Evgen Pharma Share Discussion Threads

[lovewinshatelosses] 26/9/2019 13:07

My thanks too timbo; I have also read a few of your posts over time, and value your opinions highly.
I am torn over whether to add or simply to hold here; this relentless selling on no bad news has influenced my original plan to have a little top up if it went back to circa 15p (and I may well kick myself for not being more brave here). Right, I will leave you all in peace for now, as I am conscious that I am not actually bringing anything of interest or particular note to the table here! Have a good afternoon gents and ladies.

[timbo003] 26/9/2019 12:54

Definitely not a seller Nobby, would like to buy a few more, but I probably have enough already.

[nobbygnome] 26/9/2019 12:33

Thanks timbo! So are you a buyer, a holder or a seller at this juncture?

[timbo003] 26/9/2019 12:29

A few thoughts following some of the recent comments on the SAH study

First of all, it is worth bearing in mind the market’s perceived potential value (and risk adjusted value) of the company’s clinical assets:


Finncap Initiation note (April 2019)

Metastatic breast cancer value of (£30m) 30p per share that would rise to c.£60m (60p) on a successful Phase IIb study. This excludes any upfront licensing payment that would be expected on successful completion of the proposed Phase IIb study. This could be of the order of order of $50m or c.35-40p per share. The de-risked NPV is c.£300m (excluding upfronts and/or milestones).

Subarachnoid haemorrhage value of £14m (15p per share). A positive readout of its Phase IIb study in Q3 2019 would value the potential royalty stream at c.£50m, which together with the value of a potential upfront payment (c.£30m), should the company license the asset, implies an asset value of c.£80m.

Our target price attributes no value to any investigator-initiated studies in which Evgen would supply SFX-01 for Phase II trials in fatty liver disease (NASH), autism spectrum disorder and intra-cerebral haemorrhage (ICH) whilst retaining all commercial rights.

Our target price valuation would rise to at least c.£80m (80p) on a successful Phase IIb trial result in SAH. The downside risk, should the trial fail, is around 7p in our opinion. The current share price is more than supported by the breast cancer indication alone (c.30p).



Finncap update (May 2019)

The Phase IIb trial of SFX-01 in subarachnoid haemorrhage (SAH) is expected to readout in Q3 2019, following advice from clinicians and statisticians to leave the study blinded until completion of both primary and secondary cognitive endpoints at six months post treatment. A successful outcome would see our risk-adjusted value for this indication rise from c.£15m to c.£80m.

Our forecasts are unchanged apart from cash and LPS, which is reduced to take account of the 25% enlargement of share capital. Our target price is reduced to 35p to reflect this dilution. Our risk-adjusted target valuation of c.£45m would rise to c.£110m upon a successful Phase IIb readout for SAH, implying an increase in the target price to c.85p.




On March 18th the company stated: Following advice from clinicians and statisticians, and in the light of commercial considerations, the Company has decided to announce the primary endpoints (safety, tolerability and measures of blood flow in the brain) and secondary endpoints (relating to cognitive function) at the same time, rather than announcing them separately as previously indicated.

I would have been very surprised if they hadn’t taken that decision given the study design. The primary outcome is cerebral blood flow and one of the the secondary outcomes is cognitive function ( 7 , 28, 90 and 180 days post stroke). In reality, everyone (i.e. Clinicians, Investors and potential partners) will be far more focused on the secondary than the primary, so why compromise the blinding (and the statistical significance) for the outcome which is of most interest by prematurely analysing and reporting result from the primary measure (which will be of much less interest)?

This is particularly relevant in the SAH study as the cognitive function will be assessed using the modified Rankin scale (0-6 ordinal scale)

This will inevitably involve some subjectivity when assigning a score (with the obvious exception of scoring a maximum 6), therefore it extremely important to maintain the integrity of the blinding



Given the lack lustre share price action in the last few weeks, investors are bound to ask themselves, does someone already know the outcome of the study?

I think the answer to that is almost certainly no, with the small caveat that in some blinded studies where the design is control vs active, it is sometimes possible for the investigator to make an educated guess as to whether the active is having any effect, for example when one of the outcomes is unavoidably obvious (for example mortality rate).

For SAH on average around 40% of patients on standard of care die within 30 days and for the survivors c.50% will have long-term cognitive impairment, so if the investigator sees no perceptible improvement for these measures when looking at the combined blinded placebo and active treatments, they may come to the conclusion that the active treatment is probably ineffective, on the other hand if they see the mortality rate at 30% or lower and improved (lower) Rankin scores, they may conclude that the active is probably having an effect.

[pennyfalls] 26/9/2019 12:05

Nelson “ So what you are saying is that the company has been collecting data without knowing what data they are collecting?”

No, I’m saying the data is collected independently and results revealed to the company as a later date (as in all these trials).
Primary endpoint stuff like safety seems to be pretty much guaranteed from knowledge elf Sfx001 to date , but specific secondary endpoint SAH results and analysis isn’t

[90005nelson] 26/9/2019 10:04

From RNS 28th August: .....All patients received the current standard of care, a calcium channel blocker called Nimodipine in addition to SFX-01 or the placebo. Nimodipine, first approved in the late eighties, offers a marginal clinical improvement only..... The clinical team is now focussed on the cleaning, validation and analysis of the large volume of data collected in this trial.... (Now let's go back in time) From RNS 18th March;... Following advice from clinicians and statisticians, and in the light of commercial considerations, the Company has decided to announce the primary endpoints (safety, tolerability and measures of blood flow in the brain) and secondary endpoints (relating to cognitive function) at the same time, rather than announcing them separately as previously indicated....1) Nimodipine only offers marginal improvement.2)The clinicians are doing the analysis.3) The clinicians advised for commercial purposes, 6 months beforehand. (After collecting all the primary and 27 months worth of endpoint data.

[90005nelson] 26/9/2019 09:06

So what your saying is, the company have been collecting data without knowing what data they are collecting.. hmmmm well how would they know they have collected the right data in the first place?

[pennyfalls] 26/9/2019 08:15

Morning Nelson,thanks
I was specifically referring to risks associated with the SAH trials, as it seems you feel there aren't many/any?
Evgen have no idea what the data results are for these Secondary endpoints - and will only know when all results collated and analysed independently. That's the nature of double-blind trials.
So, what I'm saying is that your thoughts about somehow they know how the secondary endpoints isn't correct.
And there-in lies the risk.

[90005nelson] 25/9/2019 13:08

To understand the risk you need to know what the future plans EVG are: Big pharma companies are very interested in SFX-01 and one even tried to buy Evgen shortly before it was floated back in December 2015.But Franklin and his team want to deliver Phase II data on both breast cancer and SAH before concluding a licensing deal or dealsThere's no guarantee of concluding any deal or deals. EVG can be bought for less than £40M.

[pennyfalls] 25/9/2019 09:24

Thanks Nelson..
so let me ask you a direct question relating to what you appear to be saying:


What is the risk here?

[90005nelson] 24/9/2019 22:16

"Following discussions with our clinicians and statistical advisers, we have decided to unblind the SAS trial's primary and secondary endpoint data at the same time. By doing this, we will fully maintain the blinded integrity of the secondary endpoint data, which in this trial are particularly important as they will form the basis of the primary endpoints in subsequent studies. This approach will maximise the commercial value of the dataset from the SAS trial."This was taken from the RNS 18th March 2019. At that time, all the primary endpoint information was in that dataset along with 27 months worth of secondary endpoint information.

[90005nelson] 24/9/2019 21:36

So the last participant was February 2019 and they had taken the last data in September 2019, several months later, how much secondary endpoint information was in the database by March 2019 (when they made the decision to maximize commercial value of database) bearing in mind, they would have started collecting the above data from December 2016.

[pennyfalls] 24/9/2019 21:23

Hi Nelson,
I'm not saying it won't be. I'm testing out opinions.
I don't need clinical data or literature to back up concerns! Concerns are born of experience and being circumspect, and pure common sense.

If there was literature to back up concerns for all fledgling drugs then there would be no trials at all ! THIS trial WILL provide the literature, with little existing antecedence.


The trials themselves and endpoints will , in themselves, be the future references for what you suggest!

What you're saying, in essence, is that there is no risk based on little evidence.. And that's risky.

[90005nelson] 24/9/2019 21:11

"SFX-01 works by activating the Nrf2 pathway which in turn activates the expression of genes that promote the body's innate capacity to control the oxidative stress and inflammation that underpin many chronic diseases." There's plenty of literature and compelling preclinical evidence to support Sulforaphane/ SFX-01, but can you provide any literature to back up your concerns that SFX-01 won't be an ideal candidate for treatment of patients with SAH?

[pennyfalls] 24/9/2019 20:36

Hi Nelson - thanks for that
But if the secondary endpoints (cognitive improvements - "among others") aren't sufficiently statistically significant, where would that leave us?

Would that leave us with a drug that is safe, has some blood flow advantages, but still leaves people cognitively impaired?
And is that of use commercially?

[90005nelson] 24/9/2019 19:41

So the first participant was in May 2016 and the last participant was February 2019. They decided in March 2019, for commercial purposes not to release the primary endpoint data until releasing the secondary endpoint data at the same time. How much primary endpoint information would they have on their database by March 2019.? "We are excited by the outcome of this blinded study in an indication where there has been no significant clinical advance in more than 20 years," added Clare."

[pennyfalls] 24/9/2019 18:30

Nelson - How can you say "SAH results nothing to worry about there"?

The primary and secondary endpoints are to be announced together, and there would be no Market anticipation if everything was all in the bag already.
We are still awaiting results !
(with a slight caveat that they've stated rather cryptically that this is for "commercial considerations". This could be seen as a teaser for all going well - or just more food for confirmation bias)


and Nobby..thanks again..

and Timbo...are you there?

[90005nelson] 24/9/2019 15:44

All the information I give out stems from their RNS announcements. Feel free to research them yourself

[nobbygnome] 24/9/2019 15:40

>> pf

Sulforaphane hits multiple targets. You can't switch that on and off so all the targets are being affected all the time. The question is whether that is a good thing in all indications. I think it is the scientist in me that wants a drug which is clean in terms of it's therapeutic effects, although I stress the multiple effects may well not be an issue and may in fact be a benefit. So it could be my own prejudice hard wired into me over many years being a scientist in the Pharma industry.

So just IMHO and DYOR. In fact I would be interested in timbo's opinion as a fellow Pharma retiree and EVG investor.

[purple11] 24/9/2019 15:33

load up at 13/14p rinse and repeat.

more please...glh

[diamondstar1] 24/9/2019 15:29

Hi 90005Nelson,
Could you let me know if an interim analysis was performed on the first 90 SAH patients, and do you know whether the results for these patients showed a +ve trend?

[90005nelson] 24/9/2019 14:34

SAH results, nothing to worry about there. They had a database from 90 participants over 34mnths before deciding to withhold primary endpoint results for commercial purposes.

[90005nelson] 24/9/2019 13:09

EVG are looking to attract a partner /co-investor and are possibly in communication with several potential's. It could well out license SFX-01 to more than one.

[pennyfalls] 24/9/2019 12:40

Ps..Like it that people are airing a few honest views. Very healthy.

[pennyfalls] 24/9/2019 12:03

Indeed ASAT91 - and that had crossed my mind too - although if that was the plan, it had a very limited effect. But, I too , wondered whether a negative RNS was to shortly follow that - although, it was a legitimate update post-trial.
Maybe I’ve just become far too cynical with the passing years( and experience of AIM !!)

Nobby
you said: “ When I asked that question at the research day last year that was effectively the answer I got. But it still nags away at the back of my mind that this could be an issue.”

Could you elaborate on why this part nags away at you please and why it could be an issue?
Much appreciated and sorry I roped you in...but this is VERY helpful to making a considered judgment.