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12-Jul-2019

MATINS study update

-                 High Clevegen dosing well tolerated: 9 patients dosed to date

-                 Switch of immune cell profiles towards immune activation seen across all study subjects immediately post dosing

-                 Filing of pre-IND package with the FDA

TURKU – FINLAND, 12 July 2019 – Faron Pharmaceuticals Oy (AIM: FARN), the clinical stage biopharmaceutical company, today announces additional data from the open label phase I/II MATINS clinical trial investigating the safety and efficacy of Clevegen, Faron's wholly-owned novel precision cancer immunotherapy, in selected metastatic or inoperable solid tumours.

Dr Markku Jalkanen, Chief Executive Officer of Faron, said: “We are thrilled with the progress the MATINS study has made during the last few months. We believe we have the first macrophage immune checkpoint drug in clinical development promoting immune activation and are encouraged by the latest data indicating potential early efficacy and good tolerability. We expect to progress the cohort expansion phase of the study in Q3 2019 in patients with late-stage colorectal cancer and as more data are generated we will seek guidance from regulators regarding the best and fastest pathway to secure initial approval of Clevegen as a single-agent treatment.

“We also hope to conclude partnering discussions during H2-2019, which should enable us to expand clinical development to include combination studies exploring the potential of Clevegen in combination with existing immunotherapies.”

 

  • Clevegen well tolerated also at high doses

Clevegen dosing reached its planned maximum of 10mg/kg in mid-June, which has continued to be well tolerated. No dose limiting toxicity (DLT) nor maximally tolerated dose (MTD) has been observed so far. The trial includes an option to administer a 20mg/kg dose, which the Company intends to propose to the trial’s independent data monitoring board. Safe administration of this higher dose would demonstrate a high tolerability and an unusually wide safety margin for Clevegen compared to other immuno-oncology (IO) products. This Directors believe this could allow the Company to move forward rapidly and initiate new clinical studies in first-line and neo-adjuvant study settings and would, in turn, help to demonstrate the full potential of Clever-1 blockade early in the treatment pathway, accelerate time-to-market and increase the market potential of Clevegen.

 

  • Continuous induction of immune activation

All MATINS study subjects have consistently shown a switch in their immune cell profiles towards increased immune activation, observed by an increase in CD8+ cells, an increased in the CD8+/CD4+ ratio, a decrease in regulatory T-cells (T-regs) and a substantial increase in mobile natural killer (NK) cells in the blood. These changes are measurable immediately post-dosing, indicating a dynamic response in the immunological switch to immune-activation after the immunotherapeutic blockade of Clever-1.

Latest data also show that dose escalation results in prolonged Clever-1 occupancy of the blood monocytes during the first two weeks of the three-week dosing cycle before a decrease to baseline levels prior to the next dosing cycle. Longer exposure of blood monocytes to Clevegen is also expected to induce a stronger pro-inflammatory response in study subjects.

 

  • Further molecular evidence of immune activation

A new discovery following study of subjects’ cellular responses, has been the identification of an increase in interferon gamma (IFNγ) production by the host immune system, accompanied by an increase in circulating Th1 differentiated CD4+ and CD8+ T cells. The Company believes the decrease in tumour burden seen in the partial responder is partially (if not completely) explained by this effect of Clevegen on the immune system. Blood myeloid cell analyses also indicate that the proportion of CD163/CD206 positive cells (considered as M2 type immunosuppressive myeloid cells) decrease, as expected, among the whole CD14 positive monocytes of the responder. This is consistent with the M2 to M1 immune switch in their immune profile towards more immune activation, induced by Clevegen, which has been previously observed in animal models.

 

  • Anti-cancer responses continue in the clinics

Among the nine subjects dosed so far, across three clinical trial sites in Finland and the UK, two subjects have shown clinical anti-cancer responses. The first patient, a partial responder with colorectal cancer (CRC) whose initial treatment progress was announced on 11 April 2019, showed a continuation of lung metastasis shrinkage according to the latest tumour imaging report at the end of May. The subject’s tumour load marker CEA (carcinogenic embryonal antigen), which measures tumour mass of CRC, has also normalised. A second subject with CRC has shown an initial decrease in CEA (-40%) and tumour stabilization.

Faron is investigating why the observed immune activation has not turned into anti-tumour activity in all study subjects. In part, the Company believes the patient’s immune system receiving Clevegen as a last line of therapy could have been adversely affected by the underlying therapies they have received prior to taking part in the MATINS study, as previous chemotherapies can inactivate bone marrow, preventing revitalization of the immune system. Majority of patients have received 5-7 different treatment lines prior entering the MATINS study.

  • Expanding clinical development plans

These data support Clevegen’s potential, with promising single-agent activity as a last-line therapy in CRC patients who are refractory to all other treatment options. The Company intends to keep the CRC expansion cohort open and enrolling and while more data is generated, to approach regulatory authorities to seek scientific advice regarding the path to regulatory approval. On the basis of Clevegen’s current safety profile and potential in patients who have exhausted by all other treatment options, the Company believes it may seek initial regulatory approval supported by data from the expanding MATINS trial by 2022. Faron also intends, subject to regulatory approval, to amend the MATINS trial to allow inclusion of hormone receptor-positive breast cancer, gastric cancer and uveal melanoma, based on striking translational data on CLEVER-1 positive cancer types and current poor survival rates. The Directors believe that earlier lines of treatment for these illnesses which currently lack successful treatments may be possible based on the safety profile of Clevegen seen to date and would allow Clevegen to activate more naïve and responsive immune systems.

Faron has recently also filed a pre-IND package to the FDA. If accepted, Faron plans to open new sites in the US and facilitate expansion of the CRC cohort as fast as possible. Similarly, Faron is planning to include top cancer centres in France and Spain as the next European countries to join the MATINS trial.

 

  • Clever-1 expression predicts resistance to other immune-oncology (IO) treatments

Increasing data from IO-treated patients has become available through publicly-accessible data sources. Interestingly, data from The Cancer Genome Atlas (TCGA, the National Cancer Institute, USA) indicate that tumours with high Clever-1 (also known as Stab-1) expression do not respond to current IO treatments (p<0.00001) and correlates to a decreased survival (p<0.001). This finding strongly supports earlier research indicating the potential synergistic anti-tumour benefit when immunotherapeutic blockade of Clever-1 is combined with other IO treatments. It also supports the potential of measuring Clever-1 (e.g. from blood myeloid cells) to provide selection criteria for current IO treatments which lack good biomarkers.

 

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").

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Last Updated: 12-Jul-2019