PRGN-3005 / Precigen - LARVOL DELTA

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

Modified Immune Cells (Autologous CAR T Cells) in Treating Patients With Advanced, Recurrent Platinum Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer (clinicaltrials.gov) - P1 | N=71 | Active, not recruiting | Sponsor: Precigen, Inc | Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Enrollment closed • Immune cell • Metastases • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor • BRCA

Modified Immune Cells (Autologous CAR T Cells) in Treating Patients With Advanced, Recurrent Platinum Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer (clinicaltrials.gov) - P1 | N=71 | Recruiting | Sponsor: Precigen, Inc | Trial primary completion date: Dec 2023 ➔ Dec 2024

CAR T-Cell Therapy • Immune cell • Metastases • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor • BRCA

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

Dr. Disis on the Rationale For Investigating PRGN-3005 With/Without Lymphodepletion in Ovarian Cancer (OncLive) - "In order to address these unmet needs, investigator's launched a phase 1/1b study (NCT03907527) to assess PRGN-3005, Disis states....The trial enrolled patients with cisplatin-refractory ovarian cancer, Disis continues, noting that this disease subtype is often challenging to treat....Intravenous delivery of PRGN-3005 led to dose-dependent T-cell expansion regardless of subsequent lymphodepletion. However, combining lymphodepletion with PRGN-3005 notably stabilized or decreased CA125 levels in 89% of patients....These results suggest that PRGN-3005 CAR T-cell therapy, with its engineered cytokine for prolonged T-cell activity, could overcome current limitations associated with the treatment of patients with difficult-to-treat ovarian cancer, Disis concludes."

Review • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Phase 1/1b study of PRGN-3005 autologous UltraCAR-T cells manufactured overnight for infusion next day to advanced stage platinum resistant ovarian cancer patients. (ASCO 2023) - P1 | "Dose level 3, IV infusion was further evaluated in pts treated with cyclophosphamide LD (60mg/kg/dayon days -4 to -3 (IV LD)). PRGN-3005 UltraCAR-T targeting MUC16 has been well tolerated with minimal toxicity. PRGN-3005 demonstrated a dose-dependent expansion and persistence in blood with or without LD. Encouraging DCR rates and a reduction in overall tumor burden have been observed in heavily pretreated, ovarian cancer pts treated with LD."

CAR T-Cell Therapy • Clinical • Metastases • P1 data • Gene Therapies • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • IL15 • MUC16

Precigen Announces Positive Phase 1 Data for PRGN-3005 Autologous UltraCAR-T Cells Manufactured Overnight for Infusion Next Day to Advanced Stage Platinum Resistant Ovarian Cancer Patients (PRNewswire) - P1/1b | N=71 | NCT03907527 | Sponsor: Precigen, Inc. | "Precigen...presented positive data at the 2023...ASCO Annual Meeting from the Phase 1 portion of the Phase 1/1b clinical study evaluating safety and efficacy of PRGN-3005 UltraCAR-T® in advanced stage platinum resistant ovarian cancer patients (Abstract# 5590)....PRGN-3005 was well-tolerated with low incidence of treatment related adverse events (TRAEs), no dose limiting toxicities (DLTs), and no neurotoxicity....Best responses in patients treated without lymphodepletion were stable disease with complete responses in individual target lesions. Incorporating lymphodepletion prior to IV infusion led to an encouraging efficacy signal as demonstrated by a decrease in tumor burden in 67% (6/9) of patients (Figure 1), with concurrent decreases in CA125 at Day 35 in 89% (8/9) of patients and stable or partial response in 90% of the individual target lesions."

P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Precigen to Present Latest Clinical Advancements for PRGN-3005 UltraCAR-T and PRGN-2009 Off-the-Shelf AdenoVerse Immunotherapy at the 2023 ASCO Annual Meeting (PRNewswire) - "Precigen...announced clinical data from the Phase 1 dose escalation study of PRGN-3005 UltraCAR-T in patients with advanced, recurrent platinum resistant ovarian cancer, and the Phase I study of PRGN-2009 AdenoVerse immunotherapy alone or in combination with an anti-PDL1/TGF-Beta trap checkpoint inhibitor in patients with HPV-associated cancers will be presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting taking place from June 2-6, 2023 at McCormick Place in Chicago, Illinois."

P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Precigen Regains Exclusive Rights to Proven CAR-T Targets, CD19 and BCMA, to Enable Unencumbered Development and Commercialization of UltraCAR-T (PRNewswire) - "Precigen...announced the amendment of its exclusive license agreement with Alaunos Therapeutics, Inc. (Alaunos). With this amendment, Precigen has the unique ability to utilize the clinically validated UltraCAR-T platform for unencumbered development and commercialization of two proven CAR-T targets, CD19 and B-cell maturation antigen (BCMA)."

Licensing / partnership • Acute Myelogenous Leukemia • Fallopian Tube Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Preclinical Evaluation of Prgn-3007, a Non-Viral, Multigenic, Autologous ROR1 Ultracar-T® Therapy with Novel Mechanism of Intrinsic PD-1 Blockade for Treatment of Hematological and Solid Cancers (ASH 2021) - P1 | "Data shown is from 8 mice/group at the start of the study. * p<0.05, ***p<0.001; log rank test."

IO biomarker • Preclinical • Gene Therapies • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • Solid Tumor • IL15 • PD-L1 • ROR1

[VIRTUAL] PRGN-3005 UltraCAR-T™: multigenic CAR-T cells generated using non-viral gene delivery and rapid manufacturing process for the treatment of ovarian cancer (AACR-II 2020) - P1 | "PRGN-3005 UltraCAR-T administered one day after non-viral gene transfer has superior anti-tumor efficacy and persistence compared traditional CAR-T cells and represent a promising opportunity for ovarian cancer treatment. Based on these results, FDA has approved an IND application and the first in human PRGN-3005 Phase I clinical trial for advanced ovarian cancer is currently under evaluation (NCT03907527)."

CAR T-Cell Therapy • IO Biomarker • Gynecologic Cancers • Hematological Malignancies • Oncology • Ovarian Cancer • CA125 • IL15

[VIRTUAL] A Phase 1/1b Safety Study of Prgn-3006 Ultracar-T™ in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndrome (ASH 2020) - P1 | "Superior efficacy of UltraCAR-T cells was demonstrated in an aggressive murine xenograft model of AML where a single administration of PRGN-3006, only one day after gene transfer, showed significantly higher expansion and persistence; effectively eliminated tumor burden; and significantly improved overall survival compared to traditional CD33 CAR-T cells lacking mbIL15 expression (Blood (2019) 134(S1): 2660)...Key inclusion criteria include an absolute lymphocyte count ≥ 0.2k/µL, KPS > 60%, absence of other active malignancy within 1 year of study entry, daily corticosteroid dose < 10mg of prednisone daily, adequate organ function and a backup allogeneic donor should bone marrow aplasia occur. Hydroxyurea is allowed for cytoreduction with cessation 3 days prior to apheresis/infusion but can be reinitiated post-infusion. To test the hypothesis that expression of mbIL15 on PRGN-3006 cells is sufficient to promote CAR-T cell expansion and persistence, study..."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Aplastic Anemia • Chronic Myelomonocytic Leukemia • Gene Therapies • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD33 • IL15

Phase 1/1b Safety Study of Prgn-3006 Ultracar-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes (ASH 2022) - P1 | "Pts received PRGN-3006 infusion without (Cohort 1, C1) or with lymphodepletion (fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 days -5 to -3; Cohort 2, C2)...Only 1 pt (DL1, C1) had transient grade 3 CRS that resolved in < 24 hours with tocilizumab and dexamethasone... Administration of PRGN-3006 UltraCAR-T cells targeting CD33, without or with lymphodepletion, have been well tolerated with low grade CRS. PRGN-3006 UltraCAR-T expressing mbIL15 demonstrated a dose-dependent robust expansion and durable persistence in blood and bone marrow with or without lymphodepletion. Encouraging objective responses have been observed in AML patients treated with lymphodepletion."

Clinical • P1 data • Acute Myelogenous Leukemia • Aplastic Anemia • Chronic Myelomonocytic Leukemia • Gene Therapies • Hematological Malignancies • Inflammation • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD33 • IL15

Precigen Reports Fourth Quarter and Full Year 2022 Financial Results and Business Updates (PRNewswire) - "PRGN-3006 UltraCAR-T® in AML...The Company received FDA clearance to incorporate repeat dosing in the Phase 1b expansion trial. A Phase 1b clinical trial data presentation is expected in 2024....PRGN-3005 UltraCAR-T® in Ovarian Cancer: The Company completed enrollment in the Phase 1 dose escalation cohorts of the intraperitoneal (IP) and intravenous (IV) arms without lymphodepletion as well as in the lymphodepletion cohort in the IV arm. A Phase 1 dose escalation data presentation is expected in the first half of 2023. The Company initiated a Phase 1b dose expansion trial of PRGN-3005. The Company received FDA clearance to incorporate repeat dosing in the trial. A Phase 1b clinical trial data presentation is expected in 2024."

P1 data • Acute Myelogenous Leukemia • Gynecologic Cancers • Hematological Malignancies • Oncology • Ovarian Cancer

Precigen Provides Pipeline and Corporate Updates at the 41st Annual J.P. Morgan Healthcare Conference (PRNewswire) - "PRGN-3005 UltraCAR-T® in Ovarian Cancer...Program Status: Enrollment was completed in the Phase 1 dose escalation cohorts of the intraperitoneal (IP) and intravenous (IV) arms without lymphodepletion as well as in the lymphodepletion cohort in the IV arm....The first patient received a repeat PRGN-3005 dose via IV infusion, following FDA clearance to incorporate repeat dosing in the study protocol. Enrollment is ongoing in the Phase 1b expansion study of PRGN-3005 UltraCAR-T at Dose Level 3 with lymphodepletion prior to IV infusion. Site activation activities are in progress at multiple major cancer centers in the US. Phase 1b clinical trial data presentation is expected in 2024."

P1 data • Trial status • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

A Phase1/1b Dose Escalation/Dose Expansion Study of Prgn-3007 Ultracar-T Cells in Patients with Advanced Hematologic and Solid Tumor Malignancies (ASH 2022) - "Study subjects undergo leukapheresis followed by lymphodepletion with either fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 for 3 days (Arm 1) or 60 mg/kg cyclophosphamide for 2 days (Arm 2). All subjects will be followed for adverse events, CAR-T-related toxicities, disease response and PRGN-3007 cell expansion and persistence. In addition, the mechanisms of safety and effectiveness of PRGN-3007 cells will be evaluated with correlative assays of specific immune response pathways."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Breast Cancer • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Ewing Sarcoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Hepatology • Indolent Lymphoma • Leukemia • Lung Adenocarcinoma • Lung Cancer • Lymphoma • Mantle Cell Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • CCND1 • IL15 • PD-L1 • ROR1

Phase 1/1b Safety Study of Prgn-3006 Ultracar-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes (ASH 2021) - P1 | "Ps receive PRGN-3006 infusion without (Cohort 1) or with lymphodepletion (fludarabine 30mg/m 2 and cyclophosphamide 500mg/m 2 days -5 to -3; Cohort 2)...Pts were heavily pre-treated with a median of 3 prior regimens (1-7), with 93% and 80% of pts being r/r to a HMA + venetoclax or intensive chemotherapy, respectively...Cytokine release syndrome (CRS) occurred in 47% of pts (n=7; G1 in 5 pts) with only 1 transient grade 3 event (DL 1, Cohort 1) that resolved in < 24 hours with tocilizumab and dexamethasone...In the setting of mbIL15, there has been a dose-dependent robust expansion and durable persistence of PRGN-3006 with encouraging responses (50%) in patients treated following lymphodepletion. Enrollment is ongoing to DL4, and updated safety, efficacy, PK/PD and cytokine data to be presented."

Clinical • P1 data • Acute Myelogenous Leukemia • Aplastic Anemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD33 • IL15 • IL6 • TNFA

Precigen Reports Third Quarter 2022 Financial Results and Progress of Clinical Programs (PRNewswire) - "PRGN 2009 AdenoVerse™ Immunotherapy in HPV-associated Cancers: The Company expects Phase 1 data to be presented in the first half of 2023; PRGN-3005 UltraCAR-T® in Ovarian Cancer: Patient follow up is ongoing and the Company expects Phase 1 data to be presented in the first half of 2023; PRGN-3007 UltraCAR-T® in Advanced ROR1+ Hematological and Solid Tumors: The Phase 1/1b umbrella study of PRGN-3007 in advanced receptor tyrosine kinase-like orphan receptor 1-positive (ROR1+) hematological and solid tumors is on track to initiate dosing in the fourth quarter of 2022."

P1 data • Trial status • Gynecologic Cancers • Hematological Malignancies • Oncology • Ovarian Cancer • Solid Tumor

Precigen Reports Second Quarter and First Half 2022 Financial Results (PRNewswire) - "PRGN-3006 UltraCAR-T in AML: The Company received FDA clearance to incorporate repeat dosing in the Phase 1b expansion phase of the study and plans to initiate in 2022. Additional data for the Phase 1/1b study is expected at a major scientific conference in Q4 2022....PRGN-3005 UltraCAR-T in Ovarian Cancer: Patient follow up is ongoing and the Company expects Phase 1 data to be presented in the first half of 2023."

Enrollment status • P1 data • Acute Myelogenous Leukemia • Gynecologic Cancers • Hematological Malignancies • Oncology • Ovarian Cancer

Incorporation of intrinsic checkpoint blockade enhances functionality of multigenic autologous UltraCAR-T® cells manufactured using non-viral gene delivery and rapid manufacturing process (AACR 2022) - "Single-cell cytokine proteomics showed significant increase in polyfunctionality of UltraCAR-T with intrinsic downregulation of CPI gene(s). In vivo, a single infusion of receptor tyrosine kinase-like orphan receptor 1 (ROR1)-specific UltraCAR-T with intrinsic PD-1 blockade resulted in rapid expansion, an increase in preferred T cell memory (TSCM/TCM) populations, and significantly improved overall survival of ROR1+ PD-L1+ tumor bearing mice.These preclinical data highlight the improved efficacy of incorporating intrinsic CPI blockade in UltraCAR-T cells using non-viral gene delivery and an established rapid, decentralized manufacturing process."

CAR T-Cell Therapy • Checkpoint inhibition • IO biomarker • Oncology • IL15 • PVR • ROR1 • TIGIT

Precigen Provides Pipeline and Corporate Updates at the 40th Annual J.P. Morgan Healthcare Conference (PRNewswire) - "Precigen announced enrollment completion for Dose Level 3 of the IV arm, completing enrollment in both the IP and IV arms in the dose escalation phase of the study....The Company has received FDA clearance to incorporate lymphodepletion at Dose Level 3 of the IV arm and will initiate the multicenter expansion phase of the study, incorporating redosing."

Clinical protocol • Enrollment status • FDA event • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Modified Immune Cells (Autologous CAR T Cells) in Treating Patients With Advanced, Recurrent Platinum Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer (clinicaltrials.gov) - P1; N=71; Recruiting; Sponsor: PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc.; Trial completion date: Apr 2026 ➔ Nov 2028; Trial primary completion date: Apr 2022 ➔ Dec 2023

CAR T-Cell Therapy • Clinical • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor • BRCA • MRI

Precigen Reports Second Quarter and First Half 2021 Financial Results (PRNewswire) - "PRGN-3005 UltraCAR-T is a first-in-class investigational therapy under evaluation in a Phase 1/1b clinical trial for the treatment of patients with advanced, recurrent platinum resistant ovarian cancer....The Company anticipates the presentation of interim data from the Phase 1 trial in the fourth quarter of 2021....PRGN-3006 UltraCAR-T is a first-in-class investigational therapy under evaluation in a Phase 1/1b clinical trial for the treatment of patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) or higher-risk myelodysplastic syndromes (MDS)....The Company anticipates the presentation of interim data from the Phase 1 trial in the fourth quarter of 2021."

P1 data • Acute Myelogenous Leukemia • Gynecologic Cancers • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Ovarian Cancer

"What’s next: an UltraCart library approach on an affordable and safe pick, mix and redose basis by @Precigen" (@Biotech2050)