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. 10
Onvansertib: First-in-Class, 3rd Generation PLK1 with Best-in-Class Attributes Copyright © 2018 Trovagene, Inc. 11
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. 12
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. 13
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) 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. 14
Onvansertib Clinical Development Roadmap Small-Cell Lung Ovarian Breast Pancreatic Prostate Colorectal Acute Myeloid Leukemia Copyright © 2018 Trovagene, Inc. 15
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. 16
Onvansertib 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. 17
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 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. 18
Phase 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. 19
Patient 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. 20
PLK1 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. 21
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 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. 22
PLK1 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. 23
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. 24
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. 25
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. 26
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. 27
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 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. 28
2019 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. 29
Thank You For additional information please contact: ir@trovagene.com Copyright © 2018 Trovagene, Inc. 30
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