Pyc Therapeutics Limited · ASX:PYC
Pyc Therapeutics — Investor Presentation (June 2021)
32 slides from Pyc Therapeutics's investor presentation, June 2021
Slide 1: Corporate Presentation June 2021
Corporate Life-changing science Presentation June 2021
Slide 2: Disclaimer
Disclaimer The purpose of this presentation is to provide an update of the business of PYC Therapeutics Limited (ASX:PYC) [‘PYC’]. These slides have been prepared as a presentation aid only and the information they contain may require further explanation and/or clarification. Accordingly, these slid
Slide 3: PYC Highlights
PYC Highlights PYC is an RNA therapeutics company developing drugs for a range of genetic conditions Novel Technology Platform built on Cell Penetrating Peptide- Leading-edge RNA PMO technology. PPMOs solve delivery challenge and get Therapeutics more drug safely into cells Programs in diseases of E
Slide 4: PYC's growing Executive Leadership team built across the US and Australia
PYC’s growing Executive Leadership team built across the US and Australia Leadership team Sahm Nasseri Dr Sue Fletcher Chief Executive Officer US, Exec. Director Chief Scientific Officer Extensive experience in commercial drug development with Leading global expert and pioneer in RNA therapeutics wi
Slide 5: Platform Technology: Proprietary P-PMOs
Platform Technology: Proprietary P-PMOs 5
Slide 6: PYC's core therapeutic technology brings together two distinctive components
PYC’s core therapeutic technology brings together two distinctive components PYC’s library of Cell- PMO (Phosphorodiamidate penetrating peptides Morpholino Oligomer) Latest generation anti-sense Naturally-derived peptide library oligonucleotide chemistry, neutral (500M sequences) backbone Precision
Slide 7: PYC's platform has been preclinically validated across ocular, CNS and systemic applications
PYC’s platform has been preclinically validated across a range of applications- ocular, CNS and systemic Retinal delivery Brain delivery Systemic delivery PMO delivery in the retina, Day 28 in the mouse eye post PMO delivery in the brain, Day 5 in the mouse brain post PMO delivery systemically, Day
Slide 8: Choosing the right peptide for the right application is a key development step
Choosing the right peptide for the right application (cell, tissue, indication) is a key development step PYC’s library leverages millions of years of This is combined with an efficient screening and evolution by micro-organisms to create a validation pipeline structurally diverse set of potential C
Slide 9: PYC is applying our technology to create life changing treatments
PYC is applying our technology to create life changing treatments, with an initial focus on diseases of the eye and CNS PYC is a multi-asset drug development company Estimated addressable Program overview Indication and stage of development patients in western world Organ Program Target Lead Discove
Slide 10: VP-001 for the treatment of Retinitis pigmentosa type 11
VP-001 for the treatment of Retinitis pigmentosa type 11 Matthew, living with RP11 10
Slide 11: VP-001 for Retinitis pigmentosa type 11
VP-001 for Retinitis pigmentosa type 11 Retinitis pigmentosa (RP) is a genetic, blinding eye disease ▪ Retinitis pigmentosa type 11 (RP11) is a form of RP caused by mutation in the PRPF31 gene ‒ Severe, progressive blinding eye disease ‒ Onset between the ages of 10 and 20 ‒ Leads to blindness betwe
Slide 12: VP-001 targets a negative regulator of the gene underlying RP11
VP-001 targets a negative regulator of the gene underlying RP11 Healthy eye Patients with RP11 VP-001 We all have two copies of each gene in Patients with RP11 have only one healthy VP-001 skips an exon in a gene (CNOT3) our chromosomes gene (and one mutated gene) that acts as a negative regulator o
Slide 13: VP-001 has already demonstrated a strong preclinical efficacy signal
VP-001 has already demonstrated a strong preclinical efficacy signal in vivo and in patient derived models PYC has demonstrated delivery to the target cells, And shown upregulation of the target protein, PRPF31, in Retinal Pigment Epithelium (RPE), for 28 days in the patient iPSC derived RPE pathoge
Slide 14: The dose dependant response shows no increasing acute toxicity in the mouse
The dose dependant response shows no increasing acute toxicity in the mouse Dose dependant increase in effect … … and no increase in toxicity markers Exon 7 skipping, Day 7 in the mouse eye ddPCR Gfap expression, for Day 7 in theGFAP expression mouse eye in Neural Retina at D7 (n=12) Neural Retina 0
Slide 15: VP-001 has demonstrated the ability to correct important functional deficits associated with RP11
VP-001 has demonstrated the ability to correct important functional deficits associated with RP11 Scanning electron microscopy of retinal pigmented epithelium (RPE) derived from control and patient iPSC. Images selected as representative of full data set. These results demonstrate VP-001’s ability t
Slide 16: VP-001 Key Takeaways and Next Steps
VP-001 Key Takeaways and Next Steps 1. RP11 represents a large, underserved market with no Next Steps: disease-modifying therapies available nor in clinical development • Larger animal 2. To date, VP-001 has been shown to: (rabbit and NHP) ▪ Reach the target cell following intravitreal injection PK,
Slide 17: VP-002 program for the treatment of Autosomal dominant optic atrophy
VP-002 program for the treatment of Autosomal dominant optic atrophy Elina, living with ADOA 17
Slide 18: VP-002 program for Autosomal dominant optic atrophy
VP-002 program for Autosomal dominant optic atrophy Autosomal dominant optic atrophy (ADOA) is a genetic disease causing progressive blindness ▪ The majority of ADOA cases are caused by mutations in the OPA1 gene leading to haploinsufficiency of the OPA1 protein1 ▪ Characteristics of OPA1 ADOA are:
Slide 19: ADOA is most frequently caused by mutations in the OPA1 gene
ADOA is most frequently caused by mutations in the OPA1 gene affecting the retinal ganglion cells ADOA is caused by the loss of retinal ganglion cells (RGCs) which make up the optic nerve ▪ This causes severe vision loss in the patient ▪ Vision loss often starts before the age of 10 Healthy Healthy
Slide 20: PYC's PPMOs increase the critical OPA1 protein in a dose-dependent and mutation agnostic manner
PYC’s PPMOs have shown an ability to increase the critical OPA1 protein in a dose-dependent and mutation agnostic manner Change in OPA1 protein levels, day 7 post PPMO treatment, patient fibroblasts Patient 1, n=3 3 Patients (pooled), n=3 per patient Statistical differences were analysed using one-w
Slide 21: PYC's PPMOs increase mitochondrial ATP production in patient derived models
PYC’s PPMOs have shown the ability to increase mitochondrial ATP production in patient derived models in a mutation agnostic manner Change in mitochondrial ATP levels, day 7 post PPMO treatment, patient fibroblasts Patient 1 and 3 harbour c.2708_2711delTTAG deletion, Patient 2 harbours the c985-1G>A
Slide 22: PYC's PPMOs protect cells against Apoptosis in patient derived models
PYC’s PPMOs have shown an ability protect cells against Apoptosis in patient derived models in a mutation agnostic manner Relative apoptosis, day 7 post PPMO treatment, patient fibroblasts Patient fibroblasts were pre-treated with PPMO at 5 and 10 µM for 7 days and were subsequently treated with apo
Slide 23: Preclinical data support PYC's PPMOs as a differentiated approach to treat OPA1 ADOA
Preclinical data support PYC’s PPMOs as a differentiated disease-modifying approach to treat OPA1 ADOA Can effectively reach the target neural retina cells in vivo, compared to alternative ASO approaches that show limited ability to reach these cells at even higher doses Can upregulate the target OP
Slide 24: VP-002 program Key Takeaways and Next Steps
VP-002 program Key Takeaways and Next Steps Next Steps: 1. OPA1 ADOA represents a large, underserved market with no disease-modifying therapies available nor in • Report additional preclinical clinical development efficacy and safety data from 2. To date, PYCs’ VP-002 program has shown PPMOs that pa
Slide 25: Beyond Rare Ocular Disease: PYC-001 for Diabetic Retinopathy
Beyond Rare Ocular Disease: PYC-001 for Diabetic Retinopathy 25
Slide 26: Diabetic Retinopathy
Diabetic Retinopathy ▪ Diabetic retinopathy (DR) is caused by changes in the blood vessels of the retina. In some cases, blood vessels may swell and leak fluid, or grow on the surface of the retina, resulting in loss of vision. ▪ The incidence of DR is expected to grow from ~8 million Americans in 2
Slide 27: PYC-001 Key Takeaways and Next Steps
PYC-001 Key Takeaways and Next Steps ▪ PYC has leveraged the unique advantages of its RNA therapeutics technology to create a modified Next Steps: VEGF therapy that addresses these shortcomings. • Report results from ▪ PYC’s approach alters the type of VEGFA produced by cells in the eye to a type no
Slide 28: PPMOs in the Central Nervous System and Other High Unmet Need Conditions
PPMOs in the Central Nervous System and Other High Unmet Need Conditions 28
Slide 29: Initial results show great promise for PYC's PPMOs in the CNS
Initial results show great promise for PYC’s PPMOs in the CNS PMO delivery to the brain, Smn exon 7 skipping, PMO distribution in the brain, Smn exon 7 skipping, Day 5 post Day 5 post single I.C.V. injection in mice1 single I.C.V. injection in mice2 1 n=2 for all groups expect PYC PPMO 1nmol group w
Slide 30: This indicates we can access regions of the brain that matter in neurodegenerative diseases
… and this indicates we can access regions of the brain that matter in neurodegenerative diseases MOUSE Cortex Alzheimer’s disease HUMAN Amyotrophic Lateral Sclerosis % denotes Smn exon 7 skipping, Day 5 post Frontotemporal dementia single I.C.V. injection in mice Corpus Callosum Neurometabolic dise
Slide 31: PYC's PPMO technology has demonstrated broad potential including preferential delivery to high value organs
PYC’s PPMO technology has demonstrated broad potential including preferential delivery to high value organs CPP-PMOs demonstrate strong uptake across high value … and preferential delivery to certain organs tissues include heart and diaphragm … such as the Kidney Exon 7 skipping (%) in tissue 1, Sin
Slide 32: Looking forward to numerous critical value inflection points throughout 2021
We are looking forward to numerous critical value inflection points throughout 2021 VP-001 for Retinitis pigmentosa type 11 VP-002 for Autosomal Dominant Optic Atrophy VP-001 Multiple interim data readouts in Full data readout in VP-001 GLP readouts for RP11 large animals (ocular PK-tissue large ani