PYC Therapeutics Sets an Aggressive Clinical Agenda and Timeline

By Mark Pachacz Posted on April 26th, 2025

PYC Therapeutics (PYC: $1.03, last raise at $1.25) has a milestone- heavy 2025, with three assets in the clinic advancing at a rapid pace. Its pipeline targets rare monogenic disorders in ophthalmology, nephrology, and now neurology.

PYC's science relies on proprietary cell-penetrating peptides, which protect RNA and guide it into the cell. Unlike its clinical competitors, PYC's candidates aim to modify the underlying disease, instead of treating symptoms.

PYC has four candidates. Two candidates, VP-001 and PYC-001, target degenerative, inherited eye diseases. One compound targets a degenerative kidney disorder (PYC-003). And PYC's newest drug candidate (PYC-002) is looking to treat the neurodevelopmental disorder Phelan-McDermid syndrome (the same disease Neuren Pharmaceuticals aims to move into Phase III studies this year).

Once known as Phylogica, the company rebranded in 2019 to PYC Therapeutics. Under its current CEO Rohan Hockings, who assumed the role in June 2018, the company has raised $342 million, including $146 million raised this year.

Science

PYC's selected indications are haplo-insufficient disorders, meaning that one ordinary copy of a gene is not enough for normal function. Theoretically, RNA-based therapies could address these conditions by increasing the expression of the single functional copy, compensating for the defective one. However, naked RNA degrades extremely quickly in human plasma, usually destroyed in minutes. RNA is both large and charged, and struggles to cross the cell membrane.

Core Technology

PYC's core technology uses a synthetic antisense oligonucleotide (ASO) called a phosphorodiamidate morpholino oligomer (PMO). PMOs can block the translation of specific RNA, allowing the cell to skip past faulty segments. PYC links PMO to cell-penetrating peptides (CPPs), which are small and correctly charged to tow the PMOs across the cell membrane.

Promising Animal Data

PYC Therapeutics' candidates have all shown impressive disease-modifying preclinical results. And encouragingly, the Phase 1 result of VP-001 for Retinitis Pigmentosa (RP11) has proven that animal models have been relatively consistent with clinical outcomes. In preclinical studies VP-001 was shown to down-regulate CNOT3 RNA expression by 30%, resulting in a 20% rise of the deficient PRPF31 gene expression in iPSC-derived retinal organoids.

1.Lead Program - VP-001 for Retinitis Pigmentosa - Early Promising Results
The company's lead program is in the genetic eye disease Retinitis Pigmentosa with its drug candidate VP-001. People with this disorder become legally blind by middle age.

Single dose

The first patient in the single ascending dose study (SAD) was treated in June 2023. In May 2024 the company had treated the full four cohorts (12 patients in total) at single doses of 3μg, 10 μg, 30μg and 75μg.

In August last year the company reported some positive efficacy results in two of the three patients in the highest dose (75μg) described as 'enhanced retinal sensitivity' (measured by microperimetry) with the third patient reporting 'visual functional improvement'.

However one of the patients in the lower dose 30μg was also measured as having a slowing in disease progression at six months compared to the untreated eye. The three patients from cohort four and two from cohort three (including the one above) have moved into an extension study to receive additional doses of VP-001.

In October the company reported that two of the patients in cohort four had received three of the highest doses of VP-001 (75μg) with no treatment related adverse events, continuing the benign safety profile seen with this drug candidate.

Multiple Dosing

In July last year PYC started a multiple dose trial (MAD or multiple ascending dose) at five sites in the US exploring doses of 30μg and 75μg. There are three patients in each cohort who were to receive three of the respective doses, eight weeks apart.

In October the company announced that in the three patients in the lower 30μg cohort after two injections (at two months) that there were improvements in eight of the nine measures taken from baseline and against the untreated eye (i.e. two patients improved in all three measures and one patient improved in just two of the measures).

In November last year the company received approval to move into multiple doses at the highest dose of 75μg of VP-001.

Overall Results Available

In November data was presented from the Phase I/II ongoing VP- 001 study. Across all parameters there were improvements over the untreated eye. These included improvements in visual function as measured by letter improvement on an eye chart, improvement in retinal sensitivity, and a reduction in the number of scotomas (non-functional areas of the retina). In one of the three patients treated out to six months, more than a 15 letter improvement was achieved in the treated eye.

Updated results from this program, including durability of effect, will be presented at the Foundation Fighting Blindness symposium and the ARVO conference early next month. So far, sustained effect has been seen through to eight months from a single injection.

Timeline for Commercialisation

PYC has an aggressive timeline in place for the development of VP-001. On completion of the Phase current I/II study, it expects to move into a registration study this year, with a data readout in 2027, and NDA to be filed towards the end of that year, and product approval in 2028, if all goes well.

2. Second Eye Disease: Autosomal Dominant Optic Atrophy (ADOA)
The second drug candidate, PYC-001, has also been validated in preclinical models. In November last year the company dosed the first patient with PYC-001 at the lowest dose. Similar to the study with VP-001, PYC will initially explore doses of 3μg, 10μg and 30μg, and may look to increase that dose.

3. Polycystic Kidney Disease - Phase I Trial Com- menced April 2025
Earlier this month PYC dosed the first human volunteer with drug candidate PYC-003 in its Phase Ia study in single gene disorder called autosomal dominant polycystic kidney disease (ADPKD). The study will move into patients in the second half of this year with dose escalation. PYC-003 has been successfully tested in several preclinical models.

4. Phelan-McDermid Syndrome

PYC-002 is still in preclinical studies for Phelan-McDermid syndrome (PMS), a rare neurodevelopmental disorder. In a wild-type rat model, a single, intrathecal injection of PYC-002 increased SHANK3 protein levels by 20%-60% over the control. Insufficient SHANK3 protein expression in the brain causes synapse dysfunction, resulting in lower intellectual and physical function.

Fast-Tracked Across the Board

PYC Therapeutics has embarked on a "High-velocity path" to get its candidates to market. VP-001 scored Fast Track Designation (FTD), Orphan Drug Designation (ODD), and Rare Paediatric Disease Designation (RPD) for RP11. PYC-00 received RPD and ODD. The remaining pair of disorders being tackled – ADKPD and PMS – are also eligible for similar incentives.

PYC is meeting with the FDA in Q2 of 2025, to establish the registration study endpoints of VP-001 in Retinitis Pigmentosa. Hockings expects the company to start the registrational trial in 2H 2025.

Phase I/II data will emerge over the next 12 months with PYC-001 in ADOA. The company is anticipating initiating a registrational study in 2026.

The Polycystic Kidney Disease trial with PYC-003 has just started, with a registration study expected to begin in 2027, pending positive Phase I/II data. And a Phase I/II study in Phelan-McDermid is expected to commence next year with a registration study the year after pending positive data.

Summary

PYC Therapeutics produced some promising early data in its first disease area that it is targeting, Retinitis Pigmentosa. The company has an aggressive commercialisation timeline and has been able to raise substantial funding for its programs.

The addressable markets it is targeting are all very large (greater than $1 billion), and being orphan diseases means that smaller registration studies will be required.

The ophthalmic diseases it is targeting will have lower technical thresholds due to the ease of access to the target, compared to renal and neurological diseases. PYC Therapeutics is capitalised at $601 million. It has a cash runway of more than $200 million, including future R&D tax rebates.

Bioshares recommendation: Spec. Buy Class A

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PYC Therapeutics Sets an Aggressive Clinical Agenda and Timeline

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