LTX-315 increases the clinical outcome of cancer immunotherapy

Recent developments of immunotherapy have demonstrated a significant clinical impact in the field of cancer treatment. The introduction of immune checkpoint inhibitors (ICIs) has greatly improved the clinical efficacy of cancer treatment. ICIs work by releasing natural brakes on the immune system so that immune cells, called T cells, can recognize and attack tumors. Unfortunately, only a low percentage of patients experience durable response after treatment with ICIs, often due to a low presence of T cells within the cancer. Thus, to enable and increase the effect of ICIs, patients with tumors that lack T-cell infiltration may require therapeutic interventions to restore T-cell entry into the tumor. Lytix Biopharma has developed a first in class oncolytic peptide, LTX-315, which has demonstrated complete regression and long-lasting tumor-specific immune responses in preclinical animal models. Clinical Phase I study has documented that intra-tumorally administered LTX-315 has an acceptable safety profile, is clinically active and contributes to immune-mediated anticancer activity. The primary objective of this project is to document in clinical and preclinical studies that LTX-315 increases the infiltration of immune T cells in tumors and thereby make them more responsive to other types of immunotherapy. Lytix Biopharma is now pursuing two different strategies to utilize LTX-315 in the treatment of several cancer indications. First, LTX-315 is being developed as a technology to invoke tumor specific T cells that can be harvested from the tumor, expanded and infused back to the patient as part of an adoptive transfer regimen. A study where patients with soft-tissue sarcoma receive LTX-315 followed by adoptive T-cell transfer, is ongoing at Herlev Hospital Copenhagen. Second, based on the data from Phase I studies, the dosing regimen of LTX-315 has been assessed and optimized to position LTX-315 as a therapeutic in combination with checkpoint inhibitor pembrolizumab in an ICIs refractory patient population, a patient population with limited therapeutic options. This study has already been initiated at MD Anderson Cancer Center TX, US. We believe LTX-315 has the potential to bring the advances in immune-oncology to a greater proportion of cancer patients and that LTX-315 will improve the clinical benefit in patients where ICIs have a sub-optimal efficacy.

The ability of LTX-315 to induce T-cell infiltration into cold tumors was assessed in genetically engineered mouse models that were resistant to conventional chemo- and immuno-therapy. LTX-315 showed strong anticancer effect that was associated with increased T-cell infiltration into the tumor. In a triple negative breast cancer model that is resistant to checkpoint inhibitors, LTX-315 showed significant synergy with chemotherapy, radiation and checkpoint inhibitors. In a Phase II single-centre study (ATLAS-IT-04), the safety and efficacy of LTX-315 and adoptive cell therapy in patients with advanced soft tissue sarcoma was assessed. Enrollment has been completed and outcome assessments are ongoing. In a Phase II multicenter study, the safety and efficacy of LTX-315 in combination with pembrolizumab will be evaluated in patient population refractory to checkpoint inhibitors. The aim is to document the ability of LTX-315 to enhance the patient´s responsiveness to checkpoint inhibitor.

Cancer is a life threatening disease despite the development of various treatments during the last years. The development of immune checkpoint inhibitors (ICI) represents a major advance in the treatment of certain cancers. Such compounds release the 'brakes' on the important T cells, which kill the cancer cells. Although ICIs have shown great promise in the fight against cancer, only a limited percentage of patients demonstrate beneficial response to immunotherapy. Recent data indicate that there is a correlation between pre-existing T cell levels in the tumour and a positive clinical outcome. Thus, there is a critical need in additional therapeutic interventions to increase the number of T cells in patients with no or low levels of T cells in their tumours. Lytix Biopharma has developed a first in class oncolytic peptide, LTX-315, which has demonstrated complete regression and long-lasting tumour-specific immune responses in preclinical animal models. In two phase I trials with a total of 42 patients, LTX-315 has demonstrated a modest safety profile and some evidence of anti-tumour activity. In addition, the data have indicated that LTX-315 increases T cell infiltration in injected tumours. The primary objective of this project is to document in clinical and preclinical studies that LTX-315 increases the infiltration of immune T cells in 'cold' tumours and thereby makes the 'hot' tumours responsive to other types of immunotherapy. LTX-315 is also being combined with adoptive T cell therapy in patients with a sarcoma, a cancer indication with high medical need. In addition, LTX-315 will be tested in combination with ICI`s and other immune-modulatory agents a multi-arm study to identify the preferred combination strategy to be developed further. We believe LTX-315 has the potential to bring the advances in immune-oncology to a greater proportion of cancer patients and that LTX-315 will improve the clinical benefit in patients where immune checkpoint therapy is currently not working alone.