Chimeric Therapeutics doses final cohort in brain cancer clinical trial, advances CHM 2101 candidate
Chimeric Therapeutics has several promising candidates under development to treat a range of cancers.
Clinical-stage cell therapy company Chimeric Therapeutics (ASX: CHM) has begun dosing of drug candidate CHM 1101 in the final patient cohort of a phase 1 clinical trial designed to treat the most aggressive and common form of brain cancer glioblastoma.
The company has also progressed its CHM 2101 candidate towards a phase 1a clinical trial.
Chimeric is focused on the discovery, development and commercialisation of cell therapies to treat patients with cancer.
One of its promising drugs candidates is CHM 1101, also known as CLTX CAR-T, is a novel chimeric antigen receptor technology (CAR-T) therapy being developed to target solid tumours.
Chimeric describes CHM 1101 as a first class therapy with the potential to treat recurrent or progressive glioblastoma.
The therapy uses chlorotoxin (CLTX), which is a peptide derived from scorpion toxin. CLTX makes up the tumour targeting component of the CAR-T.
Preclinical trials of CHM 1101 demonstrated “potent” anti-tumour activity against glioblastoma, while normal cells remained unaffected.
Clinical trials
In late January, Chimeric revealed all patients in a third dose cohort of a phase one trial to treat recurrent or progressive glioblastoma with CHM 1101 had successfully passed the 28-day safety follow-up period with no reported dose limiting toxicities reported.
This positive result has now enabled the company to progress to a fourth and final dose cohort which will see patients treated with an increased dose of CHM 1101 cells via dual routes of intra-tumoral (ICT) and intraventricular (ICV) administration.
Dosing has now begun, with patients in the final cohort to receive 440 by 106 CHM 1101 through dual administration routes.
The study is being undertaken in California at City of Hope, one of the largest cancer research and treatment organisations in the United States.
Its objectives are to evaluate the safety and efficacy of the therapy and to establish recommended dosing for a phase two trial.
‘Transformative treatment’
Chimeric chief medical officer Dr Jason Litten said it was “exciting” for the company to progress its “potentially transformative new treatment” for patients with highly aggressive brain tumours.
“Based on this clinical experience, Chimeric looks forward to building upon and expanding this program to deliver new medicines for cancer patients.”
Progressing CHM 2101 to the clinic
Meanwhile, CHM 2101, a novel, third generation CD17 CAR-T therapy is in preclinical development with a planned phase 1a trial in neuroendocrine tumours, colorectal, and gastric cancer.
The company has just completed manufacturing and quality release for CHM 2101 viral vector, which is a key milestone in progressing the drug to clinical stage trials.
Viral vector is considered the backbone for manufacture of CAR-T therapy because it holds the genetic engineering instructions.
Chimeric chief executive officer and managing director Dr Jennifer Chow said a current shortage of vector manufacturing capacity has delayed other cell therapy programs.
“Securing vector supply for the CHM 2101 phase 1A clinical trial marks a significant milestone for advancing CHM 2101 towards the clinic and patients that need novel therapies to treat advanced gastrointestinal and neuroendocrine tumours,” Dr Chow added.
Additional cell therapies in development
In addition to the current CHM 1101 study, Chimeric has planned to launch a second phase 1 clinical trial in metastatic melanoma (skin cancer).
The company said it aims to expand to additional solid tumours in the future.
Another of Chimeric’s treatments under development is CHM 0201, a clinically validated, off-the-shelf natural killer (NK) cell platform.
From this platform, the company plans to initiate development of four new generation NK and CAR NK assets to trial in solid tumours and blood cancers after data from a phase one clinical trial published last year showed safety and efficacy in these indications.
Patents, licence agreements and government support
In mid-2022, a patent was granted in Japan to Chimeric covering certain applications of CAR-T using CLTX, including the company’s clinical-stage asset CHM 1101 and preclinical stage CAR NK and CHM 1301 assets.
Chimeric has licenced the exclusive global rights to intellectual property covering the CLTX CAR-T cells from City of Hope.
Late last year Chimeric also inked an exclusive licence agreement with Case Western Reserve University for CHM 2022 following a 2021 option agreement. This deal provides Chimeric with excusive global rights to the CHM 0201 platform for oncology.
Subsequent to the half year results released this week, the company’s finances were boosted by a research and development tax refund of more than $3 million under the Australian Government’s R&D tax incentive program.