Developing the Next Generation of Drugs for Dermatological Conditions

The World Health Organization states that dermatological (or skin) diseases are amongst the most common of all human health afflictions, affecting approximately 900 million people worldwide at any one time. With so many people impacted, there is a clear need to develop novel therapeutics with the best efficacy and safety profiles as possible.

We recently spoke with Robb Knie, CEO of Hoth Therapeutics to learn more about the company’s mission, drug development pipeline, and the various dermatological conditions they are designing therapeutics for.

Laura Lansdowne (LL): For some of our readers less familiar with Hoth Therapeutics, could you tell us a little about the company mission and history?

Robb Knie (RK): Hoth Therapeutics is a publicly listed biopharmaceutical company trading under the stock symbol “HOTH” on the NASDAQ. The company is dedicated to developing and bringing new generation therapies to patients suffering from dermatological disorders. Hoth first started to develop its leading therapeutic platform to eradicate Staphylococcus aureus or S. aureus in the skin at the University of Cincinnati. One of our leading scientific advisors, Dr Andrew Herr, led this research and achieved positive results at the preclinical stage conducted at the University of Miami. Since then, the company has developed a strong intellectual property portfolio through exclusive collaborations with various universities to treat skin conditions including atopic dermatitis, chronic wounds, psoriasis and acne. Hoth recently completed a 28-day animal toxicology study in which initial data showed all animals were in good condition with no adverse safety effects. The company is planning a clinical trial in humans later in 2020.

LL: Can you tell us about the indications you are developing therapeutics for?

RK: Hoth’s pipeline currently contains clinical-stage treatments for dermatological conditions with product candidates in various stages of clinical development with exclusive licenses to patents and trademarks. Current therapies include BioLexa, VNLG-152, Z-Pods, aprepitant and genetic markers for food allergies & eczema.

• The BioLexa Platform is a proprietary, patented antimicrobial therapy, targeting atopic dermatitis (AD) or eczema and chronic diabetic ulcers. The platform is based on cutting-edge scientific research from University of Cincinnati.
• VNLG-152: Licensed from the University of Maryland, VNLG-152 targets psoriasis and acne by providing a unique approach to achieving the therapeutic benefit of retinoid therapy.
• Z-Pods: Hoth is co-developing a patented technology delivery system for drugs treating cutaneous lupus erythematosus , a chronic autoimmune disease that affects the skin, by using patented xerogel-derived nanoparticles, called Z-pods™. This topical administration will deliver—in a sustained and controlled manner—notoriously hard-to-deliver therapeutic agents, hence improving therapeutic outcome.
• Aprepitant is used to treat skin conditions and other side effects of erlotonib enabling cancer patients to complete their prescribed treatment regimens. Erlotonib is a drug that is used to combat various cancers and has been known to cause varying degrees of skin rashes, lesions, hair loss and nail changes to patients.
• Genetic Markers: Hoth holds an exclusive license from the University of Cincinnati to develop a patented technology to determine a person's propensity to suffer an allergic reaction to certain types of food, including; peanut allergy, milk allergy, general food allergy and eczema.
• Gene Therapy: Hoth also holds an exclusive license with North Carolina State University (NC State) to lead a preclinical study for the treatment of asthma and allergic inflammation. The goal of the study is to establish proof of principle by targeting the gene encoding the FcεRIβ protein in the lungs of mice and determine the best approach for targeting allergic inflammation in the airways with splice-switching oligonucleotides (SSOs).

LL: Why did you decide to focus on these indications?

RK: We found current treatments addressing these indications to be costly and ineffective particularly for our target patient population, adolescents. For example, approximately 32 million Americans suffer from AD a chronic skin condition characterized by staphylococcal colonization and biofilm formation, which represent a market opportunity for Hoth of $9.5 billion. In the US, approximately 10 to 13% of all children and 7 to 8% of adults are impacted by AD. In the current marketplace, treatments maintain rather than cure these indications through invasive, costly and topical treatments that frequently cause side effects. Hoth is working to address this unmet need to develop remedies that alleviate these conditions with minimal to no side effects, addressing a major quality of life issue for patients suffering from several dermatological disorders. Initial data shows that our leading asset platform, BioLexa, will be able to treat other staphylococcal infections triggered by post-surgical procedures such as laser skin resurfacing, cosmetic surgery, skin cancer excisions, among others.

LL: What is the BioLexa Platform™, how does it work?

RK: The BioLexa Platform, Hoth’s lead drug candidate platform, is a novel mixture of two FDA approved compounds targeting AD or eczema and chronic diabetic ulcers. The first compound breaks down the biofilm protecting the bacteria (S. aureus), allowing the second, an antibiotic, to more effectively treat the underlying infection.

First Indication: Atopic Dermatitis

Hoth is developing a patented topical non-corticosteroid approach inhibiting the formation of biofilms. Following a successful first clinical trial, investigators plan to begin human trials during the first quarter of 2020 in Australia.

Second Indication: Chronic Diabetic Ulcers

This treatment also inhibits the formation biofilms. In preclinical studies, Hoth reported positive results from a pilot animal study conducted under a Scientific Research Agreement with Massachusetts General Hospital Vaccine and Immunotherapy Center ("MGH") to test the inhibition of the formation of S. aureus biofilms in diabetic foot ulcers and chronic wounds. The findings reported majority of the treated wounds were fully closed and re-epithelialized, with better collagen deposition and increased angiogenesis.

LL: What can we expect to see from Hoth Therapeutics in 2020?

RK: We remain focused on continuing to invest in developing our current pipeline therapies, while broadening our research across various dermatological indications. Now that we have completed our animal toxicology study for BioLexa, we are preparing for our first in human trial in Australia this year targeting the adolescent patient population. Our current plan is for treatment of 10 healthy patients in a Phase IB, which will roll us into 60–80 adolescent patients with mild to moderate atopic dermatitis aged 2 to 17 years old. We are currently targeting to receive top-line data during the second half of 2020.

Robb Knie was speaking to Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.