Hi there IronPig
Good post. I think I agree. At this point BP can't offer much that IMU needs. IMU is clearly hoping for an Accelerated Approval for Vaxinia - and they definitely have the cash to get it that far (if the expansion cohort results are good).
Down the track - for any of their products - I think they need a partnership with BP just to access the marketing and distribution resources of BP. It's easy enough to buy a mfg facility, as they have, but BP marketing and distribution networks have been built up over decades and cannot easily be replicated.
You make an additional interesting statement/question - "I also think it would be a bit naive of the average punter to think that City of Hope isn’t doing a bit more with the virus if you consider the CF33 progression to OnCARlytics, so what is next? "
I have been thinking about that one myself.
Yuman owns the patent for CF33 and he co-owns the patent for OnCARlytics - along with Anthony Park and Shyambabu Chaurasiya and also (I believe) Saul Priceman.
CF33 and Oncarlytics are both licensed to Imugene. It's hard to tell what CoH might be doing with either - but because they are licensed to IMU anything CoH might do with them would benefit IMU. We know, for example, that the Check-vacc trial is being run by CoH, not IMU, and now IMU is not even funding that trial - but they will benefit from any positive outcomes. I doubt CoH is doing anything with Vaxinia - because why would they, and why would IMU agree to parallel work? The MAST trial has Yuman's full support and it is progressing extremely well. No need to duplicate.
However - I DO know that CoH/Yuman and others are continuing work with CF17.
So what is CF17??
You may recall that the original development of CF33 by Yuman was accomplished by a random recombination of 9 known orthopox viruses, which resulted in the production of 100 unique chimeric orthopox virus types. Yuman then tested these for effectiveness against the NCI 60 cancer cell lines, and he selected CF33 as being "the best of the best."
We know the history of CF33 from that point onwards....
However what hasn't been discussed here is the fact that
CF33 was not the only effective strain of orthopoxvirus produced in the experiment.
In fact
two of the new orthodox viruses were discovered to be highly effective. So CF33 has a brother/sister virus, called CF17. A paper published in the Journal of Translational Medicine on 26 April 2018 tells the story:
"
Among 100 new chimeric orthopoxvirus isolates, isolates CF17 and CF33 demonstrated significantly better cell killing (p < 0.001) in the NCI-60 solid tumor cell lines than all nine parental orthopoxvirus strains (Fig. ), indicating that virus chimerisation can generate a backbone virus that is better than its parental viruses. Both CF17 and CF33 caused significant cell death in the majority of the NCI-60 solid cancer cell lines even at the low MOI of 0.01. CF33 was chosen for further study".Source:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918769/The paper does not actually say why CF33 was "chosen for further study" ahead of CH17, but on a chart in the paper CF33 seems to be slightly more effective than CF17. The paper has a focus on Pancreatic Cancer - and CF33 did kill all 6 Pancreatic cancel cell lines - so maybe that was a difference with CF17.
But Yuman took out a patent for CF17 as well as for CF33, and Yuman and his colleagues are continuing to research CF17 for anti cancer applications. Just last month they published a paper entitled: "Peritoneal-directed chimeric oncolytic virus CF17 prevents malignant ascites and improves survival in gastric cancer peritoneal metastases "
You can read it here: https://www.cell.com/molecular-therapy-family/oncolytics/fulltext/S2372-7705(23)00083-9#:~:text=In%20vivo%2C%20i.p.%20CF17%20treatment,directed%20therapy%20in%20GCPM%20patients.
Their conclusion: "CF17 efficiently infected, replicated in, and killed GC cells in a dose- and time-dependent manner in vitro. In vivo, i.p. CF17 treatment exhibited robust antitumor activity against an aggressive GCPM model to decrease tumor burden, improve survival, and prevent ascites formation. These preclinical results inform the design of future clinical trials of CF17 for peritoneal-directed therapy in GCPM patients."
So that's interesting - but it's also interesting to note that Yuman and team are at the same time conducting
very similar studiesusing CF33. Effectively, they are studying both CF17
and CF33 as treatments for peritoneal gastric cancer. Here are the CF33 studies:
Some here may remember that earlier this year I highlighted a new publication in Feb by Yuman and colleagues titled: "Development of a novel chimeric oncolytic viral platform, CF33 and its derivatives, for peritoneal-directed CF33-OV treatment of gastric cancer peritoneal carcinomatosis. "
Source:
https://www.researchgate.net/publication/367767328_Development_of_a_novel_chimeric_oncolytic_viral_platform_CF33_and_its_derivatives_for_peritoneal-directed_CF33-OV_treatment_of_gastric_cancer_peritoneal_carcinomatosisThis was a trial of Check-vacc, because it included the anti PDL1. It was trial in mice, infected with peritoneal gastric cancer. Their conclusion: "These promising preclinical results support peritoneal-directed strategies with CF33-hNIS-antiPDL1 in GCPC patients." Their findings were also presented at the 2023 ASCO Gastrointestinal Cancers Symposium
In September there was another new publication by Yuman and colleagues, detailing their pre-clinical studies of CF33 as a treatment for gastric cancer with peritoneal metastasis:
https://www.mdpi.com/1422-0067/24/18/14189In that paper, they tested CF33 against human peritoneal gastric cancer cells - harvested from actual patients. ie it was an in vitro/test tube study - not a clinical trial - but they were using real human cancer samples. Their conclusion: "CF33-hNIS-antiPDL1 displays real potential for intraperitoneal GCPM therapy." and "These findings encourage the further development of CF33-hNIS-antiPDL1 into effective immunotherapeutic agents for the IP treatment of GCPM patients."
So what would be the game here?
Really - you would have to ask Professor Fong. My assumption is:
He knows he produced TWO excellent cancer killing virus types.
He didn't have funds or time too progress both - and he went with CF33 because it was marginally more effective. Then he entered into a licensing deal with IMU because they convinced him he could not do this alone.
We know he is delighted with the partnership - and amazed at how rapidly the development of CF33 is progressing. But Yuman is also a researcher - and he has a second virus that looks great - and he is now spending some time seeing what it can do too because - hey - science!!!
I would do exactly the same thing.
Is this competition for IMU and CF33? Well - not really. It is quite possible that anything he discovers will be relevant to the further development and use of CF33. Also, CF33 is now years ahead of CF17 in terms of testing and development. If CF17 keeps showing promise - and if it seems to perform
better than CF33 in some applications - then maybe Yuman will want to take it further. That would be well in the future but, also - as long as the relationship between IMU and Yuman stays as strong as it is, he would be most likely to develop it in partnership with IMU.
My personal view: Another reason NOT to change the IMU Board.
Cheers
Dave
(20min delay)
