True North Therapeutics Inc. raised $40 million in series C equity funding to advance development of its lead complement inhibitor, TNT009, through potential registration-enabling studies for cold agglutinin disease (CAD), while also advancing other complement inhibitors in its pipeline.

New Leaf Venture Partners led the round, which also included new investors Perceptive Advisors and Cowen Private Investments, as well as existing investors Kleiner Perkins Caufield & Byers, MPM Capital, Orbimed, SR One and Baxalta Ventures. Isaac Manke, a partner at New Leaf, will join True North's board.

The South San Francisco-based company, spun out of Iperian Inc., raised a $22 million series A round in June 2014, followed by a $35 million series B round in April. Since then, it initiated a phase Ia study with TNT009, now complete, and plans to begin a phase Ib study later this month. That study will test the drug in patients with CAD, warm autoimmune hemolytic anemia (AIHA), antibody-mediated rejection for kidney transplants and bullous pemphigoid, a rare and debilitating skin disease. (See BioWorld Today, Sept. 4, 2013, and June 18, 2014.)

The phase Ia data will be presented at the J.P. Morgan Healthcare Conference in San Francisco in January, while a readout from the phase IIb study will come sometime after the company has it in hand, around the middle of 2016, True North CEO Nancy Stagliano told BioWorld Today.

Simultaneously, the company is pursuing both FDA and EMA orphan status for CAD and warm AIHA. With data in hand, it expects to seek an FDA breakthrough designation.

CAD is a rare AIHA in which a patient's own auto-antibodies target and destroy the red blood cells, causing anemia, fatigue and potentially fatal thrombosis. It may affect as many as 20 people per million, though estimates of its prevalence vary. Current standard-of-care therapies include steroids and anti-CD20 monoclonal antibodies. However, many patients have high rates of anemia and do not respond to those treatments, according to True North.

Alexion Pharmaceuticals Inc.'s Soliris (eculizumab), another complement inhibitor, is approved for the treatment of paroxysmal nocturnal hemoglobinuria in the U.S. and Europe but not CAD, though it has also been tested against the indication. The phase II Decade study was complete in June, according to Thomson Reuters Cortellis Clinical Trials Intelligence.

"When we studied the literature and started to really understand the best characterized diseases that the classical complement system was involved in, cold agglutinin disease really reached the top of the list," said Stagliano. Working in the hematology space, in an indication such as an anemia is "very tractable" for a small company with private dollars, she said, because of the ability to get signals such as hemoglobin levels quickly in the clinic to understand whether a drug is active.

By way of example, she said, there's potential within the phase Ib for proof of concept that, after a month of treatment with TNT009, investigators would see improvements that would help the company decide whether to pursue a small registration-enabling study.

The complement system is composed of a set of more than 30 proteins that, when activated in sequence, help destroy pathogens and eliminate infection. TNT009 inhibits C1s, a serine protease within the C1-complex in the complement system that is activated by immune complexes, triggering an enzymatic cascade. Aberrant activation of the pathway can result in a range of cellular pathologies in numerous autoimmune and alloimmune conditions.

In addition to TNT009, True North is also working on another classical complement inhibitor, TNT010, which it plans to move into a phase I study next year for a yet-to-be-disclosed rare disease. Additional complement inhibitors are lined up behind those, Stagliano said.