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A guy from German Merck is on the call with questions

It just doesn't matter.

No one cares

What about Treg acquired resistance to immunotherapies?

The fact that they even bothered with a placebo in P1 is a good sign.

It was meant to be an equal split of 30 patients but they added 2 to the 0004 group at the last minute.

Who cares why? It doesn't make any difference to the percentages and it's not looking for statistical significance at this point

Reported as a cross ramp. Guy is paid PR for Hemo if not Vlad the Impaler himself.

Avoid Hemo

The significance of identifying Treg resistance means that you would effectively get a new class of drug therapy.

Elevated levels of the predictive biomarker PD1 and its ligands are approved so that patients with that biomarker can be treated with anti-Pd1 immunotherapy.

So the plan would be to get elevated levels of Tregs to be approved as a predictive biomarker for treatment with a combo therapy of 0518 with anti-pd1 immunotherapy.

This is why the biomarker data analysis is so important.

https://www.biospace.com/article/immune-checkpoint-inhibitors-market-size-to-reach-56-53-billion-and-growing-at-cagr-of-20-1-percent-by-2025-with-increase-in-awareness-of-checkpoint-inhibitor-drugs-in-the-developing-countries-/

Expected to grow to $56bn by 2025. Main sources of growth Bavencio, Imfinzi and Tecentriq all of which are anti PD-L1 where Treg resistance is a major obstacle leading to progressive disease after a period of initial benefits

Good post Michael.

But worth bearing in mind that 4 of the responders had elevated levels of Tregs while the 8 that didn't respond didn't.

So it was almost 100% success in the ones with likely Treg acquired resistance.

Merck, AZN, Pfizer, Roche and Bristol Myers Squibb are just a few of the companies that have ICIs with Treg resistance as an issue.

4D is right now a very attractive target. I noticed the other day that a Merck scientist was actually down as one of the authors of the published paper on the results of the first part of the trial so presumably they have pretty full visibility of the emerging data.

The company will be bought out by Merck or someone else.

From the December RNS
"
Part A enrolled 34 patients, randomized 1:1 to receive oral MRx-4DP0004 or placebo twice daily for 12 weeks, in addition to their usual maintenance therapy of inhaled corticosteroids (ICS) with or without long-acting beta agonist (LABA). Part A of the study was not powered for statistical significance and 29 patients were evaluable for secondary endpoints of clinical activity."

So Duncan is talking ****

I have seen some suggestions that the Treg resistance to ICIs can actually be a result of the ICIs themselves.

In that their initial stimulation of the immune system can cause exhaustion of it in some patients and the accumulation of Tregs.

This is probably one of those uncomfortable scientific truths that the likes of Merck will not want to be widely researched and know doubt finding an effective complementary treatment to overcome Treg resistance would be a lot more attractive.

The goal of most of these pre clinical drugs being studied to reduce Tregs is to deplete them without knocking out other immune stimulatory cells.

0518 shows that it can go above and beyond this by suppressing Tregs but also boosting the exhausted immune stimulatory cells.

The reference to statistical significance in the RNS was referring to looking to achieve that in Part B

The asthma trial wasn't set up for statistical significance.

They were just getting safety data and initial signs of clinical bene?t.

If I thought this was only going to 5x I wouldn't still be here.

I posted yesterday about Tusk Therapeutics which sold a pre clinical drug to Roche for $800m that it is hoped will do the same as what MRx0518 has already demonstrated in a Phase 1 trial.

If you don't know what overcoming Treg resistance to immunotherapy means I would take the time to find out.

To a layperson it sounds like nothing. It's a bit more relevant to Big Pharma.

People think the likes of Merck will take advantage of the low price with an aggressive low ball bid. That would benefit them in the short term but not when they next want to partner with a small biotech with a very promising drug.

Oliveira took part in the placing at 110p as well as buying Longevity stock at over $10

It's basically an hour long advert for ivermectin.

I have been recommended this channel by some respected immunologists.

https://m.youtube.com/playlist?list=PLFs4vir_WsTyY31efyHdmtp9l7DpR0Wvi

They have a book as well
https://www.waterstones.com/book/immune/philipp-dettmer/9781529360684

I think it's really sad that you are looking to John Campbell for your science.

I have heard about him spreading covid disinformation. I listened to about 30 seconds of the video and stopped when he mentioned the gut-lung ACCESS as opposed to axis.

Quote from the article

"If you are able to take out or partially take out the regulatory T cells from the equation, it’s like moving a rock up the mountain, where you will be able to push the boulder down and initiate a cascade of events that will end up in tumour rejection. So, for us, it’s one of the holy grails of immune regulation that if you target properly, you can get tumour control."