Tocagen Presents Updated Tumor Response Data for its Cancer-Selective Gene Therapy

VANCOUVER, Canada – October 5, 2016 – Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced updated clinical data for Toca 511 (vocimagene amiretrorepvec) in combination with Toca FC (extended-release 5-fluorocytosine) for the treatment of recurrent high grade glioma.

The new data were presented at the 10th International Oncolytic Virus Meeting in Vancouver, Canada by Douglas J. Jolly, Ph.D., executive vice president of research and pharmaceutical development at Tocagen. The podium presentation was titled Molecular analyses and immune activity of Toca 511 a retroviral replicating vector in preclinical models and three ascending dose trials in patients with recurrent high grade glioma.

The presentation included updated response and survival data from Tocagen’s Phase 1, ascending dose study of Toca 511 administered at the time of tumor removal followed by cycles of orally administered Toca FC. Both Toca 511 and Toca FC are investigational agents. In the efficacy evaluable subset of twenty four patients with recurrent glioblastoma or anaplastic astrocytoma who received higher doses of Toca 511 and met the entry criteria for Tocagen’s ongoing Toca 5 trial1, the results were as follows:

CriteriaToca 511 & Toca FC (N=24)
Median overall survival14.3 months
Overall response, n (%)5 (20.8)

(3 CR, 2 PR)*

Median duration of response, months20.7
Stable disease (SD), n (%)5 (20.8)
Progressive disease, n (%)14 (58.3)
Clinical Benefit Rate, n (%)

(CR, PR, and SD at 8 weeks)

10 (41.7)
*Complete response (CR) and partial response (PR). Data cutoff date was September 1st 2016. Responses were assessed using Macdonald Criteria including MRI assessment by independent radiology review and clinical data.

In addition, Toca 511 & Toca FC continued to demonstrate a favorable safety profile and was well tolerated by patients.

“The complete and partial responses occur 6 to 19 months after study entry, consistent with the immunologic mechanism of action observed in our preclinical models,” said Dr. Jolly. “Furthermore, all responding patients have durable responses, remain alive at 21-42 months after study entry, and were clinically stable or improved. We are very encouraged by these data and the potential of this virus treatment for cancer patients.”

The ongoing Toca 5 trial is enrolling patients with recurrent glioblastoma or anaplastic astrocytoma. A current list of participating sites can be found here and a patient/care-giver inquiry form can be submitted here.

1 A phase 2/3 study for patients with first or second recurrence of recurrent glioblastoma or anaplastic astrocytoma; no prior bevacizumab for recurrence; recurrent tumor less than or equal to 5 centimeters.

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. Tocagen has initiated a clinical trial of Toca 511 & Toca FC in metastatic cancers, including colorectal, pancreatic, lung, breast, renal and melanoma. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration for Toca 511 & Toca FC as a treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma multiforme (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information, visit www.tocagen.com or follow @Tocagen.

Tocagen to Present Clinical and Preclinical Data at Two Scientific Meetings

SAN DIEGO – September 30, 2016 – Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced clinical and preclinical data involving Toca 511 & Toca FC for the treatment of recurrent high grade glioma will be presented at the 10th International Oncolytic Virus Meeting, to be held Oct. 1-4 in Vancouver, Canada and the European Society of Gene & Cell Therapy Annual Meeting, to be held Oct. 12-21 in Florence, Italy.

Details of the International Oncolytic Virus Meeting presentation are as follows:

Presentation Type: Presentation
Title: Molecular analyses and immune activity of Toca 511 a retroviral replicating vector in preclinical models and three ascending dose trials in patients with recurrent high-grade glioma
Date and Time: Tuesday, Oct. 4, afternoon session. PT
Presenter: Douglas J. Jolly, Ph.D., executive vice president of research and pharmaceutical development at Tocagen

Details of the European Society of Gene & Cell Therapy presentations are as follows:

Presentation Type: Presentation
Title: Clinical update, molecular analyses, and proposed mechanism of action of Toca 511 a retroviral replicating vector in three ascending dose trials in patients with recurrent high-grade glioma
Date and Time: Friday, Oct. 21, 9:00 a.m. CET
Presenter: Douglas J. Jolly, Ph.D. executive vice president, research and pharmaceutical development at Tocagen

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. Tocagen has initiated a clinical trial of Toca 511 & Toca FC in metastatic cancers, including colorectal, pancreatic, lung, breast, renal and melanoma. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration for Toca 511 & Toca FC as a treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma multiforme (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information, visit www.tocagen.com or follow @Tocagen.

First Patient Enrolled in Toca 6, Tocagen’s Trial for Metastatic Cancers Evaluating Intravenously Delivered Toca 511 Virus

Study Investigates Potential Expansion Indications for
Toca 511 & Toca FC

SAN DIEGO – Sept. 22, 2016 – Tocagen, Inc., a clinical-stage, cancer-selective immunotherapy company, today announced the first patient has been enrolled in Toca 6, a Phase 1b study evaluating intravenously delivered Toca 511 (vocimagene amiretrorepvec) in combination with Toca FC (extended-release 5-fluorocytosine) in patients with metastatic cancers. The study is planned to include patients with colorectal cancer with liver metastases; metastatic renal cell carcinoma; locally advanced or metastatic pancreatic cancer or breast cancer; brain metastases from non-small cell lung cancer or breast cancers; and locally advanced or recurrent melanoma.

“We must strive for breakthroughs in the treatment of cancer and identifying therapies that work through novel mechanisms will be vital to achieve this goal,” said Jaime Merchan, M.D., oncologist at Sylvester Comprehensive Cancer Center, part of UHealth, the University of Miami Health System; associate professor of medicine at the University of Miami Miller School of Medicine; and the principal investigator of the study who also enrolled the first patient. “Based on preclinical data, a unique immune activating mechanism of action is proposed for Toca 511 and Toca FC whereby the treatment targets and destroys cancer cells wherever they are located in the body while leaving healthy cells unharmed. I look forward to continuing the investigation of this promising approach in our fight against cancer.”

The trial will evaluate if Toca 511-delivered genes and resulting proteins are detected in tumor samples, following intravenous administration of Toca 511. Safety, tumor response and survival results will also be assessed.

In this first patient, who has metastatic colorectal cancer, intravenous Toca 511 and oral Toca FC was well tolerated. Toca 511 viral genes and cytosine deaminase (CD) were present in tumor samples. Additional results from this trial will be presented at a future scientific conference.

“With the initiation of this trial we have moved one step closer to evaluating our cancer-selective gene therapy in broad indications using intravenous Toca 511 administration,” said Harry Gruber, M.D., chief executive officer of Tocagen. “We are particularly encouraged by the observation of viral transduction in this first case and we look forward to enrolling additional cancer patients with high unmet needs.”
More information about the Toca 6 clinical trial can be found by searching clinicaltrials.gov using the clinical trial identifier NCT02576665.

In three Phase 1 studies in patients with recurrent brain cancer, Toca 511 was administered in one of three methods: intravenously followed by injection into the resection cavity wall at the time of surgery; into the resection cavity wall at the time of surgery; or intratumorally, and was followed in each case by cycles of orally administered Toca FC. These studies provided support for the ongoing Phase 2/3 study of Toca 511 & Toca FC in patients with recurrent glioblastoma and anaplastic astrocytoma, which is designed to serve as a potential registration study. A summary of Tocagen’s Phase 1 clinical trials can be found on Tocagen’s website.

Tocagen’s cancer-selective gene therapy platform is built on retroviral replicating vectors (RRVs) which are designed to selectively integrate into the DNA of cancer cells which then serve as factories for these RRVs to replicate and infect neighboring cancer cells, providing long-term presence of the therapeutic gene(s). Tocagen’s lead product candidate is a combination of an investigational biologic, Toca 511, and an investigational small molecule drug, Toca FC. Toca 511 is a proprietary injectable RRV that encodes a prodrug activator enzyme, CD. Its selective delivery to cancer cells means that the infected cancer cells selectively carry the CD gene and produce CD protein. Toca FC is an orally administered, proprietary extended-release version of 5-fluorocytosine (5-FC), a prodrug that is inactive as an anti-cancer drug. The treatment is designed to convert Toca FC into the active anti-cancer drug, 5-fluorouracil (5-FU), at local high concentrations in Toca-511-infected cancer cells that are producing CD protein. 5-FU is a well-established anti-cancer agent used effectively in many conventional chemotherapy settings. In addition to the direct killing of Toca 511-infected cancer cells, 5-FU kills neighboring uninfected cancer cells and immunosuppressive myeloid cells including myeloid derived suppressor cells (MDSCs) in the tumor.

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. Tocagen has initiated a clinical trial of Toca 511 & Toca FC in metastatic cancers, including colorectal, pancreatic, lung, breast, renal and melanoma. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration for Toca 511 & Toca FC as a treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma multiforme (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information, visit www.tocagen.com or follow @Tocagen.

RiboMed and Tocagen Announce Collaboration to Analyze Epigenetic Prognostic Markers

SAN DIEGO – July 6, 2016 – RiboMed Biotechnologies, Inc. and Tocagen Inc., today announced a collaboration to analyze potential epigenetic prognostic and predictive markers, including the gene for the DNA repair enzyme O-6-Methylguanine-DNA Methyltransferase (MGMT), in Tocagen’s clinical trials evaluating the investigational treatment Toca 511 & Toca FC in patients with recurrent high grade gliomas (HGGs).

HGGs, including glioblastoma, are the most aggressive primary malignant brain tumors and are treated initially with surgery, radiation and chemotherapy, including temozolomide (TMZ, Temodar®). Response to TMZ treatment is variable and almost all tumors ultimately recur. Tumor sensitivity to TMZ correlates with the inactivation of MGMT and longer overall survival in patients with glioblastoma. Inactivation of MGMT is primarily caused by DNA methylation in the MGMT gene’s control region.

Given the prognostic and predictive value of MGMT methylation status, this test has become an informative tool in the management of glioblastoma. RiboMed has developed a new validated test, which improves the reliability and accuracy of MGMT testing. A full description and validation of this technology and comparison to other commonly used DNA methylation methods was recently published in Epigenomics (http://www.futuremedicine.com/doi/pdf/10.2217/epi-2016-0004).

“Accurate diagnostics information is critical to help inform treatment decisions and expectations for outcomes,” said David Piccioni, M.D., Ph.D., neuro-oncologist at UC San Diego’s Moores Cancer Center. “Having a test that can produce accurate and reliable MGMT promoter methylation data with minimal sample is an important advance for patients and their caregivers”.

Favorable safety and promising survival data from Tocagen’s Phase 1, open-label, ascending dose, multicenter trial, that included analysis of epigenetic markers of tumors by RiboMed were published in the cover article of the June 1, 2016 issue of Science Translational Medicine (http://stm.sciencemag.org/content/8/341/341ra75). Based on the positive results reported in this study, Tocagen is now conducting an international Phase 2/3 trial, Toca 5; more information can be found by searching www.clinicaltrials.gov using the clinical trial identifier NCT 02414165). In collaboration with RiboMed, the assay will be utilized to analyze MGMT status in tumors resected during the trial and evaluate association with potential treatment activity.

The collaborative research also includes evaluation of RiboMed’s GliomaSTRAT assay initially in tumor samples from earlier clinical trials. GliomaSTRAT is designed to stratify gliomas by both tumor aggressiveness and potential for drug activity. In addition to MGMT methylation, GliomaSTRAT includes a DNA methylation biomarker panel to determine the tumor’s CpG Island Methylator Phenotype (CIMP) and detection of the IDH1 R132H mutation known to cause CIMP. These prognostic biomarkers identify two distinct tumor subtypes that show significant differences in overall survival, independent of initial tumor grade classification.

The ability to reliably analyze HGGs for multiple DNA methylation biomarkers, particularly with minimal material from FFPE tumor samples, has only recently become possible through the development of RiboMed’s extremely sensitive detection method for measuring both DNA methylation and point mutations using its core technology, Abscription®.

About RiboMed
RiboMed Biotechnologies, Inc. is a CLIA-certified molecular diagnostic clinical laboratory and Contract Research Organization offering ultra-sensitive DNA methylation based tests for cancer and drug response related biomarkers to physicians and for use in clinical trials. RiboMed’s test for stratifying glioma brain tumors, GliomaSTRAT™, uses a combination of DNA methylation profiling and mutation analysis to both determine glioma grade (LGG vs HGG) and has been reported to predict response to first line chemotherapy with temozolomide. Research Use Only (RUO) kits, reagents, and technology licensing are also available. For more information go to www.RiboMed.com or follow @RiboMed.

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company focused on developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer from within. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in newly diagnosed HGG and metastatic cancer, including colorectal, pancreatic, lung, breast, renal and melanoma. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration for Toca 511 & Toca FC as a treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information, visit www.tocagen.com or follow @Tocagen.

Study Published in Science Translational Medicine Reports Favorable Safety and Extended Survival for Brain Cancer Patients Treated with Tocagen’s Cancer-Selective Viral Gene Therapy

SAN DIEGO – June 1, 2016Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced results from a multi-center study of an investigational immunotherapy, Toca 511 & Toca FC, have been published in the June 1, 2016, issue of Science Translational Medicine. The study, conducted in patients with recurrent brain cancer, showed extended survival compared to an external control, complete and partial tumor shrinkage determined by independent radiology review and favorable safety and tolerability profiles. This article marks the first peer-reviewed publication describing the study of a retroviral replicating vector administered to humans. Timothy Cloughesy, M.D., director of the UCLA, Neuro-Oncology Program, is the lead author of the paper.

High grade gliomas (HGGs) are among the most common and aggressive primary brain cancers. In 2016 approximately 160,000 patients worldwide are expected to be diagnosed with HGG. The two most common forms of HGGs are glioblastoma (GBM) and anaplastic astrocytoma. With current standard of care, newly diagnosed GBM patients have a median survival of approximately 16 months. Median survival after recurrence is typically seven to nine months.

  • In the published study conducted by Tocagen, 43 patients with recurrent HGG treated with Toca 511 & Toca FC had a median overall survival of 13.6 months and a probability of survival at 24 months of 31.6%.
  • In the subset of 27 patients with recurrent HGG in the higher dose cohorts, median overall survival was 14.4 months with a probability of survival at 24 months of 40%.
  • In the subset of 27 patients with recurrent GBM at first or second recurrence, median overall survival and probability of survival at 24 months were 13.6 months and 29.1%, respectively, compared to 7.1 months and 9.1% for an external control of matched GBM patients who received the standard of care chemotherapy drug lomustine.
  • Importantly, Toca 511 & Toca FC had a favorable safety profile and was well tolerated by patients.

“The safety and survival data described in this manuscript are very promising. Seeing a probability of 40 percent survival at 2 years is extraordinary for patients with recurrent brain cancer and consistent with the proposed immune mechanism for this approach,” said Tom Mikkelsen, M.D., co-director of the Hermelin Brain Tumor Center at Henry Ford Hospital and president and scientific director of the Ontario Brain Institute. “Given the high unmet need and extremely limited treatment options for these patients, we are encouraged by these data and look forward to advancing this potential new treatment option for patients suffering from this devastating disease.”

Survival results from the studies are summarized in the table below.

 Median Overall Survival (Months)Overall Survival Probability at 24 Months
Efficacy evaluable population receiving Toca 511 & Toca FC 
Recurrent HGG patients in all dose cohorts (n=43)13.631.6%
Recurrent HGG patients in higher dose cohorts (n=32)14.440.0%
First or second recurrence GBM patients in all dose cohorts (n=27)13.629.1%
External control population receiving lomustine
Matched first or second recurrence GBM patients                (n= 84)7.19.1%

Tumor samples from patients surviving greater than 12 months after treatment displayed a unique survival-related mRNA expression signature which may help support the observed clinical activity of the treatment. Statistically significant increases in CD4+ T cells in the blood were observed, suggesting immune activation may be involved. Also, durable complete and partial shrinkage of tumors reported by independent radiology review were observed in the higher dose groups. Seven of eight patients with stable disease were also in the higher dose cohorts.

“Brain cancers, including glioblastomas, are sensitive to the anticancer drug 5-FU, but side effects from systemic treatment limit its clinical utility. Tocagen’s approach minimizes side effects by producing 5-FU within the tumor, allowing it to selectively destroy cancer cells and also activate the immune system. In addition, 5-FU kills immunosuppressive cells, further powering the immune system’s ability to kill the tumor,” said Harry Gruber, M.D., chief executive officer of Tocagen. “The first publication of clinical data describing Toca 511 & Toca FC is an important accomplishment for a large number of individuals and groups who have supported this new approach to fighting cancer, including patients and their caregivers, the brain tumor care teams at our clinical sites, the dedicated brain cancer non-profit organizations, the clinical diagnostics team at Siemens Healthcare and our passionate team at Tocagen.”

Dr. Gruber also highlighted these results during a concurrent panel discussion at the Boston CEO Conference.

This study was performed in collaboration with investigators at Cleveland Clinic Foundation, Cleveland, OH; University of California, Los Angeles; University of California San Diego School of Medicine; Henry Ford Hospital, Detroit, MI; Ohio State University, Columbus, OH; Swedish Neurological Institute, WA; and JFK Medical Center, Edison, NJ. MGMT DNA methylation analyses were performed by Ribomed Biotechnologies Inc.

Sites in the United States and Canada are now recruiting patients with recurrent glioblastoma or anaplastic astrocytoma for a Phase 2/3 study of Toca 511 & Toca FC, called Toca 5. Additional sites in Germany, Israel and South Korea are planned. More information about the Toca 5 trial can be found at www.tocagen.com/toca5 or by searching www.clinicaltrials.gov using the clinical trial identifier NCT02414165.

“While the pursuit of a potential new treatment option for patients with brain cancer remains our first priority, new preclinical results showing our approach activates the immune system against other tumors has driven our plans to initiate a study later this year for patients with metastatic cancers including colorectal, pancreatic, lung, breast, renal and melanoma,” added Dr. Gruber.

About Toca 511 & Toca FC
Tocagen’s cancer-selective gene therapy platform is built on retroviral replicating vectors (RRVs) designed to selectively integrate into the DNA of cancer cells which then serve as factories for these RRVs to replicate and infect neighboring cancer cells, providing long-term presence of the therapeutic gene(s). Tocagen’s lead product candidate is a combination of an investigational RRV, Toca 511, and an investigational drug tablet, Toca FC, designed to be used together. Toca 511 is a conditionally oncolytic virus that delivers selectively to cancer cells a gene which converts Toca FC into 5-FU, a potent anticancer drug, in the tumor microenvironment. 5-FU kills the cancer cells leading to activation of the immune system against those dying cells. 5-FU also kills immunosuppressive myeloid cells, which are a major brake on the immune system in the tumor. Removing this brake dramatically increases the immune activation against the cancer. In summary, Toca 511 has a duel mechanism of action. 5-FU is a trigger to conditional oncolytic activation of the immune system and to remove an important brake on the immune system, in the tumor microenvironment.

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company focused on developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer from within. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. In 2016, Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in newly diagnosed HGG and metastatic cancer, including colorectal, pancreatic, lung, breast, renal and melanoma. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration for Toca 511 & Toca FC as a treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information, visit www.tocagen.com or follow @Tocagen.

Tocagen Announces Presentations at the 2016 BIO International Convention and Boston CEO Conference

SAN DIEGO – May 26, 2016 – Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced members of the company’s management team will participate on a panel discussing the intersection of immuno, viral and gene-based therapies for cancer treatment and present a corporate overview at the 2016 BIO International Convention, to be held June 6-9 in San Francisco.

In addition, Tocagen will participate in a panel discussion at the Boston CEO Conference, to be held May 31-June 1 in Boston, providing insight into the promises and challenges of gene therapy.

Details of the panel and presentation at the 2016 BIO International Convention are as follows:

Panel Title: Lighting the Match on Cancer: The Intersection of Immuno, Viral and Gene Therapy and the Implications for Cancer Treatment
Date and Time: Thursday, June 9, 9:00-10:15 a.m. PT
Location: West 3002
Participant: Asha Das, M.D., vice president, clinical development and medical affairs at Tocagen

Title: Tocagen Inc. Company Presentation
Date and Time: Wednesday, June 8, 5:00-5:13 p.m. PT
Location: Room 4
Speaker: Nicholas Boyle, Ph.D., vice president, business development and marketing at Tocagen

Details of the panel at Boston CEO Conference are as follows:

Panel Title: Genetic Therapies: The Promise and The Challenge
Date and Time: Wednesday, June 1, 1:30-2:00 p.m. ET
Participant: Harry Gruber, M.D., president and chief executive officer of Tocagen

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company focused on developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer from within. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. In 2016, Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in patients with metastatic colorectal, pancreatic, breast, lung, renal and melanoma cancers and in patients with newly diagnosed HGG. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration, for Toca 511 & Toca FC for the treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information, visit www.tocagen.com or follow @Tocagen.

Tocagen to Present Clinical and Preclinical Data at Three Scientific Meetings

SAN DIEGO – May 13, 2016Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced that results from the clinical investigation of Toca 511 & Toca FC for the treatment of recurrent high grade glioma will be presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, to be held June 3-7 in Chicago, and the 17th Biennial Canadian Neuro-Oncology (CNO) Meeting, to be held June 9-11 in Toronto.

In addition, preclinical data demonstrating that Tocagen’s investigational therapy induces an anti-tumor immune response will be presented at Immunology 2016TM, the Annual Meeting of the American Association of Immunologists (AAI), to be held May 13-17 in Seattle.

Details of the ASCO presentation are as follows:

Presentation Type: Poster
Title: Encouraging survival with Toca 511 and Toca FC compared to external lomustine control
Date and Time: Saturday, June 4, 1:00-4:30 p.m. CT
Presenter: Timothy Cloughesy, M.D., director of the University of California, Los Angeles, Neuro-Oncology Program

Details of the CNO presentations are as follows:

Presentation Type: Podium
Title: Cancer-selective gene therapy with Toca 511 and Toca FC for the treatment of recurrent high grade glioma
Date and Time: Friday, June 10, 2:00-3:20 p.m. ET
Presenter: Tom Mikkelsen, M.D., co-director of the Hermelin Brain Tumor Center at Henry Ford Hospital and president and scientific director of the Ontario Brain Institute

Presentation Type: Poster
Title: Toca 5: A phase 2/3 randomized, open-label study of Toca 511, a retroviral replicating vector, combined with Toca FC versus standard of care in patients undergoing planned resection for recurrent glioblastoma (GBM) or anaplastic astrocytoma (AA) (NCT02414165)
Date and Time: Saturday, June 11, 10:00-10:45 a.m. ET
Presenter: Gelareh Zadeh, M.D., Ph.D., associate professor at the Department of Surgery, University of Toronto and Wilkins Family Chair in Brain Tumor Research

Details of the AAI presentation are as follows:

Presentation Type: Poster
Title: Temporal changes in tumor-associated immune cell populations in subcutaneous Tu-2449SC tumors transduced with Toca 511 following treatment with 5-FC
Date and Time: Monday, May 16, 2:30-3:45 p.m. PT
Presenter: Leah Mitchell, Ph.D., research scientist at Tocagen

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company focused on developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer from within. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. In 2016, Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in patients with newly diagnosed HGG and other solid tumors. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration, for Toca 511 & Toca FC for the treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information visit www.tocagen.com or follow @Tocagen.

Tocagen Presents Intravenous Toca 511 Clinical Data at the 84th AANS Annual Scientific Meeting

Encouraging Survival, Proof of Mechanism, and Favorable Safety Was Demonstrated

CHICAGO – May 3, 2016 – Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced positive clinical data involving intravenously delivered Toca 511 (vocimagene amiretrorepvec) in combination with Toca FC (extended-release flucytosine) for the treatment of recurrent high grade glioma were presented at the 84th American Association of Neurological Surgeons (AANS) Annual Scientific Meeting in Chicago.

The podium presentation was delivered by Steven N. Kalkanis, M.D., chair of the department of neurosurgery and co-director of the Neuroscience Institute at Henry Ford Hospital, on behalf of the clinical investigators participating in the trial.

Highlights of results are below. More information about the presentation, including abstract number and title, can be found on Tocagen’s website.

  • Survival probability at 12 months was 61.3% and median survival was 13.6 months
  • A complete radiologic response, based on independent radiology review was noted
  • Combination of IV and intracranial Toca 511 was generally well tolerated
  • Patients received up to 47 billion transduction units of Toca 511
  • Resected tumor from 11 patients with recurrent high grade glioma treated with Toca 511 & Toca FC showed presence of viral DNA in a dose-dependent manner with 10/14 (71%) detectable overall of which 7/9 (78%) were in subjects treated with 3 day delivery
  • Expression of yeast CD transgene was detectable by immunohistochemistry
  • More information about the trial can be found at ClinicalTrials.gov using the identifier NCT01985256

“These encouraging data involving intravenously delivered Toca 511 support additional investigation in patients with primary brain cancer and metastatic cancers,” said Harry Gruber, M.D., CEO of Tocagen.

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company focused on developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer from within. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. In 2016, Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in patients with newly diagnosed HGG and other solid tumors. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration, for Toca 511 & Toca FC for the treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information, visit www.tocagen.com or follow @Tocagen.

Tocagen Presents Positive Preclinical, Proof-of-Mechanism Data at the American Association for Cancer Research (AACR) Annual Meeting

Combining Toca 511 and 5-FC with Checkpoint Inhibitors Reduces Tumor Burden in Preclinical Model

Toca 511 and 5-FC Increased Survival in Preclinical Metastatic Colorectal Cancer Model

NEW ORLEANS – April 19, 2016 – Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced positive preclinical, proof-of-mechanism data involving Toca 511 and 5-fluorocytosine (5-FC) were presented at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans. The data demonstrate the potential for this investigational therapy to be used in combination with checkpoint inhibitors, specifically anti-PD-1 or anti-CTLA-4 antibodies, and as a potential treatment for metastatic colorectal cancer.

Highlights of results from the poster presentations are below. More information about the presentations, including abstract number and title, can be found on Tocagen’s website.

Combining Toca 511 and 5-FC with Checkpoint Inhibitors Reduces Tumor Burden in Preclinical Model

  • Combining Toca 511 and 5-FC with anti-PD-1 or anti-CTLA-4 blocking antibodies significantly reduced tumor growth, compared to checkpoint inhibitor treatments alone, in a subcutaneous glioma model
  • Treatment with Toca 511 and 5-FC increased the total number of tumor-infiltrating lymphocytes in the tumor microenvironment, including significant increases in T cell populations
  • The combination of Toca 511 and 5-FC with either checkpoint inhibitor significantly reduced tumor-associated myeloid-derived suppressor cells (MDSCs) and macrophages (TAMs)

Toca 511 and 5-FC Increased Survival in Preclinical Metastatic Colorectal Cancer Model

  • Increased survival and anti-tumor immune responses were observed following intravenous delivery of Toca 511 followed by courses of 5-FC in a syngeneic model of metastatic colorectal cancer
  • Confirming previously reported results, transgene expression was observed in tumor but not adjacent normal tissue
  • Treatment with Toca 511 and 5-FC significantly reduced MDSCs in tumor and spleen
  • Anti-tumor immune memory induced by Toca 511 and 5-FC was confirmed with complete rejection of tumor upon re-challenge
  • Based on these results, an investigational Phase 1b clinical trial evaluating Toca 511 & Toca FC (extended-release 5-FC) in patients with metastatic colorectal cancer is planned. More information about the clinical trial can be found by searching clinicaltrials.gov using the clinical trial identifier NCT02576665.

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company focused on developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer from within. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. In 2016, Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in patients with newly diagnosed HGG and other solid tumors. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration, for Toca 511 & Toca FC for the treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information visit www.tocagen.com or follow @Tocagen.

Tocagen to Present Data from Clinical Trials and Preclinical Programs at Four Scientific Conferences

SAN DIEGO – April 13, 2016Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced that new results from the clinical investigation of Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine) for the treatment of recurrent high grade glioma will be presented at the 84th American Association of Neurological Surgeons (AANS) Annual Scientific Meeting, to be held April 30-May 4 in Chicago.

In addition, preclinical data supporting the combination of Toca 511 & Toca FC with checkpoint inhibitors, and demonstrating increased survival in colorectal cancer, will be presented at the American Association for Cancer Research (AACR) Annual Meeting, to be held April 16-20 in New Orleans. Tocagen’s management team will also participate in a panel discussion at the Alliance for Cancer Gene Therapy (ACGT) scientific symposium, to be held April 14 in New York City, and present new preclinical and clinical data at the American Society of Gene and Cell Therapy (ASGCT) 19th Annual Meeting, to be held May 4-7 in Washington D.C.

Details of the AANS presentations are as follows:

Presentation Type: Oral presentation
Title: Intravenous Toca 511 Delivery Leads to Viral DNA in Resected High Grade Glioma (HGG)
Date and Time: Monday, May 2, 2:00-5:30 p.m. ET
Presenter: Steven N. Kalkanis M.D., chair of the department of neurosurgery and co-director of the Neuroscience Institute at Henry Ford Hospital

Presentation Type: Oral presentation
Title: Toca 511 Followed by Toca FC in Subjects with Recurrent High Grade Glioma (rHGG)
Date and Time: Monday, May 2, 2:00-5:30 p.m. ET
Presenter: Manish Aghi, M.D., Ph.D., associate professor of neurological surgery at University of California, San Francisco

Details of the AACR presentations are as follows:

Abstract Number: 1413
Presentation Type: Poster
Title: Treatment of Mouse Liver and Brain Colon Cancer Metastases with Toca 511 and 5-fluorocytosine for Intratumoral Production of 5-fluorouracil Leads to Increased Survival, Induction of Anti-Tumor Immune Responses, and Reduction of MDSC
Date and Time: Monday, April 18, 8:00 a.m.-12:00 p.m. CT
Presenter: Maria Rodriguez-Aguirre, research associate at Tocagen

Abstract Number: 3212
Presentation Type: Poster
Title: Combining Toca 511 and 5-fluorocytosine with αPD-1 or αCTLA-4 Antibody Significantly Reduces Tumor Burden Compared to Either Checkpoint Inhibitor Alone or in Combination in a Subcutaneous Mouse Model of Glioma
Date and Time: Monday, April 19, 8:00 a.m.-12:00 pm. CT
Presenter: Leah Mitchell, Ph.D., research scientist at Tocagen

Details of the presentation at ACGT are as follows:

Presentation Type: Panel discussion
Panel Title: Clinical Development of Cell and Gene Therapy: Overview of What’s Hot in Clinical Development and the Most Important Developments Yet to Come
Date and Time: Thursday, April 14, 2:15-4:00 p.m. ET
Participant: Douglas J. Jolly, Ph.D., executive vice president of research and pharmaceutical development at Tocagen

Details of the presentations at ASGCT are as follows:

Abstract Number: 61
Presentation Type: Oral presentation
Title: Ascending Dose Trials of a Retroviral Replicating Vector (Toca 511) in Patients with Recurrent High-Grade Glioma: Clinical Update, Molecular Analysis, and Proposed Mechanism of Action
Date and Time: Wednesday, May 4, 3:30-5:30 p.m. ET
Presenter: Douglas J. Jolly, Ph.D., executive vice president of research and pharmaceutical development at Tocagen

Abstract Number: 205
Presentation Type: Poster
Title: Cytotoxic and immunotherapeutic Effects of Toca 511 and 5-fluorocytosine in an Intraperitoneal Model of Metastatic Colorectal Cancer
Date and Time: Wednesday, May 4, 5:30-7:30 p.m. ET
Lead Author: Kader Yagiz, Ph.D., research scientist at Tocagen

Abstract Number: 403
Presentation Type: Poster
Title: Toca Retroviral Replicating Vector in Tumor and Blood from Clinical Trial Subjects with Recurrent High Grade Glioma
Date and Time: Thursday, May 5, 6:00-8:00 p.m. ET
Lead Author: Daniel Hogan, Ph.D., bioinformatics scientist at Tocagen

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy company focused on developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer from within. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. In 2016, Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in patients with newly diagnosed HGG and other solid tumors. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration, for Toca 511 & Toca FC for the treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information visit www.tocagen.com or follow @Tocagen.