We would love to hear your thoughts about our site and services, please take our survey here.
CrustyPete
Please read my posts too. What I said was "Even if one claimed that we are not on funds' radar screen because of market cap (it's nonsense by the way)".
That doesn't mean we are on most funds' radar but the explanation that 4D can't attract (some) suitable II's because of its market cap doesn't make any sense.
You appear to be making a point that some funds have market cap size restrictions: and then what? Of course some of them do - some may put rules above their investment strategy, others don't. There are others that simply have the upper size of their investment dictated by market cap.
I've seen IIs (of all sorts) investing in innovative early stage companies of bigger value than 4D(!) ... in the broader UK biotech sector. ?'ve been an active investor in a couple of them!
CrustyPete,
Please see my response to Sanji. You are giving a very narrow perspective of IIs and ignoring the plethora of types of IIs (small private equity, VCs, activist investors, specialist). There is no excuse for 4D not to be on the radar screen of a good number of II investors given the stage it is at and has been! Of course funds would tend to have some limits (e.g. geography) or exposure per company but ultimately, isn't the whole point of investing to discover value when others haven't?!
Sanji
You appear to be unfamiliar with the investment side of things. You presented share price drops without showing though the respective market caps. That's quite a partial presentation of information!
For example, Seres's market cap stands at USD750m, Finch's at USD 412m and (even) Evelo's at USD 175m vs 4D's at ...USD 82m!!
Conclusion? Yes, impressive as 4D may be on the scientific front (so far), 4D management and CEO in particular are doing a staggeringly bad job in attracting credible institutional investors (given the progress across programmes). So Duncan Peyton needs to get his act together on the investor front.
The fact that it is a UK company may be relevant but only to a small extent. After all some of the 4D trials are in the US. Even very slow moving Scancell (based in the UK, isn't it?) has managed to attract II's! In fact, I'm an investor, or know well, innovative early stage / startups - in the UK - that have done a much better job than 4D in attracting VCs & other IIs.
If 4D weren't advanced enough for specialist biotech funds then VC (venture capital) funds and some of the smaller private equity/ specialist investors should still be interested.
But again, you seem unfamiliar with the investor side of things, sorry!
In my view, normally, Duncan Peyton hasn't been a bad presenter at all. Though he could try and speak a bit more clearly for the sake of non-UK investors. In general, he comes across as serious and reliable and for a biotech company that should be a good thing. In fact, I think the into-your- face loud style of salespeople with exaggerated face expressions is very off-putting - again, that's in my view.
Nonetheless, at a critical time relatively recently, when investors needed to be reassured that the back-to-back delays in 0518 didn't mean disappointing results he seem to lack the energy and the enthusiasm and came across as hesitant. That was a faux-pas as it raised questions in people's minds.
On the other hand, where there is a complete dichotomy is between the impressive (so far) track record on the scientific front and the unimpressive investor base: the 4D story hasn't attracted important new institutional investors in the last 18 months +. Even if one claimed that we are not on funds' radar screen because of market cap (it's nonsense by the way), the FAILURE to attract investment even from venture capital (who focus on earlier stage companies) is staggering: as a result, the £60m market cap (frankly anything below £200m) reflects badly on 4D and the CEO in particular.
They should be roadshowing, knocking on doors, doing everything in their power to bring in CREDIBLE INVESTORS. A ridiculously low share price is not in anyone's interest despite the fact that management have partially hedged themselves by granting options at such low prices. The 4D SP fortunes can't be tied to whether a (distressed?) investor decides to sell or not... in other words 4D shouldn't be hostage to SO or any other SO...
Finally, even though it is dangerous to assume that the market has got it wrong (or hasn't discovered us) and we have got it right, I'm staying the course until next 0518 results at least, as I think this company will deliver...
Yes of course drug approval cycles are lengthy but perhaps we didn't realise when first reading the RNS, how big a milestone is FDA clearance in case of MRx0005 and MRx0029!
FDA has been known to raise issues that can take a long time, years even, to resolve, if at all e.g. in the case of Scancell, FDA questioned the method of a drug-vaccine delivery and that delayed them for years!
Now this is a first-in-human trial for a new drug class aiming to address a neurological illness (not exactly a flu)! We have clearance from a regulator that is known to be demanding (perhaps sometimes excessively so) and significant time and efforts are required for its approvals (IF they come)!!
What a milestone!
A couple of very important "firsts" here:
- LBPs clinical trial for the treatment of Parkinson (and possibly neurological illnesses more generally);
- bringing possible solutions for a neurological illness by addressing causes and attempting to provide "fixes" rather than mere treatment of symptoms.
4D in particular enters now officially into neurological arena alongside those of oncology, respiratory and IBS.
Indeed very helpful - echoing the thanks to Phil G.
Very interesting to note:
(i) accelerated approval was given as a result of demonstration of data from a subgroup;
(ii) even within the subgroup, there was a relatively low durable objective response rate (ORR) at 16% - that sufficed and if you think about it, it makes perfect sense! Even if the percentage of patients that benefit is small, why shouldn't they have recourse to an additional option?
(iii) the range for duration of response was reasonable (range of 2.4 to 27.7 months)
Using the above as points of reference and assuming positive part B data (so far), MRx0518 should stand good chances of accelerated approval for a subgroup (at least).
Having said that, can't be sure how much difference it would make if the FDA application was made by a multinational pharma vs a small biotech. I can imagine that in some ways it would.
But assuming positive results (for the biomarker subgroup at least), would it also not make full sense for MSD to co-sign or be seen to endorse that 4D application for 0518's accelerated approval?
In fact we had just over 1.58m shares traded at closing yesterday so just exceeded the upper part of my suggested target range of 1-1.5m!
Such a decent volume was combined with a small but significant rise of 2.4% or so indicating that, on a net basis, investors are taking long positions. As good as one could hope and especially if such trend continues. We also some a good number of medium to big trades including one that I noticed for circa 140k shares.
Assuming this trend continues and barring a world crisis, we may well have turned a corner - SP wise. Hoping for an ENCORE of the August / September 20.
However, the real RE-RATING will happen as meaningful news is announced or even as the news date(s) is/are approaching. But looking again at the February presentation we can be cautiously optimistic. The presentation highlights proof-of-concept for 0518 (for both Keytruda combo and monotherapy). That's based on announced results-to-date but would they have highlighted that only a few weeks from announcing news related to 14months or so of fresh data?
Currently, if I had to choose I'd favour high volume than SP rises (with modest or low volume of trades). That's provided that SP was not sliding downwards as a result.
High volume, provided SP was under control, would imply that new investors are arriving, or are returning, and that any remaining stakes to be sold are happening sooner than later.
1-1.5m will do for today ...
We are seeing very healthy volumes today as we are at almost 1.4m just after noon and that’s hand-in-hand with a small rise in price so ... even better. I think Phil G may well have been right the other day claiming that one or more IIs may have already started building position!
Yes such rise is from vertiginously low levels but it is better than a further slide.
As for the Ukraine situation, the uncertainty could carry on for sometime. I am more inclined to agree with Crl123’position rather than GtIV’s: don’t see how Putin can be an astute chess player by managing to alienate most of the world, in different ways, including threatening a neighbour that is much more democratic than Russia. Now Sweden and Finland are thinking of joining NATO! Who’s next?
Anyway, back to 4D: irrespective of the situation and once more, it’d be great to be kept much better informed by the company. Also I agree with HRG’s position last Friday that even good 0518 trial results need to be accompanied by shrewd moves on the business side. It’s not enough to say oh that’s a nice shot, and leave it there (exaggerating a bit to make the point).
We need to learn lessons from Blautix where to-date we haven’t seen any major developments for almost two years now: why waste (so far) the opportunity to become a more established player in microbiome therapeutics after a successful phase II trial? 4D could have made much more of Blautix as the drug that PROVES 4D's platform even though it may not be the drug of top strategic importance for the company.
That way it would pave the way for QUICKER clinical and market acceptance of other, more strategically important, projects (notably 0518) assuming that we get further positive topline results.
Let’s not forget how Seres’s market cap was completely transformed (increase 7X in share price) back in August 2020 after positive results in phase III trial of a microbiome therapeutic i.e. SER-109 for recurrent C. difficile infection.
Not sure what has been going on behind the scenes but hopefully we have been planning carefully how to manage part B initial data - a good pointer as to how the rest of part B trial will unfold - which most of us expect to be good or better!
And we have a key question which would impact on the market that 0518 would potentially address:
Is 0518 a potential "fix" for a possible flaw in ICI's IF the Treg cells are actually induced by ICI's and Keytruda in particular?
OR does 0518 simply enhance the ICI's (e.g. Keytruda or Bavencio) effectiveness by complementing their action?
Of course it would be preferable if it was the latter as, in that case, it could be marketed as a synergistic drug as opposed to a drug that is fixing another drug's problem .
However, in either case the addressable market would be very significant indeed.
Phil
Re your recent posts:
- First, fully agree that a market cap of £60-70m is a joke: the valuation is that of a promising start-up (!) instead of a company at the stage of where 4D is at and with such a promising pipeline at a relatively advanced stage overall! The market cap is even very low compared to other UK biotechs: e.g. it is circa half that of SCLP which is also targeting oncology and has potential therapies at phase II trials. I am not even going to mention comparison with US biotechs and those focusing on live biotherapeutics (LBP) in particular.
- Fully agree that SO could be easily, or have been, a red herring if we had a clear, meaningful and positive update re 0518. Such a positive update, when and if it lands, would be a game changer as it would suggest a (very likely) successful outcome of a phase II LBP in oncology... wouldn't that be a first worldwide?!
In that case, market cap should be catapulted somewhere in the many hundreds of millions USD if not pole vaulting over the US$1bn mark (depending on how positive the update was). Any impact from SO would pale in comparison and possibly ... even SO would start buying again.
- The extent of the back-to-back delays in releasing some kind of progress report (not even talking about results!!) is unkind to investors who most supported 4D and doesn't do much good to the image of management and the CEO in particular Judging by the level of the share price that seems to be a general view: 12 months have lapsed (as of today) without a clear update / progress report re combo trial 0518 and keytruda if we exclude the very limited info we got in September.
- The possibility that data on 0518 won't be good has become, in my view, very low at this stage. Question is: how good will the data be? Have we seen unequivocal benefits for a percentage much higher than 10% of the enlarged sample or even for patients with a biomarker or will there be need for further work?
- Investors shouldn't take notice of the posts which are not based on substance or solid arguments (be they positive or negative). If anything, the plethora of recent posts that warn you about further SP falls and/or advise you to sell can be quite amusing :-)
Finally, there are only a few weeks left until end of Q1. Like I've said before if we don't have meaningful update by then it's gradual and orderly exit time for me unless we have a meaningful update or, as an absolute minimum, some account for the delays. Hoping and inclined to think we will have an update with strong data by then!
OK here are a couple of things I'd like to bounce off others:
(1) First, in the RNS of 30-Sep-21, the Chairman & CEO review noted:
"The main focus of our work in oncology at this time is the preparation of a pivotal development program for MRx0518 in an oncologic indication. "
Originally I thought this might be a reference to Bavencio but in the same RNS they had noted: "With our lead oncology candidate MRx0518, we have built on our ongoing work with MSD (Merck & Co.) and its anti-PD-1 immune checkpoint inhibitor (ICI) Keytruda® (pembrolizumab), announcing a new clinical collaboration and drug supply agreement with Merck KGaA and Pfizer and their anti-PD-L1 ICI Bavencio® (avelumab). In contrast to the ongoing study with Keytruda in ICI-refractory patients, the new Bavencio collaboration takes MRx0518 into earlier lines of treatment, and expands our clinical portfolio targeting the PD-1 axis."
So if it had been Bavencio why would they have taken a cryptic approach in the same RNS? Do we know to which programme they were referring? Is it still relevant?
(2) Second and as a separate point, do we know whether the specific biomarkers which make patients more likely to respond to 0518 (with or without ICIs) are induced as a result of treatment with ICIs or other cancer therapies or are they simply a characteristic of the individual patient concerned? Just trying to assess whether we are talking about a sizeable portion of refractory patients that are likely to respond.
Following extract is from RNS of 15-Sep-21
"· At baseline, patients who achieved complete response, partial response or stable disease for at least six months (collectively 'responders', N=4) from the combination of MRx0518 with Keytruda® (pembrolizumab) had significantly greater densities of CD3+FOXP3+CD8- regulatory T cells (Tregs) and CD3+KI67+ proliferating T cells in tumors at baseline, compared to patients with progressive disease (PD, N=8), p=0.0381 and p=0.0048, respectively "
Boonco,
Sorry, you are wrong. I am all up for a reasoned debate with well-founded arguments. That's one of the main reasons I post on this bb! The issue though is that you seem to adopt a "holier than though", lecturing styled approach. And, back in early November, your arguments that things were going very well with 0518 trial were quite arbitrary and flimsy. Hence my questioning of your motives and that's still the case.
After all, I have quite a significant exposure here and, back in November, I would have been all too happy to receive some (well-founded) arguments or pieces of evidence as to why things were progressing well with 0518 trials! Sangijuelas, for example, did help, at some point last fall, to join up some of the dots when 4D was drip-feeding with insufficient information.
I have considered, at times, trimming my exposure to some extent because of the lack of progress reports (with good or bad news) BUT the one main factor that kept me going is early information released and statistics. I noticed you haven't commented on the actual content of my original post on this thread.
Finally, you claimed on a different thread yesterday that you work with famous clinicians worldwide. This may or may not be true but I can't recall many comments or links from you on the science or even the pharma business front.
Let's keep the posting on 4D from whichever perspective we may be interested in the company.
MHB
Boonco,
Now you came up with the quotes, I trust you can see yourself that there is not a great deal of coherence between the claims in your earlier post today and the quotes you came up with! Sorry to state the obvious but it is actually OK for people to raise questions re an investment in which they are long and to be concerned about back-to-back delays in announcements re 4D's flagship trial!
On this note, I note you do not answer the question whether you are an investor yourself :-)
In any case, good luck with whatever it is you do.
Boonco,
From my actual posting history, can you please quote my post(s) that made you think "Not that long ago i.e. only 2-3 months ago you were saying you think things with mrx0518 haven't gone well and they've needed to change things." ?
You seem to be drawing conclusions somewhat arbitrarily, not sure why. Perhaps you are confusing the raising of a possibility especially in the absence of well overdue information (which most investors have had an issue with), with being convinced that things are or aren't going well.
As a result I have not really changed my mind and 4D and its trials are still a risky investment proposal.
Also, let me ask and please don't take this the wrong way: are you a real investor in the company or do you have some kind of (junior) PR role on this board? From the style of your posting, I have my doubts you are an investor but it could just be my idea.
Finally, were you always convinced about the success of 4D's trials?
And not only that, yesterday I increased my holding by 40% in terms of number of shares after selling a share in the O&G sector (though given my excessive exposure to 4D, that 40% is aimed to be turned around in the short term).
Well, what has kept me going despite what I perceive as management shortcomings - such as insufficient and very sporadic information flow - is … statistics.
In part A of phase I/ll Keytruda & 0518 trial a 10% clinical benefit re the very small sample of patients has been the target.
In other words, a clinical benefit in 8 or 9% of patients (i.e. say 1 patient out of 12) would have probably meant that part B was not to be, at least not without reformulation of the trial.
Initially, we saw clinical benefit in 5 which lasted more in the case of 4 then 3 patients – up until the last time we were informed.
Now, what is the probability of having 3, 4 or 5 cases seeing clinical benefits IF the probability was less than 10% say 9%? Low is the answer. How low?
https://stattrek.com/online-calculator/binomial.aspx
Try:
- probability of success on single trial = 0.09
- number of trials = 12
- number of successes = 3 then try 4 then 5
Result is that probability of number of successes being 3 or more, 4 or more, 5 or more are:
8.7% would be the probability for 3 or more successes
1.8% for 4 or more successes
0.2% for 5 or more successes
(that's when the hypothetical probability for one success is 9%, i.e. just below the success threshold of 10%: that's in a large sample of 100 patients, having 9 people seeing a clinical benefit).
In other words, EVEN for a very small sample of 12 patients the chances of having 5, 4 or even 3 patients with clinical benefit WOULD range from low to extremely low, IF the probability was below the THRESHOLD of 10%. So VERY LIKELY that the probability of success is higher than 10%!!
OK this is a simplified analysis ignoring there are different types of oncology with which we are concerned and have made the assumption of binomial distribution. However, even if the therapy was only sufficiently effective against one or two types of cancer that would undoubtedly still be a success.
These seem very strong early results judging by the clear difference between MRx-4DP0004 and placebo vis-a-vis all criteria / secondary endpoints assessing improvement in patients.
Though, arguably even more important than the positive, more detailed data on the asthma trial, is that extra mileage towards validating the 4D platform:
"These results further demonstrate the ability of 4D pharma's MicroRx platform to identify Live Biotherapeutics that are able to drive systemic effects and deliver new treatments to patients in need."
Each of the company's drugs under trial have their potential value. However, if the platform i.e. 4D's methodology of identifying potential drugs, is on the right track the company's value is much bigger than the sum of parts.
Looking forward to progress report re Keytruda/0518 trial BY END OF Q1.
Maybe SO will start buying now!
".... We look forward to working with Chariot in order to quickly progress the gas development." it helps a great deal that the government partner & joint-owner is not only on board but seems to be in a hurry. That's not to be underestimated.
There is a factor that will affect the valuation of the company in an almost binary fashion: a year of data from the combo 0518 trial. Even big investors don't like such risks: look at SNG (last year), TILS or CHAR (very recently) from the oil and gas sector. Not many IIs like taking positions shortly before the announcement of major news. But, because of the seller and the shorters in the case of 4d, a negative outcome (less likely as it may be) has effectively been priced in ... a positive one though will be a boost ... a very positive one should catapult the company into the Seres league, well for a start!