AlloVir, Inc. announced final data from the Phase 2 study of posoleucel, an investigational, allogeneic, off-the-shelf, multi-virus specific T cell therapy, for the prevention of clinically significant infections or diseases from six common and devastating viruses in allogeneic hematopoietic cell transplant (allo-HCT) recipients – adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and JC virus (JCV). These final data demonstrated a substantial reduction in the expected rate of clinically significant viral infections or diseases in this high-risk patient population despite the expected high rates of viral reactivation. Biomarker data demonstrated the persistence of posoleucel and association between expansion of functional virus-specific T cells (VSTs) and viral control.

Repeat dosing of posoleucel was generally well tolerated in the study. The majority of allo-HCT recipients reactivate one or more of posoleucel's six target viruses post allo-HCT, which can lead to clinically significant infections, prolonged morbidity, hospitalization and premature death. There are currently no effective preventive therapies that can target these viruses simultaneously to block the progression of viral reactivation to clinically significant infections.

When given as preventative therapy, posoleucel is designed to serve as an immunologic bridge, covering patients through the high-risk, post-transplant window when patients' own immune systems are rebuilding. Posoleucel selectively expands in the presence of antigens from the six target viruses, controls viral replication and contracts after viral control and the reconstitution of patients' own immune systems. Phase 2 Multi-Virus Prevention Study: This open-label Phase 2 study evaluated the efficacy and safety of posoleucel for the prevention of clinically significant viral infections or disease caused by six target viruses: AdV, BKV, CMV, EBV, HHV-6 and JCV. The prevention study encompassed both the prophylaxis of patients at high risk for viral reactivation and the preemptive treatment of patients with viral reactivation who had not yet developed clinically significant infections or disease.

Patients received up to seven biweekly posoleucel infusions and were tested for viremia by polymerase chain reaction (PCR) on a weekly basis against all six viruses over a period of 14 weeks. Following this dosing period, patients received follow-up through Week 26. The primary study endpoint was the number of new onset clinically significant infections or end-organ disease through Week 14.

The study enrolled 26 high-risk allo-HCT patients. Of these patients, 12 (46%) received transplanted cells from haploidentical donors, nine (35%) from mismatched unrelated donors, four (15%) from matched unrelated donors with T cell depletion or with lymphopenia, and one (4%) from umbilical cord blood. Out of 26 high-risk allo-HCT patients who received posoleucel in this open-label study, 22 (85%) patients experienced reactivation of at least one of posoleucel's target viruses.

Despite these expected high rates of viral reactivation, only three clinically significant infections were observed through Week 14; two asymptomatic patients initiated preemptive CMV treatment with valganciclovir following withdrawal of letermovir, and one patient started rituximab for EBV-associated post-transplant lymphoproliferative disease in the setting of receiving high-dose steroids. Biomarker analyses demonstrated that viral control was associated with expansion of functional VSTs. An increase in frequency of functional VSTs, when evaluating change from baseline (Pre) to peak response through the 14-week treatment period (Post), was observed via ELISpot.

This increased frequency of functional VSTs was associated with a reduction in viremia during the same timeframe. Cell persistence was evaluated with T cell receptor sequencing, with the presence of posoleucel confirmed both during the infusion period and up to 14 weeks after the last infusion. Treatment of up to seven doses of posoleucel over 12 weeks was generally well tolerated with no unanticipated safety signals.

Rates of GVHD (19%) were similar in frequency and severity to those expected in this high-risk allo-HCT population. Three (12%) treatment-related serious adverse events were reported. No episodes of cytokine release syndrome were reported.