Roundtable Discussion; The Future of Mineral Sands. Watch the video here.
I was hoping to see some pre-clinical data on AP103 today......left me a little disappointed. I assume they are not working over the next two weeks so the Q4 delivery promised wont be met (although I appreciate they have other bigger things ongoing at the moment)
sounds reasonable...
Does anybody know what data the Interims will actually provide us with? will we get a measure of wound closure rate at 45 days? or just safety data? or a stop/continue decision?
I just checked clintrials.gov and the primary end point is 45 days after first treatment (I had thought previously it was 90 days)...anyway, if they hit the halfway point in recruitment at the end of Sept, the interim readout must be about due (it takes a bit of time to collect the data and organise a DSMB meeting)...I suspect they now know how the study is shaping up. (somebody did buy a big chunk of shares this morning! could be a coincidence.)
The date for the primary readout in Clintrials seems wrong as they only hit the midway point in September...they will be recruiting well into the Summer, however, this impending Interim readout should tell us if the therapy works or not.
Do they really need to do a raise with 14M income from Lojuxta per year and the opening up of big markets in the UK and France?....that could see upwards of 20M per year revenue, enough to run the company and the EASE trial. AP103 is just pre-clinical at the moment and probably only going to consume 1-2M Euro I guess. The only way I see the need for a raise is if the want to buy something else to add to the portfolio.
Ain't so.....
Sept 2020 will be the end of the long term follow-up period (I think this will be much later now). With the US centres on-board now they should wrap up recruitment Q1/Q2 next year and with a 3 month treatment period, we should get a read-out on the primary endpoint of the entire study shortly thereafter...this is what matters. So Summer next year will be a date for your diary. The long term follow-up is just to add to the safety data for the therapeutic. However, I think we should see the interim data in January which should give us a good indication on how effective the treatment is. I foresee a raise after the Interims are announced....which IF positive should send the share price upwards making the dilution less painful.
I think if AP101 fails there will be a mad scramble to get AP103 into the clinic as quickly as possible to generate some value
Krystal look to be about a year to 18 months ahead of Amryt's AP103. Whist it will likely deliver benefit to EB patients and is a significant step forward in their treatment, the Krystal therapy is very much an inferior product for a variety of reasons. For a start the delivery vector is based on the herpes virus, which, despite being mostly inactivated has some unpleasant side effects...and handling viruses is no trivial matter (and gets expensive). In the presentations I have watched I don't see these issues with Amryt's product although it is early days. I think that Krystal's product will be first to market as a breakthrough gene therapy but will be superseded by Ap103 a year or two after.
excuse ignorance on this but why would they give an update on Lojuxta sales having only recently published the interim results? I would have thought the next info would be in the New Year.
Absolutely key bit of news this morning from Amryt....getting enough patients into a rare disease trial if often a major issue particularly trials of this size. Opening the IND in the US just made a very large patient population available which makes the interim and final reports much more likely to happen on time. Very happy to see this....most serious EB cases here in the US are centered in a handful of teaching hospitals which makes accessing them a simpler task. This just de-risked the study considerably in my view.....so nothing "awry" as far as I can see.
just a note to yoshie.....I looked at the literature and the active in both Imlan and Oleogel (used in the EASE trial) is indeed an extract from the bark of the birch tree, however the main component is betulin (not betulinic acid). Betulin is well known for its anti-inlammatory and wound healing potential. Publications from Birken (acquired by Amryt) and others seem to show it affects how keratinocytes in the epidermis behave and can simulate wound repair.
Also, as mentioned below rare disease indications can have much shorter development timelines compared to classical drugs. In my opinion, from where AP103 is to market authorisation may only be 5-6 years for a variety of reasons I wont bore you with. As AP103 would likely be "transformative" for the patients with life-threatening EB, I expect this to be even faster. Further, I would expect Amryt could apply for another pediatric designation voucher based on data from their first human study rather than towards the end of the development. Just my humble opinion but a second voucher might not be that far away.
just a thought....if AP101 (the wound healing gel) is a valid recipient of a accelerated review voucher for EB wouldn't Amryt's new gene therapy for treatment of the same disease also qualify? Can a company have 2 vouchers? Acquiring that EB gene therapy from UCD might have been quite a clever investment.
I saw this gene therapy technology presented at the DEBRA conference last year in Salzburg....I think there is a presentation on the DEBRA website from UCD. Finally, we seem to be getting close to a real effective treatment for EB and as a clinician I am truly optimistic about this approach. This is a devastating disease which frequently leads to cancer and early death not to mention the life long suffering for the patients and carers. As I recall, this therapy allows for the replacement of the defective collagen VII gene which could restore the "normal" structural integrity of the skin as it will allow the epidermis and dermis to knit together. Importantly, this can be done topically on the patient...this is a huge step forward. Normally for a skin gene therapy, you have to take a biopsy, grow a sheet of cells in the lab, repair the defective gene then re-graft the sheet back on to the patient....this does not make commercial sense for a variety of reasons. Repairing the gene on the patient circumvents these issues and keeps costs down. It also doesnt use virus delivery technologies with their inherent risks. It would also seem that the technology could be targeted a different subtypes of the disease depending on which gene they want to deliver. Seems a terrific opportunity to me.....for the patients and Amryt. I am sure Shire will be sniffing around this sooner or later, it is right up their street.
Sometimes there are more important things in the world than just trying to make a quick 10%. For those of us that work in this field, seeing kids like this is motivation enough to do what I can to support this company and others like it...along with supporting the academics involved in the basic research. http://www.bbc.com/news/av/health-42002086/tia-has-epidermolysis-bullosa-known-as-butterfly-skin
Looking at their interim report, I dont think they need this cash now for running costs (I am not an expert though). Maybe they will use it to acquire something...... I could be just being overly optimistic, raising cash and turning it into an asset rather than just to fund the day-to-day cash burn may not be a bad thing if that is what they are doing. Didnt they just hire a BD/Licensing guy?
There are 3 main subtypes of EB. EB Simplex, which is the mildest form but still has a wide range of severity; recessive dystrophic EB very severe but patients tend to survive to at least early adulthood and junctional EB where unfortunately most patients don't make it past infancy. Gene and stem cell therapy offer hope for something approaching a cure but this is many years away. The work being done by Stanford Uni is driving much of this. I expect the oleogel would still be used in combination. I am also curious to know what other indications oleogel could be used for....EB is a tough indication, if it works there, I am sure there are many other situations where a decent topical anti-inflammatory could be used. Worth asking them next time you get the chance. Cookie
As I read it, the analysts possibly had issues with the way the study was set up and whether it could statistically show efficacy....ie the patient numbers and the way it was stratified for example. According to Amryt their product only needs to be reapplied every 2-4 days which is a distinct advantage over Zorblisa which requires(ed) daily dressing changes which are very painful and time consuming. Zorblisa is also somewhat "sticky" which makes the dressing changes all the more painful. EB patients have very sensitive skin. The "gel" from Amryt should be non-adherent making the changes less painful. i think, if Oleogel and zorblisa both came to the market the Amryt product would have dominated but the latter could still have retained a sizeable chunk of the market. i said earlier zorblisa was the "main competitor" in-fact it is/was the only competitor in this type of therapeutic approach. There are of course gene & cell therapies in development but these are at a much earlier stage.
Could be an interesting day....Amicus' ESSENCE Phase III clinical study with SD-101/Zorblisa, Amryt's main competitor to AP101/Episalvan in the EB indication just crashed and burned, missing its primary endpoints and was no better than placebo. Whilst technically inferior to Amryt's product, it was 1-2 years ahead of Ap101 in development and would have maintained quite a slice of the market if it had been successful. I guess Amryt will be updating their revenue projections spreadsheet for AP101 in EB. Go to the Amicus Thera website for details.....could be why we are seeing a steady increase in the sp (in addition to the positive lojuxta revenue projections).
For me the portfolio of therapeutics is too diverse for Amryt to be acquired in its entirety by a single big pharma company…for example Novartis will not be interested in Episalvan, a plant-derived topical dermatology product, this would need a specialist pharma, but they would be interested in AP102. I think Amryt is here for the long run using the revenue generated from its commercial products to fund the in-licensing and development of earlier stage products which will then out-licenced. I do expect to see them at some point on the NASDAQ as they have suggested and to remain there for the long term.
Nice to be no longer losing money after holding for a year…important milestone and I think this has solid potential in the years ahead. I will stick my shares under the mattress for a couple of years I will spare you the technical details but I have seen Sompharma present their early data on a couple of occasions for AP102 (G02113 as it was then) the theory is sound. If the drug works as it is designed to it should work in a broader patient population giving it a distinct advantage over Novartis’ Sandostatin…which is still worth over a billion a year for the treatment of acromegaly and neuroendocrine tumours despite being 30 years old and only working in about 30% of the patient population. The newer drug from Novartis called Signifor (designed to be a second generation Sandostatin) may work in more patients with acromegaly but if you didn’t have diabetes when you start therapy, it will likely give it to you (or make your existing diabetes worse) and the diabetes has a higher rate of mortality than acromegaly…so Signifor doesn’t sell much in acro despite the marketing effort. Where it gets it revenue is in the treatment of Cushings Disease….much more nasty than acromegaly where the risk-benefit is slightly in its favour. In theory, AP102 could work for acromegaly, Cushings and neuroendocrine tumours. From what I read, AP102 will be in the clinic next year presumably in a Phase I safety study however the value of the drug will be seen in a Phase II efficacy study probably in late 2018 or early 2019…That is when Novartis may start sniffing around but it is a competitive field and others would be interested too…bidding war maybe??? Given Sandostatin is a blockbuster for Novartis’ and AP102 should be better….I don’t think Amryt will let it go cheaply.
...we should be getting news of the start of Phase III with Episalvan in the next week or two assuming they are on track....which it seems they are (see my post below). 164 patients according to the FDA....for epidermolysis bullosa....that is a huge global study for a rare disease. That, together with what I hope are positive results at the end of the month, I would expect to see a measurable upturn in the sp (might even start making money...finally). Will be interesting to get a first look at how the Lojuxta sales are doing in their hands.