TILT Biotherapeutics Ltd is a Finnish company developing oncolytic virus therapies for cancer. Its lead product, TLT-123 is poised to enter Phase 2 studies in patients with ovarian cancer after having demonstrated that it is safe and able to elicit responses from patients. In an interview, Victor Cervera-Carrascón, the company’s head of business development, gave three reasons why he thought the time is optimal for the biotech industry to pay more attention to oncolytic therapies.
The first is a growing awareness in the medical community about the shortcomings of checkpoint inhibitors and the need to identify new molecules for combination treatments. An oncolytic virus has the potential to boost the response to these immunotherapies, the company believes. A second reason is the improved design and sophistication of oncolytic virus therapies and a third is the prospect of easier administration. TILT is experimenting with an intravenous delivery of its drug instead of the usual intratumoural method.
In a presentation to the ESMO cancer meeting in December 2024, TILT disclosed data showing that the intravenous delivery of TLT-123 was as effective as intratumoural delivery, a finding that the company found very encouraging. “What we have reported at ESMO is first, that our treatment was able to induce anti-tumour immunity and second, that we can use the virus intravenously. That’s actually one of the biggest accomplishments that we’ve done in 2024,” the executive commented.
The oncolytic virus has a long history as a research tool but thus far only one product has been approved for marketing. This is Imlygic (talimogene laherparepvec), developed by Amgen Inc for melanoma, and authorised by the US Food and Drug Administration in 2015. Imlygic is a genetically modified live oncolytic herpes simplex virus injected directly into melanoma lesions where it replicates inside cancer cells, causing the cells to rupture and die.
TLT-123 has a different virus and construction and thus far appears to show a broader effect. It is an adenovirus which encodes for the cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2). Upon administration, the virus causes the tumour cells to break down while simultaneously modifying the immunosuppressive tumour microenvironment.
This is where the concept of a combination therapy comes into play. According to the company, early research has shown that TLT-123 can eliminate a cancer’s ability to evade immune responses, the problem faced by many checkpoint inhibitors. TILT is en route to testing this out. It has two collaborations with Merck & Co Inc to investigate TLT-123 in combination with pembrolizumab in ovarian cancer and refractory non-small cell lung cancer. This will be a chance to prove the concept.
- By Victoria English