Bexmarilimab (Clevegen) development update

Bexmarilimab (Clevegen) development update  -          Accumulating MATINS data build foundation for further clinical development -          Five patient cohorts in MATINS study Part II already fully recruited -          Higher frequency of dosing introduced to investigate potential for enhanced clinical responses -          Three new trials will study bexmarilimab treatment in neoadjuvant setting, in combination with PD(L)-1 checkpoint inhibitor and in haematological malignancies

Company announcement, 23 November 2020 at 9.00 AM (EET)

TURKU – FINLAND – Faron Pharmaceuticals Oy (AIM: FARN, First North: FARON), the clinical stage biopharmaceutical company, announces today an update on the MATINS study and further details on the clinical expansion plans for bexmarilimab, its wholly-owned novel precision cancer immunotherapy, targeting Clever-1 positive tumour associated macrophages (TAMs) in selected metastatic or inoperable solid tumours.

The expanded clinical development programme is intended to generate data beyond existing hard-to-treat cancer cohorts, exploring new patient populations and investigating combinations with existing treatments, to build full understanding of bexmarilimab’s commercial potential dependent on this unique and proprietary myeloid cell target.

MATINS study update

The ongoing phase I/II MATINS clinical trial is investigating the tolerability, safety and efficacy of bexmarilimab across ten different hard-to-treat solid tumour cohorts (cutaneous melanoma, uveal melanoma, ovarian cancer, colorectal cancer, hepatocellular cancer, ER+ breast cancer, pancreatic cancer, gastric cancer, cholangiocarcinoma, anaplastic thyroid carcinoma) in the first expansion stage (Part II) of the study. Latest data from four cohorts – cutaneous melanoma, ovarian cancer, colorectal cancer (CRC), and hepatocellular cancer – have demonstrated early signs of efficacy from bexmarilimab monotherapy which, according to the MATINS study protocol, allows them to move to Part III. Further data from all cohorts in Part II will enable the Company to evaluate which indications are most likely to achieve success and should be continued further in development.

Of the cohorts in Part II, uveal melanoma, ovarian cancer, colorectal cancer, pancreatic cancer, and cholangiocarcinoma are now fully recruited and the rest, between 50-90 per cent recruited, except anaplastic thyroid carcinoma, which is a new cohort awaiting enrolment of the first patient.

Investigating alternative dosing schedules

As a result of key pharmacokinetic and pharmacodynamic biomarkers suggesting the potential for improved clinical response of bexmarilimab administered with a higher frequency than the current three week interval, regulatory authorities have approved an expansion of MATINS to include two additional CRC cohorts receiving 1 mg/kg dosed at either weekly or two week intervals. These cohorts have started recruiting with results expected during H1 2021. Data from these cohorts will support the design of new and pivotal trials for bexmarilimab.

Study of neoadjuvant bexmarilimab in colorectal and kidney cancers

Faron expects to initiate a neoadjuvant bexmarilimab study in colorectal cancer and clear cell renal cell carcinoma (ccRCC) patients soon after diagnosis and prior to any other treatments. The Company plans to evaluate bexmarilimab’s ability to induce an anti-cancer immune response in patients previously untreated or with minimal exposure to anti-cancer treatments. Disease-free survival will be also investigated to determine the clinical benefit for neoadjuvant treatment.

Lung cancer combination study with anti-PD-(L)1 therapy

The Company previously reported that bexmarilimab administration down regulates a range of immune checkpoint molecules (CTL-4, PDL-1 and PD-1) on the peripheral immune cells of cancer patients,  signalling immune activation and removal of T cell exhaustion. This finding is consistent with the current understanding that Clever-1 is major source of T cell exhaustion and treatment resistance against marketed checkpoint inhibitors¹. Based on these findings, Faron now plans to expand the bexmarilimab programme to evaluate its safety and efficacy in a pilot study in combination with anti-PD-(L)1 therapy in non-small cell lung carcinoma (NSCLC) patients, where PD-(L)1 inhibition has become the standard of care, though resistance develops in roughly 70 per cent of patients².

Potential of bexmarilimab in haematological cancers

Faron, together with Helsinki University Hospital, Finland, plans to initiate a phase I/II bexmarilimab study in combination with standard of care in acute myeloid leukaemia (AML)/ myelodysplastic syndrome (MDS) patients in H2 2021 to investigate the safety and preliminary efficacy of bexmarilimab in haematological cancers. Both AML and MDS originate from myeloid lineage of bone marrow cells and result in impaired haematopoiesis (the production of blood and immune cells). Due to this nature of cell origin, they also express cell surface Clever-1, which has been identified as a prognostic factor in AML³. Faron believes that controlling Clever-1 activity on malignant cells can also control their replication. This is evident in ex vivo experimental settings and could be potentiated with anti-apoptotic compounds like bcl-2 inhibitors³ which promote cell death. Diagnostics and ex vivo drug screen development for bexmarilimab will be included in the study to optimise patient outcomes for targeted bexmarilimab therapy.

Dr. Markku Jalkanen, Faron's CEO, said: “Bexmarilimab is rapidly advancing through development and its exciting clinical activity across multiple cancer types continues to give us confidence in this asset’s potential as a next generation immunotherapy with broad opportunities. With the data we have seen to-date, we are pleased to expand our bexmarilimab development programme, giving us the opportunity to explore its potential to activate the immune system in early stage cancers and in combination with checkpoint inhibitors, a study of high interest for everyone in the field.”

“Our deep understanding of Clever-1 and its role in cancer immunotherapy has brought us to where we are today and we look forward to advancing this novel programme into haematological cancers, the neoadjuvant setting and combination trials, in addition to our ongoing robust basket study in late-line solid tumours, which produces continuous data and understanding of bexmarilimab as a foundational treatment for the removal of immune suppression and T cell exhaustion.”    

References:

1) Hollmén et al. Brit. J. Cancer 2020

2) Gandhi et al. N. Eng. J. Med. 2018; 378; 2078-92

3) Lin et al. Mol. Therapy Nucleic Acids 2019; 18; 476-484

For more information please contact:

Faron Pharmaceuticals Oy

Dr Markku Jalkanen, Chief Executive Officer

investor.relations@faron.com