General Comments / Chat, page-6161

Can't seem to copy across to Dartboard and post:

Forgive me @RaceOncology as I don’t have a scientific background / nor access to a lot of clinical data (which is annoying).

I did get on board with Race at IPO and direction has pivoting a fair bit since the FTO and cardio-protection discoveries. So I have been researching the viability of Race and the potential market opportunities (beyond AML and PRV).

The radio-therapy space has thrown up some interesting ideas that I am attempting to wrap my head around.

What we knowon Radiotherapy:

1. The fourth largest total addressable market as part of FTO synergy is radio:

Source: https://app.sharelinktechnologies.com/announcement/asx/395fe13c95a049043f54e822e1c1b216

2. Radio therapy appears to induce overexpression of FTO.

Source: m6Ademethylase FTO renders radioresistance of nasopharyngeal carcinoma viapromoting OTUB1-mediated anti-ferroptosis - ScienceDirect

3. An FTO inhibitor FB23-3 that has an IC50 value that is x18 times lower compared to Bisantrene IC50 was found to boost the responsiveness of radiotherapy.

4. Bisantrene was found to synergies as an ‘additive’ for radiotherapy, which was equivalent to Doxorubicin (formerly Adriamycin).

Source: Interactionbetween bisantrene and radiation - ScienceDirect

5. Cardiotoxicity of Doxorubicin, Carfilzomib and Radiotherapy appears to be vaguely induced / be connection to ionisation.

Doxorubicin: Doxorubicincauses ferroptosis and cardiotoxicity by intercalating into mitochondrial DNAand disrupting Alas1-dependent heme synthesis | Science Signaling

Carfilzomib: 7c72e0ac3bd14affe880b99e35b755b9(sharelinktechnologies.com)

Radiotherapy: Ferroptosis,radiotherapy, and combination therapeutic strategies - PMC (nih.gov)

I understand that treatments in conjunction with Radiotherapy still go through the same approval process with the FDA. But commercially it would only make sense to run a trail if it improves the standard of care. For instance, Doxorubicin is used in conjunction with radiotherapy, and, causes cardio-toxcity or is resistant to treatment.

A couple of questions at Race:

1. Is radiotherapy as a combination therapy with chemo treatments generally a commercially viable target?

2. Is it possible / practical to have a stratum that addresses a radiotherapy treatment in addition to chemotherapeutic treatment?

3. Does Race currently have any plans to explore a radio-therapy opportunity, or is this target beyond the current 3-Pillar / exit strategy?

Whilst you may not be able to answer on a public forum, perhaps a good AGM Q&A question / discussion point. My view is that if there is some sort of compelling data (even if pre-clinical) on this that Big Pharma would then need to include in its valuation for any deal. Feel free to correct me if I am wrong?

Bonus question: Is the Mechanism of Action (MOA) of Bisantrene’s cardio-protection the result of ionization / Ferroptosis the result of FTO inhibition and its upstream / downstream pathways?

4. @RaceOncology, if you had the chance to redo your PHD would the above be a good topic?

Looking forward to the response!