PYC THERAPEUTICS LIMITED — AGM Information 2016

Nov 24, 2016

AGM 25 November 2016

PHYLOGICA PLATFORMS COMBINING TO PROGRESS COMMERCIALISATION

Ms Stephanie Unwin

Chair

Disclaimer

The purpose of the presentation is to provide an update of the business of Phylogica Limited (ASX:PYC) [‘Phylogica’]. 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 Phylogica 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 Phylogica’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 Phylogica’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 Phylogica. 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.

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2016 A YEAR OF STRONG PROGRESS

Further validation of our FPP intracellular delivery technology platform

§ FPP-mediated delivery of protein cargoes is very rapid and efficient

§ Quantified approximate concentration of the protein delivered into the cell

– far superior concentrations (with a range of new cargoes) to those achievable with an extensively validated conventional cell penetrating peptide (TAT)

FPP is consistently producing better results versus the gold standard

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Identified Phylomers for use as the drug cargo itself

• § Internal iMYC cancer program continues to build an impressive proof of concept data pack on the way to formal preclinical development in the second half of 2017

• Progress on the internal discovery program

• § Narrowed the number of proprietary iMYC candidates to five and the most suitable leads will be chosen for optimisation

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iMYC candidates

• § Performing well on a number of measures

• § No evidence of FPP-mediated toxicity

• § Improvements in pharmacokinetics

§ Evidence of activity in two independent animal models of cancer even when administered intravenously

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Building confidence in the iMYC program

• § The iMYC program is our most advanced with entry into a formal pre-clinical program planned for H2 2017

• § Phylogica is planning to achieve substantial increases in the potency of both its lead FPP and its lead iMYC before further multi-parameter optimisation of the conjugate begins

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Progress on Collaborations

• § Since June we have signed three non-disclosure agreements with international pharmaceutical companies to discuss elements of Phylogica’s technology portfolio.

• § Genentech are due to make a decision regarding licensing/extension of novel antimicrobials research program in December 2016

• § Phylogica’s delivery technology (in the form of its FPPs) is being examined by multiple third parties (Academic, Biotech and Pharma) for the delivery of various proprietary drug cargoes

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Phylomer Platform

• § The core intellectual property of Phylogica is our extensive library made up of protein fragments expressed from the genetic material of micro-organisms (Phylomers)

• § For several years, our team of scientists, managers and advisers has been working hard to utilise our to discover more efficient to deliver a Phylomer library peptides

• range of biologics cargoes into the inside of cells

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Platform continued

• § has the of as well as

• Phylogica significantly expanded landscape druggable targets enhancing the specificity and sensitivity of these drug-target interactions

• § our extensive to that be used as Searching through library identify Phylomers may the drug cargo in conjunction with the Functional Penetrating Phylomers (FPPs) led to our iMYC program

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2016 summary

§ Shortlisted oncology drug candidates for lead optimisation

• Potential for formal pre-clinical studies in second half of 2017

§ FPP cell delivery system is showing excellent results and remains highly competitive

• See the next presentation from Paul Watt, our Chief Scientific Advisor

We thank all of our hard working scientific team and our loyal shareholders for their support, as Phylogica gets closer to reaching commercial outcomes from its exceptional Phylomer library

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Technology Overview and Update

Adjunct Professor Paul Watt Chief Scientific Advisor

Phylogica Value Creation Engines

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§ Discovery (Phylomers)

§ Delivery (FPPs)

§ Development (iMYCs)

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DELIVERY:

Functional Penetrating Phylomers “FPPs”

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Biologics drugs are trapped within endosomes and thus their therapeutic effects are constrained

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Drug
Drug Contact triggers
Drug contacts cell Budding formation of endosomes
membrane endosome
Cell
Membrane
80% of potential drug targets are inside cells
Endosome
BIOLOGICS?
Drug
BIOLOGIC
99.9% of drug trapped in
S? endosome
Cell
Small Molecule Drugs (10%)
Membrane
Undrugged targets (90%)
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PYC’s Endosomal Escape Trap Assay identifies Phylomers that can liberate cargoes OUT of endosome

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Biotin Tag
Enzymatic Streptavin
attachment
Phylomer
Phylomer
Phylomer
Release and Capture
Trapped Phylomer (Streptavidin Beads)
Escaped Phylomer
+ Cargo
+ Cargo
Avitag
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§ Rare Phylomers identified that can deliver cargoes into cells and then liberate cargoes from the endosome are called ‘FPPs’

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Phylomer FPPs can deliver a diverse range of biologics cargoes into cells

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Peptides ✔
Toxins ✔
FPP Scaffolds ✔
✔
Enzymes
✔
Oligonucleotides
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Phylomer FPPs can deliver a diverse range of biologics cargoes into cells - continued

• § Examples of cargoes delivered with FPP01 or its derivatives

• § FPP versatile enough to deliver multiple cargoes with diverse size and charges

Cargo Class	Cargo	Size/Charge	IC50*	**MED
Toxin / large protein	Bouganin	28-50kDa, pI 7.8 (different constructs)	20nM	ND
Small protein scaffold	Omomyc	11kDa, pI 9.6	700nM- 5µM	ND
Enzymatic protein	𝛽-lactamase	42 KDa, pI 5.5	ND	ND
Large disordered protein	PAS	50kDa MW, 600kDa equiv. hydrodynamic radius, pI 5.9	ND	5µM
Peptide	Apoptotic (PAP) PPI inhibitor (DPMI⍺) Split protein complementation (S11 of GFP) Bcl-2 family inhibitory peptides – 26aa	17aa, pI 10.7 15aa, pI 8.26 30aa, pI 6.75 26aa, pI 6.28	1.7µM 8µM ND 1.6µM	1.25µM 1.25µM
Bispecifics	Bcl-2 inhibitory peptide + Omomyc scaffold	37kDa, pI 8.02	190nM	156nM
Oligonucleotides	Exon-skipping Morpholinos	24 base pairs, neutral	ND	50nM

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IC50s tested in various cell lines *Minimal Effective Dose ND - Not determined (only tested when relevant)

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Further evidence for superior delivery of FPP vs. TAT: quantified delivery of larger (iMyc) cargoes

• § Two distinct FPP-iMyc fusion proteins applied to mammalian cells for 60min

• § Assay that specifically quantifies the efficiency of cell entry & escape of iMyc from the endosome to the cytoplasm

• § FPPs again show vastly superior uptake and endosomal escape compared to the conventional CPP TAT, particularly at lower concentrations FPP conjugates of iMyc cargoes (0113 and 0177) show

• greater endosomal release than equivalent Tat conjugates at all concentrations tested

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iMyc&0113&Endosomal&Release:&FPP_01.1&versus&Tat& iMyc&0177&Endosomal&Release:&FPP_01.1&versus&Tat&
30000 35000
30000
25000
25000
20000
16uM 20000 16uM
15000
4uM 4uM
15000
2uM 2uM
10000
10000
5000
5000
0 0
FPP_01.1 TAT FPP_01.1 TAT
Alpha&signal&(A.U) Alpha&signal&(A.U)
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Evidence of efficacy following intravenous delivery in E µ Myc lymphoma model

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Mice injected daily with 40 nanomoles of Phylomer FPP-Omomyc fusion for 4 days
EuMyc cells/mouse
(in 100uL PBS)
At each time point:
-
D0 D3 D4 D6 D8D5 D7 D9 2 mice per group are
Extract spleen cells at day 7 (6 mice/cohort) culled and weighed
Measure labelled E - Spleens (and weigh) m Myc lymphoma cells
by flow cytometry and bone marrow
collected for FACS
Spleen D7 - 2.5x10 Weigh&prior&to& [5] EµMyc cells Spleen D7 - 5x10 [5] EµMyc cells
start&of&exp&
1.0 1.0

0.8 0.8
0.6 0.6

rou
0.4 Groups (8 mice per 0.4 g p)
1) 2x10 [5] cells/mouse
0.2 0.2
2) 2x10 [4] cells/mouse
0.0 0.0
Saline 3) C27_Omyc_V5 2x10 [3] cells/mouse Saline C27_Omyc_V5 Omyc
Mock FPP-Omomyc 4) Naive Mock FPP-Omomyc
% Tumour burden % Tumour burden
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• § 4 daily* injections of FPP-Omomyc reduced growth of lymphoma cells in spleen

• § Also saw a reduction in lymphoma cells in the bone marrow with FPP-Omomyc injections

• § FPP-Omomyc demonstrates efficacy following IV injection, prior to any optimisation

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*Limited to 4 daily injections due to previous animal ethics constraints. Potential to increase dose numbers in future experiments.

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FPPs – What we have now established

§ Enables endosomal escape

• § Compatible with wide range of cargoes

• § Outperforms other intracellular delivery technologies

• § Functional in multiple cell types

• § Viable manufacturing and strong IP Position

§ Better understanding of mechanism of action

• § Preliminary evidence of in vivo efficacy

• § Promising initial safety signals

Further validation of FPP Platform is generating increased external interest

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iMYC Program

(FPP combined with iMYC cargo)

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iMYC Program Development Timelines

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Good progress with proof-of-concept discovery program

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SUMMARY

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Multiple commercialisation opportunities for FPPs

‘Value Adding’

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Improve delivery of existing or new drugs

Commercial & Academic Collaborations

Functional Penetrating Phylomers

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‘Phylomer Therapeutics’

Fully integrated drug delivery/discovery platform

iMYC, STAT5 & YB1 programs

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Platform

Products

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Commercialisation Progress

§ Academic and Commercial Collaborations progressing

• Murdoch University – Oligonucleotides for Muscular Dystrophy

• ONJCRI (formerly Ludwig Institute) – Myc and Bcl2/Mcl1 Bispecifics

• Genentech – Next generation Antimicrobials

• 5 active other (confidential) collaborations

• 5 new NDAs with Pharma/Biotech signed since end of Q1, 2016

§ iMYC program

• Early engagement underway with pharma/biotech

• On track for formal preclinical in 2H17 – next value milestone

§ Phylomer Libraries

• Phoremost target and small molecule discovery alliance

• Potential to generate novel targets and new chemistry

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Thanks to our talented R&D team for their hard work and to our shareholders for support

• Katrin Hoffmann, DRSO

• Heique Bogdawa

• Nadia Milech

• Karen Kroeger

• Paula Cunningham

• Tatjana Heinrich

• Laura Florez

• Rob Dewhurst

• Marie Scobie

• Richard Francis

• Leanne Neville

• Jasmin Heng

• Maria Kerfoot

Emanuela Ferrari

• Ferrer Ong

Brooke Longville

• Scott Winslow

• Danie Champain

• Tracy Chai

• Suzy Juraja

• Mark Anastasas

• Renae Barr

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