IMU product line - CF33, page-47

Hi everybody and thank you for a useful thread. I've been following Imugene for a few months after I heard the first results from the MAST study. The results announced Nov -23 and Jan -24 were extremely encouraging even for me who is a big sceptic for pharmaceutical research in which FDA has put the bar really low for approving new (cancer) drugs. Many Ph III RCTs have really fishy trial designs and big N of patients enabling statistical detection of small effects between trial groups.

First a few questions if somebody like davybabyk already knows the answer. Otherwise I'll try my luck with Imugene investor relations:

1. MAST results are highlighted to have good / better response for GI cancers (Bile, CRC, etc). Is there any indication in the preclinical research of CF-33 why that would be the case? Ofc these results to date could be due to small sample size and random variation in patient characteristics, doses etc. One simplistic hypothesis could be that gastrointestinal system has a different immunological system than other parts of the body (bacteria, viruses, immune cells in bowel) and contributes better performance for immune response (tumor recognition and tumor killing).

2. After the OBD or the highest dose tested is achieved in the MAST study. How much it would speed up the capabilities of trial recruitment if other criteria are unchanged (all solid tumors), from 1 per week to 3-4/week or 5-10/week (depends on dozen of factors)? The faster the better for upcoming trials.

3a. The most recent ASCO MAST poster had immunological markers (amount of different T-cells for "responders" and "non-responders" between day 1, 8, and 21. Is this something that is well documented in other established immunotherapy (checkpoint inhibitors, CAR T etc)?

3b. Conventionally a "response" can be evaluated by any precision 3-4 months after start of the treatment. If we take the CR bile duct patient as a 'role model', she had first pseudoprogression, +50% of tumor 'growth', in 6 week scan and CR at 4 month scan. That doesn't fast forward the response evaluation at all compared to conventional chemo. If some of the immunology markers would be come established for response (for CF-33 or OVs in general), it could replace the CT scan surrogates (PFS etc) and bring the evaluation time for drug effectiveness from quarters to weeks? That would be appreciated in the day to day clinical practice and perhaps later on new indication approvals could be assessed based on these markers (sic!)?

More on the statement side of notes:

1. Cost and timeline of drug approvals (VAXINIA fast track).
The better the drug, the shorter the timeline and lower the study costs - and vice versa. Simple, right?
If CF-33 with OBD or later on CF-33+Azer-Cel combination would have sensational effectiveness, that doesn't need RCT of N=100 vs 100 and 2y survival. I'm not here for possible marginal effects such as 3month PFS improvement.
To make the point. If we would not have human insulin till to date and all the children with DM1 would die in few weeks time from ketoacidosis, does somebody believe more than one or two complete responses would be needed for insulin approval? Also, if somebody could come by new Alzheimer drug that would have "complete responses" for end stage Alzheimer patients who can't speak or move due to progressed brain degeneration and paratonia. I bet under a handful CRs in a row would be needed in that case, and I'm eager to point out (in my clinical practice) when the evidence is subpar or non-existent for many of the things that we do regularly with out best hopes.