Vision Above and Beyond - Solebury Trout Access
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Vision Above and Beyond
AsclepiX Therapeutics is focused on transforming the treatment of ocular diseases
and cancer through the rapid clinical development of groundbreaking therapies
aimed at empowering patients and their families around the world with the
freedom to live their best lives.
July 2020
C O N -FCI D
N O ENNF TI D
I AELN T/ /I A2 L0 2/ 0/ 2 0 2 0 Vision Above and Beyond 1
Company Overview
• Computational biology approach to identify Potent Peptide regulators of vascular and cellular homeostasis
• Strong Global IP with initial focus in Ophthalmology
• Recently announced completion of $35 million Series A financing round led by Perceptive Xontogeny
Venture Fund
Unmet Need with Strong and • Anti-VEGF monotherapies have hit a ceiling for efficacy and short duration of action
Growing Commercial Opportunity
• Current and growing Opportunity of $10B+ worldwide
• Potentially Best in Class agent that Inhibits VEGF and Activates Tie2 as a Monotherapy
• AXT107 is derived from a Cryptic Peptide within Collagen IV that works by activating naturally existing,
AXT107 has Novel Dual homeostatic mechanisms of angiogenesis that have evolved over millions of years
Mechanism of Action
• AXT107 was identified using a computational biologic approach and selected as a drug candidate for its
strong efficacy
Superior Efficacy • AXT107 demonstrated Superiority and more Durability to Eylea in animal models
Long Durability • Potentially only 1 intravitreal injection per year to dramatically reduce the treatment burden
Well Tolerated Safety Profile • Safety demonstrated in animal and toxicology studies for 15 months
IND Filing • AXT107 expected to Enter the Clinic in 2H 2020
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 2
Board of Directors
Welcoming 2 new board members from PXV Fund from recent completion of Series A
Steven Altschuler, MD Ben Askew, PhD Josh Barer Chris Garabedian
Chairman Xontogeny Hibiscus Bioventures and Xontogeny and PXV Fund for
Managing Director, Ziff Capital Barer & Son Capital Perceptive Advisors
• Spark Therapeutics • Xontogeny • Hibiscus Bioventures • Xontogeny
Former Founder/Chair-Board of Directors Partner, Research and Development Managing Director CEO
• Ziff Capital Partners • SciFluor Life Sciences • Barer & Son Capital • PXV Fund for Perceptive Advisors
Managing Director-Healthcare Ventures VP, Research Managing Partner Manager
• Children’s Hospital of Philadelphia • Third Rock Ventures • Trout Capital / Trout Group • Sarepta Therapeutics
(CHOP) Entrepreneur-in-residence Senior Associate President and CEO
President and CEO
Jordan Green, PhD Aleksander Popel, PhD Kevin Slawin, MD Sapna Srivastava, PhD
AsclepiX, Founder & CTA AsclepiX, Founder & CSA Rapha Capital Management Abide Therapeutics
Professor, Professor, Biomedical • Abide Therapeutics
Biomedical Engineering Engineering, Oncology • Rapha Capital Management, LLC Most recently Chief Financial and Strategy
Ophthalmology, Oncology Director, Systems Biology Founder/Managing Partner Officer
Lab • Bellicum Pharmaceuticals, Inc. • Intellia Therapeutics
Presidential Early Founder Chief Financial and Strategy Officer
Career Award
Visiting Professor • Professor, Baylor College of Medicine, • Goldman Sachs / Morgan Stanley /
Houston, Texas ThinkEquity, LLC
PhD, Bob Langer Lab Senior Analyst, Biotechnology
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 3
Clinical Pipeline
Product Candidates Program Area Preclinical Phase 1 Phase 2/3
Ophthalmology
Diabetic Macular Edema
AXT107
wet AMD
Retinal Vein Occlusion
Oncology
AXT201 Triple-Negative Breast Cancer
Solid Tumor
Oncology
AXT301, AXT501
Solid Tumor
Early Research
Early Pipeline
Various Indications
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 4
Leadership Team
Theresa Heah, MD, MBA
Kevin Slawin, MD Theresa Heah, Officer
Chief Medical MD, MBA Niranjan Pandey, PhD Huan Sheng, MD, PhD
Interim CEO/Board Member CMO/EVP Operations VP, Head of R&D VP, Clinical Research
Founder/Managing Partner Chief Medical Officer Director, R & D Sr. Director Clinical Research
and Drug Safety
VP, Global Head of Clinical Research,
Founder Medical and Cancer Therapeutics Sr. Clinical Lead and Sponsor
Professional Affairs Medical Expert
Professor, Baylor College of Global Strategic Marketing Genetics and
Medicine, Houston, TX Immunology Tom Principal Clinical Research
Director, Sr. Global Region Europe
Maniatis Scientist/Clinical Lead
& Canada Medical Affairs
Gary Musso, PhD Gary Novack, PhD Denis Roy, PhD
Manufacturing Regulatory Consultant Toxicology Consultant
& CMC Consultant
Head, Nonclinical Safety
Clinical and Regulatory
& Development
Worked with Development with SciLucent, LLC
20+ Development 25 + years Experience with a
Peptide Programs Broad Range of Ophthalmic Bristol-Myers Squibb
Amylin Pharmaceuticals, Inc.
Drugs and Devices
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 5
Computational Biologic
Approach to Drug Discovery
• Uses computational biology to identify potent peptide regulators of vascular and cellular
homeostasis with an initial focus on Ophthalmology
• Clinical candidate peptides discovered by AsclepiX tap into these naturally existing self-
regulating mechanisms, evolved over millions of uses, that the body uses to maintain
homeostasis and thus restore and maintain health
• Lead candidate AXT107 is a novel monotherapy investigational product
• Inhibits VEGF-A and VEGF-C and activates Tie2
• Potential to transform the treatment of ocular disease with best-in-class efficacy
and a long duration of action that could support up to once yearly dosing
• AXT107 is expected to enter the clinic in H2 2020
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 6
Scientific Excellence
Founders Extensive Experience Top-Tier Support
$11M in Non-Dilutive Funding
FOCUSED ON EXECUTION
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 7
Opportunities in Ocular Diseases
More Efficacious Therapies that Require Fewer Injections
AXT107
Injection Monotherapy with Superior Efficacy and
Longer Durations than Current Therapies
$10.8 BILLION
WW MARKET FOR ANTI-VEGF DRUGS
Diabetic
Diabetic Retinopathy Retinal Vein Occlusion
Macular Edema wet AMD
(DR) (RVO)
(DME)
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 8
AXT107: Potential to be Meaningfully Differentiated
First Line Treatment Breakthrough Next Generation
Therapy for Retinal Diseases
Combination Dual MOA
Monotherapies Therapy Therapy
AXT107 Eylea Lucentis Beovu GB-102 KSI-301 OPT-302 Faricimab
Inhibits
VEGF Binds to αvβ3 Integrin
VEGF-A VEGF-A VEGF-A
VEGF-A, VEGF-B,
VEGF-A VEGF-C / VEGF-D VEGF-A / Ang2
VEGF-A and VEGF-C VEGF-C, VEGF-D
Activates
*
Tie2 Binds to α5β1 Integrin
Potential
Potential Dose Loading Doses Dosed 1 month
1 Injection Loading Doses
followed by 2
Loading Doses
followed by 1
Loading Doses
followed by 2-3 once 6 followed by less Combined with
Doses less than
4 months
months month months months than 6 months anti-VEGF
Per Year
*Dependent on Endogenous Low Levels of Ang1 to Activate Tie2
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 9
AXT107 Strongly Inhibits VEGF and Activates Tie2
1 Molecule – 2 Pathways
αvβ3 α5β1
AXT107 AXT107
VEGF TIE2
Integrin Integrin
Co-Receptor Co-Receptor
Inhibition of VEGF Activation of Tie2
VEGFR2
Stops Vascular Receptor AXT107 Tightens Junctions
Leakage and Binds to Co-Receptors Inhibits VEGF & Activates Tie2 to Stop Vascular
Neovascularization Suppressing Leakage
Adhesion, Migration, Proliferation
INHIBITS REGRESSION
Vascular Leakage of Neovasculature
Inhibition of VEGF and Activation of Tie2
Leads to Strong Inhibition of Vascular Leakage and Neovascularization
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 10AXT107 Once Yearly Dosing to Dramatically Reduce Treatment Burden NON-CONFIDENTIAL // 2020 Vision Above and Beyond 11
DME: AXT107 has Superior Efficacy to Eylea with
Longer Duration in Pre-Clinical Animal Models
Rabbit VEGF Induced Vascular Edema Model
Day 30 Day 60
Fluorescein Leakage Fluorescein Leakage
(%) (%)
** *
***
AXT107Eylea
Eylea Eylea
Control AXT107 Eylea Control
• Single administration of AXT107 and Eylea show • Single administration of AXT107 inhibits
statistically significant inhibition of leakage for 30 leakage to 60 days, while Eylea is
days inactive at day 60
• Leakage remaining is reduced by 55% compared to
Eylea
1. Lima e Silva , P Campochiaro et al Tyrosine Kinase Blocking Peptide Supresses Ocular Neovascularization and Vascular Leakage, Sci. Transl. Med. 9 , eaai8030 (2017) 18 January 2017
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 12DME: AXT107 Inhibits VEGF Induced Exudative
Retinal Detachment More Potently then Anti-VEGF Treatments
Tet/Opsin/VEGF Mouse Model¹
AXT107
Control
Eylea
25 Tet/Opsin/VEGF Mouse Model²
20 *
Control Number 15
of eyes 10
5
AXT107
0
AXT107 inhibits VEGF induced exudative retinal Lucentis Control Avastin Control
detachment more potently than Eylea, Lucentis, * P < 0.05 against Lucentis
and Avastin
1. Lima e Silva , P Campochiaro et al Tyrosine Kinase Blocking Peptide Supresses Ocular Neovascularization and Vascular Leakage, Sci. Transl. Med. 9 , eaai8030 (2017) 18 January 2,017
2. Miki , P Campochiaro et al, Effects of Intraocular Ranibizumab and Bevacizumab in Transgenic Mice Expressing Human Vascular Endothelial Growth Factor, Ophthalmology, Vol 116, Number 9, September 2009
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 13Wet AMD: AXT107 Causes Regression
of Neovasculature
Treatment Model for Wet AMD AXT107 Results in
Regression of Neovasculature
Baseline (BL) 1µg AXT107 Control 0.040
0.035
0.030
Total Area
of NV 0.025
(mm2) 0.020
0.015
*
0.010
0.005
0
Laser Laser + Laser + BL AXT107 Control
AXT107 Placebo
1. Lima e Silva , P Campochiaro et al Tyrosine Kinase Blocking Peptide Supresses Ocular Neovascularization and Vascular Leakage, Sci. Transl. Med. 9 , eaai8030 (2017) 18 January 2017
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 14AXT107 Inhibits VEGF-C Induced Proliferations and Signalling in Endothelial Cells NON-CONFIDENTIAL // 2020 Vision Above and Beyond 15
AXT107 Activates Tie2 Inhibiting Vascular Leakage in Mice Ang2 overexpression and AXT107 treatment scheme 1. A Mirando et al Collagen IV Derived Peptide Disrupts α5β1 Integrin Potentiates Ang2 Tie2 Signaling JCI Insight February 21, 2019 NON-CONFIDENTIAL // 2020 Vision Above and Beyond 16
AXT107 Potently Strengthens Endothelial Cell
Junctions Reduces Vascular Leakage & Restores
Vascular Integrity
1
Well formed
endothelial cell
junctions with
co-localized Actin
and VE-Cadherin 2
1. A Mirando et al Collagen IV Derived Peptide Disrupts α5β1 Integrin Potentiates Ang2 Tie2 Signaling JCI Insight February 21, 2019
2 . I Chrifi et al CMTM4 regulates angiogenesis by promoting cell surface recycling of VE-cadherin to endothelial adherens junctions Angiogenesis 2019
Inhibition of VEGF and Activation of Tie2 Leads to Strong Inhibition of Vascular Leakage and Neovascularization
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 17AXT107 Suppresses Inflammation by
Activating Tie2
Vehicle
Vehicle
• NFκB is normally in • TNFα causes NFκB • AXT107 activates Tie2 to inhibit
the cytoplasm – to enter the nucleus TNFα
shown in green where it activates
transcription of • AXT107 suppresses
• Nucleus is stained in inflammatory inflammation as NFκB remains
blue proteins like VCAM- in cytoplasm and levels of
1 and ICAM-1 inflammatory proteins like
VCAM-1 and ICAM-1 are reduce
Mirando, A.C.; Lima e Silva, R.; Chu, Z.; Campochiaro, P.A.; Pandey, N.B.; Popel, A.S. Suppression of Ocular Vascular Inflammation through Peptide-Mediated
Activation of Angiopoietin-Tie2 Signaling. Int. J. Mol. Sci. 2020, 21, 5142.
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 18AXT107 Generally Well Tolerated
in 15 Month Animal Study
• AXT107 well tolerated following a single intravitreal
injection at multiple dose levels
• No adverse test-article related findings observed on
ophthalmic examination in male Dutch-Belted rabbits
• No findings of inflammation or increased intraocular
pressure observed
• GLP Toxicology program ongoing
CONFIDENTIAL // 2020
NO
NNO -NC- O
CNO FN IFDI E
DNE TN ITAI LA L/ / / 2
/ 022002 0 Vision Above and Beyond 19AXT107 Gel in Dutch Belted Rabbits
Day 1 Day 4 Day 31 Day 61
Day 91 Day 121 Day 151 Day 181
Day 211 Day 241
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 20AXT107 Gel in Gottingen Minipig
Pretest Day 1 Day 8
Day 15 (+/- 1) Week 5 Week 13
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 21AXT107 has the Potential for Extended Durability
Due to its Half Life
AXT107 half life
5.5 – 7 months
n= 4-6 eyes / timepoint
AT PC-04: AXT107 DB Rabbits Covance 8404881 15 Month PK Study
Preliminary Data – Study is on-going, data may vary once QC’d/finalized
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 22Sequestration of AXT107 in the Retina
During Transit Through the Eye
100 µg dose; Days: 91, 181, 225, 271, and 315 (Statistical outliers removed)
Boxes: Height = Median AXT107 concentration (ng/g) - base of box is 0, top = the median
Bars: Top = 3rd quartile of the AXT107 concentration (ng/g)
Indicates 100 ng/g threshold (retina only) Indicates 250 ng/g threshold (retina only)
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 23Sequestration of AXT107 in the Retina
During Transit Through the Eye
AXT107 Gel Content (ng)
at Month 6 in Minipigs
120,000
AXT107 half life
100,000 7 – 8 months
84,307
80,000
61,764
60,000
40,000 30,139
20,000 15,280
0
25 50 100 150
AT PC-03: AXT107 Gottingen Minipig Experimur SN 18-1041 6 Month Safety Study n=3 minipigs per dose
Preliminary Data – Data may vary once QC’d/finalized
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 24AXT107: Potential to be Meaningfully Differentiated
First Line Treatment with Longer Duration of Effect
AXT107 EYLEA Lucentis Beovu GB-102 KSI-301 OPT-302 Faricimab
Single-chain Microparticle Antibody Bispecific
Integrin disrupting VEGFR-1/-2 Antibody VEGFR-3
Format antibody VEGFR Tyrosine Biopolymer antibody
peptide Fc fusion protein fragment (Fab) fusion protein
fragment Kinase Sunitinib Conjugate (CrossMab)
V V
Molecular structure CC
H H
LC HC V V
22
3 3 L H
L H
1
Integrin αVβ3
VEGF-A/-B and VEGF-A and
Targets (VEGFR2) VEGF-A VEGF-A VEGF-A/-B/-C/-D VEGF-A VEGF-C/-D
PGF Ang-2
Integrin α5β1 (Tie2)
Inhibition of
Inhibition of Inhibition of Inhibition of Inhibition of VEGF- Inhibition of Inhibition of Inhibition of
VEGF-A/-C
Biological effect VEGF-A/-B and VEGF-A VEGF-A A/-B/-C/-D VEGF-A VEGF-C/-D VEGF-A
Strong Activation of
PGF Inhibition of Ang2
Tie2
Molecular weight, kDa 2.357 97–115 48 26 0.514 950 121 150
Kd (Integrin αVβ3), nM 1.3 N/B N/B N/B N/B N/B N/B N/B
Kd (Integrin α5β1), nM 2.2 N/B N/B N/B N/B N/B N/B N/B
Kd (VEGF-A165), pM See above 0.45–0.49 46–172 1.6–27.0 N/B 6.75 N/B 3500
Estimated vitreous t1/2,
~180 9.1 7.2 4.3 ~30 ~28 ~8 Not reported
days
N/B = non-binding
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 25Development: Timeline
2019 2020 2021 2022
OCULAR
DISEASES To IND Clinical Phase 1/ 2
Diabetic Macular Edema IND-Enabling Tox Phase 1 Phase 2/3
AXT107
Wet AMD IND Phase 1 Phase 3
AXT107
Retinal Vein Occlusion Phase 1 Phase 3
AXT107
CANCER – EARLY STAGE
DEVELOPMENT
Triple Negative Breast
Cancer
Solid Tumors
AXT 201
AXT 301
AXT 501
NON-CONFIDENTIAL // 2020 Vision Above and Beyond 26THANK YOU. NON-CONFIDENTIAL // 2020 Vision Above and Beyond 27
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