Cystic fibrosis has become the poster child for precision medicine – most new therapies are carefully tailored to a CF patient’s genetic makeup. University of North Carolina spinout Spyryx Biosciences is proposing a one-size-fits-all approach to the disease: It’s developing a peptide-based therapy that, in theory, could be effective among all CF patients.
This startup’s still pre-IND and in the final stages of selecting a lead compound – it’s only now beginning to emerge from stealth mode. The underlying research comes from University of North Carolina School of Medicine researcher Robert Tarran.
“He found a whole new mechanism on how the lung manages fluid on its surface – which is the primary issue in cystic fibrosis,” CEO John Taylor said.
Spyryx has more than $100,000, largely from angel investors, though it also has taken out a loan from the North Carolina Biotechnology Center. Spyryx is aiming to raise a Series A round and also study the drug’s efficacy in COPD, though it’s starting out with CF.
The hallmark of CF lungs is that they excrete thick and sticky mucus, which winds up clogging airways and making it difficult to breathe. This happens because of a mutation of the CFTR gene, which makes the epithelial sodium channel hyperabsorbative – upsetting the fluid regulation in the lungs and drying out the mucus.
Tarran found a peptide derived from the SPLUNC1 protein that may, in essence, stop this channel from getting overactivated – normalizing the excretion of mucus in the lungs.
“We’ve taken that peptide, and optimized that to a therapeutic,” Taylor said.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Spryx intends to develop this synthesized peptide, called S18, as an inhaled peptide replacement therapy that’s meant to work for all CF patients – it won’t be genotype dependent.
There are a number of cystic fibrosis drugs in development and on the market – but the most effective (and costliest) drug, Kalydeco, only works in a small subset of patients. Though the Vertex Pharmaceuticals drug demonstrates how impactful precision medicine can be, the market could use a CF drug that is effective regardless of which mutation a patient has, Taylor said.
“There are a lot of people working on CF, because the business model is quite well-established. It’s a very large orphan disease, and quite en vogue at the moment,” Taylor said. “But most want to fix the CFTR mutation the way that Vertex has. We think that the Kalydeco mode of treatment is an inefficient way to approach this disease.”
Another company that’s developing a peptide-based approach is Rhode Island’s Calista Therapeutics that also aims to treat a larger swath of CF patients. Though it uses a different mechanism than Spyryx, it also aims to regulate CFTR transport and prevent mucus buildup.
In any case, this epithelial sodium channel has been a target for CF researchers for some time, Taylor said. But small molecule therapies have been ineffective to fix this channel – thanks in part to the safety profile, Taylor said. Small molecule drugs have historically crossed into the bloodstream and caused a fluid imbalance in the kidneys, he said – making researchers more averse to this approach.
“Our safety profile is dramatically different,” Taylor said, noting that the company has plans to conduct IND-enabling studies later this year.
