Elissa Martin

Inozyme Pharma, a new biotech company founded by School of Medicine professor Demetrios Braddock, has raised $49 million to develop enzyme replacement therapies for rare diseases involving overcalcification of soft tissues and undermineralization of bone.

Researchers at the startup are currently working on a treatment for infants with generalized arterial calcification of infancy, or GACI. Inozyme plans to use the funding to bring the preclinical therapy into human testing and ultimately the clinic in two to three years. Over the span of 18 months, the startup has gotten funding from Longitude Capital, New Enterprise Associates, Novo Ventures and Sanofi Ventures.

“We’d like to get this drug into the vulnerable patient population, which desperately needs it, as fast as possible,” Braddock said.

Braddock founded Inozyme in 2016 after discovering a promising target to treat GACI, which was only recognized as a disease in 2001. GACI develops within the first week of life and results in death by six months in most patients, according to a press release from Inozyme.

The disease arises from a deficiency in an enzyme called ENPP1, which is responsible for making pyrophosphate, a molecule that inhibits calcification. To treat calcification diseases, Inozyme will design therapies to replace patients’ faulty enzymes with a circulatory form of ENPP1 that can raise pyrophosphate levels in a systemic manner, according to Robert Terkeltaub, professor of medicine at University of California San Diego and member of Inozyme’s Scientific Advisory Board.

“Inozyme is a company focused on technology and drug delivery and helping patients with rare diseases using exquisite molecular technology,” Terkeltaub said. “It takes an innovative approach to multiple genetic diseases and could be a landmark medical advance.”

Before even studying GACI, 10 years ago, Braddock’s lab at Yale had been working with molecular biophysics and biochemistry professor and Head of Branford College Enrique De La Cruz’s lab to study a family of enzymes that included ENPP1 for its relation to cancer. The idea to focus on rare diseases of calcification emerged when Braddock and De La Cruz stumbled across a related homolog of ENPP1 in this family, De La Cruz said.

Knowing that GACI was a disease associated with the loss of function of ENPP1, Braddock came up with the idea to use this homolog as a potential treatment for GACI.

The researchers knew that this enzyme held promise as a drug because it was stable and long-lived, Braddock said. They next modified the enzyme for drug delivery in the body. This process involved making the enzyme soluble through protein engineering and more stable in solution by forming a fusion protein with another stable protein.

Although the company raised $49 million last year, the journey up to this point has been challenging, Braddock and De La Cruz said.

“This company, were it not for persistence and support from three different Yale departments — MB&B, pathology and pharmacology — would not exist, and this entire research program would’ve been viewed as a failed research program because it would not get the support from federal funding agencies,” De La Cruz said.

Rejected multiple times by federal grant programs, the labs turned to Joseph Schlessinger, chair of pharmacology at the School of Medicine and a member of Inozyme’s Scientific Advisory Board. On Schlessinger’s recommendation, the team formed its own company to seek funding from potential investors.

GACI is not the only disease that Inozyme will work on, according to the researchers. The company is looking to expand into other diseases involving paradoxical mineralization, the physiological disease state involving issues of calcification and bone mineralization.

This range of diseases includes one called pseudoxanthoma elasticum, or PXE, which is also caused by a deficiency in ENPP1 and results in artery calcification, in which calcium deposits form in the arteries and narrow them. Terkeltaub noted that some patients who survive GACI in infancy later develop PXE.

The researchers said they hope to use the $49 million to validate this strategy of enzyme replacement therapy — treating patients with this drug, effectively raising pyrophosphate levels and leading to clinical improvement. Braddock said they hope to start treating children within two to three years.

“As an investor, you might ask how many lives are saved,” De La Cruz said. “But as a parent, every parent knows that one is enough, and I know that’s what motivates us.”

Amy Xiong | amy.xiong@yale.edu