'Reverse' DNA vaccine bursts into the spotlight with promising Type 1 diabetes data

A brand new biotech created by a team of professors from Stanford University burst into public view today, drawing headlines around the world for a new therapeutic approach to Type 1 diabetes that aims to completely change the standard of care in the field.

Stanford Professor Lawrence Steinman spearheaded the creation of Tolerion and yesterday reported that the company had achieved key proof-of-concept data for a new "reverse" DNA vaccine--TOL-3021, described as an engineered DNA plasmid that expresses proinsulin--that is designed to rein in the errant T-cell attack that triggers juvenile diabetes by protecting the pancreatic beta cells needed to keep the patient healthy.

Over the course of a Phase II study 80 patients received one of four doses over 12 weeks. The investigators tracked an improvement in C-peptide--a prime biomarker for pancreatic beta cell functioning and insulin production.

"For example, at week 15, C-peptide increased by 19.5% from baseline with the 1 mg dose of TOL-3021, compared to a decrease of 8.8% in patients on placebo (p<0.026)," says the company's release. "Furthermore, an indicator of underlying disease activity, the number of CD8 T-cells reactive to proinsulin, declined with TOL-3021 treatment, while T-cells against other antigens, such as infectious pathogens, were unaffected (p<0.006)."

Investigators have been trying for years now to create synthetically engineered DNA vaccines that can produce an immune response against targets like HIV. But Tolerion is using the technology to suppress the immune system, specifically targeting those T-cells that attack the pancreas.

The news was picked up by all the major financial news wires, with patient groups adding their applause.

"For the first time we have evidence that this particular type of vaccine has an effect in preserving insulin production in humans," said Karen Addington, the U.K. chief executive of the Type 1 diabetes charity JDRF. "This is a significant step forward on the journey towards a world without Type 1 diabetes. We will build on this exciting DNA vaccine approach. Research into Type 1 vaccines is a priority for JDRF's multimillion-pound global research program. But it is early days. Clinical use is still some time away."

Up until now the only treatment for Type 1 diabetes was insulin replacement, a 100-year old therapy that often disrupts patients' lives with a host of side effects, Steinman tells FierceBiotech today. On the other hand, it's also well understood by doctors and patients, who can live normal lives with the proper care. The challenge here is to develop a new treatment that is safe for patients with a targeted immunosuppressant that controls diabetes but won't disable the immune system, exposing patients to serious diseases.

Tolerion was set up only two months ago, he adds, but its history dates back 10 years. Bayhill Therapeutics originally had the platform technology and a $350 million deal with Genentech. But an attempt to go public in 2008 was derailed by the financial crisis, says Steinman, and Genentech decided to drop their involvement after Roche acquired the company. Bayhill was wound down and now Tolerion has the platform technology--which Steinman says can be used to develop other therapies for diseases like hyperthyroidism and hemophilia A. And the four founders from Stanford are scouting for venture backing as well as a major league partner to take this forward.

Type 1 diabetes has proven to be a very tough target in the biopharma world. Tolerx partnered with GlaxoSmithKline ($GSK) on their antibody, otelixizumab, which failed decisively in a Phase III study that read out in the spring of 2011. Like Tolerion, Tolerx had tried to protect pancreatic beta cells, looking for a significant improvement in C-peptide by targeting the CD3 receptor on T cells. But months after the late-stage failure the company was wrapped up, wiping out a $150 million in investment cash. Another anti-CD3 antibody at MacroGenics--partnered with Eli Lilly ($LLY)--failed a Phase III study in late 2010.

Diabetes is also a very expensive disease field to work in, which is why the anti-CD3 companies both had big pharma partners to fund late-stage work. Tolerion will now see if its rebirth coinciding with promising Phase II data can spur a few of the big players in this disease space to take a closer look.  

- here's the press release