Developing Targeted Therapeutics - Providing Safe and Effective New Treatment Options for Patients Most Likely to Respond
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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
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 chemo
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
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
Licensed Global Development & Commercialization
Rights to Onvansertib (PLK1 Inhibitor) from NMS
► Largest oncology research and development
company in Italy
► Developed anthracycline class of drugs
(doxorubicin)
► 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
Copyright © 2018 Trovagene, Inc. 5
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
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. 7
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 + Bevacizumab
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. 8
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
Copyright © 2018 Trovagene, Inc. 9
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. 10Onvansertib: First-in-Class, 3rd Generation
PLK1 with Best-in-Class Attributes
Copyright © 2018 Trovagene, Inc. 11Onvansertib: 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. 12Onvansertib 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. 13Onvansertib: 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)
Leukemias
Camptosar® Onvansertib 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
Copyright © 2018 Trovagene, Inc. 14Onvansertib Clinical Development Roadmap
Small-Cell Lung
Ovarian
Breast
Pancreatic
Prostate
Colorectal
Acute Myeloid
Leukemia
Copyright © 2018 Trovagene, Inc. 15Acute 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. 16Onvansertib Positioning in AML
Patient Selection Algorithm
Responders Consolidation
50-70% Treatment
Eligible for
Induction
Treatment
~11,000
AML Relapsed
Diagnosis &
18,3761 Refractory
cases/year 30-50%
3,300 to
5,500
Ineligible
for Onvansertib in combination with
Induction standard-of care chemotherapy
Treatment and/or targeted therapeutics2
~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. 17Ongoing 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
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. 18Phase 1b/2 Trial Anti-Leukemic Activity
► Phase 1b objective is to assess the safety and tolerability of Onvansertib in combination with
standard-of-care chemotherapy
► Of the 19 patients evaluable for safety, 12 patients had an evaluable bone marrow biopsy to
assess anti-leukemic activity based on criteria from the 2017 ELN recommendations1
► Of the 12 patients evaluated for preliminary anti-leukemic activity, 1 patient had a PR, 9 patients
had SD and 2 patients had PD2
%% B M Marrow
Bone b la s t rBlast
e d u cReduction
t io n fr o mfrom
b a sBaseline
e lin e
1000
P r o g r e s s iv e d is e a s e
900
% c h a n g e f r o m b a s e lin e
S t a b le d is e a s e
P a r t ia l r e s p o n s e
800
150
100
50
0
-50
-100
-150
1 Dohner et al., Blood, 2017. 2 American Society of Hematology (ASH) Conference Poster Presentation - December 2018
Copyright © 2018 Trovagene, Inc. 19Patient Case Overview1
► 75 year-old male, diagnosed with AML in 2009 and treated with induction chemotherapy; relapsed
in March 2018 and entered trial in April 2018 on Onvansertib + Decitabine
► Onvansertib entry dose of 12 mg/m2 and was increased to 18 mg/m2 at cycle 6
► Patient reached PR as of the end of cycle 4 / beginning of cycle 5 and is currently on cycle 8 of
treatment
► % bone marrow blast decreased from 94% (at screening) to 2% (cycle 7) and circulating blasts
decreased from 92% (C1D1) to 4% (C7D15)
Patient 07-009
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
75
C irc u la tin g b la s ts
% o f le u k o c y t e s
B o n e m a rro w b la s ts
50
25
0
1 5 22 1 5 22 1 5 22 1 5 22 1 5 22 1 5 22 1 5 22
D a y s o f c y c le
3 American Society of Hematology (ASH) Conference Poster Presentation - December 2018
Copyright © 2018 Trovagene, Inc. 20PLK1 Inhibition Can Be Monitored Through
pTCTP Status
► pTCTP as a marker of PLK1 activity:
– PLK1 phosphorylates the translational control tumor protein (TCTP) on
serine 461
– pTCTP was identified as a specific marker for PLK1 activity in in-vivo
preclinical models1
No Onvansertib Onvansertib
TCTP Onvansertib TCTP
P
P
PLK1
PLK1
P
TCTP TCTP
1 Cucchi et al., Anticancer Res., 2010
Copyright © 2018 Trovagene, Inc. 21Simple 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
Onvansertib
Control vial, - +
no Onvansertib Target pTCTP
Engagement
Assess target Eligible Subject TCTP
AML subject:
obtain 2 vials engagement by
of blood Onvansertib Onvansertib
- +
Treatment vial, NO Target pTCTP
contains Onvansertib Engagement
Non-Eligible Subject TCTP
Copyright © 2018 Trovagene, Inc. 22PLK1 Inhibition by Onvansertib is Correlated
with Higher Response to Treatment1
► The 5 patients with target engagement showed a decrease in circulating blasts of ≥50% on the
last time point recorded compared to baseline
► 3 of 5 patients with target engagement had a decrease of ≥50% in their last BM biopsy compared
to baseline
► Decreases in circulating and bone marrow blasts were significantly higher in patients with target
engagement compared to patients without target engagement
% Circulating
% C ir c u la t in g Blasts
b la s t s ininp aPatients
t ie n t s w itwith
h t a r gTarget
e t e n g a gEngagement
em ent %%Bone
B M bMarrow
la s t r e dBlast
u c t io n f r o m bfrom
Reduction a s e lin e
Baseline
Onvansertib 12mg/m2
1000
100 0 1 -0 0 2 N o T a rg e t E n g a g e m e n t
C y c le 1 C y c le 2
% c h a n g e fro m b a s e lin e
0 7 -0 0 9 900
T a rg e t E n g a g e m e n t
% C ir c u la t in g b la s t s
80 0 7 -0 1 1
800
Onvansertib 27mg/m2 150
60
0 8 -0 2 7 100
40 0 5 -0 3 0 50
0
20
-5 0
0 -1 0 0
1 5 8 15 22 1 5 8 15 22 -1 5 0
D a y s o f tre a tm e n t
3 American Society of Hematology (ASH) Conference Poster Presentation - December 2018
Copyright © 2018 Trovagene, Inc. 23Metastatic 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. 24Ongoing 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. 25Colorectal 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. 26Onvansertib: 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. 27Planned 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
24 mg/m2
18 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. 282019 Value Creating Milestones
ü Initiate mCRC Phase 1b/2 trial
ü Efficacy and safety data in AML, mCRPC
ü AACR Presentations in AML, mCRPC
ü Data Readouts (AML, mCRPC,
ü Complete enrollment of AML Phase 2 mCRC)
ü Complete enrollment of mCRPC Phase 2 ü Begin Enrolling Phase 2 mCRC
ü AML Companion Diagnostic ü AML – ASH Presentation
Q4’18 Q2 Q4
Q1 Q3
ü AML identify recommended Phase 2 dose ü Efficacy and safety data readouts
(RP2D) (AML and mCRPC)
ü Begin enrolling AML Phase 2 trial ü Assess dose escalation Phase 1b
mCRC trial and identify Phase 2 dose
ü mCRPC ASCO-GU Presentation
ü Efficacy and safety data readouts (AML and
mCRPC)
ü Formalize Japan Partnering Collaboration
Copyright © 2018 Trovagene, Inc. 29Thank You
For additional information please
contact: ir@trovagene.com
Copyright © 2018 Trovagene, Inc. 30You can also read
