First Patient Dosed for AdenoVerse Immunotherapy for Recurrent Respiratory Papillomatosis

Precigen announced the first patient has been dosed in the Phase I study of PRGN-2012, a first-in-class, investigational off-the-shelf (OTS) AdenoVerse™ immunotherapy in adult patients with recurrent respiratory papillomatosis (RRP). The US Food and Drug Administration (FDA) recently granted Orphan Drug Designation for PRGN-2012 in RRP in March 2021.

PRGN-2012 is an innovative therapeutic vaccine with optimized antigen design that uses Precigen's gorilla adenovector technology, part of Precigen's proprietary AdenoVerse platform, to elicit immune responses directed against cells infected with HPV 6 or HPV 11. Gorilla adenovectors have numerous advantages, including the ability for repeat administration, the inability to replicate in vivo, which may improve safety, and the ability to deliver large payload capacity. In preclinical models, PRGN-2012 has demonstrated strong and specific immune response against HPV 6 and HPV 11.

PRGN-2012 is under development through a Cooperative Research and Development Agreement (CRADA) with the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), which is part of the National Institutes of Health (NIH). This CRADA has allowed Precigen to rapidly and cost-effectively advance PRGN-2012 to the clinic. The Phase I clinical study of PRGN-2012 is led by Scott M. Norberg, DO, Assistant Research Physician, Genitourinary Malignancies Branch, of CCR NCI, and Clint T. Allen, MD, Principal Investigator, Section on Translational Tumor Immunology, of the National Institute on Deafness and Other Communication Disorders (NIDCD), which is also part of the NIH.

The Phase I study follows 3+3 dose escalation of PRGN-2012 as an adjuvant immunotherapy following standard-of-care surgical removal of visible papillomatosis disease. Patients receive up to four injections of PRGN-2012. The primary objective of the study is to determine safety and tolerability and recommended Phase II dose (RP2D) of PRGN-2012. The study will enroll 3 to 6 subjects at each dose level, and 12 patients will be treated at the maximum tolerated dose.

"Dosing the first patient with PRGN-2012, the first in the infectious disease setting, represents a significant milestone for the OTS AdenoVerse platform. RRP patients need new adjuvant treatment options to reduce the number of devastating repeat surgical procedures commonly associated with this disease," said Helen Sabzevari, PhD, President and CEO of Precigen. "We look forward to producing clinical data to build upon the encouraging signals we have seen in preclinical studies in which PRGN-2012 was shown to induce robust HPV 6 and HPV 11-specific T-cell response in RRP patient samples in vitro."

RRP is a rare, difficult-to-treat and sometimes fatal neoplastic disease of the upper and lower respiratory tracts that is caused by infection with HPV 6 or HPV 11. RRP is classified based on age of onset as a juvenile or adult. Juvenile-onset disease has an incidence of 4 per 100,000 and adult-onset RRP has an incidence of 2 to 3 per 100,000. There is no cure for RRP and the current standard-of-care is repeated endoscopic debulking with ablation or excision of papillomatous lesions. Recurrence of papilloma after surgical removal is very common and repeated procedures are required to debulk and monitor the disease, which exposes patients to anesthetic and surgical risks, and emotional distress. RRP morbidity and mortality results from the effects of papilloma mass on the vocal cords, trachea, and lungs, which may cause voice changes, stridor, airway occlusion, loss of lung volume, and/or post-obstructive pneumonia Although rare, one to three percent of RRP cases can transform into invasive squamous cell carcinoma.