Despite progress in targeted therapy and immunotherapy, lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) representing 85% of total cases. Although the use of immunotherapy (immune checkpoint inhibitors (ICIs)) has been approved with great results in a limited but growing subpopulation of NSCLC patients, a majority of patients still do not respond and develop resistances. The use of ICI(s) with chemotherapy, has shown better efficacy than chemotherapy alone and thus is now considered a standard treatment option for patients with advanced lung cancer, non-eligible for targeted therapy. While these immunotherapy/chemotherapy combinations are the standard of care in most cases, the conventional chemotherapy, given intravenously, presents many limitations in terms of targeted exposure, systemic toxicities, and consequently frequency of treatments. InhaTarget Therapeutics has developed an innovative approach to administer these proven widely used molecules through the pulmonary route and to considerably improve the benefit/risk ratio of the drug, in combination with immunotherapies.
The key value leverage of this approach is based on the following contemplated added values:
Higher frequency of treatment (5 times weekly inhalation for our CIS-DPI product vs every 3 weeks for the conventional iv cisplatin) thanks to the bypass of systemic toxicities with the inhalation route;
Higher exposure of the tumor site to the drug;
A patient-centered approach thanks to the choice of the dry powder formulation, enabling a safe, non-invasive and user-friendly administration at home;
An increased efficacy through (i) the higher exposure of the tumor cells to the cytotoxic drug and (ii) the local immunogenic properties of our inhaled chemotherapies (significant increase of dendritic cells and CD8 T lymphocytes, a higher infiltration by T cells for antitumor activity and an upregulation of PD-L1 in tumor cells). These immunogenic properties make of our CIS-DPI product (and other inhaled chemotherapy products currently under development) an excellent drug candidate for combinations with immunotherapy in the treatment of lung cancer.
Our company lead product is a cisplatin-based dry powder formulation, for the treatment of lung cancer.
Cisplatin is a platinum-derivative chemotherapy drug administered as a standard of care in most lung cancer patients. The new route of administration of this well-known drug aims at proposing the following advantages:
to overcome systemic toxicities, hence increasing the frequency of local treatment,
to increase the local drug exposure, hence inducing a local and anti-tumour immune response through its immunogenic properties.
CIS-DPI is to be administered 5 times weekly (5 days-on – 2 days-off) at the patient’s home, in combination with current Standards of Care. (either pembrolizumab or pembrolizumab combined with an iv platinum-doublet)
Our lead product is currently investigated in a Phase I/IIa trial in 5 clinical centers in Belgium.
To learn more about this trial, visit the clinical trial page.
The company is currently developing a breakthrough technology based on inhaled nanomedicine targeting the STING pathway. STING (stimulator of interferon gene)controls transcription factors IRF3 and NF-kB, which regulate the transcription of sets of genes including type I interferons and pro-inflammatory cytokines. Activation of STING and the subsequent production of type I interferons in the tumour microenvironment induces an anti-tumour immune response.
This makes STING a hot target in immuno-oncology, with the first generation of agonists tested in the clinic less than a decade ago. These faced multiple challenges, the biggest being a short half-life and systemic immune activation when administered intravenously. To overcome these barriers, most agonists inclinical development are injected intratumorally, limiting the type of cancers to these accessible by the clinician.
Our functionalized nanocarrierencapsulating STING agonists, allows an enhanced uptake by a subset ofimmunosuppressive type of tumor associated macrophages (TAMs). The presence ofthese immunosuppressive TAMs is associated with poor outcome in lungadenocarcinoma. Targeting immunosuppressive TAMs does not only results in theproduction of type I interferons key to induce an anti-tumour immune response, but also induce the activation these TAMs toward a pro-inflammatory phenotype, contributing to the anti-tumour defense. This product is a first-in-class medication which is currently in preclinical development.
Moreover, this technology has potential beyond the field of lung cancer. Indeed, recent papers showed that the pharmacological activation of STING blocks SARS-CoV2 infection and that STING activation inhibits multiple families of arbo and respiratory viruses.