PBCAR269A / Precision BioSci - LARVOL DELTA

A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A, With or Without Nirogacestat, in Study Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=48 | Terminated | Sponsor: Precision BioSciences, Inc. | Completed ➔ Terminated; Study was terminated due to lack of sufficient therapeutic effect

Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology • CRP

[VIRTUAL] BCMA-Directed CAR T-Cells: Early Results and Future Directions (SOHO 2021) - "Other Constructs of Interest Orva-cel (orvacabtagene autoleucel) is an anti-BCMA CAR T product with a construct containing a fully human scFv, an optimized spacer, a 4-1BB co-stimulatory domain, and a CD3z activation domain...Bb21217 has an identical construct to ide-cel except for coculturing with the phosphoinositide 3 kinase inhibitor (PI3K) bb007 during ex vivo culture to enrich for T cells displaying a memory-like phenotype...The ORR was 94%.17 P-BCMA-101 is a novel construct using an anti-BCMA Centyrin™ fused to a 4-1BB costimulatory domain and CD3z signaling domain...Both ide-cel and cilta-cel are being evaluated in various patient populations, including early-relapse and newly diagnosed high-risk patients...The first results of an allogeneic BCMA-directed CAR-T was with ALLO-715. The initial results from the UNIVERSAL phase 1 study in RRMM are encouraging, with responses reported and more attenuated toxicity.26 Others, including CTX120, BCMAUCART, UCART CS1, and..."

CAR T-Cell Therapy • Hematological Malignancies • Multiple Myeloma • Oncology • CD19 • CD4 • CD8 • SDC1 • TNFA

A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A, With or Without Nirogacestat, in Study Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=48 | Completed | Sponsor: Precision BioSciences, Inc. | Recruiting ➔ Completed | Trial completion date: Dec 2021 ➔ Oct 2022 | Trial primary completion date: Dec 2021 ➔ Oct 2022

Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • CRP

Precision BioSciences Provides Update on Allogeneic CAR T Programs and Path Forward with Its Lead PBCAR0191 Candidate for CAR T Relapsed Patient Population (Businesswire) - P1/2 | N=48 | NCT04171843 | Sponsor: Precision BioSciences, Inc. | "...Precision opted to expedite the next round of manufacturing process optimization for PBCAR19B. This manufacturing optimization was implemented in the first quarter of 2022. New clinical trial material is expected to be released and dosing at the next cohort, DL2 (flat dose of 540 million cells), in the third quarter of 2022....For PBCAR269A, Precision has continued to enroll subjects in its PBCAR269A Phase 1/2a study in combination with nirogacestat...Precision has completed DL2 (2.0 × 106 cells/kg) of PBCAR269A plus GSI and is initiating the next cohort at DL3 to further evaluate efficacy. To date, peak expansion rates observed at DL2 plus the GSI have been equivalent to DL4 (960 × 106 cells flat dose) monotherapy with no dose limiting toxicities observed. The company expects to also provide an update on this program around year end."

P1/2 data • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Precision BioSciences Reports Fourth Quarter and Fiscal Year 2021 Financial Results and Provides Business Update (Businesswire) - "PBCAR19B: Precision plans to commence dosing at the next dose level with clinical trial material from an optimized manufacturing process once released and expects to provide a program update in mid-2022; PBCAR269A: Precision is evaluating PBCAR269A in a Phase 1/2a study in combination with nirogacestat, a gamma secretase inhibitor developed by SpringWorks Therapeutics and expects to provide an update in mid-2022."

Trial status • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Reports Clinical Program Updates for Its Allogeneic CAR T Pipeline (Businesswire) - P1/2, N=48; NCT04171843; Sponsor: Precision BioSciences, Inc.; "PBCAR269A Phase 1/2a Program Update:...The following has been observed among 14 patients that have been evaluated for clinical activity and safety across four dose levels of PBCAR269A4 monotherapy following sLD: No Grade ≥ 3 CRS or ICANS; Dose-dependent increase in PBCAR269A peak expansion. Overall, PBCAR269A monotherapy response observed in the Phase 1/2a trial was not comparable with autologous CAR T profiles....Initial clinical data from the combination cohort is expected to be presented in mid-2022."

P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Precision BioSciences Reports Third Quarter 2021 Financial Results and Provides Business Update (Businesswire) - "PBCAR19B: PBCAR19B is being administered at flat dose levels starting at 2.7 × 108 CAR T cells per patient, the same as Dose Level 3 for PBCAR0191. Precision expects to provide an initial study update in 2022...PBCAR269A: Precision expects to provide an interim update on the monotherapy arm of the study during its conference webcast on December 11, 2021....PBCAR20A: Treatment with PBCAR20A did not result in compelling response rates in a Phase 1/2a clinical study. Precision will not continue development of PBCAR20A. All subjects enrolled in the study and evaluated for treatment with PBCAR20A..."

Trial status • Acute Lymphocytic Leukemia • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Reports Second Quarter 2021 Financial Results and Provides Business Update (Businesswire) - "Precision has completed Dose Level 3 (4.8 × 108 cells per patient given as a fixed dose) of its Phase 1/2a anti-CD20 study of PBCAR20A and has paused the study until PBCAR0191 and PBCAR19B durability is demonstrated. Precision expects to provide an interim update for PBCAR20A in 2021; Precision continues to enroll patients in its Phase 1/2a study of PBCAR269A targeting B-cell maturation antigen (BCMA) for patients with R/R multiple myeloma...Precision expects to provide an interim update on the monotherapy arm of the study in 2021."

Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A, With or Without Nirogacestat, in Study Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2; N=48; Recruiting; Sponsor: Precision BioSciences, Inc.; Trial completion date: May 2021 ➔ Dec 2021; Trial primary completion date: May 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • CRP

Precision BioSciences and SpringWorks Therapeutics Dose First Patient in Expanded Phase 1/2a Clinical Trial Evaluating PBCAR269A with Nirogacestat in Patients with Relapsed/Refractory Multiple Myeloma (Businesswire) - "Precision BioSciences...announced that the first patient has been dosed in the combination arm of Precision’s Phase 1/2a trial evaluating PBCAR269A. In the study, Precision’s investigational allogeneic BCMA-targeted CAR T cell therapy will be combined with nirogacestat, SpringWorks’ investigational gamma secretase inhibitor (GSI), in patients with relapsed/refractory (R/R) multiple myeloma."

Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Precision BioSciences Reports First Quarter and 2021 Financial Results and Provides Business Update (Businesswire) - “PBCAR0191…Precision will continue to monitor the results for durability from this eLD regimen and expects to report updated interim results in June at ASCO 2021. PBCAR20A…Precision expects to provide an interim update for the PBCAR20A study in 2021. PBCAR269A…Precision expects to provide an interim update in 2021. Precision also expects to initiate the combination arm of its ongoing Phase 1/2a clinical study with PBCAR269A and nirogacestat, SpringWorks Therapeutics’ investigational gamma secretase inhibitor, in the first half of 2021. PBCAR269B…Precision is conducting IND-enabling studies for PBCAR269B and expects to file an IND application in early 2022."

IND • New P1/2 trial • P1/2 data • Preclinical • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Solid Tumor

SpringWorks Therapeutics Reports First Quarter 2021 Financial Results and Recent Business Highlights (GlobeNewswire) - "The Company expects to report additional clinical data from the ReNeu trial at a medical conference this year and to complete enrollment of the trial in the second half of 2021. SpringWorks expects to report topline data from the Phase 3 DeFi trial in the second half of 2021, as previously disclosed....SpringWorks also expects that two additional collaborator-sponsored trials will initiate in the first half of 2021, as previously disclosed: nirogacestat + Pfizer’s elranatamab and nirogacestat + Precision Biosciences’ PBCAR269A."

New trial • P2 data • P3 data • Desmoid Tumors • Multiple Myeloma • Neurofibromatosis • Oncology

Precision BioSciences Reports Fourth Quarter and Fiscal Year 2020 Financial Results and Provides Business Update (GlobeNewswire) - “PBCAR269A: Precision continues to enroll patients in its Phase 1/2a study of PBCAR269A, its wholly-owned investigational allogeneic CAR T candidate targeting B-cell maturation antigen for the treatment of R/R multiple myeloma…Precision expects to report interim data in 2021. Precision also expects to initiate, in the first half of 2021, the combination arm of its ongoing Phase 1/2a clinical study with PBCAR269A and nirogacestat, SpringWorks Therapeutics’ investigational gamma secretase inhibitor. Precision announced its clinical collaboration with SpringWorks in 2020.”

New P1/2 trial • P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology

SpringWorks Therapeutics Reports Third Quarter 2020 Financial Results and Recent Business Highlights (GlobeNewswire) - “B-cell Maturation Antigen (BCMA) Combinations in Multiple Myeloma…to evaluate nirogacestat in combination with...teclistamab, in patients with relapsed or refractory multiple myeloma. A Phase 1 study is expected to commence by early 2021, pending discussions with regulators…to evaluate nirogacestat in combination with Pfizer’s BCMA CD3 bispecific antibody, PF-06863135, in patients with relapsed or refractory multiple myeloma. A Phase 1b/2 study is expected to commence in the first half of 2021. An IND application is expected to be filed by the end of 2020 to evaluate nirogacestat in combination with Allogene’s BCMA AlloCAR T therapy, ALLO-715, in patients with relapsed or refractory multiple myeloma….to evaluate nirogacestat in combination with…PBCAR269A, in patients with relapsed or refractory multiple myeloma. A Phase 1/2a clinical study is expected to commence in the first half of 2021.”

IND • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Precision BioSciences Reports Third Quarter 2020 Financial Results and Provides Business Update (GlobeNewswire) - “Expanded Development Collaboration with Servier: In September 2020, Precision announced, in collaboration with Servier, that the companies had added two additional hematological cancer targets beyond CD19 and two new solid tumor targets to its existing CAR T development and commercial license agreement. With the addition of these new targets, Precision expects to receive milestone payments in the remainder of 2020 and in 2021; PBCAR0191: Precision expects to present updated interim clinical data from both the NHL and B-ALL cohorts of this trial before year-end 2020; PBCAR269A: Precision’s Phase 1/2a clinical study, which is expected to commence in the first half of 2021, pending discussions with regulators.”

Financing • P1/2 data • Trial status • Acute Lymphocytic Leukemia • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences and SpringWorks Therapeutics Announce Clinical Collaboration to Evaluate PBCAR269A in Combination with Nirogacestat in Patients with Relapsed or Refractory Multiple Myeloma (GlobeNewswire) - "Precision BioSciences, Inc…and SpringWorks Therapeutics, Inc...announced they have entered into a clinical trial collaboration agreement. Per the agreement, PBCAR269A, Precision BioSciences' wholly-owned investigational allogeneic chimeric antigen receptor (CAR) T cell therapy candidate targeting B-cell maturation antigen (BCMA), will be evaluated in combination with nirogacestat...'I look forward to the data generated from this investigational study to see if PBCAR269A plus nirogacestat improves clinical outcomes in patients with relapsed or refractory multiple myeloma'...Under the terms of the agreement, Precision BioSciences will assume all development costs of the expanded Phase 1/2a study of PBCAR269A to include nirogacestat and evaluate the safety and preliminary clinical activity of the combination therapy. Precision BioSciences and SpringWorks will form a joint development committee to oversee the clinical study, which is expected to commence in the..."

Licensing / partnership • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Precision BioSciences Receives Fast Track Designation from U.S. Food and Drug Administration for PBCAR269A, an Investigational Allogeneic CAR T Therapy for Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - "Precision BioSciences, Inc…announced the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to PBCAR269A for the treatment of relapsed/refractory multiple myeloma. This is the company’s second allogeneic chimeric antigen receptor (CAR T) cell therapy to receive Fast Tack Designation for which the FDA previously granted Orphan Drug Designation."

Fast track designation • Hematological Malignancies • Multiple Myeloma • Oncology

Precision BioSciences announces dosing of first patient in phase 1/2a clinical trial of PBCAR269A for multiple myeloma (GlobeNewswire) - "Precision BioSciences, Inc…announced that the first patient has been dosed in a Phase 1/2a clinical trial of PBCAR269A, its third allogeneic chimeric antigen receptor (CAR) T cell therapy candidate. Wholly-owned by Precision, PBCAR269A targets the B-cell maturation antigen (BCMA) and is being evaluated for the treatment of relapsed/refractory multiple myeloma."

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Precision BioSciences reports first quarter 2020 financial results and provides business update (GlobeNewswire, Precision Biosciences) - "PBCAR0191 Phase 1/2a Trial is Progressing with Updated Interim Data Expected in 2020; Phase 1/2a Trial of PBCAR269A in Patients with Multiple Myeloma Expected to Begin in 2020."

New P1/2 trial • P1/2 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Multiple Myeloma • Oncology

A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A in Study Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2; N=48; Recruiting; Sponsor: Precision BioSciences, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Precision BioSciences reports fourth quarter and fiscal year 2019 financial results and provides business update (GlobeNewswire) - “Precision expects to announce additional clinical data from the PBCAR0191 trial for both the NHL and B-ALL cohorts during 2020…In September 2019, the FDA cleared the Investigational New Drug (IND) application for PBCAR20A, Precision’s second and wholly-owned CAR T therapy candidate, which is expected to enter the clinic in Q1 2020…In January 2020, the FDA also cleared Precision’s IND application for its third CAR T therapy candidate, PBCAR269A…dosing of patients in a Phase 1/2a clinical trial is expected to begin in 2020.”

Enrollment status • New trial • P1/2 data

Precision BioSciences announces FDA acceptance of IND for PBCAR269A, a BCMA targeted genome edited allogeneic CAR T therapy candidate for multiple myeloma (GlobeNewswire) - “Precision BioSciences, Inc….announced that the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for PBCAR269A, the Company’s third allogeneic chimeric antigen receptor (CAR) T cell therapy candidate. The FDA has also granted Orphan Drug Designation to PBCAR269A for the treatment of multiple myeloma….Precision plans to initiate dosing in this Phase 1 clinical trial in 2020.”

Enrollment status • IND • Orphan drug