OnCARlytics (Imugene)

Five clinical trials across three prioritized immuno-oncology platforms with encouraging safety and efficacy signalsEncouraging early results from the VAXINIA (CF33) oncolytic virus trial, including one complete response in a patient with cholangiocarcinoma (bile tract cancer) and two partial responses in patients with melanoma; two out of three of the responses were achieved with monotherapy CF33; receipt of US FDA Fast Track Designation for bile duct cancerPotential near-term registrational study and fast-to-market strategy for azer-cel allogeneic CAR T therapy in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) who progressed after autologous CAR T therapiesWorld-first onCARlytics trial designed to convert “targetless” tumors to CD19-expressing solid tumors that are otherwise hard to treat; trial combines a CD19-expressing oncolytic virus with a CD19 targeting drug SYDNEY, Australia, Feb. 22, 2024 (GLOBE NEWSWIRE) -- Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, highlighted recent progress across the company's immuno-oncology portfolio and provided an update on anticipated upcoming milestones. Imugene Managing Director & CEO Leslie Chong said: “We are encouraged by the initial safety and efficacy signals seen to date. Notably, in our Phase 1 MAST CF33 oncolytic virus trial, we’ve seen encouraging response rates during dose escalation, including one complete response in a patient with cholangiocarcinoma, and two partial responses in melanoma as we continue to dose escalate with no safety issues. Importantly, two out of three of these responses were achieved with CF33 monotherapy. In addition, we have seen encouraging response rates with azer-cel, our allogeneic CAR T cell therapy for patients with diffuse large B cell lymphoma who have failed auto CAR T treatments, and we look ahead to a potential registrational trial.” Ms. Chong continued: “In addition, we continue to advance our novel onCARlytics combination immunotherapy program that, in simple terms, a mark-and-kill approach. onCARlytics uses an antigen/target-armed CF33, followed by treatment with a CD19 targeting therapy directed against that antigen or target. We believe onCARlytics may provide a new solution for clinicians to treat previously untreatable solid tumours.” Program Highlights Oncolytic virus (CF33) - a chimeric vaccinia (pox) virus known as CF33 that has the potential to act as both a target delivery vehicle and an oncolytic agent. The engineered CF33 virus selectively replicates itself in tumor cells, causing the cell to rupture, releasing new virus particles capable of infecting other tumor cellsCF33 has demonstrated multiple ways to kill cancer cells: by direct killing, by the activation of immune cells to kill cancer cells, and by priming the tumor environment to enhance the immune response; CF33 has been shown to turn cold tumors hotThe Phase 1 MAST trial assesses the safety and efficacy of CF33 administered alone, or in combination with pembrolizumab and either dosed intravenously (IV) or intratumourally (IT)As of January 2024, 34 heavily pre-treated patients had been dosed with VAXINIAData presented at ASCO-GI in January demonstrated the following: 31 patients were evaluable for efficacyResponse rates seen during dose escalation at doses lower than the current dose In the IT cohorts (14 patients), 7 of 15 (47%) injected lesions had a reduction in tumor burden, 3 lesions were completely eradicated3 patients (21%) had an objective response: 1 monotherapy complete response (CR) by iRECIST in a patient with cholangiocarcinoma who previously failed three lines of chemotherapy; the patient has been in remission for over a year and half2 partial responses in patients with melanoma (skin cancer) by RECIST, one with monotherapy and one in combination with pembrolizumab. In IV cohorts (17 patients), 53% of patients achieved stable disease as their best response All treatments to date have been determined safe and tolerable The company received US FDA Fast Track Designation for bile duct cancer in November 2023Expansion of cholangiocarcinoma and other indications are planned for 2024Biliary tract cancer, also known as cholangiocarcinoma, is a rare but aggressive malignancy that originates in the bile ductsIt’s estimated that the total incident population of biliary tract cancers (BTC) is around 38,000 in the U.S., the EU-4 (Italy, Spain, France, and Germany), the United Kingdom and Japan2 The U.S. accounted for 10,064 total incident cases of BTC in the year 2023, which is expected to increase at a moderate rate2 Azer-cel: allogeneic (off-the-shelf) CAR T cell therapy targeting CD19 for the treatment of hematological malignancies. Allogeneic, or off-the-shelf, CAR T-cell therapy, uses T cells from healthy donors, making the treatment immediately available to patients, more potent, and less expensive than current approved autologous CAR T treatmentsOngoing Phase 1b clinical trial in patients with non-Hodgkin’s lymphoma (NHL) who relapsed following autologous CAR T therapyData from prior Phase 1 azer-cel trial demonstrated clinically meaningful activity with an acceptable safety profile in 84 patients across leading US centres. Results from 18 patients with DLBCL who relapsed from prior autologous CAR T showed: 83% Overall Response Rate (ORR)61% Complete Response (CR)55% of patients achieving durable responses greater than or equal to six months in patients with DLBCL who had relapsed following auto CAR T therapy (n=18) Positive FDA guidance on the potential registrational study, which could start after completion of the confirmation study; if successful, azer-cel has the potential to become the first approved allogeneic CAR T cell therapy for cancerDLBCL is the most common type of NHL, with approximately 80,500 cases per year1 and approximately 30,000 new cases per year in the U.S.Relapsed/refractory DLBCL has a high unmet medical need; 60-65% of patients treated with autologous CD19 CAR T relapse onCARlytics (CF33-CD19) – A novel engineered oncolytic virus (CF33) that can deliver a CD19 target to “targetless” solid tumors that are otherwise hard to treat onCARlytics is a CD19-expressing oncolytic virus that enters tumor cells and forces them to express the CD19 protein on the cell surface, presenting a target for CD19 targeting therapiesSolid cancers like breast, lung, gastric, and colon, etc. don’t have a common target such as CD19 on their cell surface; the goal of onCARlytics is to present a target for CD19 therapiesSolid tumors make up 90 percent of the cancer market; if successful onCARlytics could make CD19 therapy an option to treat patients with solid tumorsThe Phase 1 OASIS trial is a world-first in combining a CD19-expressing oncolytic virus with CD19 targeted therapy (blinatumomab, Blincyto®)The primary objective of the trial is to evaluate the safety and efficacy of onCARlytics, either by intratumoural (IT) injection or intravenous (IV) infusion, either alone, or in combination with blinatumomab, in approximately 52 adult patients with advanced or metastatic solid tumorsThe first patient in the monotherapy IT arm was dosed in October 2023; the first patient in the monotherapy IV arm was dosed in February 2024The next step is to combine onCARlytics with azer-cel allogeneic CAR T therapy, a combination strategy that has shown preclinical proof-of-principle *iRECIST and RECIST: (immune) Response evaluation criteria in solid tumors*PFU: Plaque Forming Unit References: 1NIH National Library of Medicine, PDQ Cancer Information Summaries, May 18, 2023; 2DelveInsight Business Research LLP Biliary Tract Cancers (BTCs) - Market Insight, Epidemiology And Market Forecast - 2032 For more information please contact: Leslie ChongManaging Director and Chief Executive Officerinfo@imugene.com General Investor Enquiriesshareholderenquiries@imugene.com U.S Investor EnquiriesHeather Armstrongharmstrong@imugene.com Media EnquiriesMatt Wright matt@nwrcommunications.com.au Connect with us on LinkedIn @Imugene LimitedFollow us on Twitter @TeamImugeneWatch us on YouTube @ImugeneLimitedJoin us on InvestorHub; investorhub.imugene.com About Imugene (ASX:IMU) Imugene is a clinical stage immuno-oncology company developing a range of new and novel immunotherapies that seek to activate the immune system of cancer patients to treat and eradicate tumours. Our unique platform technologies seek to harness the body’s immune system against tumours, potentially achieving a similar or greater effect than synthetically manufactured monoclonal antibody and other immunotherapies. Our pipeline includes an off-the-shelf (allogeneic) cell therapy CAR T drug azer-cel (azercabtagene zapreleucel) which targets CD19 to treat blood cancers. Our pipeline also includes multiple immunotherapy B-cell vaccine candidates and an oncolytic virotherapy (CF33) aimed at treating a variety of cancers in combination with standard of care drugs and emerging immunotherapies such as CAR T’s for solid tumours. We are supported by a leading team of international cancer experts with extensive experience in developing new cancer therapies with many approved for sale and marketing for global markets. Our vision is to help transform and improve the treatment of cancer and the lives of the millions of patients who need effective treatments. This vision is backed by a growing body of clinical evidence and peer-reviewed research. Imugene is well funded and resourced, to deliver on its commercial and clinical milestones. Together with leading specialists and medical professionals, we believe Imugene’s immuno-oncology therapies will become foundation treatments for cancer. Our goal is to ensure that Imugene and its shareholders are at the forefront of this rapidly growing global market.

Precision BioSciences’ most advanced cell therapy for a type of blood cancer is on track for a pivotal clinical trial, but that study is no longer its responsibility. The biotech is outlicensing rights to the therapy in a deal that extends its cash runway and enables it to focus on its in vivo gene-editing programs. The buyer is Imugene Limited, which is paying $21 million up front for global rights to azercabtagene zapreleucel, or azer-cel, an allogeneic CAR T-therapy for blood cancers. The Australian company will take over developing the therapy for large B-cell lymphoma (LBCL) in patients who have relapsed following treatment with a highly personalized cell therapy made from their own immune cells. Imugene’s license includes an option to develop up to three additional cancer research programs. CAR T-therapy provides a treatment option for advanced cases of blood cancers. The currently available versions of these therapies are autologous, manufactured by harvesting a patient’s immune cells, engineering and expanding them in a lab, and then infusing them back into the patient. It’s a lengthy and cumbersome process, and many companies are trying to improve on it. Durham, North Carolina-based Precision is one of the companies developing CAR T-therapies readily available “off the shelf.” Azer-cel is produced from donor cells engineered by Precision’s proprietary gene-editing technology, ARCUS. The engineering is intended to avoid graft-versus-host disease, a complication risk associated with donor-derived cell therapies. In May, Precision reported data for 61 evaluable patients in a Phase 1 dose-escalation study. The overall response rate was 83%; the complete response rate was 61%. In late July, Precision announced it had received the final minutes of its FDA meeting to discuss the therapy’s path forward. Based on that discussion and azer-cel’s clinical data, the company said it was proceeding with discussions with “multiple potential strategic partners” for its cell therapy assets. Imugene, which is publicly traded in Australia, is a cancer immunotherapy developer. Its pipeline spans an oncolytic virus currently in Phase 1 testing and a B-cell immunotherapy in mid-stage clinical development. The deal with Precision gives the Australian biotech its most advanced program. In a video of the announcement posted to the company’s website, Imugene CEO Leslie Chong said the company expects to begin a registrational study for azer-cel “as early as 2024.” The outlicensing of azer-cel makes Precision a preclinical-stage company again, but one focused on in vivo editing therapies. The company has said its ARCUS platform employs cutting enzymes that are smaller than those in other editing technologies, such as CRISPR. The smaller size enables in vivo edits and complex edits, such as gene insertion. The most advanced in vivo gene editing program in the Precision pipeline is PGENE-HBV, a wholly owned hepatitis B therapy in preclinical development. In regulatory filings, the company said it expects to submit an investigational new drug application in 2024. Precision is also working with Novartis, which last year paid $75 million up front to collaborate in the development of in vivo editing therapies for inherited blood disorders such as sickle cell disease and beta thalassemia. A separate alliance with Eli Lilly is developing an in vivo editing therapy for Duchenne muscular dystrophy. That partnership is also pursuing liver and central nervous system disorder targets, but specific diseases have not been disclosed. Both big pharma companies are providing research funding for the partnered programs. Precision has also a deal with startup iECURE, which has rights to apply the ARCUS technology in four liver indications. The upfront payment from Imugene is a mix of cash and equity. According to a Precision regulatory filing, it’s $8 million in cash and $13 million in convertible notes that will mature on the first anniversary of the deal’s closing date. The transaction also puts Precision in line for an $8 million near-term payment, also in cash and equity. That payment is contingent on successful completion of Phase 1b dosing in patients with relapsed large B-cell lymphoma. Precision could receive up to $198 million in milestone payments, plus royalties from sales of an approved product. For each additional program that Imugene selects, Precision is eligible to receive up to $145 million in milestone payments as well as royalties from sales. In its report of second quarter financial results early this month, Precision reported a cash position of $137.8 million. By offloading its allogeneic cell therapy work, Precision expects to reduce operating expenses by about $20 million. Those savings along with the cash from the Imugene transaction extend Precision’s cash runway through the third quarter of 2025, the company said. “As we pivot our full attention and resources to leveraging the core features of ARCUS for differentiated in vivo gene editing programs, we are prepared to capitalize on the utility of ARCUS to produce a profound impact on diseases in the liver and beyond, including those that are best suited for gene insertion or excision of large defective gene sequences,” CEO Michael Amoroso said in a prepared statement.