Pharma, Startups

For new Rhode Island firm, peptides hold hope for disease-altering cystic fibrosis treatments

It’s been nearly two-and-a-half decades since the gene associated with the inherited disease cystic fibrosis […]

It’s been nearly two-and-a-half decades since the gene associated with the inherited disease cystic fibrosis was discovered, paving the way for disease-modifying drugs. In that time, only one such drug has been approved in the U.S. and Europe — Vertex’s Kalydeco. And that drug is only approved for the 4 percent of CF patients who have one particular gene mutation.

Among the companies working toward a treatment for the other 96,000 CF patients is a new company called Calista Therapeutics, which is doing preclinical work on peptide drugs that would alter the course of the genetic disease.

Calista has used a proprietary peptide drug platform to discover and develop two drug candidates that target the underlying molecular defect in a gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein plays a critical role in trafficking liquids through cells in many of the body’s organs. When a mutation is present in the CFTR gene, that trafficking is impaired and cells that line the passageways of those organs produce mucous that is abnormally thick and sticky. In these patients, impaired lung function usually becomes fatal by age 40.

Procaftor, Calista’s lead candidate, is designed to restore function to the CFTR transporter in the lungs and prevent the buildup of thick mucus. President and CEO Andrew Mallon said that preclinical studies have suggested clinical efficacy with no signs of toxicity.

It’s still at least six years away from potential regulatory approval, according to the company, but would come in the form of a powder and be used as a once-daily therapy inhaled through a nebulizer. It could also be used in conjunction with other therapies, Calista says.

A second candidate called Calcaftor, which targets CFTR through a different mechanism, is also in preclinical development.

Mallon said the startup he formed in May of last year is now working with partners like Cystric Fibrosis Foundation Therapeutics to confirm Procaftor’s efficacy, nontoxicity, shelf life and stability. The company also has two SBIR grant applications pending, he said.

But Calista will need a lot more cash — at least $8 million — to get Procaftor through phase 2a clinical trials, at which point Calista would have the desired data to lure a potential licensee. Mallon said he’s hoping to use some of his time at the MassChallenge accelerator this summer developing relationships with partners and investors.

There are other companies far ahead of Calista in their work on disease-altering CF drugs: PTC Therapeutics is in phase 3 studies of its drug Ataluren and Vertex Pharmaceuticals has another candidate in phase 3. Pfizer is also working in a partnership with the Cystic Fibrosis Foundation on preclinical research. But peptide drugs for CF present a promising proposition for a few reasons, according to Mallon.

For one, there’s great need in the CF community, which is supported by well-funded patient advocate groups. On the medical side, Mallon said the preclinical model for CF is more clinically predictive than models for many other diseases. And on the science side, the chemistry of peptide drugs allows for relatively cheap production of large quantities. “With peptide drugs, you can do a lot more design and a lot less testing,” he said.

Peptides have posed a challenge to drug developers in the past because of their poor oral bioavailability. By making its drugs inhalable, Calista is topically applying them to the lungs, where they need to be absorbed.

Mallon is a neuroscience researcher and biotech entrepreneur who’s also co-founded Ardane Therapeutics to develop drugs for stroke, glaucoma and autism. Rounding out the Calista team is chief operating officer Gary Robinson, who brings experience in strategic planning and operations support for early stage companies, and Vice President of Preclinical Research Ron Wold, who specializes in toxicology assessment.

Mallon said he’s hopeful that Procaftor could additionally be useful in other diseases as it appears to also have immunoprotective capability. “We have a strategic opportunity to develop peptide therapeutics through the lungs more broadly,” he said.

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