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Retinitis Pigmentosa Type 11 - a USD1- 2B P.A

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Retinitis Pigmentosa Type 11 - a USD1- 2B P.A Corporate Life-changing science Presentation February 2021 Overview PYC is an RNA therapeutics company with an initial focus on diseases of the eye § RNA therapeutics have come of age But their ongoing success is impeded by inefficient or toxic delivery inside cells § PYC’s cell-penetrating peptide (CPP) delivery platform solves this ‘delivery’ problem PYC’s competitive advantage is getting more drug safely into the target cell § PYC is applying this advantage to develop drugs for eye disease: an area of unmet need PYC’s lead program is the first disease-modifying therapy for Retinitis Pigmentosa type 11 - a USD1- 2B p.a. target market § PYC’s technology scales rapidly in the eye: same delivery tech for other RNA cargoes PYC has two other defined drug programs, each with blockbuster potential, addressing Diabetic Retinopathy and Autosomal Dominant Optic Atrophy § Building on its success in the eye, PYC is expanding the application of its technology The Company’s initial focus outside the eye is on neurodegenerative diseases 2 Corporate Snapshot (ASX: PYC) Financial Information (29 January 2021, AUD) Share Price Performance (12 months) ASX website Share price $0.14 Number of shares 3,170M Market Capitalisation $445M Cash $57M Debt Nil Enterprise Value $388M Board of Directors Alan Tribe – Chairman Sahm Nasseri– Chief Executive Officer (USA) Dr Rohan Hockings – Chief Executive Officer (Australia) Building out a US base to complement Australian discovery hub Dr Bernard Hockings – Non-Executive Director • Early discovery and candidate proof of concept development led by PYC Australia Top Shareholders (29 January 2021) % • Pre-clinical, clinical development and regulatory engagement to be led by PYC US Alan Tribe 30.11% • Corporate HQ shifting to US through 2021, in-line with corporate development activities David Sietsma 8.96% • Broaden Board of Directors to include US membership Dr Bernard Hockings 8.41% • Evaluating most appropriate corporate development path with a base-case approach of delivering a Anthony Barton and Associates 6.10% US-listing through ADR in next 12-18mths 3 Leadership team Executive management Sahm Nasseri, Chief Executive Officer US Kaggen Ausma, Chief Business Officer Extensive experience in commercial drug development Previous roles in McKinsey & Co across Strategy, with Merck, incl. product leadership, investor relations Commercial, VC and PE, and public market finance and business development. Consultant with McKinsey with CLSA Asia-Pacific & Co prior to Merck. Professor Sue Fletcher, Chief Scientific Officer Dr Rohan Hockings, Chief Executive Officer Australia Leading global expert and pioneer in RNA therapeutics. Experience across both clinical and commercial Co-inventor of Exondys-51, Vyondys-53, and Casimersen, roles including Private Equity, Commercial Law, commercialised by Sarepta. Prof. Fletcher leads PYC’s and Strategy, prior to joining PYC discovery team and is the co-inventor of VP-001 Advisory Board Dr Fred Chen Professor Judy Lieberman Asc. Professor Rakesh N. Veedu MBBS (Hons), PhD, FRANZCO MD, PhD MSc, PhD, MRACI Chair Ophthalmic Advisory Board Scientific Advisory Board Member Scientific Advisory Board Member Retinal clinician, co-inventor of Leader and pioneer in the field of Extensive expertise in basic and VP-001 and leader of Ocular siRNA, Chair in Cellular and translational research in the field Tissue Engineering Laboratory at Molecular Medicine at Boston of oligonucleotide therapeutic Lions Eye Institute Children’s Hospital, Professor of development Pediatrics at Harvard Medical School 4 PYC combines World-class RNA therapy design + Revolutionary delivery technology World-class RNA drug design specialists, leveraging Delivery technology that enables RNA drugs to Antisense Oligonucleotides reach their target inside the cell § Team led by Chief Scientific Officer- Prof. Sue Fletcher – co- § The single greatest challenge for RNA drugs is the ability to cross inventor of two FDA approved RNA therapeutics with others in late- the cell membrane to reach their target stage clinical development § PYC’s delivery technology is based on a unique library of Cell § RNA drugs are precision therapeutics that act on the inside of cells Penetrating Peptides, nature’s solution to safely access cells § They occupy a unique position in the pharmaceutical landscape due § Cell Penetrating Peptides safely deliver the RNA drug: to their balance of durability and titratability § i) to the cell; and § PYC has the capability to identify highly valuable targets and § ii) across the cell membrane where it can engage its design tailored RNA intervention strategies to match intended target in the cell nucleus 5 Delivery remains the rate limiting step for RNA drugs PYC’s CPPs have a competitive edge in solving this problem Delivery technology Companies Cargoes Tech dev. stage Technologies core mechanism of action Naturally derived cell- PMO Pre-clinical § Utilise library of natural peptide to identify penetrating peptides peptide sequence driven uptake for delivery of cargoes into the cell Chemically derived cell- PMO Phase 1/2 § Utilise chemically derived, highly charge dense penetrating peptides and/or constrained peptides to enable delivery of cargoes into the cell Antibody conjugates ASO and Pre-clinical § Utilise an antibody to bind to a cell surface siRNA receptor and transport to traffic cargoes into the cell Ligand conjugates ASO and Marketed § Utilise a ligand to bind to a cell surface receptor siRNA and transport to traffic cargoes into the cell Lipid conjugates siRNA Pre-clinical § Utilise a fatty acid to bind to a cell surface receptor and transport to traffic cargoes into the cell Exosomes/LNP siRNA, ASO, Pre-clinical § Utilise exosomes to present or deliver ASOs plasmid using the exosomes trafficking ability Chemically modified ASO Marketed § Modify the ASO backbone chemistry to improve backbone uptake and/or efficacy 6 PYC’s CPP-PMO technology offers several advantages over other genetic therapy modalities PYC CPP-PMO advantages Why it matters AAV gene ASO siRNA therapies • PMOs do not bind or sequester positively charged Safe delivery of drug to splicing factors as do negatively charged ASOs, nucleus hence cause lower toxicity • PMOs have higher resistance to intracellular Durability of drug within degradation vs. other ASOs which provides potential cell for longer duration of effect • CPP-PMO is distributed broadly across tissue— Broad distribution within critical for treating diseases affecting tissue a target tissue structure and for accessing hard to reach cells • CPP-PMO has potential applicability to a range of Effective delivery to a target tissues and cell types vs. other delivery range of target tissues modalities (e.g., GalNAc and antibodies) • Like other ASO approaches, CPP-PMO allows precise Precise modulation of intervention to modulate cellular pathways to treat target gene multifactorial diseases • Like other RNA therapies, CPP-PMOs avoid risk of over- Retention of endogenous expression of proteins which can cause additional cellular control disease, esp. in diseases caused by haploinsufficiency 7 PYC is applying our technology to create life changing treatments, with an initial focus on diseases of the eye PYC is a multi-asset drug development company Program overview Indication and stage of development Estimated market size Lead Organ Program Target Discovery IND-enabling Clinical Marketed selection Eye VP-001 PRPF31 Retinitis Pigmentosa Type 11 US$1-2 billion p.a. PYC-001 VEGF Diabetic Retinopathy >US$5 billion p.a. Autosomal dominant optic VP-002 OPA1 ~US$1 billion p.a. atrophy Multiple Undisclosed Discovery pipeline Multiples of programs CNS Multiple Undisclosed Discovery pipeline Multiples of programs PYC has 100% ownership of PYC-001 and 90% ownership of VP-001 and VP-002 (10% ownership by Lions Eye Institute, Australia) 8 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 Pigmented Epithelium (RPE), for 28 days in patient iPSC derived RPE pathogenic mutations in PRPF31 the mouse %D7 RPE isolate (28 days) (each patients with a different mutation) 100 Exon 7 skipping in RPE1, Day 28 in the mouse eye post IVT PRPF31 protein levels2, RPE, 5µM treatment, (n=1 per patient) 80 2.5 Day 2 Day 5 Day 12 Untreated 60 60 d Treated e t (%) 2.0 a e * r t n u Smn r 1.5 4040 e v o Anticipated disease e 19.1 g correction threshold 1.0 n a h 20 13.7 c 20 d l o 0.5 5.0 F 0.0 Exon Skipping 0 0.0 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Vehicle 1.6µg 3.2µg 6.4µg Non-penetrant Penetrant g/eye) g/eye) g/eye) µ Leadµ CPP-PMOµ 1 Day 28 post intravitreal injection in mice. A readout of drug delivery, Exon-skipping of Survival of Motor Neuron (Smn) in the mouse retina across 3 dose cohorts (n=12 for each dose cohort, n=4 for vehicle) 2 For anticipated disease correction threshold see ‘Venturini, G. CNOT3 Is a Modifier of PRPF31 Mutations in Retinitis Pigmentosa with Incomplete Penetrance. PLOS Genetics November 2012’ 9 See ASX Announcement 22 July 2020; 7 October 2020 Vehicle control Full-d-HPG0031-Ext2-3'SMN1Full-d-HPG0031-Ext2-3'SMN1Full-d-HPG0031-Ext2-3'SMN1 (1.6 (3.2 (6.4 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 Gfap expression,dd PDayC R7 info ther G mouseFAP eye
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