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June 2017
Copyright © 2017
2
This presentation contains forward-looking statements that involve substantial risks and
uncertainties. All statements, other than statements of historical facts, contained in this
presentation, including statements regarding our strategy, future operations, future
financial position, future revenues, projected costs, prospects, plans and objectives of
management, are forward-looking statements. The words “anticipate,” “believe,”
“estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,”
“would,” “could,” “should,” “continue,” and similar expressions are intended to identify
forward-looking statements, although not all forward-looking statements contain these
identifying words.
Forward-looking statements are neither historical facts nor assurances of future
performance. Instead, they are based only on our current beliefs, expectations and
assumptions regarding the future of our business, future plans and strategies,
projections, anticipated events and trends, the economy and other future conditions.
Because forward-looking statements relate to the future, they are subject to inherent
uncertainties, risks and changes in circumstances that are difficult to predict and many of
which are outside of our control. We may not actually achieve the plans, intentions or
expectations disclosed in our forward-looking statements, and you should not place
undue reliance on our forward-looking statements. Actual results or events could differ
materially from the plans, intentions and expectations disclosed in the forward-looking
statements we make. We assume no obligation to update any forward-looking
statements, except as required by applicable law.
Forward-Looking Statements
Copyright © 2017
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Validated
Pipeline
Aggressive
Clinical
Development
leap
Compelling
Science
Targeting Wnt
Biology and
Immune
Agonists
Differentiated
Antibodies
Clinical and
Biological
Activity
Targeted
Populations
Mechanism-
driven
Combinations
Copyright © 2017
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Proof of
Concept
TRX518(GITR
Agonist)
Non-Small Cell Lung Cancer (monotherapy)
Biliary Tract Cancer (gemcitabine+cisplatin)
Esophagogastric Cancer (monotherapy + paclitaxel)
Solid Tumor Malignancies (monotherapy)
Ongoing and Planned Clinical Studies
DKN-01(anti-DKK1) Wnt
Pathway
Alterations
Immuno-
therapy
Hepatocellular Carcinoma (monotherapy + sorafenib)
Gynocological Endometrioid (monotherapy + paclitaxel)
Gastric Cancer (monotherapy + paclitaxel)
Esophagogastric Cancer (PD-1 or PD-L1 antagonists)
Combo with PD-1 or PD-L1 antagonists (targeted solid tumors)
Combo with Chemotherapy (targeted solid tumors)
Proof of
Concept
Combos
Leap Pipeline
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DKN-01 Overview
DKN-01: A DKK1 Inhibitor
Rationale Overexpression of DKK1 and Wnt-beta catenin
pathway alterations linked to poor prognosis
Proof of Concept
Data to Date
Biliary Tract Cancer (BTC)
Esophagogastric Cancer (EGC)
Non-Small Cell Lung Cancer (NSCLC)
Multiple Myeloma
Targeted
Population
Patients with Wnt Pathway Alterations
Combination
Approach
Immune Effects of Wnt Signaling modulation
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• Overexpression of DKK1 linked to poor prognosis
• Tumor cells secrete DKK1 promoting proliferation, metastasis, and
angiogenesis
• DKK1 suppresses anti-tumor immune responses
DKK1 in Cancer
NK, MDSC, T Cells
CSC = Cancer Stem Cells
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DKN-01 Clinical Proof of Concept
ORR 31.8%, DCR 95.5%
PFS 9.4 months
ORR 24%, DCR 61%
-100%
-80%
-60%
-40%
-20%
0%
20%
40%
60%
80%
100%
DKN-01 + gemcitabine/cisplatin in
treatment-naïve advanced biliary
tract cancers
DKN-01 + paclitaxel in advanced
relapsed/ refractory esophagogastric
cancers
Historical gemcitabine/cisplatin studies:
• Overall response rates: 19.5 to 25.5%
• Disease control rate: 68.3 to 81.4%
• PFS: 5.8 to 8 months
Historical paclitaxel 2nd line and later
studies:
• Overall response rates: 5-15%
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Durable Responses to DKN-01 Therapy
Biliary Tract Cancer
-40%
-55%-48%
-53%
-65%-70%-73%
-78% -78%
First Dose
Discontinued Paclitaxel
-100%
-80%
-60%
-40%
-20%
0%
20%
M-1
5J-1
5J-1
5A
-15
S-1
5O
-15
N-1
5D
-15
J-1
6F
-16
M-1
6A
-16
M-1
6J-1
6J-1
6A
-16
S-1
6O
-16
N-1
6D
-16
J-1
7F
-17
M-1
7A
-17
M-1
7J-1
7
Targ
et
Lesio
n C
han
ge
Long-Term Monotherapy Response in Esophagogastric
Cancer
• Ongoing response for 2+ years
• Response deepened on DKN-
01 monotherapy
• Patient has Wnt/β-catenin
mutation
Responders and long-term
stable disease patients
identified with Wnt pathway
alterations
• 20 additional patients added to
study
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• Tumors with stabilizing β-catenin mutations have elevated levels of DKK1
Targeting Wnt Pathway Alterations
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Targeting Populations with Wnt/β–Catenin Alterations
Esophagogastric
Cancer
Liver
Cancer
Uterine and Ovarian
Cancer
US
Incidence
Esophagus: 17,000
Stomach: 28,000
Liver: 40,000
Biliary: 6,000
Endometrial: 61,000
Ovarian: 22,000
β-catenin
Mutational
Frequency
Gastric: 6-9% of patients HCC: 27-36% of patientsEndometrioid: 29-30% of
patients
Leap
Clinical
Plans
• Ongoing arm of
esophagogastric study
• IST with University of
Mainz• Study planned
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• Combination targets the tumor, as well as adaptive and innate immunity
• β-catenin frequently elevated in “cold” tumors or tumors acquiring resistance
to checkpoint inhibitors
DKN-01 and PD-1/PD-L1 Antibody Combination
• Clinical study planned to begin 2H-17 testing combination of
DKN-01 and PD-1/PD-L1 antibody
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DKN-01 Summary
Novel mechanism targeting oncogenic
and immunosuppressive
protein
Proof of concept as single agent and
with various backbone therapies
Targeted patient populations and
novel immunotherapy combinations
Targeted patient populations and
novel immunotherapy combinations
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TRX-518 Overview
TRX-518: GITR Agonist
Rationale GITR stimulation enhances immune response
Data to Date Single dose, dose escalation study in solid tumors
Target
Population
Diverse solid tumors
Combination
Approach
Immunotherapeutics and chemotherapy
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GITR Stimulation Enhances Immune Responses
GITR Stimulation on Teff and Tregs
Reduced Suppression
Tumor Cells
Anti-GITR Agonist Ab
Teff Cells
Treg Cells
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• TRX518 is a differentiated, humanized non-depleting IgG1 GITR agonist mAb
• GITR agonist without FcR binding signals to and does not deplete GITR
expressing T cells
TRX518: Engineered to Maximize GITR Activation of Immune Response to Tumors
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• TRX518 single-dose, dose-escalation study completed in advanced solid
tumors
– Well tolerated
– Drug saturation of GITR on peripheral T lymphocytes confirmed
• Two repeat-dose monotherapy studies ongoing
– Now in dose expansion cohort of TRX518-003 study
• Demonstrated clinical activity
– Two patients with reductions in tumor burden, one for 11+ cycles
• Patient previously had progressive disease while on three different
clinical trials
• Reductions in peripheral and intratumoral Tregs
– Intra-tumor Foxp3+ Tregs were significantly reduced after treatment
– Intra-tumor reductions correlate with reductions in peripheral Tregs
TRX518 Clinical Summary
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TRX518 Modulates Peripheral and Intratumoral Tregsin Single Dose Phase 1 Study
Fold
change
rela
tive to
baselin
e
baseline2hrs4hrs
Day2
Day8
Day15Wk3Wk6
Wk12
0.0
0.5
1.0
1.5
2.0
2.5
Tre
gs/C
D4 %
(r
ela
tive to b
aselin
e)
0102-0002 (cohort 6, melanoma)
0273-00022 (cohort 7, colon)
0002-0004 (cohort 7, lung)
0002-0005 (cohort 7, lung)
0102-0003 (cohort 7, melanoma)
0002-0009 (cohort 8, colon)0102-0005 (cohort 9, melanoma)0002-0006 (cohort 9, bladder)
baseline2hrs4hrs
Day2
Day8
Day15Wk3Wk6
Wk12
0.0
0.5
1.0
1.5
2.0
2.5
Tre
gs/C
D4 %
(r
ela
tive to b
aselin
e)
0102-0002 (cohort 6, melanoma)0273-00022 (cohort 7, colon)
0002-0004 (cohort 7, lung)0002-0005 (cohort 7, lung)
0102-0003 (cohort 7, melanoma)
0002-0009 (cohort 8, colon)
0102-0005 (cohort 9, melanoma)0002-0006 (cohort 9, bladder)
Peripheral Blood
Tregs
0002-0004
0002-0005
0102-0003
0002-0006
0102-0005
0273-00022
0102-0002
0002-0009
01234
100
200
300
400
#Foxp3+CD4+_All_SITC2016
Pre-Tx
Post-Tx
***
***
n.s. n.s. ***
# F
oxp3
+C
D4
+
0002-0004
0002-0005
0102-0003
0102-0002
0273-00022
0101-0009
0
1
2
3
100
200
300
400
#Foxp3+CD4+_All_SITC2016
Pre-Tx
Post-Tx
***
***
n.s. n.s.
Wk6
Wk12Wk12
Wk7
Wk3
Wk6
Wk3Wk3
Intra-tumoral Tregs
• Wolchok Lab (MSKCC); SITC 2016 and AACR 2017
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• Strong preclinical and mechanistic rationale to combine with other
immunotherapeutics and chemotherapies
• Combination study planning underway in diverse solid tumors
TRX518 and anti-PD-1 or PD-L1 Combination
Control
GITR
anti-CTLA4
Gemzar
GITR + anti-CTLA4
Gemzar + GITR
Gemzar + anti-CTLA4
Triple Combination
Preclinical GITR Agonist Synergy
with Chemo and Checkpoint Inhibitors
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TRX518 Summary
Differentiated GITR agonist
Evidence of clinical and biologic activity
Two ongoing repeat dose studies to further evaluate
pharmacodynamics
Combination study planning underway
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Leadership
Chris Mirabelli
CEO
Company
ExperienceGus Lawlor
COO
Doug Onsi
CFO Approved
Drugs
Christopher Mirabelli, Chairman of the Board, CEO of Leap
James Cavanaugh, Managing Director at HealthCare
Ventures
John Littlechild, Managing Director at HealthCare Ventures
Thomas Dietz, Chairman and CEO of Waypoint Holdings
Joseph Loscalzo, Chairman, Department of Medicine,
Physician-in-Chief, Brigham and Women’s Hospitals
Nissim Mashiach, President and CEO of Macrocure Ltd.
William Li, CEO of the Angiogenesis Foundation
Board of Directors
Christopher T. Walsh, Chair of Leap SAB, Hamilton Kuhn professor
of biological chemistry and pharmacology at Harvard Medical School
Carl F. Nathan, Professor and Chairman of Department of
Microbiology and Immunology at Weill Cornell Medical College
David Tuveson, Director of Research, the Lustgarten Foundation,
Roy J. Zuckerberg Professor of Cancer Research at CSHL
Eric P. Winer, SVP and Chief Clinical Strategy Officer; Chief, Division
of Women's Cancers, DFCI; Director, Breast Oncology Program,
Susan F. Smith Center for Women's Cancers; Thompson Chair in
Breast Cancer Research Institute Physician; Professor of Medicine,
Harvard Medical School
Xi He, PhD, Endowed Research Chair, Professor of Neurology,
American Cancer Society Research Professor, Boston Children’s
Hospital and Harvard Medical School
Scientific Advisory Board
Management Team
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Historical Financials
Amount in Thousands
Quarter
Ended Mar
31
Year
Ended
December
31
Q1-17 2016
Operating expenses:
Research and development $6,404 $23,292
General and administrative 3,804 4,229
Total operating expenses 10,208 27,521
Loss from operations (10,208) (27,521)
Interest income 50 2
Interest expense - related party (121) (1,233)
Other income 865 3,120
Net loss (9,414) (25,632)
Accretion of preferred stock to redemption
value(244)
Net loss attribute to common
stockholders($9,658)
March 31,
2017
(in thousands)
Assets
Current assets:
Cash and cash equivalents $23,800
R&D incentive receivable 3,167
Prepaid expenses and other current assets 319
Total current assets 27,286
Property and equipment, net 159
R&D incentive receivable, net of current portion 397
Deferred offering costs -
Other assets 937
Total assets $28,779
Liabilities, Convertible Preferred Stock and Stockholders' Equity
Current liabilities:
Accounts payable $2,793
Accrued expenses 1,819
Notes payable and accrued interest - related party -
Total current liabilities 4,612
Stockholders' equity (deficiency)Common stock, $0.001 par value; 100,000,000 and
58,500,000 shares authorized as of March 31, 2017 and
December 31, 2016, respectively; 9,392,414 and 0 shares
outstanding as of March 31, 2017 and December 31, 2016,
respectively 9
Additional paid-in capital 134,347
Accumulated other comprehensive income (loss) (105)
Accumulated deficit (110,084)
Total stockholders’ equity (deficiency) 24,167
Total liabilities, convertible preferred stock and
stockholders' equity (deficiency) $28,779
Copyright © 2017
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Upcoming Milestones
Upcoming Milestones
Response data from 20 additional pts
Efficacy data from combo + mono tx
arms
Enrolling patients, prelim data late 17/Q1-
18
Start enrolling Q4-17
Start enrolling 2H-17
Start enrolling 2H-17
Data from both studies including
response data and biomarker data
Start enrolling 2H-17
Start enrolling 1H-18
Proof of
Concept
TRX518(GITR
Agonist)
Non-Small Cell Lung Cancer (monotherapy)
Biliary Tract Cancer (gemcitabine+cisplatin)
Esophagogastric Cancer (monotherapy + paclitaxel)
Solid Tumor Malignancies (monotherapy)
Ongoing and Planned Clinical Studies
DKN-01(anti-DKK1) Wnt
Pathway
Alterations
Immuno-
therapy
Hepatocellular Carcinoma (monotherapy + sorafenib)
Uterine Endometrioid (monotherapy + paclitaxel)
Gastric Cancer (monotherapy + paclitaxel)
Esophagogastric Cancer (PD-1 or PD-L1 antagonists)
Combo with PD-1 or PD-L1 antagonists (targeted tumors)
Combo with Chemotherapy (targeted solid tumors)
Proof of
Concept
Combos
Copyright © 2017
23
Validated
Pipeline
Aggressive
Clinical
Development
leap
Compelling
Science
Targeting Wnt
Biology and
Immune
Agonists
Differentiated
Antibodies
Clinical and
Biological
Activity
Targeted
Populations
Mechanism-
driven
Combinations