After failed cancer test, Tocagen slashes staff

Tocagen will be showing 65% of its staffers the exit after its failed test. (Pixabay)

Just last month, Tocagen posted a failed late-stage trial for its gene therapy attempt to boost survival in brain cancer and said it was seeking an “operational review.”

Review done, and the results are in: 65% of staffers will face the ax, leaving just 30 full-timers at the biotech by year’s end.

So what happened? Tocagen had recently moved its gene therapy asset known as Toca 511 and Toca FC into a phase 3, targeting patients with recurrent high-grade glioma (HGG) undergoing resection.

But data out three weeks ago showed the the so-called Toca 5 test was a failure: It missed the primary endpoint of overall survival compared to standard-of-care treatment (11.1 months median compared to 12.2 months), with a p-value of more than 0.6.

This is a tough-to-treat cancer and has seen a growing pile of drugs miss their survival goals.

But this failure cut deep for the biotech, and, to add to the woe, all secondary endpoints “showed no meaningful difference between the arms of the trial,” according to the brief update.

Toca 511 is a cancer-selective immunotherapy comprised of an investigational biologic and an investigational small molecule, Toca FC, that are designed to be used together.

Toca 511 is an injectable retroviral replicating vector that encodes a prodrug activator enzyme, cytosine deaminase (CD). CD is derived from yeast, and humans do not naturally have this gene. Its selective delivery to cancer cells means that the infected cancer cells selectively carry the CD gene and produce CD.

Toca FC, meanwhile, is an investigational oral prodrug, 5-fluorocytosine (5-FC), that is inactive as an anticancer drug. In animal models, Tocagen says it has seen 5-FC converted into the anticancer drug 5-FU at high concentrations in Toca 511-infected cancer cells that are producing CD.

Things looked brighter two years ago when the company got off an IPO in April 2017 worth $85 million toward its gene therapy tests.

Six months down the line, and the San Diego biotech said that after talks with the FDA, it would “immediately accelerate” development of its therapy by cutting out its midstage test and instead move into a pivotal late-stage trial: a Toca 5 trial.

It had been in a phase 2, but was amended and molded into a phase 3, although this did nothing to help its outcome. That year, Toca 511 was given the European Medicines Agency’s PRIME designation and an FDA breakthrough tag for its phase 1 work.

The company is also running a phase 1b exploratory study of the therapy in advanced solid tumors (Toca 6), planning a trial in newly diagnosed HGG (Toca 7) and working on a candidate targeting PD-L1 before year-end.

The biotech’s shares were eviscerated Sept. 12 when that failed trial news broke. They got dragged down into penny stock territory.

Today, it has a market cap of just $14 million and is trading under 60 cents a share.

"We have an extraordinary team at Tocagen, which makes this an extremely difficult decision, and we are deeply grateful for the contributions that all of our employees have made to the advancement of our founding vision that No One Should Die Of Cancer," said Marty Duvall, chief executive at Tocagen.

"With the extended cash position from this restructuring, our immediate priorities are to complete the analysis of the Toca 5 trial data, present the results thereof at the upcoming Society for Neuro-Oncology Annual Meeting in November 2019, and interact with the regulatory agencies to determine potential next steps for Toca 511 & Toca FC in recurrent high grade glioma."