During various investor webinars Rohan repeatedly refers to...

During various investor webinars Rohan repeatedly refers to competitors in the same space - even using their figures and marketing in some slides.

Rohan uses lots of comparisons in his presentations, which I personally like. He uses them for a variety of reasons.

Guidance towards sales potential - in the May 2024 presentation, Argenx’s Vyvgart Hytrulo drug is mentioned. It’s not a competitor drug; it’s not even an antisense therapy. But it has been approved in a condition that affects less than 1 in 100,000 people and is predicted to reach peak sales of US$1.5bn. The relevance to PYC here is that PYC’s lead drug is addressing a condition that has a prevalence of 1 in 100.000 people.

To draw attention to the competitive advantages of PYC’s drugs - a couple of times Rohan has mentioned Regulus Therapeutics, which is also developing an antisense therapy for ADPKD. When asked about Regulus at last year’s AGM, Rohan used the opportunity to explain some key differences and advantages that PYC’s drug has over that of Regulus. He also explained that having a drug like this a year or two ahead can be useful in identifying a clear regulatory pathway – that is, one can “borrow” from the competitor’s clinical program to inform one’s own program.

To highlight the real possibility for PYC to strike an early stage deal - Rohan has spoken about how competitor antisense companies, Entrada, Stoke and Wave, achieved high-value, very early-stage licensing deals. Thus, PYC also has the chance to achieve a licensing deal of value even while its programs are still early stage.

To highlight how the class of drug that PYC is developing has a far higher chance of success than other classes of drugs - in the presentation in October last year, Rohan used the example of Alnylam’s RNAi platform to highlight the much higher probability of clinical success for drugs which target a single gene mutation (overall POS of 64.3% vs 5.7% for standard drug). PYC, by the way, has no pipeline programs that compete with Alnylam.

To highlight the superior efficacy of PYC’s PPMO to a naked PMO - early last year, Rohan compared a naked PMO’s ability to engage its target in various regions of the brain vs PYC’s PPMO. The PPMO was vastly superior. Yet Sarepta’s approved antisense drugs for DMD are all naked PMOs and have led it to becoming a ~US$15 bn market cap company. Sarepta, by the way, has no competing therapies in the indications which PYC is targeting.

To demonstrate the potential for growth in market cap as PYC advances its lead drug through clinic - Rohan also used the example of Sarepta to demonstrate its rise in market cap by > 20 times during the period from early preclinical to approval of its first PMO drug.


They all seem to have one thing in common - they are a bit or a lot ahead of PYC in most areas - polycystic kidney disease, GVHD, and some ophthalmology conditions.

Firstly, PYC isn’t developing a therapy for GVHD. Perhaps you’ve confused this with MSB.

The ophthalmology assets – one for RP11 and the other for ADOA - are PYC’s lead assets. VP-001 for RP11 is in Phase 1 MAD studies. Commencement of the PYC-001 in ADOA trial is imminent.

With respect to RP11, there are no competitors ahead of PYC, although there are other companies attempting to develop gene therapies for the broad indication of RP.

There is a competing antisense therapy for ADOA, developed by Stoke Therapeutics. It received clearance to start a clinical trial last year but is yet to commence. The company now says that it will commence sometime in 2024. It is possible that PYC will lead Stoke into clinic.

PYC’s third asset for APKD is due to enter clinic early next year. There is a competitor antisense therapy perhaps two years ahead (Regulus Therapeutics). As already mentioned above, PYC’s drug has several potentially competitive advantages (in both safety and efficacy) over the Regulus drug.

PYC’s asset for Phelan McDermid syndrome (PMS) is due to enter clinic next year. There is currently no competitor antisense therapy in development for PMS. Neuren Pharmaceuticals is developing an oral peptide therapy for PMS and will commence Phase 3 next year.

Neuren’s drug (NNZ-2591) has a broad action and addresses some of the symptoms of PMS but does not address the root cause of disease -haploinsufficiency of the SHANK 3 protein - like PYC’s drug.


Is this a cause for concern?

Not for me. I suspect it’s almost impossible these days to find a competition-free, commercially viable indication in which to develop a drug. Hence, it’s crucial that any drug chosen for development must have competitive advantage. Rohan has stated that each of the drugs that PYC is developing must have multiple layers of competitive advantage.


Rohan repeatedly emphasises the potential market size, but then references a competitor - thereby reducing the potential market size.....

All biotechs will reference the prevalence of the disease they’re chasing and will typically also provide a potential market size. As explained in all of PYC’s presentations (check the footnotes), the potential market size is calculated by multiplying patient prevalence in the indication by the median orphan drug price of US$150k p.a. (By the way, US$150,000 is not an exaggeration. Neuren’s first approved drug, DayBue, is priced at an average of US$375,000 p.a., after discount.)


I'm struggling to compare the two statements tbh.

Particularly in the early stages, all biotechs reference the total addressable market for an indication rather than how much of that market they think they’ll grab. In PYC’s case, one thing is clear - there is currently an unmet need in all indications it is pursuing. But one cannot know, if and when one’s drug is approved, if competitor drugs will still be standing and, if they are, how impressive their safety and efficacy profiles will be. PYC’s ambition is that, should there be a competitor therapy already approved when it enters the market, PYC’s drug will have a superior profile.

No drug ever sells to the total addressable market. Typically, further down the track, analysts will estimate a likely market penetration rate for a drug based upon things like its efficacy, safety, tolerability, patient convenience and price, as well as its “position in the queue”. There is no guarantee that being the first approved drug equals financial success. A drug can be first to market and still be a total sales dud.


Is anyone else concerned about not being 'first in the queue' and the potential of diminishing returns?

Not me.