Atlas backs a longtime Vertex employee’s quest to bring CF success to numerous other diseases
One of Vertex’s longest-tenured employees believes he can take the biotech’s biggest medical and scientific accomplishments and use it to develop treatments for more than just cystic fibrosis.
Three years ago, Jonathan Moore, a scientist and then executive at Vertex from 1990 to 2018, founded a company to develop treatments for diseases that, like CF, are caused by mutations in a “super family” of proteins known as ABC transporters.
Jonathan MooreHe’s since managed to convince a few investors. On Thursday, Moore, Atlas Venture and a handful of other blue-chip funds debuted Rectify Pharmaceuticals, backed with $100 million in Series A funds to find small molecules that can correct such mutations in a broad suite of genetic disorders. They’ll start in the liver, but eventually plan to hit diseases in nearly every organ in the body.
“These are expressed in all different organs, liver, lungs, brain, and they play an important role in the body,” CEO Rajesh Devraj told Endpoints News. “You can imagine the amount of targets that are available and delivered for us to go after.”
The new company builds off Vertex’s success in developing a type of drug that essentially had never been built before, a small molecule that can take a mutant, dysfunctional protein and morph it back into a functional one.
That work, conceived of and funded in part by the CF Foundation, ultimately led to four iterations of molecules and combinations of molecules that over a decade turned one of the most common genetic diseases from a likely death sentence into a treatable condition for most patients.
The protein behind CF, known as CFTR, is not unique, though. It’s a transport protein, shepherding salts into and out of cells. And the constantly whirling, busy, huffy place that is the human body has many such transport proteins — 48 to be exact. Accordingly, humankind has many diseases associated with mutations in those proteins.
There are numerous benefits to going after this class of disease, Devraj points out: They are monogenic and researchers can be certain that, if they successfully correct the protein, they can slow or reverse the disease; and it’s been done before, including by Rectify’s founder.
Small molecules are also easier to develop, make and deliver than gene therapy or other biologic drugs, especially for rare diseases that often get overlooked by drug developers.
“We are — I think we are the foundation,” Devraj said. “We are the leaders in ABC transporter biology.”
But there are also key hurdles. Although Vertex proved that one could develop a small molecule to transform a mutant protein, no one has yet done it successfully for any other disease. The big biotech has had its own troubles applying the strategy to a new condition.
Among the biggest challenges with these diseases, Devraj acknowledged, is that often different patients with a single disease have different genetic mutations. Like words, genes can be mispelled in any number of ways.
That means Rectify will potentially need different drugs or different combinations of drugs to fix all or most of the mutations in a given disease. It took Vertex a decade to find the right triad of molecules that work for 90% of patients’ CF and it could be even harder, both scientifically and economically, to do the same for disorders that are even more rare — as the ones Rectify pursues will almost certainly be.
To overcome those challenges, Rectify is applying some of the same tricks Vertex did, including developing tests that, in theory, could allow them to quickly tell in a lab whether a molecule is having its intended effect and restoring shipping lanes into and out of cells. Devraj said they have already developed the first assays but declined to describe them.
The company is keeping its indications undisclosed for now, too, except that they will start in the liver, before hopefully expanding to the lung and central nervous system. The current financing, co-led by Omega, Forbion and Longwood, should get them through proof-of-concept clinical trials for the first molecule.
“Nothing is going to be easy,” Devraj said. That’s “why we do this job.”
