Member Info for Sangijuelas1

Part A of the Phase I/II trial saw five out of the 12 patients (42%) show a clinical response, with these individuals achieving stable disease for six months or longer.

The hope is that this combination with Keytruda can help patients who have already failed on a different first line checkpoint inhibitor.

“What we are saying is we can re-engage your immune system so that Keytruda effectively starts to work,” said Peyton. “In patients who have been on checkpoints but who start to progress, who are then given MRx0518 plus Keytruda, saw 42% clinical benefit.

He added: “Last week, we reported a couple of those patients who have now been on the drug with stable disease shrinkage in tumor sizes for over 18 months now. So, that’s a pretty phenomenal response.”

The 42% disease control rate observed in Part A easily exceeded the predefined 10% threshold for expansion in Part B, and the company is now recruiting more patients onto the trial.

The company has just received more good news, with the 8 February announcement of a collaboration and supply agreement with Merck KGaA and Pfizer to study MRx0518 in combination with their checkpoint inhibitor, Bavencio (avelumab). This will be as first-line maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

The forthcoming SPAC merger and the funding it generates plus the new collaboration are encouraging signs for the company. However, 4D Pharma needs to drum up much more funding in order to progress its trial program, as it only has a clear financing runway up to Q3 2021.

If it can generate more investor interest, the company can start to spend in other promising candidates in its preclinical pipeline, including CNS diseases. The company is investigating possible live biotherapeutics which could work across the gut-brain-axis as treatments of neurodegenerative conditions such as Parkinson's disease.

Peyton told Scrip that the company had struggled to gain momentum in recent years, its share price battered by volatility in its UK-based AIM listing, and lack of specialist investor knowledge in the local market.
“We've been looking in the US for a period of time, because it offers a greater depth of capital, but also more specialist health care investors,” said Peyton.
“We were doing all the right things in the company, we had [generated] great cancer data, but we just weren't getting the recognition that we wanted and that was probably a metric of the markets and the UK industry.”
The company’s AIM-listed share price currently stands at 129p ($1.79) with a market cap of just £170m ($236m). This is up from a low point last year where its market cap plunged to £70m, but it still does not give it the option of a standard IPO.
“Even today, we are probably too small to do a traditional IPO. So we're doing [a SPAC] to get a NASDAQ listing, and get some certainty of capital in to the business. We feel that provides a great platform to access US investors, and then we can use this to bring more capital into the business.”

Peyton believes the move to dual UK and US listing will help it demonstrate the strength of its live biotherapeutics, derived from the human microbiome via proprietary drug discovery platform.

He indicated that this would make it very different from other microbiome companies rushing into the space that talk vaguely of “good and bad gut bacteria,” a trend which has made some investors wary of hype around the field.

4D Pharma says it is developing an understanding of the mechanism of action by which single strain bacteria can activate a range of immune responses.

MRx0518 is based on a Gram-positive, motile, anaerobic bacterium of the genus Enterococcus. The bacterium’s whip-like flagellin protein is understood to be a potent TLR5 agonist, which has been shown to activate both innate and adaptive anti-tumor immune responses. Phase I data analysis of 17 solid tumor cancer patients in which MRx0518 was used as a neoadjuvant monotherapy provided a clear picture of its immunostimulatory effect, the company said.
The study, carried out in collaboration with Imperial College London showed the oral, twice-daily capsules increased activity of tumor CD8+ T, natural killer (NK) and cytotoxic cells as well as systemic immunostimulatory cytokines and chemokines. The company said responses were particularly marked in five breast cancer patients, where a reduction in Treg cells and neutrophils were also recorded, suggesting this as another lead indication for the therapy in future trials.
Keytruda Combination Study
Meanwhile, initial results from the study combining MRx0518 with Keytruda, being carried out by Shubham Pant, professor of investigational cancer therapeutics at University of Texas MD Anderson Cancer Center, are also promising.

4D Pharma Joins The SPAC Trend To Fund Its Keytruda-Boosting Biotherapeutic

While the US biotech sector has boomed during the pandemic, with dozens of start-ups going public via mergers with special purpose acquisition corporations (SPACs), European companies have so far largely missed out.

That is about to change, with UK-based 4D Pharma, plc due to complete a NASDAQ listing this month, by way of a $37.6m merger with a SPAC.

US-listed SPACs are essentially shell companies that exist to merge with private companies – or in the case of AIM-listed 4D Pharma, a company that trades publicly outside the US. The private or ex-US firm becomes a publicly traded company in the US via the SPAC merger. The money that SPACs raise in their IPOs goes into a trust to be used for the acquisition and operation of the target company.

Dozens of investment firms formed SPACs focused on health care and life science opportunities then launched IPOs to fund the entities in 2020. (Also see "IPO Year In Review: Record-Year Bodes Well For 2021, And For More SPACs" - Scrip, 27 Jan, 2021.) 4D Pharma is merging with the publicly listed shell company Longevity Acquisition Corp., a transaction first announced in October. (Also see "Finance Watch: A SPACtacular Week For Biopharma Deals And Dollars" - Scrip, 23 Oct, 2020.)

Last year, the average amount of dollars put into trusts by SPACs following an IPO was $400m, up from $200m in 2016, across all industries, according to a McKinsey report. Traditional biotech IPOs raised an average of $193m in 2020, by comparison.
For 4D, the merger will bring in much need funding, but very little disruption: existing shareholders will still own around 87% of the company, and there are no plans to change its strategic direction; all its existing directors will continue to serve in their current roles.

The move will make 4D Pharma the first UK biotech to use the alternative route to market, and should provide it with a much greater visibility to US investors, who it hopes will fund development of its pipeline based on live biotherapeutic products (LBPs).

LBPs are orally delivered single strains of bacteria that are naturally found in the healthy human gut, and act to stimulate the immune system. The company’s lead candidate MRx0518 is currently in a Phase I/II study in combination with Merck & Co., Inc.'s immunotherapy blockbuster Keytruda (pembrolizumab) in solid tumors.

Seven years on from its founding, CEO Duncan Peyton believes the company is on the cusp of securing its future by providing proof-of-concept of its platform. Initial data from the Phase I/II study published in November showed promising responses in a handful of heavily pre-treated renal cell carcinoma and non-small cell lung cancer patients who had developed resistance to checkpoint therapies.

Can anyone get on this interview? On the link you can register for the free trial but it has to be using business email
https://mobile.twitter.com/4dpharmaplc/status/1362064186101149698

Nice comment Michael. I realise that my comments are disturbing to those who are here for a quick profit.
I aim to be here for the duration and I am conscious of future obstacles to realising substantial gains.

Davetherave-the latter part of your comment is exactly right. Shares bought in Primary market (IPO or placing) need to be able to be sold in the secondary market (us lot) otherwise no one would buy them.
Imagine everyone sold out of unethical investments and into "ethical" it would be easier to raise capital for worthy causes.

Just thought they might want big investors or Cantor Fitzgerald clients only I guess. I am interested in the other company that's presenting as well- BiomX- looking to commercialise Bacteriophages, which was the alternative to antibiotics in the old Soviet Union.

Anyone else going to join me. I expect I will be kicked out but I have the link

I have heard previously that HL can hold ADRs in a Sipp but check with them. AJ Bell say they will look at it on a case by case basis but they will not do anything not settled on Crest.

It's HMRC ISA rules on American Depositary Receipts.

I moved from Fidelity to AJ Bell to be able to hold US stock

Today at 3pm. No doubt some other LTHs will be too!

Just to clarify last comment, it would only be ineligible in Isa if delisted from Aim

Rog you can hold Loac because it is a full Nasdaq listing. It is being reverse mergered with 4D and converted to ADRs and so for Isa purposes it will become ineligible. It should still be OK for a Sipp but depends on the providers rules. I would maybe check with your broker and get a definitive answer from them. Either way it can still probably be transferred to a standard dealing account.

2 UK biotechs listed on Nasdaq. Verona Pharma and Mereo Bio pharma (held by Woodford as well).
They then both delisted from Aim and UK shares were converted to the US American Depositary Receipts. Once this happens they can no longer be held in an Isa due to HMRC tax rules and so have to be in a dealing account and so subject to CGT. AJ Bell have said that they can't be held in a Sipp either but other providers may allow this.

I am also invested in Tiziana who I think will also delist. I can't buy the US shares as they don't settle on Crest. Again AJ Bell, I have heard that other UK providers do allow this.

A measure of a company is how it treats its small shareholders. I would like to know if LBPS is going to settle on Crest as then I will start buying LOAC shares as our biggest shareholder Steven Oliveira is doing.

It's not saying that they see value, it's that value will be realised in the US. Email to investor relations below.

Hi,

My questions are being asked as I am concerned that there might be a future delisting from Aim by 4D.
Can you confirm that LBPS will settle on the Crest system? Tiziana have a US listing but this can't be bought by my broker AJ Bell as not on Crest.

Duncan has commented today about Woodford in CityAM and said that value in UK biotechs like 4D will be realised in the US and not the UK. This does not sound good for UK shareholders prospects as I believe it hints at an eventual delisting from Aim.

I would like to know what safeguards are in place to protect the interests of UK shareholders, some of whom have been supportive of 4D to help it get to the point where it can attract US investors. For example, if there is an Aim delisting this will mean that US shares can no longer be held in an Isa and maybe not a Sipp either.

I note from the SEC statement and prospectus for the Nasdaq listing that the board received no opinion as to whether the Nasdaq listing was in the interest of UK holders and the board themselves concluded that it was.

So what do you think he means when he says value will be realised in the US and not the UK?

Delisting from Aim?

Why would he buy a few million Aim shares if DP is saying value will be realised on Nasdaq and not in the UK?

I think he would have done better to keep his mouth shut. Woodford didn't lose his own
money, he lost over £1bn of small investors money by running a fund that made a mockery of the FCA rules.
His name is mud, you only need to read the comments under any FT article about him to get an idea of the depth of bad feeling towards him.

"US investors will benefit from companies which I feel are undervalued in the UK and value will ultimately be recognised in the US,” Peyton said. “

I find this quote quite disturbing. Sounds like prepared to put US shareholders interests before UK ones.