Ann: Successful Toxicology Studies Pave Way for Human Trials, page-63

Linsanity, just a broad response from me.

PPMOs heralding a new exon-skipping branch of genetic precision medicine? All I know is that it’s still early days for PPMO drugs, with none yet approved or even in late-stage clinical development.

But PPMOs certaily offer a promising therapeutic approach, with Sarepta currently leading the way with its candidate, SRP 5051, which is still in Phase 2 development. In this investing article, the author makes the observation that while gene therapy and gene editing get all the glory, no one is talking about the PPMO approach, making it "a major opportunity hiding in plain sight". The author views Sarepta’s PPMO platform as an important upgrade to a proven, FDA-approved therapeutic modality that could result in safer, more effective, and more convenient treatment options and concludes that Sarepta’s PPMO platform is a significant economic opportunity.

The only other biotechs, of which I am aware, that are also developing CPP conjugated PMOs are PepGen and Entrada. While PepGen is focused exclusively on PMOs, Entrada is employing its cell penetrating peptide technology in the delivery of oligonucleotides, antibodies and enzymes.

Sarepta, PepGen and Entrada all have lead PPMO programs in either Duchenne Muscular dystrophy (DMD) and/or Myotonic Dystrophy Type 1 (DM1). PepGen’s lead program in DMD is about to advance to Phase 2 and Entrada’s in DMD was about to commence Phase 1 but the FDA put a hold on the IND the week before Christmas. My experience with Neuren Pharmaceuticals suggests that this could mean a 6 month delay in IND approval for Entrada.

Both PepGen and Entrada have market caps ~A$500m, more than double that of PYC.

I think that PYC’s lead program in an eye disease has attracted less investor interest than, say, a CNS indication. In fact, Rohan Hockings specifically stated at the 2021 AGM that US investor interest is in CNS, with less interest in orphan eye diseases.

But while PYC is currently the underdog, it may still come on top.

Odds of success are higher in both eye disease and orphan drugs, making RP11 a prudently chosen initial indication for PYC’s pipeline. A further advantage for PYC is its partnership with the Lions Eye Institute. And although many investors are underwhelmed by orphan drug programs because of their small patient populations, the fact is that orphan indications have the advantage of less competition, a potentially faster and cheaper pathway to market, easier to identify/access patient populations, ability to command higher prices and special market exclusivity provisions. In the case of Neuren, pivotal trial success in its lead orphan drug program swiftly changed the attitude of some investors towards orphan drugs. Neuren’s market cap has subsequently risen from ~$220m to $1.15bn.

I like what PYC is doing. I’m keen on the PPMO approach, I agree with PYC’s strategy in choosing an orphan eye disease for its lead program and I very much like that PYC has not chosen DMD (despite Sue Fletcher’s extensive experience in developing PMOs in this indication) as I see it as a very crowded field.

I’m sure we all agree that PYC is currently undervalued and that the share price sucks. But if and when PYC releases successful clinical data and/or strikes a deal with pharma, investor (and pharma) interest will rise, along with the share price.