onCARlytics (CF33-CD19) / Imugene - LARVOL DELTA

Imugene secures core US patent for onCARlytics virotherapy platform (Proactiveinvestors) - "Imugene Ltd...has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for its patent application covering the onCARlytics oncolytic virotherapy platform, CF33-CD19. The approval secures protection for the method of composition and method of use of the technology until August 10, 2038..The patent, titled Oncolytic Virus Expressing a CAR T Cell Target and Uses Thereof, marks a strategic advance in the US, the largest healthcare and oncology market globally. It follows a similar allowance in China earlier this year, reinforcing Imugene’s growing intellectual property position in major therapeutic regions."

Patent • Solid Tumor

A Study of onCARlytics (CF33-CD19) in Combination With Blinatumomab in Adults With Advanced or Metastatic Solid Tumors (OASIS) (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Imugene Limited | N=33 ➔ 50

Enrollment change • Oncology • Solid Tumor

Imugene Advances Phase 1 onCARlytics Trial with IV Dose Escalation for Solid Tumours (Proactiveinvestors) - "Imugene Ltd has cleared the first dose level in the intravenous (IV) combination arm of its Phase 1 onCARlytics clinical trial, following Cohort Review Committee (CRC) approval. The OASIS study targets adult patients with advanced or metastatic solid tumours and will now proceed to a higher dose level as part of its planned escalation process....The trial is being conducted across seven sites in the United States, including City of Hope, MD Anderson Cancer Center, and University of Pittsburgh, with potential expansion to 10 sites. Full recruitment is expected to include 40–50 patients with advanced, treatment-resistant solid tumours."

Trial status • Solid Tumor

OnCARlytics patent allowance in China (Imugene Press Release) - "Imugene Limited...is pleased to announce receipt of a Notice of Allowance from the Chinese Patent Office, for City of Hope’s patent application number 201880064280.9 which protects the CD19-expressing oncolytic virus, onCARlytics. The patent, titled 'ONCOLYTIC VIRUS EXPRESSING A CAR T CELL TARGET AND USES THEREOF' protects the method of composition and method of use of onCARlytics through to 2038. Exclusively licensed to Imugene, OnCARlytics is a CD19-expressing oncolytic virus that enters solid tumour cells and forces them to express the CD19 protein on the cell surface, presenting a target for CD19 targeting therapies."

Patent • Solid Tumor

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

Phase 1 onCARlytics Trial Doses First Patient in Intratumoural (IT) Combination Arm (Imugene Press Release) - "The colorectal cancer patient was dosed at Northwestern University...Imugene Limited...announced the dosing of the first patient in the intratumoural (IT) combination arm of its Phase 1 onCARlytics (CF33-CD19) clinical trial. This development is part of the OASIS trial, which is designed to assess the safety and efficacy of Imugene's CD19 oncolytic virotherapy in patients with advanced or metastatic solid tumours...The OASIS trial is a Phase 1 dose escalation study that explores two routes of administration, intratumoural (IT) injection and intravenous (IV) infusion. onCARlytics, a CD19-expressing oncolytic virus, is being investigated both as a monotherapy and in combination with the CD19-targeting bispecific antibody blinatumomab, an established cancer immunotherapy....Subject to the rate of patient enrolment, preliminary IT and/or IV combination status is expected in the fourth quarter of 2024."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of OnCARlytics (CF33-CD19) in Combination with Blinatumomab in Adults with Advanced or Metastatic Solid Tumors (OASIS) (clinicaltrials.gov) - P1 | N=33 | Recruiting | Sponsor: Imugene Limited | N=52 ➔ 33 | Trial completion date: Sep 2025 ➔ May 2029 | Trial primary completion date: Sep 2024 ➔ Jun 2027

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Combination therapy with the oncolytic virus CF33-CD19 and blinatumomab for the treatment of advanced solid tumors. (ASCO 2024) - P1 | "doi: 10.1126/scitranslmed.aaz1863. PMID: 32878978."

Combination therapy • IO biomarker • Metastases • Oncolytic virus • Oncology • Solid Tumor • CD19

Imugene doses first patient in Phase 1 onCARlytics IV infusion combination trial (Proactiveinvestors) - "Imugene Ltd...dosed the first patient in the intravenous (IV) infusion combination arm of its Phase 1 onCARlytics trial. The patient, diagnosed with cholangiocarcinoma, received treatment at City of Hope in California....The trial began dosing its first IV monotherapy patient with bile tract cancer in February, with early combination data expected by Q4 2024."

P1 data • Trial status • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

ALA‐101 + ONCARLYTICS COLLABORATION UPDATE (Arovella Therap Press Release) - "Arovella Therapeutics Ltd...announces that the partnership to combine ALA-101 and onCARlytics has ended...On 26 September 2022, Arovella announced that it had entered into a research collaboration with Imugene to combine Arovella’s ALA-101 with Imugene’s onCARlytics platform. Imugene has advised Arovella that it no longer wishes to continue the collaboration, which will be terminated with immediate effect. As such, in vivo data for the combination of ALA-101 and onCARlytics will no longer be generated....The termination of the collaboration will not impact Arovella’s development of ALA-101 for CD19-positive blood cancers. Since initiating the Imugene collaboration 18 months ago, Arovella has also secured a globally leading target for gastric and pancreatic cancers (claudin 18.2) and its IL-12-TM armouring technology, which it will continue to develop for a range of solid tumours. There is no financial impact from the cessation of the collaboration for Arovella."

Licensing / partnership • Hematological Malignancies • Oncology • Solid Tumor

Phase 1 onCARlytics solid tumour trial advances to combination arm treatment (GlobeNewswire) - "Imugene Limited...is pleased to announce that its Phase 1 clinical trial of CD19 oncolytic virotherapy drug candidate onCARlytics (on-CAR-19, CF33-CD19 HOV4) has cleared its first cohort within the intratumoral monotherapy arm of the study and is therefore ready to commence combination dosing solid tumour patients with CD19 targeting drug blinatumomab (Blincyto marketed by Amgen)....OASIS is a dose escalation trial that will be conducted across multiple sites across the United States, with 52 patients proposed to take part in the trial."

Trial status • Oncology • Solid Tumor

Phase 1 onCARlytics trial doses first patient in intravenous monotherapy arm (Imugene Press Release) - "Imugene Limited...is pleased to announce that its CD19 oncolytic virotherapy drug candidate onCARlytics (on-CAR-19, CF33-CD19 HOV4), has dosed the first patient in the intravenous monotherapy arm of the Phase 1 clinical trial...Known as OASIS, the first-in-class clinical trial is targeting adult patients with advanced or metastatic solid tumours....OASIS is a dose escalation trial being conducted in the United States, with the first IV patient dosed at City of Hope in California. Additional sites are expected to open for recruitment across the US with 52 patients proposed to take part in the trial."

Trial status • Oncology • Solid Tumor

Imugene thrilled as first patient dosed in Phase 1 OASIS trial (Yahoo Finance) - "Imugene Ltd...has marked a milestone with the start of its Phase 1 clinical trial for onCARlytics, a CD19 oncolytic virotherapy drug candidate. The trial, known as OASIS (Oncolytic Assessment and Safety in Solid Tumours), represents a world-first in clinical research, combining CD19 oncolytic virotherapy with a CD19 targeting bispecific monoclonal antibody, blinatumomab (Blincyto^® Amgen). The primary objective of the OASIS trial is to assess the safety and tolerability of onCARlytics (CF33-CD19) when administered intravenously or intratumorally in combination with blinatumomab."

Trial status • Oncology • Solid Tumor

A Study of onCARlytics (CF33-CD19) in Combination With Blinatumomab in Adults With Advanced or Metastatic Solid Tumors (OASIS) (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: Imugene Limited | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Oncology • Solid Tumor

A Study of onCARlytics (CF33-CD19) in Combination With Blinatumomab in Adults With Advanced or Metastatic Solid Tumors (OASIS) (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: Imugene Limited

Combination therapy • Metastases • New P1 trial • Oncology • Solid Tumor

Oncology stocks advance at pace despite lukewarm market (Proactiveinvestors) - "...Arovella intends to achieve several critical milestones, including:...Reporting initial animal data on ALA-101 in combination with Imugene’s onCARlytics (H2 CY23); Optimising and scaling up its CAR-iNKT manufacturing process suitable for phase I clinical trials, including completing cGMP manufacture of its lentiviral vector (H2 CY23); Completing Investigational New Drug (IND)-enabling non-clinical safety and efficacy studies (H1 CY24); Manufacturing clinical batches for phase I clinical trials (H1 CY24); Securing an Investigational New Drug (IND) application with the FDA and/or regulatory filing with TGA to conduct a phase I clinical trial in Non-Hodgkin’s lymphoma (H2 CY24)..."

Commercial • IND • New P1 trial • Non-US regulatory • Preclinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Imugene wins US FDA approval to begin onCARlytics first-in-class clinical study (Proactiveinvestors) - "Imugene Ltd...has received the US Food and Drug Administration (FDA) Investigational New Drug (IND) approval to begin a first-in-class clinical study for its oncolytic virotherapy candidate onCARlytics (on-CAR-19, CF33-CD19, HOV4). In a giant leap forward, the clinical stage immuno-oncology company can now begin patient recruitment and dosing in the clinical study for the onCARlytics platform in patients with solid tumours."

IND • Oncology

Effective Combination Immunotherapy Using onCARlytics and Artemis® CD19 T Cells Against Hepatocellular Carcinoma (HCC) (ASGCT 2023) - "Currently, there are six systemic therapies available for patients with advanced disease including atezolizumab in combination with bevacizumab, lenvatinib, regorafenib, cabozantinib and ramucirumab while curative treatments include ablation, surgical resection, and liver transplantation...We have harnessed this capability of OV and developed a chimeric vaccinia-based OV called CF33-CD19t (onCARlytics) that delivers a non-signaling, truncated CD19 (CD19t) antigen to solid tumors allowing CD19-specific T cells to target them...In addition, this combination approach demonstrated impressive in vivo anti-tumor responses in a human xenograft HepG2 tumor model. By using this combination OV and CAR T cell strategy, we have now broadened the utility of CD19 ARTEMIS® T cells to otherwise target-less tumors such as HCC, which we anticipate can be applied to a wide array of solid cancers as an effective immunotherapy approach."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • Transplantation • AFP • CD19 • GPC3

"#onCARlytics and #ArtemisTcells combination presented as part of abstract at #ASGCT23 $IMU https://t.co/Oyl4wmYGeQ" (@1stOncology)

Combination immunotherapy using a novel chimeric oncolytic virus to redirect CD19 bispecific T cell engagers to target solid tumors (SITC 2022) - "Building on this, we generated an OV that expresses a non-signaling, truncated CD19 antigen (CF33-CD19t or onCARlytics, in collaboration with Imugene Limited), onto the surface of infected tumor cells prior to virus mediated tumor lysis, which redirected CD19-targeting chimeric antigen receptor (CAR) T cell activity against solid tumors (Park et al . Results Tumors infected with CF33-CD19t along with blinatumomab show specific tumor cell killing in vitro and robust anti-tumor efficacy using in vivo human triple-negative breast cancer xenograft models. Conclusions Using this approach, we show that a clinically-approved CD19-directed BiTE can be combined with oncolytic viruses to activate and redirect endogenous anti-tumor immunity against solid tumors."

Oncolytic virus • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Breast Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Liver Cancer • Lung Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD19

CF33-CD19t Oncolytic Virus (onCARlytics) in Combination with Off-the-shelf Allogeneic CyCART-19 T Cells Targeting de novo CD19+ Solid Tumors (SITC 2022) - "This combination approach demonstrated impressive in vivo anti-tumor response in human tumor xenograft models. Conclusions In summary, our results have demonstrated that further development of this combination immunotherapy for the potential treatment of a wide array of solid tumors is warranted."

Combination therapy • Oncolytic virus • Hematological Malignancies • Oncology • Solid Tumor • CD19

CF33-CD19t oncolytic virus (onCARlytics) targets hepatocellular carcinoma (HCC) and in combination with Artemis CD19 T cells results in significant tumor killing (SITC 2022) - "For majority of patients with advanced-stage disease, treatment with agents such as sorafenib, lenvatinib, and atezolizumab/bevacizumab and other investigational agents yield modest success rates and justify the need for further development of new therapies. Results When administrated after onCARlytics, CD19 ARTEMIS® T cells were able to induce potent cytolytic activity against HCC tumor cells and demonstrated robust in vivo anti-tumor efficacy against human HCC tumor xenografts. Conclusions In summary, ARTEMIS® CD19 T cells combined with onCARlytics is a potentially effective immunotherapy strategy for the treatment of patients with HCC and can be applied to other solid tumors."

Combination therapy • Oncolytic virus • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • AFP • CD19 • GPC3

Imugene’s onCARlytics to be showcased in three abstracts at SITC Annual Meeting (1stOncology) - "Imugene Limited...reported that its onCARlytics (CF33-CD19) oncolytic virus technology will be featured in three abstracts at the renowned Annual Meeting for the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), to be held in Boston, USA on 8-12 November 2022."

Preclinical • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

"#Imugenes #OnCARlytics to be showcased in three abstracts at #SITC22 $IMU https://t.co/xfgyzilvNZ" (@1stOncology)

Oncology

Imugene and Eureka Therapeutics Announce Strategic Collaboration to Accelerate Advancement of Oncolytic Virus and T-Cell Therapy in Solid Tumours (Businesswire) - "The Collaboration will evaluate Eureka’s anti-CD19 ARTEMIS® T-cell therapy in combination with Imugene’s CD19-expressing oncolytic virus onCARlytics in solid tumours Potential to address lack of tumour-specific targets in solid tumours for T-cell therapies by using oncolytic virus to force tumours to express CD19...Imugene Ltd...and Eureka Therapeutics, Inc...announced a strategic collaboration to evaluate Imugene’s CD19 oncolytic virus onCARlytics technology in combination with Eureka’s anti-CD19 ARTEMIS® T-cell therapy for the treatment of solid tumours."

Licensing / partnership • Oncology • Solid Tumor