Clevegen (bexmarilimab)

P1/2, N=181, Recruiting, Faron Pharmaceuticals Ltd | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Apr 2025

P1/2, N=181, Recruiting, Faron Pharmaceuticals Ltd | Trial primary completion date: Dec 2023 --> Dec 2024

Spatial transcriptomics profiling of DC and non-DC tumors demonstrates bexmarilimab-induced macrophage activation and stimulation of IFNγ and T cell receptor signaling selectively in DC patients. These data suggest that bexmarilimab therapy is well tolerated and show that macrophage targeting can promote immune activation and tumor control in late-stage cancer.

P1/2, N=216, Completed, Faron Pharmaceuticals Ltd | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Oct 2023

We further showed that bexmarilimab was most efficacious in macrophages with low baseline IFN signaling, as chronic IFNγ priming abolished bexmarilimab-induced TNFα release. These results highlight an approach to target immunologically cold tumors and to increase the likelihood of their subsequent response to immune checkpoint inhibitors.

Treatment of AML bone marrow cells with BEX alone or in combination with azacitidine/venetoclax results in enhanced antigen presentation capacity and increased activation markers on effector T cells with synergistic effect on cell death. Additional clinical and pharmacodynamic data of the completed Ph1 of the study will be presented during the meeting. Ph2 of BEX plus azacitidine will open in the 2nd half of 2023 in HMA-failed r/r AML and/or higher risk MDS patients.

P1/2, N=216, Active, not recruiting, Faron Pharmaceuticals Ltd | Trial primary completion date: Nov 2024 --> Sep 2023

Conclusions Bexmarilimab demonstrates promising anti-tumour activity as a monotherapy in several refractory solid tumours. A dose of 1mg/kg Q3W is considered feasible for further monotherapy studies in solid tumors.

P1, N=0, Withdrawn, The University of Texas Health Science Center at San Antonio | N=36 --> 0 | Not yet recruiting --> Withdrawn

P1/2, N=216, Active, not recruiting, Faron Pharmaceuticals Ltd | Recruiting --> Active, not recruiting | N=700 --> 216

Treatment of AML bone marrow cells with BEX alone or in combination with azacitidine/venetoclax results in enhanced antigen presentation capacity and increased activation markers on effector T cells with synergistic effects (4). The initial data show that BEX treatment is well-tolerated without additional toxicity to standard treatment. Preliminary efficacy shows 3 responses out of 5 patients in the first dose cohort. The study is ongoing.

PD-L1/Clever-1 IHC staining ratio may be used to predict bexmarilimab responding patients. These patients have a low PD-L1 staining and low IFNg levels as reported previously, and are often refractory to checkpoint inhibitors and other T cell activating agents. Bexmarilimab provides a novel therapy option for a tumor group that is otherwise poorly responsive to immune therapies.

P1, N=36, Not yet recruiting, The University of Texas Health Science Center at San Antonio | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=36, Not yet recruiting, The University of Texas Health Science Center at San Antonio | Initiation date: Sep 2022 --> Dec 2022

In vivo, bexmarilimab showed dose-dependent duration of monocyte Clever-1 receptor occupancy in cynomolgus monkeys but did not induce a cytokine storm up to a dose of 100 mg/kg. In conclusion, these data support the clinical development of bexmarilimab for the restoration of immune response in cancers.

P1, N=36, Not yet recruiting, The University of Texas Health Science Center at San Antonio | Trial completion date: Jan 2025 --> Dec 2025 | Initiation date: Apr 2022 --> Sep 2022 | Trial primary completion date: Jan 2024 --> Dec 2024

Samples were treated for 48h with bexmarilimab alone, or in combination with azacytidine and/or venetoclax. Furthermore, NK and CD8+ T cells showed decreased PD-1 and increase of activation markers. These results confirm the therapeutic potential of bexmarilimab in myeloid malignancies and await further validation in clinical trials.

P1, N=36, Not yet recruiting, The University of Texas Health Science Center at San Antonio | Initiation date: Jan 2022 --> Apr 2022

P1, N=36, Not yet recruiting, The University of Texas Health Science Center at San Antonio

Our results reveal a non-redundant role played by the receptor Clever-1 in suppressing adaptive immune cells in humans. We provide evidence that targeting macrophage scavenging activity can promote an immune switch, potentially leading to intratumoral proinflammatory responses in metastatic cancer patients.

FP-1305 is a novel IgG4-antibody targeting CLEVER-1 and induces a phenotypic M2 to M1 immune switch of TAMs...Funding: Faron Pharmaceuticals LTD. Clinical trial identification: NCT03733990.

Full safety, pharmacokinetic and efficacy results of MATINS trial (Part 1) will be presented for the first time in a final late breaking abstract. Research Funding: Faron Pharmaceuticals

FP-1305 is the first macrophage checkpoint inhibitor candidate promoting immune switch with promising tolerability and clinical anti-tumor activity. FP-1305 represents a novel treatment option to provoke immune response against cold tumors.Legal entity responsible for the study: Faron Pharmaceuticals. Funding: Finnish Academy, Finnish Cancer Foundations, Sigrid Juselius Foundation, Faron Pharmaceuticals.