Tocagen, a gene therapy developer focused on treating brain cancer, will seek to raise $86 million through an initial public offering, according to an S-1 registration statement filed with the U.S. Securities and Exchange Commission.

Tocagen’s lead product candidate is a combination of biologic Toca 511 (vocimagene amiretrorepvec) and small-molecule Toca FC, designed to be used together toward directly killing cancer cells and immune-suppressive myeloid cells thus resulting in activation of the immune system against cancer.

Toca 511 is an injectable retroviral replicating vector that encodes a prodrug activator enzyme, the yeast-derived cytosine deaminase (CD). Upon selective delivery to cancer cells, the infected cancer cells carry the CD gene and can produce the CD enzyme.

Toca FC is an oral, extended-release version of 5-fluorocytosine (5-FC), a prodrug that is inactive as an anticancer drug. According to Tocagen, Toca FC is designed to work by being absorbed and carried through the bloodstream, crossing the blood–brain barrier, and diffusing into cancer cells.

5-FC is converted by the CD enzyme into the active anticancer drug 5-fluorouracil (5-FU) within cancer cells infected by Toca 511. The 5-FU directly kills infected cancer cells and neighboring uninfected cancer cells, and also kills immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), Tocagen says.

“Unlike classical oncolytic viruses, our virus can first stealthily spread through a tumor before inducing killing via the prodrug. This illustrates the importance of the virus being conditionally lytic,” Harry Gruber, M.D., Tocagen’s president and CEO, told GEN last year.

Toca 511/Toca FC is now in multiple clinical trials, led by the Phase II/III Toca 5 trial assessing the combination in patients with recurrent high-grade glioma (HGG). The Phase II/III trial is designed to serve as a potential registrational study. The Phase II portion of Toca 5 has completed patient enrollment, the company said February 23, with topline results anticipated in the first half of 2018, Tocagen said.

The combo treatment is also under study in the Phase I Toca 6 study in patients with metastatic cancer. Tocagen said last month it plans to expand Toca 6 to include patients with recurrent HGG, as well as launch an additional trial, the Phase I Toca 7 in patients with newly diagnosed HGG.

Last month, Toca 511/Toca FC won the FDA’s Breakthrough Therapy designation. The combo in 2015 received the FDA’s Fast Track status for recurrent HGG, and the agency’s Orphan Drug designation for treatment of glioblastoma multiforme.

Uses for Proceeds Outlined

According to the S-1, Tocagen will use unspecified portions of its proceeds to fund:

  • Manufacturing scale-up and validation for Toca 511 and Toca FC;
  • The Phase II portion of its Phase II/III clinical trial of Toca 511 and Toca FC in recurrent HGG through review of topline results from the Phase II portion;
  • Other ongoing and planned clinical development activities for Toca 511 and Toca FC through the completion of ongoing and planned Phase Ib clinical trials for the treatment of newly diagnosed HGG and for the intravenous treatment of metastatic colorectal, pancreatic, breast, lung, melanoma, and renal cancers;
  • Working capital and other general corporate purposes, including the additional costs associated with being a public company.

“We may also use a portion of the net proceeds from this offering to in-license, acquire, or invest in complementary businesses, technologies, products, or assets. However, we have no current plans, commitments, or obligations to do so,” Tocagen stated. “We believe that the net proceeds from this offering and our existing cash, cash equivalents, and marketable securities, together with interest thereon, will be sufficient to fund our operations through at least the next 12 months.”

Founded in 2007, Tocagen is based in San Diego. The company plans to trade its shares on NASDAQ under the symbol TOCA.

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