Hi Maple
You are welcome!
I think Imugene has a few reasons for running a combo of Vaxinia with Keytruda\ as an extra arm of the MAST trial. You have listed a couple of good ones for sure.
Keytruda(Pembrolizumab) is the world's biggest selling drug. Annual sales in 2023 were $25 billion USD and tipped to exceed $27b this year. Wow.... That makes it a very high profile treatment indeed, with a rapidly expanding range of approved and off label applications - but it's not an absolute magic bullet. "Results vary," as they say - and Keytruda is not a universally appropriate treatment for all solid tumours, nor does it work for everyone in the applications where it is potentially effective, and when it does work the degree of efficacy varies. It can also have quite significant side effects.
So if a Vaxinia/Keytruda combination demonstrates a significantly improved efficacy compared to Keytruda alone then yes - for sure - that would be a big attention grabber and a strong incentive for the FDA to expedite approvals.
Also - yes - as you suggest, Merck would have to be hugely interested. Keyruda/Pembro comes off patent in 2028 - which is not far away at all now, and Merck is actively looking for new combinations to give them an edge beyond 2028. This recent short article describes some of that activity: https://www.biopharmadive.com/news/merck-dealmaking-15-billion-keytruda-cliff-davis/706309/#:~:text=Another%20key%20part%20of%20Merck's,following%20patent%20expiry%20in%202028.
In an ideal world Vaxinia would be so effective that a combination with Keytuda is not relevant - but cancer is complex and "sneaky" and most experts seem to feel that combination therapies are the future. Part of what Vaxinia does is that it make cancer cells visible to the immune system - turning "cold" tumours "hot" so that the natural immune system then also attacks the cancer cells. However, Cancers are also pretty good at turning the immune system's T Cells off again through activating immune checkpoints. Keytruda and other "Checkpoint Inhibitor" drugs can stop that happening, so it makes sense to me that a Keytruda combo may well turn out to be even more effective than Vaxinia as a monotherapy.
IMU is testing that out with the combo arm - which is a smart thing to do. If adding Keytruda/Pembro doesn't make a major difference - then hopefully Vaxinia alone will be sufficiently impressive to drive it to FDA approval as a monotherapy. On the other hand - if it
does make a big difference, then IMU will have the FDA's complete attention and a potential huge deal with Merck. omg..... I mean - IMU has nothing to lose here and much they could gain.
A third reason: although some have lost patience with the B-cell vaccine platform I think IMU remains confident that PD1-vaxx - Imugene's own checkpoint inhibitor drug - may prove to be just as effective as Keytruda, and without the nasty side effects (as well as being cheaper and easier to administer). So if the Vaxinia/Keytruda combo does show extra benefit, you can bet that Imugene will be looking towards a future combo of
Vaxinia with PD1-vaxx. It would take a while to get there, but I find that a deeply interesting possibility.
If Imugene can demonstrate real success for any single outcome of either Vaxinia alone, or an OnCARlytics/CAR-T combo, or Azer-Cel alone, or PD1-vaxx alone (and I haven't given up on Her-vaxx either) - then the current market cap and share price will be a hilarious memory.
The reason I have stayed with IMU - and added whenever I can - is that they have real chances of success in
more than one of the above.
And then on top of that, they have real chances of success with Vaxinia in combo with Keytruda; OnCARlytics in combo with their own Azer-cel (or any other commercial CAR-T or with Blincyto), or Vaxinia in Combo with PD1-vaxx, or Her-vaxx in combo with PD1-vaxx......
These possible outcomes all have different time frames but some are potentially quite close in Biotech terms - and the number and variety of potential "hits" - as well as the potential market sizes - is quite simply astonishing.
I have always emphasised that Imugene is a speculative investment - and I believe that is still true - but I am starting to feel that the speculation is around the number and size of the successes, rather than the likelihood of success vs total failure.
Of course, I am a former rockclimber and I still do some interesting outdoor adventury things, so maybe I have a distorted attitude to risk - but on the other hand I am in my 60's now and still in one piece (so far), so I'm not totally reckless.
Everyone needs to make their own investment decisions. I am heavily invested in Imugene, which may colour my opinions. Also - unlike a few of my climbing escapades - I am not betting the farm on this. Life - like climbing - is about balance more than strength.....
Cheers
Dave
(20min delay)