お知らせ • Jan 25
Precigen, Inc. Announces Positive Phase 1 Dose Escalation and Expansion Cohort Data for Investigational Off-the-Shelf PRGN-2012 AdenoVerse Immunotherapy in Patients with Recurrent Respiratory Papillomatosis
Precigen, Inc. announces positive Phase 1 dose escalation and expansion cohort data as of the January 12, 2023 cutoff for the investigational, potential first-in-class PRGN-2012 off-the-shelf (OTS) AdenoVerse immunotherapy in patients with recurrent respiratory papillomatosis (RRP). The company will host an R&D Day virtual event on January 24, 2023at 4:30 PM ET to showcase the data and will feature presentations by Clint T. Allen, MD, Senior Investigator, Surgical Oncology Program, Center for Cancer Research, National Cancer Institute (NCI) and lead associate investigator for the PRGN-2012 clinical trial, and Precigen's President and CEO, Helen Sabzevari, PhD. Participants may register and access the live webcast through Precigen's investor relations website in the Events & Presentations section. 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 juvenile or adult. There is no approved therapeutic treatment for RRP and the current standard-of-care is repeated endoscopic debulking with ablation or excision of papillomatous lesions. Surgeries are not curative and 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. Patients with aggressive RRP can undergo hundreds of lifetime surgeries to control their disease. 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, RRP has potential for malignant transformation in 3% to 7% of adult patients. 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. The Phase 1 clinical trial (clinical trial identifier: NCT04724980) evaluated safety and efficacy of PRGN-2012 as an immunotherapy following standard-of-care RRP surgery. Trial design included initiation of a 3+3 dose escalation cohort followed by a dose expansion cohort to enroll additional patients at the recommended Phase 2 dose (RP2D). Adult patients with severe, aggressive RRP, defined as greater than or equal to three surgeries in the prior 12 months, were enrolled to the clinical trial. Baseline patient characteristics of the 15 adult patients included a median age of 51 years (range: 30-73). Ten patients were male and 5 were female. Patients had an average of 6.2 surgeries (range: 3-10) in the last 12 months before enrolling in the trial. Patients were diagnosed with RRP for an average of 15 years prior to enrollment. Repeated administrations of PRGN-2012 were well-tolerated with no dose-limiting toxicities and no treatment-related adverse events (TRAEs) greater than Grade 2. All patients received four administrations of PRGN-2012 at the intended dose level. TRAEs were all mild and reduced in frequency over the treatment interval. The most common TRAE was injection site reaction, which occurred in all of the patients. Most other TRAEs occurring in more than one subject were similar to seasonal vaccines and the most common were fatigue, fever, and chills. The lack of a significant neutralizing antibody response to gorilla adenovector over time with subsequent additional vaccinations highlights the ability to deliver repeated administrations of PRGN-2012, a differentiating feature of the AdenoVerse platform. Clinical data show PRGN-2012 treatment significantly reduced the need for surgeries for severe, aggressive RRP patients treated at Dose Level 2. At Dose Level 2, 50% (6 out of 12) patients had a Complete Response, which is defined as no surgeries needed during the 12-month period following PRGN-2012 treatment completion (TABLE 3). All complete responders remained surgery-free post PRGN-2012 treatment as of the cutoff date. Patients in Dose Level 2 had a 58% (7 out of 12) Overall Response Rate, defined as greater than or equal to 50% reduction in the surgeries in 12-months post PRGN-2012 treatment completion compared to 12-months pre-treatment. 83% (10 out of 12) of patients treated at Dose Level 2 had reduced surgeries post PRGN-2012 treatment. The number of RRP surgeries in the patients (N=12) in Dose Level 2 reduced from a median of 6.5 surgeries (range: 3-10) in the 12-months pre-treatment to 0.5 surgeries (range: 0-6) in 12-months post PRGN-2012 treatment completion. Further, PRGN-2012 treatment showed significant improvement in anatomical Derkay scores, a tool used for research purposes to quantify RRP severity based on involvement of laryngeal structures, and voice quality, evaluated using the validated Vocal Handicap Index-10 (VHI-10), at 24-weeks post PRGN-2012 treatment completion compared to baseline. Phase 1 data show that PRGN-2012 treatment resulted in an increase in HPV 6/11-specific T-cell response in the peripheral blood of RRP patients. Furthermore, the T-cells infiltrating papillomas from patients who had an objective response and a biopsy sample available showed an increase in HPV 6/11-specifc T-cells in papillomas after PRGN-2012 treatment. Precigen initiated dosing in the Phase 2 trial at Dose Level 2 and is rapidly enrolling patients, with 20 patients enrolled to date in the Phase 2 trial, bringing the total number of enrolled patients to 32 at Dose Level 2. The Phase 2 clinical trial evaluates PRGN-2012 as an immunotherapy following standard-of-care surgery in adult patients with RRP.