A Cancer-Selective Gene Therapy Company - No One Should Die Of CancerTM - Jefferies
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No One Should Die Of CancerTM A Cancer-Selective Gene Therapy Company
Forward-Looking Statements
This presentation contains forward-looking statements about Tocagen Inc. Words such as “believes,” “anticipates,” “plans,” “expects,” “indicates,” “will,” “should,” “intends,”
“potential,” “suggests,” “assuming,” “designed” and similar expressions are intended to identify forward‐looking statements. These statements are based on the Company‘s
current beliefs and expectations. These forward‐looking statements include statements regarding: the success, cost, timing and potential indications of Tocagen’s product
development activities and clinical trials, including ongoing clinical trials of Toca 511 & Toca FC; Tocagen’s ability to obtain and maintain regulatory approval of product
candidates, including Toca 511 & Toca FC, in any of the indications for which it plans to develop them, and any related restrictions, limitations, and/or warnings in the label of
an approved product candidate; Tocagen’s ability to obtain funding for its operations, including funding necessary to complete the clinical trials of any of our product
candidates, including Toca 511 & Toca FC; Tocagen’s plans to research, develop and commercialize its product candidates, including Toca 511 & Toca FC; Tocagen’s ability to
attract and retain collaborators with development, regulatory and commercialization expertise; and regulatory developments in the United States and foreign countries.
Actual results may differ materially from those expressed or implied in this presentation due to the risk and uncertainties inherent in the company’s business, including,
without limitation, risks described in Tocagen’s filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward‐looking
statements, which speak only as of the date hereof, and Tocagen undertakes no obligation to revise or update this presentation to reflect events or circumstances after the
date hereof. Further information regarding these and other risks is included under the heading "Risk Factors" in Tocagen's most recent annual report on Form 10-K filed with
the Securities and Exchange Commission and its other reports, which are available from the SEC's website (www.sec.gov) and on Tocagen’s website under the heading
"Investors." All forward‐looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E
of the Private Securities Litigation Reform Act of 1995.
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Tocagen At-A-Glance
• San Diego, California biotechnology company
with ~85 employees
• Founded by pioneers of gene therapy
• Vision: No One Should Die Of Cancer
• Core technology is a differentiated retroviral
replicating vector (RRV) platform
Lead program in fully-enrolled Phase 3 trial under FDA Breakthrough Therapy and EMA PRIME designations
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Cancer-Selective Gene Therapy is in Our Name…TO CAncer GENe
DISCOVER DEVELOP COMMERCIALIZE
Leaders in Retroviral Vector Technology
• Leverage core capabilities in gene therapy • Toca 5 trial continues to final analysis • Commercial launch planning in US
• Technology platforms drive pipeline • NRG ndGBM trial activation in progress • Consider partners in ex-US geographies
• Toca 511 & Toca FC lead product regimen • Solid tumor expansion opportunities • Initial focus on brain cancer
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Retroviral Replicating Vector (RRV) Gene Therapy Platform
Selective Infection, Spread and Persistence in Cancer Cells
RRVs Infect Immune Deficient Cancer Cells But Not Does Not Initially Activate Immune System,
Normal Cells With Intact Immune Systems Enabling Viral Spread
Brain tumor with RRV
stained brown
(infected)
Normal brain cells
not stained brown
(uninfected)
Cancer cell interferon pathway genetic defects
reduce anti-retroviral resistance Non-lytic RRV budding from infected cell
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RRV Platform Has the Potential to Deliver a Variety of Therapeutic Genes
Non-Lytic Virus Infects and Persists Selectively in Cancer Cells
Cytosine deaminase (Toca 511) with prodrug (Toca FC)
Enzymes Thymidine kinase
Purine nucleoside phosphorylase
scFv ab αPD-L1
Immune
OX40L
Agonists
siRNA Anti-PD-L1
IL-2
Cytokines IL-12
IL-15
Gene Combos GMCSF + cytosine deaminase
6 Jefferies Healthcare Conference – June 2019
7 Jefferies Healthcare Conference – June 2019
Lead Program - Toca 511 & Toca FC
Immune Activation Via the Tumor Microenvironment
1 2 3
Gamma retrovirus Toca 511 Toca FC prodrug locally converts to 5-FU also eliminates
selectively infects tumor, persists 5-FU chemotherapeutic within the immunosuppressive myeloid
and spreads through tumor while tumor, killing cancer cells and cells (MDSCs and TAMs),
delivering the CD gene resulting in activation of antigen activating antitumor immunity
presenting cells and T cell priming
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Toca 511 & 5-FC
Activates a Durable Anti-Cancer Immune Response
Pre-Clinical Evidence of Durable Immune Activation ` “Cured” Mice Reject Re-Challenge of
Same Tumor in Flank
CONTROL
IMMUNE
DEFICIENT
IMMUNE
COMPETENT T Cells From “Cured” Mice Increase
Adapted from Hiraoka et al., Neuro-Oncol. 2017.
Survival in Adoptive Transfer Model
Locally, within tumor microenvironment, Toca 511 & Toca FC alter immune profile
• Increased T cell immune infiltrates in tumor (COLD → HOT)
• Immune effects are CD4 & CD8 T cell-dependent and correlate with immune-
suppressive myeloid cells depletion
Adapted from Mitchell et al., Neuro-Oncol. 2017 and
Hiraoka et al., Neuro-Oncol. 2017.
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Complete Response (CR) in a Patient with Progressive GBM, IDH1 wt
Alive with CR
> 38 months
CR by independent Radiology Review, Macdonald criteria
Toca FC cycle is every 6 weeks
Adapted from Cloughesy et al. Neuro-Oncol, 2018.
10 Jefferies Healthcare Conference – June 2019Phase 1 Resection Study:
Long-Term Survival in Higher Dose Cohort (Toca 5 eligible patients)
All Responses are Durable Complete Responses & Associated with Long Term Survival
Toca 511-11-01 Overall Survival and the Best Response
1st/2nd Recurrence, No prior bevacizumab,Toca 5 Pivotal Phase 3 Trial – Enrollment Completed
One of the Largest Trials in rHGG with Enrollment of 403 Patients
Eligibility
Toca 511* Toca FC** • GBM or AA
Surgery • First and 2nd recurrence
And 1:1
• Tumor ≤ 5cm
Randomization
N=403 Chemotherapy** Biomarker Monitoring
(lomustine or temozolomide) or • Lymphocytes
Stratify by IDH1 mutation bevacizumab • Immune activation markers
status, KPS (70-80 vs. 90-100)
and geographic region * Administered at time of surgery • Cytokines
** Begins 6 weeks post-surgery • Tumor-infiltrating lymphocytes
• Immune-suppressive myeloid cells
ClinicalTrials.gov Identifier: NCT02414165
12 Jefferies Healthcare Conference – June 2019Toca 5 Pivotal Phase 3 Trial – Final Analysis Projected Q4, 2019
Final Analysis of Toca 5 Trial Represents Culmination of Statistical Plan
Toca 5 Trial - Statistical Overview
Interim Analysis at 75% of events – reported May 21, 2019
Patients: 403 randomized. Stats based on 257 events. • Alpha spend of 0.0162
• Efficacy assessment focused only on primary endpoint,
Primary endpoint: Overall Survival
safety assessment involved all Toca 5 patients
Secondary endpoints: • IDMC recommendation: Continue without modification
Durable Response Rate (PR/CR ≥ 24 weeks)
Durable clinical benefit rate (PR/CR ≥ 24 weeks, SD ≥ 18 mos) Final Analysis at 257 events – projected Q4, 2019
Duration of durable response • Higher alpha spend of 0.0307
Overall survival at 12 months • Longer follow-up helps capture immunotherapy “tail of survival”
HR, Power: 0.685, 85% particularly for those randomized in the 2nd enrollment period
• Efficacy assessment includes primary and secondary endpoints
Treatment effect versus SoC (months):
4.5 months (14.3 vs 9.8)
13 Jefferies Healthcare Conference – June 2019Key Differentiators for Toca 511 & Toca FC in Brain Cancer 14 Jefferies Healthcare Conference – June 2019
Launch Planning Ongoing
Attractive Opportunity Driven by a Small Specialty Team
~8,500 Eligible Patients Chronic RX Opportunity Small Specialty Sales Team ofTocagen Pipeline
Candidate Indication Discovery Preclinical Phase 1 Phase 2 Phase 3
Recurrent high grade glioma Final analysis projected in Q4, 2019
Toca 511 Newly diagnosed
& Toca FC glioblastoma (in collaboration NRG-BN006* Phase 2/3 trial initiation
expected by end of 2019
with NRG Oncology)
Advanced solid tumors
(CRC, pancreatic, sarcoma & Data updates
anticipated in Q4 2019
lung)
Multiple
RRV-gene Oncology
candidates
*NRG Oncology is the study sponsor; Funded by the National Cancer Institute.
16 Jefferies Healthcare Conference – June 2019Financial Position and Near-Term Catalysts
Cash, cash equivalents and marketable securities are $80.1M at March 31, 2019
Estimated cash burn in 2019 totals ~$65M with $16.5M reported for Q1
Toca 5 interim analysis expected in the second quarter of 2019
• Toca 5 final analysis planned for the fourth quarter of 2019
• Prepare to initiate a rolling Toca 511 & Toca FC biologics license application in
recurrent high grade glioma
2019 • Build U.S. commercial team for potential launch of Toca 511 & Toca FC
• NRG Oncology to initiate NRG-BN006 clinical trial evaluating Toca 511 & Toca FC
in newly diagnosed GBM by year-end 2019
• Report updated Toca 6 safety and immune activity data in advanced solid tumors
17 Jefferies Healthcare Conference – June 2019Looking Forward to Achieving More Milestone Moments…
Thank you to all of the patients and families who have supported our work.
Financial support also provided by:
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