True North Therapeutics Inc. took advantage of "incredibly strong momentum" following disclosure of initial data from an ongoing phase Ib study of its lead complement inhibitor, TNT009, in cold agglutinin disease (CAD) to lasso an oversubscribed $45 million series D financing, according to CEO Nancy Stagliano.

The late-breaking oral presentation, reported in June at the European Hematology Association (EHA) in Copenhagen, revealed consistent and positive responses to TNT009 in CAD patients based on the correction of disease-associated anemia and hemolysis.

"That data set the stage for a lot of progress and interest in the financing from high-quality crossover investors as well as our insiders," Stagliano told BioWorld Today. "Investors were clearly impressed by the encouraging clinical data that we shared."

The round was led by new investors HBM Healthcare Investments and Redmile Group and existing investor Perceptive Advisors and included participation by additional new investor, Franklin Templeton Investments, and existing investors.

The financing – the company's largest so far – gives the South San Francisco-based firm "continued flexibility and optionality" to accelerate development of TNT009 in CAD beyond the phase Ib and to explore the asset's potential in other rare diseases targeting the complement system, Stagliano said.

As the initial indication, CAD is a rare autoimmune disease that presents later in life, manifested when autoantibodies target and destroy red blood cells, causing severe anemia, fatigue and potentially fatal thrombosis.

The EHA presentation covered the first five CAD patients dosed in True North's phase Ib study. Each received an initial dose of 10 mg/kg of TNT009 followed by a full dose of 60 mg/kg one to four days later, and three additional weekly doses of 60 mg/kg. Data showed that four of the five patients responded to TNT009 within the first 24 hours. Of the four responders, three patients achieved complete response (hemoglobin > 12 g/dL) after the four-week dosing period.

TNT009 was well-tolerated without need for premedication, and no serious, drug-related adverse events occurred.

"We thought this was a strong demonstration – to have gotten a signal in this disease – of the biology and the science that we're leading with this classical pathway inhibition," Stagliano said. "Given this success, we want to get this drug to patients as quickly as possible. We have really high hopes for what TNT009 will continue to do in this indication."

'We're at the tip of the iceberg'

Last week, True North disclosed that the FDA granted TNT009 orphan drug designation to TNT009 to treat autoimmune hemolytic anemia, including CAD, following similar designation by the EMA in February. No drug therapies to treat CAD are approved in the U.S. or Europe.

Considering that TNT009 selectively blocks the classical complement pathway by targeting C1s, a serine protease within the C1-complex – and that True North is believed to be the first company to show early proof of that activity in the clinic – the company has identified warm autoimmune hemolytic anemia, antibody-mediated transplant rejection and bullous pemphigoid as additional potential indications for the drug.

"All of these rare diseases share the same biology that we're the first to drug," Stagliano said.

The company is following the science to determine where the pursuit of treatments for classical complement dysregulation may lead.

"There's clearly a deep bench here in terms of our expertise in this space," she said. "We're conducting considerable ongoing research to make sure that we're exploring all the indications that make sense. Whether that's with TNT009 or our next-generation anti-C1s antibodies, we're at the tip of the iceberg in terms of the difference these drugs might make to patients' lives."

True North was spun out of privately held Ipierian Inc. in 2013, using a portion of a $30 million equity round by the parent company as its series A. That decision was driven by advancements in Ipierian's two monoclonal antibody programs – one targeting the tau protein and the other the complement pathway. (See BioWorld Today, Sept. 5, 2013.)

Less than six months later, Bristol-Myers Squibb Co., of New York, picked up Ipierian, also headed by Stagliano, and its tau program for $175 million in cash and up to $550 million in development and regulatory milestone payments, plus royalties on net sales. (See BioWorld Today, April 30, 2014.)

Between June 2014 and the end of last year, True North extended its A round to $22 million, closed a $35 million series B and landed a $40 million series C to advance TNT009 and its as-yet undisclosed next-gen anti-C1s antibodies. (See BioWorld Today, June 18, 2014, and Dec. 4, 2015.)

The company has grown to 19 employees – a comfortable head count for now, according to Stagliano – and is willing to entertain but in no hurry to rush into partnerships.

"Obviously, a financing like this one and those we've done in the past give us the ability to continue to develop our options independently," she said. "We've been talking with potential partners. Clearly, there's a lot of interest in the complement system as evidenced by the companies playing in this space. As we continue to show progress, I believe that interest will continue to grow."