ascend biopharmaceuticals limited · asn-002/small molecule asn-002 chemo-immuno therapy recurrent...

ASCEND BIOPHARMACEUTICALS LIMITED

Ascend Biopharmaceuticals LimitedCorporate Overview

October 2016

ASCEND BIOPHARMACEUTICALS LIMITED 2

Disclaimer

This presentation is being provided for the sole purpose of providing the recipients with background information about Ascend

Biopharmaceuticals Limited’s (“Ascend”) business. This presentation, including the information contained in this disclaimer, does not

constitute an offer, invitation or recommendation to subscribe for or purchase any security, and neither the presentation, disclaimer nor

anything contained in them forms the basis of any contract or commitment. This presentation does not purport to summarize all

information that an investor should consider when making an investment decision. Before making an investment decision you should

consider whether it is suitable for you in light of your own investment profile and objectives and financial circumstances and the merits and

risk involved.

No representation, express or implied, is made as to the fairness, accuracy, completeness or correctness of information, opinions and

conclusions contained in this presentation, including the accuracy, likelihood of achievement or reasonableness of any forecasts,

prospects, returns or statements in relation to future matters contained in the presentation (“forward-looking statements”). Such forward-

looking statements are by their nature subject to significant uncertainties and contingencies and are based on a number of estimates and

assumptions that are subject to change (and in many cases are outside the control of Ascend and its Directors) which may cause the

actual results or performance of Ascend to be materially different from any future results or performance expressed or implied by such

forward-looking statements. Forward-looking statements are provided as a general guide only and should not be relied upon as an

indication or guarantee of future performance.

To the maximum extent permitted by law, neither Ascend nor its related corporations, directors, employees or agents, nor any other

person, accepts any liability, including, without limitation, any liability arising from fault or negligence, for any loss arising from the use of

this presentation or its contents or otherwise arising in connection with it.

You represent and confirm by attending and/or retaining this presentation, that you accept the above conditions. This presentation does

not constitute an offer to sell or a solicitation of an offer to buy securities in the United States.


Ascend Company Highlights

Ascend is an immuno-oncology company targeting regulated cell death and immune pathways with:

a high value lead opportunity: lead candidate addresses a major high-value clinical need in nodular BCC patients considered to be poor candidates for surgery

a clinically de-risked lead with prospects of an expedited pivotal program: lead candidate has good safety and clinical benefit results in 3 different skin cancers

phase 2 data available shortly: current Phase 2 study in nodular BCC will have top-line interim data in November 2016 and final data in 1H, 2017

lead candidate with multiple follow-on opportunities: potential to address multiple high-value follow-on indications in recurrent ovarian cancer and recurrent cutaneous squamous cell carcinoma

*Based on regulatory precedence for Aldara in Superficial BCC patients who were not good surgery candidates


Board & Management

Dr Clement Leong, PhD,

MBA

CEO

• Over 20 years of biotech, pharma and venture capital experience in Australia and United States

• Commercial and development roles with Schering Plough, Entelos, SciVentures; lead investor on multiple

private/public biotech and med. tech transactions

• PhD from University of Western Australia; MBA from the Australian Graduate School of Management

Dr. Richard Stead, MD.

Non-executive Director

• Over 25 years directing clinical trials in Industry and licensing transactions

• Formerly Med. Director at Amgen & VP Clinical Res at Immunex; involved in approval of Epogen & Neupogen

• MD from Stanford University; Postdoc training at the Brigham and Woman’s Hospital, Harvard Medical School

Mr George Tsiamis

Non-executive Director

• Over 30 years’ experience in funds management

• Formerly Head of Operations for ANZ Asset Management, $15B in Funds under Management.

• Formerly Chief Financial Officer of the publicly listed McMillan Shakespeare Ltd (ASX: MMS).

Dr. Paul Weiden MD

Chief Medical Officer

• Over 30 years as medical oncologists and directing/assisting with clinical trials

• Formerly a member of the University of Washington, Fred Hutchinson and Virginia Mason Medical Center

• MD from Harvard Medical School.

Dr. Satish Menon, PhD

CMC Director

• Over 26-years of experience in protein based therapeutics R&D and manufacture

• Directed process and bioprocess development for Schering Plough, DNAX, Genitope and Allergan

• Ph.D. from the Indian Institute of Science, Bangalore and Postdoc at Harvard Medical School.

Dr Geoffrey Pietersz, PhD

Director of Technology

Development

• Over 30 years as an organic chemist working in cancer & infectious diseases

• Formerly a Professor at the Burnet Institute, expert in bio-conjugation of therapeutics (e.g., vaccine; antibody

drug conjugates) and inventor of the ASN-004 technology

• Ph.D. from the University of Melbourne.


Pipeline

CBCL Cutaneous B cell lymphoma; BCC Basal Cell Carcinoma; H&N SCC Head and Neck Squamous Cell

Carcinoma; RCD induction of multiple regulated cell death pathways; IT Immunotherapy; OC Ovarian Cancer;

PC Peritoneal Cancer

Product Composition Indication

ASN-002 ASN-002 Monotherapy Cutaneous BCL Completed

Bladder ASN-002 ASN-002 Monotherapy Nodular BCC H1, 2017 complete

Cutaneo ASN-002/small molecule ASN-002 Chemo-immuno therapy Head & Neck SCC H2 2017 start

ASN-002/small molecule ASN-002 Chemo-immuno therapy Recurrent OC H2, 2017/2018 start

ASN-002/small molecule PlannedASN-002 Chemo-immuno therapy Nevoid BCC H2, 2017/2018 start

ASN-006 Mannan-genetic adjuvant Peritoneal Cancer H2, 2017

Breast ASN-008 Replicon vector - RCD genes* Refractory cancers on-going

Replicon vector - Neoantigens Refractory cancers on-going

Preclinical Phase 1 Phase 2 Phase 3

Addressing high-value clinical opportunities

* Preclinical work performed in collaboration with Fox Chase Cancer Centre in Philadelphia, USA


The Opportunity: nodular Basal Cell Carcinoma

Basal cell carcinoma is the most common cancer

worldwide arising in ~3 Million patients annually (~2

million with nodular BCC and ~1 million with superficial

BCC)

Prognosis is good if excised but if untreated can cause

significant morbidity/disfigurement

Surgical excision is the main treatment option for nBCC

It is estimated that around 25-30% of nBCC patients

(over 500,000 patients annually) can be considered poor

candidates for surgery

A significant clinical and commercial opportunity in high-risk nBCC

Most nBCC lesions occur on the face, head and neck, making excision and wound closure more difficult

If untreated BCCs become locally invasive and can cause extensive disfigurement

Excision margins of 2 to 5 mm (all around the whole of the outer tumour mass) are appropriate for most BCC resections

The risk of recurrence is determined by the patients age, immune status, and the location and subtype (histology) of the tumour


Current Non-surgical Treatment Options

Existing options have major disadvantages or are clinically inadequate

Telfer NR Br J Dermatol 2008 159(1) 35-48 Guidelines for the management of basal cell carcinoma; Arch Dermatol August 2012

Small Lesion Large Lesion Comments

Photodynamic Therapy Generally a poor choice Generally a poor choice Poor efficacy for High-risk nBCC

5-FU Poor choice Poor choice Poor efficacy for High-risk nBCC

Radiotherapy Generally good clinical

clearance

Generally good clinical

clearance

Risk of radiation induced secondary

cancers

Aldara Generally a poor choice Should not be used Poor efficacy for High-risk nBCC

Cryosurgery Generally fair choice Generally a poor choice Poor efficacy for High-risk nBCC

Vismodegib/Sonidigib

(Smoothened

inhibitors)

Not recommended Recommended for Locally

advanced basal cell skin

cancer patients with residual

disease in whom surgery and

radiation are contraindicated

Major adverse effects (hair loss,

muscle cramps, taste disturbance)

Secondary resistance

High-risk nBCC


Rationale for ASN-002 in Nodular BCC

Strong Biological Rationale for the use of Interferon in BCC:

Interferons can be effective in up to 100%* of nBCC patients

o Recombinant Interferon therapy requires multiple daily injections (e.g., schedules of 9-12 administrations)

A single injection of ASN-002 can result in sustained local expression of Interferon for up to 2 weeks

Favorable pathway to registration

• Availability of nodular BCC patients in Australia and US – many productive sites available

Histological clearance an FDA approvable endpoint (prospects for shorter on study time)

No registered therapeutics approved for nodular BCC in target patient setting^

o First mover advantage in high-risk BCC indication possible

o Vehicle-controlled Phase 3 possible (lower hurdle for demonstrating clinical superiority)

*Libby Edwards et al, J Am Acad Dermatol 1990;22:496-500; Stephen B. Tucker et al, J Am Acad Dermatol 2006;54:1033-8.

^Different target patient population to Vismodegib


ASN-002: Mechanism of Action

A proven and well understood mechanism of action

ASN-002 is an adenovirus (a type of cold-virus) engineered to produce Interferon-g


Previous ASN-002 Clinical Experience

CR PR

Total

Patients

Patient

Responses

16% 25% 32 41%

53% 32% 19 84%

23% 16% 13 39%

Patients Evaluated 64

Advanced Melanoma

Cutaneous T Cell Lymphoma

Cutaneous B cell Lymphoma

Good safety and clinical outcome data in three types of skin cancers

*For the Advanced melanoma trial – ASN-002 was administered in combination with T cell therapy

*

Advanced cutaneous melanoma patient treated over 4 months


Milestone and Time-table

Treatment

Follow-up

o Cohort 1. 5x1010 virus particles per injection once a

week for three weeks – up to 6 patients

o Cohort 2 1.5x1011 virus particles per injection once

a week for three weeks – up to 6 patients

o Cohort 4* 3.0x1011 virus particles per injection

once a week for 3 weeks – up to 6 patients

o Cohort 5 2.25x1011 virus particles per injection

once a week for 3 weeks – up to 6 patients (Cohort

5 is only recruited if AEs found in Cohort 4)

17 weeks

Screening (Day -15 to -1)

Week 1 Baseline

Week 2

Week 3

Week 8

Week 4

Week 12

Week 17 (Exit visit)

Dosing: weekly injections for 3 weeks

Interim results expected in Q4, 2016 *In a protocol amendment, cohort 3 was superseded and replaced by cohort 4

Current 18 patient Phase 2 nodular BCC trial with approval for 36 patients


Registration Strategy


Next Steps and Development Time-table

Major clinical activities that are planned

- A Type B FDA meeting in 1H, 2017

- Phase 2b/3 pivotal study in BCCNS/Nevoid BCC patients (40-60 patients)

- Phase 1/2a in recurrent locally advanced head and neck cSCC (~24 patients) and chemotherapy resistant locally

advanced ovarian cancer (~24 patients)

- Phase 2b trial in nodular BCC (64 patients)

Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2

2016 2017 2018 2019 2020

Phase 1/2a nBCC

Phase 2b/3 BCCNS (~40-60 patients)

Phase 1/2a H&N cSCC (~24 patients)

Phase 1/2a Ovarian Cancer (~24 patients)

Phase 2b nBCC (~64 patients)

Phase 3 nBCC (~320-400 patients)

*Pre-IND Mtn FDA

*Open IND


Estimated Addressable Population by Geography

Significant and high value clinical opportunity

Assumes pricing of $800 and $1600 for small and large lesions in Australia/Europe/ROW and *$1800 and $3000 for the US

High Risk nBCC

'difficult surgeries' Small lesion

Large

lesion Small lesion Large lesion

Australia 70,000 59,500 10,500 $47,600,000 $16,800,000

USA* 240,000 204,000 36,000 $367,200,000 $108,000,000

EU 200,000 170,000 30,000 $136,000,000 $48,000,000

RoW 15,000 12,750 2,250 $10,200,000 $3,600,000

525,000 446,250 78,750 $561,000,000 $176,400,000

Market Size AU$


Transactions

Transactions of comparable products

Potential revenues

• nBCC opportunity could potentially generate over $7 billion in worldwide revenue from 2022 to 2031

• LA OC and LA H&N SCC could generate worldwide revenues of $7.4B and $12.7B over a similar period

*The assumptions and models used to generate these revenue figures are available upon request

Company Candidate Value Date

Completed

Stage Indications

Biovex OncoVec US 425M in cash

and US 575M in

milestones

Jan-11 Phase 3 on-

going

Metastatic

melanoma

Peplin PEP005 US 287.5M Sep-09 Phase 3 on-

going

Actinic Keratosis

Ceptaris

Therapeutics

Valchlor US 25M and US

250M on approval

Aug-12 Phase 3

completed

Cutaneous T cell

Lymphoma


Additional Slides


Pipeline inducing Multiple Cell Death Programs

Neo-antigens

Chemokine(s)recruiting cross-presenting dendritic

cells

Immunogenic cell death

DAMPS


DNA launched SRIPs (Single Round Infectious Particles)

SRIP DNA vectors can be conjugated to targeting moieties (e.g., antibody)

Transfected SRIP DNA vectors produce infectious particles that can transduce cells within the TME

SRIP RNA encode a self-amplifying replicon RNA leading to high levels of gene expression

SRIP RNA can encode immunotherapy payloads such as cytokines, chemokines, antibodies

SRIPs are viral vectors produced within the tumour microenvironment launched from a DNA plasmid

Delivery to stromal or neo-vasculature within the TME SRIPs can encode immuno-oncology genes

SRIP DNA can be conjugated to various targeting moieties

ASN-008 is being developed to induce highly immunogenic cell death


Ascend Biopharmaceuticals Ltd

Level 1, 159 Dorcas St, South Melbourne VIC 3205, Australia

ACN 106 265 098

Ph: +61 3 8606 3488

Fax: +61 3 9686 9866

Email: [email protected]

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