Syncona Ltd GBP · LSE:SYNC
Syncona Ltd GBP — Anaveon — Investor Presentation (July 2020)
26 slides from Syncona Ltd GBP's investor presentation, July 2020
Slide 1: Antibody directed IL-2 for tumor immunotherapy
Antibody directed IL-2 for tumor immunotherapy Non-Confidential Introduction July 2020 1
Slide 2: Important notice
Important notice In this statement, "presentation" means this document together with any oral presentation, any question or answer session and any written or oral material discussed or distributed during any meeting at which this document is made available. This presentation speaks as of its date an
Slide 3: Vision: Use our expertise in cutting-edge immunology
Basel Vision: Use our expertise in cutting-edge Anaveon is a spin-out of University immunology to design and of Zurich and Novartis, founded in Switzerland in 2017 by leading develop patient treatments experts in the field of that benefit society immunotherapy For Business Use Only 3
Slide 4: Company highlights
Company highlights Lead program is ANV419, a Anaveon is well Well funded and backed highly potent fusion protein of positioned to be best in by a world-class team an IL-2 and an anti-IL2 class in the field of antibody that is redirected engineered IL-2 and toward the β/γ receptor therapeutic cytokin
Slide 5: Who we are
Who we are Management Board Martin Murphy, PhD Allison Jeynes, MD Dominic Schmidt, PhD Chairman Independent Director Partner, Syncona Investment CEO, Syncona CEO, Avillion LLP Management Ltd Investment Management Ltd Andreas Katopodis, PhD Christoph Huber, PhD Christoph Bucher, MD Chief Executive Of
Slide 6: IL-2 is a key regulator of anti-tumor biology
IL-2 is a key regulator of anti-tumor biology IL-2 is a key component of immune response to tumors ▪ IL-2 acts on immune cells (including effector and regulatory T cells, NK cells) ▪ Tumor immunotherapy success correlates with restoration of CD8+ T cell function T cell trafficking T cell priming and
Slide 7: The first wave of IL-2 immunotherapy treatment and Proleukin
The first wave of IL-2 immunotherapy treatment and PROLEUKIN® Proleukin® (recombinant IL-2) is approved for metastatic melanoma and RCC 100 % survival 90 Proleukin® 80 70 Natural course 60 Survival over time of patients 50 with metastatic melanoma 40 30 20 10 0 0 1 2 3 4 5 6 7 8 9 10 Years after dia
Slide 8: From Proleukin to ANV419
From PROLEUKIN® to ANV419 Lack of selectivity Excellent selectivity for effector cells Dose-limiting toxicity Good therapeutic window Short in vivo half-life Extended half-life For Business Use Only 8
Slide 9: ANV419 is a leading next-generation IL-2
ANV419 is a leading next-generation IL-2 ANV419 is a fusion protein of IL-2 and an anti-IL-2 antibody which specifically blocks IL-2Ra binding This strategy allows redirection of IL-2 to the dimeric receptor without the mutations and inherent unknows of IL-2 “muteins” ANV419 properties support a bes
Slide 10: ANV419 is selective by design
1 ANV419 is selective by design ANV419 was designed to selectively redirect IL-2 in three steps: ▪ Generation of anti-IL-2 antibodies – Highly specific antibodies were selected to permit binding to IL-2Rb/g and block binding to IL-2Ra ▪ Selection of the lead antibody – Optimal pharmacodynamic and ph
Slide 11: ANV419 selectively allows binding to IL-2Rb/g by interfering with IL-2Ra
1 ANV419 selectively allows binding to IL-2Rb/g by interfering with IL-2Ra Crystal structure of the IL-2/IL-2R Crystal structure of ANV419 tertiary complex (including IL-2 component) IL-2 IL-2Rg IL-2Rb IL-2 ANV419(VH) ANV419(VL) IL-2Ra ANV419 maintains the same key intramolecular contacts with IL-2
Slide 12: ANV419 demonstrates selectivity for human CD8 T cells vs. Treg
2 ANV419 demonstrates selectivity for human CD8 T cells vs. Treg In vitro triggering of IL-2 receptor signalling on human Tregs and CD8 T cells by ANV419 as measured by pSTAT5 analysis Tregs CD8 T cells Proleukin ® ANV419 100,0 100,0 % pSTAT5+ % pSTAT5+ 80,0 80,0 60,0 60,0 40,0 40,0 20,0 20,0 0,0 0,
Slide 13: ANV419 selectively promotes CD8 T and NK cells vs. Treg cells
2 ANV419 selectively promotes CD8 T and NK cells vs. Treg cells, in mice and non-human primates CD8 T cells NK cells In Mice In NHP Treg cells 100,0 100,0 % Ki-67+ cells % Ki-67+ cells 80,0 80,0 60,0 60,0 40,0 40,0 20,0 20,0 0,0 0,0 1 5 7 9 11 15 1 4 8 12 15 Day Day In vivo selective induction of pr
Slide 14: ANV419 inhibits tumor growth in mouse models
2 ANV419 inhibits tumor growth in mouse models ANV419 Vehicle H22 B16F10 Renca Liver cancer model Melanoma model Renal cell carcinoma model 2500 Tumor Volume mm3 2500 3000 Tumor Volume mm3 Tumor Volume mm3 2000 2500 2000 1500 2000 1500 1500 1000 1000 1000 500 500 500 0 1 3 5 8 10 12 15 17 19 22 0 0
Slide 15: ANV419 is long acting and has a favorable safety profile in NHPs
3 ANV419 is long acting and has a favorable safety profile in NHPs ANV419 has a very good safety profile at multiples of the expected maximal human dose in NHPs ▪ Maximal dose tested was 6x expected effective dose in human ▪ Dose-dependent exaggerated pharmacology typical for IL-2 was observed in th
Slide 16: High level comparison of novel IL-2 modalities
High level comparison of novel IL-2 modalities Selectivity in vivo Low risk for Stage Partnered Long half-life Safety Selectivity to (for CD8, NK cells) immunogenicity effector cells NKTR-214 vs. Tregs (Nektar) Phase 3 BMS THOR707 (Synthorx/Sanofi) Phase 1/2 Sanofi * KY1043 bispecific (Kymab) Precli
Slide 17: ANV419 is selective for IL-2Rb
ANV419 is selective for IL-2Rb Affinity of ANV419 to IL-2R a and b was determined by Biacore KD IL-2Ra (CD25) KD IL-2Rb (CD122) ANV419 No binding 377 nM IL-2 (published) 10 nM ~500 nM NKTR-214 (1-PEG)1 190 nM 1770 nM THOR-7072 No binding >IL-2 Neo-2/153 No binding 11 nM MDNA194 No binding 2 nM → ANV
Slide 18: Example of Anaveon's best-in-class selectivity in non-human primates
Example of Anaveon’s best-in-class selectivity in non-human primates Comparison of proliferation in peripheral blood, %Ki-67 in CD8 T cells and Tregs at peak day CD8 T cells Synthorx (THOR-707)* Anaveon (ANV419)# Regulatory T cells 100 100 % Ki-67+ cells % Ki-67+ cells 80 80 60 60 40 40 20 20 0 0 30
Slide 19: Example of Anaveon's best-in-class selectivity in non-human primates
Example of Anaveon’s best-in-class selectivity in non-human primates Comparison of CD8 T cell proliferation in peripheral blood Nektar (NKTR-214)* Anaveon (ANV419)# 50 50 % Ki-67+ in CD8 T cells % Ki-67+ in CD8 T cells % Ki-67+ in CD8 T cells 40 40 30 30 20 20 10 10 0 0 1 8 1 8 Cycle 1 Cycle 2 Day D
Slide 20: Example of Anaveon's best-in-class selectivity in non-human primates
Example of Anaveon’s best-in-class selectivity in non-human primates Comparison of Treg expansion in peripheral blood Nektar (NKTR-214)* Anaveon (ANV419)# 30 30 % Tregs in CD4+ T cells % Tregs in CD4+ T cells 20 20 10 10 0 0 1 8 1 8 Cycle 1 Cycle 2 Day Day ANV419 does not expand Tregs in peripheral
Slide 21: Anaveon's route to the clinic
Anaveon’s route to the clinic Lead candidate ANV419 selected | ANV419 proof of concept in NHPs | CMC feasibility completed 2020 2021 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Preclinical Clinical GLP Toxicity studies TODAY Manufacturing/release of clinical supply First clinical data on safety, PK and PD Regulatory submi
Slide 22: Manufacturing/CMC and Clinical Supply
Manufacturing/CMC and Clinical Supply Excellent yields and purity at cell culture level ▪ Upstream culture conditions have been optimized and locked Downstream purification yields high drug 2020 substance (DS) recovery GLP toxicity supply ▪ Purification process fully optimized and locked Today DP en
Slide 23: ANV-419 Clinical Development Plan
ANV-419 Clinical Development Plan Leveraging available data on target, pathway and PK/PD Single agent Optimize time and patient number towards recommended phase 2 dose Part B: ▪ ANV419 NHP and in vitro data will be combined with Part A: Dose escalation Part C: Expansion Dose confirmation within-clas
Slide 24: Exploration of Combination Options for ANV419
Exploration of Combination Options for ANV419 ANV419 has the potential to be combined with multiple anti-cancer modalities Combination agents Potential applications Multiple licensing and Checkpoint inhibitors Melanoma, renal cell cancer, bladder partnership opportunities cancer Innate immunity agon
Slide 25: Why Anaveon
Why Anaveon Next-generation biased IL-2 agonist Excellent cell line productivity and with best-in-class potential protein stability, straight-forward and fast pre-clinical development program ANV419 A A D D Sterically blocks IL-2Ra engagement Systemic therapy with potential to be a safe B B C C whil
Slide 26: Thank you
Thank you For Business Use Only 27