PBCAR19B / Precision BioSci - LARVOL DELTA

PBCAR19B, an Immune Evading Allogeneic CAR T Stealth Cell, Demonstrates Potent Anti-Tumor Responses and Prolonged B Cell Depletion Supporting Sustained Immune Evasion in Patients with Relapsed/Refractory (R/R) B-Cell Lymphoma (NHL) (ASH 2024) - "Two lymphodepletion (LD) regimens were tested, including standard (sLD), fludarabine 30 mg/m2/day × 3 days + cyclophosphamide 500 mg/m2/day × 3 days, and an augmented cyclophosphamide (Aug-Cy LD) regimen where 750 mg/m2/day × 3 days with standard fludarabine. Conclusions : PBCAR19B demonstrated promising efficacy (ORR 70%) with a high frequency of CR in DLBCL, prolonged CD19+ B cell depletion, and a favorable safety profile. Delayed T cell and NK cell recovery supports mitigation of CAR T host rejection by the immune cloaking construct."

Clinical • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • B2M • CD19 • HLA-E

Dose-escalation Study of Safety of PBCAR19B in Participants With CD19-expressing Malignancies (clinicaltrials.gov) - P1 | N=13 | Completed | Sponsor: Precision BioSciences, Inc. | Recruiting ➔ Completed | N=24 ➔ 13

Enrollment change • Trial completion • Hematological Disorders • Hematological Malignancies • Oncology • CD19

Precision BioSciences Completes Strategic Transaction with Imugene for Azer-Cel in Cancer (Businesswire) - "Precision BioSciences...announced completion of a strategic transaction with Imugene Limited (ASX: IMU) for global rights to Azercabtagene Zapreleucel (azer-cel), Precision’s lead allogeneic CAR T candidate, for cancer. Imugene will assume ongoing clinical execution for azer-cel in the large B-cell lymphoma (LBCL) population who have relapsed following autologous CAR T treatment. The license also includes an option to develop up to three other cancer research programs in the future....Precision eligible to receive up to $227 million in upfront economics and milestone payments for Azer-Cel in addition to double-digit royalties on sales....Precision’s PBCAR19B stealth cell and its CAR T assets targeting multiple myeloma, as well as all rights to non-oncology indications for azer-cel, remain available for development through partnership only."

Licensing / partnership • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Reports Second Quarter 2023 Financial Results and Provides Business Update (Businesswire) - "Research and Development Expenses: Research and development expenses were $21.9 million for the quarter ended June 30, 2023, as compared to $22.9 million for the same period in 2022. The decrease of $1.0 million was primarily due to decreases in PBCAR19B external development, outsourced research and development, employee-related costs, and contract manufacturing organization expenses partially offset by increases in in vivo external development and azer-cel external development costs."

Commercial • Oncology

Precision BioSciences Provides Update on Allogeneic CAR T Programs and Regulatory Path Forward (Businesswire) - P1 | N=24 | NCT04649112 | Sponsor: Precision BioSciences, Inc. | "The Company also provided the first clinical update on PBCAR19B stealth cell, which is in development as a potential best-in-class allogeneic CAR T therapy for patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL), with primary focus on DLBCL....As of May 30, 2023, in Phase 1 results we observed an acceptable safety profile with high overall response rates among all evaluable subjects with evidence of molecular remission (MRD-) and preliminary durability at Dose Level 2 (540 million cells). Out of seven evaluable subjects at Dose Level 2, five with DLBCL and two with mantle cell lymphoma, PBCAR19B achieved 71% ORR and 43% CR rate. In DLBCL patients, ORR was achieved in 80% of subjects and 60% achieved a CR (MRD-)."

P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Reports First Quarter 2023 Financial Results and Provides Business Update (Businesswire) - "Precision continues to progress its Phase 1/2a clinical trial of azer-cel, the Company’s lead investigational anti-CD19 allogeneic CAR T candidate, in adult subjects with non-Hodgkin lymphoma (NHL) who have relapsed following CAR T treatment. Precision plans to provide an update on the expansion cohort as well as additional long-term follow up from the previously presented azer-cel cohorts in May 2023. As of May 1, 2023, seven patients have been treated in the expansion/Phase 2a cohort with a lower dose lymphodepletion regimen, in addition to the 12 patients who were treated in previous cohorts. PBCAR19B...The Company also expects to provide a program update on seven patients treated at Dose Level 2 in May 2023."

P1/2 data • Trial status • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Reports First Quarter 2023 Financial Results and Provides Business Update (Businesswire) - "Research and development expenses were $22.2 million for the quarter ended March 31, 2023, as compared to $20.0 million for the same period in 2022. The increase of $2.2 million was primarily due to an increase in direct research and development expenses related to our azer-cel and PBCAR19B product candidates as well as consulting fees related to our increased focus on quality management, partially offset by a decrease in expenses related to manufacture of materials for use in preclinical studies, PBCAR20A external development costs, and share-based compensation expense from recent forfeitures."

Commercial • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Reports Fourth Quarter and Fiscal Year 2022 Financial Results and Provides Business Update (Businesswire) - "The Company also plans to complete Phase 1 dose escalation for PBCAR19B in the earlier line NHL setting. CAR T Portfolio Update: Precision plans to provide a CAR T update once investigators complete enrollment of the current azer-cel cohort of six CAR T relapsed subjects with sufficient follow-up to support a meeting with the FDA to discuss clinical plans. Subjects are being treated with optimized azer-cel product at the planned final dose level (500 million CAR T cells following a lymphodepletion regimen consisting of 3 days of fludarabine and cyclophosphamide). Based on current enrollment, the update is now expected to occur in the April/May 2023 time frame, once appropriate follow-up from the current cohort is available."

P1/2 data • Trial status • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Recaps 2022 Accomplishments and Outlines 2023 Corporate Priorities and Planned Portfolio Milestones (Businesswire) - "Today, Precision announced its key priorities and planned upcoming milestones for 2023, including: Progress azer-cel to decision point for Phase 2 trial in non-Hodgkin lymphoma (NHL) subjects who have relapsed following autologous CAR T treatment. Complete Phase 1b cohort for azer-cel to determine final dosing schedule; request FDA clinical meeting pending data; Complete Phase 1 dose escalation for PBCAR19B in the earlier line NHL setting; Present CAR T clinical update in the first quarter of 2023, based on patient accrual and follow-up."

FDA event • Trial status • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Reports Third Quarter 2022 Financial Results and Provides Business Update (Businesswire) - "PBCAR19B: Precision expects to provide an update in late Q4 2022 or early Q1 2023, depending on patient accrual and follow-up, on its two distinct CD19 targeted products, including azer-cel which is aiming to achieve a potential first-in-class allogeneic CAR T therapy in the CAR T relapsed population, and PBCAR19B which is seeking to displace autologous CAR T in the second/third line DLBCL population."

P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"Another new INN: PBCAR0191 = azercabtagene zapreleucel. But wasn't $DTIL supposed to be switching focus to next-gen PBCAR19B? #ASH22" (@JacobPlieth)

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

Dose-escalation Study of Safety of PBCAR19B in Participants With CD19-expressing Malignancies (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Precision BioSciences, Inc.; Trial completion date: May 2023 ➔ Sep 2023; Trial primary completion date: Jun 2022 ➔ Sep 2022

Trial completion date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Oncology • CD19

Precision BioSciences Reports Clinical Program Updates for Its Allogeneic CAR T Pipeline (Businesswire) - "The Phase 1 clinical study of PBCAR19B is actively enrolling subjects with R/R NHL. Flat doses of PBCAR19B CAR T cells following standard lymphodepletion (sLD)3 are administered starting at Dose Level 1 (2.7 × 108 CAR T cells). The company has dosed the first three subjects at Dose Level 1....'we are continuing to enroll patients in the PBCAR19B clinical trial and expect to share initial results for this program in mid-2022'."

P1 data • Trial status • Hematological Malignancies • Non-Hodgkin’s Lymphoma • 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 Doses First Patient in Phase 1 Allogeneic CAR T Clinical Trial of PBCAR19B Immune Evading Stealth Cell for Relapsed/Refractory Non-Hodgkin Lymphoma (Businesswire) - “Precision BioSciences, Inc…announced that the first patient has been dosed in its Phase 1 clinical trial with PBCAR19B, an immune evading allogeneic CAR T stealth cell candidate for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).”

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

Precision BioSciences Reports Progress on Two Strategies Designed to Optimize Durability of Allogeneic CAR T Therapy in R/R Non-Hodgkin Lymphoma (Businesswire) - P1/2, N=92; NCT03666000; Sponsor: Precision BioSciences; “Precision BioSciences…announced encouraging progress on two strategies designed to optimize the durability of allogeneic CAR T therapy in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). The Company reported updated interim results from its Phase 1/2a study of PBCAR0191…The Company also reported preclinical data demonstrating the potential mechanism by which its investigational immune evading stealth cell, PBCAR19B, may avoid rejection by T cells and natural killer (NK) cells…A single dose of PBCAR0191 cells following eLD yielded clinical responses in the majority of patients, with overall response rates (ORR) and complete response (CR) rates of 75% and 50%, respectively at Day ≥ 28…and cytokine release syndrome (CRS) compared to patients who received sLD.”

Cytokine release syndrome • P1/2 data • Preclinical • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Dose-escalation Study of Safety of PBCAR19B in Participants With CD19-expressing Malignancies (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Precision BioSciences, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hematological Disorders • Hematological Malignancies • Oncology • CD19

Precision BioSciences Reacquires Global Rights to its Allogeneic CAR T Programs (Businesswire) - "Precision BioSciences...announced it has entered into a Program Purchase Agreement to reacquire all global development and commercialization rights for all CAR T partnered programs covered under its Development and Commercial License Agreement with Servier. This includes its two clinical stage CD19-targeting allogeneic CAR T candidates, PBCAR0191 and PBCAR19B stealth cell, as well as four additional product targets...Servier eligible to receive milestones and royalties based on program success...Precision intends to monitor the results for durability from this eLD regimen and report updated interim results by mid-2021. By the end of May 2021, Precision expects to dose the first patient with PBCAR19B."

Licensing / partnership • P1/2 data • Trial status • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Reports Fourth Quarter and Fiscal Year 2020 Financial Results and Provides Business Update (GlobeNewswire) - “PBCAR0191: Precision expects to provide updated interim data for PBCAR0191 by mid-2021; PBCAR19B: The Phase 1 study is expected to begin by mid-year 2021 and will be a non-randomized, open-label, single-dose, dose-escalation and dose-expansion study to evaluate the safety and clinical activity of PBCAR19B in patients with R/R NHL; PBCAR20A: Precision also continues to enroll patients in its Phase 1/2a clinical trial of PBCAR20A, a wholly-owned investigational allogeneic anti-CD20 CAR T therapy for patients with R/R NHL including patients with R/R chronic lymphocytic leukemia or R/R small lymphocytic lymphoma…The Company expects to report interim data for the PBCAR20A study in 2021.”

P1/2 data • Trial status • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

"The @US_FDA cleared @PrecisionBioSci’s IND application for its CAR T-cell therapy PBCAR19B https://t.co/nsqMenVFwQ" (@ASHClinicalNews)

CAR T-Cell Therapy

Precision BioSciences Receives Notice of Allowance for U.S. Patent Application Covering PBCAR19B, a Stealth Cell, CD19 Allogeneic CAR T Candidate for Non-Hodgkin Lymphoma (GlobeNewswire) - “Precision BioSciences, Inc…announced it has received a Notice of Allowance from the U.S. Patent and Trademark Office for a patent application covering PBCAR19B, a next-generation, stealth cell, CD19 product candidate for patients with relapsed/refractory (R/R) Non-Hodgkin Lymphoma (NHL)…Once issued, patents arising from this patent family will have standard expiration dates in April 2040.”

Patent • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Announces FDA Accepts IND for PBCAR19B, a Next-Generation, Stealth Cell, CD19 Allogeneic CAR T Candidate for Non-Hodgkin Lymphoma (GlobeNewswire) - “Phase 1 clinical trial of PBCAR19B for patients with relapsed/refractory NHL expected to begin by mid-2021…Precision BioSciences, Inc…announced that the U.S. Food and Drug Administration (FDA) has accepted the Investigational New Drug (IND) application for PBCAR19B, a next-generation, stealth cell, CD19 product candidate for patients with relapsed/refractory (R/R) Non-Hodgkin Lymphoma (NHL).”

IND • Trial initiation date • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Precision BioSciences Reports Positive Interim Results from PBCAR0191 Phase 1/2a Trial in Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma (NHL) and R/R B-cell Acute Lymphoblastic Leukemia (B-ALL) (GlobeNewswire) - P1/2, N= 92; NCT03666000; Sponsor: Precision BioSciences, Inc.; "Acceptable Tolerability and Safety Profile in 27 Patients with No Graft versus Host Disease (GvHD), No Grade ≥ 3 Cytokine Release Syndrome (CRS), and No Grade ≥ 3 Neurotoxicity (ICANS); PBCAR0191 Demonstrated Longest Durability of Response to 11 months in B-ALL; PBCAR0191 with Enhanced Lymphodepletion Resulted in Objective Response Rate (ORR) of 83% (5/6) in NHL and B-ALL...Completed Preclinical Work for PBCAR19B, Next Generation CD19 'Stealth Cell'Candidate; Expect to Enter Clinical Trials in 2021"

Cytokine release syndrome • New trial • P1/2 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology