PYC THERAPEUTICS LIMITED — AGM Information 2017

Nov 26, 2017

Phylogica: Pivot to Platform

AGM Presentation By CEO Stephanie Unwin November 2017

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.

==> picture [307 x 539] intentionally omitted <==

We must pivot from developing drugs to commercialising the platform

Value proposition: Enhance existing drugs to address a large and growing $250Bn USD market 1 2 3 Bring drugs Enhance Reduce to the right properties of discovery place drugs (e.g., cycle time (i.e., to improve (strongly intracellular therapeutic improving targets) window) profile)

• Our advantage is in using our assets as a platform to solve Pharma problems

… Phylogica has unique, valuable assets

• … for a huge potential market

• Complex, rich Phylomer library –target identification or drug discovery

• Well validated platform technology – in vivo work demonstrates delivery and we have landed multiple Pharma deals

• Unmet need – undruggable $250Bn growth market, intracellular hurdles

• • Blue sky potential – enhancing Phylomer library to screen for new cargoes and carriers

• Strong patent position - international patents in place, latest endothelial cell structures granted in October

• –

• De-risked investment opportunity platform intracellular delivery, and screen for new targets

Value to Pharma shown by validating diverse sets of cargoes and cell types

FPP01 validation matrix

Oligo- Expand to Peptides Scaffolds Enzymes Antibodies nucleotide new cargoes Breast tumour Blood cancer Bone cancer Heart Muscle Diaphragm Liver Expand to new targets Conceptual In vitro validation In vivo validation

Phylogica is validating FPP’s across a matrix of possible cargoes and targets:

• each matrix ‘cell’ opens up another potential market

• Multiple offerings allows Phylogica to operate at scale serving many Pharma

2018: PYC funded to validate cargoes/ targets increasing Pharma interest in partnering for drug discovery

==> picture [412 x 268] intentionally omitted <==

----- Start of picture text -----

b-actin
Cre
----- End of picture text -----

==> picture [124 x 125] intentionally omitted <==

==> picture [420 x 252] intentionally omitted <==

6

Phylogica shortens Pharma discovery phase

==> picture [847 x 379] intentionally omitted <==

----- Start of picture text -----

Typical drug PRECLINICAL CLINICAL
DRUG DISCOVERY FDA APPROVAL
discovery process (animal testing) (human trials)
5 years 1.5 years 6 years 1-2 years
Typical Timelines
Regulatory
Determination Drug safety Drug safety &
approval for
of a suitable & efficacy in efficacy in
commercialisa
Key Milestones drug animals humans
-tion
Value of PYC
platform
Highly attractive for Pharma customers

Significantly improve the profile of customer drugs

Massively shorten the discovery phase

Customers reach their value inflection points faster
----- End of picture text -----

In the platform landscape, PYC uses its technology for the undruggable

Value

Pharmacokinetic technology

Therapeutic discovery

Drugging the undruggable

Application

Diverse Matrix of targets and cargoes targets/ Dendrimer platforms across Protein, mAb, Cas9 cargoes modalities Peptide discovery Protein, siRNA PK for biologics Oncology and Oncology mAb focus Focused antibiotic-focused CNS-specific PK targets/ drug discovery Focused on ADC cargoes Single oncology target focus

BIO: Customer feedback

Lots of interest from target customers…

… who clearly see the need for our platform technology

==> picture [134 x 73] intentionally omitted <==

==> picture [115 x 111] intentionally omitted <==

==> picture [104 x 104] intentionally omitted <==

==> picture [184 x 27] intentionally omitted <==

==> picture [85 x 97] intentionally omitted <==

==> picture [163 x 45] intentionally omitted <==

==> picture [199 x 39] intentionally omitted <==

” primary therapeutic isn’t ” working …need ” a back up plan “ we need delivery to ” the cytosol

“ ’ You ve come a long way since ” we last saw you

” Interested in your platform, very exciting”

“ We are facing intracellular ” hurdles…

To achieve PYC – the Platform: Phylogica is laser focused on 3 goals

Outcome :

Further • More in vivo functional validation

prove the • Improve our FPPs 1 value of our • Enrich and validate our library platform

Transform • Reduce discovery and validation

operations 2 cycle times with automation

to achieve • Engage CROs to drive scale scale

• across Close multiple deals Step up our therapeutic areas commercial 3 • Grow existing collaborations engine

Thank you

For more information contact Stephanie Unwin at stephanieu@phylogica.com

~~Significant constraints in existing drug~~ discovery approaches

==> picture [844 x 269] intentionally omitted <==

----- Start of picture text -----

Our
The
solution?
Phylomer
problem?
CPP
Biologics
-
Antibodies
-
Scaffolds
-
rProteins We can bring
Drug discovery growth
biologics into the
stagnating as biologics
cell, unlocking the
currently limited to
Therapeutic Cargoes potential of these
extracellular targets •
(unable to enter cells) Biologics• Phylomers powerful drugs by
• Antibodies allowing them to
• Scaffolds reach intracellular
• Small Molecules
• Toxins targets
----- End of picture text -----

Our Functional Penetrating Peptides (FPPs) can deliver biologics into the cell

==> picture [130 x 29] intentionally omitted <==

Harnessin the Microbiome for new Ph lomer libraries g y

==> picture [177 x 71] intentionally omitted <==

----- Start of picture text -----

Current Phylomer libraries
(size indicates number of genomes)
Future Phylomer libraries
----- End of picture text -----

Hug, Laura A et al. 2016. “A New View of the Tree of Life.” Nature Microbiology 1(5): 1-6

==> picture [130 x 29] intentionally omitted <==

Board meeting – Science update

2

~~PYC has shown conclusively~~ that FPPs work in animal models

Inhibition of tumor growth in mouse cancer model

==> picture [473 x 103] intentionally omitted <==

==> picture [369 x 210] intentionally omitted <==

Restoring dystrophin levels by FPP mediated delivery of DMD PMO

==> picture [363 x 328] intentionally omitted <==

----- Start of picture text -----

Treated mice
DMD oligo FPP1-DMD oligo
Leg
Diaphragm
Heart
Collaborator: Sue Fletcher, Centre for Comparative Genomics 3
----- End of picture text -----

Collaborator: Pilar Blancafort, Harry Perkins Institute

~~FPP1 has been significantly improved upon,~~ and new variants are being validated in vitro

==> picture [861 x 373] intentionally omitted <==

----- Start of picture text -----

Flow
cytometry
N=2
Phylogica’s FPP
improvement
Negative Control FPP 1 FPP 2
program through
rational design has
Confocal
demonstrated the
microscopy
ability to enhance
potency with no
increase in toxicity
----- End of picture text -----

4

~~Into 2018, PYC is validating a comprehensive matrix~~ of FPPs - delivery of cargoes into different cell types

==> picture [124 x 125] intentionally omitted <==

b-actin Cre

==> picture [130 x 29] intentionally omitted <==

5

~~In progress validation - FPP peptide~~ vaccine retards tumor growth

==> picture [531 x 104] intentionally omitted <==

• Subcutaneous B16 melanoma model engineered to express glycoprotein B (gB) from Herpes Simplex Virus

• Peptide vaccine contains a well characterized CD8+ T cell gB peptide epitope with and without FPP

==> picture [315 x 173] intentionally omitted <==

Our FPP peptide vaccine approach:

• Primes tumor specific CD8+ T-cells

• FPP containing peptide vaccine retards tumour growth greater than nonFPP control

• FPP-peptide vaccines have the potential to synergize with existing immunotherapies

==> picture [46 x 31] intentionally omitted <==

Collaborator: Jason Waithman, Telethon Kids Institute

6

~~Partnering strategy - Genentech work~~ continues to be successful

• Isolating Phylomers that can help kill gram-negative bacteria (multi-drug resistant “super bugs”)

• Evaluation period end of CY 2019

==> picture [650 x 180] intentionally omitted <==

----- Start of picture text -----

gram-positive gram-negative
Antibiotic ✔ ✗
Phylomer ✗ ✗
-
Phylomer Antibiotic ✔ ✔
Pseudomonas aeruginosa
----- End of picture text -----

==> picture [219 x 16] intentionally omitted <==

----- Start of picture text -----

increased antimicrobial range
----- End of picture text -----

==> picture [130 x 29] intentionally omitted <==

==> picture [642 x 117] intentionally omitted <==

----- Start of picture text -----

PYC
September ‘17 October November December January ‘18
Screen of Top 24 6 Phylomer-antibiotic fusions Synthesis of 13 MIC
3 bacterial Phylome → 1 positive for bacterial killing (MIC Phylomer-antibiotic assa
strains r hits assay) fusions y
Top 30 Synthesis of 30 MIC
NGS and
Screen of 1 new bacterial strain Phylome Phylomer-antibiotic assa
Bioinformatics
r hits fusions y
2015
2017
----- End of picture text -----

7

~~Building on the success of the past, turning towards~~ the future of FPPs

Building Therapeutics Logically

New technologies

HTP automation to rapidly discover the best molecules in our new libraries

• Identify FPPs that work well in different cell types and tissues

Working with some of the best chemists in USA and Asia to use FPPs for siRNA delivery

• Select best FPPs for each cargo

• Provide the tools that will allow us to optimize our customer’s drugs

• “ Cell specific delivery of siRNA by FPPs would

• open a universe of therapeutic opportunities ”

Pharma Exec

==> picture [98 x 166] intentionally omitted <==

Collaboration with alternative scaffold company under discussion

• Small, super stable, antibody-like proteins, that bind to therapeutic targets with excellent affinity

• Easy to rapidly identify those that inactivate proteins involved in disease

==> picture [130 x 29] intentionally omitted <==

8