Amryt Pharma Share Discussion Threads

[moneytree1] 25/4/2018 13:58

Keep Digging Pappy.

[papillon] 25/4/2018 13:57

Well digadee, I've had a quick perusal of diamondstar's posts since the beginning of March and I can't see any mention of OpenOrphan. Have a look yourself. I can't remember anyone else mentioning it on this bb. Perhaps you could provide a post number where it's mentioned?

[digadee] 25/4/2018 13:26

Hi papsThink dmondshare already picked this up a few weeks back, posted on the board when he found out about openorphan

[moneytree1] 25/4/2018 12:58

nice work if you can get it Paps.

[papillon] 24/4/2018 16:05

Just 35,019 shares traded so far today. Absolutely no investor interest in AMYT. I seriously don't know why AMYT continue to spend management time giving these presentations. Either buyers are just not "turned on" by them, or buyers don't turn up and attend them. Either way they are a complete waste of time.

[moneytree1] 23/4/2018 17:28

sad isn't it Pappy:(

[papillon] 23/4/2018 17:25

Unfortunately I was correct last week. Yet another AMYT presentation that doesn't attract any buyers (or sellers for that matter). These seemingly endless presentations are a complete waste of time because they appear to have no impact on the sp, or volume. Only REAL news does that and unless we get another Lojuxta type deal in the meantime that REAL news is 6 months away

[timbo003] 21/4/2018 07:00

A few notes (on AP103) from the Amryt meetings on Wednesday:

AP103 is the Gene therapy product to treat EB, licenced in from University College Dublin. Amryt acquired rights to the product at a bargain price (six figure sum) with only modest development milestones and royalties on sales.

Initial results from studies employing other gene therapy treatments for EB look promising, but these studies employed herpes virus as a vector to deliver the corrective gene to the cell nucleus, with the cell modification conducted ex-vivo, which means that cells are taken from the patient and modified in the lab using the virus, before being reintroduced back into the patient.

AP103 will employ a different, more patient friendly, potentially safer approach, whereby a hyper-branched polymer is used as the vector for the correct replacement gene (rather than a virus) and the whole transfer process will take place in vivo (i.e. inside the patient). Initial preclinical results using a mouse xenograft model appear very promising (see slide 45).

For valuation comparison purposes, Krystal Biotech is a gene therapy company which recently listed on Nasdaq raising $35M. Their lead product is KB103, a viral based gene therapy for EB, is at a similar stage of development to AP103, yet their market cap is $103m.

[timbo003] 21/4/2018 06:47

I think Amryt are at the UK Investor show today, they are scheduled to talk at 11:40, so that might generate some interest.


I shall go along and drop by their stand, but may miss the presentation, as I have to spend some time at the show doing a couple of shifts at the ShareSoc stand, extolling the virtues of membership and encouraging attendees to sign up.

[greendragon777] 21/4/2018 00:26

Wow...great bit of detective work there Paps. I was getting increasingly worried about the placebo issue.

It's been great discussing this here over the last few days....some really good insights from you guys! 👍

[timbo003] 20/4/2018 19:52

Yes thanks Papillion, that is a very useful find

There is a bit more useful information on the placebo to match AP101 in the May 2017 Proactiveinvestor meeting report (post number 1163)

[digadee] 20/4/2018 19:00

Great find paps

[diamondstar1] 20/4/2018 18:54

Thanks Paps - you have made my day :)

[papillon] 20/4/2018 18:45

diamondstar the following link shows that AP101 (Episalvan/Oleogel-S10) has previously been successfully tested versus Sunflower Oil (SFO) for EB ........

"The ideal formulation of Oleogel-S10 has further been examined by Steinbrenner et al. [32]. The group tested the effect of different oils on wound healing when used alone or in combination with TE. The majority of oils seemed to hinder wound healing to some extent, SFO being among the least impairing oils when used alone. However, when using SFO with TE as in Oleogel-S10, wound healing was significantly improved as compared to both sunflower oil (SFO) and SFO with ethyl cellulose for an improved viscosity."



The link describes the following clinical trial:

"Clinical Study
Betulin-Based Oleogel to Improve Wound Healing in Dystrophic Epidermolysis Bullosa: A Prospective Controlled Proof-of-Concept Study
Agnes Schwieger-Briel,1,2 Dimitra Kiritsi,1 Christoph Schempp,1,3 Cristina Has,1 and Hauke Schumann1
1Epidermolysis Bullosa Centre, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany
2Department of Pediatric Dermatology, University Children’s Hospital Zurich, Zurich, Switzerland
3Research Centre Skinitial, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany

Correspondence should be addressed to Agnes Schwieger-Briel; [e-mail]

Received 20 February 2017; Accepted 18 April 2017; Published 22 May 2017"

This successful clinical study (published 22/5/2017) is most probably the reason why AMYT chose to compare AP101 against SFO for their EASE phase III trials. I'm now much more confident of a successful phase III trial after reading this clinical study. My BULLISHNESS has returned!!!!!!!!!!!!!!!!!!!!! :-)

PS Someone needs to post this link (or my complete post) on the lse bb for Bronxville to see.

[diamondstar1] 20/4/2018 18:23

Yes, these are clearly risks to the EASE Ph 3 program.

Firstly, the choice of placebo using sunflower oil gel. Their Ph 2 in EB used non-adhesive wound dressings only. And from what I can see from their 3 studies in Partial Thickness Wounds, they also used non-adhesive wound dressings as placebo. It appears to me that this is the first time they may be using sunflower oil gel as placebo. If someone else finds more information on this, do let me know.

Secondly, the variability in the baseline EB patient population could also confound the study. To give you a simple example, the Zorblisa Scioderm Ph 2b data (N=48) showed wound age in this study ranged between 21 to a maximum of 1639 days. Imagine that one patient in this study had this skin lesion for 4.5 years. Clearly, inclusion of such patients with very old skin lesions can bias the results. What is the chance of a skin lesion healing with Zorblisa or Episalvan or anything after 45 days (Primary Endpoint) if it has been there for 4.5 years! The Ph 3 protocol for EASE inclusion criteria allows patients with skin lesions > 21 days, but there is no upper limit to the age of the lesions.

[greendragon777] 20/4/2018 15:46

Thanks a mil for the notes Timbo, very helpful indeed and good to get the insight.

Diamondstar makes a very interesting observation re the placebo effect and how sunflower oil can potentially aid healing. I always thought that placebo was practically of no substance. It would be a real shame to fail because placebo actually has medical benefit.

I can see now why you apply a 55% to 60% chance of success. Amazing what you find as you dig deeper. Very informative!

[moneytree1] 20/4/2018 15:34

Pappy

I hope youre not looking for some action.

[greendragon777] 20/4/2018 15:28

Thanks Diamondstar, very thought provoking indeed. Quite sobering to read ever the Phase 2 results for Zorblisa as everything seemed to be going swimmingly yet failed in Phase 3.

I don't know anything about the technical details of why it failed but I take your point that one should be very mindful of it's potential to fail despite all the positive signs like approval for treating PTWs etc.

I'm still happy to roll the dice on it however and just hope that the trial adjustments will increase it's chance of success.

It would be great though if they could bag more Lojuxta type deals so it could at least fully underpin the share price.

[moneytree1] 20/4/2018 15:19

I concur.well done.

[papillon] 20/4/2018 15:17

Many thanks, timbo and diamondstar for your excellent, informative, posts.

[diamondstar1] 20/4/2018 14:56

Hi Digadee,

Thank you for your feedback. This was not meant to be a judgement analysis. I was not saying that you should not invest in Amryt because Amicus failed at Ph 3, despite excellent Ph 2 results. You are right- if we applied this simplistic rule to all pharmaceutical investment decisions, we will just sit back and bury our money under our pillows.
What I am trying to explore here is what can we learn from the Amicus program that can be applied to Episalvan.
Several months ago, I was extremely optimistic about the EASE study - because they had succeeded in 3 Partial Wound Thickness studies and a Ph 2 study. Combining the results of these studies, I was happy to estimate that the probability of success of the EASE Ph 3 study was as high as 70-80%. Importantly, Episalvan is a topical drug, so it does not have major safety issues like oral drugs, which is a major cause of drug termination.
What have I learnt from reviewing Amicus Ph 2 and 3 data? Firstly, they were was lots of patient variability at baseline - wound age was between 21 - 1639 days in the Ph 2b. The efficacy was fantastic - with median time to complete healing in Zorblisa of 31 days vs. 91 days in placebo. Yes, I would have personally invested in Scioderm based on this data. So what happened in the Zorblisa Ph 3? Amicus press release on Sept 13th by CEO John Crowley states, ‘A higher than expected placebo effect, perhaps due to s higher level of bandaging and wound care, could have confounded the results’. My personal understanding is that Episalvan actually has some modest efficacy in wound healing (about 20% improvement). However, modest efficacy does not guarantee positive EASE results. The major challenge they are likely facing in EASE Ph 3 are 1) high variability in patient baseline characteristics in EB patients 2) A potential placebo effect i.e. an effect in patients given sunflower oil gel. Note that some previous research has suggested that sunflower oil might be effective in animal models of wound healing (Marques, 2004). In summary, my CoS or PTS (probability of the technical success) score for EASE is now 55-60%, which is very close to industry average rates for Ph III studies. Their recent adjustments by Amryt i.e. increase in sample size and excluding EBS patients will likely push it nearer to the 60% level. This is my personal analysis on the current situation.

[timbo003] 20/4/2018 14:40

A few notes on AP101 from the meeting arranged by the PR agency on Wednesday afternoon with Rory and Jo (this was before the Amryt presentation at Sharesoc), I will endeavor to write up some further notes on Lojuxta and other developments over the weekend


The data obtained from Amicus’s failed Zorblisa study (ESSENCE) has been extremely useful, especially for estimating the likely placebo effect for the primary endpoint (wound healing at 45 days) in the ongoing EASE study with AP101.

In the ESSENCE study, the sub group of patients with EB simplex showed significant wound healing at 45 days when treated with placebo so it is not unreasonable to assume that that there would be a similar placebo effect observed in the EASE study. Taking the data into account, the EASE study with the original protocol appeared underpowered (power <80%) thus necessitating a modification in the inclusion/exclusion criteria and an increase in patient numbers, so now even using quite conservative assumptions, the modified study power is >80%.

Even though EB Simplex patients are now excluded from the EASE study and they will not be included in the SPC (product label), Amryt estimate that the market potential for AP101 to treat EB is only reduced by 20% for the simple reason that EB non-simplex patients will require far more AP101 than EB Simplex patients.

Amicus were very willing to share their data, even though there was no potential for any direct monetary gain. The Amicus Chairman and CEO is deeply committed to the search for new treatments for rare diseases and he has been personally effected with one such rare disease with two of his children suffering from Pompe disease.

There are three orphan diseases for which AP101 could be used under the EU partial thickness wound licence (see slides 28 and 29), these are as follows:

• Stevens-Johnson Syndrome (SJS): 1-2 cases per million
• Bullous Pemphigoid (BP): 26 – 280 cases per million
• Pemphigus Vulgaris (PV): 175 cases per million

AP101 could be used under the existing licence in Europe for these three indications, however, the product licence stipulates the product should only be used for four weeks and both BP and PV are chronic conditions and would probably require continuous treatment to remain effective. The commercial opportunity in Europe would be much larger if there was supporting clinical trials data for one or more of these three indications and furthermore this additional clinical trial data would also open up the possibility of obtaining US approval for these additional indications.

Regarding current treatments for these three indications, an effective treatment for SJS is the greatest unmet clinical need (there are no drugs recommended for the current SOC) but the condition is extremely rare. BP and PV are more common, both these conditions are currently treated with high dose steroids (both oral and topical), however patients have to suffer the accompanying unpleasant side effects, so an effective treatment largely devoid of side effects, remains an unmet clinical need.

The SJS indication will be the first to progress. There is some hearsay evidence that in Germany Imlan Crème [which contains the same active as AP101 (Betulin) but at a lower dose], has been used successfully to treat SJS. One German Physician recently approached Amryt with a request for supplies of AP101 for use in an open label clinical trial to treat SJS, Amryt subsequently agreed to supply material on a compassionate use basis.

[moneytree1] 20/4/2018 14:32

out in the garden Paps!

stop idling your days away on the lappi,gambling the pension away.