My 2 cents on PD1-Vaxx and especially the Neo-POLEM trial...The...

My 2 cents on PD1-Vaxx and especially the Neo-POLEM trial...

The CF33 suite, in all its forms, is the ‘rock star’ in the IMU stable, so to speak. But, as we all know, IMU is not a one-trick pony. Just look at our latest acquisitions and combos.

The new PD1-Vaxx trial has been discussed on these threads, and quality posters like Davy, Ben and several others, have raised many good points, but I wonder how many others here (on HC) realise its true potential.

The data tells us that Colorectal cancer (CRC) is the third most commoncancer, so it’s a ‘big one’. And importantly, it is fast becoming clear that the anti-tumourimmune response plays a key role in the clinical outcome for CRC patients.

Oncologists have known for a while that some 15 percent of operableCRC patients have deficient (DNA) mismatch repair (MMR) machinery (dMMR), andthis brings with it its own challenges. But, as the team at Southamptonhospital note ... “recent small trials of immunotherapy drugs appear to work exceptionally well in this subtype of cancer”. And this is where PD1-Vaxxsteps in, with its potential, as a vaccine approach, to provide “a durable effect”.

Note: There is currently a 40% chance of cancer recurrence is this dMMR subgroup.

This trial, if successful, could see PD1-Vaxx jump to the head of the queue and become standard of care (SoC) in this group of cancer patients. Yes, PD1-Vaxx could become SoC !

It would be used prior to surgery and/or chemo so becoming‘neoadjuvant’ ... not the 2^nd, 3^rd or last line of treatment, a position that immunotherapy, as a relatively new treatment, often finds itself.

I began communicating with Nick Ede, about this Neo-POLEM trial, as far back as April. Even then he was excited because, in his words, there was “a group of world-class GI oncologists, who approached us,wanting to conduct a trial with our PD1-Vaxx”. The wider oncology community was already following the progress of our PD1-Vaxx trial and some had identified the potential of this treatment.

I emailed Nick again this week to discuss an area which had tweaked my curiosity. I asked, “will IMU-201 (PD1-Vaxx) be given enough time, to show its efficiency, before the surgeons step in to remove tumours?” A fair question I thought. He replied that both IMU and external oncologists “are pretty keen on Neo-POLEM”. By the way, I am too.

His response, in part, continued... “A big question iswhether PD1-Vaxx can generate enough anti-PD1 antibodies in this short 6 week,with 3 doses of vaccine, period. Time will tell however we are encouraged by the fact that the patient’s immune system is strong at thisearlier stage of disease. Everyone is also quietly excited about the potential for the “vaccine” to keep working after the patient has had theirtumour, or what’s left of it, resected. This setting truly could be where PD1-Vaxx really shines.” (my emphasis added)

Is this the breakthrough trial that PD1-Vaxx needs? It certainly could be. As Ben wroterecently ...

“This could see Imugene jump a few places up the pecking order if the drug outperforms in patients with stronger levels of immunity than those administered in Imugene trials to date”.

Note: PD1-Vaxx to date,has proven to be very, very safe. And this could be the key, especially if its efficacy is equal to, or better than its main rivals here like Dostarlimab.

“Dostarlimab strengthens your immune system to help it attack cancer cells, but it may also attack healthy cells and youcould develop serious or fatal side effects”. see- https://www.drugs.com/mtm/dostarlimab.html

The list of side effects noted for Dostarlimab is so extensive I don’t have space here to list them, but they include ... sepsis, acute kidney injury and urinary tract infection, to name just a few.

PD1-Vaxx could indeed become the SoC in this area, and that would be a huge win for IMU. Who knows where this might lead? I will be watching this trial with great interest, and it is easy to see why the IMU team is so excited by this development.

Again, in Nick’s words ... This setting truly could be where PD1-Vaxx really shines.

So, that’s the Neo-POLEM trial ... but what about the ongoingIMPRINTER 1b trial?

This trial is due to read out in 2026 and is running in mono and in combo with atezolizumab (Tecentriq). By the way, Tecentriq sales in 2022 amounted to over $4 billion USD. Nice!

Atezolizumab is a type of targeted therapy drug called animmune checkpoint inhibitor (note: there are several already on the market). It is a monoclonal antibody that works by binding to the protein PD-L1 onthe surface of some cancer cells, which keeps cancer cells from suppressing theimmune system.

So why this trial structure?

Well, some patients treated with PD-1/PD-L1 blockers may develop “a primary or secondary resistance” to therapy (note: Sharma, Hu-Lieskovan et al. 2017). But our own PD1-Vaxx, is a chimeric B-cell cancer vaccine. This vaccine can produce polyclonal B-cell antibodies, and these can potentially induce memory B-cell and T-cell responses, while as the same time reducing immune evasion and suppression. So, put simply, PD1-Vaxx could prove to be a perfect partner to a ‘traditional’ PD-L1 blocker.

So, here’s ‘the rub’ ... the trial may be due to read out in 2026 but it is ‘open label’. This means that both the researchers and participants know which treatment is being administered, and that the researchers are able to see if its working!

If promising signs are seen, the company may decide to do an early data cut, at any time!
Just imagine if that was just before a major conference?
That would certainly catch many punters unaware, and do wonderful things for our SP.

I guess that the key point I am making here is ... don’t overlook PD1-Vaxx. It could be our tipping point.

All opinion only, of course.