TILT Biotherapeutics has joined forces with Merck and Pfizer to evaluate the combination of its oncolytic adenovirus TILT-123 ((Ad5/3-E2F-D24-TNFa-IRES-IL2) with the duo’s avelumab for the treatment of solid tumours that are refractory to routine modalities.
TILT-123 has been engineered to selectively replicate only in cancer cells that produce the TNFa and IL-2 immunostimulatory cytokines locally at the tumour as shown in various in vivo and in vitro studies.
The oncolytic adenovirus has been designed to have increased entry to cancer cells, and can be administered by systemic and also local routes, which makes it potentially applicable for the treatment of wide range of cancers, said TILT Biotherapeutics.
The company claims that the characteristics of TILT-123 make it suitable particularly for evaluation with checkpoint inhibition as both therapies are considered to work in parallel to maintain anti-tumour immune responses. Immunosuppression in tumour microenvironment is counteracted by the combination of virus replication, spreading of tumour antigen and the cytokines, said TILT Biotherapeutics.
On the other hand, avelumab, which has been co-developed by Merck and Pfizer, is a human anti-programmed death ligand-1 (PD-L1) antibody, which has been designed to engage both the adaptive and innate immune functions.
The drug, which has the trade name Bavencio, has been approved in combination with axitinib by the US Food and Drug Administration (FDA) for the first-line treatment of patients having advanced renal cell carcinoma (RCC). It also has accelerated approval for the treatment of metastatic Merkel cell carcinoma (mMCC) among other indications in the US.
Currently, Avelumab has approval for MCC in more than 45 countries with most of the approvals in a broad indication that is not contained to a particular line of treatment.
According to TILT Biotherapeutics, anti-PD-L1 is required for disabling the ability of cancer cells to suppress T-cell activity through PD-1 signalling. The company believes that there is a potential beneficial interaction between the anti-PD-L1 and oncolytic adenovirus treatments.
TILT Biotherapeutics plans to carry out clinical trials with TILT-123 in Europe and the US in multiple solid tumour indications.
TILT Biotherapeutics CEO and founder Akseli Hemminki said: “We are pleased to initiate a collaboration with Merck KGaA, Darmstadt, Germany and Pfizer to translate our findings into patients. Preclinical results with TILT-technology and anti-PD(L)1 agents suggest immune activation and efficacy in certain animal models.”