True North Therapeutics Presents Preclinical Results Showing Potential of TNT009 to Treat Complement-Mediated Rare Diseases

Oral presentation of data at the ASH 2013 annual meeting

Lead antibody drug candidate shows novel mechanism for selectively inhibiting the classical complement pathway

South San Francisco, CA – December 9, 2013 – True North Therapeutics, a biotechnology company developing novel therapies that selectively inhibit the Complement system to treat rare diseases, presented data today from preclinical efficacy studies of TNT009 for the treatment of Cold Agglutinin Disease (CAD), a rare autoimmune hemolytic anemia, at the 2013 American Society for Hematology (ASH) International Conference in New Orleans. TNT009, the company’s lead monoclonal antibody drug candidate, was shown in preclinical studies to be a potent and specific inhibitor of the Classical Complement pathway and demonstrated the ex vivo ability to prevent Complement deposition, phagocytosis, and hemolysis of red blood cells induced by autoantibodies from CAD patients.

The results presented validate the novel mechanism of TNT009 to selectively inhibit C1s, a serine protease specific to the Classical Complement pathway, and thereby interrupt disease processes at one of the earliest points in the Complement cascade. Based on these and other results, True North plans to file an Investigational New Drug (IND) application for TNT009 with the U.S. Food and Drug Administration in late 2014.

“These studies clearly reveal the potential of TNT009 to meet unmet medical needs of patients with a variety of Complement-mediated autoimmune and inflammatory disorders, in addition to Cold Agglutinin Disease,” said Nancy Stagliano, Ph.D., CEO of True North Therapeutics. “By selectively targeting proximally in the Classical Complement pathway, TNT009 has shown potential to be a first-in-class monoclonal antibody with a novel mechanism of action that could effectively prevent downstream disease processes involving phagocytosis, inflammation, and cell lysis. Encouraged by the success of these studies, we plan to file an IND with TNT009 within the next year.”

Highlights from the oral presentation at ASH included:

  • TNT009 is a high-affinity humanized monoclonal antibody against C1s, resulting in selective blockade of the Classical Complement Pathway (CCP). TNT009 has a novel mechanism of action which may be superior in antibody-mediated autoimmune diseases to other approved agents targeting the Complement system.
  • Cold agglutinin disease (CAD) is an autoimmune hemolytic anemia in which autoantibodies bind to red blood cells (RBC) at temperatures below 37°C, resulting in activation of the CCP. CCP activation leads to hemolysis either extravascularly, when C3b (cleavage fragment of Complement component 3) deposits onto the RBC surface and results in sequestration by the reticuloendothelial system or intravascularly, by formation of the membrane attack complex. In assays measuring C3b deposition, phagocytosis, and cell lysis, TNT009 was shown ex vivo to prevent Complement-dependent activity induced by CAD patient autoantibodies in each of these assays.
  • The presented data show that TNT009 inhibited production of the anaphylatoxins C3a, C4a, and C5a (cleavage products of Complement components 3, 4 and 5), suggesting that TNT009 is a specific and potent inhibitor of the upstream CCP and differentiating it from downstream, terminal Complement inhibitors.

About TNT009

TNT009 is a first-in-class molecule developed to selectively inhibit C1s, a serine protease specific to the Classical Complement pathway of the immune system. By precisely targeting the Classical Complement pathway, TNT009 offers a novel approach for treating Complement-mediated diseases with significant unmet medical needs in the hematologic, renal, and neurological therapeutic areas. With a unique mechanism of action and high target specificity, TNT009 selectively inhibits disease processes in the Classical Complement pathway cascade while maintaining the important immune surveillance provided by the Alternative Complement Pathway and Lectin Complement Pathway. With preclinical and ex vivo data demonstrating TNT009’s efficacy, True North Therapeutics anticipates initiating the first clinical program with TNT009 in late 2014.

About True North Therapeutics

True North Therapeutics is a biotechnology company developing novel therapies that selectively target the Complement pathway of the immune system to address fundamental mechanisms in diseases with high unmet need, including rare diseases. The company’s lead monoclonal antibody drug candidate, TNT009, selectively inhibits a target in the Classical Complement pathway, thereby preventing downstream disease processes involving phagocytosis, inflammation, and cell lysis. True North’s drug development programs are focused on Complement-mediated diseases in the hematologic, renal, and neurological therapeutic areas. True North Therapeutics is located in South San Francisco, California. For more information, please visit www.truenorthrx.com.

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