Chimeric Therapeutics accelerates development of CAR T therapy as it looks to boost pipeline with additional therapies

Chimeric Therapeutics Ltd (ASX:CHM) is rapidly accelerating the development of its chlorotoxin CAR T therapy (CLTX CAR T) cell therapy as it looks for additional therapies to bring into its pipeline.  The clinical-stage biotech company is looking at more curative therapies for patients with cancer, and not just therapies that delay disease progression.  Chimeric Therapeutics chief operating officer Jennifer Chow said: “The company is now focused on its pipeline because we do believe that by building out a bigger pipeline or a stronger pipeline with additional assets that have the same type of promise to patients, we're actually going to be able to help more patients in the long term.” Chimeric’s CAR T cell therapy uses a unique tumour-targeting domain – deathstalker scorpion venom – to look specifically for glioblastoma cells, the most fatal brain cancer (GBM). CLTX CAR T-cells utilise chlorotoxin (CLTX), a peptide component of scorpion venom, as the tumour-targeting component of the Chimeric antigen receptor (CAR), which is programmed to seek out an antigen on a tumour and kill it, effectively leveraging on the patient’s own cells to treat the cancer. The therapy is a novel immunotherapy that has the potential to extend the range of solid tumours targetable by CAR T cells and has the scope to deliver a broad immune-oncology platform. "Significant milestone" The company has initiated the treatment of the first patient in the second dose cohort in City of Hope’s Phase 1 clinical trial evaluating the safety and tolerability of its CLTX CAR T) cell therapy.  This milestone marks the introduction of dual routes of administration of CLTX CAR T cells with both intracranial intratumoral (ICT) and intracranial intraventricular (ICV) dosing.  Chow added: “We are very encouraged by the continued progress of the trial, moving to this important next phase with dose escalation and dual routes of administration. “This is another significant milestone in the development of this important therapy for patients with progressive or recurrent glioblastoma.” City of Hope’s Phase 1 clinical trial is expected to enrol 18 to 36 patients with MMP2+ progressive or recurrent glioblastoma over a 24-month period. CLTX CAR T therapy CLTX CAR T cell therapy is a potentially best-in-class CAR T cell therapy that has the potential to address the high unmet medical need of patients with recurrent/progressive GBM. Research to develop the intellectual property covering this CAR T cell therapy took place at City of Hope. CLTX has been shown in preclinical models to bind more broadly and specifically to GBM cells than other targets like EGFR, HER2 or IL13Rα2. In preclinical models, CLTX CAR T cells also demonstrated potent antitumor activity against GBM while not exhibiting any off-tumour recognition of normal human cells and tissues, indicating a potentially optimal safety and efficacy profile. CLTX CAR T abstract at ASCO meeting Chimeric Therapeutics had the first CLTX CAR T abstract accepted for presentation at the prestigious annual meeting of the American Society of Clinical Oncology (ASCO) in early June. The abstract highlights City of Hope’s phase 1 clinical trial design and objectives for CLTX CAR T. GBM an unmet medical need GBM accounts for 60% of brain tumours in adults and has a poor prognosis with a five-year survival of only 5.1% and a median overall survival of 10 months. According to the National Cancer Institute, there are around 23,820 cases per year of brain and other nervous system cancers in the US, and another 64,600 in Europe, according to the International Agency for Research on Cancer. In its research report in January, Edison noted that if the program yields positive data, the US Food and Drug Administration (FDA) may grant a breakthrough therapy designation (BTD), which would help accelerate the program development. There are 15 separate active trials within GBM using CAR T but only five are sponsored by companies while the rest are at the academic stage. Further Chimeric is only one of two companies outside of China, leading the broker to think that Chimeric has the opportunity to be a leader in this area if it advances the CLTX-CAR T program. Future direction Results from this first-in-human Phase 1 study are expected to demonstrate the safety and feasibility of dual delivery of CLTX-CAR T cells in patients with recurrent or progressive GBM. The Phase 1 study will also determine the maximum tolerated dose and the recommended Phase 2 dosing plan.