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Forward-Looking Statements This presentation contains forward-looking statements about Tocagen Inc. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "should," "intends," "potential," "sug

Key Takeaway: 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

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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 financial report 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.
Tocagen At-A-Glance San Diego,
California biotechnology company with ~75 employees Founded in 2007 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
pivotal Phase 3 trial under FDA Breakthrough Therapy Designation and EMA PRIME Designation
Executive Team with a Proven Track
Record Marty J. Duvall Chief Executive Officer Mark Foletta EVP & Chief Financial Officer Lori Kunkel, M.D. Acting Chief Medical Officer Doug Jolly, Ph.D. Founder, EVP, Research and Pharm Development Harry Gruber, M.D. Founder, President Science
Cancer-Selective Gene Therapy is in Our
Name TO CAncer GENe EXPLORE EXECUTE Leverage Phase 1 data: CRs and survival Move Toca 511 & Toca FC to front-line HGG Advance opportunity in key geographies EXPAND BTD and PRIME designations in rHGG Accrual to Toca 5 Phase 3 study in rHGG
Commercial launch planning in US Achieve POC in other solid tumors with Toca 6 Investigate new opportunities using RRV platform
Retroviral Replicating Vector (RRV)
Gene Therapy Platform Selective Infection, Spread and Persistence in Cancer Cells RRVs Infect Immune Deficient Cancer Cells But Not Normal Cells With Intact Immune Systems Cancer cell interferon pathway genetic defects reduce anti-retroviral
resistance Does Not Initially Activate Immune System, Enabling Viral Spread Brain tumor with RRV stained brown (infected) Normal brain cells not stained brown (uninfected) Non-lytic RRV budding from infected cell
RRV Platform Has the Potential to
Deliver a Variety of Therapeutic Genes IL-2 IL-12 IL-15 PD-L1 (Toca 521) Cytosine deaminase (Toca 511) with prodrug (Toca FC) Thymidine kinase Purine nucleoside phosphorylase Anti-PD-L1 OX40L scFv ab Cytokines Enzymes siRNA Immune Agonists
GMCSF + cytosine deaminase Gene Combos Non-Lytic Virus Infects and Persists Selectively in Cancer Cells
Tocagen Pipeline Candidate Indication
Discovery Preclinical Phase 1 Phase 2 Phase 3 Toca 511 & Toca FC Recurrent high grade glioma Advanced solid tumors (CRC, Melanoma, Pancreatic, Lung & Breast) Newly diagnosed glioblastoma (in collaboration with NRG Oncology) Toca 521 Oncology
RRV-Anti-PD-L1 2nd interim analysis projected 1H 2019 and final analysis by end-2019 Data updates anticipated in 2019 Advancing into IND-enabling studies 2H 2018 First patient enrolled expected in 2H 2019 NRG-BN006
Lead Program Toca 511 & Toca FC
Lead Program - Toca 511 & Toca
FC Immune Activation Via the Tumor Microenvironment 5-FU also eliminates immunosuppressive myeloid cells (MDSCs and TAMs), activating antitumor immunity Gamma retrovirus Toca 511 selectively infects tumor, persists and spreads through tumor while
delivering the CD gene 1 2 3 Toca FC prodrug locally converts to 5-FU chemotherapeutic within the tumor, killing cancer cells and resulting in activation of antigen presenting cells and T cell priming
Toca 511 & 5-FC Activates a
Durable Anti-Cancer Immune Response 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 T Cells From "Cured" Mice Increase Survival in Adoptive Transfer Model "Cured" Mice Reject Re-Challenge of Same Tumor in Flank IMMUNE COMPETENT IMMUNE DEFICIENT CONTROL
Adapted from Hiraoka et al., Neuro-Oncol. 2017. Pre-Clinical Evidence of Durable Immune Activation ` Adapted from Mitchell et al., Neuro-Oncol. 2017 and Hiraoka et al., Neuro-Oncol. 2017.
Toca 511 & 5-FC Activate Immune
System in Tumor Micro-Environment Preclinical Mouse Glioma Model TAM: tumor associated macrophages; MDSC: myeloid derived suppressor cells Increase in immune activating lymphoid cells Decrease in immune suppressive myeloid cells Mitchell et al.
Neuro-Oncology, 2017 T-regs not significantly impacted
Executing in recurrent High Grade
Recurrent High Grade Glioma (rHGG)
Newly diagnosed GBM Standard of care includes surgery, radiation, temozolomide mOS from initial diagnosis to death ~16 months Limited treatment options Development in HGG: A Deadly and Aggressive Disease Newly diagnosed GBM Recurrent GBM or AA Brain
tumor by MRI Surgery, radiation, temozolomide Recurrence by MRI Approved drugs and or trials (e.g. Toca 5) Hospice 8 months 8 months Recurrent HGG Treatments include bevacizumab, lomustine, carmustine wafer Similar mOS for surgical and non-surgical
studies (pooled study analyses reported by Clarke Neuro-Oncol 2011 and Gorlia EJC 2012). NCCN guidelines recommend consideration of clinical trials
Key Differentiators for Toca 511
& Toca FC in Brain Cancer Preclinical MOA, CR's, OS data supported BTD and PRIME designations and peer-reviewed publications Notorious blood brain barrier mitigated with local Toca 511 delivery and precedent for 5-FC to treat brain fungus
Multiple mechanisms support robust anti-cancer activity Consistent trial design from Phase 1 to Phase 3 (Toca 5)
Phase 1 Experience in 127 rHGG
Patients RESECTION INTRATUMORAL INTRAVENOUS Favorable safety profile Increased survival vs historic benchmarks 6 durable CRs - all remain alive (up to 4.8 years and counting) Phase 1 patients at Toca 5 dose and entry criteria^ 5/23 CRs 43.5%
clinical benefit rate mOS of 14.4 months 26.1% survival at 3 years Resection Study - Data Highlights* Injection into cavity wall after tumor debulking n=56 Direct injection into the brain tumor n=54 Injection IV prior to resection and into
cavity wall at resection n=17 *Efficacy evaluable patients (n=53). ^ n=23. Data cutoff date December 20, 2017. NOTE: Survival across all Phase 1 trials ranged from 13.6 - 14.4 months at high doses of Toca 511.
Phase 1 Resection Study -
Patients had Advanced Disease Population All Patients N=56 Toca 5 Dose and Entry Criteria Subset N=23 Median Age (range) 58 (24-75) 58 (24-70) n (%) n (%) Male 43 (77) 20 (87) Karnofsky Performance Score 70-80 90-100 17 (30) 39 (70) 5 (22) 18 (78)
Initial Tumor Histology GBM Anaplastic Astrocytoma Other gliomas 45 (80) 6 (11) 5 (9) 19 (83) 4 (17) N/A Number of Recurrences Including Current 1 2 3 or greater 28 (50) 14 (25) 14 (25) 19 (83) 4 (17) N/A Cloughesy et al., STM, June 2016
Data cutoff date December 20th, 2017. Cloughesy et al. Neuro-Oncol, 2018.
Adverse Events Related to Toca 511
and Toca FC Data Pooled Across Three Phase 1 Studies Treatment-Related AEs Toca 511 & Toca FC N=127 Grade 1/2 Grade 3/4 n (%) n (%) Any treatment-related event 62 (48.8) 11 (8.7) Treatment-related event 5% patients Fatigue 37 (29.1) 1
(<1) Diarrhoea 17 (13.3) 1 (<1) Nausea 14 (11.0) 0 Headache 8 (6.2) 1 (<1) Decreased appetite 7 (5.5) 0 Data cutoff 04Jan2018; excludes data from continuation study Low Incidence of Grade 3/4 Treatment-Related AEs Low Incidence of
Treatment-Related SAEs AE leading to death Toca 511 & Toca FC N=127 n (%) Any AE leading to death 3 (2.4) Brain herniation 1 (<1) Intracranial tumor hemorrhage 1 (<1) Hemorrhagic stroke 1 (<1) Treatment-Related SAEs Toca 511 & Toca
FC N=127 Grade 1/2 Grade 3/4 n (%) n (%) Any treatment-related event 1 (<1) 8 (6.3) Treatment-related event 1% patients Vasogenic cerebral oedema1 0 2 (1.6) 1 Both SAEs were Grade 3; no Grade 4 SAE
Phase 1 Resection Study: Survival
Exceeds Historical Data Population Toca 511 & Toca FC Resection Study Median Overall Survival Months1 Historical Data in Recurrent Disease Recurrent High Grade Glioma 12.4 (n=43) 7.2 (n=110)2 Recurrent High Grade Glioma and higher doses 13.2
(n=30) 7.2 (n=110)2 Higher doses and Toca 5 entry criteria3 14.4 (n=23) 8.5 (n=437)4 Glioblastoma at 1st or 2nd recurrence 13.6 (n=27) 7.1 (n=84)5 1 Data cutoff date August 15th 2017 2 Carmustine wafer. Brem et. al., Lancet 345: 1008-1012, 1995 3
Higher doses (cohorts 4-7a) and 1st and 2nd recurrence, no prior Avastin in rHGG, tumor not > 5cm 4 Estimate based on weighted average of lomustine (Batchelor 2013, Taal 2014, Wick 2010, EORTC 2610185: n=352) and Avastin historical controls
(n=85) and assumed percentage of enrollment 5 Wick 2010
Phase 1 Resection Study: All 6
Responders Received Higher Toca 511 Dose and are Durable Complete Responders Response Category1 All Efficacy Evaluable Patients N=532 Higher Doses and Toca 5 Entry Criteria Subset3 N=23 Durable response rate (CR or PR 24 weeks), n (%) 6
(11.3); All CRs 5 (21.7); All CRs Median duration of durable response Not reached (median follow-up 36.5 mos) Not reached (median follow-up 37.4 mos) Stable disease, n (%) 12 (22.6) 5 (21.7) Progressive disease, n (%) 35 (66.0) 13 (56.6) Clinical
Benefit Rate, n (%) (CR, PR, and SD 8 wks) 16 (30.2) 10 (43.5) response duration compares favorably: Bev ~4.2 mos Lomustine ~6.2 mos Wick, JCO 2010; Avastin PI 1 Includes MRI by independent radiology review and clinical data. Data cutoff
date 20Dec2017. 2 Of 56 safety evaluable patients, 53 patients who received Toca 511 & Toca FC are efficacy evaluable and of these 2 were not evaluable for response. Includes 4 IDH wildtype and 2 IDH mutant patients. All 6 responders were in the
higher dose cohorts and include 1 patient who received the Toca regimen in combination with bevacizumab. 3 Higher doses (cohorts 4-7a) and meet Toca 5 entry criteria of 1st and 2nd recurrence, no prior bevacizumab in rAA or rGBM, tumor not > 5cm.
Toca 511-11-01 Overall Survival and
the Best Response 1st/2nd Recurrence, No prior bevacizumab, <=5cm, Higher Dose Cohorts (N=23) Phase 1 Resection Study: Long-Term Survival in Higher Dose Cohort All Responses are Durable Complete Responses & Associated with Long Term Survival
AA, IDH1 mt GBM, IDH1 wt GBM, NA GBM, IDH1 wt AA, IDH1 mt GBM, IDH1 wt mOS Toca 511 & Toca FC = 14.4 months Responses occurred gradually over time ~ 6-19 months, consistent with immunologic response All Responders alive 3.2+ years to 4.8+ years,
so far CRs received no additional brain cancer treatment after entering trial Each CR occurred in a different clinical site and all are confirmed Median DoR not reached with median follow up of 37.4 months Progressive Disease Stable Disease Partial
Response Complete Response Alive at Last Contact KEY
Final Results from Phase 1 Study of
Toca 511 & Toca FC in rHGG Extended survival in patients who meet dose/eligibility criteria for Phase 3 Toca 5 Trial Cloughesy et al. JSGCT, 2018 Data cut off 20 Dec 2017 Estimated Probability of Survival (KM) Time (Months) + Censored Numbers at
Risk: Median follow-up of 47.8 months Median survival 14.4 months 3-year survival rate 26% Proportion of Long-Term Survivors Consistent With Other IO Therapies 23 23 22 15 9 8 8 8 7 6 5 5 2 2 1 0
Complete Response in a Patient with
Progressive GBM, IDH1 wt Adapted from Cloughesy et al. Neuro-Oncol, 2018. CR by independent Radiology Review, Macdonald criteria Toca FC cycle is every 6 weeks Alive with CR > 38 months
Toca 5 Pivotal Phase 3 Trial -
Patient Follow-up Ongoing One of the largest trials in rHGG with enrollment completed Sept 2018 Primary Endpoint: Overall Survival Exploratory Secondary Endpoint: Durable Response Rate Eligibility GBM or AA First and 2nd recurrence Tumor 5cm
ClinicalTrials.gov Identifier: NCT02414165 * Administered at time of surgery ** Begins 6 weeks post-surgery Surgery And Randomization N=380 Toca 511* Toca FC** Chemotherapy** (lomustine or temozolomide) or bevacizumab Stratify by IDH1 mutation
status, KPS (70-80 vs. 90-100) and geographic region 1:1 Biomarker Monitoring Lymphocytes Immune activation markers Cytokines Tumor-infiltrating lymphocytes Immune-suppressive myeloid cells
Toca 5 Pivotal Phase 3 Trial -
Patient Follow-up Ongoing Statistical Plan Set for Two Analyses of Overall Survival by End-2019 Toca 5 Trial - Statistical Overview Patients: 380 Primary endpoint: Overall Survival MOA- Driven exploratory endpoint: Durable Response Rate (PR/CR
24 weeks) HR, Power: 0.685, 85% Treatment effect versus SoC (months): 4.5 months (14.3 vs 9.8) 1st Interim Analysis at 50% of events - completed August 2018 Low alpha spend of 0.0031 IDMC recommendation - "Continue without
Modification" (as expected) 2nd Interim Analysis at 75% of events - projected 1st Half 2019 Higher alpha spend of 0.0162 Successful outcome may trigger rolling BLA filing Final Analysis at 257 events - projected year-end 2019
Higher alpha spend of 0.0307 Longer patient follow-up helps capture immunotherapy "tail of survival"
Launch Planning Ongoing Significant
Revenue Opportunity Driven by a Small Specialty Team Commercial and medical affairs footprint to target ~80 high volume sites, majority of which have participated in Toca 511 & Toca FC development Over 8,000 Eligible Patients Small Specialty
Sales Team of <40 Chronic RX Opportunity Virus Injection Oral Tablets Mohamed Ladha VP, Head of Commercial Tocagen Pricing commensurate with value delivered and expected to be in line with reference immunotherapy drugs Recurrent High Grade Glioma
continues to be a disease of high unmet need with very few treatment options - provides opportunity to make major impact
Expanding to realize potential of
Newly Diagnosed HGG Opportunity Toca
511 injection at time of regular surgical resection Standard resection recovery time allows for viral spread Potential amplification of effect of temozolomide + radiation Newly diagnosed GBM Recurrent GBM or AA Brain tumor by MRI Stupp Regimen:
Surgery, radiation, temozolomide Recurrence by MRI Approved drugs and or trials (e.g. Toca 5) Hospice 8 months 8 months Pre-clinical data demonstrate Toca regimen synergistic with chemo and radiation ~ ~ Toca 511 & Toca FC Potential
Last updated: Dec 12, 2018