Member Info for Sangijuelas1

Nice of you to say so.

I got stick a month or so for querying the statement someone made that it's a risk free proposition. This was said when it was in the 90p range.

It's certainly not risk free but I think there is a good balance of risk /reward potential.

That 4D for me resemble Tesla.

Disruptive tech- potential switch from medicines with unpleasant side effects to ones with minimal adverse reactions.

Preferring in-house manufacturing so as to oversee quality control of product.

Vertical production process with patents not just on the bacterial strains but on each step required from discovery to manufacturing.

The multiple shots on goal, from potential platform partnerships, licensing out promising candidates to finance further discoveries and potential blockbuster in 0518.

Here is the price chart. Set to 5 years
https://www.google.com/search?q=tesla+share+price&oq=tesla+share+price+&aqs=chrome..69i57.7644j0j7&sourceid=chrome-mobile&ie=UTF-8

CRL you asked why did Oliveira sell as he is not short of cash. He just lost $50m on Forte Biosciences a few weeks back

I bought them between 130-200

Yeah but they split the shares up by 5 so they would be worth about 3500 a share

From recent ESMO RNS

"At the core of 4D pharma's platform is the importance of understanding the impact of Live Biotherapeutics on human biology to rationally select and develop candidates, predict and measure response. 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."

"Furthermore, the monotherapy data demonstrates that a short course of MRx0518 treatment is able to positively modulate prognostic indicators of immunotherapy response," he added. "We look forward to utilizing and implementing these important new findings as we work to progress this novel oncology Live Biotherapeutic through development towards approval."

DP in interview last October

"In our initial population of 12 patients with growing tumors, some of whom had received seven or eight different prior treatments, five had durable responses to MRx0518 in combination with Keytruda.
That was a fantastic result and we’re excited to conduct later stage trials, with an APPROVAL NEXT YEAR potentially on the cards."

https://themedicinemaker.com/manufacture/a-living-elixir/amp.html

Remember the primary aim is not getting 0518 approved as a stand alone drug for every indication.

The approval being sought is Keytruda + 0518 in say NSCLC or RCC where Keytruda has full approval. Data submissions to the FDA will be with the expert input of Merck and likely connections they have with the FDA.

Here’s an example of a combination therapy receiving Breakthrough Therapy Designation from Phase 1b interim data earlier this year.

"This designation was granted based on interim results from the phase Ib M15-531 study investigating Venclexta/Venclyxto plus azacitidine in people with previously untreated, higher-risk MDS. BTD is designed to accelerate the development and review of medicines intended to treat serious or life-threatening conditions with preliminary evidence that indicates they may demonstrate a substantial improvement over existing therapies."

https://www.roche.com/media/releases/med-cor-2021-07-21.htm

Keytruda got Breakthrough Therapy designation in NSCLC in 2014 following Phase 1b data and also check the ESMO mention at the end of the article

https://journals.lww.com/oncology-times/fulltext/2014/11250/fda_s_breakthrough_designation_to_keytruda_for.37.aspx#:~:text=The%20Food%20and%20Drug%20Administration,epidermal%20growth%20factor%20receptor%20(EGFR)

https://en.m.wikipedia.org/wiki/Pivotal_trial

Breakthrough Therapy Designation

"A BTD, on the other hand, requires “preliminary clinical evidence” that indicates that the drug “may demonstrate substantial improvement on a clinically significant endpoint(s) over available therapies,” the FDA’s expedited programs guidance explains.

Consistent with the BTD’s higher threshold for efficacy evidence than fast track status, breakthrough designations are generally awarded when products are more advanced in development. An earlier Pink Sheet analysis found that BTDs are most commonly based on Phase II data, with a sizeable minority (about one third of designations) supported by pivotal-stage clinical trial data. (Also see "Breakthrough Therapy Designations: Phase II Data Is Sweet Spot For US FDA Award" - Pink Sheet, 17 Feb, 2020.)

https://pink.pharmaintelligence.informa.com/PS144170/Half-Of-US-FDAs-Breakthrough-Therapy-Designations-Have-Resulted-In-Approval

Worth comparing 0518 with the Tils drug Foralumab. Before trying in target patient groups Tils had to trial in healthy volunteers.

The FDA have delayed their clinical trials in patients due to concerns with that particular class of monoclonal antibody.

4D did not have to trial dose escalation in healthy volunteers (typical P1). They were able to go straight to max dose in very sick cancer patients.

I think 4D is much further down the road than we think

As I said before any early approval would be because of fast track designation so they would still have to continue with trials.

Some people bought Tesla at 350. It dropped to 130. People will have sold. Others would have stayed the course. I made the mistake of selling when it had quadrupled in value.

The term pivotal relates to conclusive data that means ready for market.

If the data was solid enough in the NSCLC or RCC patients (where there's more data than other indications) with the right biomarkers it could lead to early approval in that group given that there are no treatment options left for them.

4D intend to show FDA how it works and also why it works better in some patients than others.

So life extending treatment with favourable safety profile. Hard to say no when it comes to making it available for patients in such circumstances.

Trial readouts normally involve an initial notice of the topline data (like the Merck Covid pill or the first Blautix news)

This is normally followed by a more comprehensive analysis. So often a biotech can release promising topline data which later doesn't look so good on the later analysis. (Seems like the reverse was the case with Blautix)

It is starting to sound like 4D want to combine the topline data with further analysis as they mentioned reporting on the tumour biomarker data at the same time.

If they can show that say 30% of the NSCLC or RCC patients had these tumour biomarkers and that 0518 worked in a high percentage of these I definitely think that could result in Breakthrough Therapy designation which would allow 0518 to be approved for the market although further trials would still need to be conducted whilst on the market.

This would be because there's a high unmet need in these late stage cancer patients with no treatment options available.

From the same article

"From our perspective, we’re closing in on bringing a live biotherapeutic drug to market. But we’re talking about a single strain of a single microorganism. The human microbiota consists of something like 1000 different species of microorganisms, so it’s fair to say we haven’t even begun to scratch the surface of what might be possible in terms of pharmaceutical development. We’re talking about an entirely new class of medicines with the potential to transform how we treat many diseases."

DP in interview last October

"In our initial population of 12 patients with growing tumors, some of whom had received seven or eight different prior treatments, five had durable responses to MRx0518 in combination with Keytruda.
That was a fantastic result and we’re excited to conduct later stage trials, with an APPROVAL NEXT YEAR potentially on the cards."

https://themedicinemaker.com/manufacture/a-living-elixir/amp.html

Posted this 2 weeks before aimhardy

MRx0518 Flagellin10 Aug 2021 12:39
Been taking a look at some of the science behind the effects of 0518, which are heavily linked to the protein flagellin from a strain of enterrococus gallinarum. 4D scientists say that they have isolated a very strong source of this protein in 0518 , which is well known for its immonomodulatory effects.

https://www.nature.com/articles/emm2017172#:~:text=Traditionally%2C%20flagellin%20was%20viewed%20as,of%20immunity%20during%20microbial%20infections.

https://www.frontiersin.org/articles/10.3389/fimmu.2018.03054/full

The second link describes its use in vaccines

This has led me to think that 0518 may actually be one of the candidates being studied for its potential as a vaccine adjuvant in the MSD collaboration.

It is also mentioned in this very recent paper by the Merck Exploratory Science Centre who 4D have been working with.

https://www.frontiersin.org/articles/10.3389/fimmu.2021.643255/full#:~:text=10.3389%2Ffimmu.2021.643255-,Immunomodulation%20by%20the%20Commensal%20Microbiome%20During%20Immune-Targeted%20Interventions%3A%20Focus,Checkpoint%20Inhibitor%20Therapy%20and%20Vaccination&text=Emerging%20evidence%20in%20clinical%20and,the%20state%20of%20the%20microbiome.

I think a potential vaccine target would be for influenza as this seems to keep coming up when vaccines are mentioned.

Flagellin is also protective against radiation, so the results of the pancreatic cancer trial of 0518 with radiation therapy could be interesting.

https://pubmed.ncbi.nlm.nih.gov/28323577/

This is another good article on the CAR-T potential for 4D
https://www.labiotech.eu/trends-news/car-t-cell-therapy-microbiome/

https://www.nature.com/articles/s41573-021-00189-2

It is a very interesting development. The main thing is that CAR-T has only been shown to be effective in blood cancers and this is pre clinical work on solid tumours, which would be really important

See this Nature article for more on CAR-T and solid tumours