Clevegen downregulates a range of major immuno-oncology (IO) checkpoints in MATINS cancer patients Biomarker analysis could guide future combination therapies with Clevegen

TURKU – FINLAND – Faron Pharmaceuticals Oy (AIM: FARN, First North: FARON), the clinical stage biopharmaceutical company, today announces new data from MATINS -trial patients to be presented at the ESMO Immuno-Oncology Congress 2019 in Geneva, Switzerland. Faron’s scientific network will present the data in a plenary lecture and more detailed biomarker data in a Mini Oral session.

The phase I/II MATINS clinical trial is investigating the tolerability, safety and efficacy of Clevegen, Faron's wholly-owned novel precision cancer immunotherapy (Clevegen) targeting Clever-1 positive tumour associated macrophages (TAM), in selected metastatic or inoperable solid tumours. The Company has previously announced that Clevegen administration results in an immune switch from immune suppression to immune activation.

First available set of cell surface biomarker data from a group of seven patients to be presented at the congress show that: 1) anti-Clever-1 treatment in cancer patients decreases a broad range of checkpoints including PD-1, PD-L1, CTLA-4, OX40, 41BB, LAG3 and 2) co-stimulation markers CD28 and ICOS on circulating T cell populations whereas 3) it increases the expression of activation markers CD25 (IL-2RA), CXCR3 and CD69. In addition, anti-tumour responses with anti-Clever-1 treatment are found to associate with an increase in plasma interferon gamma (IFN-gamma), which is one of the tools the immune system is using to fight against cancer.

The analysis of checkpoints (also known as exhaustion markers) and activation markers can potentially also be used to guide the best possible checkpoint inhibitor(s) combination treatment with anti-Clever-1 therapy. Cell surface markers like PD-1, PD-L1, CTLA-4, LAG3, and TIM, can then be used to monitor a patient’s response to anti-Clever-1 therapy and to evaluate the need for combination therapy in addition to anti-Clever-therapy. The present finding potentially provides a method for choosing the best combination agent(s) to initiate treatment together with anti-Clever-1 therapy after observed changes in one or more checkpoint or activation marker expression. The Company has filed a related patent to protect this method.

Commenting on these findings, Dr. Markku Jalkanen, Faron’s CEO, said: “We have always believed Clever-1 to be a master regulator of immunity, but we are very encouraged to find that Clevegen can down regulate a range of major inhibitory immune checkpoints, that current IO therapies aim to suppress. We intend to carry out further analysis of other MATINS patients and aim to understand which combination of IO therapies would build the optimal host immune activation for various cancer types or individuals. To have one single and safe treatment as early as possible would improve patient outcome. These results indicate that Clevegen treatment could potentially allow increased efficacy of other IO treatments through the biomarker analysis of patient’s blood cells post Clevegen induced immune activation, finally offering a biological rational to guide combination therapies.”  

About the MATINS study

The MATINS study is the first-in-human open label Phase I/II clinical trial with an adaptive design to investigate the safety and efficacy of Clevegen in selected metastatic or inoperable solid tumours. The selected tumours under investigation are cutaneous melanoma, hepatobiliary/hepatocellular, pancreatic, ovarian and colorectal cancer, all known to host a significant number of Clever-1 positive tumour associated macrophages (TAM). All together these five target groups consist of approximately 2 million annual cases worldwide. Cancer patients with high Clever-1 expression are identified with a simple blood myeloid cell staining with Clevegen ("liquid biopsy").

Part I of the trial deals with tolerability, safety and dose escalation to optimize dosing. As the trial is an open label study, the Company expects to report findings as the dosing progresses. The cohort expansion during part two will focus on identification of patients who show an increased number of Clever-1 positive circulating monocytes and the safety and efficacy of the treatment. The Company has already announced that colorectal cancer (CRC) has been selected as the first expansion cohort in Part II. During Part III, the main focus will be on assessing the efficacy of Clevegen on study subjects who show an increased number of Clever-1 positive circulating monocytes, making the treatment precisely targeted and maximizing the chances of success for efficacy. The treatment, if successful, may ultimately be used as a standalone therapy or in combination with other immunotherapies like PD-1 inhibitors.

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 ("MAR").