Newly Published Phase 2 Data Show Tolerion's Reverse Vaccine May Have Disease-Modifying Potential in Type 1 Diabetes

Newly Published Phase 2 Data Show Tolerion's Reverse Vaccine May Have Disease-Modifying Potential in Type 1 Diabetes

--Novel Approach May Have Potential to Revolutionize Treatment of Certain Autoimmune Diseases By Selectively Neutralizing Destructive Self-Antigens While Leaving Rest of Immune System Unaffected--

--In Phase 2 trial, TOL-3021 Increased Pancreatic Beta Cell Function and Reduced Disease-Specific T-Cell Activity in Patients with Type 1 Diabetes--

Portola Valley, CA – June 26, 2013 – Tolerion Inc., today announced the publication of results from a Phase 2 trial demonstrating that lead product TOL-3021 may have the potential to alleviate or even shut down the destructive disease process in type 1 diabetes. The Phase 2 study results reported in today's edition of Science Translational Medicine1 demonstrated that TOL-3021 preserved pancreatic beta-cell function while reducing destructive disease-specific T-cell activity in patients with type 1 diabetes. Tolerion is a newly formed clinical-stage biopharmaceutical company leveraging its proprietary reverse vaccine technology to develop disease-modifying therapies for autoimmune diseases.

Type 1 diabetes is a life-long condition affecting an estimated three million individuals in the U.S. In type 1 diabetes, which typically begins in childhood, the body mistakenly views the insulin-producing pancreatic beta cells as foreign, and the immune system develops specific destructive T-cells that attack and destroy them. Patients with type 1 diabetes require frequent injections of insulin and monitoring of their blood glucose levels. Diabetics are also subject to other health issues resulting from their condition, such as an increased risk of cardiovascular disease, kidney disease, blindness and nerve damage.

Unlike conventional vaccines, which act to stimulate the immune system, the reverse vaccine TOL-3021 is designed to selectively suppress specific elements of the immune system that are inappropriately activated in type 1 diabetes. TOL-3021 contains an engineered DNA plasmid that expresses proinsulin, which is associated with the autoimmune-caused destruction characterizing type 1 diabetes. The Phase 2 trial was designed to assess whether TOL-3021 could decrease these autoimmune attacks on pancreatic beta cells and improve their functioning.

The Phase 2 trial was a randomized, blinded, placebo-controlled, dose escalation trial in 80 adult type 1 diabetics. Patients received one of four doses of TOL-3021 as an injection once a week for 12 weeks.

The data indicate that TOL-3021 was safe and well-tolerated, with no serious adverse events and no increase in adverse events overall compared to placebo.   C-peptide, a marker of pancreatic beta cell function, improved after administration of all doses of TOL-3021 compared to placebo. 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).  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). 

Dr. Lawrence Steinman, the George A. Zimmermann Professor at the Stanford University School of Medicine and a co-founder of Tolerion, commented, "Until now the only treatment for type 1 diabetes was insulin replacement, a 100-year old therapy that is very disruptive to patients' lives and involves serious long-term health risks. These promising Phase 2 data indicate that TOL-3021 may stop the destruction of pancreatic beta cells and improve the long-term outlook for patients with type 1 diabetes, even in adults with long-established disease. Based on these results, we are eager to test TOL-3021 in a larger trial with longer dosing beyond 12 weeks, and to assess whether it might slow or stop disease progression entirely in younger patients when administered before large numbers of beta calls have been destroyed." 

Rights to the reverse vaccine technology and associated product pipeline have been licensed to Tolerion by Stanford University.

1. Plasmid-Encoded Proinsulin Preserves C-Peptide While Specifically Reducing Proinsulin-Specific CD8 T Cells in Type 1 Diabetes, BO Roep, N Solvason, PA Gottlieb, JRF Abreu, LC Harrison, GS Eisenbarth, Liping Yu, M Leviten, WA Hagopian, JB Buse, M von Herrath, J Quan,  R King, WH Robinson, PJ Utz, H Garren, L Steinman, Science Translational Medicine, 26 June 2013, Vol 5 Issue 191,191ra82

About Type 1 Diabetes

According to the Juvenile Diabetes Research Foundation International, about three million people in the U.S. have type 1 diabetes, and over 15,000 children are newly diagnosed each year. Type 1 diabetes is an autoimmune disease that results from the immune system attacking and destroying insulin-producing islet cells in the pancreas.  Patients with type 1 diabetes require life-long self-administration of insulin to keep blood glucose at or near normal levels.  Short-term effects of poor glucose control include diabetic ketoacidosis, a condition that can lead to coma and death. Long-term effects of elevated glucose levels include blindness, kidney disease, heart disease, peripheral vascular disease and stroke.  Insulin replacement therapy, the only approved treatment, does not address the autoimmune response or restore normal glucose regulation, and thus may not fully prevent the long-term complications of diabetes. 

About Tolerion Inc.

Tolerion is a newly formed clinical-stage biopharmaceutical company leveraging its proprietary reverse vaccine technology to develop disease-modifying therapies for autoimmune diseases. Tolerion's product candidates are designed to restore patients' immune system "tolerance" to disease-causing self-antigens, by selectively eliminating specific, harmful immune responses while leaving the rest of the immune system unaffected. This unique targeted and selective approach gives Tolerion's product candidates the potential to deliver superior efficacy, safety and tolerability relative to current therapies, and potentially to even cure some autoimmune diseases. Tolerion's lead product, TOL-3021, is a reverse vaccine for the treatment of type 1 diabetes. Recently-published results from a Phase 2 study showed that TOL-3021 is safe and that it reduces disease-specific destructive T-cell activity while preserving pancreatic beta cell function.  Further clinical studies are planned. For more information, contact [email protected].