Amplia Therapeutics Limited - ASX:ATX Amplifying Immunology - July 2019
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Amplia Therapeutics Limited
ASX:ATX
Amplifying Immunology
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
2
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
3
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
4
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.
5
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.
6
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.
7
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
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
9The 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
10Focal 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
11Why 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
12Ablation 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)
13Pancreatic 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
14AMP886 & 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.
15AMP886 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)
16Amplia’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
17The 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
18Amplia’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.
19High-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.
20Value 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
21The 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
22Competitive 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
23Financing
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
24Core 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
25John Lambert
Chief Executive Officer
john@ampliatx.com
+61 0409 525 259
www.ampliatx.com
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