WARREN, N.J. — Tevogen Bio today announced positive topline results from its Proof-of-Concept (POC) clinical trial designed to evaluate the safety and feasibility of TVGN 489, the company’s first clinical product of its precision T Cell therapy platform, for the treatment of acute high-risk COVID-19 patients. TVGN 489 is a genetically unmodified, off-the-shelf, allogeneic cytotoxic CD8+ T lymphocyte (CTL) product with precise targets across the SARS-CoV-2 genome, not just the Spike protein. To date, TVGN 489 targets, identified early in the pandemic, persist in the most recent SARS-CoV-2 variants. The open label comparative trial was conducted at Thomas Jefferson University Hospital in Philadelphia to assess the safety and feasibility of TVGN 489 when given at one of four escalating doses. Twelve ambulatory patients with newly diagnosed COVID-19 infection who were at higher risk for infection-related complications due to advanced age or CDC-defined comorbid conditions such as heart, lung, liver, and kidney disease, hypertension, diabetes, cancer, or obesity were treated on the trial. 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.
The treated patients had between 2 to 5 comorbidities each and 6 out of 12 (50%) were immunocompromised due to treatment for cancer or autoimmune disease. Multiple COVID-19 variants were detected in the group. Safety endpoints included infusion reactions, grade 4 adverse events, GVHD, marrow aplasia, neurotoxicity and CRS.
Table 1. Treatment arm (n=12)
|
Safety Criteria as Defined in the Study Protocol |
Trial Result |
|
Infusion Reactions (≥ Grade 3) |
0/12 |
|
Cytokine release syndrome, (Grade ≥ 2) |
0/12 |
|
Neurotoxicity (Grade ≥ 2) |
0/12 |
|
Graft versus Host Disease |
0/12 |
|
Grade ≥4 Adverse Events (Related to the CTL therapy & outside the spectrum of identified COVID related adverse events) |
0/12 |
Safety endpoints were reviewed after each dose level and confirmed by an independent Data and Safety Monitoring Committee at Jefferson and by both internal and external Medical Monitors who provided permission to escalate to the next dose level. Based on the data in Table 1, safety was confirmed with the minimum required number of patients per dosing level. In addition to safety endpoints, secondary endpoints measuring the reduction of viral load and the presence of cellular and humoral anti-COVID-19 responses after treatment were also met.
Enrollment was completed in nine months, and six-month follow-up for all patients concluded on January 19, 2023. In the treatment arm, no patient experienced progression of their COVID-19 infection and all patients returned to their baseline level of health within 14 days of treatment. There were no incidences of COVID-19 reinfection or Long COVID observed in any treated patient through the 6-month follow-up period. While patients in the treatment group experienced COVID-19 symptom relief in a rapid, consistent timeframe as self-reported and confirmed by the investigators, patients on the observation arm showed improvement in a less consistent, and in some cases, longer time frame.
The study investigators plan to submit the full data for publication in a peer-reviewed journal in the upcoming weeks.
“The highly encouraging data of TVGN 489 allows us to turn our attention to the critical unmet need in the COVID-19 landscape. Immunocompromised and the elderly and infirm usually do not benefit from currently available prevention or treatment strategies for COVID-19 and remain highly vulnerable to poor outcomes with a COVID-19 infection. These patients, as well as those individuals with Long COVID, urgently require new treatment options,” said Dr. Dolores Grosso, DNP, the Principal Investigator of the trial.
“I’m greatly encouraged by the POC trial experience of TVGN 489 and hopeful that our investigational COVID-19 therapy will eventually offer hope to a substantial segment of patients,” said Dr. Neal Flomenberg, MD, Tevogen’s Chief Scientific Officer.
“Tevogen’s goal is to provide access to the vast and unprecedented potential of personalized immunotherapies for large patient populations impacted by common cancers and viral infections. The ability to administer TVGN 489 in the outpatient setting and the ongoing work by Tevogen scientists to use this product in diverse patient populations, highlights Tevogen Bio’s commitment to patient accessibility,” said Tevogen founder and CEO Dr. Ryan Saadi, MD, MPH.
Tevogen’s research pipeline includes treatment for other serious viral infections and cancers using their precision T Cell platform.