Member Info for Sangijuelas1

So why don't you sell up and buy your shares back at a lower price?

Everyone wants to jump on a little pharma like 4D and jump off having doubled their money.

People want risk free high returns and then start blaming the board when their trade didn't work out.

Wasn't meaning to rub anything in. Just saw the Evelo opportunity so sold some PATH at a loss. Made it up buying Evelo at 5.74 and selling at 6.75 and bought more 4D.

Not expecting an RNS, because the timing of any positive news would have been unlikely to coincide with the conference.

As I said for me the news is that the vaccines collaboration is still ongoing and that it merits a discussion in front of others at a pharma networking event to talk about the benefits of partnering.

62.9

And don't bother replying as chances are you will have been green boxed.

There's about 5-6 people that post useful stuff here. I have filtered everyone else

Am I really the only one here hoping for it to drop even lower?

I really don't think 4D are that concerned about some dumb ass PIs that are upset because they didn't make a quick buck

Rebiotix very much focused on gastrointestinal but they seem to have made good progress with c-diff and could still win the race to get the 1st microbiome drug approved

Ok but this is already as good as an RNS. We are going to a conference where the theme is Partnerships between companies to discuss the partnership with MSD.

If it wasn't going well why would anyone bother?

Quote from the MSD scientists article. Stating that Flagellin is an important stimulator of response to influenza vaccine. Very potent flagellin is what makes 0518 so effective, so I think that is one of the candidates MSD are looking at.

"Notably, several studies have identified specific microbial products or host factors that mediate the effects of the microbiome on vaccine response. Broadly expressed microbe-associated molecular patterns (MAMPs) may mediate key effects of the microbiota on vaccine response. Indeed, a recent study demonstrated that signaling by the pattern recognition receptor (PRR) TLR5, stimulated by the MAMP flagellin, is important for vaccine adjuvanticity"

I suspect the vaccine program will relate not only to new vaccines being developed but also ones that have already been developed like polio but not effective in all groups

I am very encouraged. All the more so that we are about to start another trial with Merck KGaa (this is not US Merck but an entirely separate German company) and Pfizer for Bavencio.

You do need to try and get to grips with the science, clinical trial readouts, published research and the wider context of what small biotechs are doing in a particular area.

If I hadn't I wouldn't have known to get the hell out of one UK Aim biotech and why I am comfortable holding here

The science is indeed complicated. I tend to read the abstract and summary of any articles rather than go down rabbit holes of stuff I don't understand.

I think this recent article is really important by the MSD scientists about the microbiome and vaccines/immunotherapies. Will give it another skim read later.
https://www.frontiersin.org/articles/10.3389/fimmu.2021.643255/full

I was at the point where I was prepared to write off the vaccine collaboration due to some comments made by DP in a recent article but am now really excited again by it.

I see 4D as a Tesla type company in that there are so many strings to their bow that could exponentially increase their value over time.

That's why I participated so heavily in the Oliveira Firesale

Worth reading the abstract on this article titled "Predictive biomarkers for immune checkpoint blockade and opportunities for combination therapies"

https://www.sciencedirect.com/science/article/pii/S235230421930042X

This is worth a read from May 2019 with regard to the need to see good science backing up good data before big pharma really want to get involved.

As an idea of scepticism among mainstream investors I read the FT pretty much every day and I can't remember seeing any articles about microbiome based therapeutics whereas they have often featured stuff like Crispr gene therapies.

https://www.labiotech.eu/in-depth/human-microbiome-research/

From the horse's mouth just under a year ago.

"Studying the microbiome adds a new dimension to our current research and development processes,” says Gokul Swaminathan, associate principal scientist, investigational biology. “The role of the microbiome in regulating the immune system and how it contributes to vaccine responses is of particular interest right now. We are conducting both preclinical and clinical research to better understand how vaccine responses differ in the very young, in whom the microbiome is evolving, versus in older people given that the microbiome changes with age.”

https://www.msd.com/stories/msd-scientists-probe-how-our-bodies-bugs-impact-immunity-and-disease/

If you look at the Angle RNS about their Parsortix system you will see how they are talking about using it to harvest circulating tumour cells for biomarkers to be used in clinical trials for immune checkpoint inhibitors.

It would be interesting to see a comparison between the 2 ways of getting tumor biomarker data. But it shows how important it is being able to use biomarkers in trials as they are building a business around it.

So some of us, including me, have been impatiently waiting for them to release a progress update on the 0518 1b trial. Understandable since we were told to expect it by early Autumn.

However, we have been given an update of sorts via the ESMO news, which as lay persons we are struggling with. Yet this does seem very significant and explains why they might be pushing it back.

4D do need to take the interests of shareholders into account. But the shareholders they will consider are not traders who have bought in expecting a quick doubling of the SP within a 12 month time frame. And for the company and more patient investors, what matters is not rushing out data to satisfy the concerns of the Impatient but putting together a comprehensive package of data that will help get 0518 approved.

So we are not listening to what they are saying.
-ESMO was a formal announcement that they have identified tumour biomarkers that show which patients are most likely to respond to 0518/Keytruda combo.
-Any update on the 0518 1b will be not just safety and efficacy data but also data from tumour analysis of responders and non-responders.
-If they can then present data of this nature to the FDA showing that 0518/Keytruda is extending the life of this group of patients with these tumour biomarkers then whilst further studies will be needed it could open the door to Breakthrough Therapy approval meaning the combo could be put on the market even though studies ongoing. This because it is a life extending/saving treatment.

As you are progressing through trials making the discovery that the treatment is more likely to work in one group of patients than another for biological reasons is pretty damn important and something that we seem to be minimising claiming that we don't understand despite it being clearly stated in the RNS.

"These data indicate the potential for MRx0518 to overcome Treg-mediated acquired resistance to cancer treatment, and presents a biomarker potentially able to identify patients most likely to respond to immunotherapy based on MRx0518. Further tumor sample analysis is ongoing for additional patients recruited into the study".

These new biomarker data provide us with critical guidance on the biological and mechanistic impact of MRx0518 therapy in patients with various solid tumors," said Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma. "These new findings indicate the potential to predict patients most likely to respond to MRx0518 therapy based on tumor biology."

I bought a lot of shares on the drop. I am happy to hold them.

https://www.4dpharmaplc.com/en/delivering-therapies/our-collaborations

They were careful not to comment on the data coming out of the 0518 trial. If they had it would have been materially significant info.

They are still recruiting until the end of the year. I wonder if they can use the latest biomarker data to guide recruitment.

There would be a medical and ethical justification if they thought they could prove a higher likelihood of efficacy in those with the right biomarkers as it is potentially life extending.

The point about increasing the potential of getting ICIs to work better as first line therapies is also relevant here and especially so when the Bavencio trial goes live