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 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
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 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
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
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
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
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
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. 10Onvansertib: First-in-Class, 3rd Generation
PLK1 with Best-in-Class Attributes
Copyright © 2018 Trovagene, Inc. 11Onvansertib: 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. 12PLK1: 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. 13Onvansertib: 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. 14Onvansertib 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. 15Onvansertib: 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. 16Clinical Trial Roadmap
Acute Myeloid Leukemia (AML)
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Colorectal Cancer (mCRC)
Copyright © 2018 Trovagene, Inc. 17Clinical 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. 18Acute 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. 19Onvansertib 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. 20Ongoing 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. 21Anti-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. 22Patient 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. 23PLK1 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. 24PLK1 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
t
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. 25Simple 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. 26Metastatic 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. 27Ongoing 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. 28Early 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. 29Colorectal 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. 30Onvansertib: 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. 31Planned 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. 32Key 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
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