azercabtagene zapreleucel (PBCAR0191) / Precision BioSci, Imugene, TG Therap - LARVOL DELTA

Imugene secures FDA fast track designation for CAR T-cell therapy azer-cel to combat blood cancer (Proactiveinvestors) - "Imugene Ltd has garnered fast track designation from the US Food and Drug Administration (FDA) for its allogeneic CAR T-cell therapy, azer-cel (azercabtagene zapreleucel), in the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL)....This status provides Imugene with access to more frequent FDA interactions, rolling submission reviews and potential eligibility for Accelerated Approval and Priority Review....Clinical data from the ongoing Phase 1b trial has demonstrated promising results, particularly in patients who have failed multiple prior treatments, including autologous CAR T therapy."

Fast track • Diffuse Large B Cell Lymphoma

TG Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "2025 Development Pipeline Anticipated Milestones: Commence pivotal program of subcutaneous ublituximab; Commence a pivotal program based on data from the ENHANCE trial with the goal of enhancing the patient experience on intravenous BRIUMVI; Enroll participants into the ongoing trial evaluating BRIUMVI in autoimmune diseases outside of MS; Enroll participants into the Phase 1 azer-cel trial in autoimmune disease, beginning with progressive forms of MS; Present updated data at major medical conferences throughout the year."

Clinical data • Enrollment status • New trial • Immunology • Multiple Sclerosis

MaxCyte Signs Strategic Platform License with TG Therapeutics to Advance its Autoimmune Cell Therapeutics Programs (GlobeNewswire) - "TG Therapeutics to use MaxCyte’s Flow Electroporation technology and ExPERT platform to support the development and commercialization of azer-cel, its allogeneic CD19 CAR T cell therapy program, for the treatment of autoimmune diseases....TG received clearance by the U.S. Food and Drug Administration (FDA) of an Investigational New Drug (IND) application for azer-cel in progressive forms of multiple sclerosis (MS) and is targeting commencement of a Phase 1 trial in 2025."

Licensing / partnership • New P1 trial • Immunology • Multiple Sclerosis

Azer-cel demonstrates two additional Complete Responses in CD19 CAR-T Phase 1b Trial with 57% Complete Response Rate (Imugene Press Release) - "Two additional Complete Responses (CRs) have been observed in Imugene’s Phase 1b trial of azer-cel, an allogeneic off-the-shelf CD19 CAR T therapy in relapsed/refractory diffuse large B-cell lymphoma (DLBCL), a type of blood cancer; Four out of seven patients (Cohort B, see ASX announcement 2 September 2024) have now achieved a complete response following treatment with azer-cel, lymphodepletion (chemotherapy), and low-dose interleukin 2 (IL-2); 13 US sites and up to 5 sites in Australia will actively enrol into the trial."

Trial status • Diffuse Large B Cell Lymphoma

A Study to Assess the Safety and Clinical Activity of Azer-cel in Participants With B-cell Mediated Autoimmune Disorders (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: TG Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology

Administration of Low-Dose, Subcutaneous (SC) Interleukin-2 (IL-2) Markedly Enhances the Pharmacokinetic (PK) Profile of Azercabtagene Zapreleucel (azer-cel), an Allogeneic Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy, without Compromising Safety and Early Evidence of Clinical Activity in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Who Have Relapsed after Prior... (TCT-ASTCT-CIBMTR 2025) - P1 | "All patients received lymphodepletion with Aug/Cy (fludarabine 30 mg/m 2 /day and cyclophosphamide 750 mg/m 2 /day × 3 days) prior to azer-cel infusion (500 × 10⁶ cells) on Day 0. IL-2 markedly improved CAR T expansion (Figure 1) without impacting safety, with 3 CRs reported in 4 evaluable patients, and 1 with ongoing response past 120 days. Administration of low-dose IL-2 after treatment with azer-cel and Aug/Cy lymphodepletion may provide clinical benefit with predictable and manageable toxicity and markedly improved PK (~2 log increase in C max )."

CAR T-Cell Therapy • Clinical • PK/PD data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Bone Marrow Transplantation • Cytomegalovirus Infection • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • IL2

TG Therapeutics Provides Preliminary Fourth Quarter and Full Year 2024 Net Revenue and 2025 Anticipated Development Milestones (GlobeNewswire) - "BRIUMVI U.S. net product revenue expected to be $103.6 million and $310 million for the fourth quarter and full year of 2024, respectively....2025 Development Pipeline Anticipated Milestones: Commence pivotal program of subcutaneous BRIUMVI; Commence pivotal programs to consolidate the Day 1 and Day 15 dose of BRIUMVI, and to evaluate 30 minute BRIUMVI maintenance infusions; Enroll participants into the ongoing trial evaluating BRIUMVI in autoimmune diseases outside of Multiple Sclerosis (MS); Present updated data at major medical conferences throughout the year."

Clinical data • Enrollment status • New trial • Sales • Multiple Sclerosis

First Australian patient dosed in Phase 1b azer-cel clinical trial (Imugene Press Release) - "Imugene Limited...is pleased to announce that the first Australian patient has been dosed in the Phase 1b clinical trial of its allogeneic CAR T-cell therapy azer-cel (azercabtagene zapreleucel), at the Royal Prince Alfred Hospital (RPAH) in Sydney. The trial is focused on patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), one of the most challenging and aggressive forms of non-Hodgkin’s lymphoma."

Trial status • Diffuse Large B Cell Lymphoma

Imugene receives substantial capital injection; extends cash runway to end of 2025 in support of ongoing trials (Proactiveinvestors) - "Imugene Ltd...is positioned to raise up to A$46 million via the issue of convertible notes and warrants to CVI Investments, Inc. to support its clinical pipeline...Funds are to be put toward ongoing trials for IMU’s azer-cel, onCARlytics and VAXINIA programs, as the company anticipates key clinical data readouts in the coming 12 months....The issuance involves A$20 million of senior, unsecured, zero-coupon, convertible notes and up to a further A$26 million through the issue of unlisted warrants."

Clinical data • Financing • Hematological Malignancies • Solid Tumor

Azer-cel accepted for presentation at ASTCT Tandem Meetings event (Imugene Press Release) - "Imugene Limited...is pleased to announce that an abstract regarding its allogeneic CAR T-cell therapy azer-cel has been accepted for a poster presentation at the upcoming 2025 Tandem Meetings event for the Transplantation & Cellular Therapy Meetings of ASTCT (American Society for Transplantation and Cellular Therapy) and CIBMTR (Center for International Blood and Marrow Transplant Research). The event will be held 12-15 February 2025 in Hawaii, USA."

P1 data • Diffuse Large B Cell Lymphoma

A Study to Assess the Safety and Clinical Activity of Azer-cel in Participants With B-cell Mediated Autoimmune Disorders (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: TG Therapeutics, Inc.

New P1 trial • Immunology

Imugene opens first Australian site for azer-cel clinical trial targeting lymphoma (Proactiveinvestors) - "Imugene Ltd...has opened the first Australian site for its azer-cel (azercabtagene zapreleucel) Phase 1b clinical trial, which expands its allogeneic CAR T-cell therapy program for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The Royal Prince Alfred Hospital in Sydney will spearhead Australian patient recruitment, which begins in November 2024, becoming Australia’s only actively enrolling allogeneic CAR T-cell trial."

Trial status • Diffuse Large B Cell Lymphoma

Imugene reports promising results in Phase 1b trial for azer-cel in DLBCL (Proactiveinvestors) - P1/1b | N=129 | NCT03666000 | Sponsor: Imugene Limited | "Imugene Ltd...discuss positive results from its Phase 1b clinical trial of azer-cel (azercabtagene zapreleucel), an allogeneic off-the-shelf CD19 CAR T therapy, in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL)....Results showed three complete responses, with two in Cohort B and one in Cohort A. The complete responses in Cohort B have been durable, with one exceeding 120 days and another more than 90 days. All four patients in Cohort B remain in the trial, and more patients will be enrolled. The treatment has been safe and tolerable....Imugene plans to continue patient enrolment..."

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

Precision BioSciences Receives $13 Million in Proceeds from Imugene Convertible Note Maturity as Part of the August 2023 Azer-cel Deal (Businesswire) - "Precision BioSciences, Inc...announced maturity of a $13 million convertible note from its previously announced strategic transaction with Imugene Limited (ASX: IMU) for azercabtagene zapreleucel (azer-cel) in oncology. The proceeds to Precision BioSciences include $9.75 million in cash and $3.25 million in Imugene ordinary shares."

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

Precision BioSciences Announces Investigational New Drug Clearance by Partner TG Therapeutics for Investigation of Azer-Cel for Multiple Sclerosis (Businesswire) - "TG Therapeutics anticipates commencing a phase 1 clinical trial in 2024....In January 2024, Precision BioSciences announced a licensing deal with TG Therapeutics for the CAR T therapy azer-cel...Precision received upfront and potential near-term economics valued at $17.5 million and up to $288 million in other milestone payments based on achievement of certain clinical, regulatory, and commercial milestones."

Licensing / partnership • New P1 trial • Multiple Sclerosis

Imugene progresses clinical trials supported by strong cash runway (Proactiveinvestors) - "Imugene Ltd...is in a strong cash position with A$93 million as of June 30, 2024, excluding an expected R&D tax rebate of ~A$11 million, to continue progressing four Phase 1/1b/2 clinical trials which are recruiting in the US, Australia and the UK...This financial position provides a runway to support the company's clinical pipeline and operations into late 2025...Azer-cel continues to enrol in Phase 1b study...Once the Phase 1b study is complete there is potential to start a registrational Phase 2/3 study in 2025 and become the first approved allogeneic CAR T cell therapy for cancer...VAXINIA bile tract cancer trial opened; MAST trial higher dose cohort open for enrolment."

Enrollment status • New P2/3 trial • Biliary Tract Cancer • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

TG Therapeutics Reports Second Quarter 2024 Financial Results and Raises BRIUMVI (ublituximab-xiiy) Full Year Revenue Guidance (GlobeNewswire) - "BRIUMVI U.S. net product revenue of $72.6 million for the second quarter of 2024, representing >350% growth over the second quarter of 2023...Initiated a phase 1 clinical trial evaluating subcutaneous ublituximab in RMS, with the first patients now dosed. Received clearance by the U.S. Food and Drug Administration (FDA) of an Investigational New Drug (IND) application for azer-cel in progressive forms of multiple sclerosis (MS)....Remaining 2024 Development Pipeline Anticipated Milestones: Present additional data from the ENHANCE Phase 3b CD20 switch trial."

IND • P3 data • Sales • Trial status • Immunology • Multiple Sclerosis

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

PBCAR0191-01: Dose-escalation, Dose-expansion Study of Safety of Azer-cel (PBCAR0191) in Patients With r/r NHL and r/r B-cell ALL (clinicaltrials.gov) - P1 | N=129 | Recruiting | Sponsor: Imugene Limited | Trial completion date: Mar 2028 ➔ Jun 2027 | Trial primary completion date: Mar 2026 ➔ Jun 2025

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRP

PBCAR0191-01: Dose-escalation, Dose-expansion Study of Safety of Azer-cel (PBCAR0191) in Patients With r/r NHL and r/r B-cell ALL (clinicaltrials.gov) - P1 | N=129 | Recruiting | Sponsor: Imugene Limited | Phase classification: P1/2 ➔ P1 | Trial completion date: Jun 2024 ➔ Mar 2028 | Trial primary completion date: Mar 2024 ➔ Mar 2026

Phase classification • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRP

Imugene and Kincell Bio Announce Strategic Manufacturing and Process Development Partnership (GlobeNewswire) - "Imugene, Ltd...announce a strategic manufacturing and process development partnership, which includes the sale of Imugene’s North Carolina Current Good Manufacturing Practice (CGMP) manufacturing facility and the transfer of process and analytical development activities to Kincell. Under the terms of an asset purchase agreement between Imugene and Kincell, Kincell will acquire Imugene’s CGMP-compliant cell therapy manufacturing facility in North Carolina for a total consideration of up to $6M USD in upfront and milestone-driven payments. Both parties have entered into a manufacturing supply agreement whereby Kincell will manufacture Imugene’s Azer-cel to support ongoing clinical trials. Imugene will also transfer process and analytical development of Azer-cel to Kincell in order to support process and method optimization for commercial readiness."

Licensing / partnership • Hematological Malignancies • Oncology

Azer-cel hits major milestone with first patient dosed in Phase 1b Allogeneic CAR T Clinical Trial (Imugene Press Release) - P1 | N=120 | NCT03666000 | Sponsor: Precision BioSciences, Inc. | "First patient in Phase 1b follows successful Phase 1 trial in 84 patients at leading US Centres...The Phase 1b trial is a precursor to a Phase 2 registrational (subject to FDA agreement) in 2024...Strong safety and efficacy signals to date from 84 Phase 1 patients dosed with azer-cel...The patient who was dosed at Banner Health (Phoenix Arizona) suffers from a difficult to treat sub-set of NHL called Diffuse-Large B-cell lymphoma (DLBCL)....The Phase 1b allogeneic (allo) CAR T study is an ongoing multi-centre Phase 1b clinical trial in patients with non-Hodgkin’s lymphoma (NHL) and B-cell acute lymphocytic leukemia (ALL)."

New P2 trial • P1 data • Trial status • Acute Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

TG Therapeutics Provides Business Update and Reports Fourth Quarter and Year-End 2023 Financial Results (GlobeNewswire) - "BRIUMVI U.S. net product revenue of $39.9 million and $88.8 million for the fourth quarter and full year of 2023, respectively....2024 Development Pipeline Anticipated Milestones: Commence clinical development of subcutaneous BRIUMVI; Commence a trial evaluating BRIUMVI in an additional autoimmune disease outside of multiple sclerosis (MS); Commence a trial evaluating azer-cel in autoimmune disease; Present data from the ENHANCE Phase 3b CD20 switch trial at multiple conferences throughout the year."

New trial • P3 data • Sales • Immunology

MaxCyte Signs Strategic Platform License with Imugene to Advance their Cancer Immunotherapy Programs (GlobeNewswire) - "MaxCyte, Inc...and Imugene...today announced the signing of a strategic platform license (SPL)....Under the terms of the agreement, Imugene obtains non-exclusive clinical and commercial rights to use MaxCyte’s Flow Electroporation technology and ExPERT platform. In return, MaxCyte is entitled to receive platform licensing fees and program-related revenue....With our new partnership, we will continue to support the development of azer-cel along with additional novel cell therapy programs."

Licensing / partnership • Hematological Malignancies • Oncology

TG Therapeutics Provides Preliminary Fourth Quarter and Full Year 2023 Net Revenue and 2024 Anticipated Milestones (GlobeNewswire) - "2024 Development Pipeline Anticipated Milestones: Commence clinical development of subcutaneous BRIUMVI; Commence a trial evaluating BRIUMVI in additional autoimmune diseases outside of Multiple Sclerosis (MS); Commence a trial evaluating azer-cel in autoimmune disease; Present data from the ENHANCE Phase 3b CD20 switch trial at multiple conferences throughout the year."

Clinical • New trial • P3 data • Immunology • Multiple Sclerosis