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With $22M, True North Points Toward Rare-Disease Clinical Trials

True North Therapeutics has topped off a $22 million round of Series A funding, the company said Tuesday, and will push its lead drug candidate into clinical trials next year.

The South San Francisco, CA-based startup is a sequel, of sorts. It started out as a second research program at iPierian, which, after a tumultuous first few years that included a management revolving door, focused its cutting-edge stem cell science to explore neurodegenerative disease.

The program that became True North was left to the side for a while. Last summer, as part of a $30 million funding for iPierian, True North’s work was cleaved off into a new company. An undisclosed amount of that cash was rolled into True North’s Series A, which has now finally closed. The firm is targeting the complement system, a family of proteins in the human innate immune system that help antibodies kill bacteria. They lie dormant until an antibody latches on to a suspected invader. But the system is far from perfect, and the complement proteins can misfire or go haywire and cause severe, sometimes deadly inflammation. That’s why something as relatively mild as a bee sting can put someone into anaphylactic shock (named after the anaphylatoxins released when the system is triggered).

True North’s work aims to subdue the complement system’s classical pathway, one of three complicated series of proteins that trigger and affect one another and lead to the clearance of pathogens. Because the complement system does plenty of necessary work, too, drugging a part of it is risky business. In the previous decade, CEO Nancy Stagliano (pictured) was part of the team at Millennium Pharmaceuticals that brought to market bortezomib (Velcade), the first drug approved to target the ubiquitin protease system, another tangled biological network.

“When we had Velcade approved at Millennium, we taught the world we could drug a very complicated system that’s involved in normal body function,” said Stagliano.

Much of the cash raised in True North’s Series A came from iPierian investors; the only new non-iPierian investor on board True North is Baxter Ventures, an arm of the drug maker Baxter International. The holdover investors—Kleiner Perkins Caufield & Byers, SROne (the venture arm of GlaxoSmithKline), MPM Capital, and Biogen Idec New Ventures—will reap at least some reward from iPierian, which was acquired in April by Bristol-Myers Squibb for $175 million guaranteed and $550 million in potential milestone payments.

iPierian raised north of $60 million in venture capital, so at least some milestones need to kick in for a generous return. Some of that unfulfilled promise has carried over to True North, which is producing antibody therapies against rare autoimmune and inflammatory diseases. True North hasn’t yet chosen a specific disease to tackle, says CEO Nancy Stagliano (pictured above), who was CEO at iPierian from 2011 until its purchase this year, but the Series A cash should allow the firm to get into a Phase 1 clinical program to look at several disorders. Of interest, said Stagliano, are autoimmune hemolytic anemias, a group of rare diseases in which a patient’s antibodies turn against her own red blood cells and essentially blow them up.

Despite its origins at iPierian, the True North program has little to do now with the stem cell discovery work that helped iPierian crudely approximate human neurological models. Instead, the company will move its compound toward the clinic by testing it in human blood, an unusual research path blazed by Alexion Pharmaceuticals, which has turned its antibody that targets the complement pathway, eculizumab (Soliris), into one of biotech’s biggest rare-disease success stories.

“We’d be crazy not to follow the path to some extent that Alexion did with Soliris,” said Stagliano. There was no animal equivalent, or model, that could be used in preclinical testing, so regulators accepted “ex vivo” proof of concept—using blood samples from patients with the disease Soliris was ultimately approved for: paroxysmal nocturnal hemoglobinuria (PNH), a rare genetic blood disease that creates anemia, blood clots and in a small minority of patients, leukemia. True North has already done tests with blood samples from patients with cold agglutinin disease, one of the autoimmune hemolytic anemias that seems to be triggered by lower body temperature. “We were able to block that,” said Stagliano.

One difference between Alexion’s Soliris, which is being tested for several other indications, and True North’s TNT009, is that ‘009 inhibits a specific target, C1s, at the beginning of the classical pathway, while Soliris targets C5, a protein at the end of all three pathways in the complement system.

Imagine three liquid streams pouring into a single funnel. Soliris, and other C5 inhibitors in development elsewhere, are disrupting the stream as it leaves the funnel, while True North is disrupting one of the streams as it enters. “We believe hitting upstream will have an advantage in certain disease settings. There’s a whole lot of action between C1 and C5” that C5 inhibitors do not address, Stagliano said.

The $22 million Series A is tranched and should last True North through its Phase 1 clinical trials into 2016, according to Stagliano.