Tevogen Bio is highlighting the publication of Phase I clinical trial data for TVGN 489, an investigational allogeneic SARS-CoV-2 specific Cytotoxic CD8+ T lymphocytes (CTLs) immunotherapy. The study, published in Blood Advances, showcases the potential of TVGN 489 in treating high-risk COVID-19 patients.
The open-label comparative trial, conducted at Thomas Jefferson University Hospital, enrolled twelve ambulatory patients with newly diagnosed SARS-CoV-2 infection who were at higher risk for infection-related complications due to advanced age or CDC-defined comorbid conditions. Eighteen patients, who also met these criteria but did not receive TVGN 489 because of lack of HLA matching, were enrolled on an observational arm in the study and treated with standard of care including monoclonal antibodies.
Key Findings from the Phase I Trial
The interventional arm patients, including a significant proportion of immunocompromised individuals (50%) and those with pre-existing cancers (40%), received a single infusion of TVGN 489 at escalating doses. The product contained 68.5% SARS-CoV-2-specific CD8+ CTLs/total cells.
Key observations from the trial include:
- Symptom Improvement and Resolution: Patients in the treatment arm experienced more consistent and rapid symptom improvement and resolution compared to the observation group.
- Viral Elimination: Nasal swab PCR data indicated 88% or greater viral elimination in 92% of patients by day +4 and > 99% viral elimination in all patients by day +14.
- Absence of Disease Progression or Long COVID: No progression of disease or development of Long COVID was observed in the treatment group, despite the prevalence of immunocompromised patients.
- Preservation of Immune Response: TVGN 489 did not interfere with the development of endogenous anti-SARS-CoV-2 humoral or cellular responses.
- T Cell Persistence: T cell receptor beta (TCRβ) analysis showed persistence of donor-derived CTLs through the end of the 6-month follow-up period.
Safety and Tolerability
TVGN 489 was well-tolerated at all four doses tested. The primary study endpoints were related to safety. No dose-limiting toxicities or significant adverse events related to TVGN 489, including Cytokine Release Syndrome, were observed in any patient at any dose level.
Expert Commentary
Afshin Beheshti, PhD, University of Pittsburgh Professor at School of Medicine, highlighted the importance of developing curative and sustained therapies against evolving viruses. "T cells target the whole viral genome and thus avoid being rendered rapidly ineffective with mutagenesis at one site such as the Spike protein in SARS-CoV-2... CTLs can directly target viral proteins in patients with weakened immune systems, such as the elderly and immunocompromised, and may also be effective for Long COVID treatment for which there is currently no known treatment at all."
Neal Flomenberg, Tevogen’s Chief Scientific Officer, noted the unexpected persistence of TVG-489 CTLs. "Due to the high degree of immune mismatch between the treated patients and the CTL donor, we suspected that after an initial reaction against the SARS-CoV-2 virus, the CTLs would have been quickly eliminated by the patients. Persistence of allogeneic T-cells has been associated with disease control in many settings, therefore, the further exploration of the reason for the persistence and the potential implications is important."
Future Implications
Ryan Saadi, CEO of Tevogen Bio, expressed optimism about the company's ExacTcell™ technology platform. "The full potential of T cell therapies has yet to be realized. We believe our allogeneic, precision T cell technology platform, ExacTcell™, represents a significant scientific breakthrough with the potential to mainstream cell therapy through a new class of off-the-shelf T cell therapies, manufactured and stored for immediate use, with diverse applications across virology, oncology, and neurology."
