SAN DIEGO, – Nov. 23, 2015 – Tocagen Inc., a clinical-stage, cancer-selective immunotherapy company, today announced interim data from ongoing Phase 1 and preclinical studies of Toca 511 in combination with Toca FC were presented at the 20th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO) and the SNO-SCIDOT Joint Conference on Therapeutic Delivery to the CNS in San Antonio, TX.
Together, the presented data demonstrate Toca 511 & Toca FC continue to show potential benefits, including a favorable safety profile and extended overall survival (OS) in patients with recurrent high grade glioma (HGG) compared to historical benchmarks. In addition, data supported further evaluation of intravenous (IV) delivery of Toca 511 in metastatic solid tumors, and evidence of anti-cancer immune activation following treatment with Toca FC was reported.
Highlights of results from the podium and poster presentations are below.1 More information about the presentations, including abstract number and title, can be found on Tocagen’s website. In the ongoing clinical studies, Toca 511 is administered first and followed by cycles of orally administered Toca FC.
Survival Data from Administration of Toca 511 at the Time of Tumor Removal (Resection/Injection)
- Survival rates for patients with recurrent HGG at 12 and 24 months were 52.5 percent and 31.6 percent, respectively
- Patients with recurrent HGG had a median survival of 13.6 months (N=43)
- Patients with first or second recurrence of HGG and no prior bevacizumab (the patient population to be studied in Tocagen’s ongoing Phase 2/3 clinical trial) had a median survival of 14.6 months (N=30)
- Patients with first or second recurrent glioblastoma (GBM) had a statistically significant improvement (p=0.0028) in OS of 13.6 months compared to 7.1 months for an external lomustine historic data set
- Higher dose cohorts had a median OS of 14.4 months compared to 11.9 months for lower dose cohorts in patients with recurrent HGG, suggesting a dose-response trend for survival
IV Administration of Toca 511
- Following IV delivery of Toca 511, the tumor was removed and Toca 511 administered to resection cavity walls
- Ten of eleven patients in this ongoing clinical trial remain alive with follow up of up to 15.4 months
- Viral DNA and cytosine deaminase (CD) protein were present in resected tumor, with increasing levels of viral DNA with increasing dose
- Trial results support evaluation of IV delivery of Toca 511 in metastatic solid cancers, including breast, lung, colorectal, melanoma and renal
Administration of Toca 511 via Biopsy Needle or Convection Enhanced Delivery (Intratumoral)
- Median survival for patients with recurrent HGG who were not surgical candidates was 13.8 months using biopsy needle delivery (transcranial) versus 7.9 months using convection enhanced delivery (non-biopsy needle delivery)
Evidence of Safety and Mechanism of Action
- Across all ongoing studies, Toca 511 & Toca FC continue to be well tolerated
- Quantitative viral RNA and DNA from Toca 511 was cleared from blood by all patients within early cycles of Toca FC, and detected at low levels in the urine or saliva of a few patients
- Tumor resections from patients previously receiving Toca 511 demonstrate Toca 511 selectively infects and persists in tumor cells in situ
Independent Radiology Reviews
- Objective responses seen in the resection/injection clinical trial and the intratumoral clinical trial
Evidence of Anti-Tumor Immune Activation Following Toca FC Treatment in Patients
- Average increases of 42 percent and 21 percent were observed in total CD4 and CD8 counts respectively
- Nearly significant association (p=0.0587) for CD8 increase with better survival in multivariate model
Toca 5, Phase 2/3 Clinical Trial in Patients with First or Second Recurrent High Grade Glioma Undergoing Resection, Now Enrolling Patients
- Randomized, controlled Phase 2/3 clinical trial designed to serve as potential registrational trial
- Primary endpoint is OS; investigators may choose chemotherapy (lomustine or temozolomide) or antiangiogenic therapy (bevacizumab) for control arm
- More information about the clinical trial can be found at www.tocagen.com/toca5 or by searching clinicaltrials.gov using the clinical trial identifier NCT02414165
About Toca 511 & Toca FC
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, designed to be used together. Toca 511 is a proprietary injectable RRV that encodes a prodrug activator enzyme, cytosine deaminase (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-FC, a prodrug that is inactive as an anti-cancer drug. Toca FC is converted into the active anti-cancer drug, 5-FU, at 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 myeloid derived suppressor cells (MDSCs) in the tumor.
About Tocagen Inc.
Tocagen is a clinical-stage, cancer-selective immunotherapy 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 product candidate, Toca 511 & Toca FC, 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. 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. For more information visit www.tocagen.com or follow @Tocagen.