DHFR inhibitors(Vyera Pharmaceuticals LLC)

Cambridge biopharma startup Spero Therapeutics is raising a $30 million Series B round for its therapies that increase the potency of existing anti-infective drugs. How? By making Gram-negative bacteria susceptible to drugs geared toward Gram-positive bacteria. Spero’s is developing a pipeline of drugs that treat both Gram-negative and Gram-positive bacteria, fungi and protists. Its platform, called the Potentiator, is essentially a combination therapeutics that target drug resistant microbes. The company’s developing small molecular “potentiators” that interact with the outer membrane of Gram-negative bacteria to increase its permeability – allowing Gram-positive antibiotics to enter these cells, and kill them. It’s readying itself to submit this platform for IND, so it can begin human trials. Another compelling part of Spero’s approach is its use of DHFR, an enzyme that – when inhibited – disrupts bacterial cell growth and division. The antibiotic trimethoprim, a DHFR inhibitor, has been used for more than 50 years – but resistance is growing to this drug. Spero’s idea is to develop a next generation of DHFR inhibitors, though it’s still conducting preclinical work for this pathway. Spero is also developing an MvfR program, which is meant to blunt the virulence of infections, which it says can “buy time” so antibiotics can take effect. The company has partnered with Roche on this approach. Funding comes from Atlas Venture, SR One, MRL Ventures, Lundbeckfond Ventures, the Kraft Group and Partners Innovation Fund.