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Major leap towards human trials for Western Australia’s PYC Therapeutics

Australian biotechnology company PYC Therapeutics has advanced its RNA platform closer to human trials after determining safe and well tolerated doses of its co-lead drug candidate for retinitis pigmentosa 11 (RP11) in monkeys.

The ASX-listed firm has RNA drug design capabilities and a proprietary drug delivery technology that it hopes will work together to create a new generation of RNA therapeutics, initially focused on blinding eye diseases.

As part of its program, the company – with laboratory facilities in Perth and regulatory operations in San Diego, California – is developing a therapy called VP-001 for currently untreatable RP11. It is a dominantly inherited retinal degenerative disease caused by mutations in the PRPF31 (pre-mRNA processing factor 31) gene.

According to the company, PRPF31 mutations cause retinal disease by haploinsufficiency, a disease mechanism that occurs when one copy of a gene is inactivated or deleted, and the remaining functional gene does not produce sufficient protein to preserve normal function.

The strategy of VP-001, its lead drug candidate, is to overcome haploinsufficiency that causes RP11 by moderating CNOT3, an “off-switch” (negative regulator) of PRPF31, and thereby increase functional PRPF31 protein from the remaining healthy gene.

VP-001 is owned by Vision Pharma Pty Ltd which is a collaboration between PYC Therapetuics (90% shareholder) and the Lions Eye Institute (10% shareholder).

The purpose of the recent dose range finding toxicity study was to evaluate the potential ocular tolerability and toxicity of VP-001 when administered via a single intravitreal injection to cynomolgous monkeys, otherwise known as non-human primates (NHPs).

PYC announced on 16 November that it has obtained data for safe and well-tolerated doses of VP-001 from the study to support continued non-clinical development of this program.

The company reported that the results represent a key step towards Good Laboratory Practice (GLP) toxicity studies – scheduled for Q1 2022 – that will then support the first in-human studies.

Importantly, the findings further validate the company’s drug delivery technology utilised across PYC’s pipeline consisting of five therapies for blinding eye diseases, as well as future ocular programs. As a result, PYC said “the outcome therefore has positive read-through implications”.

“These results from the NHP studies continue our approach of systematic evaluation of our dual technology platform of RNA therapies to treat eye diseases,” PYC’s chief development officer Dr Glenn Noronha said.

“Drug development requires that data are built from a foundation, layer by layer, and each step in this process provides information toward the potential for bringing therapies to patients. This is one such important step toward first in human clinical evaluation.”

On 28 September, the company also announced that, in a separate trial, its RNA therapeutic modality reached high value target cells within the retina of rabbits.

In the study, its therapy reached all layers of the retina following intravitreal administration in the rabbit eye; reached the nucleus of the target cell type in the its RP11 program; and successfully engaged the target pre-messenger RNA resulting in the desired change in the target messenger RNA.

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