The first drug for neurofibromatosis type 1 (NF1) is available to patients following the FDA’s approval of the AstraZeneca treatment earlier this year. Biotech startup NFlection Therapeutics is vying to be runner-up, but its founders say they can eventually win out with a drug that takes a different approach than the commercialized pill while also offering a safer and more effective way of addressing the tumors and skin bumps caused by the rare disease.
NFlection is developing its drug as a topical gel. CEO Christopher Powala says that unlike oral drugs that travel throughout the body and spark a range of side effects along the way, this gel delivers its therapeutic benefits directly to the skin. The drug, NFX-179, is designed to quickly break down upon reaching the liver, reducing the risk of toxic effects compared to others in this drug class, known as MEK inhibitors.
“We’re able to dose very high concentrations in the skin,” Powala says. “Should it enter the bloodstream, it will have no effect. We feel very confident we won’t have the issues associated with oral MEK inhibitors.”
NFlection recently unveiled a $20 million Series A round of investment from venBio Partners and F-Prime Capital. The Wayne, PA-based startup plans to apply the new capital toward clinical tests of its topical gel.
NF1 is a genetic disorder caused by a mutation to the NF1 gene, which codes for a tumor suppressor protein called neurofibromin. Nonfunctioning or reduced levels of this protein lead to tumor growth. NF1 is characterized by spotting on the skin and tumors called neurofibromas that develop on nerves. These tumors form under the skin and, in some cases, within organs in the body. While benign, the tumors can be disfiguring. Surgery is one treatment option but not all NF1 tumors can be addressed this way.
FDA approval of the AstraZeneca (NYSE: AZN) drug, selumetinib (Koselugo), covers NF1 patients whose tumors can’t be removed surgically. The drug blocks MEK, an enzyme that’s key to a signaling pathway that drives the growth of cancer cells. The first FDA-approved MEK inhibitor was GlaxoSmithKline (NYSE: GSK) drug trametinib (Mekinist), for melanoma. Side effects for this drug class include skin rash, diarrhea, nausea, and fatigue. Those side effects are listed on selumetinib’s label, which also flags potential heart, eye, and muscle problems.
Selumetinib didn’t start out as a prospective NF1 treatment: Research at the National Cancer Institute led to its initial development by Boulder, CO-based Array Biopharma, which evaluated it in lung cancer, melanoma, and thyroid cancer. A partnership with AstraZeneca put the compound in the hands of the British pharmaceutical giant, which first tested it in non-small cell lung cancer.
NFlection’s drug was developed from the startup’s internal research, which dates to 2017, according to Mark de Souza, the company’s co-founder and executive chairman. The gel, intended for once daily application, is designed to penetrate the outer layer of skin and reach nerve cells over a span of 24 hours, then stay there in high concentrations—“much higher than you would get from oral administration,” he says.
In preclinical testing, Powala says the NFlection gel was able to resolve NF1 tumors. The next step is a Phase 2a clinical trial enrolling about 48 patients. The study will assess the drug’s ability to suppress biological indicators of neurofibroma progression. It will also evaluate a range of doses to determine which one to advance to a larger Phase 2b clinical trial.
NFlection is also eying other applications for its drug. The first is to remove birthmarks formed by the same signaling pathway that drives tumor growth in NF1. Some of these birthmarks can cover a large portion of the scalp, face, and neck, making them cosmetically significant, Powala says. Surgery and laser treatments are options for birthmark removal, but he says the NFlection drug could offer patients a way to address disfiguring marks without the risk of scarring or other complications. A study in childhood birthmarks is expected to start this summer.
Treating squamous cell carcinoma, the second most common form of skin cancer, is another potential application of the NFlection drug. Pawala says the company hopes to start a Phase 1 study in that form of cancer in mid-2021.
“We have a pipeline and a product for the first compound in these three indications,” de Souza says. “There are other [potential targets]. This is where we’re focused right now.”
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