Turn Therapeutics Reports Significant IGA and Cytokine Inhibition, Advances to Plans for In-Human Trial

Image Credit: © Ольга Тернавская - stock.adobe.com

In a new development, Bradley Burnam, founder and CEO of Turn Therapeutics, has shared exclusive insights with Dermatology Times regarding their latest study. Turn’s flagship formula and atopic dermatitis (AD) candidate, Hexagen, an antimicrobial petrolatum-based topical therapy, is currently in the clinical stages of development for moderate to severe AD.

In a 7-day study involving pre-treatment and induction periods, Burnam and Turn found that the candidate achieved significant inhibition of Investigator Global Assessment (IGA) scores and cytokine inhibition, particularly interleukin (IL)-31. IL-31 is considered to play a significant role in the pathogenesis of eczema and atopic dermatitis.¹

The newest development comes just 1 month after Turn reported findings from an in-vivo model demonstrating the candidate’s ability to achieve a 57% reduction in overall AD disease severity in as few as 7 days.²

Study Objectives and Methodology

Burnam said that historically, treatments for eczema have addressed symptoms and secondary inflammatory pathways, but Turn’s team sought to investigate how effectively their candidate could intervene at the disease's source.

"We wanted to understand the inhibition profile, if any, of our eczema candidate. We have done a lot of work to determine that it is effective in reducing IGA. And then there's the big ‘why?’ question,” Burnam said. “There's been a hypothesis, a theory, that I've had for a long time, that we inhibit cytokines, especially the ones at the skin surface, and especially the initiating one, IL-36, but we had yet to prove it."

The study employed a model from the National Institutes of Health involving pre-treatment and fungal colonization to simulate eczema-like inflammation. Burnam detailed the approach.

"We pre-treated 40 animals for 4 days, and then we colonized using the traditional staph induction model for 3 days. At the end of those 3 days, only relying upon the preload that we created during that pre-treatment, we took a look at a broad array of cytokines,” he said.

Image Credit: © Dermatology Times

Key Findings: Broad Spectrum Cytokine Inhibition

The results demonstrated a significant inhibition of several cytokines, including IL-4, IL-31, IL-36 alpha, and IL-36 gamma.

Three days after pre-treatment, when examining the profiles of IGA and cytokine inhibition, Turn found that the candidate achieved 66.67% inhibition of IGA score (p value = 0.0000000008), 67.7% inhibition of IL-31 (p value = 0.0000011200), 50.08% inhibition of IL-36 alpha (0.0000000000), and 49.05% inhibition of IL-36 gamma (p value = 0.0000000435).

Burnam expressed his excitement about these findings.

"The broad spectrum is, of course, extremely welcome. The excitement for me is that this is a skin disease, and we found out that we can treat the skin disease at the skin, at the source, with IL-36 alpha in particular, because IL-36 gamma seems to be more involved with psoriasis,” he said.

He also elaborated on the implications of inhibiting IL-36 alpha.

"It's a large proportion of inhibition," Burnam said. “The majority of the cytokine was inhibited."

Next Steps: Human Trials and Future Directions

With these promising results, Turn is preparing to advance to human trials. Burnam outlined the next steps.

"The next step is that we are going to do our first efficacy trial in humans. I feel very confident in our safety profile, which is something that is unusual when you're going into a clinical trial to know, ‘yes, it's safe.’ It's already been FDA-cleared 3 times with the words 'non-sensitizing,' 'non-irritating,' 'not cytotoxic.'"

Exploring Broader Applications

Beyond AD, Burnam suggested that the formula might have potential for other dermatological conditions, such as psoriasis.

"This seems to be the beginning of a potentially multi-indication formula,” he said. “We have now learned via these biomarker studies what other things it might be good at. For example, pustular psoriasis, general psoriatic disease. If you can get IL-36 alpha and gamma, you have a chance with general psoriasis, rosacea."

Conclusions

"I'm a patient-focused person, because I'm a patient first and foremost. That's why I started this company,” Burnam said. “It's a really wonderful feeling to think: This is tens of millions of people, between eczema, psoriasis, and to give them a non-injectable, non-steroid option, potentially, is something that I want dermatologists to look forward to."

Burnam anticipates that in-human trials will validate the treatment’s effectiveness in real-world settings. Turn expects to commence in-human trials at the beginning of 2025.

References

1. Hänel, KH, Pfaff, CM, Cornelissen, C, et al. Control of the physical and antimicrobial skin barrier by an IL-31–IL-1 signaling network. J Immunol. 2016;196:3233-3244
2. Turn Therapeutics atopic dermatitis candidate reduces disease severity by 57% in-vivo. News release. BioSpace. June 20, 2024. Accessed July 31, 2024. https://www.biospace.com/article/releases/turn-therapeutics-atopic-dermatitis-candidate-reduces-disease-severity-by-57-percent-in-vivo/#:~:text=All%20(816%2C573)-,Turn%20Therapeutics%20Atopic%20Dermatitis%20Candidate,Severity%20by%2057%25%20In%2DVivo&text=LOS%20ANGELES%2D%2D(BUSINESS%20WIRE,in%20disease%20severity%20versus%20placebo