New York-based Hoth Therapeutics Inc. said preliminary preclinical data on a topical nanoparticle formulation of the endocannabinoid anandamide (AEA) it licensed from Zylö Therapeutics Inc. represents "a positive step toward underlining the transformative potential" of the early stage therapy for the skin disease cutaneous lupus erythematous (CLE). Developed in partnership with Zylö, it's using that company's extended-release Z-pods technology to both sustain the drug's duration of effect and, at least in mice, significantly improve lesion scores.
Hoth CEO Robb Knie told BioWorld that his team next plans to contact the FDA to schedule a pre-IND meeting, hopefully in the second quarter of this year, to discuss running either a phase I or even a phase II study. The latter, he said, might be supported by the vast amount of scientific literature on anandamide, which has been explored extensively in immunology and other research.
After an initial spike, Hoth's shares (NASDAQ:HOTH) fell 4.7% following the news to $4.72 on Feb. 12. Formed in 2017, the company launched its IPO in February 2019 at $5.60 per share for net proceeds of $5.8 million.
Cutaneous forms of lupus, those that affect only the skin, account for about 10% of the estimated 5 million lupus cases worldwide. Current treatments typically include corticosteroids, but can also have side effects, such as skin-thinning associated with overuse.
Meanwhile, Hoth is already advancing other programs in its portfolio, starting with Biolexa. It's a noncorticosteroid for pediatric atopic dermatitis (AD) that the company plans to test first in Australia. If successful, it could ultimately compete against Pfizer Inc.'s topical PDE4 inhibitor, Eucrisa (crisaborole), as well as other medicines, such as blockbuster AD drug Dupixent (dupilumab, Regeneron Pharmaceuticals Inc. and Sanofi SA). It's also advancing a topical aprepitant to counter the dermatological related side-effects of erlotinib therapy in cancer patients and a preclinical gene therapy program for asthmatics.
The company has about four full-time employees and 11 heavily involved scientific consultants who help plan its preclinical work and trials, an arrangement that helps "bypass a lot of the speed bumps when it comes to your PK and different tox studies, or manufacturing the therapeutic and how the APIs work," Knie said.
In starting Hoth, Knie said his main goal was to make therapies that are accessible and affordable. "I think we're doing that," he said. For each program, he said, he talks with his team about how to pursue them in a way that's "cost-controlled, and where we're not spending a ton of money" that would necessitate charging patients high prices.
Based in Greenville, S.C., Zylö was founded to commercialize a sustained-release delivery technology developed at New York's Albert Einstein College of Medicine. Its Z-pods employ highly engineered silicon-based xerogel particles which, when applied to the skin, can embed in its top layer (the stratum corneum), to release a chosen payload over an eight- to 24-hour period before naturally sloughing off. Though powder-like in appearance, they can be blended with creams, gels or ointments for application. When rubbed into the skin, the Z-pods form what the company has characterized as "a patchless patch."
In the context of treating CLE, the Z-pods carry AEA which, delivered via a coconut oil vehicle alone has some impact on reducing plaques in the mice tested to date. However when delivered via Z-pods, the effect is even greater. While the exact mechanism of action isn't entirely clear yet, Zylö CEO and founder Scott Pancoast told BioWorld that it may or may not have to do with the way the pods lodge in the pores and follicles of treated areas for sustained release. It may also be attributable to the way the Z-pods help AEA bypass enzymes that could break it down prematurely.
While there are still several mice left to evaluate in the preclinical study, Pancoast said that "the data are quite clear" so far. Silica particles have a long and deep track record on the safety front. Being applied topically, I think they're going to have good luck with the FDA," he said.