Transforming the treatment of Asia prevalent cancer

Transcription

1 Transforming the treatment of Asia prevalent cancer Dr Carl Firth CEO & Chairman Corporate presentation October 2017

2 Disclaimer All materials and information set out herein are for reference only and whilst we make every effort to ensure accuracy and completeness, we cannot guarantee this. We make no recommendation as to the competence or suitability of persons or entities referenced herein (if any). Nothing herein constitutes an invitation or offer to invest in or deal in the securities of ASLAN. Anyone considering investment in ASLAN should refer to the information officially published the Taiwan Stock Exchange Market Observation System (MOPS). All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on such forward-looking statements, which are inherently unreliable, and you should not rely on them. Any such forward-looking statement will have been based on ASLAN s expectations, assumptions, estimates and projections about future events on the date(s) made. Actual outcomes are subject to numerous risks and uncertainties, many of which relate to factors beyond ASLAN s control, that could cause them to differ materially from those expressed in a forward-looking statement. ASLAN has no obligation to update or otherwise revise any forward-looking statements to reflect the occurrence of unanticipated events or for any other reason. 2

3 Oncology therapeutics focused on Asia prevalent tumours Strategy Pipeline Partnering Focus on Asia prevalent tumours that are orphan diseases in West Asia-based clinical development with Singapore HQ In-licensing of development compounds by veteran industry team Development pipeline of 5 drugs, IO and other targeted therapies Varlitinib in pivotal trials for biliary tract cancer and gastric cancer with interim data expected in 2018 and potential to file in 2019 ASLAN003 phase 1 completed, phase 2 in AML initiated with initial data expected in early 2018 Partnerships with world-leading pharma and biotechs including Array, BMS, CSL and Almirall Ongoing in-licensing and out-licensing discussions Financial Listed on Taipei Exchange in June 2017 US$ 130M raised since inception, US$ 33M IPO proceeds Pro forma cash balance of US$ 70M, runway into

4 Company overview 4

5 Many Asia prevalent tumours are orphan in West Focus on tumour types that are prevalent in Asia and orphan diseases in the West Asian data can support Western approval Patients in US Patients in Asia 8,000 Biliary tract cancer (BTC) 220,000 32,000 Gastric cancer 1,200,000 27,000 Hepatocellular carcinoma 482,000 21,000 Esophageal cancer 340,000 47,000 Cervical cancer 807,000 Studies run in Asia where the majority of patients live Data is leveraged for approvals in US, EU and other global markets where often these are orphan diseases Few if any approved therapies for these indications 5

6 Headquartered in Singapore, developing globally ASLAN will commercialise in US and selected Asian markets Will work with partners in Japan and Europe US EU ASLAN China ASLAN Singapore South Korea HK Japan ASLAN Taiwan Philippines Australia ASLAN offices Other countries where we operate New Zealand 6

7 Veteran management team, blockbuster experience Position Dr Carl Firth CEO Experience Head of New Portfolio (China) Head of BD (Asia) Head of Asia Healthcare Banking Dr Bertil Lindmark CMO Head of Development, R&I Head of Development, Japan Global Head of R&D CSO Dr Mark McHale COO Jeff Tomlinson CBO Head of Molecular Sciences, R&I Head of Early Asthma Portfolio Ben Goodger General Counsel Senior Partner and Head of IP Partner Kiran Asarpota VP of Finance Group Finance Director Chih-Yi Hsieh GM Taiwan, VP Medical Medical Advisor Oncologist, Taipei VGH 7

8 Scientific advisory board, world-renowned expertise Position Sir David Lane Chairman Experience Chief Scientist Head of P53 Research Institute Founder and CEO Professor Patrick Tan Professor Associate Director Dr Yong Wei Peng Senior Consultant Adjunct Senior Research Fellow Dr Matthew Ng Medical Oncologist Deputy Director 8

9 Our portfolio 9

10 Development pipeline Therapies target biomarker-defined subsets of disease Program Discovery Preclinical Phase 1 Phase 2 Pivotal Originator Biliary tract cancer Varlitinib (ASLAN001) Gastric cancer Breast cancer Colorectal cancer ASLAN003 AML ASLAN004 Inflammation Oncology ASLAN005 Oncology Modybodies ASLAN002 Oncology Solid tumours BMS acquired global rights in

11 Varlitinib 11

12 Overview of Varlitinib (ASLAN001) B D UP DA TE Small molecule based reversible pan-her inhibitor with balanced inhibition across all HER receptors Global rights (all indications) licensed from Array BioPharma Studied in over 300 patients to date, with good tolerability and demonstrated efficacy in BTC, gastric, breast, CRC Orphan status approved for CCA and GC by US FDA Strong IP protection including composition of matter in major territories 12

13 HER2 HER1 HER3 HER4 HER2 Potential to block growth in range of tumours HERCEPTIN HERCEPTIN Downstream signalling blocked. No growth / proliferation The HER family of receptors is responsible for driving growth in many tumours Many approved drugs target these receptors HER-selective drugs such as Herceptin target only one type of HER receptor (HER2) Effective in certain patient subsets that are driven specifically by HER2 Downstream signalling leading to growth and proliferation Blocking just one of these receptors is ineffective for the majority of patients Many of these are driven by combinations of HER1, HER2, HER3 and HER4 VARLITINIB Varlitinib is a pan-her inhibitor that blocks all of these receptors, shutting down growth in a much broader range of tumours Downstream signalling blocked. No growth / proliferation 13

14 Key studies in varlitinib development ONGOING STUDIES Pivotal study Biliary tract (2 nd line) Phase 1 program (Array) Phase 2A GC (3 rd line) Phase 1B Combo with doublet chemo Phase 2/3 Gastric (1 st line) Phase 2 Breast (2 nd line) Phase 2 CRC (2 nd line) Other ongoing studies not shown above: Phase 1/2 - BTC (first line) Phase 1 - Japan HCC (IIT) Neoadjuvant breast cancer (IIT) Breast cancer with brain mets (IIT) 14

15 B D UP DA TE Summary of earlier clinical studies Phase 1 studies conducted by Array showed promising signs of activity, including responses when combined with chemotherapy: Study n Countries Results Phase 1 monotherapy (alt salt form) 96 US, Canada MTD 400mg DLT fatigue (<10% G3/4) Phase 1 monotherapy 31 Canada MTD 500mg DLT fatigue (<10% G3/4) Phase 1 combo with cap 29 US, Canada MTD 400mg DLT fatigue, AST/ALT Phase 1 combo with doc 27 US MTD 500mg DLT diarrhoea, nausea (10% G3/4) Phase 1/2 combo with gem 20 US MTD 300mg DLT fatigue, thrombo, anemia Phase 2 study in 3 rd line HER1/HER2 coexpressing gastric cancer (23 patients*): Varlitinib monotherapy blocked downstream growth pathways Biomarker p-mapk 86% Ki67 (cell proliferation) 71% TUNEL (apoptosis) 60% ESMO (2014) Abstract 664P Kim, Bang et al Patients showing favourable change in biomarker * 23 patients included HER2-amplified and HER1/HER2 coexpressing cohorts 15

16 Maximum tumour shrinkage (%) Combining with GC standard of care chemo showed impressive responses in difficult to treat tumours Phase 1b combining varlitinib with doublet chemotherapy: 60% 40% 20% 0% * * * Response duration (wk) % -40% -60% -80% -100% Tumour type n Response rate Disease control Biliary tract 15 20% 87% Gastric 5 40% 100% Colorectal 11 18% 100% Breast 2 0% 100% Other 7 0% 86% Total 40 18% 93% ASCO (2017) Abstract e15671 All patients received mg varlitinib and doublet chemo for 6 cycles then monotherapy Most patients had received at least 2 prior treatments, including Herceptin, Kadcyla and chemotherapy. Some patients had as many as 13 prior treatments Not all patients have completed 4 cycles of therapy * These patients did not have measurable lesions, but declared SD by investigator based on non-measurable tumour mass 16

17 Varlitinib demonstrated greater tumour shrinkage in 2nd line HER2+ mbc compared to lapatinib 2 nd line BC patients (HER2+) varlitinib + capecitabine lapatinib + capecitabine Randomised, open label, phase 2 50 patients enrolled Primary endpoint: ORR Secondary endpoint: PFS Varlitinib Lapatinib 12-wk tumour shrinkage* 36% 18% p-value ORR 60% 46% PFS / OS No difference (not powered for PFS/OS) Safety: Diarrhoea 12% grade 3, 0% grade 4 No anti-diarrhoea prophylaxis used, all diarrhoea clinically managed Studies ongoing in neoadjuvant BC and BC with brain metastasis * Excluding patients on therapy for less than one month 17

18 Biliary tract cancer Classification BTC is a subset of liver cancer, categorised into 4 types: IHCCA, EHCCA, gall bladder, papilla vater Over 70% of BTC cancers express one or more HER family receptors 1 st line BTC patients Chemo (gem/cis) PFS 8 mon Current treatment 35% patients undergo surgical resection, however recurrence rate over 65% No therapies globally approved. Chemotherapy typically used off-label Poor prognosis with two year survival less than 10% and median overall survival 11 months 2 nd line Chemo (cap) Varlitinib target patients PFS 3 mon Drugs in development FGFR2 and IDH1 inhibitors, both in phase 3, target a 10% subset of patients 18

19 Biliary tract cancer Global market size US$1,400M US 12,000 BTC patients EU5 13,000 BTC patients China 170,000 BTC patients Japan 20,000 BTC patients 6,000 target 7,000 target 18,000 target 10,000 target Market $350M Market $220M Market $240M Market $270M Target patients: Unresectable Eligible for chemotherapy 2 nd line In China: can afford innovative drug 19

20 Biliary tract cancer the pivotal TreeTopp study Pivotal TreeTopp study initiated in April 2017 in 2nd line BTC 60 sites including US, EU, Japan, China, AsiaPac Led by Dr Milind Javle (MD Anderson) Study design agreed with US FDA Retrospective analysis of HER biomarkers Potential to file for approval in 2019 Also running: 1st line BTC study Pivotal China BTC study 2 nd line BTC patients varlitinib + capecitabine capecitabine Double-blind, randomised Placebo-controlled 120 patients Primary endpoint: ORR Secondary endpoints: PFS, OS 20

21 Gastric cancer Classification 4 th most prevalent cancer globally Highest cause of cancer mortality in Asia Adenocarcinoma represents majority of GC Classified as intestinal (common) or diffuse HER2 only biomarker used in practice Four molecular subtypes: EBV, MSI, chromosome instable, genome stable 1 st line Metastatic gastric cancer patients HER2-amp Herceptin + Doublet chemo HER1+/HER2+ Doublet chemo Varlitinib target patients HER1-/HER2-10% 40% 50% Doublet chemo Current treatment Surgical resection is used in over 50% patients however most patients will recur Poor prognosis with median overall survival of 11 months Only targeted therapy approved in first line is Herceptin, increasing survival to 17 mon 21

22 Gastric cancer Global market size US$3,000M US 26,000 GC patients EU5 57,000 GC patients China 730,000 GC patients Japan 117,000 GC patients 6,000 target 15,000 target 32,000 target 9,000 target Market $550M Market $820M Market $700M Market $400M Target patients: Stage IIB - IV 1 st line HER1+/HER2+ coexpressing In China: can afford innovative drug 22

23 Gastric cancer pivotal study underway Global phase 2/3 study underway with interim readout in 2018 Double-blind randomised placebo controlled 27 sites including China, EU and AsiaPac Phase 2 ORR readout of first 40 patients in st line GC patients (HER1/HER2) varlitinib + doublet chemo doublet chemo Primary endpoint: OS Secondary endpoints: PFS, ORR 23

24 ASLAN003 24

25 ASLAN003 is a key inhibitor of cancer metabolism ASLAN003 is a first-in-class (oncology) DHODH inhibitor ASLAN licensed global rights for ASLAN003 from Almirall Phase 1 completed Now moving into development for AML and solid tumours with the initiation of a phase 2 study in AML Expect first clinical data in early 2018 Mechanism of action DHODH is an enzyme in the mitochondria responsible for pyrimidine synthesis, one of the building blocks of DNA ASLAN003 ATP depletion Pyrimidine depletion Increase in P53 DNA damage Impaired DNA damage response Apoptosis (cell death) 25

26 DHODH inhibitors identified as key target in AML In 2016, a group at Harvard showed the critical role of DHODH inhibitors inducing differentiation of AML blast cells In 2017, ASLAN demonstrated striking results in a wide variety of AML cell lines with low concentrations of ASLAN003 THP-1 26

27 Phase 2 in AML underway AML patients ineligible for standard treatment Cohort 1 100mg (6 pts) Cohort 2 200mg (6 pts) Cohort 3 300mg (6 pts) Expand selected cohort to 20 pts Patients dosed with ASLAN003 monotherapy for 28 days or until progression Primary endpoint: CR / CRi rate AML mutation analysis and ex-vivo bone marrow differentiation will allow identification of patients that are sensitive to ASLAN003 27

28 Potential to also be used in PTEN mutated tumours PTEN is mutated or LoF in 50% of tumours 70% prostate, 60% HCC, 50% breast PTEN mutated tumours channel glutamine away from Krebs cycle and into pyrimidine (DHODH) pathway to drive proliferation PTEN mutated tumours are 4-fold more sensitive to DHODH inhibitors than tumours with wild type PTEN Testing underway in PTEN mutant tumours PTEN mutated tumours Activation of PI3K pathway Activation of DNA replication Generation of a large nucleotide pool via DHODH 28

29 Financials and summary 29

30 Financial summary Listed on Taipei Exchange on 1 June 2017, proceeds US$ 33M FY16 revenue of US$ 11.5M (licensing revenues) Cash balance of US$ 70M (2Q 2017) Cash runway until 2H 2019 Pro forma (kusd) H 2017 Revenue ,547 0 Expenses (12,514) (13,280) (20,121) (16,826) Operating income (12,514) (13,280) (8,699) (16,826) Pre-tax profit (12,587) (13,572) (9,048) (17,393) Net profit (loss) (12,587) (13,572) (9,048) (17,393) Profit per share (USD) (0.24) (0.25) (0.09) (0.15) financial statements have been audited by Deloitte 30

31 Partnering summary BMS exercised buyback option in 2016 in US$ 100M+ deal Potent, first-in-class small molecule inhibitor of cmet and RON, an immune checkpoint inhibitor licensed from BMS ASLAN successfully completed phase 1 clinical study, manufacturing campaign and several preclinical studies elucidating role of RON as a novel immune checkpoint inhibitor BMS bought the drug back in July 2016 on the following terms: Upfront US$10M Future potential milestones of over US$50M Royalties on global sales Varlitinib licensed to Hyundai in Korea 2015 Upfront and development milestones US$4.5M Royalties on sales and sales milestones 31

32 Future milestones 2017 Varlitinib ASLAN003 Regional partnering deal FPI phase 2 in AML 2018 Varlitinib ASLAN003 Readout phase 2 in GC Readout China BTC (2 nd line) Readout phase 2 in BTC (1 st line) Regional partnering deal Readout phase 2 in AML Regional partnering deal ASLAN004 FPI phase Varlitinib File for BTC approval in all major markets 32