Hi Sorest2016
Well that is of course a good question. Cancer research is a big field, with many players, and there is serious competition. No-one can be across the whole field - not even the incredible team at Imugene, and certainly not me.
There are definitely other allogeneic CAR-T's in development. In fact Imugene has already been in a partnership with one of those competitors!
The who have been here a while (or done a lot of reading) will know that back on 5 August 2021 IMU announced a partnership with Celularity Inc (USA) to collaborate in the development of OnCARlytics with Celularity's "Cycart-19" experimental Allogeneic CAR-T. Source:
https://celularity.com/imugene-and-...ombination-for-the-treatment-of-solid-tumors/
On 10 August 2021 IMU clarified that the partnership was for an initial 12 months.
https://app.sharelinktechnologies.com/announcement/asx/d3c55407df036f4e75a691caaddc887f
Cycart-19 is derived from human placenta tissue, and is "cryopreserved, allogeneic and available off-the-shelf to clinicians." Like Azer-cel, it targets the CD19 protein, and could therefore be a good combination with OnCARlytics for use against old tumour types.
Celularity certainly carried out very successful pre-clinical studies of the two drugs in combination, and published the results at a major conference in November 2022:
https://app.sharelinktechnologies.com/announcement/asx/1bc0ced3d50a0ed55fe373de06b7bf7d
It is unclear to me whether the collaboration between IMU and Celularity is ongoing in any way - but I suspect that Imugene's acquisition of Azer-cel now takes precedence, and it certainly puts IMU and Celularity in competition.
I also believe that Azer-cel is
much further down the regulatory and testing pathway than Cycart-19, Celularity only applied for IND for Cycart-19 in early 2022, and the FDA did not immediately grant it. Instead the FDA requested additional information in April last year. Celularity was hoping to start a Phase 1 trial in late 2022 : Source:
https://www.sec.gov/Archives/edgar/data/1752828/000119312522151903/d338161dex991.htm
But I don't think that has happened yet, because their website still shows it at IND enabling stage, with the Stage 1 trial yet to start: Source:
https://celularity.com/pipeline/
Back on January 26 this year Celularity announced a "strategic review." It contained two relevant references:
1. They announced that they would continue to develop Cycart-19, and to address FDA questions. They were hoping to start the Ph1 Clinical trial sometime "in 2023" - exact quote: "Hematologic Cancers and Solid Tumors. Celularity will continue to develop CYCART-19, an allogeneic placental-derived T-cell therapy engineered with a CD19 chimeric antigen receptor (CAR) with T-cell receptor (TCR) knockout that has demonstrated potent anti-tumor activity both in vitro and in vivo. The Company continues to work to address FDA questions on its IND and anticipates commencing its Phase 1 trial in 2023."
2. They also said they were continuing with the partnership with IMU: "Celularity will continue to partner with Imugene Ltd. (ASX: IMU) to utilize its novel onCARlytics (CF33-CD19) technology to prime solid tumor cells to express CD19, making them a target for CD19 CAR-T therapy. Celularity also will continue to advance other select innovative T-cell programs through preclinical development.cryopreserved, allogeneic and available off-the-shelf to clinicians."
Source:
https://celularity.com/celularity-c...zation-of-next-generation-product-candidates/
As I say, I suspect that Imugene's acquisition of Azer-cel may kill or at least "de-prioritise" the active partnership with Celularity - but Azer-cel is already years ahead of Cycart-19 in the regulatory and clinical trial pathway. The Azer-cel Phase 1a trial started on 11 March 2019 and they are now in progress with a Phase 1b, with a Phase 2 expected in 2024, whereas Cycart-19 has not even started a Phase 1 trial yet.
Are there other allogeneic CAR-T's in development? You bet! A journal article from August this year identified 61 CAR-T studies which might be classified as Allogeneic. You can hurt your brain here if you want:
https://ehoonline.biomedcentral.com/articles/10.1186/s40164-023-00435-w#Sec9
However, the paper does not identify all the individual drugs, and it does not attempt to analyse or compare how far each has progressed. The paper is just an analysis of the various methods/approaches for developing an allogeneic CAR-T. Note that it DOES highlight the various potential advantages of allogenic CAR-T cells over the currently available autologous CAR-T's.
It also describes one of the problems of Allogenic CAR-T - graft to host rejection. ie. Allogenic CAR-T cells are NOT derived from the patient's own cells, and can therefore run the risk of the body rejecting them. Azer-cel however has been genetically modified to reduce or eliminate that problem, and indeed it achieved excellent safety in the Phase 1 trial, with no adverse reactions of grade 3 or above, and with seriously encouraging effectiveness data. Read more here:
https://investor.precisionbioscienc...iosciences-provides-update-allogeneic-car-t-0
So who will win the race to get the first Allogeneic CAR-T approved??
There is no way of knowing - but IMU looks to be in there with a very good chance. If it was certain, then our share price would be many multiples of what it is now, and the risk of investing would be lower, but the potential capital gain would also be
far lower.
SO - evaluate the risk/reward equation for yourself, and make your own decisions about investing. I review my own decision every time new information becomes available but - so far - the case for investment just seems (to me/in my opinion) more and more compelling.
I do think we will know whether I'm right, or wrong. within the next 12 months - and maybe much sooner. (Not for all IMU programs, but it will only take one decent commercial deal to make the share price soar).
Cheers
Dave
(20min delay)