PRGN-2009 / Precigen - LARVOL DELTA

Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer (clinicaltrials.gov) - P2 | N=16 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | N=29 ➔ 16 | Trial completion date: Nov 2028 ➔ Jul 2030 | Trial primary completion date: Nov 2025 ➔ May 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4

Phase II trial of neoadjuvant chemotherapy (NAC) docetaxel-cisplatin alone (DC) or with anti-human papillomavirus (HPV) gene therapy PRGN-2009 (DCP) followed by surgery in patients (pts) with newly diagnosed HPV-associated oropharyngeal cancer (HPV-OPC). (ASCO 2025) - P2 | "Supportive measures include pre-infusion dexamethasone, antiemetics, neutropenia primary prophylaxis. 8 of 60 pts planned have been enrolled. Clinical trial registry: NCT06223568."

Clinical • Gene therapy • P2 data • Surgery • Fibrosis • Gastrointestinal Disorder • Gene Therapies • Head and Neck Cancer • Immunology • Neutropenia • Oncology • Oropharyngeal Cancer • Otorhinolaryngology • Solid Tumor

PRGN-2009 and bintrafusp alfa for patients with advanced or metastatic human papillomavirus-associated cancer. (PubMed, Cancer Immunol Immunother) - P1/2 | "PRGN-2009 was well tolerated, and immune responses were observed to PRGN-2009. Encouraging anti-tumor activity and OS were noted in the combination with BA arm, consisting mainly of checkpoint-resistant patients. Trial Registration ClinicalTrials.gov Identifier: NCT04432597."

Journal • Cervical Cancer • Gene Therapies • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • CXCL8 • TGFB1

Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer (clinicaltrials.gov) - P2 | N=29 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Nov 2027 ➔ Nov 2028 | Trial primary completion date: Nov 2024 ➔ Nov 2025

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4

PRGN-2009-201: PRGN-2009 in Combination with Pembrolizumab Versus Pembrolizumab in Patients with Recurrent or Metastatic Cervical Cancer (clinicaltrials.gov) - P2 | N=46 | Recruiting | Sponsor: Precigen, Inc | Initiation date: Aug 2024 ➔ Nov 2024

Combination therapy • Metastases • Monotherapy • Trial initiation date • Cervical Cancer • Oncology • Solid Tumor

Precigen Reports Third Quarter 2024 Financial Results and Business Updates (PRNewswire) - "Key Program Highlights:...(i) PRGN-2009 AdenoVerse Gene Therapy in HPV-associated cancers: PRGN-2009 Phase 2 clinical trials under a cooperative research and development agreement (CRADA) with the National Cancer Institute (NCI) in recurrent/metastatic cervical cancer and in newly diagnosed HPV-associated oropharyngeal cancer are ongoing...; (ii) PRGN-3006 UltraCAR-T in AML and MDS: The Company has completed enrollment of the Phase 1b trial for PRGN-3006 in acute myeloid leukemia (AML)...and is preparing for an end of Phase 1b meeting with the FDA to discuss next steps."

FDA event • Trial status • Acute Myelogenous Leukemia • Cervical Cancer • Myelodysplastic Syndrome • Oropharyngeal Cancer

Precigen Strategically Prioritizes Portfolio to Focus on First Potential Gene Therapy Launch (PRNewswire) - "PRGN-2009 AdenoVerse Gene Therapy Clinical Trials: The Company plans to continue PRGN-2009 Phase 2 trials under a cooperative research and development agreement (CRADA) with the National Cancer Institute (NCI) in recurrent/metastatic cervical cancer and in newly diagnosed HPV-associated oropharyngeal cancer. PRGN-2009 clinical trial enrollment at non-NCI clinical sites will be paused. UltraCAR-T Clinical Programs: The Company has completed enrollment of the Phase 1b trial for PRGN-3006 in acute myeloid leukemia (AML), which received Fast Track designation from the US Food and Drug Administration (FDA), and is preparing for an end of Phase 1b meeting with the FDA to discuss next steps. The Company will pause all other UltraCAR-T clinical programs, including PRGN-3005 and PRGN-3007."

Discontinued • Pipeline update • Cervical Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Precigen Reports Second Quarter and First Half 2024 Financial Results and Business Updates (PRNewswire) - "Key Program Highlights:...(i) PRGN-2009 AdenoVerse Gene Therapy Clinical Trials: The Company plans to continue PRGN-2009 Phase 2 clinical trials under a cooperative research and development agreement (CRADA) with the...NCI in recurrent/metastatic cervical cancer and in newly diagnosed HPV-associated oropharyngeal cancer. PRGN-2009 cervical cancer clinical trial enrollment at non-NCI clinical sites will be paused; (ii) UltraCAR-T Clinical Programs: The Company has completed enrollment of the Phase 1b trial for PRGN-3006 in acute myeloid leukemia (AML)...and is preparing for an end of Phase 1b meeting with the FDA to discuss next steps. The Company will pause the PRGN-3005 and PRGN-3007 clinical trials. The Company will minimize UltraCAR-T spend and focus on strategic partnerships to further advance UltraCAR-T programs."

FDA event • Trial status • Acute Myelogenous Leukemia • Cervical Cancer • Fallopian Tube Cancer • Oropharyngeal Cancer • Ovarian Cancer • Peritoneal Cancer

Phase II trial of immunotherapeutic HPV vaccine PRGN-2009 with pembrolizumab before standard treatment in subjects with newly diagnosed HPV-associated oropharyngeal cancer. (ASCO 2024) - P2 | "Biopsies are mandatory at baseline and at completion. This study is presently open in the NCI with 4 patients enrolled as of February 2024."

Clinical • P2 data • Head and Neck Cancer • Human Immunodeficiency Virus • Immunology • Infectious Disease • Oncology • Oropharyngeal Cancer • Solid Tumor • CD4

A phase 2 study to evaluate efficacy and safety of PRGN-2009, a novel gorilla adenovirus-based immunotherapy, in combination with pembrolizumab versus pembrolizumab monotherapy in patients with recurrent or metastatic cervical cancer. (ASCO 2024) - P2 | "The primary endpoint is objective response rate (ORR) following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab monotherapy, and will be tested using Fleming's two-stage design and the stopping boundaries for futility and efficacy applied. The study is currently recruiting patients with recurrent or metastatic cervical cancer (NCT06157151)."

Clinical • Combination therapy • Metastases • Monotherapy • P2 data • Cervical Cancer • Human Papillomavirus Infection • Infectious Disease • Oncology • Solid Tumor

Phase II Trial of Neoadjuvant Chemotherapy (NAC) Alone or in Combination With Immunotherapy Vaccine PRGN-2009 in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal (Head and Neck) Cancer (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Precigen Reports First Quarter 2024 Financial Results and Business Updates (PRNewswire) - “PRGN-2009 in OPSCC and Cervical Cancer: An abstract titled, ‘Phase II trial of immunotherapeutic HPV vaccine PRGN-2009 with pembrolizumab before standard treatment in subjects with newly diagnosed HPV-associated oropharyngeal cancer’ will be presented as a trial-in-progress poster presentation on June 2, 2024 from 9:00 AM to 12:00 PM CT at ASCO; An abstract titled, ‘A Phase 2 study to evaluate efficacy and safety of PRGN-2009, a novel gorilla adenovirus-based immunotherapy, in combination with pembrolizumab versus pembrolizumab monotherapy in patients with recurrent or metastatic cervical cancer’ will be presented as a trial-in-progress poster presentation on June 3, 2024 from 9:00 AM to 12:00 PM CT at ASCO.”

Trial status • Cervical Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor

Peripheral immune analyses from phase I trial of HPV vaccine PRGN-2009 in combination with bintrafusp alfa in patients with HPV-associated cancers (AACR 2024) - P1/2 | "The majority of patients developed HPV16/18 specific T-cell responses after repeat administration of PRGN-2009 in combination with BA. Transient increases in IL-8 and TNFα 2-4 weeks after start of treatment were associated with worse outcomes, suggesting that early changes in cytokines may reflect disease course. Furthermore, the early expansion of CD8+ T cell subsets in the patient developing a CR with HPV45+ disease after receiving a vaccine targeting HPV16 and HPV18 epitopes suggest a broadening and boosting of T cell responses that enabled potent anti-tumor activity."

Clinical • Combination therapy • P1 data • Oncology • CD8 • CXCL8 • HAVCR2 • IFNG • PD-1 • TGFB1 • TNFA

PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer (clinicaltrials.gov) - P2 | N=46 | Recruiting | Sponsor: Precigen, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Cervical Cancer • Oncology • Solid Tumor

Phase II Trial of Neoadjuvant Chemotherapy (NAC) Alone or in Combination With Immunotherapy Vaccine PRGN-2009 in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal (Head and Neck) Cancer (clinicaltrials.gov) - P2 | N=70 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

Combination therapy • New P2 trial • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer (clinicaltrials.gov) - P2 | N=46 | Not yet recruiting | Sponsor: Precigen, Inc

New P2 trial • Cervical Cancer • Oncology • Solid Tumor

20-C-0104: HPV Vaccine PRGN-2009 Alone or in Combination With Anti-PDL1/TGF-Beta Trap (M7824) in Subjects With HPV Associated Cancers (clinicaltrials.gov) - P1/2 | N=39 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=20 ➔ 39 | Trial completion date: Oct 2023 ➔ Nov 2025

Enrollment change • Trial completion date • Anal Carcinoma • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Penile Cancer • Rectal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Vaginal Cancer • Vulvar Cancer • CD4

Precigen Reports Third Quarter 2023 Financial Results and Progress of Clinical Programs (PRNewswire) - "Precigen, Inc...today announced third quarter 2023 financial results and progress of clinical programs...The Phase 2 (NCT05996523) combination arm (PRGN-2009 in combination with pembrolizumab) in OPSCC is enrolling patients...As previously communicated, based on portfolio reprioritization efforts, the Company will not add an extensive number of new sites this year. Instead, a new site will be activated under the Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) to continue the advancement of the PRGN-3005 Phase 1b dose expansion study without incurring major clinical/contract research organization (CRO) costs...The Company presented additional preclinical data (Abstract# P469) for PRGN-3007 at the ESGCT 30th Annual Congress in a poster presentation..."

Enrollment status • Preclinical • Trial status • Fallopian Tube Cancer • Gynecologic Cancers • Head and Neck Cancer • Hematological Malignancies • Oncology • Oropharyngeal Cancer • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer (clinicaltrials.gov) - P2 | N=29 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4

PRGN-2009 Plus Bintrafusp Alfa Shows Early Activity in HPV-Associated Malignancies (OncLive) - P1/2 | N=20 | NCT04432597 | "Treatment with the replication-incompetent gorilla adenovirus targeting HPV 16/18, PRGN-2009, in combination with bintrafusp alfa (M7824) elicited responses and had acceptable tolerability in patients with recurrent or metastatic human papillomavirus–associated cancers, according to data from a phase 1 trial....In evaluable patients who received PRGN-2009 at the recommended phase 2 dose plus bintrafusp alfa (arm 1b; n = 10), the objective response rate (ORR) was 30% (95% CI, 6.7%-65.3%), which comprised 1 complete response (CR) and 2 partial responses (PRs). One patient had stable disease (SD) and 6 patients experienced progressive disease (PD)."

P1 data • Anal Carcinoma • Cervical Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Oropharyngeal Cancer

PRGN-2009 Plus Bintrafusp Alfa Shows Early Activity in HPV-Associated Malignancies (OncLive) - "The real unmet clinical need is in patients who have [HPV-associated] cancer and have been treated with immunotherapy, but that immunotherapy is now no longer working for them,' James L. Gulley, MD, PhD, explained in an interview with OncLive. 'Coming in with combination approaches to get the immune system reengaged in fighting the cancer is going to be critical as we seek cures in these patients.'"

Interview

Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer (clinicaltrials.gov) - P2 | N=29 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P2 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4

Phase I evaluation of PRGN-2009 alone and in combination with bintrafusp alfa in patients (pts) with recurrent/metastatic (R/M) HPV-associated cancers (HPV-C). (ASCO 2023) - P1/2 | "PRGN-2009 is safe, well-tolerated, and induces HPV-specific T-cell immune responses. Further, PRGN-2009 combined with BA demonstrated clinical activity in pts with pretreated HPV-associated cancers, naïve or resistant to checkpoint blockade. Clinical trial information: NCT04432597."

Clinical • Combination therapy • Metastases • P1 data • Fatigue • Hematological Disorders • Mucositis • Oncology • TGFB1

Precigen Announces Positive Phase 1 Data for Off-the-Shelf PRGN-2009 AdenoVerse Immunotherapy Alone and in Combination with an Investigational Checkpoint Inhibitor in Patients with Recurrent/Metastatic HPV-associated Cancers (PRNewswire) - P1/2 | N=20 | NCT04432597 | "Precigen...presented positive clinical data from the Phase 1 study of the off-the-shelf (OTS) PRGN-2009 AdenoVerse™ immunotherapy alone and in combination with an investigational anti-PDL1/TGF-Beta Trap checkpoint inhibitor (bintrafusp alfa) in patients with recurrent/metastatic (R/M) HPV-associated cancers...at the 2023...ASCO Annual Meeting....Tumor responses were observed in patients after treatment with PRGN-2009 in combination with bintrafusp alfa (Arm 1B), including in ICB-resistant patients. PRGN-2009 combined with bintrafusp alfa resulted in a 30% ORR in patients with pretreated R/M HPV-associated cancers....The Phase 2 portion of the study is ongoing at the RP2D and enrollment was completed in the monotherapy arm with 20 evaluable patients with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC). An interim clinical data presentation from the Phase 2 monotherapy arm is expected in the second half of 2023."

P1/2 data • Trial status • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor

Precigen Receives FDA Clearance of IND to Initiate Phase 2 Study of PRGN-2009 Off-the-Shelf AdenoVerse Immunotherapy in Combination with Pembrolizumab to Treat Patients with Recurrent or Metastatic Cervical Cancer (PRNewswire) - "Precigen, Inc...announced that the US Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application to initiate a Phase 2 study of the first-in-class PRGN-2009 Off-the-Shelf (OTS) AdenoVerse™ immunotherapy in combination with pembrolizumab in patients with recurrent or metastatic cervical cancer. The Phase 2 randomized, open-label, two-arm, multicenter study will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab versus pembrolizumab monotherapy in patients with recurrent or metastatic cervical cancer who are pembrolizumab resistant. The study will enroll approximately 46 patients who previously have been treated with pembrolizumab for recurrent or metastatic disease."

IND • New P2 trial • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor