Delinia Inc.'s $35 million series A sets up the Cambridge, Mass.-based startup to drive straight down the fairway in targeting regulatory T cells (Tregs) to treat autoimmune diseases. Sofinnova Partners and Atlas Venture were co-leads in the round, with Atlas venture partner Saurabh Saha named president and CEO.

Delinia's platform focuses on augmenting Tregs, which represent a relatively small population of T cells, to restore balance to the immune system rather than broadly suppressing it as current medicines do. The company's lead program is a selective agonist of the IL-2 receptor on Tregs that activates and augments a natural regulator of the human immune response.

Saha credited Jeffrey Greve, Delinia's co-founder and chief scientific officer, as the "creative genius" behind the company's technology. The prolific researcher most recently served as vice president of research at Atyr Pharma Inc., which is developing physiocrines, or naturally occurring proteins, initially in rare indications resulting from the immune-related consequences of genetic disease. Previously, Greve served as executive director of stem cell sciences at Exelixis Inc., where he managed the company's long-running notch alliance with Roche AG unit Genentech Inc. and established a drug discovery program around stem cell biology. (See BioWorld Today, June 6, 2005.)

Delinia came together through the opportune convergence of several factors, starting with a body of research suggesting the imbalance between effector T cells and Tregs can be modulated.

"Expanding Tregs, qualitatively and quantitatively, is an emerging concept that is gaining traction very, very rapidly and a potential paradigm shift for the treatment of autoimmune diseases," Saha told BioWorld Today. "We're extremely excited about this."

Trained as a cancer geneticist, Saha was recruited in 2005 from McKinsey & Co. to become global head of the new indications discovery unit at Novartis Pharmaceuticals. He next helped to form Biomed Valley Discoveries Inc. (BVD), a hybrid biotech company funded by the Stowers Institute for Medical Research that seeks to address unmet medical needs in areas considered too early, unconventional or unprofitable for traditional biopharma. As chief scientific officer and, subsequently, president of BVD, Saha helped to push into the clinic the ERK kinase inhibitor, ulixertinib (BVD-523), and a bacteriolytic immunotherapy known as C. novyi-NT (BVD-CNV). (See BioWorld Today, Aug. 14, 2014.)

Saha then was named chief medical officer at Synlogic Inc., another Cambridge, Mass.-based startup incubated by Atlas, which co-led its series A round. (See BioWorld Today, July 23, 2014.)

'OUR STRATEGY IS SIMPLE'

In December, Saha joined Atlas full-time, exposing him to the hundreds of projects sifting through the venture firm's filters. He was immediately drawn to the Delinia story.

"I'm a cancer guy," Saha said, "but when I saw the therapeutic concept and a mechanism of action that was so well-validated, in animals and in humans, I felt I had to lead this company."

Lijun Wu, Delinia's senior vice president of preclinical and early clinical development, also has deep roots in biopharma, with tenure at Concert Pharmaceuticals Inc., Resolvyx Pharmaceuticals Inc., the Novartis Institutes for Biomedical Research and Millennium Pharmaceuticals Inc. – now Takeda Oncology Inc.

Sofinnova partner Henrijette Richter and Atlas partner David Grayzel sit on Delinia's board, which is chaired by Jeffrey Tong, entrepreneur in residence at Third Rock Ventures and former president and CEO of Nora Therapeutics Inc. (See BioWorld Today, April 18, 2014.)

Delinia is pursuing the thesis that expanding the Treg population will prompt a pleiotropic effect, suppressing local inflammation, auto-antibody formation and T-cell mediated autoimmunity. "Tregs sit above all of the bad players that cause autoimmune disease," Saha pointed out. "If we can affect the function of T cells and B cells, we have the potential to go into a number of different autoimmune diseases."

Those indications could include type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, scleroderma, Crohn's disease, rare diseases such as pemphigus vulgaris – a B-cell mediated disease – and chronic graft-vs.-host disease.

"There's a whole host of possibilities," Saha said. "It's one of those molecules that comes along once in a generation or even a lifetime."

The science has advanced to the point where development could move quickly. Saha drew an analogy between Treg biology and immuno-oncology, noting that the former is on the same trajectory as the latter, but at an earlier stage of evolution.

"Where checkpoint inhibitors were first used to activate immune cells to fight cancer, we're now activating an immune cell type, Tregs, to fight autoimmune disease," he said.

Delinia plans to move its first candidate into the clinic in the second half of next year; the company has not yet decided whether initial trials will take place in the U.S. or overseas. A safety study in healthy volunteers is expected to begin shortly with the goal of proving the mechanism in humans. The series A will allow the company to complete that study and up to two proof-of-concept studies in autoimmune indications.

The company has four full-time employees and will expand slowly, as it builds a portfolio of Treg-based candidates behind its lead molecule. Delinia is working with collaborators at the University of California at San Francisco (UCSF) on discovery efforts. Three of the school's faculty members sit on the company's scientific advisory board, which is chaired by Delinia co-founder Michael Rosenblum, assistant professor of dermatology at the UCSF School of Medicine.

Long term, "our strategy is simple," Saha maintained. "Since we believe this is such an important molecule, we want it to benefit as many patients with autoimmune disease as possible. We'll be open to whatever mechanism allows us to do that."