The Pipeline
Tribbles 2 inhibition
Filamon has a pipeline of two Trib2 inhibitors.
FLM-JG1
As a repurposed drug, FLM-JG1 offers significant cost- and time-saving advantages in (i) having an established profile as a well-tolerated drug, (ii) holding marketing approval in all major territories, and (iii) having an established large-scale manufacturing process.
FLM-JG1 is being developed in the first instance as a drug to prevent or reverse resistance in prostate cancers to androgen receptor signalling inhibitors - enzalutamide (Xtandi®️), abiraterone (Zytiga®️), apolutamide (Erleada®️) and darolutamide (Nubeqa®️). Resistance to these drugs is a significant problem, with 20-30% of men failing to respond at the outset and others eventually developing acquired resistance within 1-2 years.
FLM-JG1 currently is being used on a named patient basis in men whose prostate cancers are progressing on enzalutamide or abiraterone. The study aims to provide clinical experience in the drug’s use.
That experience is intended to inform the design of a Phase Ib/IIa two-arm trial in non-prostate cancer patients experiencing tumour progression on standard of care (Arm A, dose-escalation) and in prostate cancer patients (Arm B, dose-expansion) experiencing tumour progression on enzalutamide or abiraterone. This trial is scheduled to start Q2-2024.
FLM-TRX Program
This is a drug discovery program based on the Company’s proprietary knowledge of the way in which FLM-JG1 is binding to and degrading Trib2. That knowledge is guiding the design of a new class of molecules with potent action against Trib2.
A new lead compound will be developed as an anti-cancer agent for the treatment of such cancers as acute myelogenous leukemia and neuroendocrine tumours (NETs).
hGIIA-sPLA2 inhibition
FLM-c2 is being developed as a drug to inhibit the inflammatory disease processes contributing to the growth, invasiveness and spread of cancer.
It is envisaged that FLM-c2 would be used early in the disease process, designed to delay the need for more aggressive treatment such as use of androgen ablation therapy in prostate cancer. The intention is that FLM-c2 become standard of care across most forms of solid cancer, replacing the use of steroidal anti-inflammatory drugs like dexamethasone with its unwanted inhibitory effects on immune function.
FLM-c2 has undergone a first-in-human clinical safety study in men with hormone-sensitive prostate cancer using a limited 6 weeks of treatment with low drug dosages in combination with hormone therapy.
- Oral bio-availability confirmed
- No adverse events related to FLM-c2
- Falls in both blood hGIIA levels and PSA levels observed in 25% patients.
This is a major outcome given the toxicity experienced with previous attempts to block hGIIA-sPLA2 function. To have achieved lack of toxicity at dosages indicating therapeutic benefit is an important breakthrough.
An open-label, Phase I/II, two-arm (dose-escalation, dose-expansion) trial in patients with solid cancers progressing on standard of care treatment and displaying blood evidence of inflammatory markers is intended to commence late-2024. Compared to the earlier Phase I study, this larger study will use higher dosages of FLM-c2 (from 20 mg up to 200 mg daily) and for longer treatment periods (up to 3 months vs 6 weeks).
- Arm 1 (dose-escalation) will be patients with any form of solid cancer displaying blood markers of inflammation.
- Arm 2 (dose-expansion) will be patients with locally advanced or metastatic solid prostate cancer displaying blood markers of inflammation.
JUN/FosB/FosB modulation
The FLM-BT2 program is pursuing two major indications based on the drug’s apparent ability to correct malfunctions rather than to shut down all functions, good and bad.
Wet age-related macular degeneration
wet AMD) is the main cause of blindness in the elderly, affecting 45% of people >85 years of age and is caused by abnormal growth of leaky blood vessels in the retina. Current treatment involves the direct injection of drugs into the eyeball, an uncomfortable, painful procedure done monthly on a rest-of-life basis and associated with side-effects resulting in a high drop-out rate. Current drugs also fail to work in about 1 in 3 patients.
FLM-BT2 is being developed as a topical (eye dropper) with the intention of revolutionizing the treatment of this insidious and life-changing disease in two main ways:
- Greater efficacy. FLM-BT2 targets 10 different parts of the wet AMD disease process vs 1-2 parts with existing drugs providing greater anti-angiogenic activity.
- More patient friendly. FLM-BT2 is a small molecule allowing it to be self-administered by eye dropper, avoiding the pain, side-effects and monthly procedures in a clinic.
Combination treatment with checkpoint inhibitor therapy in melanoma
FLM-BT2 is intended to be used in combination with PD-1 inhibitors in patients with metastatic melanoma delivering dual anti-cancer actions – (i) a direct cytotoxic effect on cancer cells, and (ii) reversal of T-cell exhaustion.
FLM-BT2 currently is undergoing pre-clinical work-up with a view to commencing a first-in-human study late-2024.
