8-K: Invivyd Forms SPEAR Study Group to Investigate Monoclonal Antibody Therapy for Long COVID and Post-Vaccination Syndrome

Invivyd, Inc. announced the formation of the SPEAR Study Group with leading researchers to rigorously assess the effects of monoclonal antibody therapy, including PEMGARDA, for Long COVID and COVID-19 Post-Vaccination Syndrome.

Summary

• Invivyd, Inc. has formed the SPEAR (Spike Protein Elimination and Recovery) Study Group with leading investigators to explore the effects of broadly neutralizing anti-SARS-CoV-2 spike protein monoclonal antibody (mAb) therapy for Long COVID and Post-Vaccination Syndrome (PVS).
• The SPEAR Study Group will design and guide anticipated clinical trials to evaluate mAb therapy in patients suffering from Long COVID or PVS, conditions believed to be mediated by persistent viral reservoirs or circulating spike protein.
• The initiative was prompted by a growing number of anecdotal case reports and series suggesting meaningful symptom relief/remission of Long COVID following the use of PEMGARDA (pemivibart), a monoclonal antibody currently authorized for pre-exposure prophylaxis of COVID-19 in certain immunocompromised individuals.
• PEMGARDA is not currently authorized by the U.S. FDA for the treatment of Long COVID, and the emerging reports are uncontrolled and anecdotal, necessitating rigorous clinical investigation.
• The study group includes Dr. Michael Peluso (UCSF), Dr. Amy Proal (Polybio Research Foundation, Mount Sinai CoRE), and Dr. David Putrino (Mount Sinai CoRE), who are key thought leaders in Long COVID and PVS.
• Initial clinical efforts will focus on assessing monoclonal antibody safety, translational biology, and exploratory efficacy in patient populations characterized by persistent virus or circulating SARS-CoV-2 spike protein.
• The SPEAR Study Group intends to launch collaborative, multi-center translational clinical research on Long COVID, including PVS, as soon as practicable, potentially including next-generation mAb candidates like VYD2311.
• Long COVID affects as many as 5% or more of Americans, representing a significant public health burden with no approved treatments.
• Invivyd plans to meet with the FDA early in Q3 to discuss rapid approval pathways for COVID-19 mAbs.

Sentiment

Score: 7

Explanation: The sentiment is generally positive due to the proactive formation of a study group with leading experts to address a significant unmet medical need (Long COVID) using a promising therapeutic approach (mAbs). However, the early stage of the research, reliance on anecdotal evidence, and the need for rigorous clinical trials temper the overall enthusiasm.

Positives

• Formation of the SPEAR Study Group with leading researchers addresses a significant unmet medical need for Long COVID and Post-Vaccination Syndrome.
• The initiative explores a mechanistically plausible hypothesis that reducing persistent SARS-CoV-2 spike protein or viral material through mAb therapy may offer a promising therapeutic approach.
• Anecdotal reports suggest PEMGARDA may offer meaningful symptom relief/remission in some Long COVID patients, warranting further investigation.
• Collaboration with key thought leaders like Drs. Peluso, Proal, and Putrino brings significant expertise to the study group.
• The research aims to lay the groundwork for future efficacy studies that could deliver real therapeutic options to patients.
• Invivyd's existing mAb, PEMGARDA, has demonstrated in vitro neutralizing activity against major SARS-CoV-2 variants, including JN.1, KP.3.1.1, XEC, and LP.8.1.
• The company is developing next-generation mAb candidates like VYD2311, which may offer more patient-friendly administration routes (e.g., intramuscular).

Negatives

• PEMGARDA is not authorized for the treatment of Long COVID, and its current use for this condition is off-label.
• The initial reports of PEMGARDA's benefit in Long COVID are anecdotal and uncontrolled, requiring rigorous clinical validation.
• There are limitations to the data supporting the benefits of PEMGARDA, as immunobridging was based on different populations and SARS-CoV-2 variants that are no longer circulating.
• The emergency use authorization for PEMGARDA is temporary and subject to termination or revocation.
• Certain SARS-CoV-2 viral variants may emerge that have substantially reduced susceptibility to PEMGARDA, potentially rendering it ineffective.
• The company's forward-looking statements involve risks and uncertainties, including the timing and success of clinical trials, regulatory approvals, and the ability to maintain funding.

Risks

• The timing, progress, and results of the SPEAR Study Group and associated clinical development activities are uncertain.
• Results of nonclinical studies or clinical trials may not be predictive of future results, and interim data are subject to further analysis.
• Unexpected safety or efficacy data could be observed during preclinical studies or clinical trials.
• The predictability of clinical success of product candidates based on neutralizing activity in nonclinical studies is not guaranteed.
• Potential variability in neutralizing activity of product candidates tested in different assays (e.g., pseudovirus vs. authentic assays).
• Variability of results in models and methods used to predict activity against SARS-CoV-2 variants.
• Uncertainty whether the epitope that pemivibart and VYD2311 target remains structurally intact amidst viral evolution.
• Whether product candidates are able to demonstrate and sustain neutralizing activity against major SARS-CoV-2 variants, particularly in the face of viral evolution.
• Whether mAb therapy is able to offer a therapeutic approach to Long COVID.
• The ability to gain alignment with applicable regulatory authorities on clinical trial designs and regulatory pathways for COVID-19 mAbs, and the timing thereof.
• Changes in the regulatory environment could impact development and approval processes.
• Uncertainties related to the regulatory authorization or approval process and available development and regulatory pathways.
• Future clinical trial site activation or enrollment rates may not meet expectations.
• The duration of the EUA granted by the FDA for PEMGARDA is uncertain, and the EUA could be revised or revoked.
• The ability to maintain a continued acceptable safety, tolerability, and efficacy profile of any product candidate following regulatory authorization or approval.
• Changes in expected or existing competition could impact market potential.
• Reliance on third parties for various aspects of development and manufacturing.
• Complexities inherent in manufacturing mAb therapies.
• Macroeconomic and political uncertainties could affect operations and funding.
• The company's ability to continue as a going concern.
• Whether the company has adequate funding to meet future operating expenses and capital expenditure requirements.

Future Outlook

Invivyd and the SPEAR Study Group plan to launch collaborative, multi-center translational clinical research on Long COVID and Post-Vaccination Syndrome as soon as practicable, including the use of next-generation monoclonal antibody candidates like VYD2311. The company anticipates meeting with the FDA early in Q3 to discuss rapid approval pathways for COVID-19 mAbs, aiming to generate data to inform future studies and potential regulatory pathways for Long COVID treatments.

Management Comments

• Dr. Michael Peluso stated, "It is now clear from a growing body of high-quality, peer-reviewed research that persistent spike protein or viral reservoirs can be identified in a meaningful portion of people with Long COVID. For the first time in years, there is a company with the capability to explore this space using active, broadly neutralizing monoclonal antibodies. This research marks an essential step toward understanding what may cause debilitating COVID-driven chronic disease, and we hope will lay the groundwork for future efficacy studies that could deliver real therapeutic options to patients who have waited far too long."
• Marc Elia, Chairman of the Board at Invivyd, commented, "Long COVID is a pervasive, debilitating, and underappreciated public health challenge affecting millions of adults and children in the U.S., with no approved treatments. Monoclonal antibodies have already demonstrated efficacy in preventing acute COVID-19 infections and treating acute COVID-19 infections, including long-term infections, and emerging anecdotal reports suggest pemivibart may have potential in addressing symptoms in some Long COVID patients. We believe that monoclonal antibodies are key to managing the ongoing burden of endemic COVID-19 disease in all forms, and as previously disclosed, we will be meeting with the FDA early in 3Q to discuss rapid approval pathways for COVID-19 mAbs. Meanwhile, our formation of the SPEAR Study Group is a critical step toward potentially unlocking a Long COVID treatment opportunity for patients in need by generating data needed to inform future studies and potential regulatory pathways. We look forward to sharing future milestones as we advance this important initiative."

Industry Context

The announcement addresses Long COVID, a pervasive and debilitating public health challenge affecting millions in the U.S. with no currently approved treatments. This initiative positions Invivyd at the forefront of exploring a novel therapeutic approach (monoclonal antibodies) for a significant unmet medical need, potentially expanding the application of mAbs beyond acute COVID-19 prevention and treatment to chronic post-viral syndromes. The focus on persistent viral reservoirs or spike protein aligns with emerging research in the field.

Stakeholder Impact

• **Shareholders:** Potential for expansion into a new, large market (Long COVID treatment) could create significant value, but also carries clinical and regulatory risks.
• **Patients (Long COVID/PVS sufferers):** Offers hope for a potential new treatment option for a debilitating condition with no approved therapies.
• **Healthcare Providers:** Provides a framework for rigorous investigation into a potential new therapeutic approach for a challenging patient population.
• **Researchers:** Fosters collaboration with leading experts and provides resources for critical research into disease biology and efficacy endpoints.

Next Steps

• The SPEAR Study Group will structure and guide anticipated clinical trials evaluating the effects of broadly neutralizing anti-SARS-CoV-2 spike protein mAb therapy.
• Launch collaborative, multi-center translational clinical research on Long COVID, including PVS, as soon as practicable.
• Conduct initial SPEAR clinical efforts aimed at rigorous, controlled assessment of monoclonal antibody safety, translational biology, and exploratory efficacy.
• Invivyd will meet with the FDA early in Q3 to discuss rapid approval pathways for COVID-19 mAbs.
• Share future milestones as the SPEAR Study Group initiative advances.

Key Dates

Keywords

Long COVID, Post-Vaccination Syndrome, Monoclonal Antibody, PEMGARDA, Invivyd, SARS-CoV-2, Clinical Trials, Biopharmaceutical, Spike Protein, COVID-19, EUA, FDA, VYD2311