 0–2 starting at the same time as other cohorts. Elia said recent input from the DECLARATION independent data monitoring committee to broaden subject eligibility to include pregnant women, along with removal of certain safety check-ins, “speaks to the increasing appreciation of the potential safety profile of low-dose monoclonal antibodies by key counterparties.” The planned pediatric trial is named DRUMMER and would be pursued contingent on success in DECLARATION and the broader REVOLUTION program, he said.

Variant commentary: Invivyd downplays “Cicada” lineage and cites external data

Dr. Allen addressed the BA.3.2.2 lineage, which he said has been “sensationalized” and referred to as the “Cicada variant.” He said Invivyd has tracked it for over a year and described it as “not in any way new,” arising from recombination of Omicron BA.1 and BA.2 lineages. Allen characterized BA.3.2.2 as “not particularly fit,” and said he does not expect it to drive a meaningful wave or sustain dominance.

Allen said Invivyd does not yet have its own proprietary neutralization data against BA.3.2, but he cited independent laboratory-published VYD2311 results that he called “attractive.” He added that Invivyd selected one next-generation COVID antibody candidate last year in part due to potency against a panel that included BA.3.2.2, and suggested that if viral evolution is approaching equilibrium, a single antibody that does not need updating could be possible.

Measles program: VMS-063 positioned as potential first-in-class monoclonal antibody

Invivyd also unveiled VMS-063, a measles monoclonal antibody candidate that the company described as potentially first-in-class. Allen said the program began after physicians responding to U.S. measles outbreaks asked Invivyd if it could develop a measles antibody for clinical use. He said Invivyd studied the native human antibody repertoire against measles and performed extensive sequence analysis and structural biology to optimize candidates, ultimately selecting VMS-063.

Allen said VMS-063 has shown “highly potent neutralization” of key circulating and ancestral measles variants in authentic and pseudovirus systems, and that the company has initiated preclinical development and plans engagement with public health and regulatory authorities on development pathways.

Dr. Mina provided context on measles epidemiology and clinical need, describing measles as among the most infectious viruses, with an R0 of approximately 17. He said the U.S. is experiencing outbreaks “at a scale we’ve not seen for over 30 years,” attributing the trend to more than vaccine hesitancy alone. Mina said population-level immunity may be weakening as cohorts with lifelong high titers from prior natural infection decline and as vaccine-induced titers shape herd immunity dynamics—an effect he said is reflected in declining anti-measles antibody titers in pooled donor sera and IVIG over decades.

Mina also challenged the idea that measles is benign, citing risks including hospitalization, death, encephalitis, immune amnesia, opportunistic bacterial infections, and rare late complications. He noted there are currently no approved or authorized measles treatments, with supportive care, IVIG, and vitamin A among available options.

On potential use cases, Mina said a precision monoclonal antibody could be used across treatment and prophylaxis settings and could complement vaccines. He highlighted a potential “bridge to vaccination” use case in infants—helping protect babies before scheduled vaccination without compromising optimal vaccine response timing. He also cited possible relevance for populations that cannot be vaccinated, including pregnant women and immunocompromised individuals, and for patients who may not respond well to vaccines.

During Q&A, Elia said Invivyd is still evaluating which measles indication to prioritize and that regulatory and public health considerations could influence development strategy. The company asked investors to “bear with us” as those conversations progress, and said it plans to provide more detail as plans become more defined.

About Invivyd NASDAQ: IVVD

Invivyd, Inc, a commercial-stage biopharmaceutical company, focuses on the discovery, development, and commercialization of antibody-based solutions for infectious diseases in the United States. The company developed INVYMAB, a platform that combines viral surveillance and predictive modeling with advanced antibody engineering. Its pipeline includes PEMGRADA (pemivibart) injection, a half-life extended investigational monoclonal antibody (mAb) for the prevention of COVID-19 in adults and adolescents; VYD2311, an mAb candidate which is in preclinical studies for the prevention or treatment for COVID-19; and adintrvimab, that is in phase 3 clinical trials for the prevention or treatment of COVID-19.

This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to contact@marketbeat.com.