Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond

 
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Developing Targeted Therapeutics

Providing Safe and Effective New Treatment
Options for Patients Most Likely to Respond
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Forward-Looking Statements

Certain statements in this presentation are forward-looking within the meaning of the Private
Securities Litigation Reform Act of 1995. These statements may be identified by the use of
words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar
terms or expressions that concern Trovagene's expectations, strategy, plans or intentions.

These forward-looking statements are based on Trovagene's current expectations and actual
results could differ materially. There are a number of factors that could cause actual events
to differ materially from those indicated by such forward-looking statements. While the list of
factors presented in the 10-K is considered representative, no such list should be considered
to be a complete statement of all potential risks and uncertainties. Unlisted factors may
present significant additional obstacles to the realization of forward-looking statements.
Forward-looking statements included herein are made as of the date hereof, and Trovagene
does not undertake any obligation to update publicly such statements to reflect subsequent
events or circumstances.

                                     Copyright © 2018 Trovagene, Inc.                             2
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Investment Thesis
   Nasdaq: TROV

               Oncology Expertise
Oncology Drug Development                                                 Attractive Investment Thesis
               Focus
► Onvansertib – only first-in-class, 3rd                      ► Clinical development programs in three key
  generation Polo-like Kinase 1 (PLK1) inhibitor                indications of significant medical need for new
  in development                                                treatment options
                                                                      –      Phase 1b/2 in Acute Myeloid Leukemia in combination
► Three active Investigational New Drug (IND)                                with standard-of-care chemotherapy
  Applications: Hematologic and Solid Tumor                           –      Phase 2 in metastatic Castration-Resistant Prostate
  Cancers                                                                    Cancer in combination with Zytiga®
                                                                      –      Phase 1b/2 in metastatic Colorectal Cancer in
                                                                             combination with FOLFIRI + Avastin®
► Completed and published Phase 1 study in
  solid tumor cancers                                         ► Working with leading investigators and cancer
                                                                institutions who approached Trovagene
► Orphan Drug Designation in Acute Myeloid
  Leukemia (AML) in the U.S. and Europe                       ► Demonstrated synergy with Onvansertib in
                                                                combination with already approved drugs
► Biomarker strategy to identify patients most
  likely to respond to treatment                              ► Proven safety, tolerability and preliminary data
                                                                demonstrating treatment benefit
► Funding to advance development programs
  well into 2019                                              ► Patent protection out to 2032

                                          Copyright © 2018 Trovagene, Inc.                                                         3
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Onvansertib Market Opportunity
                                                Market Potential By Indication Per Year of Treatment
                                                           Estimated Total ~10.5 Billion1
                     3000

                     2500
                                                                                                        Pancreatic
                                                                                                          2,216              Breast
Sales ($ Millions)

                     2000                                                                                                    2,070
                                                                                                                                                Small Cell
                                                                                                                                                  Lung
                                                                                                                                                  1,750
                     1500                                                                Prostate
                                                                    Colorectal            1,470
                                                                      1,265                                                           Ovarian
                     1000                                                                                                              1,056

                                                   AML
                                                   650
                         500

                             0
                              2020                2021                2022                2023            2024               2025     2026       2027        2028
                                                                                    Approximate Year of FDA Approval
                     1   2018 statistics https://seer.cancer.gov/statfacts/html/common.html

                                                                                          Copyright © 2018 Trovagene, Inc.                                          4
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Licensed Global Development & Commercialization
Rights to Onvansertib (PLK1 Inhibitor) from NMS
                       ► Largest oncology research and development company
                         in Italy and highly regarded throughout Europe and US

                       ► Leader in protein kinase drug development (Polo-like
                         Kinase Inhibitors)
                       ► Identification and validation of molecular targets
                         focused on driver oncogenes

                       ► Excellent track record licensing innovative drugs to
                         pharma/biotech companies including: Genentech
                         (Roche), Ignyta (Roche), Novartis

                       ► Oncology specialized contract development and
                         manufacturing organization
                       ► cGMP compliant and FDA validated production of API
                         (active pharmaceutical ingredient) and finished
                         dosage forms
                       ► Analytical services, clinical supply management and
                         CMC regulatory support

                  Copyright © 2018 Trovagene, Inc.                               5
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Nerviano Oncology Portfolio Success

► Excellent track record licensing innovative drugs to pharma/biotech companies that
  have subsequently received FDA breakthrough status and priority review designation

   Licensed      Preclinical            Phase 1                 Phase 2          Phase 3       Registered

               Encorafenib (B-RAF IP) Melanoma Braf mutation in combination with binimetinib

               Entrectinib (TRK, ROS, ALK) Non-Small Cell Lung

               Milciclib (CDK, other kinases) Thymic Cancer

               Onvansertib (PLK1 inhibitor) AML, mCRPC, mCRC

               MPS1 Inhibitor Solid Tumors

               ADC (PNU-652)

               ADC (NMS-P945)

                                          Copyright © 2018 Trovagene, Inc.                                  6
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Partnering Strategy

► Engaging in clinical trial collaborations
  across a number of major tumor types

► Identifying regional pharma partners for
  collaboration (Japan, Europe)

► Establishing partnerships to fund
  clinical trials (Phase 1b/2 mCRC)

                                Copyright © 2018 Trovagene, Inc.   7
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Strategy for Developing Onvansertib

► 3 active INDs in place

► Leveraging a proven cancer target, PLK1

► Biomarkers to identify patients most likely to respond to treatment

► Orphan Drug Designation in AML
► Combination therapy with already approved drugs
   – Phase 1b/2 trial of Onvansertib + cytarabine or decitabine in Acute Myeloid Leukemia (AML)
   – Phase 2 trial of Onvansertib + Zytiga® in metastatic Castration-Resistant Prostate Cancer
     (mCRPC)
   – Phase 1b/2 trial of Onvansertib + FOLFIRI and Avastin® in metastatic Colorectal Cancer (mCRC)
► Phase 1b/2 trial-ready in pancreatic, ovarian, breast and lung cancer

                                     Copyright © 2018 Trovagene, Inc.                                8
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Onvansertib – Pipeline Within a Molecule
Opportunities in Leukemias/Lymphomas and Solid Tumors

► Three active Investigational New Drug (INDs) Applications in place with the FDA

                         Preclinical                           Phase 1                     Phase 2
  Leukemias &      Acute Myeloid Leukemia – Orphan Drug Designation in the U.S. and Europe
  Lymphomas        Phase 1b/2 trial in combination with low-dose cytarabine (LDAC) or Decitabine

                   Metastatic Castration-Resistant Prostate (CRPC)
                   Phase 2 trial in combination with Zytiga® (abiraterone acetate)/prednisone

                   Colorectal (CRC)
                   Phase 1b/2 trial in combination with FOLFIRI + Avastin ®

                   Pancreatic
                   Phase 1b/2 trial ready

                   Ovarian
                   Phase 1b/2 trial ready
  Solid Tumor
                   Breast
   Cancers         Phase 1b/2 trial ready

                   Small Cell Lung
                   Phase 1b/2 trial ready

                                       Copyright © 2018 Trovagene, Inc.                              9
Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
Advancement of PLK Inhibitor Drug Class

► 1st Generation PLK Inhibitors                                          ► 2nd Generation PLK Inhibitors
    – GSK – 461364                                                              – BI – Volasertib
    – BI – 2536

              2010 - 2014                                                                   2012 - 2016

                    Limited Clinical                                                             PLK1 Proven Drug
                        Activity                                                                      Target

                                                                                  PanPLK                          Phase 2/3 Trials in
                                       Off-Target                                                                  Combination with
PanPLK Inhibitors                                                                    IV
                                       Toxicities                                                                 SOC demonstrated
                                                                                Long Half-life                    Clinical Response

                    IV (Intravenous                                                               Lethal Infections
                     Formulation)                                                                      Led to
                                                                                                  Discontinuation

                                                    Copyright © 2018 Trovagene, Inc.                                                    10
Onvansertib: First-in-Class, 3rd Generation
PLK1 with Best-in-Class Attributes

                  Copyright © 2018 Trovagene, Inc.   11
Onvansertib: Selective Only for PLK1
No Off-Target Adverse Events

► PLK1 is a master regulator of cell division

► Onvansertib has demonstrated safety and tolerability

► Phase 1 Safety Study:
   – No dose-limiting toxicities at the recommended Phase 2 dose (24 mg/m2)
   – No gastrointestinal, mucositis or alopecia
   – Expected myelosuppressive effects observed (thrombocytopenia and
     neutropenia) deemed related to the mechanism-of-action and reversible
   – No other clinically relevant safety findings were observed

                              Copyright © 2018 Trovagene, Inc.                12
PLK1: Established Target for Cancer Therapy

             PLK1 Plays a Critical Role in Initiation, Maintenance and Completion of Mitosis

                                                                                ► Polo-like Kinase 1 (PLK1)
                                                                                       – Belongs to a family of kinases
                                                                                         (PLK1,2,3,4,5)
                                                                                       – Dysfunction leads to cancer formation
                                                                                         and progression
                                                                                       – Over-expressed in dividing cancer cells
                                                       Cell-cycle arrest               – Inhibition leads to cancer cell death

1   Liu et al- PLK1, A Potential Target for Cancer Therapy; Translational Oncology – Vol. 10 – pp. 22-32; February 2017

                                                                           Copyright © 2018 Trovagene, Inc.                        13
Onvansertib: Highly-Selective Only for PLK1

                                                                                                    Onvansertib
                                                                        PLK Member
Selective PLK1 Inhibitor                                                                             IC50* (μM)

► Tested against >260 kinases                                           PLK1                            0.002

                                                                        PLK2                               > 10
► PLK1 was the only active target
  (IC50 of 2nM)                                                         PLK3                               > 10

                                                                                     Tumor Cell Division
Causes cancer cell death by G2M arrest
► Onvansertib blocks cell division (mitosis)
                                                                           Onvansertib Blocks Tumor Cell Division

 1   Data on File, Trovagene, Inc.

                                     Copyright © 2018 Trovagene, Inc.                                               14
Onvansertib Combination Therapy Strategy

► Cornerstone of precision cancer medicine

► Demonstrated synergy with chemotherapies and targeted therapeutics

► Enhances efficacy (targets key pathways by synergy or additive
  effect)1
► Reduces drug resistance, while providing therapeutic benefits
1   Mokhtari, R et al - Combination Therapy in Combatting Cancer – Oncotarget, 2017, Vol. 8 (No. 23), pp: 38022-38043

                                                                     Copyright © 2018 Trovagene, Inc.                   15
Onvansertib: Synergy May Enhance Efficacy
     of Standard of Care (SOC) Therapies1
                                                                                      Prostate

                                                                                      Zytiga®
                             Pancreatic
                               Breast                                               (abiraterone)                                     Colorectal
                              Ovarian                            Taxol®                                        Avastin®                Breast
                         Non-Small Cell Lung                   (paclitaxel)                                  (bevacizumab)        Non-Small Cell Lung

   Acute Myeloid Leukemia                       Venclexta®                                                                                    Leukemias (Acute
                                                                                                                          Cytarabine
Chronic Lymphocytic Leukemia                   (venetoclax)                                                                                   Myeloid Leukemia)

                                                                                 Onvansertib                                                      Leukemias
                                           Camptosar®
                                                                                                                           Doxorubicin           Lymphomas
                    Colorectal             (Irinotecan)                          Synergistic in                                                    Ovarian
                                                                              Combination with SOC                                                  Breast
                                                                                   Therapies

                                                Beleodaq                                                                                          Ovarian
                 T-Cell Lymphoma                                                                                          Cisplatin               Bladder
                                                (belinostat)
                                                                                                                                             Non-Small Cell Lung
                                                                                                                                               Small-Cell Lung

                                    Acute Myeloid               Quizartinib                                     Gemzar®            Pancreatic
                                      Leukemia                                                                (gemcitabine)          Breast
                                                                                                                                    Ovarian
                                                                                       Velcade®                                Non-Small Cell Lung
                                                                                     (bortezomib)
       1   Data on File, Trovagene, Inc.
                                                                                  Multiple Myeloma                                     Onvansertib current clinical trials

                                                                          Copyright © 2018 Trovagene, Inc.                                                                   16
Clinical Trial Roadmap

                 Acute Myeloid Leukemia (AML)

   Metastatic Castration-Resistant Prostate Cancer (mCRPC)

             Metastatic Colorectal Cancer (mCRC)

                       Copyright © 2018 Trovagene, Inc.      17
Clinical Advisors and Collaborators

Jorges Cortes, MD                Filip Janku, MD, PhD               Sandra Silberman, MD, PhD

            David Einstein, MD             Glenn Bubley, MD                 Michael Yaffe, MD, PhD

   Afsaneh Barzi, MD             Heinz-Josef Lenz, MD, FACP                      Daniel Ahn, DO

                                         Copyright © 2018 Trovagene, Inc.                            18
Acute Myeloid Leukemia1
Significant Need for New Treatment Options

► Aggressive hematologic malignancy of
  immature blood cells
                                                                                                                   Acute Myeloid Leukemia
► 20,000 new cases, 10,400 deaths annually,
  and 5 year survival rate of 25%
► Treatment options vary based on patient
  condition / age, but can include:
      – Chemotherapy / Radiation / Stem Cell Transplant

► Preclinical in-vitro and in-vivo data demonstrate
  efficacy of Onvansertib* as single agent and in
  combination with drugs used to treat AML

*Orphan Drug Designation granted for Onvansertib by the FDA September, 2017 and by the EMA in July, 2018 ;1National Cancer Institute SEER 2016; 2Valsasina et al., Mol
Cancer Ther; 11(4) April 2012

                                                                 Copyright © 2018 Trovagene, Inc.                                                                        19
Onvansertib Positioning in AML
Patient Selection Algorithm

                                                                                                            Responders              Consolidation
                                                                                                             50-70%                  Treatment
                                               Eligible for
                                               Induction
                                               Treatment
                                                ~11,000

               AML                                                                          Relapsed
            Diagnosis                                                                           &
             18,3761                                                                        Refractory                Onvansertib in combination with
            cases/year                                                                       30-50%                   standard-of care chemotherapy
                                                                                             3,300 to                  and/or targeted therapeutics2
                                                                                              5,500

                                                Ineligible
                                                   for
                                                Induction
                                                Treatment
                                                 ~7,400

 1   Visser et al. (2012), Eur J Cancer (48). Estimated cases in EU27 per year; 2e.g. Midostaurin for FLT3 mutation

                                                                      Copyright © 2018 Trovagene, Inc.                                                  20
Ongoing Phase 1b/2 Clinical Trial in AML

  Onvansertib in Combination with Either Low-Dose Cytarabine or Decitabine in
                  Patients with Acute Myeloid Leukemia (AML)

Phase 1b: Dose escalation to assess safety and identify recommended Phase 2 dose
                                                                                  Enrolling
                                                                     Completed
                                          Completed                              60 mg/m2
                     Completed                                       40 mg/m2
                                         27 mg/m2
    Completed
                    18 mg/m2
   12 mg/m2

► Administered orally, once daily on days 1-5 of each cycle (21-28 days)

Phase 2: Assess safety and preliminary antitumor activity

► Efficacy Endpoints: Rate of complete response (CR + CRi) defined as morphologic
  leukemia-free state (MLF)

► Exploratory Endpoints: Evaluation of pharmacodynamic and correlative biomarkers

                                  Copyright © 2018 Trovagene, Inc.                            21
Anti-Leukemic Activity
                                              ► Of the 26 patients evaluable for safety, 19 patients had an evaluable bone marrow biopsy to assess
                                                anti-leukemic activity

                                              ► Preliminary efficacy in the evaluable population showed ~90% overall patient benefit: CR (1), CRi (1),
                                                MLFS (2), PR (1), SD (12)
                                                    % Bone Marrow Blast Reduction from Baseline Onvansertib + Decitabine                                                                                                                                                  % Bone Marrow Blast Reduction from Baseline Onvansertib + LDAC
                                             150                                                                                                                                                                                                            1000
                                                                                                                   S ta b le d is e a s e (S D )                                                                                                                     18                                                          P r o g r e s s iv e d is e a s e ( P D )

                                                                                                                                                                                                                       % c h a n g e fr o m b a s e lin e
       % c h a n g e f r o m b a s e lin e

                                             100                                                                                                                                                                                                             900
                                                                                                                   P a rtia l re s p o n s e (P R )                                                                                                                                                                              S ta b le d is e a s e ( S D )
                                                    18
                                                         18                                                        C o m p le te re s p o n s e w ith                                                                                                        800
                                              50                27                                                                                                                                                                                           150
                                                                                                                                                                                                                                                                                                                                 M o r p h o lo g ic a l L e u k e m ic F r e e S ta te ( M L F S )
                                                                                                                   in c o m p le te h e m a to lo g ic a l re c o v e ry (C R i)
                                                                       18                                                                                                                                                                                    100           12 40
                                                                                                                                                                                                                                                                                                                                                                                                       2
                                                                                                                                                                                                                                                                                                                                 D a ta L a b e ls r e p r e s e n t o n v a n s e r tib d o s e (m g /m )
                                                0                                                                  C o m p le te re s p o n s e (C R )
                                                                                                                                                                                                                                                              50                    27 40
                                                                                                                                                                                      2                                                                                                        27
                                              -50                                                                  D a ta L a b e ls re p re s e n t o n v a n s e rtib d o s e (m g /m )                                                                       0
                                                                              12    40                                                                                                                                                                                                                27 12
                                                                                                                                                                                                                                                             -5 0
                                             -100
                                                                                           18     27    40                                                                                                                                                  -1 0 0                                               18 40
                                             -150                                                                                                                                                                                                           -1 5 0

                                                                                                                   currently on onvansertib 27mg/m2

                                                                                                                                                                                                                12 mg/m2
12 mg/m2

                                                    *                                                                        Onvansertib + Decitabine                                                                                                                                                                                     Onvansertib + LDAC
                                                                                                                                                                                                                                                                     *
                                                                                                                                           Best Response                                                                                                                                                                                            Best Response

                                                                                                                                                                                                                18 mg/m2
18 mg/m 2

                                                                                                                                               Ongoing                                                                                                                                                                                                   Ongoing
                                                                                                                                                PR                                                                                                              *                                                                                        MLFS
                                                                                                                                                         SD                                                                                                                                                                                                       SD

                                                                                                                                                                                                                27 mg/m 2
27 mg/m2

                                                         *                                                                                               CRi                                                                                                                                                                                                      CRi
                                                                                                                                                         CR                                                                                                                                                                                                       CR
                                                                                                                                                         PD
                                                                                                                                                                                                                40 mg/m2

                                                                                                                                                                                                                                                                                                                                                                  PD
40 mg/m2

                                                                                                                                              *          No BM data                                                                                                                                                                                     *         No BM data
                            0                       50        100       150        200       250       300   350                                                                                                                           0                         50     100       150       200        250       300   350

                                                              T r e a t m e n t d u r a t io n (d a y s )                                                                                                                                                                   T r e a t m e n t d u r a t io n (d a y s )

                                                                                                                                                                                      Copyright © 2018 Trovagene, Inc.                                                                                                                                                                                22
Patient Cases
                                                                                                                                                                                                                     25
                                                                                                                                                                                                                                               C y c le 1                                         C y c le 2

►   76 year-old male, diagnosed with AML in 2015; treated with induction chemotherapy; relapsed in December 2018;
    entered trial in January 2019 on onvansertib 40mg/m2+ decitabine
                                                                                                                                                                                                                     20
                                                                                                                                                                                                                                                                                                                                        B o n e m a r r o w b la s t s
                                                                                                                                                                                                                                                                                                                                        C ir c u la t in g b la s t s

                                                                                                                                                                                              % o f b la s ts
                                                                                                                                                                                                                     15

►   Patient reached CR as of the end of cycle 2 and is currently in cycle 3                                                                                                                                          10

►   % bone marrow blasts decreased from 22% (at screening) to less than 5% at the end of cycle 2; circulating blasts                                                                                                     5
                                                                                                                                                                                                                                                                                                                                               CR
    remained low during the entire treatment (0.2 to 2.2%)                                                                                                                                                               0
                                                                                                                                                                                                                                 1                                   22        1                                           29

                                                                                                                                                                                                                                                                 D a y s o f c y c le

►   68 year-old female with MDS progressed after 6 cycles of azacytidine; diagnosed with AML in September 2018;                                                                                                  50
                                                                                                                                                                                                                                     C y c le 1                  C y c le 2                     C y c le 3                      C y c le 4

    entered trial in October 2018 on onvansertib 27mg/m2 + decitabine                                                                                                                                            40                                                                                                                           B o n e m a r r o w b la s ts

                                                                                                                                                                                                                                                                                                                                              C ir c u la tin g b la s ts

►   Onvansertib dose reduced to 18mg/m2 at cycle 5

                                                                                                                                                                                          % o f b la s ts
                                                                                                                                                                                                                 30

►   Patient reached CRi at then end of cycle 4 and is in cycle 6                                                                                                                                                 20

                                                                                                                                                                                                                 10                                                                                                                                   CRi
►   % bone marrow blasts decreased from 20% (at screening) to 1% (cycle 4) and circulating blasts decreased from 43%
    (C1D1) to 1% (C4D21)                                                                                                                                                                                             0
                                                                                                                                                                                                                             1                      22     1                    21      1                    21        1                    21
                                                                                                                                                                                                                                                                          D a y s o f c y c le

►   68 year-old female with MDS progressed after 6 cycles of azacytidine; diagnosed with AML in September 2018;                                                                                                 15

                                                                                                                                                                                                                                          C y c le 1                                        C y c le 2                           C y c le 3

    entered trial in October 2018 on onvansertib 27mg/m2 + decitabine
                                                                                                                                                                                                                10

►   Onvansertib dose was reduced to 18mg/m2 at cycle 5

                                                                                                                                                                                        % o f b l a s ts
                                                                                                                                                                                                                                                                                                                                                      B o n e m a rro w b la s ts

                                                                                                                                                                                                                                                                                                                                                      C irc u la tin g b la s ts

►   Patient reached CRi at then end of cycle 4 and is in cycle 6                                                                                                                                                 5

                                                                                                                                                                                                                                                                                                                                              MLFS
►   % bone marrow blasts decreased from 20% (at screening) to 1% (cycle 4) and circulating blasts decreased from 43%                                                                                             0

    (C1D1) to 1% (C4D21)                                                                                                                                                                                                 1       5        10          17        22         1

                                                                                                                                                                                                                                                            D a y s o f c y c le
                                                                                                                                                                                                                                                                                    5   9          15        22             1

►   75 year-old male, diagnosed with AML in 2009; treated with induction chemotherapy; relapsed March
                                                                                                                                100       C y c le 1     C y c le 2    C y c le 3     C y c le 4                             C y c le 5            C y c le 6         C y c le 7                C y c le 8            C y c le 9       C y c le 1 0

    2018; entered trial April 2018 on onvansertib 12mg/m2 + decitabine                                                           75
                                                                                                                                                                                                                                                                                                                                                      B o n e m a rro w b la s ts

                                                                                                             % o f b la s t s
                                                                                                                                                                                                                                                                                                                                                      C irc u la tin g b la s ts

►   Onvansertib dose increased to 18mg/m2 cycle 6; 27mg/m2 cycle 11                                                              50

►   Patient reached PR at end of cycle 4 and is currently in cycle 11                                                            25                                                                                                                                                                                                                       PR
►   % bone marrow blasts decreased from 94% (at screening) to 10% (cycle 10) and circulating blasts                               0
                                                                                                                                      1           22 1          22 1           22 1                             22 1                 22        1           22 1                22           1           22        1             22 1          22

    decreased from 92% (C1D1) to 7% (C10D22)                                                                                                                                                                                          D a y s o f c y c le

                                                            Copyright © 2018 Trovagene, Inc.                                                                                                                                                                                                                                                                              23
PLK1 Inhibition Can Be Monitored Through
     pTCTP Status
    ► pTCTP as a marker of PLK1 activity:                                                          No Onvansertib                        Onvansertib

              – PLK1 phosphorylates the translational                                                          TCTP               Onvansertib         TCTP

                control tumor protein (TCTP) on serine 461                                                            P
                                                                                                                                                                P
                                                                                                PLK1
                                                                                                                                         PLK1
              – pTCTP was identified as a specific marker
                for PLK1 activity in in-vivo preclinical                                                                  P

                models1                                                                                    TCTP
                                                                                                                                                       TCTP

► In the Phase 1b AML trial, 8 out of the 22 subjects (36%) tested showed a decrease in
  % pTCTP at 3h post-dose compared to pre-dose
                                           Target Engagement                                                   No Target Engagement
                                     12 mg/m2          27 mg/m2         40 mg/m2                         12 mg/m2               27 mg/m2             40 mg/m2

                               01-002      07-009   08-027     05-030   07-036                        07-004    07-013        01-024    07-033       07-035
                              0h 3h         0h 3h   0h 24h 0h     3h    0h 3h                         0h 3h      0h 3h        0h 3h 0h          3h   0h 3h
                  pTCTP                                                                   pTCTP
                    TCTP                                                                    TCTP

1   Cucchi et al., Anticancer Res., 2010

                                                                   Copyright © 2018 Trovagene, Inc.                                                                 24
PLK1 Inhibition by Onvansertib is Correlated
with Higher Response to Treatment
► Patients with target engagement had a significantly higher decrease in bone marrow blasts
  compared to patients with no-target engagement
► 4 out of the 7 patients with target engagement had a decrease in bone marrow blasts ≥50%

► Conversely, only 1 out of the 9 patients with no-target engagement showed a decrease in bone
  marrow blasts upon treatment

    % Bone Marrow Blast Change Relative to Baseline                                                                                                         % Bone Marrow Blast Reduction from Baseline

                                                      300                                                                                                  1000                                 T a rg e t E n g a g e m e n t
                                                                             **
           % b la s ts re la tiv e to b a s e lin e

                                                                                                                                                             900

                                                                                                                       % c h a n g e fro m b a s e lin e
                                                                                                                                                                                               N o T a rg e t E n g a g e m e n t
                                                      200                                                                                                    800
                                                                                                                                                             150
                                                                                                                                                             100
                                                      100                                    p=0.009                                                          50
                                                                                                                                                                0                                                          *
                                                        0
                                                                                                                                                             -5 0
                                                                                                                                                            -1 0 0
                                                                     t
                                                                t

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                                                                     n
                                                             e

                                                                                  e

                                                                                         t
                                                                     e
                                                            rg

                                                                              rg

                                                                                         n

                                                                                                                                                            -1 5 0
                                                                 m

                                                                                      e
                                                        a

                                                                             a
                                                                 e

                                                                                     m
                                                       T

                                                                             T
                                                             g

                                                                                  e
                                                             a

                                                                         o

                                                                                 g

                                                                                                                                                           *patient sample had low % circulation blasts (~1%) and showed a
                                                            g

                                                                         N

                                                                                 a
                                                        n

                                                                             g
                                                       E

                                                                             n

                                                                                                                                                           40% reduction in pTCTP
                                                                         E

                                                                                                Copyright © 2018 Trovagene, Inc.                                                                                                    25
Simple Blood Test for Predicting Response
to Onvansertib
► Biomarker assay uses a blood sample to test whether a patient has a greater
  likelihood to respond to Onvansertib
► If patient is positive for biomarker assay, then drug is administered
► Blood test examines the extent that Onvansertib inhibits PLK1 enzymatic activity
  (called target engagement) within circulating cancer cells

                       In-vivo sampling (current method)

                      Patient receives                                                               Onvansertib
       Pre-dose       a single dose of                   3h post-dose       Assess target              -    +
        sample          onvansertib                         sample          engagement
                                                                                             pTCTP

                                                                                             TCTP
                       Ex-vivo sampling (in development)
                                                                                                     Onvansertib
                                         Control vial,
                                         Vehicle                                                       -    +
                                                                                             pTCTP
            Obtain 2 vials         Treat blood sample with                   Assess target
            of blood from        onvansertib or vehicle control              engagement      TCTP
                patient
                                         Treatment vial,
                                         Onvansertib

                                                   Copyright © 2018 Trovagene, Inc.                                26
Metastatic Castration-Resistant Prostate Cancer
    Opportunity to Increase Duration of Response to Therapy

    ► 25,000 men die from metastatic prostate cancer
      annually and the five-year survival rate is 37%2
    ► Treatments
           – Zytiga® (Johnson & Johnson)/prednisone                                                                          Prostate Cancer
           – Xtandi® (Astellas/Pfizer)

    ► Ongoing need to increase duration of response to
      treatment
           – Patients develop resistance within 9-15 months4 and do
             not respond well to subsequent therapies

    ► Preclinical studies demonstrate synergy between
      Onvansertib and Zytiga®
           – PLK1 inhibition improves abiraterone efficacy by
             repressing the androgen signaling pathway3,4

12017 Annual Report on Prostate Disease – Harvard Health Publications; 2GlobalData. Prostate Cancer—Global Drug Forecast and Market Analysis to 2023. Apr, 2015; 3 National
Cancer Institute Metastatic cancer. Mar, 2013. Available at: http://www.cancer.gov/about-cancer/what-is-cancer/metastatic-fact-sheet; 4GAntonarakis, Emmannel – Current
Understanding of Resistance to Abiraterone and Enzalutamide in Advanced Prostate Cancer; Clinical Advances in Hematology & Oncology – May 2016 – Volume 14, Issue 5

                                                                  Copyright © 2018 Trovagene, Inc.                                                                            27
Ongoing Phase 2 Clinical Trial in mCRPC

    Onvansertib in Combination with Zytiga® and Prednisone in Patients with
          Metastatic Castration-Resistant Prostate Cancer (mCRPC)

       Dosing Regimen                       Duration                     Evaluation

    Onvansertib – 24 mg/m2
                                                                       Disease Control
    Days 1-5 (21-Day Cycle) +       4 Cycles = 12 Weeks
                                                                      based on PSA level
    Zytiga®/prednisone daily

Efficacy Endpoints
Effect of Onvansertib in combination with Zytiga®/prednisone on disease control assessed
by prostate-specific antigen (PSA) decline or stabilization pre- and post-treatment
Safety Endpoint
Safety of Onvansertib in combination with Zytiga®/prednisone
Exploratory Endpoint
Target inhibition of PLK1, evaluation of relevant biomarkers and correlation with patient
response and genomic profile

                                   Copyright © 2018 Trovagene, Inc.                         28
Early PSA Response Observed with Addition
of Onvansertib to Daily Zytiga®
                                                                                  T ro v 5 3 _ 0 3 -0 1 3 _ P S A le v e ls

► 6 patients have completed 4 cycles (3                               50

  months) of treatment with onvansertib +                             40
                                                                                                                                                            E ffic a c y e n d p o in t
                                                                                                                                                            2 5 % o f b a s e lin e P S A ( C 1 D 1 )
  abiraterone

                                                 P S A ( n g /m L )
                                                                      30
► 2 of 6 patients had observed declines in                                                                                                                   CT scan at end of 12 weeks
  PSA levels after dosing with onvansertib                            20
                                                                                                                                                             (efficacy endpoint) indicates
                                                                                                                                                             ~30% tumor shrinkage
► To date, 1 patient has achieved the                                 10

  efficacy endpoint of disease stabilization
  based on PSA levels (primary endpoint)                               0

                                                                              0

                                                                                      2

                                                                                           -6

                                                                                                    1

                                                                                                            8

                                                                                                                    1

                                                                                                                            8

                                                                                                                                    1

                                                                                                                                            1

                                                                                                                                                    1
                                                                           -6

                                                                                  -3

                                                                                                  D

                                                                                                          D

                                                                                                                  D

                                                                                                                          D

                                                                                                                                  D

                                                                                                                                          D

                                                                                                                                                  D
                                                                                          y

                                                                                                1

                                                                                                        1

                                                                                                                2

                                                                                                                        2

                                                                                                                                3

                                                                                                                                        4

                                                                                                                                                5
                                                                          y

                                                                                  y

                                                                                       a

                                                                                              C

                                                                                                      C

                                                                                                              C

                                                                                                                      C

                                                                                                                              C

                                                                                                                                      C

                                                                                                                                              C
                                                                      a

                                                                              a

                                                                                      D
                                                                      D

                                                                              D
                                                                                          Day 1                                         Day 85          Efficacy evaluation at Day 85
                                                                                      C TCs ARV7+

                                                                           D a y -6 is th e s c r e e n in g P S A v a lu e .
                                                                                                                          Abiraterone +
                                                                                  Abiraterone
                                                                                                                           Onvansertib

► PSA trajectory in patient achieving primary efficacy endpoint changed from 100% increase
  (16.05ng/ml to 34.23 ng/ml) in the 60 days prior to adding Onvansertib to only an 8.4% increase
  during 84 days on treatment
► Tumor assessed at Cycle1 Day 1 as a variant known as AR-V7, considered an aggressive tumor
  that is resistant to anti-androgen therapy

                                       Copyright © 2018 Trovagene, Inc.                                                                                                                                 29
Colorectal Cancer: Unmet need in mCRC

► 140K new cases of CRC in 2018 with 64.5% 5 year
  survival1
   – ~51K deaths per year from mCRC1
► Tumor biomarkers drive therapy decisions for 1st line                                                                            Colorectal Cancer
  mCRC therapy2
  – ~50% mCRC is RAS mutant (Kras)
  – Targeted therapies exclude patients with RAS
    mutations
► Large unmet need in RAS mutant CRC2
  – No targeted therapies are available for RAS mutant
     CRC
  – Standard-of-care is chemotherapy (FOLFOX/FOLFIRI)
  – 2nd line therapies have ~5% response rate in metastatic
     CRC (mCRC)

 1https://seer.cancer.gov/statfacts/html/colorect.html; 2King et al, Frontline Strategies for Metastatic CRC, 2016, Amer J Hem/Onc; Loree&Kopetz, Recent Developments in
 treatment of mCRC, 2017, Ther Adv Med Onc;

                                                                   Copyright © 2018 Trovagene, Inc.                                                                        30
Onvansertib: Synergy in Combination with
Irinotecan (FOLFIRI)
► Combination of Onvansertib with                                                          Vehicle

  Irinotecan significantly reduces tumor                                                   Onvansertib 45 mg/kg
                                                                                           Onvansertib 60 mg/kg
  growth compared to either drug alone                                                     Irinotecan 45 mg/kg
                                                                                           Irinotecan 45 mg/kg +
                                                                                           Onvansertib 45 mg/kg
► In 3 independent models tested,
  Onvansertib induced maximal tumor
  regression of ~84% compared to vehicle

                                                                                         Wild Type                 Mutated
► Kras mutation is a biomarker for
  Onvansertib sensitivity

► KRAS mutated NIH3T3 cells showed
  higher sensitivity to Onvansertib compared
  to KRAS wild-type (WT) cells1
 1   Investigator Brochure, Data-on-file, Trovagene

                                                      Copyright © 2018 Trovagene, Inc.                                       31
Planned Phase 1b/2 Clinical Trial in mCRC

Onvansertib in Combination with FOLFIRI + Avastin for Second-Line Treatment of
         Metastatic Colorectal Cancer in Patients with a Kras Mutation

Phase 1b: Dose escalation to assess safety and identify recommended Phase 2 dose

                                                                     18 mg/m2
                                    15 mg/m2
                  12 mg/m2

► Administered orally, once daily on days 1-5 every 14-days (2 courses per 28-day cycle)

Phase 2: Assess safety and preliminary antitumor activity

► Efficacy Primary Endpoint: Objective response rate (ORR) in patients who receive at
  least 1 cycle (2 courses) of Onvansertib in combination with FOLFIRI and bevacizumab

► Efficacy Secondary Endpoint: Preliminary efficacy defined as complete response (CR)
  plus partial response (PR) plus stable disease (SD)

                                  Copyright © 2018 Trovagene, Inc.                         32
Key Inflection Points – Q2’19 – Q1’20

     Clinical
                                  Q2’19                          Q3’19                           Q4’19                      Q1’20
   Development
Acute Myeloid            ü AACR Phase 1b Data          ü ESMO Phase 2 Data               ü ESH Phase 2 Data         ü MDS initial safety and
Leukemia (AML)             Presentation (4/1)            Presentation (9/27)               Presentation (10/24)       efficacy data readout

                         ü FDA Meeting Phase 2         ü MDS – Investigator              ü ASH Phase 2 Data         ü Phase 2 AML trial
                           AML and biomarker             Initiated trial enrolling         Presentation (12/7)        data readout
Myelodysplastic
                           plans (4/8)
Syndrome (MDS) –
Investigator Initiated
                         ü Phase 2 AML trial
                           enrolling (6/6)

metastatic               ü AACR Data                   ü Asian-Pacific Prostate          ü EMUC Conference          ü ASCO-GU Phase 1b
Castration-Resistant       Presentation (4/2)            Cancer Conference                 presentation of safety     safety and efficacy
Prostate Cancer                                          Presentation (8/24)               and preliminary            data (2/13)
(mCRPC                   ü Arm B – 14-day                                                  efficacy from 14-day
                           schedule enrolling          ü ESMO Data                         dosing schedule
                           (4/25)                        Presentation (9/27)               (11/14-17)

metastatic Colorectal    ü Sites activated and         ü Clinical collaboration          ü Gastrointestinal         ü ASCO-GI Phase 2
Cancer (mCRC)              enrolling patients (5/1)      with large-cap biotech            Oncology Conference        efficacy data (1/23-25)
                                                                                           (10/10-11) Preliminary
                                                                                           Phase 1b safety and
                                                                                           efficacy data

                                                      Copyright © 2018 Trovagene, Inc.                                                      33
Thank You

                        For additional information please
                        contact: ir@trovagene.com

 Copyright © 2018 Trovagene, Inc.                           34
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