Member Info for Sangijuelas1

It doesn't look good. I really don't think Avacta will want to be associated with a company linked to an £85m deal which could result in criminal charges for one or more government ministers.

This article says that the FDA approval rate for de novo devices is actually quite high this year and they are on track for a record number of aplrovals

www.evaluate.com/node/17030/amp

That's cos you are invested in ABDX. I imagine Al has sensible cut any ties with them given that they are at the centre of a massive corruption scandal.

You can't get through to them George. It's like talking to anti vaxxers or Qanon devotees. Completely delusional

4D already tweeted about this the other day. They have partnered with them and provided funding in the past and 4D Cork was a spin out from them.

Don't know the full story and not sure what the current relationship is

https://mobile.twitter.com/4dpharmaplc/status/1425022568050872320

They gave the same message 3-4 months back if you were able to read between the lines.

They were sent back to get more data in mouse trials before the FDA were going to authorise any further in person trials. That's why they have to do everything in Brazil

It's an individual expanded access programme. They can't just add patients to it. They can apply for another Individual EAP or a group EAP but they can't just add patients to it.

They are giving it to the patient for compassionate reasons. Many pharma companies don't like to do it because it is too much hassle for no commercial benefit.

I have explained this to you before.
It's an Individual Expanded Access Program. But don't let facts get in your way. Anyone would think you were looking to wilfully mislead potential new investors here.

"Purpose

The biggest difference between an EAP and a clinical trial is the purpose that they serve. A clinical trial is conducted by a drug manufacturer that wants to get its IND approved and licensed for use. In order to receive approval, the manufacturer has to prove to the national health regulatory body that the drug is safe to use, and that it is as good as, if not better than, current medication being used on the market. Clinical trials allow a manufacturer to use its drug, in a controlled and regulated setting, to treat patients in order to collect this necessary safety and efficacy data.

An EAP is different. Although an IND manufacturer can still collect safety and efficacy data from patients enrolled in an EAP, these programs are not established to help get a new drug onto the market. Instead, these programs are set up solely to provide much needed medication to where there is an unmet medical need. The drug manufacturer usually provides the drug through an EAP because it is the patient’s last hope, not because it has a lot to gain."

https://www.wepclinical.com/eap-versus-clinical-trial/#:~:text=The%20biggest%20difference%20between%20an,the%20purpose%20that%20they%20serve.&text=An%20EAP%20is%20different.,new%20drug%20onto%20the%20market.

She left BMS in 2019 after 7 years. Makes you wonder what she and Axel Glasmacher are doing at a tiny UK biotech.

She seems quite engaged with the project as she always likes the 4D posts on LinkedIn so they come up on her feed

In addition to the potential life extending treatment for cancer patients who have exhausted other treatment options we have

Blautix for IBS-M for which there is no treatment.

Mrx 0004 for severe asthma. It potentially reduces both neutrophilic and eosinophilic inflammation. Severe asthma has typically been treated with oral corticosteroids, whose side effects get worse with ongoing use. Some monoclonal antibody therapies have been developed for eosinophilic asthma but only steroids for neutrophilic.

CAR-T therapies have only really been effective in blood cancers and not solid tumours. The recent pre clinical research with MRX 1299 demonstrates a possible route to treat solid tumours with CAR-T, which would have pretty big implications. The CAR-T market as it stands is expected to be worth $6bn by 2025.

The board was really strengthened last year with the appointments of Katrin and Axel Glasmacher.

I just noticed that the Phillips University in Marburg that published the paper on the 4D second gen cancer drug and CAR-T therapy is the same one she got her PhD from. Wonder if there's a link?

She also did a lot of work for Bristol Myers Squibb with global regulatory affairs for their immunotherapy drug Opdivo.

BMS have had at least 2 failed partnerships/trials with microbiome therapies and Opdivo. They must be aware of 0518 and no doubt Katrin would have the connections.

I think in terms of amy further oncology partners I think they will have to do more than just provide their drugs for free. I think with the limited 4D bandwidth they would have to come up with some cash upfront.

The 1 patient being dosed is not a clinical trial. Stop implying it is.

It's an expanded access programme for compassionate use. The company will have to collect safety data but no valid efficacy data will be generated.

To avoid confusion I mean it is flagellin mentioned in the Merck paper not 0518

Very good article from last year. Mentions potential for fast track approval for 0518

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

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/

late summer start?

Letting that horse kick you in the head was pretty dumb too

0518 is the first LBP Immunotherapy for Cancer

Once the Bavencio trial starts it will add to the other 3 clinical trials

0518 with Keytruda
0518 monotherapy as alternative to chemo prior to surgery
0518 with radiation therapy on pancreatic cancer (results due later this year)

I have been looking again at the criteria for FDA Breakthrough Therapy designation.

A lot of the criteria seem to be achievable. I wonder if 4D have applied for it?

They have mentioned discussions with the FDA about accelerated approval pathways previously.

An example of the 1 in 4 success rate. Say there are 1000 patients that don't respond to Keytruda and will die but with 0518 there are now 250 that will survive and hopefully have a tumour reduction or at least stable disease.
That would be very significant.