Transforming the treatment of Asia prevalent cancer Dr Carl Firth - - PowerPoint PPT Presentation

Transforming the treatment

• f Asia prevalent cancer

Dr Carl Firth CEO & Chairman Corporate presentation December 2017

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

• ccurrence of unanticipated events or for any other reason.

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Oncology therapeutics focused on Asia prevalent tumours

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Strategy

• 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

Pipeline

• 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 Partnering

• 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$ 60M, runway into 2019

Company overview

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Patients in US Patients in Asia 12,000 Biliary tract cancer (BTC) 220,000 26,000 Gastric cancer 1,200,000 27,000 Hepatocellular carcinoma 482,000 21,000 Esophageal cancer 340,000 47,000 Cervical cancer 807,000

Many Asia prevalent tumours are orphan in West

Focus on tumour types that are prevalent in Asia and orphan diseases in the West

• 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

Asian data can support Western approval

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Headquartered in Singapore, developing globally

• ASLAN will commercialise in US and selected Asian markets
• Will work with partners in Japan and Europe

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ASLAN offices Other countries where we operate

ASLAN Singapore ASLAN Taiwan ASLAN China

New Zealand HK South Korea Japan Philippines US Australia EU

Position Experience

Dr Carl Firth CEO

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

Head of Molecular Sciences, R&I Head of Early Asthma Portfolio

Jeff Tomlinson CBO 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

Veteran management team, blockbuster experience

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Position Experience Sir David Lane Chairman

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

Scientific advisory board, world-renowned expertise

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Our portfolio

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Development pipeline

Program Discovery Preclinical Phase 1 Phase 2 Pivotal Originator Varlitinib (ASLAN001) ASLAN003 ASLAN004 ASLAN005 Modybodies ASLAN002

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Biliary tract cancer Gastric cancer Inflammation AML Oncology Breast cancer Colorectal cancer

BMS acquired global rights in 2016

Oncology

Therapies target biomarker-defined subsets of disease

Oncology Solid tumours

Varlitinib

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Overview of Varlitinib (ASLAN001)

• 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 400 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

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B D UP

DA TE

Potential to block growth in range of tumours

• 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
• f HER receptor (HER2)
• Effective in certain patient subsets that are driven

specifically by HER2

• 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 is a pan-HER inhibitor that blocks all of these

receptors, shutting down growth in a much broader range of tumours

13 Downstream signalling leading to growth and proliferation Downstream signalling blocked. No growth / proliferation HERCEPTIN HERCEPTIN Downstream signalling blocked. No growth / proliferation VARLITINIB

HER2 HER2 HER1 HER3 HER4

• 100%
• 80%
• 60%
• 40%
• 20%

0% 20% 40% 60%

* * *

Response duration (wk) 32 13 48 36 32 63 30

Combining with GC standard of care chemo showed impressive responses in difficult to treat tumours

• All patients received 300-500mg 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

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Maximum tumour shrinkage (%)

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

* These patients did not have measurable lesions, but declared SD by investigator based on non-measurable tumour mass

Phase 1b combining varlitinib with doublet chemotherapy:

Varlitinib demonstrated greater tumour shrinkage in 2nd line HER2+ mBC compared to lapatinib

• 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

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2nd 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 0.075 ORR 60% 46% PFS / OS No difference (not powered for PFS/OS)

* Excluding patients on therapy for less than one month

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 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 Drugs in development

• FGFR2 and IDH1 inhibitors, both in phase 3, target a

10% subset of patients

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BTC patients Chemo (gem/cis) 1st line Chemo (cap)

Varlitinib target patients

2nd line PFS 8 mon PFS 3 mon

Biliary tract cancer

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Global market size US$1,400M

US

12,000 BTC patients 6,000 target Market $350M

EU5

13,000 BTC patients 7,000 target Market $220M

China

170,000 BTC patients 18,000 target Market $240M

Japan

20,000 BTC patients 10,000 target Market $270M

Target patients:

• Unresectable
• Eligible for chemotherapy
• 2nd line
• In China: can afford innovative drug

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

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2nd line BTC patients varlitinib + capecitabine capecitabine

Double-blind, randomised Placebo-controlled 120 patients Primary endpoint: ORR Secondary endpoints: PFS, OS

Gastric cancer

Classification

• 4th 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 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

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Metastatic gastric cancer patients

Doublet chemo

Varlitinib target patients

1st line Doublet chemo Herceptin + Doublet chemo

HER2-amp 10% 40% 50% HER1+/HER2+ HER1-/HER2-

Gastric cancer

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Global market size US$3,000M

US

26,000 GC patients 6,000 target Market $550M

EU5

57,000 GC patients 15,000 target Market $820M

China

730,000 GC patients 32,000 target Market $700M

Japan

117,000 GC patients 9,000 target Market $400M

Target patients:

• Stage IIB - IV
• 1st line
• HER1+/HER2+ coexpressing
• In China: can afford innovative drug

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 2018

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1st line GC patients (HER1/HER2) varlitinib + doublet chemo doublet chemo

Primary endpoint: OS Secondary endpoints: PFS, ORR

ASLAN003

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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
• f a phase 2 study in AML
• Expect first clinical data in early 2018

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Mechanism of action DHODH is an enzyme in the mitochondria responsible for pyrimidine synthesis, one

• f the building blocks of DNA

ASLAN003 ATP depletion DNA damage Pyrimidine depletion Impaired DNA damage response Increase in P53 Apoptosis (cell death)

DHODH inhibitors identified as key target in AML

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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

Expand selected cohort to 20 pts

Phase 2 in AML underway

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AML patients ineligible for standard treatment Cohort 1 – 100mg (6 pts) Cohort 2 – 200mg (6 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

Cohort 3 – 300mg (6 pts)

Development pipeline

Program Discovery Preclinical Phase 1 Phase 2 Pivotal Originator Varlitinib (ASLAN001) ASLAN003 ASLAN004 ASLAN005 Modybodies ASLAN002

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Biliary tract cancer Gastric cancer Inflammation AML Oncology Breast cancer Colorectal cancer

BMS acquired global rights in 2016

Oncology

Therapies target biomarker-defined subsets of disease

Oncology Solid tumours

Financials and summary

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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$ 60M (3Q 2017)
• Cash runway until 2H 2019

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2013-2016 financial statements have been audited by Deloitte

Pro forma (kUSD) 2014 2015 2016 1Q-3Q 2017

Revenue 11,547 Expenses (12,514) (13,280) (20,121) (24,701) Operating income (12,514) (13,280) (8,699) (24,701) Pre-tax profit (12,587) (13,572) (9,048) (25,362) Net profit (loss) (12,587) (13,572) (9,048) (25,362) Profit per share (USD) (0.24) (0.25) (0.09) (0.21)

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

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Future milestones

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2018 Varlitinib

• Readout – phase 2 in GC
• Readout – China BTC (2nd line)
• Readout – phase 2 in BTC (1st line)
• Regional partnering deal

ASLAN003

• Readout – phase 2 in AML
• Regional partnering deal

ASLAN004

• FPI – phase 1

2019 Varlitinib

• File for BTC approval in all major markets