Ann: Race investor briefing & updated presentation, page-6

So there's a phase 1 dose escalation study and another FTO-directed preclinical program focused on lung cancer starting this year.



Phase 1 Dose Escalation
From the information provided in the announcements, it seems like the P1 dose escalation study will involve melanoma and ccRCC patients. Unsure whether it will include other patients with advanced cancers. Personally, I would like to see this trial done in the US in conjunction with the City of Hope, since they have access to patients, are US based, have international credibility as well as the FDA and BP, know bisantrene as an FTO inhibitor, and have spokenly openly about their desire to work with Bisantrene in the clinic. I would also like to see other advanced cancers included like Glioblastoma (due to BBB penetration) and treatment of Bisantrene with advanced drug delivery technology, but I suspect that it would require preclinical work first. We'll see.

Preclinical FTO-directed Lung Program
With regards to the FTO-directed preclinical lung cancer program, I found the use of the word "safety" odd. And so, while TKI treatment is a primary treatment option, I suspect that this will be determining whether Bisantrene sensitizes lung cancer cells to radiotherapy. My reasoning is as such;

- FTO overexpression has been clearly associated with lung cancer progression



- Treatment options for melanoma and ccRCC are the two largest cancer therapy markets, namely anti-PD1 therapies and TKI inhibitors, respectively. The next largest drug market to be addressed is radiotherapy, where FTO has been implicated to cause resistance to therapy (in cervical squamous cell carcinoma and not lung; my only contention with this theory).



- While radiotherapy is the third largest known potential synergy with FTO inhibition, it is also deemed as an important therapy for lung cancer.



Since the discovery of the FTO inhibitory properties of Bisantrene and the downstream sensitization of cancer cells to other therapies, I suspect RAC are trying to determine how well Bisantrene synergises with other therapies! Importantly, TKI treatment is also very common in lung cancer, so we could see another combination preclinical study, as this is the second largest drug market and isn't necessarily addressed in the ccRCC FTO-directed preclinical program.

Exciting time to be an RAC holder!