Chimeric Therapeutics adds armor to latest cancer fighting cell platform

Cell therapy pioneer Chimeric Therapeutics (ASX: CHM) has obtained positive in vitro data from new testing of its CHM 0301 solution which is aimed at developing a new range of cancer treatments.

A next generation armored natural killer (NK) cell platform, CHM 0301 is already showing significant promise as a potential treatment for cancers such as leukemia.

Chimeric’s latest CHM 0301 NK cell platform is now being evaluated in what is the first clinical trial to combine NK cells with Vactosertib, an oral TGFβ receptor inhibitor.

Key immune-suppressive factor

TGFβ has been identified as a key immune-suppressive factor that is expressed in the tumour microenvironment and is known to inhibit the anti-tumour activity of NK cells and T cells.

Studies have broadly linked TGFβ expression to tumour invasion and metastasis, immune evasion and poor prognosis across multiple types of cancer.

CHM 0301 builds on the successful foundation provided by its CHM 0201 platform, which has previously demonstrated early signs of clinical activity in Acute Myeloid Leukemia (AML) and Colorectal Cancer (CRC) patients.

Two “armoring” upgrades

Dr David Wald, the inventor of the CHM 0201 NK cell platform, says the CHM 0301 NK cell platform adds two “armoring” upgrades to the CHM 0201 cells which are designed to maximise potency, enabling the cells to overcome immune-suppressive tumour microenvironments.

It has been found that CHM 0301 cells express a dominant-negative TGFβ receptor molecule on the cell surface and is able to secrete the immunostimulatory cytokine interleukin 15 (IL-15).

When evaluated with in vitro models of human AML and CRC, CHM 0301 demonstrated significant enhancement of TGFβ resistance and potency compared to first generation CHM 0201 cells.

Notably it was found to be around three times more resistant to TGFβ suppression and provided up to around 25% more potency in the absence of TGFβ.

Studies also discovered an approximately 80% relative increase in potency in the presence of TGFβ.

Successful collaboration research

Dr Wald, the associate director for Basic Research at the Wesley Centre for Immunotherapy at UH Seidman Cancer Centre and Associate Professor of Pathology Case Western Reserve University (CWRU) School of Medicine, is teaming up with Chimeric under a sponsored research collaboration.

In the initial six months of that collaboration Chimeric and Dr Wald’s team designed, produced and characterised CHM 0301 to maximise potency and increase the resistance of CHM 0201 NK cells to TGFβ.

Through the collaboration, an initial manufacturing process was established, building on the proprietary CHM 0201 NK production platform, that delivers viral transduction efficiencies in the range of current chimeric antigen receptor (CAR) T-cell therapies.

“The activity of CHM 0301 is highly encouraging and provides compelling support for this platform as the foundation for a new generation of NK cell therapies,” said Dr Wald.

Next level studies underway

Studies are now looking to further characterise the behaviour and activity of CHM 0301 and to introduce Chimeric’s other developments, CLTX and CDH17 CARs, into its NK cell platform as part of the CHM 1301 and CHM 2301 CAR NK programs.

Eliot Bourk, Chimeric’s chief business officer and head of external innovation, says Dr Wald and his team at CWRU have achieved highly promising in vitro results to date.

“We look forward to further advancing our next-generation armored NK platform and initiating work on our lead CAR NK programs for solid tumours as we continue our collaboration.”

The company has a diversified portfolio that includes leading autologous CAR T cell therapies and NK cell therapies.

Chimeric is progressing developments across multiple different disease areas in oncology with 3 current clinical programs and plans to open additional clinical programs in 2023.