toca-8k_20191122.htm

 

 

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

November 22, 2019

Date of Report (Date of earliest event reported)

Tocagen Inc.

(Exact name of registrant as specified in its charter)

 

Delaware

001-38052

26-1243872

(State or other jurisdiction

(Commission File Number)

(IRS Employer Identification No.)

of incorporation)

 

 

 

4242 Campus Point Court, Suite 500

San Diego, California

92121

(Address of principal executive offices)

(Zip Code)

Registrant’s telephone number, including area code: (858) 412-8400

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligations of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b–2 of the Securities Exchange Act of 1934 (§ 240.12b–2 of this chapter).

Emerging growth company

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading Symbol(s)

 

Name of each exchange on which registered

Common Stock, par value $0.001 per share

 

TOCA

 

The Nasdaq Global Select Market

 

 

 


 

Item 7.01 Regulation FD Disclosure.

 

Tocagen Inc. (the “Company”) has updated its corporate presentation that it uses when meeting with investors, analysts and others. A copy of the Company’s updated corporate presentation is attached as Exhibit 99.1 to this Current Report on Form 8-K.

 

The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1, is being furnished pursuant to Item 7.01 and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, and it shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or under the Exchange Act, whether made before or after the date hereof, except as expressly set forth by specific reference in such filing to this item of this report.

 

Item 8.01 Other Events.

 

Management and the Board of Directors of the Company have initiated a process to explore and review a range of strategic alternatives focused on maximizing stockholder value. The Company is exploring the potential for a company merger, asset sale or other strategic transactions.

 

The Company has engaged Ladenburg Thalmann & Co. Inc. to act as a strategic advisor for this process. There can be no assurance that this exploration of strategic alternatives will result in the Company entering or completing any transaction.  

 

Item 9.01Financial Statements and Exhibits.

(d) Exhibits.

 

Exhibit

Number

 

Description

99.1

 

Corporate Presentation.

 

 

Forward-Looking Statements

 

Statements contained in this report regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the Company’s focus on strategic alternatives, including the potential for merger, asset sale or other strategic transactions. Risks that contribute to the uncertain nature of the forward-looking statements include, but are not limited to, the Company’s ability to carry out its strategic alternatives plan and uncertainties regarding completing such merger, asset sale or other strategic transactions. These and other risks and uncertainties are described more fully under the caption “Risk Factors” and elsewhere in the Company’s filings and reports with the United States Securities and Exchange Commission. All forward-looking statements contained in this report speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

 

 

 

 

 


 

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

 

 

Tocagen Inc.

 

 

 

 

Date: November 22, 2019

 

 

By:

/s/ Mark Foletta

 

 

 

 

Mark Foletta

 

 

 

 

Chief Financial Officer

 

 

toca-ex991_7.pptx.htm

Slide 1

A Cancer-Selective Gene Therapy Company Exhibit 99.1

Slide 2

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 plans to research, develop and commercialize its product candidates.. 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.

Slide 3

Tocagen At-A-Glance San Diego, California biotechnology company Founded by pioneers of gene therapy Vision: No One Should Die Of Cancer Core technology is a differentiated retroviral replicating vector (RRV) platform Currently exploring strategic alternatives* *Tocagen has retained Ladenburg Thalmann & Co. to advise the Company

Slide 4

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 Brain tumor with RRV stained brown (infected) Normal brain cells not stained brown (uninfected) Does Not Initially Activate Immune System, Enabling Viral Spread Non-lytic RRV budding from infected cell

Slide 5

RRV Platform Has the Potential to Deliver a Variety of Therapeutic Genes IL-2 IL-12 IL-15 αPD-L1 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

Slide 6

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

Slide 7

Toca 511 & 5-FC Activates a Durable Anti-Cancer Immune Response in Preclinical Models 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 ` Adapted from Mitchell et al., Neuro-Oncol. 2017 and Hiraoka et al., Neuro-Oncol. 2017. IMMUNE COMPETENT IMMUNE DEFICIENT CONTROL Adapted from Hiraoka et al., Neuro-Oncol. 2017. Pre-Clinical Evidence of Durable Immune Activation

Slide 8

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 Cloughesy et al. JSGCT, 2018; Data cut off 20 Dec 2017

Slide 9

Toca 5 Phase 3 Trial in Recurrent High Grade Glioma One of the Largest Trials in rHGG with Enrollment of 403 Patients ClinicalTrials.gov Identifier: NCT02414165 * Administered at time of surgery ** Begins 6 weeks post-surgery Surgery And Randomization N=403 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 Primary endpoint (OS) not met: 11.1 months for Toca regimen versus 12.2 months for SOC (HR=1.06, p=0.6154) Secondary endpoints not met Pre-planned subgroup of patients at 2nd recurrence (N=60) showed a 57% risk reduction for death when treated with Toca 511 and Toca FC (21.82 months median OS compared to 11.14 months, HR=0.43, p=0.0162 for SOC)^ ^ This subgroup represented one of 26 pre-specified subgroups.

Slide 10

Toca 5 Primary Endpoint - Overall Survival Did Not Meet Statistical Significance Intention-to-treat (ITT) Nominal significance level for this analysis 0.0232 HR=1.06 (95%CI: 0.83, 1.35) p-value=0.6154 Median OS: Toca: 11.07 months SOC: 12.22 months Intention-To-Treat – Overall Survival

Slide 11

Secondary Endpoints Did Not Meet Statistical Significance Intention-to-Treat Population   Toca 511 and Toca FC arm (N=201)  SOC arm (N=202)  HR (95% CI) p-value Durable response rate (%) 5 (2.5) 9 (4.5) NA 0.4156 Durable clinical benefit rate (%) 5 (2.5) 9 (4.5) NA 0.4156 Duration of durable response (months) 11.17 6.93 0.59 (0.14, 2.56) 0.5161 OS-12 (%) 45.6 51.4 NA 0.2848

Slide 12

Toca Regimen Favored in 2nd Recurrence, AA, and IDH1mt Pre-Specified Subgroups - Forest Plot for Overall Survival Hazard Ratio Favoring Toca Favoring SOC Hazard Ratio (Toca vs. SOC) & 95% C.I. (Log Scale) P-values not adjusted for multiple settings 1 2 3

Slide 13

Overall Survival – Intention-To-Treat (ITT) IDH1mt Subgroup and AA Subgroup HR=0.64 (95%CI: 0.33, 1.24) p-value=0.1853 Median OS: Toca: 17.64 months SOC: 12.45 months Intention-To-Treat – IDH1mutant Intention-To-Treat – Anaplastic Astrocytoma (AA) HR=0.57 (95%CI: 0.28, 1.14) p-value=0.1057 Median OS: Toca: 16.39 months SOC: 11.99 months 1 2

Slide 14

Overall Survival (ITT) - Second Recurrence Subgroup Toca 511 & Toca FC Showed ~2X Median Survival over SOC Intention-To-Treat – Second Recurrence HR=0.43 (95%CI: 0.21, 0.87) p-value=0.0162 Median OS: Toca: 21.82 months SOC: 11.14 months   Toca 511 and Toca FC (N=28) Standard of Care (N=32) Total (N=60) KPS Category  70-80 8 (28.6%) 8 (25.0%) 16 (26.7%) 90-100 20 (71.4%) 24 (75.0%) 44 (73.3%) IDH Mutation Status  Present (Mutant) 8 (28.6%) 10 (31.3%) 18 (30.0%) Absent (Wild Type) 20 (71.4%) 22 (68.8%) 42 (70.0%) 1p/19q Co-Deletion Status  Present (Co-Deletion) 0 (0.0%) 0 (0.0%) 0 (0.0%) Absent (No-Co-Deletion) 28 (100.0%) 32 (100.0%) 60 (100.0%) Tumor Histology at Study Entry Anaplastic Astrocytoma (AA) 7 (11.7%)   6 (10.0%)  13 (21.7%)  Glioblastoma (GBM) 21 (35.0%) 26 (43.3%) 47 (78.3%) Total 28 (46.7%) 32 (53.3%) 60 (100.0%) MGMT Status Methylation 10 (16.7%)   9 (15.0%)  19 (31.7%)  Un-Methylated 18 (30.0%) 21 (35.0%) 39 (65.0%) Missing - 2 (3.3%) 2 (3.3%) Total 28 (46.7%) 30 (53.3%) 60 (100.0%) 3

Slide 15

Overall Survival – Second Recurrence Survival By Tumor Histology (post hoc analysis) Glioblastoma Multiforme (GBM) Anaplastic Astrocytoma (AA) HR=0.73 (95%CI: 0.35, 1.53) p-value=0.4051 Median OS: Toca: 13.17 months SOC: 11.17 months HR=NE (95%CI: NE, NE) p-value=0.0007 Median OS: Toca: NR SOC: 9.07 months NE not estimable NR not reached

Slide 16

Overall Survival – Second Recurrence Survival by IDH1 Mutation Status (post hoc analysis) HR=0.68 (95% CI: 0.30, 1.52) p-value=0.3456 Median OS: Toca: 14.85 months SOC: 11.17 months HR=0.14 (95% CI: 0.03, 0.69) p-value=0.0063 Median OS: Toca: NR (Not Reached) SOC: 10.87 months NR=Not Reached IDH1 wild type IDH1 mutant

Slide 17

Overall Survival – Second Recurrence Survival by MGMT Methylation Status (post hoc analysis) HR=0.35 (95%CI: 0.11, 1.10) p-value=0.0609 Median OS: Toca: 22.47 months SOC: 13.01 months HR=0.57 (95% CI: 0.23, 1.40) p-value=0.2126 Median OS: Toca: 14.85 months SOC: 10.87 months MGMT Methylated MGMT Unmethylated

Slide 18

Overall Survival – Second Recurrence Survival by Extent of Resection (post hoc analysis) Complete Resection Incomplete Resection HR=0.34 (95% CI: 0.06, 1.82) p-value=0.1897 Median OS: Toca: 27.43 months SOC: 13.01 months HR=0.45 (95% CI: 0.21, 0.98) p-value=0.0394 Median OS: Toca: 14.85 months SOC: 9.77 months Overall in the 2nd Recurrence subset, a higher percentage of SOC patients had a complete resection

Slide 19

Number of Cycles of Treatment Toca FC Metronomic TMZ  TMZ   Lomustine Bevacizumab n 197 18 31 66 26 Mean (SD) 3.4 (3.36) 4.7 (3.80) 4.4 (3.64) 2.3 (1.68) 6.2 (5.49) Median 2 3 3 2 4 Min, Max 1, 21 1, 11 1, 15 1, 7 1, 24 Lomustine as a single oral dose of 110 mg/m2 repeated every 6 weeks, or, Temozolomide either at a dose of 50 mg/m2 once daily continuously (m_TMZ), or, Temozolomide at an initial dose of 150 mg/m2 once daily for 5 consecutive days per 28-day treatment cycle that may be raised to 200 mg/m2 once daily for 5 consecutive days in the following 28-day treatment cycles ,or, Bevacizumab at 10 mg/kg by intravenous (IV) infusion every 2 weeks;1 cycle is defined by 2 courses of bevacizumab SOC Toca Toca 5: Median Cycles of Toca FC and SOC are Low Pre-clinical evidence suggests multiple cycles are necessary

Slide 20

Improvement of Survival is Dependent on Number of Toca FC Cycles Overall Survival – Toca 511 & Toca FC Arm (post hoc analysis) Intention-To-Treat – Toca 511 & Toca FC Arm 1 cycle 4+ cycles 3 cycles 2 cycles

Slide 21

Overall Survival – ITT population Trend between Treatment Duration Analysis and Survival (post hoc analysis) HR=0.658 p-value=0.3230 Median OS: Toca: 31.97 months SOC: 24.74 months HR=0.497 p-value=0.2607 Median OS: Toca: NR (Not Reached) SOC: 24.74 months Treatment duration > 6 months Treatment duration > 9 months

Slide 22

Baseline Immune Balance Between Toca Arm and SOC Arm Tumor PBMCs No significant differences were observed between the two arms at baseline Standard of Care Toca 511 & Toca FC Standard of Care Toca 511 & Toca FC

Slide 23

Baseline Immune Differences Observed Between GBM and AA Tumor# PBMCs * More robust immune profile for AA patients at baseline * AA GBM AA GBM #All significant Significant *

Slide 24

Baseline Immune Differences Observed Between IDH1wt and IDH1mt PBMCs Greater potential to generate anti-tumor responses for patients with IDH1mt at baseline * * * * Tumor# IDH1wt IDH1mt IDH1wt IDH1mt #All significant Significant *

Slide 25

Baseline Immune Differences Observed Between 1st & 2nd Recurrence PBMCs More Robust immune profile for patients with 2nd recurrence at baseline Tumor# #All significant * * * * * * * * * * 1st recurrence 2nd recurrence 1st recurrence 2nd recurrence Significant *

Slide 26

Trial Remains on Track to Activate by end-2019 Chemoradiation à maintenance TMZ Chemoradiation à maintenance TMZ & Toca FC Surgery 1:1 Randomization Stratification Factors Age KPS (Optune® allowed) (No Optune® allowed) Toca 511 SOC NRG-BN006: Phase 2/3 Trial of Toca 511 & Toca FC in ndGBM Standard of Care +/- Toca 511 & Toca FC in Newly Diagnosed GBM (ndGBM)

Slide 27

Phase 1b Trial in Advanced Solid Tumors Design Phase 1b, multicenter, open label (up to 30 patients) Patients with advanced solid tumors or lymphoma Study Results Favorable safety and tolerability (n=20) Confirmed vector deposition in “hot” and “cold” areas of metastatic tumors – Toca 511 penetrates various tumor microenvironments Peripheral blood monitoring suggests immune modulation consistent with observations in rHGG studies Next Steps Updated data presented at SITC meeting in November Data supported advancement of Toca 511 & Toca FC into NMIBC (Toca 8 trial) and will continue to inform future development Continue to evaluate safety, vector deposition, immune activity changes and efficacy over time Toca 6 Trial – Study Schema

Slide 28

Toca 8: Phase 1 Trial of Intravesical Toca 511 Followed by Toca FC in Non-Muscle Invasive Bladder Cancer Objectives Primary - Safety and tolerability Secondary – Viral transduction and Phase 2 dose Exploratory – MOA and clinical “proof of concept” in a subset of patients unresponsive/intolerant to BCG Scientific and Clinical Rationale Supportive preclinical data Safety data from prior trials supports wide safety margin MDSCs may play a role with BCG resistance Routine access to tumor samples and urine provides information on MOA, vector deposition and replication Intravesical delivery allows high multiplicity of infection Toca FC prodrug reservoir in bladder Next Steps Plan to initiate patient enrollment in 2020

Slide 29

Tocagen Pipeline Candidate Indication Discovery Preclinical Phase 1 Phase 2 Phase 3 Toca 511 & Toca FC Recurrent high grade glioma Newly diagnosed glioblastoma (in collaboration with NRG Oncology) Advanced solid tumors (CRC, pancreatic, sarcoma & lung) Recurrent high grade non-muscle invasive bladder cancer Gene Therapies Oncology TBD Data updates presented at SITC Phase 2/3 trial activation planned by end-2019 *NRG Oncology is the study sponsor; Funded by the National Cancer Institute. NRG-BN006* Final analysis presented at SNO Potential Phase 1 trial activation in 2020

Slide 30

2019: Updated Financial Position and Near-Term Catalysts Toca 5 interim analysis expected in the second quarter of 2019 Advance Toca 511 & Toca FC in non-CNS tumor* Toca 5 topline results Report updated Toca 6 safety and immune activity data at Society for Immunotherapy of Cancer 2019 Present full Toca 5 data at Society for Neuro-Oncology 2019 NRG Oncology to initiate NRG-BN006 clinical trial evaluating Toca 511 & Toca FC in newly diagnosed GBM Provide update on potential next steps for recurrent brain cancer program Prepare to initiate a rolling Toca 511 & Toca FC biologics license application in recurrent high grade glioma^ Build U.S. commercial team for potential launch of Toca 511 & Toca FC^ Cash, cash equivalents and marketable securities are $55.3M at Sept. 30, 2019 Prepayment of $23.3M toward loan agreement completed Oct. 31, 2019 * New milestone, not initially guided. ^ No longer applicable given Toca 5 results.

Slide 31

Thank you to all of the patients and families who have supported our work. Financial support also provided by: