Member Info for rhubarbmk2

Oh - and if you don't feel fully versed in some of the tech, there are loads of friendly posters here - easy to spot the genuine ones - who will always be happy to add some meat to the bones if you have genuine questions that you'd like to ask pal.

No I don't think you're a de-ramper at all, and you highlight well the pitfall of this platform. But I suppose it is useful to "DYOR". For example, I personally wouldn't invest in much at all outside biotech, because that's my area and I am capable of doing my own research. If you have knowledge or skills in, for example, engineering or minerals, obviously that'd be a good area to invest in more comfortably.

Inanaco,

The primary objective of this Phase 1/2a study has encompassed an examination of the tolerability and safety of VAL201. I think we can agree that this has been a resounding success. Another objective was to garner early indications of efficacy. Although we await a thorough breakdown for this, the compound was dosed across a range of heterogeneous (in the genetic sense) range of tumors, in patients with both local and metastatic disease, and in patients both sensitive and refractory to previous medication. We know that, in over half of these patients, they responded to treatment. Now, VAL could have chosen to carefully select patients, co-administer adjuvant therapies (e.g. MRx0518; 4D, SCIB2, Scancell), or indeed surgically retract the primary tumors before therapy first (e.g. SCIB1; Scancell). Let’s say for argument that this approach resulted in a positive response of 85%. Nice RNS, lower utility; fewer patients potentially helped. My reasoning is that VAL saw this as a first-in-class drug to be used across a relatively “broad-brush”, a bit like good old anti-testosterones.

You make an excellent point about a subsequent Phase 3 study. I’m so glad that you mentioned that. As a measure of clinical “utility”, the trade-off will be efficacy versus safety. By this stage, the patient selection criteria will probably have been narrowed, and the dose will have been fully optimised. Will it work as well or even better than the current Standard of Care? Maybe; maybe not. Will it have fewer side effects?; most probably. We know VAL201 would likely to score incredibly highly in the safety stakes. Will it be the next “statin” for Benign Prostatic Hyperplasia? Who knows?; this is where we can all postulate, but this is where we go.

You ask about performing further Phase 1 studies with shareholder money, maybe to generate further data. Drilling down to those with specific forms of this disease, along with higher challenge doses, as you know, can easily be done during the Phase2b study. Why didn’t VAL do it now? Because they want to crack on, maximise the patent, and not delay the expansion of the dataset properly, which will require external investment. Furthermore, they know all too well that they’d like to examine the utility of VAL201 in other therapy areas – e.g. breast, uterine, and ovarian tumors. VAL could fiddle about with this ad infinitum to satisfy the desire to know what happens at 16mg/kg, for example, but they don’t need to yet. They want to write up what they have, find a partner, save you as a shareholder – cough – money, and crack on.

I think that this has encapsulated your questions, and is all I can add, but, as I said yesterday, the QandA is open for questions. If you’ve determined any perceived serious flaws in the study design, or RNS release, and don’t use this channel to have it addressed, I think that would be what the kids call "trolling". Have a good day pal.

EyeGuy; good insight. As Grace says, the contributions were getting more barrel scraping as time went on. Let's hope there are progressive tie ups announced in due course; I think that would finally empty that barrel! Grace; good insight into the patients from the first phase. I'm also thinking the same re. Initial numbers, and hope that's the case. The further indications also excite me and I hope that some if these alternatives can be explored in the next studies. It may be the case that a couple of preclinical bridging studies in alternative targets would bolster this approach.

Grace,

There's not much to add to your post. You do yourself a disservice in your modesty. I tried to tackle points three and four of that particular poster's "concerns" this morning, and you've really reinforced that better than I could. An acute observation that I have made, as yourself, is the appearance of "scientific" posters on here, who like to come on and pick holes in the study design. I'm not sure what their motivation is, but I take solace in their posts, because they do have that motivation, so there must be a driver. It is easy to pull out the limitations of any given study; you've done it succinctly and concisely yourself. As scientists, we can see the potential limitations, and also the opportunities. Peer reviewing with the retrospectoscope is easy. If we had time, we could all pop over to other Biomed forums and ask why they dosed their compounds in combination, and how that may have masked the true effect of their great hopes etc etc, but we chose not too. Because we like to concentrate on our own concerns and interests. I'm not sure of the psychology behind it, but it seems to bring pleasure to those who have been fortunate to have had a scientific education, to strike fear into those maybe less well-versed. I await more data myself, and hope that my personal actions do not encourage or discourage people to invest. However, when there's flagrant whipping up of fear, for no reason other than to satisfy the sad ego of someone who really should take a look at themselves, then it is up to those of us who can shed at least some light to step in. And, to be fair, you're taking the prize for that. So please do keep contributing, because I for one really, really, enjoy your posts.

By the way; I have every confidence that Suzy, Kevin et al. know the potential of this test article for patients (as a toxicologist and pathologist I'm still flabbergasted with that lack of meaningful side-effects), which looks to be very kind indeed. And I know that they know that this could extend beyond prostate. I can also guarantee that they are not the types to get blind-sided or flattered by the "big" pharma boy and girls. Finally, the fact that they have managed to sign a collaboration agreement with a Japanese Pharma company (form experience, this is incredibly difficult; having to manage big group buy-ins and team ownership), I have every confidence that they certainly know how to handle VAL201.

So many options make it hard to specifically value; Joint Venture with external funding; Joint Venture with the collaborator footing the bill and upfront, milestone, and commercial payments (preferred option), or outright sale. Either way, if option 2, based upon recent acquisitions, someone may as well buy the company; because, and this is a personal opinion, an upfront payment could likely be worth substantially more than the current market cap. But as a shareholder, I'd be voting that option down. I'd like to think, however, that this would be unlikely, as we do not have a current shareholder (to my knowledge) with >25% of the shares, who could start pursuing a movement toward exercising majority rights. For reference, see what happened to John Moulton/Redmile/RedX.

Genuinely don't know pal, but it looks like Suzy's next Q and A will be a thrilling instalment.

I would imagine that the protocol wording permitted intra-patient dose escalation at "up to" 16mg/kg, rather than "at". The detail will be logged with the MHRA if you're interested. I doubt they'd remove the authority if they just simply didn't need to do it.

Not dose limiting for the purposes of the evaluation, but dose limiting as per the preclinical allowances.

I'm guessing that, possibly due to metabolic differences, the human exposures were higher than could be predicted from the rodent. Protocol wording would have dictated not to exceed the exposures evaluated in a rat tox. They were getting efficacy and tolerability at the exposures measured for 8mg/kg; no need, for the purposes of this study, therefore, to amend the protocol, delay, and go higher. An expanded Phase 2 would look at amended protocol wording, perhaps using bridging.

I know - imagine; efficacy, negligible side effects, and you've not even pushed the dose.

I didn't mean you pal; you weren't ramping. I was just being conscious not to get carried away with myself.

Hi Nelson,

Slow and steady, I don't like to ramp, but in answer to your question; yes. It has been tested in the AR-expressing MCF-7 xenograft. This is still based upon it's anti-androgenic potential, not to mention other growth factor (oestrogen/EGF) possibilities. There is talk of expanding future trials into other tumor types - there may be potential in breast, ovary, and uterus, to name the "big hits". I may ask Suzy if she could compile a summary of preclinical efficacy testing undertaken so far, at least that which is in the public domain. I think that this would be helpful and would certainly be something I'd like to catalogue for assessment.

As you say, many big issues have already been resolved - e.g. metabolism, pharmacology etc, using this preliminary human trial.

Hi Nelson,

There should already be potential partners on the horizon. Yes, they'll do due diligence; this can take weeks, and it depends upon the "expanded" dataset available from these studies, and if/when it is available. They'll want to dig into that, plus any preclinical work that was performed. They'll see if a bringing study is needed to increase clinical exposures, in a greater cohort of patients; all that and more. There were probably partners that were already taking a look at the preclinical stage. And yes, there may be more than one. I can't answer these questions definitively.

However, the one thing that I can tell you is that the chances of a good JV deal often burn down to personality and emotional intelligence, sometimes as much as the science (a bit like the reaction on Monday in some ways)! For me, this is where the REAL strength in the new management lies. Folk have noticed on this board that BOD members respond to e-mails, with clarity, and swiftly. Honestly, I've worked with groups like this all of my professional career, and this is, I have to say, one of the friendliest and most determined set I've encountered. They're solid, and, with a bit of enhanced PR (I'd personally like some google news hits, Proactive Investor interviews etc), which is in-hand, everyone can then see what I have encountered, for themselves. Then investors can make an informed decision. I personally think that confidence will return, day traders will stop using it as a short, and we can then hopefully see some real and sustained growth.

Starting today you will see Suzy. Very smart bean; enthusiastic! And then hopefully you'll start to see some of the other BOD members. Kevin Cox; balanced, knowledgeable, intelligent.

What's been missing here is PR. What isn't missing, and is much harder to "buy in", is scientific quality and personality.

When you've seen Suzy today, ask yourselves if you could work with her. I could, and, with a bit of luck, I won't be the only one.

Have a good day pal.

Oh - and with 54%, there should be no shortage of recruiting.

Hi Thoth2. You are right to interrogate the data available. I'm a bit rushed, but I'll just tell you that your points 3 and 4 are exactly the same reasons that excite me. The Phase 1/2a was crude in the fact that it wasn't specifically aimed at genetic subtypes, nor in specifically targeted patient populations, with, for example, certain resistance or sensitivities to previous therapies. You have really reinforced why the results may even be better than they suggest. Phase 1 after Phase 1 studies are now delineating specific and targeted patient populations to trial (see 4D). Whilst there is merit in doing this, it can obviously raise success rates. At a 54% response, in a "broad-brush" sweep; well, that's exciting, at least for me. Hopefully the data collated will now be able to define exactly who to go into, when, and with what exposure etc.

Apart from most of them knock you out like a sack of spuds; this one looks to be positively homeopathic in it's side-effects.

Bang on; then take the disease heterogeneity and lower doses out MathsProf (when the data arrives).

Morning all,
I have more, but I'm still sub 4% "new" threshold", so there won't be an RNS; maybe the website will be updated to reflect this.
Two things:
1. There is not going to be a placing.
2. There is going to be an interview.
Have a good day everyone, A