Precigen Advances PRGN-2012 for RRP Towards BLA Submission
核心洞察
Precigen is set to submit a rolling BLA for PRGN-2012 in recurrent respiratory papillomatosis (搜索) (RRP) in Q4 2024 under an accelerated approval pathway.
The company's pivotal study showed that 51% of RRP patients achieved complete response with PRGN-2012, requiring no surgeries post-treatment.
Preclinical data presented at SITC 2024 highlights PRGN-3008, a next-generation UltraCAR-T targeting CD19 (搜索), with potential for oncology and autoimmune diseases.
Precigen, Inc. (Nasdaq: PGEN) has announced significant progress in its biopharmaceutical programs, particularly with PRGN-2012 for recurrent respiratory papillomatosis (搜索) (RRP), as detailed in their third-quarter 2024 financial results and business update.
The company is on track to submit a rolling Biologics License Application (BLA) to the FDA in the fourth quarter of 2024 for PRGN-2012, an AdenoVerse gene therapy, under the accelerated approval pathway. This follows a pre-BLA meeting with the FDA where full alignment was achieved on the BLA content, including the Chemistry, Manufacturing, and Controls (CMC) module.
PRGN-2012: Targeting Recurrent Respiratory Papillomatosis
PRGN-2012 is an investigational off-the-shelf AdenoVerse gene therapy designed to stimulate immune responses against human papillomavirus (HPV (搜索)) 6 or HPV 11, the causative agents of RRP. The therapy has been granted Breakthrough Therapy and Orphan Drug Designations by the FDA and Orphan Drug Designation by the European Commission.
Pivotal clinical study results, presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting, demonstrated promising outcomes:
- Complete Response: 51% (18 out of 35) of patients achieved complete response, eliminating the need for surgeries post-treatment. These responses have shown durability beyond 12 months, with a median follow-up of 20 months (data cutoff: May 20, 2024).
- Reduced Surgical Interventions: 86% of patients (30 out of 35) experienced a decrease in surgical interventions in the year following PRGN-2012 treatment compared to the previous year. The median number of RRP surgeries decreased from 4 (range: 3-10) pre-treatment to 0 (range: 0-7) post-treatment.
- Safety Profile: PRGN-2012 was well-tolerated, with no dose-limiting toxicities or treatment-related adverse events greater than Grade 2.
- Immune Response: The treatment induced HPV 6/11-specific T cell responses in RRP patients, with a significantly greater expansion of peripheral HPV-specific T cells in responders compared to non-responders.
- Quality of Life: PRGN-2012 significantly (p < 0.0001) improved Derkay scores and quality of life scores in complete responders.
Precigen is also advancing its commercial and manufacturing readiness campaign in anticipation of a potential 2025 launch. A confirmatory clinical trial for PRGN-2012 is ongoing, initiated in accordance with FDA guidance prior to BLA submission.
UltraCAR-T Platform Advancements
Precigen continues to innovate with its UltraCAR-T platform. Preclinical data for PRGN-3008, a next-generation UltraCAR-T targeting CD19 (搜索), were presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting. The data showcased the potential of PRGN-3008 to be a best-in-class CD19-targeting CAR-T treatment in oncology and autoimmune diseases.
In vivo tumor models demonstrated that a single administration of PRGN-3008 enhanced expansion and persistence, produced robust antitumor efficacy with complete tumor clearance, and significantly prolonged survival compared to conventional CD19 (搜索) CAR-T cells. In a simulation of tumor relapse, PRGN-3008 exhibited persistence and long-term antitumor immunity, extending overall survival without additional treatment.
In a humanized mouse model of lupus nephritis, PRGN-3008 led to complete elimination of B-cells and a decrease in antibodies to double-stranded DNA (dsDNA), a specific marker of lupus.
Other Pipeline Developments
Precigen is preparing for an end-of-Phase 1b meeting with the FDA in early 2025 for PRGN-3006 in acute myeloid leukemia (搜索) (AML), which has received Fast Track designation from the FDA. Enrollment in the Phase 1b trial for PRGN-3006 in AML has been completed.
However, as part of a strategic reprioritization, the company has paused enrollment in the Phase 2 clinical trial of PRGN-2009 in recurrent/metastatic cervical cancer (搜索) at non-NCI sites. Trials at NCI sites are ongoing.
Financial Management
Following a public equity offering in August 2024, Precigen reported net proceeds of approximately $30.9 million. The company has strategically prioritized its clinical portfolio and streamlined resources, including a workforce reduction of over 20%, to focus on the potential commercialization of PRGN-2012.
"The strategic reprioritization of our portfolio announced last quarter has enabled us to focus our team and allocate resources to advance PRGN-2012 as rapidly as possible," said Helen Sabzevari, PhD, President and CEO of Precigen.