Precigen, Inc. (NASDAQ:PGEN) is a dedicated discovery and clinical-stage biopharmaceutical company at the forefront of advancing the next generation of gene and cell therapies. With a focus on improving outcomes for patients with significant unmet medical needs, Precigen is leveraging its proprietary technology platforms to develop a robust pipeline of therapies across its core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases.
Business Overview
Precigen's primary operations are located in the State of Maryland, with two wholly owned subsidiaries - Precigen ActoBio, Inc. ("ActoBio") and Exemplar Genetics, LLC, doing business as Precigen Exemplar ("Exemplar"). ActoBio is pioneering a proprietary class of microbe-based biopharmaceuticals that enable expression and local delivery of disease-modifying therapeutics, with its primary operations located in Ghent, Belgium. Exemplar is committed to enabling the study of life-threatening human diseases through the development of Yucatan MiniSwine preclinical research models and services, as well as enabling the production of cells and organs in its genetically engineered MiniSwine for regenerative medicine applications. Exemplar's primary operations are located in the State of Iowa.Precigen's Innovative Technology Platforms
Precigen's proprietary technology platforms provide a strong foundation to realize the core promise of precision medicine. These platforms include the UltraCAR-T therapeutics platform, the "off-the-shelf" AdenoVerse immunotherapy platform, and the ActoBiotics platform.The UltraCAR-T therapeutics platform allows Precigen to precision-engineer UltraCAR-T cells to produce a homogeneous cell product that simultaneously expresses antigen-specific chimeric antigen receptor (CAR), kill switch, and proprietary membrane-bound interleukin-15 (mbIL15) genes. Precigen's decentralized and rapid manufacturing process enables the overnight manufacturing of UltraCAR-T cells at a medical center's current good manufacturing practices (cGMP) facility, followed by same-day patient reinfusion. This process aims to improve upon current CAR-T manufacturing approaches, which can result in the exhaustion of CAR-T cells prior to administration.
Precigen's AdenoVerse immunotherapy platform utilizes a library of proprietary adenovectors for the efficient gene delivery of therapeutic effectors, immunomodulators, and vaccine antigens. The platform's proprietary gorilla adenovectors are designed to have superior performance characteristics compared to current competition, including the ability to enable repeat administrations without the development of neutralizing antibodies.
The ActoBiotics platform, developed by Precigen ActoBio, is a unique delivery platform that enables the expression and local delivery of disease-modifying therapeutics. ActoBiotics combine the advantages of highly selective protein-based therapeutic agents with local delivery by the well-characterized, food-grade bacterium Lactococcus lactis.
Pipeline and Clinical Progress
Precigen has developed an extensive pipeline of therapies across multiple indications within its core focus areas. The company's lead clinical programs include:PRGN-2012: A first-in-class, investigational "off-the-shelf" AdenoVerse immunotherapy for the treatment of recurrent respiratory papillomatosis (RRP). PRGN-2012 has been granted Breakthrough Therapy Designation by the FDA and is currently in a Phase 1/2 clinical trial.
PRGN-2009: A first-in-class, "off-the-shelf" investigational immunotherapy designed to activate the immune system to recognize and target human papillomavirus-positive (HPV+) solid tumors. PRGN-2009 is currently being evaluated in a Phase 2 clinical trial for newly diagnosed oropharyngeal squamous cell carcinoma patients and a Phase 2 clinical trial in combination with pembrolizumab for recurrent or metastatic cervical cancer.
PRGN-3006: A first-in-class, investigational autologous CAR-T therapy that utilizes Precigen's UltraCAR-T platform to express a CAR targeting CD33, mbIL15, and a kill switch gene. PRGN-3006 is currently being evaluated in a Phase 1/1b clinical trial for the treatment of relapsed or refractory (r/r) acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS).
PRGN-3005: A first-in-class, investigational autologous CAR-T therapy that utilizes the UltraCAR-T platform to express a CAR targeting the unshed portion of the Mucin 16 antigen, mbIL15, and kill switch genes. PRGN-3005 is currently being evaluated in a Phase 1/1b clinical trial for the treatment of advanced, recurrent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer.
PRGN-3007: A first-in-class, investigational autologous CAR-T therapy that utilizes the next-generation UltraCAR-T platform to express a CAR targeting ROR1, mbIL15, a kill switch, and a novel mechanism for the intrinsic blockade of the programmed death 1 (PD-1) gene expression. PRGN-3007 is being evaluated in a Phase 1/1b clinical trial for patients with advanced ROR1-positive hematological and solid tumors.
In addition to these clinical programs, Precigen has a robust pipeline of preclinical programs across its core therapeutic areas.
Financial Performance
For the full year 2023, Precigen reported annual revenue of $6,225,000, a decrease from the prior year. The company's annual net loss was $95,904,000, and its annual operating cash flow and free cash flow were -$66,930,000 and -$68,466,000, respectively.On a quarterly basis, Precigen reported the following financial results:
Q4 2023:
- Revenue: $1,379,000
- Net Loss: $19,795,000
- Operating Cash Flow: -$15,164,000
- Free Cash Flow: -$15,400,000
Q3 2023:
- Revenue: $1,800,000
- Net Loss: $21,053,000
- Operating Cash Flow: -$17,000,000
- Free Cash Flow: -$17,200,000
Q2 2023:
- Revenue: $2,043,000
- Net Loss: $22,056,000
- Operating Cash Flow: -$19,766,000
- Free Cash Flow: -$20,000,000
The decrease in revenue was primarily due to a reduction in services performed at Precigen's Exemplar subsidiary, as well as the recognition of revenue in the first quarter of 2022 related to agreements for which revenue was previously deferred that did not occur in 2023. The increase in net loss and negative operating and free cash flow was driven by continued investment in Precigen's clinical development programs and commercial readiness activities.
Liquidity and Capital Resources
As of September 30, 2023, Precigen had cash, cash equivalents, and short-term investments of $79.0 million. The company believes its existing liquid assets will enable it to fund its operating expenses and capital requirements for at least the next 12 months.Precigen has been evaluating various opportunities to strengthen its balance sheet as it approaches the planned launch of PRGN-2012 and transitions from a clinical to a commercial-stage company. The company remains confident in its ability to secure additional funding to support its ongoing operations and future growth.
Outlook
Precigen is poised for a transformative year in 2024. The company is on track to present pivotal Phase 2 data for its lead asset PRGN-2012 in the second quarter of 2024 and intends to submit a Biologics License Application (BLA) in the second half of the year. The FDA has agreed that the ongoing Phase 1/2 study of PRGN-2012 will serve as a pivotal study for the purpose of filing an accelerated approval request.Additionally, Precigen continues to advance its other clinical programs, including PRGN-2009, PRGN-3006, PRGN-3005, and PRGN-3007. The company expects to provide updates on the interim data for PRGN-3007 by the end of 2024 and plans to move the program into the expansion phase, Phase 1b, based on the data.
Precigen is also making progress on the commercial readiness front, with the construction of its drug substance manufacturing facility in Germantown, Maryland, on track, and the recent hiring of a Head of Commercial Operations to build out the company's commercial function in preparation for the expected launch of PRGN-2012 in 2025.
Risks and Challenges
As a clinical-stage biopharmaceutical company, Precigen faces several risks and challenges, including:- Regulatory approval and commercialization risks: The company's ability to obtain regulatory approvals for its product candidates and successfully commercialize them.
- Clinical development risks: The inherent risks associated with the research and development of novel gene and cell therapies, including the potential for adverse events and the ability to demonstrate safety and efficacy in clinical trials.
- Manufacturing and supply chain risks: Challenges in scaling up manufacturing capabilities and maintaining a reliable supply chain to support the commercialization of its products.
- Competition and market acceptance risks: Competition from other therapies and the ability to gain market acceptance for Precigen's innovative treatments.
- Financing and capital requirements: The need to secure additional funding to support the company's ongoing operations and future growth.