Precigen(PGEN) - 2023 Q4 - Annual Report

PART I Business Overview Precigen is a discovery and clinical-stage biopharmaceutical company advancing gene and cell therapies for immuno-oncology, autoimmune disorders, and infectious diseases, leveraging proprietary technology platforms Overview Precigen is a discovery and clinical-stage biopharmaceutical company focused on gene and cell therapies for immuno-oncology, autoimmune disorders, and infectious diseases - Precigen is a discovery and clinical-stage biopharmaceutical company focused on gene and cell therapies for immuno-oncology, autoimmune disorders, and infectious diseases[31] - The company leverages proprietary technology platforms including UltraCAR-T, AdenoVerse immunotherapy, and ActoBiotics[32] - Key operating tenets include Financial Discipline, Active Portfolio Management, Rapid Execution, and Strategic Partnerships[37] Our Strategy The company's strategy focuses on advancing clinical programs, systematically evaluating preclinical data, and leveraging synthetic biology for precision medicines - Strategy focuses on advancing lead clinical programs towards proof-of-concept and commercialization, either independently or with collaborators[40] - Systematically evaluates preclinical data for rapid 'go' and 'no go' decisions to allocate resources to programs with the highest probability of success[40] - Leverages proprietary synthetic biology technologies across therapeutic areas to create optimized biological processes for efficient and cost-effective precision medicines[40] Our Clinical Pipeline Precigen's clinical pipeline includes investigational therapies across immuno-oncology, autoimmune disorders, and infectious diseases Precigen Clinical Pipeline Overview | Platform | Product | Target | Indication | Status | | :--- | :--- | :--- | :--- | :--- | | AdenoVerse Immunotherapy | PRGN-2012 | HPV 6/11 | RRP | Phase 1B (Breakthrough Therapy Designation, Orphan Drug Designation) | | AdenoVerse Immunotherapy | PRGN-2009 | HPV 16/18 | OPSCC/Head & Neck Cancer | Phase 1B | | AdenoVerse Immunotherapy | PRGN-2009 (+pembrolizumab) | HPV 16/18 | R/M Cervical Cancer | Phase 2 IND cleared | | UltraCAR-T | PRGN-3005 | Unshed MUC16 | Ovarian Cancer | Phase 1B | | UltraCAR-T | PRGN-3006 | CD33 | R/R AML, MDS | Phase 1B (Fast Track Designation, Orphan Drug Designation) | | UltraCAR-T | PRGN-3007 | ROR1 | ROR1* Hematological & Solid Tumors | Phase 1/1B | | ActoBiotics | AG019 | hPINS + hIL-10 | Type 1 Diabetes | Phase 1B/2A completed | Our Healthcare Business The healthcare business comprises Biopharmaceuticals (Precigen and ActoBio) for gene and cell therapies, and Exemplar for research models - The Biopharmaceuticals segment includes Precigen and ActoBio, focusing on gene and cell therapies for immuno-oncology, autoimmune disorders, and infectious diseases[43][44] - The Exemplar segment, a wholly-owned subsidiary, develops MiniSwine Yucatan miniature pig research models and services for healthcare research applications[43][138] Biopharmaceuticals Precigen's biopharmaceutical segment develops gene and cell therapies using precision technology, leveraging proprietary platforms for gene program design, delivery, and expression control Precigen's Technology Platforms Precigen utilizes advanced synthetic biology platforms for gene program design, delivery, and expression control in therapeutic development - UltraVector platform: Utilizes advanced DNA construction and computational models to design optimized multigenic programs for therapeutic approaches[46] - Gene delivery systems: Includes non-viral Sleeping Beauty transposon/transposase system, AttSite recombinases for stable site-specific gene integration, and the AdenoVerse library of engineered adenovector serotypes (e.g., gorilla adenovectors)[47][48] - Gene expression control: Employs RheoSwitch Therapeutic System for inducible gene expression, kill switches for selective cell elimination, and tissue-specific promoters for localized expression[49] Precigen's Therapeutic Platforms Key therapeutic platforms include UltraCAR-T and AdenoVerse, designed to address complex disorders and advance precision medicine - Key therapeutic platforms include UltraCAR-T and AdenoVerse, developed to address complex disorders and realize precision medicine[50] "Off-the-shelf" AdenoVerse Immunotherapy The AdenoVerse immunotherapy platform uses proprietary gorilla adenovectors for efficient, safe, and repeatable gene delivery, with internal cGMP manufacturing - Key advantages of AdenoVerse immunotherapy: large genetic payload capacity (up to 12kb), suitability for repeat administration (low seroprevalence of gorilla adenoviruses), and replication incompetence for safety[52][53][54] - Internal cGMP manufacturing capabilities for AdenoVerse-based therapeutics in Germantown, Maryland, aim to reduce risks and costs associated with outsourcing[57] - Most advanced programs are PRGN-2012 for RRP and PRGN-2009 for HPV-associated cancers[58] PRGN-2012 PRGN-2012 is an investigational "off-the-shelf" AdenoVerse immunotherapy for Recurrent Respiratory Papillomatosis (RRP), with Breakthrough Therapy and Orphan Drug Designations - PRGN-2012 is an investigational "off-the-shelf" AdenoVerse immunotherapy for Recurrent Respiratory Papillomatosis (RRP), a rare disease caused by HPV6/11 with no approved therapeutic treatment[59][60] - Phase 1 data showed PRGN-2012 was well-tolerated with no DLTs or TRAEs greater than Grade 2. At Dose Level 2, 50% of patients achieved a Complete Response (no surgeries in 12 months post-treatment) and 58% had an Overall Response Rate (ORR)[66][68] - PRGN-2012 has received Breakthrough Therapy Designation and Orphan Drug designation from the FDA and Orphan Drug Designation from the European Commission for RRP. Phase 2 data is anticipated in Q2 2024, with BLA submission planned for H2 2024 and potential commercial launch in 2025[73][74] PRGN-2009 PRGN-2009 is an "off-the-shelf" immunotherapy targeting HPV type 16 and 18 positive solid tumors, showing promising response rates in clinical trials - PRGN-2009 is an "off-the-shelf" immunotherapy designed to target HPV type 16 and 18 positive solid tumors, leveraging UltraVector and AdenoVerse platforms for optimized antigen design and delivery[75] - Phase 1 data showed PRGN-2009 was well-tolerated. In combination with bintrafusp alfa, it achieved a 30% objective response rate (ORR) in pretreated recurrent or metastatic HPV-associated cancers[79][80] - A Phase 2 clinical trial is ongoing in collaboration with NCI for HPV-associated oropharyngeal cancer, and an IND has been cleared for a Phase 2 randomized trial in combination with pembrolizumab for R/M cervical cancer[83][84] UltraCAR-T The UltraCAR-T platform offers rapid, decentralized, overnight CAR-T manufacturing, utilizing a non-viral multigenic delivery system for enhanced persistence and safety - UltraCAR-T platform aims to disrupt CAR-T treatment by shortening manufacturing time from weeks to days, decreasing costs, and improving outcomes through overnight, decentralized manufacturing[86][93] - Features an advanced non-viral multigenic delivery system (Sleeping Beauty) to co-express CAR, kill switch, mbIL15, and intrinsic checkpoint blockade without gene editing, enhancing persistence and safety[89][91][92] - The proprietary UltraPorator electroporation device has received FDA clearance for manufacturing UltraCAR-T cells in clinical trials[94] PRGN-3005 PRGN-3005 is an UltraCAR-T therapy targeting MUC16 for advanced ovarian, fallopian tube, or primary peritoneal cancers, demonstrating promising preclinical and Phase 1 clinical results - PRGN-3005 is an UltraCAR-T therapy targeting the unshed portion of Mucin 16 (MUC16) for advanced ovarian, fallopian tube, or primary peritoneal cancers, where MUC16 is overexpressed in over 80% of tumors[98][100] - Preclinical studies demonstrated robust MUC16-specific cytotoxicity, a stem-cell like memory phenotype, and superior anti-tumor response and durable persistence in mouse models[102][103] - Phase 1 data showed PR