Ann: 2023 AGM Chairman's Address and CEO Presentation, page-11

A few more snippets from the AGM last Friday, taken from my notes....


Risk correlation between programmes

The risk correlation between PYC’s various clinical programs was recently raised here and was put to RH at the AGM. He said that the only correlation between the current programs was in the safety readout in the RP11 and ADOA programs. If the safety readout is bad for the current RP11 clinical program, that could have negative implications for the following ADOA program. Conversely, good safety data in the RP11 program would bode well for safety in ADOA.


ADOA program

The company is looking to accelerate the ADOA asset into the clinic by completing Phase 1 in Australia and Phase 2 in the US. My assumption is that this is because in the US an IND has to be submitted before any drug can be tested in humans. A Phase 1 conducted in Australia can happen simultaneously with the completion of all the necessary studies and paperwork required for an NDA submission, allowing faster progression into a Phase 2 trial in the US.

RH also mentioned that there seemed to be a lack of awareness that a Phase 1 study only needs to be done once for a drug. This means that clinical testing in further indications of the same drug, providing the same dose and same route of administration are used, can start at Phase 2. This is something that Neuren has recently done - launching Phase 2 trials in four separate indications of its second drug following a single Phase 1.

In the case of PYC’s ADOA program it is possible that the same drug could be tested for efficacy in a number of other indications. In fact, RH said that clinicians had already expressed interest in using this drug to treat patients with other bioenergetic diseases of the retinal ganglion cells, which is what the ADOA drug (PYC-001) targets. One condition he mentioned was Leber Hereditary Optic Neuropathy, which appears to have a roughly similar market size to ADOA. There were one or two other conditions mentioned but I didn’t catch their names.  Glaucoma was then also mentioned as a possibility. With 80m+ people worldwide living with glaucoma, this is obviously a huge market.

So, potentially, the ADOA program could be just the first of multiple programs in indications that address haploinsufficiency of the OPA1 gene in retinal ganglion cells.

Phelan McDermid program

Clinicians at Mt. Sinai in New York (location of the Seaver Autism Center for Research and Treatment where clinical research on Phelan McDermid has previously been conducted) are said to believe that RNA is the right approach to this disease and are excited by PYC preclinical results to date in the disorder. RH said that the one piece of information still missing is preclinical evidence to answer the question of whether what PYC has achieved in the reporter cell (as used in the rat model) can be achieved in neurons.

PYC is due to report the answer to that question early next year. If positive, RH said it’s full speed ahead towards clinic with this program.


Funding

RH was asked if he was confident that PYC would be able to fund the progression of so many programs. No real ifs or buts, just a slight smile and an assurance that yes, he is confident.