Think ‘Shark Tank,’ without the teeth

Jeffrey Smith has an idea for a drug, but he could use some help.

He’s developing a new treatment that can increase the concentration of protective melanin in the skin, which could improve the quality of life for those extremely sensitive to sunlight. People with porphyria, for instance, can develop significant burns after a few minutes outside.

But there’s still much more that Smith, Harvard Medical School assistant professor of dermatology at Brigham and Women’s Hospital, wants to consider before moving too far along in the process. Which particular condition should researchers target in early clinical trials? Are there implications for his skin pigmentation antibody that he’s overlooked?

Smith talked through his research and the potential impacts of his work at “Guppy Tank,” Harvard Office of Technology Development’s tongue-in-cheek knock-off of ABC’s “Shark Tank.”

Like the hit TV show, Smith pitched the idea — co-developed with Andrew Kruse, professor of biological chemistry and molecular pharmacology in the Blavatnik Institute at Harvard Medical School — to a panel of four investors who gave feedback.

Unlike the show, the judges didn’t yell at one another or pressure Smith to make a major business decision on the spot.

“We’re hopeful that the comments are more guppy than shark,” said Grant R. Zimmermann, managing director of business development for the Blavatnik Biomedical Accelerator.

Smith’s presentation centered around the new treatment developed with Kruse.

“We have a melanocortin-1 receptor agonist that can tan the skin,” he said in his opening, “and that’s the pitch.”

The drug would not be the first to target this skin-pigmentation mechanism. One approved drug already treats porphyria through the same mechanism.

While the existing treatment can be effective, 46 percent of those who use it develop nausea. It’s also not especially convenient, requiring an implant a half-dozen times a year.

Smith and Kruse’s treatment is less invasive. Patients can get an injection every six months.

Broadly, Smith said he could see the drug used for skin-cancer prevention. He also mentioned conditions like xeroderma pigmentosum (XP), a genetic disorder that leaves patients unable to repair UV damage from the sun; they experience squamous cell carcinoma at a rate 10,000-fold higher than average. (The rare disease currently has no approved treatment.) As a practicing dermatologist, he sees potential to treat transplant recipients, who have an elevated cancer risk because they take anti-rejection drugs to suppress their immune systems.

Panelists provided feedback about the potential target, dosing, and insurance implications of the drug.

Mike Schlabach, a senior vice president at the venture capital firm Curie Bio, asked Smith about how the mechanism worked in animal models. He suggested that if the models showed significant decreases in nausea versus other drugs, it could be a meaningful quality-of-life improvement over the approved drug.

That said, if the alternative is severe and rapid burns to the skin, the nausea side effect might not be so bad.

Smith said the specific skin receptors don’t match up well between humans and mice, but it was at least promising that, in one study, the mice didn’t show any concerning side effects.

Schlabach added that because some of the target diseases Smith identified are quite rare, the drug would need to show dramatically better outcomes than existing options. Otherwise, insurers are going to suggest simpler solutions, like wearing more sun-protective clothing.

Elias Quijano, a principal at venture capital firm Northpond Ventures, asked whether Smith and Kruse had looked into the mechanism of action for other effects aside from melanin production. He wondered whether there were other activity or repair pathways that the mechanism displayed.

Smith said early research did seem to show that it protected skin from cancer in ways besides darkening the skin.

Gunes Bozkurt, director of venture investments at Beiersdorf, wondered about modulating the dosage of the drug. What if people experience more pigmentation than they desired or uneven skin tone changes?

Smith said that different cases had different priorities. Those suffering from a debilitating illness would likely not care as much about cosmetic imperfections — provided the treatment was effective.

In the distant future, if the drug was approved for cosmetic purposes, he thought people would likely want a version that had a shorter half-life so they could regularly adjust the dosage and their appearance.

Chaya Patel, a principal at Mission BioCapital, asked whether a future trial would compare their drug to the implant or a placebo. Smith said he’d love to run the drug head-to-head against a competitor — an option he thinks would be possible considering the similar primary endpoints his drug and existing ones would target in relatively small trials.

As for questions about what indication the drug would target first, Smith cited XP as a possibility. While the disease is extremely rare in the U.S. (with about a 1 in 1 million incidence), it is more common in Japan (about 1 in 20,000), where patients are funneled to dedicated centers upon diagnosis.

Smith imagined a “very small, focused trial” in Japan — helping the drug get approved in a specific indication before expanding to other uses, including potential cosmetic ones.

Unlike on “Shark Tank,” there was no dramatic conclusion. Smith didn’t have to sell his company, partly due to the fact that no company yet exists. But much of the feedback and suggestions that emerged from “Guppy Tank” will likely prove valuable as he and Kruse move along the path of drug development.