Member Info for Sangijuelas1

I was a bit unnerved by the info about the delay in the PC trial data but can now see it was only preliminary data promised.

Also I am satisfied that the FDA delay is legit and understandable.

As always at times of SP stress I have taken a deeper dive into the information previously released and looked for independent verification of its relevance for the field. I am extremely satisfied with some of the results of the research.

It was also good to know that the $18m from Oxford Capital is still on the table.

Even if there was another capital raise I wouldn't be overly concerned as it would just mean a smaller portion of a potentially very large pie.

As well as seeing 0518 as very valuable as an element in ICI combo therapy I think it likely has a lot of potential as a monotherapy.

Also the 2nd gen oncology drug looks pretty tasty too. A lot of other pharmas will see value there.

If you look at what Moderna and BioNTech are trying to achieve with developing MRNA cancer vaccines it is very similar to what 4D are already demonstrating with 0518.

In terms of immune system stimulation it is worth thinking of 0518 in terms of a cancer vaccine

You sold your shares and a year or two later 4D was up there with Moderna and BioNTech

Not as far fetched as it sounds if you look a bit more closely at what 4D is doing.

Take a look at the changes in the gene and metagene signatures following a short course of 0518 in the monotherapy trial.

I have been suspecting that the biomarker analysis was likely a requirement specified by Merck.

A hint in this direction from looking at a Danish company called IO Biotech. They are also running a trial with Merck for what they call a cancer vaccine.

Biomarker studies will be included.

IO Biotech are not a Microbiome company but they do look to stimulate the immune system in a way similar to 4D to improve the reach of ICIs.

They listed last year with a market cap of about $500m and are now half that despite having no bad news. Just another casualty of the biotech bear market.

It's like sitting in the dark feeling scared when you could turn the lights on

The thing is if you can get the science you can get an idea of the value

On the events page of the 4D website there is a very detailed presentation from May last year focused on immune checkpoint inhibitors and bladder cancer.

Keytruda and other ICIs like AZNs Imfinzi have had mixed results in this indication and Imfinzi was actually withdrawn as a treatment for bladder cancer as a monotherapy and in combination with Tremelimumab.

They will likely be on the lookout for a way to reintroduce it in combination with another drug.

Bladder cancer is one of the main indications in the 0518 /Keytruda combo trial and is also the one for the upcoming 0518 Bavencio trial.

Funny how people assume Oliveira is selling cos he KNOWS something.

Well he didn't KNOW **** about what was coming his way with Forte

Keytruda and other ICIs kick the immune system into action by stimulating anti tumor cells.

When Keytruda stops working its often because the anti tumour cells have been exhausted and are no longer being produced. So the patient will die because there's no way of getting their immune system going again either because the anti tumour cells are exhausted or they are suppressed by Tregs.

The fact that 0518 can reinvigorate the exhausted immune system is incredible and I think this is linked to the gene and metagene signature changes in the tumour that enable the reawakening of the anti tumour cells that were analysed in the monotherapy study.

I have been reading quite a bit about t-cell exhaustion as a possible cause of Long Covid so I think microbiome therapies will likely have to be explored there in future.

Been revisiting some of the science behind the 0518 and Keytruda combo by skimming thru some scientific papers.

What 4D is doing is science at the cutting edge and is potentially of significant value to Merck.

The Keytruda combo trial is in patients that stopped responding to the drug but the initial data from Part 1 showed that they began responding again with 0518.

One reason that Keytruda can stop working is due to Treg resistance to the therapy which suppresses the anti tumour activity of the immune system. (Possible even that Keytruda causes this to occur and so stop working)

Keytruda is very effective in some cancer patients but there are many it doesn't work in and discovering the reasons why and finding solutions is a number 1 priority for them.

One therapy that has been identified as a way of suppressing Tregs is a monoclonal antibody type called agonist anti - GITR. Merck did a trial a couple of years ago with this in combination with Keytruda and presented results at ESMO.

https://www.esmo.org/oncology-news/GITR-Is-an-Attractive-Target-for-Immunotherapy#:~:text=Glucocorticoid-induced%20tumour%20necrosis%20factor,hamper%20regulatory%20T%20cell%20suppression.

This worked fine in patients that had not previously been treated with an immune checkpoint inhibitor but had no responders in the ones that had previously received ICI treatment.

4D had previously confirmed a reduction in Tregs from the topline data from Part 1. The biomarker data they provided is from the tumour microenvironment, which is a still emerging field, and was further confirmation of the likely reason for 0518 working was because it worked in the 4 in 12 patients who had much higher levels of Tregs in their tumour.

The reason for the delay in the topline data has been given as they are going to present it with the biomarker data, which involves a tissue biopsy and I suspect would be conducted by a 3rd party specialist.

I think they will be providing the readouts to Merck who will then basically come back with an offer or to the FDA for approval.

I had imagined they would be tougher than that and maybe linked to market cap.

That's very good news indeed. Basically another $18m reasy and waiting providing bare minimum achieved.

Great spot RP- those milestones are eminently achievable.

And also reaffirm that an efficacy rate of as little as 10% would be commercially meaningful.

Robins, you always seem to be looking for someone to reassure you.

The other day you were taking the Pig seriously. It's pharma, there's a lot of uncertainty. Reassurance isn't worth ****

They aren't providing a counselling service for disgruntled investors Robins.

The information they have provided to date is more than sufficient.

And the post was also liked by the Executive Director of Business development and Licensing at Merck Vaccines and Immunology Division.

So while investors might not like 4D it looks like industry does hold them in high esteem

They are offering a salary of $80-100k for the microbiome scientist role and they only say microbiome experience is preferable, not essential!

Which goes to show the scientists like Imke Mulder at 4D are potentially very valuable to other companies and they do need to be offered incentives like the options

The fact that the likes were from Alexion AZN is very interesting.

They specialise in rare disease but AZN are looking to use their expertise in immunology to exploit synergies between them.

AZN identify Glioblastoma (most common brain cancer) as one important area for them and Alexion.

This is a cancer that checkpoint inhibitors have not worked with and I think the way 0518 modulates the tumour microenvironment could be a way to get them to work.

There is also a very strong interest at AZN with CAR-T cell therapies and 4D have the 2nd generation oncology candidates, which would be very attractive

Article they published 6 months ago. They are looking to recruit microbiome scientists at one of their US sites.

https://www.astrazeneca.com/what-science-can-do/topics/disease-understanding/unlocking-the-microbiome-to-discover-novel-drugs-within-you.html

AZN had a partnership with Seres Therapeutics for their immune checkpoint inhibitor Imfinzi but the collaboration ended last year.

AZN are very interested in the microbiome and they bought Alexion for their experience with immunology and rare diseases. There are a lot of synergies in terms of the areas of research. Auto immune, neurology, asthma, ibd and of course oncology.

I sometimes look at who has "liked" the 4D Pharma posts on LinkedIn.

When they posted about John Doyle taking up the CFO role there were 3 likes from senior staff including a VP at Alexion which merged with AZN last year. Also another like from a Head of Research at AZN

Never seen them before. Initially thought they were formerly involved with JD but can't find any link between him and them