PYC THERAPEUTICS LIMITED — Investor Presentation 2021

Aug 16, 2021

Life-changing science

August Investor Update

August 2021

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 slides and the information they contain should be read in conjunction with past and future announcements made by Phylogica and should not be relied upon as an independent source of information. Please contact PYC and/or refer to the Company's website for further information.

The views expressed in this presentation contain information derived from publicly available sources that have not been independently verified. No representation or warranty is made as to the accuracy, completeness or reliability of the information.

Any forward looking statements in this presentation have been prepared on the basis of a number of assumptions which may prove incorrect and the current intentions, plans, expectations and beliefs about future events are subject to risks, uncertainties and other factors, many of which are outside PYC's control. Important factors that could cause actual results to differ materially from assumptions or expectations expressed or implied in this presentation include known and unknown risks. Because actual results could differ materially to assumptions made and PYC's current intentions, plans, expectations and beliefs about the future, you are urged to view all forward looking statements contained in this presentation with caution.

This presentation should not be relied on as a recommendation or forecast by PYC. Nothing in this presentation should be construed as either an offer to sell or a solicitation of an offer to buy or sell shares in any jurisdiction.

Who's on today's call

PYC US Development and Corporate Hub PYC Australia Discovery Hub

Sahm Nasseri, Chief Executive Officer US

Extensive experience in commercial drug development with Merck, incl. product leadership, investor relations and business development. Consultant with McKinsey & Co prior to Merck.

Dr Glenn Noronha, Chief Development Officer

Over 20 years leading drug development programs in ophthalmology, oncology, CNS and GI; multiple retina programs spanning candidate nomination through clinical development and approval. Previous C-suite & leadership roles at BridgeBio, Clearside and Alcon

Kaggen Ausma, Chief Business Officer

Previous roles in McKinsey & Co across Strategy, Commercial, VC and PE, and public market finance with CLSA Asia-Pacific

Professor Sue Fletcher, Chief Scientific Officer

Leading global expert and pioneer in RNA therapeutics. Coinventor of Exondys-51, Vyondys-53, and Amondys-45, commercialised by Sarepta. Prof. Fletcher leads PYC's discovery team and is the co-inventor of VP-001

Dr Rohan Hockings, Chief Executive Officer Australia

Experience across both clinical and commercial roles including Private Equity, Commercial Law, and Strategy, prior to joining PYC

PYC's distinctive PPMO technology offers key advantages

Flexible and precise RNA therapeutic molecule with potential for broader therapeutic window, longer duration of effect and application to a range of tissue and cell types

PYC's platform has been preclinically validated across a range of applications - ocular, CNS and systemic

PMO delivery in the retina, Day 28 in the mouse eye post single IVT injection

PMO delivery in the brain, Day 5 in the mouse brain post single ICV injection

PMO delivery systemically, Day 2 in the mouse post single IV injection

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

PYC has 100% ownership of PYC-001 and 90% ownership of VP-001 and VP-002 (10% ownership by Lions Eye Institute, Australia)

6 1 See ASX announcement 'Technical Presentation - October 2020' dated 9 October 2020; National Eye Institute (US) prevalence estimates for Diabetic Retinopathy ; see Nasca A, et al. 'Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations.' Orphanet J Rare Dis. 2017 May 12;12(1):89

Commenced larger animal preclinical studies for VP-001 program for Retinitis Pigmentosa type 11, with readouts in 2 species expected in early 4Q. IND filing on-track for mid-2022

Released critical in vivo and in vitro data for PYC's second program targeting OPA1 for the treatment of Autosomal Dominant Optic Atrophy, enabling progression to lead selection and preclinical development. IND filing targeted 1H2023

Successfully delivered high levels of PYC's PPMO to the mouse brain in first proof-of-concept data in Central Nervous System (CNS) discovery efforts, potentially overcoming a major barrier to other CNS targeted drugs

Continued to build PYC's presence in the U.S. including HQ in San Diego, build out of drug development team and broad engagement with US investor and BD community

PYC is making good progress towards our critical 2021 deliverables shared at the beginning of this year

8

Execute	□VP-001 through large animal studies in mid-2021 paving the way forIND submission in mid-2022□VP-002 for ADOA proof-of-concept and preclinical efficacy readout□PYC-001 for DR to proof-of-concept readouts
Establish	□Establish US management team□Build US preclinical and clinical development capabilities□Appoint US based and industry experienced Board Directors□Engage with US capital markets and drive business and corporatedevelopment
Expand	□Expand Ocular pipeline towards additional development programs□Showcase distinctive delivery of PPMO into the Central NervousSystem (CNS)□Identify first CNS development program for importantneurodegenerative disease

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

• Proof of concept data for PYC-001 for Diabetic Retinopathy in 2021

• Anticipate development of further ocular drug candidates leveraging the de-risked ocular

Ocular

PPMO platform

Autosomal dominant optic atrophy (ADOA) program targeting mutations in the OPA1 gene

Elina, living with ADOA

Autosomal dominant optic atrophy program targeting OPA1

Autosomal dominant optic atrophy (ADOA) is a genetic disease causing progressive blindness

• Characteristics of OPA1 ADOA are:
  • ‒ Severe, progressive blindness
  • ‒ Caused by mutations in the OPA1 gene leading to haploinsufficiency of the OPA1 protein1
  • ‒ Onset between the ages of 5 and 20
  • ‒ Primarily affects central vision
  • ‒ Leads to blindness between 40-50 years of age

A disease-modifying therapy addressing all patients with ADOA caused by haploinsufficiency of OPA1

• There are no approved drugs nor any in clinical development for treatment of these patients
• 9,000-16,000 estimated addressable patients in the western world1

ADOA is most frequently caused by mutations in the OPA1 gene, affecting the retinal ganglion cells

ADOA is caused by mutations in the OPA1 gene that result in the loss of retinal ganglion cells (RGCs), which make up the optic nerve

This causes severe vision loss, often beginning before the age of 10

The cascade linking the OPA1 protein insufficiency to the phenotype is well understood

Decreased OPA1 protein levels

Reduction in mitochondrial health (protein expression and mitochondrial fragmentation)

Reduced cellular bio-energetics (ATP, membrane potential and oxygen consumption rate)

• Increase in reactive oxygen species and apoptosis
• Atrophy of retinal ganglion cells and reduced vision

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

Statistical differences were analysed using one-way ANOVA; * p≤0.05 ** p≤0.01 *** p≤0.001 Patient 1 & 3: c.2708_2711 delTTAG Patient 2: c.985-1G>A

Further optimized PMO candidates have shown an ability to even further increase the OPA1 protein

Change in OPA1 protein levels, day 2 post PMO transfection, patient fibroblasts (n=3)

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 apoptotic stimuli for 4 hr prior to analysis. Apoptotic cells were analysed using flow cytometry. Bar graph represents relative apoptosis in patient fibroblasts treated with PPMO 7 days post-treatment (mean+SEM). Patient fibroblast without PPMO treatment was indexed to 100% apoptosis. Statistical differences were analysed using one-way ANOVA; * p≤0.05 ** p≤0.01 *** p≤0.001 **** p≤0.0001

See ASX Announcement 9 June 2021

PYC's PPMOs can reach the target cell in vivo and show functional delivery to mouse retinal ganglion cells

PYC's PPMOs demonstrate dose dependant uptake and long duration in the mouse neural retina

Exon-skipping in mouse neural retina, single IVT injection1

PYC's PPMOs demonstrate uptake in the Retinal Ganglion Cells in a mouse model

PPMO uptake in the mouse retina2, Day 7 single 1.6µg1 IVT injection

1 1.6µg is equivalent to 32.1µM concentration in the vitreous and 0.14nmols; 3.2µg is equivalent to 64.2µM concentration in the vitreous and 0.28nmols; 6.4µg is equivalent to 128.4µM concentration in the vitreous and 0.56nmols 2 PPMO localization us hybridization probes, using Basescope from ACDBio targeting SMN1 PPMO. Red dots are exon skipped mRNA, blue is full length mRNA

Preclinical data support PYC's PPMOs as a differentiated disease-modifying approach to treat OPA1 ADOA

Can upregulate the target OPA1 protein by >1.5 fold and increase mitochondrial bioenergetics and ATP production in a dose-dependent and mutation agnostic manner

Can protect cells from ADOA patients from apoptosis in a mutation agnostic manner, rescuing the critical functional deficit observed in ADOA patients to near functional levels observed in healthy cells with no mutations present

Can effectively reach the target neural retina cells in vivo, compared to alternative ASO approaches that show limited ability to reach these cells at much higher doses

Benefits from the positive attributes observed in the profile of PYC's PPMO technology

Path forward for the VP-002 program

Key Steps	Target timing
Additional preclinical efficacy and safety assessments inpatient-derived retinal models and animal models	Late 2021
Conclude lead selection and optimization of target PPMOmolecule through multiple in vitro and in vivoassessments of tolerability, efficacy, and biodistribution	Early 2022
IND-enabling studies (including dose-range finding tolerabilityfollowed by GLP toxicity) for lead PPMO molecule	Throughout 2022
Investigational New Drug filing with the FDA (clinical	1H 2023

Investigational New Drug filing with the FDA (clinical development anticipated to commence shortly thereafter)

VP-001 for the treatment of Retinitis pigmentosa type 11

Matthew, living with RP11

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 between 40-50 years of age

VP-001 has the potential to be transformational to patients

• There is no treatment for patients with RP11
• 4,000-8,000 patients in the western world
• Unmet need with no other drugs in clinical development

20

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 to correct the structural deficiency in patient derived retinal cells that is one of the key causes of vision loss in RP11 patients1

1 Buskin A. Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa. Nat Commun. 2018 Oct 12;9(1):4234.

PYC has assembled a world class clinical advisory board of leaders in the Retinitis Pigmentosa field

PYC's Clinical Advisory Board for the development of VP-001

Mark Pennesi, M.D., Ph.D. Professor of Ophthalmology and Chief of the Ophthalmic Genetics Division, Casey Eye Institute at Oregon Health and Science University

Jacque L. Duncan, M.D. Professor of Clinical Ophthalmology, University of California San Francisco

Fred K Chen, M.D., Ph.D. Ophthalmologist, Head of the Ocular Tissue Engineering Lab, Lions Eye at Lions Eye Institute in Western Australia

David Birch, Ph.D.

Scientific Director, Retina Foundation of the Southwest, Rose-Silverthorne Retinal Degenerations Laboratory

2021's key milestones for VP-001 centre on large animal studies

	Rabbit Dose-rangefinding [DRF]toxicity study	Non-humanprimates [NHPs]DRF toxicity study	GLP animal toxicitystudies	Formal regulatory(FDA) engagement
3Q21	3Q21	Late 3Q21	Initiate in late 2021	Late 2021
Understand oculartolerability in a largeeyeConfirm low to nosystemic levels,Obtain an initialunderstanding of theocular biodistributionin a larger animaleye, andIn part, inform a	In a dose descending toxevaluation obtain data to:Understand at what•dose toxicity may beobserved, and•Inform through theseearly data what dosesmay be selected forfurther tolerabilityevaluations includingfor the GLP study inrabbits	In a dose descending toxevaluation obtain datato:Understand at what•dose toxicity may beobserved, and•Inform throughthese early datawhat doses may beselected for furthertolerabilityevaluations includingfor the GLP study in	Under GLP conditions:Evaluate toxicity data•at more than onedose to support theFIH clinical studyplanned for 2H22•Obtain acute andChronic toxinformation, and•Inform doses for theFIH clinical trial	Informs our developmentplanning including the:•Early regulatorystrategy, and confirmspath forGLP tox studies,••FIH clinical trials, and•CMC efforts to supportclinical studies
••••	Rabbit pharmacokinetics [PK] andtissue distributionFollowing an intravitreousinjection of VP-001:dosing paradigm		NHPs

Targeted outcomes from upcoming VP-001 larger animal studies:

VP-001 achieves appropriate distribution in a larger animal retina, reaching relevant cell layers

VP-001 dosing in a larger animal eye provides information to inform dosing for GLP toxicity studies, thereby providing guidance for dosing in a first-in-human clinical trial

VP-001 has duration of effect supporting a 2-4 times a year or less frequent intravitreal dosing regimen

VP-001 demonstrates target engagement in a larger animal eye following intravitreal dosing

2021 is a transformative year for PYC Therapeutics

• Furthest a PYC Therapeutic has ever advanced in preclinical development—testing VP-001 in larger animals ahead of IND submission
• Multiple ocular assets running in parallel with key catalysts throughout 2021
• Expansion into the CNS, a highly attractive new therapeutic area with significant unmet patient needs
• Execution of a new operating model across Australia and the US to ensure access to critical expertise and partners to unlock the full potential of PYC's science

Q&A