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

4

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