Hi Kronberg,
I would agree that things are looking positive for PLX and for PRX-102's potential to receive AA.
Myself what I liked hearing from the call was that they did indeed have the meeting with the FDA this quarter as they had planned, and that from the meeting the FDA concluded that yes they would be able to use surrogate markers like GB3 inclusions from kidney biopsies as was the basis for both Fabryzyme and Galafold, but not only that, the FDA would also be wanting to look at the eGFR data, which is something that Fabryzyme and Galafold didn't have in their AA data submission, and so I believe based on the eGFR data we have seen from the Phase II 2+ year data as well as the most recent Bridge data, that the eGFR data is not only the critical data point to assess the true efficacy of Fabry products, but is also a point where PRX-102 should show marked improvement over currently approved treatments. Good.
I also like that before rushing in with an AA submission, they are going to have an additional meeting with the FDA to go deep into the data, thereby providing a clear understanding to the FDA on PRX-102's potential and also making the potential AA submission have a greater chance of success by not missing out any particular type of data the FDA might like to have pre Accelerated Approval. Nice.
Additionally, as you also brought to light, I find it very encouraging that all those patients that have concluded the Bright study that are on an arguably slightly less strong dose of PRX-102 (at 2mg/kg/4weeks), have with their clinician decided to stay on PRX-102 and not go back to Fabryzyme. That should be a good indication from clinical and convenience benefit for the less rapid progressing disease patients segment. For this now we just need to see the eGFR data which Moshe said we would see that interim data for this year, hopefully not too too much longer, perhaps up to an additional 6 months from now at the latest I would assume.
The Bridge data again saw that nice reversal in eGFR slope on the aggregate and for many patients both male and female and which were in more severe/rapid progressing circumstances and should hopefully mean good clinical out-come from the more severe patient segment too. Now we just need to see that corroborated with the final unblinded data from the Balance trial. Here I am again cautiously optimistic that we should see a similar trend as seen the Bridge trial, as from the previous research papers I wrote about here some time ago covering a few hundred patients, the efficacy and benefit of Replagal and Fabryzyme were non-clinically different from one another. If Balance does show the same trend as Bridge, then I believe PRX-102 should become the best treatment for Fabry for almost all Fabry patients.
On the financial side, they have the funds to get them to mid-2020, which if all goes well with the next FDA meeting in 2019Q2 should be enough runway to get to AA approval. To-date, they said they have recognised only 25 million of the 69 million already received from Chiesi, so I understand this as they should have more funds to recongnise and extend the runway if they choose to, however don't quote me on that, sometimes these financial instruments get a bit fuzzy for what they mean.
The gentleman from HC Wainright asked some good poignant questions, one of which let us understand that for the remaining convertible debt, they know the debt holders very well, and while a number of options are available to the holders, I would suspect an extension is the most likely scenario as would both help PLX and themselves at the same time.
Another aspect that was touched on by his questions, allowed Moshe to expand on previous statements, such that if PRX-102 does get AA, that the Balance trial would serve as the final confirmatory data and no further trial would be needed. This is great as for both Fabryzyme and Galafold that didn't have the all important eGFR data as part of their AA submission, they had/have to do this additional trial to prove the clinical benefit. eGFR is already included in all the PRX-102 trials so I totally agree with the FDA and makes sense that all data needed will already have been generated by PLX's Phase III trials. And obviously would save PLX much time/effort/funds that could be better spent on newer programs, while also doing away with any investor concerns on the outcome of the confirmatory trial, one of the main reasons for why I believe Galafold has not had the uptake as one might expect. Good.
I have to say I like the way they are running the company. I can agree with both them and their potential partners on the 110 data, which while very good, it being a designed as a cross-over study doesn't provide as much of the robust and ease of clarity as a double blind trial. Also a further complication was the apparently odd much lower than expected efficacy of Pulmozyme as the comparator. While I don't doubt the way the trial was carried out, any confusion will make it a more difficult sell at this time. Also I agree on deprioritising 110 for 106, as 110 would be for a 3 billion dollar market, whereas 106 would be aiming at an 8 billion dollar market of IBS, and with some no-brainer (e.g. oral and no side effect) benefits as well as apparent high efficacy.
So finally on 106 I agree with them that they should think very carefully about how they play this one. Personally with my current understanding and belief in the data from PRX-102 to-date, that AA should be in the cards. If so then I would like to see them wait for AA, get significant milestones from Chiesi and quickly pump some of that into one very robust 106 phase III trial, provided the FDA allows them to go straight to Phase III on that instead of a larger Phase II.
I would also like this way of doing it, as while the waiting period of deciding to go alone or with a partner for the next phase of 106 development is annoying, the actual speed of conducting an IBS trial would be relatively fast vs the Fabry trial and this 'lost time' would be 'made-up' from that perspective, putting PLX in hopefully a much more superior negotiating position than otherwise. Then a shiny new multi-billion dollar product for which PLX and we shareholders can enjoy the greatest potential benefit from that molecule.
With the milestone cash too, they could do the new 110 trial too so as not to need to lose much time on that.
Dependent on the similarity of Balance data to Bridge data I would be expecting higher revenues than 113.19M in 2020. I would expect something like 100-200 million in 2020 simply based on the accelerated approval situation and data from Bridge and Bright, but then given we should have the Balance Full Top-Line data (for Europe) and 1 of the 2 years for FDA by probably mid 2020, that should should give both European and USA physicians a strong positive perspective on PRX-102 and give PLX & Chiesi about 6 final months of 2020 to really drive the gains home and thereby I would expect going into at least the 300-400 million mark for 2020.
Indeed at the moment it is a waiting game, but things are looking good.
Hope this was helpful.
AI
