Slide 1: Phylogica: Pivot to Platform
For personal use only Phylogica: Pivot to Platform § BioShowcase Presentation § By CSO Dr Robert Hayes § January 2018
Slide 2: Disclaimer
Disclaimer For personal use only 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. Acc
Slide 3: Pivot from developing drugs to commercialising the platform
Pivot from developing drugs to commercialising the platform For personal use only Value proposition: Enhance existing drugs to address a massive 250B USD (CAGR 10.6%) market 1 2 3 Bring drugs to Enhance Reduce the right place properties of discovery cycle (i.e. to drugs (i.e. time (by intracellular
Slide 4: Our advantage is in using our assets as a platform to solve pharma problems
Our advantage is in using our assets as a platform to solve pharma problems For personal use only Phylogica has a unique selection of valuable … huge potential market assets … • Unmet need – undruggable $250Bn • Complex, rich Phylomer library – provides growth market, intracellular hurdles tremendou
Slide 5: Significant constraints in existing drug discovery approaches
Significant constraints in existing drug discovery approaches For personal use only The Our problem? solution? Phylomer FPP Biologics - Antibodies - Scaffolds - Proteins Drug discovery growth We can bring stagnating as biologics biologics into the currently limited to cell, unlocking the extracellul
Slide 6: The Problem: drug cargoes are trapped in the endosomes
The Problem: drug cargoes are trapped in the endosomes For personal use only Conventional CPPs are often only active at concentrations of > 10 µM limiting feasible clinical applications (toxicity and high costs) 5
Slide 7: Harnessing the Microbiome for new Phylomer libraries
Harnessing the Microbiome for new Phylomer libraries For personal use only Current Phylomer libraries (size indicates number of genomes) Future Phylomer libraries Hug, Laura A et al. 2016. “A New View of the Tree of Life.” Nature Microbiology 1(5): 1-6 6
Slide 8: Our Solution: Phylogica's endosomal escape screen
Our Solution: Phylogica’s endosomal escape screen For personal use only Avitag Phylomer -Repeat 4. SA V biopanning (x2) - Sequencing 1. T7 Phage Library 3. 1. Phage is taken up by 2. endosomes 2. FPP mediates phage release BirA 3. Biotinylation of Avitag 4. Capture of biotinylated phage on Streptavi
Slide 9: Phylogica's FPPs allow functional delivery of therapeutic cargoes into the cytoplasm
Phylogica’s FPPs allow functional delivery of therapeutic cargoes into the cytoplasm For personal use only FPP Cargoes Cell Type Cargo Peptides/proteins Cancer cell lines Drug target (Blood, breast, bone) Enzymes Oligonucleotides Immunotoxins Dendritic cells FPP-cargo Bispecifics Liver and kidney 60
Slide 10: PYC has shown conclusively that FPPs work in animal models
PYC has shown conclusively that FPPs work in animal models For personal use only Inhibition of tumor growth in mouse cancer model Restoring dystrophin levels by FPP mediated delivery of DMD PMO Treated mice DMD oligo 1746c27-DMD oligo Leg PBS Omomyc Diaphragm Intratumoral 1746 injections 1746-Omomyc
Slide 11: Efficient cytosolic delivery of proteins using a split b-lactamase complementation assay
Efficient cytosolic delivery of proteins using a split b-lactamase complementation assay For personal use only Stably'transfected mammalian' cell Only endosomal NBLA escape leads to CBLA NBLA CBLA b-lactamase complementation and signal development 30 min 60 min 120 min CHO-CBLA cells incubated with
Slide 12: 1746c27 has been significantly improved upon, and new variants are being validated in vitro
1746c27 has been significantly improved upon, and new variants are being validated in vitro For personal use only 100 4uM Beta-lactamase Positive (%) 80 2uM 1uM 60 0.5uM Flow cytometry 40 CHO-K1 cells N=2 N=2 20 (1 h treatment) 0 FPPFPP varients variants FP l 1 2 o P P tr FP on C e iv at eg N Negati
Slide 13: Into 2018, PYC is validating a comprehensive matrix of FPPs
Into 2018, PYC is validating a comprehensive matrix of FPPs - delivery of cargoes into different cell types For personal use only Cre Hasegawa et al, 2013, Exp. Anim.62(4), 295-304 12
Slide 14: Phylogica's collaboration with Cancer Immunology at the Telethon Kids Institute
Phylogica’s collaboration with Cancer Immunology at the Telethon Kids Institute For personal use only • Phylogica co-located with the Telethon Kids Institute in Perth • In 2015, Phylogica started collaborating with Jason Waithman, the head of TKI’s Cancer Immunology group, to investigate melanoma •
Slide 15: FPP efficiently targets cross presenting dendritic cells for an effective peptide vaccine
FPP efficiently targets cross presenting dendritic cells (DCs) for an effective peptide vaccine For personal use only 1746-Ag 1746-Ag 2. Internalisation, XCL1 XCL1 endosomal escape and MHC loading 1. Targeting 3. T cell expansion Only FPPs escaping into the cytosol will result in CD8+ T cell 4. CD8+
Slide 16: In progress validation - FPP peptide vaccine retards tumor growth
In progress validation - FPP peptide vaccine retards tumor growth For personal use only Our FPP peptide vaccine approach: • Subcutaneous B16 melanoma model engineered to • Primes tumor express specific CD8+ T- glycoprotein B (gB) 100 FPP-gB (n=5) cells from Herpes Simplex 80 gB (n=5) • FPP containin
Slide 17: Partnering strategy: Genentech work continues to be successful
Partnering strategy: Genentech work continues to be successful For personal use only • Isolating Phylomers that can help kill gram-negative bacteria (multi-drug resistant “super bugs”) • Evaluation period end of CY 2019 gram-positive gram-negative Antibiotic ✔ ✗ Phylomer ✗ ✗ Phylomer-Antibiotic ✔ ✔
Slide 18: Building on the success of the past, turning towards the future of FPPs
Building on the success of the past, turning towards the future of FPPs For personal use only Building Therapeutics Logically New Technologies ü Identify FPPs that work well in HTP automation to rapidly discover the best different cell types and tissues molecules in our new libraries Working with so
Slide 19: Phylogica shortens Pharma discovery phase
Phylogica shortens Pharma discovery phase For personal use only 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 Drug safety Drug safety & Regulatory Determination of & efficacy in ef
Slide 20: To achieve PYC – the Platform: we need to be laser focused on 3 goals
To achieve PYC – the Platform: we need to be laser focused on 3 goals For personal use only Proving the • Deliver in vivo functional validation value proposition of 1 • Demonstrate the improvement potential of existing FPPs Outcome: our platform • Enrich and validate our library A validated, sought
Slide 21: Thank you
For personal use only Thank you For more information contact Dr Robert Hayes at roberth@phylogica.com 20