Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019

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Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
Amplia Therapeutics Limited
ASX:ATX

          Amplifying Immunology
Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
Notice
The information contained in the presentation is not intended to be an offer for subscription, invitation or recommendation with respect to shares of
Amplia Therapeutics Limited (“Amplia”) in any jurisdiction. No representation or warranty, express or implied, is made in relation to the accuracy or
completeness of the information contained in this document or opinions expressed in the course of this presentation. The information contained in
this presentation is subject to change without notification.

This presentation contains forward-looking statements which can be identified by the use of words such as “may”, “should”, “will”, “expect”,
“anticipate”, “believe”, “estimate”, “intend”, “scheduled” or “continue” or similar expressions. Any forward-looking statements contained in this
presentation are subject to significant risks, uncertainties, assumptions, contingencies and other factors (many of which are outside the control of,
and unknown to Amplia, and its officers, employees, agents or associates), which may cause the actual results or performance to be materially
different from any future result so performed, expressed or implied by such forward-looking statements.

There can be no assurance or guarantee that actual outcomes will not differ materially from these statements. The data and results pertaining to
clinical subjects used in this presentation are illustrative of medical conditions and outcomes associated with potential applications of Amplia’s
acquired product pipeline. Actual results from clinical trials may vary from those shown.

July 2019

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Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
Corporate Snapshot (ASX:ATX)

 Key Statistics as at 24 June 2019                                                Significant Holders
                                                                                  Citicorp Nominees Pty Ltd                14.3%
 Share price                                       A$0.11 (12 mths 9.4c to 41c)
                                                                                  CTxT Pty Ltd (Cancer CRC)                10.1%
 Shares on issue                                                    44,623,303
                                                                                  Elk River Holdings (Chris Behrenbruch)    5.6%
 Market Cap                                                       ~A$5 million    34th Avenue Pty Ltd (Mark Devlin)         5.0%
 Options                                          5,070,000 (A$0.15 to A$4.00)    Christopher Burns                         5.0%

 Cash                                     A$1.2 million (Appendix 4C 31/03/19)    Warwick Tong and Mark Sullivan (each)     3.7%
                                                                                  Cancer Research UK                        3.0%

 Register

 Top 20                                                                   64%

 Total shareholders                                                      2,885

 Voluntary Restricted Shares (May 2020)                             18,460,308

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Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
Amplia Therapeutics

   • A pharmaceutical company advancing a pipeline of Focal Adhesion Kinase (FAK) inhibitors for
     cancer and fibrosis
   • Experienced team with a strong track record
   • Assets and intellectual property exclusively licensed worldwide to Amplia
   • FAK inhibitors offer therapeutic potential in cancer and fibrosis
        o   Current focus is on oncology indications

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Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
Experienced Management

     Warwick Tong                    John Lambert                        Robert Peach                          Christian Behrenbruch
     MB ChB MPP GAICD                       PhD                                 PhD                                D.Phil (Oxon) MBA JD
                                   Chief Executive Officer                                                                 Director
         Chairman                                                        Independent Director
                                 18+ years experience in drug     25+ yrs experience including senior         Seasoned biotech entrepreneur.
    Ex-GSK, experienced drug     discovery and development        executive and scientific positions at    CEO of Telix Pharmaceuticals (ASX : TLX)
   developer. Former CEO and
                                                                 Apoptos, Biogen Idec, IDEC and Bristol-
      Director, Cancer CRC.    Ex-Biota, Medicines Development
                                                                             Myers Squibb.
                                       for Global Health
                                                                 Co-founder and CSO of Receptos (2009)
                                                                   which was acquired by Celegen for
                                                                           US$7.8B in 2015.

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Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
Experienced Advisors

           Chris Burns                              Mark Devlin                           Mark Sullivan                         Damian Slizys
      PhD, FRSC FRACI Director                 PhD, Chief Scientific Advisor           Regulatory Affairs Adviser      BSc(Hons), LLB(Hons), PhD Intellectual
                                                                                                                                 Property Adviser
  Over 20yrs experience in Pharma,                   Experienced drug                Experienced drug development
       biotech and academia.                        discovery biologist.              professional (ex GSK, Gilead).       Principal Falkenheim Advisory.
   Discovered clinically trialed drugs        COO for Cancer Research CRC.           Founder and Managing Director,       Previously FPA Patent Attorneys.
    momelotinib and lexibulin. 50+                                                  Medicines Development for Global
                                            Previously Director of Translational
  scientific publications, 30+ patents.                                                         Health.
                                          Cancer Biology for the CTx where he has
                                           worked extensively on FAK inhibitors.

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Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
A Key ‘Asset’ – Our Scientific Advisors

  Prof. Margaret                     Prof. Neil                          Alan Serrels                         Prof. Phil Hansbro                       Assoc Prof. Lara Lipton
                                                                                 PhD                                         PhD                                 MBBS, PhD, FRACP
      Frame                          Carragher
         OBE, PhD                          PhD                     Research Fellow, MRC Centre for           Director, Centenary UTS Centre for            Medical oncologist and clinical
                                                                       Inflammation Research.                     Inflammation at Sydney.              researcher with extensive experience in
Science Director and Chair of   Professor of Drug Discovery                                                                                                      pancreatic cancer.
Cancer Biology, University of    and Director of Edinburgh    Identifying FAK’s role in suppressing anti-         Internationally recognized
         Edinburgh.               Cancer Discovery Unit.          tumour responses and strategies for       researcher in the role fibrosis plays in
                                                                  combination treatment strategies to        diseases such as COPD, asthma and
Global thought leader in FAK.   Experienced FAK researcher.
                                                               overcome this cancer defense mechanism.          idiopathic pulmonary fibrosis.

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Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
Immuno Oncology Primer

• Many cancers evade detection by the immune
  system by supressing the anti-tumour immune
  response
• One such immunosuppressive action is
  achieved by upregulation of checkpoint
  proteins such as PD-L1
• Interaction of PD-L1 with PD-1 blunts the
  ability to cytotoxic lymphocytes to kill cancer
  cells
     o   PD-L1 and PD-1 are then referred to as
         ‘checkpoint proteins’
• Checkpoint inhibitors block the PD-L1/PD-1
  interaction and restore the anti-tumour
  immune response

                                                    Reproduced from National Cancer Institute   8
Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
Immuno Oncology Primer

• Most current cancer immunotherapies are monoclonal
  antibodies which block checkpoint proteins PD-1, PD-L1 or                                                                                                              2018
                                                                                     Name                      Sponsor             Target          Approved
  CTLA-4                                                                                                                                                                 Sales
                                                                           Yervoy (ipilimumab)             Bristol-Myers           CTLA-4             2011
• Several new immunotherapies have been approved in recent                                                 Squibb
                                                                                                                                                                     $8.1B#
                                                                           Opdivo (nivolumab)                                       PD-1              2014
  years benefiting many patients whose cancers were
                                                                           Keytruda
  previously difficult to treat                                            (pembrolizumab)
                                                                                                           Merck                    PD-1              2014           $7.2B^

• Sales of these products are expected to grow steadily over               Tecentriq (atezolizumab)        Genentech                PD-L1             2016
  the next decade
                                                                                                           EMD Serono
                                                                           Bavencio (avelumab)                                      PD-L1             2017
• Indications approved so-far include:                                                                     / Pfizer                                                      $2B
     o   Melanoma; small cell lung cancer; cervical cancer; primary        Imfinzi (durvalumab)            Astra-Zeneca             PD-L1             2017
         mediastinal large B-cell lymphoma; gastric cancer; MSI-H                                          Regeneron
                                                                           Libtayo (cemiplimab)                                     PD-1              2018
         cancers, noncolorectal and colorectal cancers; hepatocellular                                     / Sanofi
         carcinoma; Merkel cell carcinoma; Hodgkin lymphoma;               # Bristol-Myers Squibb Reports Fourth Quarter and Full Year Financial Results, January 2019
         urothelial carcinoma; renal cell carcinoma; non–small cell lung   ^ Merck Announces Fourth-Quarter and Full-Year 2018 Financial Results, February 2019
         cancer

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The Need

                                                             • Although immunotherapeutic drugs have revolutionised
                                                               cancer treatment, response rates to these agents are still
                                                               low
                                                             • Only 44% of all cancer patients are eligible to receive IO
                                                               drugs and, of these, only 13% respond to therapy
                                                             • New therapies are required to address the current unmet
                                                               needs of the ~87% of eligible patients who do not yet
                                                               respond
                                                             • Big pharma is assessing numerous combination therapies
                                                               and is searching for new agents with novel mechanisms of
                                                               action to combine with their immunotherapeutic agents
                        Adapted from
Haslam A, Prasad, V., JAMA Network Open. 2019;2(5):e192535

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Focal Adhesion Kinase

• FAK is upregulated in many cancers
• FAK plays multiple roles
     • Involved in cellular adhesion and migration
     • Promotes cancer cell survival by preventing cancer cell death
     • Regulates cancer cell proliferation
     • Contributes to the establishment of an immunosuppressive tumour microenvironment
          o   Regulation of immunosuppressive chemokines and cytokines
          o   Suppression of the antitumour CD8+ T-cell response

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Why Inhibit FAK?

• Current scientific theory is that certain tumour types become ‘FAK dependent’ to survive
     o   FAK ‘buffers’ tumour cells from stress caused by immune system attack or chemotherapy
     o   FAK activates chemokine pathways that alter the tumour microenvironment
           − FAK blunts a robust immune response to the tumour
     o   FAK promotes fibrosis which alters the tumour’s physical environment
• Preclinical studies show that blocking FAK amplifies the efficacy of a wide range of cancer therapeutics,
  particularly immuno-oncology drugs

                                                  Amplia’s premise
           FAK inhibitors will improve the efficacy of front-line cancer immunotherapies by suppressing the
                                          tumour-protective properties of FAK

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Ablation of FAK Causes Tumour Regression

•   Inhibiting FAK decreases immunosuppressive cell
    populations in tumours
•   When transplanted into immune-competent mice,
    malignant squamous cell carcinoma (SCC) cells with
    ablated FAK (FAK-/-) undergo regression, unlike SCC cells
    with wild type FAK (FAK-wt)

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Pancreatic Cancer is Responsive to FAK Inhibition

High FAK activity and related
poor CD8+ cytotoxic T cell
infiltration, is associated with
poor overall survival in patients
with pancreatic ductal
adenocarcinoma (PDAC)                        •   In transgenic mice, FAK inhibition rendered PDAC tumours responsive
                                                 to both gemcitabine chemotherapy and checkpoint immunotherapy
                                             •   3-way combination treatment conferred 100% survival

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AMP886 & AMP945 Sensitize Human Pancreatic
Cancer to Gemcitabine in Preclinical Model

                          Tumour growth AUC analysis for
                          human Panc-1 study of
                          gemcitabine (GEM50/40) in
                          combination with FAK inhibitors
                          AMP945 and AMP886.

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AMP886 Sensitizes Human Pancreatic
Cancer Model to Irinotecan

                                AMP886 combined with irinotecan,
                                has a significant impact on tumour
                                growth and survival in mouse
                                models of pancreatic cancer (human
                                Panc-1)

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Amplia’s Therapeutic Focus

• Current cancer targets
    o   Fibrotic cancers including pancreatic and ovarian cancer
          − Pancreatic cancer has the worst survival outcome of the 21 most common cancers
          − Ovarian cancer ranks fifth in cancer deaths among women
• FAK also plays a significant role in a number of chronic diseases, such as idiopathic pulmonary
  fibrosis (IPF)
    o   Upside potential for the Amplia pipeline

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The Amplia FAK Assets

• Amplia’s complementary assets offer broad clinical utility
     • AMP945 is a highly selective FAK inhibitor with superior specificity
     • AMP886 is a multi-action molecule that hits two other important cancer pathways – VEGFR3
       and FLT3
• Excellent potency, selectivity and pharmacokinetics
     • Scale-up (kg scale) chemistry already developed
     • GMP production of clinical trial material completed
• Pre-clinical toxicology initiated and on-track
• Strong intellectual property position
     • Issued patents in all commercially important jurisdictions (exp. 2033/34)
     • Optimised formulation application filed March 2019

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Amplia’s Early Clinical Development Strategy

• Perform first-in-human studies in healthy volunteers to establish a safety baseline
• Use established safety profile as a foundation for multiple combination opportunities
• Advantages:
     • ‘Clean’ safety data without confounding effects of disease symptoms;
     • Safety data will be a key differentiator in post-Phase 1 partnering discussions with Pharma;
     • Phase 1 data can be used to support Phase 2 programs in multiple indications and not just cancer;
     • Shorter, more predictable timelines as healthy volunteers are more readily recruited than patients;
     • Costs reduced and allows earlier arrival at significant value inflexion points
     • Consistent with recommendations of SITC Combination Therapies Taskforce.

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High-level Development Plan (18 months)

                         In progress                                  Phase 1 early 2020        IND / Phase 2 Ready end 2020

                                                                                                        Cancer Indication
              Further Disease                   Phase 1                                               I-O Combo Trial (IND)
 AMP945           Models
                (I-O Focus)
                                              Enabling GLP
                                                  Tox
                                                                           Healthy Volunteer
                                                                           Phase 1 (~50 pts)
                                                                                                        Fibrosis Indication

 AMP886                                Disease Model validations of
                                        chemo combos & cancers
                                                                                                     Phase 1 Enabling
                                                                                                         GLP Tox

                AMP945
               Production
                                                                                Phase 1 single ascending dose and multiple
   CMC        Scale-Up and
                                         GMP
                                         CTM
                                                          Complete              ascending dose healthy volunteer study designed
                GMP tox                                                         to also confirm target (FAK) engagement.
                material
                                                                                Data will support Phase 2 trials in multiple
                                                                                combinations/therapeutic areas.

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Value Proposition

• Amplia’s strategy is to position its assets to maximize opportunities for combination efficacy studies in
  cancer
     • Fibrosis indications further underpin value
• Amplia’s experienced drug development team is ideally suited to
  optimise asset value
• Multiple near- and mid-term value inflection points
     • Phase 1 trial in healthy volunteers in 2020
     • IND opening Q3 2020
     • Phase 2 ready late 2020
     • Ongoing partner engagement and opportunities to
       combine with approved products

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The Commercial Opportunity – Recent Benchmarks

• Merck to Acquire Tilos Therapeutics (June 2019)
     • Pipeline of anti-latency-associated peptide antibodies
          o   Mediators of the immune microenvironment and the fibrotic processes associated with cancer
     • Total potential consideration of up to $773 million, including an upfront payment as well as contingent
       milestone payments
• Gilead and Carna Biosciences Collaboration to Develop Novel Immuno-Oncology Therapies (June 2019)
     • R&D collaboration on small molecule compounds in immuno-oncology
     • Upfront payment of $20 million and an additional $450 million in potential milestone payments
     • Royalties on net sales

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Competitive Landscape

Agent                   Company                       Status                        Notes

VS-4718 (PND-1186)      Verastem                      PI (various studies)          First generation candidate
                                                      PI (NCT01335269) &
BI-853520               Boehringer-Ingelheim                                        Two trials completed (Aug 14 & Dec 15)
                                                          (NCT01905111)
                                                                                    Unknown status. Last update Mar 17. Single site China. Questions
CT-707                  Centaurus Pharma              PI (NCT02695550)
                                                                                    about selectivity
                                                                                    Combo with chemo (Trametinib) in pancreatic cancer (n=16). Target
GSK-2256098             GSK                           PII (NCT02428270)
                                                                                    completion Dec 19
                                                                                    1 terminated, 1 completed Apr 17 (?) not reported, 1 recruiting
VS-6063 (PF-04554878)   Verastem                      3 x PII (monotherapy)
                                                                                    target completion Sep 19
                                                                                    Combo with Pembrolizumab in several cancers
VS-6063                 Verastem                      PI/II (NCT02758587)
                                                                                    (Target n=59). Target completion Dec 21
                                                                                    Combo with SOC chemo in ovarian cancer
VS-6063                 Verastem                      PI/II (NCT03287271)
                                                                                    (Target n=90). Target completion Oct 24
                                                                                    Combo with Pembrolizumab in pancreatic cancer (Target n=36).
VS-6063                 Verastem                      PII (NCT03727880)
                                                                                    Target completion Feb 23

                              • Established target but little commercial congestion due to lack of highly selective FAK inhibitors
                              • Clinical development now focused on combo therapy in oncology setting
                              • Verastem (NASDAQ: VSTM, Market Cap USD $140m) nearest comparator however our
                                molecules are highly differentiated, both in their selectivity and multi-action effect
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Financing

Amplia is raising up to A$2,760,000 to position lead drug candidate AMP945 ready for a Phase 1 in 2020 and provide further
working capital. The financing comprises:
     1. An Initial Placement of 3,600,000 ordinary shares @ $0.10 per share to raise $360,000 was completed on Friday 14
        June 2019.
     2. A Directors and Management Placement of 1,700,000 ordinary shares @ $0.10 per share
        to raise $170,000, subject to shareholder AGM approval on 30 August 2019.
     3. A one for two (1:2) non-renounceable Rights Issue of shares @ A$0.10 (or NZ$0.11)
        per share to raise up to $2.2 million:
          • Personalised Entitlement and Acceptance Forms will be dispatched on Monday 8 July
          • The Rights Issue Short Prospectus is available at www.ampliatx.com
          • The Rights Issue will close at 5pm (AEST) on Friday 26 July
     4. All three raises include one free attaching option for each two new shares. The options will have an exercise price
        of A$0.15 and an expiry date of 30 June 2022

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Core IP Granted or ‘National Phase’

               Patent / Application number                                     Filing Date                                    Status
Selective FAK Inhibitors     FAK Inhibitors
[AMP945]                     [AMP886]            Territory   AMP945                 AMP886             AMP945                     AMP886
US 61/443,773               US 61/443,773        USA         17th Feb, 2011         17th Feb, 2011    Priority Filing            Priority Filing
US 61/523,489               US 61/523,503        USA         15th Aug, 2011         15th Aug, 2011    Supplemental               Supplemental
US 61/579,729               US 61/579,719        USA         23rd Dec, 2011         23rd Dec, 2011    Supplemental               Supplemental
PCT/GB2012/000176           PCT/GB2012/000175    UK          17th Feb, 2012         17th Feb, 2012    PCT filing                 PCT filing
US 9120761                  US 9012461           USA         6th July, 2012         6th July, 2012    Granted                    Granted
EP 2675794                  EP 2675793           Europe      Sept, 2013             Sept, 2013        Granted                    Granted
US 9174946                  US 9421205           USA         15th Aug, 2013         11th Feb, 2015    Granted                    Granted
AU 2012216894               AU 2012216893        Australia   12th Aug, 2013         13th Aug, 2013    Granted                    Granted
CA 2827172                  CA2827171            Canada      12th Aug, 2013         12th Aug, 2013    National phase filing      Granted
[JP] 5937112                [JP] 5937111         Japan       19th Aug, 2013         Aug, 2013         Granted                    Granted
IN 1744/MUMNP/2013          IN 1743/MUMNP/2013   India       16th Sept, 2013        16th Sept, 2013   National phase filing      National phase filing
ZL201280018816.6            ZL201280018969       China       16th Oct, 2013         17th Oct, 2013    Granted                    Granted
AU 2019901050 (Salt & Crystal form)              Australia   28th Mar 2019                            Filed

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John Lambert
Chief Executive Officer
   john@ampliatx.com
    +61 0409 525 259
    www.ampliatx.com

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