Slide 1: PYC Presentation Materials for BIO Conference
31 October 19 April 2023 2022 For personal use only PYC PRESENTATION MATERIALS FOR BIO CONFERENCE • PYC is attending BIO 2023 – one of the industry’s primary business development events - in Boston in June • The Company’s presentation materials for the conference are attached PERTH, Australia and SA
Slide 2: For personal use only
other factors, many of which are outside the Company’s control. Important factors that could cause actual results to differ materially from assumptions or expectations expressed or implied in this ASX announcement include known and unknown risks. Because actual results could differ materially to ass
Slide 3: Life-changing science – BIO 2023
For personal use only Life-changing science BIO 2023 April 2023
Slide 4: Disclaimer
Disclaimer For personal use only The purpose of this presentation is to provide an update of the business of PYC Therapeutics Limited (ASX:PYC) [‘PYC’]. Theseslides have been prepared as a presentation aid only and the information they contain may require further explanation and/or clarification. Ac
Slide 5: Executive Summary
Executive Summary For personal use only PYC Therapeutics: • Is a clinical-stage drug discovery and development company • Uses its proprietary drug delivery platform to make first-in- class and disease-modifying RNA drug conjugates for patients with rare diseases • Focuses on monogenic disease (genet
Slide 6: PYC's strategy is anchored on four critical features
PYC’s strategy is anchored on four critical features For personal use only A HIGHER PROBABILITY A FASTER PATH LIKELY RAPID UPTAKE ORPHAN DRUG OF SUCCESS TO MARKET IN MARKET PRICING PYC focuses on The potential for First-in-class drugs in Median list price of monogenic indications. approval following
Slide 7: PYC's drug delivery platform extends the reach of RNA therapies
PYC’s drug delivery platform extends the reach of RNA therapies to new disease indications For personal use only PYC combines existing RNA drug design technology PYC’s drug delivery platform is used to assist with its proprietary drug delivery platform to the RNA drug reach its target inside the cel
Slide 8: PYC has built a pipeline of RNA therapies
PYC has built a pipeline of RNA therapies based on this non- viral facilitated delivery platform For personal use only Current progress Progress expected in 2023 Organ Program Target Discovery Pre-clinical IND enabling Clinical Trials Marketed VP-001* PRPF31 Retinitis Pigmentosa Type 11 PYC-001 OPA1
Slide 9: PYC's lead programs focus on the retina
PYC’s lead programs focus on the retina – a tissue in which the technology has an ideal profile For personal use only 1. High potency: >60% target engagement at 10 µg dosing in rabbits1 2. Patient-preferred dosing interval: 20-day retinal half life in rabbits/NHPs supporting a 100-day dosing interva
Slide 10: PYC's RNA conjugates represent a differentiated modality in the retina
PYC’s RNA conjugates represent a differentiated modality in the retina – an area of major unmet patient need For personal use only A) High target engagement1, 2 B) At safe and well tolerated doses >60% target engagement in rabbit No evidence of treatment related adverse retina following a single 10
Slide 11: Strategy to create first-in-class drugs in monogenic haploinsufficiency
PYC’s strategy is to leverage this profile to create first-in-class and disease-modifying drugs in monogenic haploinsufficiency For personal use only PYC is applying its technology in a well-defined domain: • Genetically-validated targets – highest probability of success in the clinic1 • Localised d
Slide 12: Human data from May 2023 and potentially rapid path to market
PYC will begin generating human data in May 2023 and has a potentially rapid path to market in its lead indications For personal use only 1. PYC is now in the human 2. With the potential for 2 clinical 3. And precedents for rapid data generation window trials to support approval market uptake if suc
Slide 13: VP-001 Retinitis Pigmentosa Type 11
For personal use only VP-001 Retinitis Pigmentosa Type 11 A progressive and blinding eye disease of childhood for which there are no available treatment options PYC THERAPEUTICS 11
Slide 14: VP-001 is a first-in-class potentially disease-modifying drug for RP11
VP-001 is a first-in-class and potentially disease- modifying drug for Retinitis Pigmentosa type 11 (RP11) For personal use only VP-001 1. The first potential treatment option for RP11 patients to enter the clinic 2. Capable of completely rescuing the haploinsufficiency responsible for causing the d
Slide 15: RP11 is a progressive blinding eye disease with no treatments
RP11 is a progressive and blinding eye disease of childhood for which there are no treatments available For personal use only Retinitis Pigmentosa type 11 (RP11) Degenerative sight of an RP11 patient • Severe and progressive blinding eye disease that begins in childhood 6 YEARS OLD • 5,000 – 10,000
Slide 16: RP11 likely has a subtle disease correction threshold
RP11 is likely to have a subtle disease correction threshold (due to incomplete penetrance in patient families)1,2 For personal use only Asymptomatic (AS) carriers of a PRPF31 mutation express the gene at levels only slightly higher than those in symptomatic (S) patients p < 0.01 PRPF31 mRNA copy nu
Slide 17: Non-clinical data support potential of VP-001 disease modification
Non-clinical data support the potential of VP-001 to drive disease modification in the clinic For personal use only PK/Tox PD Functional outcome PK/Retinal Delivery Target engagement Phenotypic rescue Safety/Tolerability NOAEL defined as highest dose assessed (50 µg in NHPs) in GLP-tox studies1 PK/P
Slide 18: VP-001 fully rescues PRPF31 expression in patient-derived iPSC-RPE
VP-001 fully rescues the haploinsufficient gene expression (PRPF31) that causes RP11 in patient-derived iPSC-RPE For personal use only Unaffected RP11 RP11 + VP-001 Scrambled control oligo Dose-dependent target gene rescue to wild type levels Confirms the VP-001 effect is on-target 1.2 Normalised ex
Slide 19: VP-001 effect in patient-derived 3D organoid models
VP-001’s disease-modifying potential is also visible in RP11 patient-derived 3D organoid models For personal use only VP-001 treatment increases PRPF31 protein expression in RP11 patient-derived photoreceptors1,2 Nuclear stain PRPF31 Untreated RP11 Unaffected RP11 RP11 + VP-001 10 Normalised Mean Fl
Slide 20: Correcting PRPF31 insufficiency rescues appearance and function of cells
Correcting the PRPF31 gene insufficiency rescues both the appearance and function of affected cells in RP11 For personal use only Retinal pigmented epithelium (RPE) cells derived from: 1. A HEALTHY INDIVIDUAL 2. A PATIENT WITH RP11 3. A PATIENT WITH RP11 AFTER A SINGLE DOSE OF VP-001 VP-001 restores
Slide 21: VP-001 in early-stage clinical trials with rapid path to market
VP-001 is currently in early-stage clinical trials with the potential for a rapid path to market (single registrational study) PYC initiated an interventional study (PLATYPUS) : First Patient Dosing Expected in May 2023 For personal use only 2023/24 2024/25 2025/26 Single Ascending Dose (SAD) Multip
Slide 22: Comprehensive endpoints to assess visual function
A comprehensive set of endpoints to assess visual function and functional vision has been included in the study designs For personal use only Natural History Study First in Human Interventional Study (Quokka) (Platypus) • Functional Assessments • Functional Assessments • Best Corrected & Low Lumines
Slide 23: Perimetry and low-luminance mobility endpoints for early efficacy insights
Perimetry and low-luminance mobility are the endpoints on which early insights into potential efficacy will likely be visible For personal use only Anecdotal natural history studies in RP11 have observed meaningful deterioration within a year across visual field, ERG and EZ area Reduction in Visual
Slide 24: PYC-001 Autosomal Dominant Optic Atrophy (ADOA)
For personal use only PYC-001 Autosomal Dominant Optic Atrophy (ADOA) A progressive and blinding eye disease of childhood for which there are no available treatment options PYC THERAPEUTICS 22
Slide 25: PYC-001 is a first-in-class potentially disease-modifying drug for ADOA
PYC-001 is a first-in-class and potentially disease-modifying drug for ADOA For personal use only 1. ADOA is a progressive and blinding eye disease with no treatment options available today 2. PYC-001 addresses the underlying cause of ADOA by increasing OPA1 protein expression1 3. PYC-001 is a diffe
Slide 26: ADOA is a progressive blinding eye disease with no treatments
ADOA is a progressive and blinding eye disease of childhood for which there are no treatment options available For personal use only Autosomal Dominant Optic Atrophy (ADOA) Degenerative sight of an ADOA patient • A progressive and irreversible blinding eye disease 10 YEARS OLD • 9,000 – 16,000 addre
Slide 27: PYC-001 rescues OPA1 gene expression in ADOA patient-derived models
PYC-001 rescues OPA1 gene expression and improves functionality in ADOA patient-derived models PYC has demonstrated the potential to address the root cause of ADOA in a mutation independent For personal use only manner (validated in material derived from multiple patients) Fibroblasts iPSC-RGC (targ
Slide 28: PYC-001 is a differentiated approach to ADOA treatment
PYC-001 is a differentiated approach to the treatment of ADOA – even within the RNA therapeutic class For personal use only 1. Effectively reach the 2. Maintain the isoform 3. Favourable re- target cells in vivo balance of OPA1 dosing profile in eye PYC’s PPMO is ~100-fold more Essential for full re
Slide 29: PYC-001 drug-like profile and non-clinical data pack
PYC-001 has an ideal drug-like profile with a compelling non- clinical data pack supporting clinical progression For personal use only PK/Tox PD Functional outcome PK/Retinal Delivery Target engagement Phenotypic rescue Safety/Tolerability Safe and well tolerated at relevant doses Read-through from
Slide 30: PYC expected to begin clinical trials for ADOA next year
PYC is expected to begin clinical trials for ADOA next year^ For personal use only 2023 2024 H1 PYC intends to leverage clinical insights from lead program to support Anticipated CMC for GLP • H2 progression of PYC-001 development studies initiated timeline and • GLP tox. studies H1 milestones initi
Slide 31: Board, Executive and Advisory Boards
Board, Executive and Advisory Boards For personal use only Alan Tribe Dr Rohan Hockings Sri Mudumba Andrew Taylor Prof Sue Fletcher Chairman Chief Executive Officer Chief Research & Development Officer Chief Financial Officer Chief Scientific Officer Experience commercialising Australian Dual-traine