MAKING MEANINGFUL
MEDICINES
Tolero Pharmaceuticals, Inc.
BIO Utah: November 2014
Company Overview
Founded:
2011
Series A:
2013 $3.3M
Series B:
2014 $22.4M
Headquarters:
Employees:
Focus:
Lehi, UT / Salt Lake City, UT
~25 (70% R&D)
Oncology: Hematology & Solid Tumors
Business Model: Discover, Develop & Commercialize New
Chemical Entities for the treatment of cancer
and other serious human diseases.
1
Tolero Pipeline
Lead product candidate, Alvocidib, advancing toward approval in front-line
and Relapsed/Refractory AML
•
•
•
Experience with 400 patients across five Phase II clinical trials
Most recent trial in 165 patients revealed striking CR rates vs. SOC (p<0.003)
Tolero has a rich pre-clinical pipeline and is advancing three additional
product candidates into the clinic
Addressing orphan diseases and large unmet needs
Expect to file 2 IND’s in 2015
Indication(s)
Next Milestone
Alvocidib
Front-line AML
Relapse/Refractory AML
End of Phase II meeting with FDA
Initiate Phase III clinical trial
BMP Signaling
Hepcidin-Driven Anemia,
(Anemia of Chronic
Inflammation, Cancer)
IND enabling studies prior to Phase I clinical trial
AXL Inhibitor
Head and Neck, Lung Cancer,
AML
IND enabling studies prior to Phase I clinical trial
PIM Inhibitor
Psoriasis, AML, Prostate
Cancer, Multiple Sclerosis
IND enabling studies prior to Phase I clinical trial
Preclinical
Program
Clinical
•
•
2
Experienced Management Team
Name/Title
Experience
David Bearss, PhD
CEO
 Founder, Chief Scientific Officer at Montigen Pharmaceuticals
 Chief Scientific Officer at Supergen (Nasdaq: SUPG)
 Co-director of the Center for Investigational Therapeutics at the Huntsman Cancer Institute
Dallin Anderson, MBA
Chairman & President
 Founder, Chairman, Chief Executive Officer and President at Montigen Pharmaceuticals
 Senior Vice President of Development at Supergen (Nasdaq: SUPG)
 MBA, Harvard
Steve Weitman, MD, PhD
Senior Advisor, Clinical &
Regulatory Strategy
 Physician and Director of the Institute for Drug Development, UTHSC-San Antonio
 Chief Medical Officer and SVP at Ilex Oncology
 Led team for FDA approval of Clofarabine
Michael McCullar, PhD, MBA 
COO

Senior Vice President of Business Development, Astex Pharmaceuticals (Acquired by Otsuka
Pharmaceuticals)
Vice President of Strategy and Development, SuperGen, led approval of Dacogen in US,
acquisitions of Montigen Pharmaceuticals and Astex Therapeutics, LLC
Steve Warner, PhD
VP, Discovery & Development
 Translational Genomics Research Institute
 Manager, Discovery Biology at Supergen (Nasdaq: SUPG)
 Senior Manager, Drug Discovery at the Huntsman Cancer Institute
Michael Bernstein, MPH
VP, Regulatory Affairs
 11 years at the FDA as Project Manager, Administrative Assistant to the Division Director
Joe Nilson
Director, Business Development
 20 years of product development, commercialization and licensing of healthcare and
and Executive Secretary to the PCNS and PDAC
 Senior Director of Regulatory Affairs at Ilex Oncology
 Career to date includes over 20 INDs/CTXs and 9 NDAs/BLAs/MAAs submissions
consumer products
 Vice President of Business Development at various subsidiaries of a privately held company
3
Alvocidib Overview
• Exclusive license from Sanofi in 2013
• Potent pan-CDK inhibitor
• Significant activity across 400 AML patients
• Potential for a meaningful advance in the
treatment of AML
4
Alvocidib Mechanism of Action
Kinase Inhibition of CDK Family
Kinase
CDK9
CDK4/6
CDK7
CDK11
CDK5
CDK8
CDK3
CDK2
Alvocidib IC50
(nM)
6
9
23
57
110
120
410
550
5
BRD4 mediates the recruitment of
P-TEFb (Cdk9/CyclinT)
7SK RNA Bound
Inactive P-TEFb
CyclinT
/ Cdk9
7SK
HEXIM1
Brd4 Bound
Active P-TEFb
CyclinT
/ Cdk9
Brd4
CTD
2P
CyclinT
/ Cdk9
2P
Brd4
2P
2P
RNA PII
6
Alvocidib in Acute Leukemias
Alvocidib has demonstrated both clear single-agent activity and also striking
efficacy in seqence with ara-c and mitoxantrone (FLAM regimen)
Single Agent Activity
• Phase 1 single agent study at Ohio State University
• Three-days dosing of alvocidib resulted in an average of 87%, 76% and 82%
reduction of circulating blast counts in untreated, relapse and refractory
patients, respectively.
• Overall response rate of 83%.
Combination Activity
• Phase II FLAM in front-line int/high-risk adult AML (N=45) showed a 67% CR
• Phase II FLAM in front-line int/high-risk adult AML (N=78) showed a 67% CR
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Alvocidib in Combination in AML
In intermediate and high risk patient populations, alvocidib in combination
shows significant improvement over 7+3, the current AML standard of care.
Randomized Phase II Study
2:1 165 Patients
FLAM (109 patients)
• Alvocidib: 50 mg/m2 IV day 1-3
• Ara-C 2 g/m2 IV over 72 hr, day 6-8
• Mitoxantrone 40 mg/m2 IV day 9
7+3 (56 patients)
• Ara-C 100 mg/m2/day IV days 1-7
• Daunorubicin 90 mg/m2 IV days 1-3
NCI-8972 Final Results:
% Complete Remission
FLAM
7+3
P Value
70%
46%
0.003
No Adverse
25/25 (100%)
13/18 (72%)
0.009
Adverse Genetics
Cytogenetics
Complex
Monosomal
FLT3 ITD+
30/58 (52%)
22/48 (46%)
14/30 (47%)
13/24 (54%)
9/13 (69%)
10/27 (37%)
6/21 (29%)
3/16 (19%)
3/12 (25%)
3/6 (50%)
0.16
0.2
0.11
0.16
0.62
Secondary AML
31/52 (60%)
9/26 (35%)
0.05
>1 High-risk feature
51/84 (61%)
13/38 (34%)
0.01
Primary Endpoint:
CR rate
CR by Risk Factors:
Randomized Phase II trial provides conclusive data to support further development
8
Alvocidib/FLAM in Relapse/Refractory AML
Clinical experience to-date from 5 trials:
trials
156 patients treated with FLAM across 4 relapsed/refractory AML
19 patients treated with monotherapy alvocidib in 1
relapsed/refractory trial
175 patients treated in Relapse/Refractory AML
• Alvocidib/FLAM has produced dramatic Complete
Remissions in Relapsed AML:
• Bolus alvocidib dose:
• Hybrid bolus/infusion dosing:
CR 75%
CR 92%
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Alvocidib Development Plan
Frontline and Relapse/Refractory AML
• Convene FDA End-of-Phase II meeting to discuss the planned
Phase III studies
• Launch concurrently 2015
Chronic Lymphocytic Leukemia
Combination
Solid Tumors
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Thank You!