Transcript Moving mountains to serve cancer patients

Moving mountains to serve cancer patients
Steve Carchedi – CEO
[email protected]
908-720-1786
APEX
-1-
Company Overview
•
Apexian is a clinical stage biotech company with first-in-class therapy targeting the
APE1 protein
•
Our lead compound, APX3330 an oral anticancer agent has shown preclinical efficacy
against a variety of APE1-expressing tumors
•
APX3330 safety has been confirmed in 10 Phase I/II human studies of non-cancer
indications with over 422 patients
•
The phase I oncology study of APX3330 is ready for execution. IND approved by FDA,
first site has IRB approval and clinical supplies are ready to ship
•
Pipeline of oral anticancer agents APX2009, APX2014. Additional oncology and nononcology indications could lead to broad clinical utility
•
Key value inflection points in the near term (2017-18)
•
Robust IP estate and plan seeking Orphan Drug Designation, Fast Track and Priority
Review at the appropriate time
•
Experienced management team in discovery, development and commercialization of
oncology products
•
Currently seeking funding or clinical development partnership
APEX
-2-
Leadership Team

Steve Carchedi - Chief Executive Officer
•

Mark Kelley, Ph.D. - Chief Scientific Officer
•

Former CMO of ProNAi Therapeutics, with a 25+ years of clinical and pre-clinical drug-development experience
in industry (Endocyte, Eli Lilly), government (NCI, NIH) and academia (University of Michigan, Michigan State
University).
Roger Miller – Chief Operating Officer
•

Professor at Indiana University School of Medicine (IUSM); Betty and Earl Herr Chair of Pediatric Oncology
Research; Professor in Departments of Pediatrics, Biochemistry & Molecular Biology and Pharmacology &
Toxicology, Associate Director, IU Simon Cancer Center. Devoted more than 25 years exploring APE1/Ref-1
and its role in redox signaling, DNA repair, cancer and other diseases.
Rich Messmann, M.D., M.H.S., M.Sc. - Chief Medical Officer
•

Former President and CEO of Cornerstone Pharma. 25+ years of specialty pharmaceutical executive
experience in Fortune 500 companies (BMS, Eli Lilly, J&J and GE) as well as biotech firms (Endo and Sunesis).
More than 40 years of experience at Eli Lilly, Targanta, BioCriteria, Beta Cat and Salarius leading development,
manufacturing, quality and clinical trial operations.
Bill Current, PhD – Vice President, Regulatory Affairs
•
More than 30 years of experience at Eli Lilly, Targanta, BioCriteria and other companies leading regulatory
affairs for multiple therapeutic areas.
APEX
-3-
Board Members and Scientific Advisors

John Barnard – chairman, BOD
•

David Broecker – member BOD and SAB
•

Professor at Indiana University School of Medicine (IUSM); Betty and Earl Herr Chair of Pediatric Oncology
Research; Professor in Departments of Pediatrics, Biochemistry & Molecular Biology and Pharmacology &
Toxicology, Associate Director, IU Simon Cancer Center. Devoted more than 25 years exploring APE1/Ref-1
and its role in redox signaling, DNA repair, cancer and other diseases.
Martin Haslanger, Ph.D. – CEO Emeritus, member BOD and SAB
•

Named CEO of Apexian in 2016. Former CEO of Cornerstone Pharmaceuticals with 25+ years of specialty
pharmaceutical executive experience in several Fortune 500 companies as well as biotech firms.
Mark Kelley, Ph.D. – Chief Scientific Officer
•

CEO of APEX from 2014 to 2016. Former CEO of Alkermes and has served in executive leadership positions
at Eli Lilly and Company and several biotech firms. Currently he is CEO of Indiana Bioscience Research
Institute
Steve Carchedi – CEO, member BOD and SAB
•

Founder of Barnard Associates and Pearl Street Venture Funds. Former financial executive at Eli Lilly and
Company. Has assisted in the formation of many successful new companies.
CEO of APEX from founding until 2014. Former discovery and development executive at Eli Lilly and
Company, Squibb and Schering-Plough.
Homer Pearce, Ph.D. – member BOD and chairman, SAB
•
.
Former Vice President, Cancer Research and Clinical Investigation and Distinguished Research Fellow at Eli
Lilly & Company. Led discovery and development of Gemzar™ and Alimta™
APEX
-4-
APE1/Ref-1 Overview
•
APE1 (apurinic/apyrimidinic endonuclease),
also called Ref-1 (redox effector factor 1), is
a multifunctional cellular protein with two
distinct and separate functions:
• APE1 Redox Function: Redox regulation
of transcription factors (TFs) effecting
critical aspects of cancer cell survival and
growth including HIF-1, STAT3, NF-KB, and
others.

We can target multiple signaling
pathways relevant to various cancers
with one protein— as APE1 regulates
transcription factors (TFs) HIF1a,
STAT3, NFkB and others.

APX3330 inhibits only the APE1
redox signaling activity.
• DNA Repair Function: DNA base repair
caused by oxidative stress, alkylating
agents, and ionizing radiation
•
Various cancers, including treatment resistant
tumors, have shown elevated expression of
APE1 suggesting adaptation and unique
survival mechanisms through this pathway.
APEX
-5-
APE1/Ref-1 Overview (Cont.)
• The drug has a direct and selective interaction with APE1 as
demonstrated by chemical footprinting, mass spectrometry, and
other biochemical data.
• Although multiple pathways may be modulated, unacceptable
toxicity following APE1 inhibition has not been observed in animal
or human studies.
• Preclinical data supports the use of the drug as a single agent;
future directions indicate partnering APX3330 with various
clinical agents such as JAK2 inhibitors (Ruxolitinib, LY3009104.
etc), STAT3 inhibitors, gemcitabine and Abraxane (nab-paclitaxel).
APEX
-6-
Alteration of APE1/Ref-1 protein expression has
been shown to be elevated in:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Non-small cell lung cancer
Colorectal cancer
Breast cancer
Prostate cancer
Gynecologic cancers (ovarian, cervical)
Pancreatic cancer
Glioblastoma multiforme, meduloblastoma
Renal cancer
Gastric cancer
Germ cell tumors
Head-and-neck cancers
Multiple myeloma (hematologic cancer)
Osteosarcoma and Rhabdomyosarcoma (pediatric)
APEX
-7-
APX3330 inhibits APE1 Redox Function Blocking TF Activity
APX3330
(reduced
APE1)
C65
C93
Redox
active site
X
HIF-1a
NFkB
STAT3
AP-1
NRF2
X
(oxidized APE1)
(oxidized APE1)
TF
APEX
(oxidized TF)
X
TF
(reduced TF)
(reduced TF binds to target
DNA)
Target gene expression:
Growth
Inflammation
Angiogenesis
X
-8-
APX3330 inhibits APE1 redox function in tumor cells
APX3330
DNA
Stat3
APX3330 uM
APEX
APX3330 uM
APX3330 uM
Luciferase
APX3330 uM
-9-
APX3330 Reduces Tumor Growth and Metastasis
Panc253
Patient-derived cells
PaCa-2
% Growth (Mean ± SEM)
800
700
Control
APX3330
600
500
400
300
200
25 mg/kg
100
0
1
4
8
11 15 18 22 25 29
Day
Human PDAC
Metastasis
Number of lymph
node metastases
# of Lymph Node Metastases
18
16
Individual Mice
Average
14
12
10
8
*
6
4
2
* p<0.01
0
Vehicle
•
•
•
•
Overall Preclinical Results and
Conclusions:
3+ fold reduction in PaCa-2 tumors
2+ fold reduction in Panc254 tumors
Significantly less metastasis PDAC
Multiple models, consistent results
E3330
APX3330
SOURCE: Fishel ML, Jiang Y, Rajeshkumar NV, Scandura G, Sinn AL, He Y, Shen C, Jones DR, Pollok KE, Ivan M, Maitra A, Kelley MR.
(2011). Impact of APE1/Ref-1 Redox Inhibition on Pancreatic Tumor Growth. Molecular Cancer Therapeutics. Sep;10(9):1698-708.
APEX
- 10 -
APX3330 Enhances Gemcitabine
1200
Mean Tumor Volume (mm3)
1000
Vehicle
800
APX3330 25mg/kg
All drug treatments
stopped on day 30
APX3330 25+Gem
Gem 35mg/kg
600
400
*
200
*
0
APX3330 12
Gem
16
22
29
34
37
41
Days after Implantation
APEX
44
*
*
49
55
63
Error bars were removed from graph for
clarity. * =p<0.05 between Gem+APX3330
and Gem alone. All drug treatments were
significantly different from the vehicle control
p<0.01.
- 11 -
Role of APE1 in Cancer Immunotherapy
• PD-L1 and APE1 …findings suggest
that high expression of PD-L1 and
APE1 is a risk factor of gastric cancer
and a new biomarker to predict the
prognosis of gastric cancer….
• …findings suggest that targeting the
PD-L1 and APE1 signaling pathways
may be a new strategy for cancer
immune therapy and targeted
therapy for gastric cancer…
Kaplan–Meier analysis demonstrated that PD-L1
and APE1 co-positivity was significantly related to
a poor prognosis (P=0.003).
Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer. Qing, et al.
PMC4338255. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338255/
APEX
- 12 -
Prior development of APX3330
Eisai conclusion:
•
•
•
No significant acute toxicity on neurologic, cardiovascular, or pulmonary
function in patients administered APX3330
Improvements in transaminase levels in patients with hepatitis B and C
Eisai ended APX3330 development after in-licensing Revovir® (clevudine)
for the treatment of hepatitis B and Humira (adalimumab) for treatment of
rheumatoid arthritis, IBD and other indications.
Note: Eisai detected human serum concentrations of APX3330 at 147µM; a level
well above that required for anti-tumor effect in our xenograft models of pancreatic
cancer.
APEX
- 13 -
Apexian Clinical Plans for APX3330
•
Apexian will complete a two-part phase I oncology study:
•
•
•
Increasing doses in patients with treatment-refractory solid tumors
20-40 patients
Study endpoint:
•
•
Identify the RP2 dose of APX3330
Based upon
•
•
•
•
IND accepted by the FDA (July 2016):
•
•
•
tolerability of the agent
evidence of anti-tumor effect
pharmacokinetic and pharmacodynamic
All study documents are ready and sites identified
Contracts pending completion of the funding round
Additional safety, tolerability and efficacy POC
APEX
- 14 -
APX3330:
Robust Global IP Portfolio, Orphan Drug Designation & Near Term Approval
US Patent No.
9,040,505
US Patent No.
9,089,605
“Use of APX3330
in treatment of
cancer and
angiogenesis”
“Composition of
matter for
quinone
derivatives”
Expiration Date:
2030
Expiration Date:
2029
US Patent No.
9,193,700
“Composition of
matter for
quinone
compounds for
treating APE1
diseases”
Expiration Date:
2032
US Patent No.
9,315,481
“Methods and
compounds for
ref-1 inhibition in
leukemia”
Expiration Date:
2033
Application No.
PCT
US2016/0309045
“Use of APX3330
in treatment of
ChemotherapyInduced
Peripheral
Neuropathy”
Earliest
Projected
Expiration Date:
2036
Portfolio Patent Estate
Over 70+ issued or filed patents worldwide
 APX3330 is IP protected until 2030 and beyond across US, Australia, EU, Japan,
China, Brazil and other key countries
 Seeking orphan drug designation by the US FDA for the treatment of relapsed and
refractory solid tumors
 APX3330 near term approvals within 2019 – 2020
APEX
- 15 -
Sustainable Horizons for Growth
APX3330
Targeting Large Unmet Need in Terms of Patient Pool
Step 3
Business Plan
Phase 3
Program
Step 2
Phase 2 Program
Step 1
Phase I Program
R/R Solid Tumors
(Accelerated Path to Approval)
Phase 1B
Phase 1A Safety
Study
20-30 Patients
2017
APEX
(APE1
Expressing
Targeted
Indications)
10 patients
Pilot Single
Agent &
Combination
Studies
Proof of
Concept
Studies
Registration
Studies
Pursue Other
High Unmet Need
Tumors
2018-19
2020
- 16 -
Apexian Company Summary
Company
Privately held, clinical stage, biotech company with first-in-class
therapy targeting the APE1 protein
Our Lead Compound
APX3330 an novel oral anticancer agent has shown preclinical
efficacy against a variety of APE1-expressing tumors
Phase I oncology study of APX3330 is ready for execution. IND
approved by FDA and IRB approval by 1st clinical site
Clinical Plan
Robust manufacturing process with clinical supplies available
APX3330 safety has been confirmed in 10 Phase I/II human
studies of non-cancer indications with over 422 patients
Strong Portfolio
Robust IP
Our Management
APEX
Pipeline of oral anticancer agents (APX2009, APX2014).
Additional oncology and non-oncology indications could lead to
broad clinical utility
Robust IP estate and plan seeking Orphan Drug Designation
Extensive experience in discovery, development and
commercialization of oncology products
- 17 -
“Moving mountains to serve cancer patients”
www.ApexianPharma.com
APEX
- 18 -