Precigen, Inc. released positive Phase 1/2 pivotal study results for the investigational PRGN-2012 off-the-shelf (OTS) AdenoVerse gene therapy in patients with recurrent respiratory papillomatosis (RRP). Results were presented in a late-breaking oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting by Scott M. Norberg, DO, Associate Research Physician, Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute and a lead investigator for the PRGN-2012 clinical study. The Company will host a webcast event on June 3, 2024 at 6:00 PM CT /7:00 PM ET to detail the results presented at ASCO.

Pivotal Study Design and Endpoints: The Phase 1/2 clinical study (clinical trial identifier: NCT04724980) evaluated safety and efficacy of PRGN-2012. The study design included an initial 3+3 dose escalation cohort to identify the recommended Phase 2 dose (RP2D). Adult RRP patients who had three or more surgeries in the prior 12 months were eligible for the study.

The Phase 1/2 study enrolled a total of 38 patients. Of these, 3 patients received four administrations of PRGN-2012 at 1x 1011 particle units (PU)/dose and 35 patients received four administrations of PRGN-2012 at RP2D (5 x 1011 PU/dose) over a 12 week treatment period via subcutaneous injection. Primary endpoints included safety and Complete Response rate defined as the percentage of patients who require no RRP surgeries in the 12-month period after PRGN-2012 treatment completion.

Key secondary endpoints included HPV-specific immune responses, extent of papilloma growth as measured by Derkay scoring, and quality of life measurement as measured by Vocal Handicap Index-10 (VHI-10). Patient Characteristics: Baseline patient characteristics of the 35 adult patients included a median age of 49 years (range: 20-88); 20 of the patients were male and 15 were female. Patients had a median of 4 surgeries (range: 3-10) in the 12 months before PRGN-2012 treatment initiation.

Average years since RRP diagnosis was 20 (range: 1-65) with 12 and 23 patients with juvenile and adult onset RRP, respectively. Clinical Efficacy: Primary efficacy endpoint analysis demonstrated that 51% (18 out of 35) (95% CI: 34-69) patients achieved Complete Response, defined as no need for RRP surgeries in the 12-month period following completion of PRGN-2012 treatment. The Complete Response rate was 50% (6 out of 12) and 52% (12 out of 23) in the Phase 1 and Phase 2 portions of the study, respectively (TABLE 1).

Complete Responses were durable. Median durability of response has not yet been reached with median follow up of 20 months as of the data cutoff date of May 20, 2024. PRGN-2012 treatment significantly (p < 0.0001) reduced the need for surgeries in RRP patients compared to pre-treatment history (FIGURE 1).

PRGN-2012 treatment reduced the need for RRP surgeries in 86% (30 out of 35) of patients compared to their pre-treatment history. RRP surgeries were reduced from a median of 4 (range: 3-10) in the 12 months pre-treatment to 0 (range: 0-7) in the 12 months post PRGN-2012 treatment completion. PRGN-2012 treatment showed significant (p < 0.0001) improvement in anatomical Derkay scores, a tool used for research purposes to quantify RRP severity based on involvement of laryngeal structures, with mean Derkay scores reducing from 9 (range: 5-19) at baseline to 1 (range: 0-5) at 24 weeks post-treatment in patients with Complete Response.

Quality of life, as evaluated using the validated VHI-10, significantly (p < 0.0001) improved from a mean of 25 (range: 12-38) at baseline to 7 (range: 0-30) at 24 weeks post PRGN-2012 treatment in patients with Complete Response. PRGN-2012 treatment induced HPV 6/11-specific T cell responses in RRP patients with a significantly greater expansion of peripheral HPV-specific T cells observed in responders compared with non-responders. Safety: PRGN-2012 treatment was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events (TRAEs) greater than Grade 2 (TABLE 2).

All patients received four administrations of PRGN-2012 at the intended dose levels. TRAEs were mostly mild with no treatment-related serious adverse events reported. The most common TRAE was injection site reaction.

Other common TRAEs occurring in more than one subject were fatigue, chills, and fever. There was no meaningful anti-drug antibody response with repeat administrations of PRGN-2012.