By the end of this year, the people at Tolerx will have a good sense of what they’ve created with $150 million of investment over the past decade. If the Cambridge, MA-based company has played its cards right, it should have positive results from a pivotal clinical trial of a drug with an unorthodox approach for fighting Type 1 diabetes.
The company announced back in early January that it completed enrollment of all 240 patients in a clinical trial known as Defend-1. Those people will be followed up for 12 months to see if Tolerx’s experimental treatment is doing what it is supposed to do scientifically, and whether that adds up to a meaningful benefit for patients with diabetes. I got an update on where this all stands from Tolerx co-founder and CEO Doug Ringler.
“This is a new therapeutic paradigm. It represents opportunities and challenges,” Ringler says. “This isn’t a cure, but the data we have so far suggest it’s the closest thing to a cure we have.”
Tolerx, for those new to the story, was founded in 2000 by Hermann Waldmann of the University of Oxford and Ringler, who previously played a role in developing an antibody drug for leukemia, alemtuzumab (Campath). It has raised cash from HealthCare Ventures, Skyline Ventures, and Sprout Group, and secured support from the Juvenile Diabetes Research Foundation. Pharmaceutical giant GlaxoSmithKline signed on to co-develop Tolerx’s lead drug candidate, otelixizumab, back in October 2007, in a deal that could be worth as much as $760 million over time.
From the start, Tolerx’s idea was that it could create drugs that could treat autoimmune diseases by training the immune system to “tolerate” the healthy tissues that it attacks in such ailments, which include Type 1 (sometimes called juvenile) diabetes, rheumatoid arthritis, and psoriasis. The idea of inducing immune tolerance as a means of therapy has long intrigued researchers; Tolerx is pursuing the vision initially in people who are newly diagnosed with Type 1 diabetes. If the company is right, it could eventually offer an 8-day course of daily intravenous infusions of otelixizumab that could help preserve diabetes patients’ natural ability to produce insulin for years, reducing the amount of insulin they need to inject on a daily basis to control their blood sugar. If the drug proves its mettle in this Defend-1 trial, it could be a big step for about 30,000 patients diagnosed with Type 1 diabetes in the U.S. each year, and for a similar number in Europe.
Tolerx’s drug is designed to alter the balance between two key classes of immune system cells: the T effector cells that attack viruses and bacteria and the T regulatory cells, or “T regs” that normally keep the T-effectors in check. One theory with Type 1 diabetes is that this balance tilts too heavily toward T effectors, which wind up attacking the insulin-producing cells of the pancreas, known as beta cells. So Tolerx’s idea was to design an antibody to hit CD3, a marker on T effector cells.
The Defend-1 trial was designed to catch people who were diagnosed early enough that they still have about 30 percent of their beta cells left, which means they only need to take a little insulin to maintain blood sugar control, Ringler says. The belief was
