Pelage Presents Late-Breaking Data at AAD 2024 Meeting Demonstrating PP405 Activates Human Hair Follicle Stem Cells Ex Vivo and in Phase 1 Clinical Study

- Potent topical MPC inhibitor, based on discovery of a metabolic switch, reawakens dormant hair follicle stem cells to stimulate hair growth

- PP405 demonstrates statistically significant activation of Ki67 in the hair follicle, a well-established marker of stem cell proliferation

LOS ANGELES, March 9, 2024 /PRNewswire/ -- Pelage Pharmaceuticals, a clinical-stage regenerative medicine company pioneering a new generation of treatments for hair loss, today presented positive translational and Phase 1 clinical data demonstrating the company's novel small molecule therapy PP405 reactivates dormant hair follicle stem cells to trigger hair growth. Data were presented in a late-breaking oral session of the American Academy of Dermatology (AAD) 2024 Annual Meeting in San Diego, titled Inhibition of pyruvate oxidation activates human hair follicle stem cells ex vivo.

"The translational data derived from our ex vivo studies on human facelift skin have been further validated in a Phase 1 first-in-human clinical trial demonstrating PP405 effectively reactivates dormant hair follicle stem cells," said Daniel Gil, Ph.D., CEO of Pelage Pharmaceuticals. "This therapy represents an exciting new option for not only treating but reversing hair loss. We look forward to advancing PP405 to Phase 2 clinical studies this year."

PP405 is a potent topical mitochondrial pyruvate carrier (MPC) inhibitor that acts on the cellular metabolic pathway to upregulate lactate dehydrogenase (LDH), which stem cells are particularly sensitive to, resulting in their activation and hair growth.

Data presented at AAD showed in human facelift skin, single topical applications of 0.006% and 0.06% PP405 led to an increase in LDH activity in hair follicle stem cells within 24 hours. The LDH activity corresponded with a significant increase in Ki67 signal in the hair bulge, indicating a proliferative response of the hair follicle stem cells. The findings demonstrated proof of mechanism in human explanted skin consistent with the results in animal models.

The data informed Pelage's Phase 1 clinical trial that concluded in January 2024, which demonstrated that PP405 was safe and well-tolerated, with the target pharmacokinetic profile achieved. Additionally, the Phase 1 study demonstrated proof of mechanism and target engagement in patients with androgenetic alopecia. There was a statistically significant increase in the Ki67 signal compared to baseline after just seven days of 0.05% PP405 topical treatment. Evidence of newly emerging hair germs – the hallmark of the telogen to anagen transition - was also observed. The topical molecule also received positive formulation reviews from patients.

"We are incredibly excited about this data, and PP405 offers an opportunity to change the landscape of alopecia treatment through directly targeting hair follicle stem cells at the source through a clear mechanistic pathway," said Qing Yu Christina Weng, M.D., CMO of Pelage Pharmaceuticals. "The Phase 1b study of PP405 demonstrates a strong safety profile, confirms daily topical dosing with no detectable drug levels in the blood, and demonstrates proof of mechanism with statistically significant activation of hair follicle stem cells. We can also see the structural architecture of the follicle on biopsy moving through the hair cycle from resting to growing as the stem cells become activated." 

Pelage will begin its multi-center Phase 2a trial of PP405 in mid-2024, recruiting both men and women with androgenetic alopecia. PP405 may also have applications for other forms of alopecia, including telogen effluvium (stress-induced hair loss) and chemotherapy-induced hair loss.

About Pelage Pharmaceuticals

Pelage Pharmaceuticals is a clinical-stage regenerative medicine company developing novel treatments for hair loss including androgenetic alopecia and chemotherapy-induced-alopecia. With a focus on molecular and stem cell biology, Pelage is advancing a new class of treatments designed to reactivate dormant hair follicle stem cells and restore the body's ability to naturally grow hair. Its lead program, PP405, is currently in clinical trials. Through its rigorous scientific foundation, topical formulation, and novel mechanism of action, Pelage is pioneering first-in-class hair growth solutions for people of all hair types experiencing hair loss.

About PP405

PP405 is a novel, non-invasive, topical small molecule designed to reactivate dormant hair follicle stem cells and restart hair growth. Through a regenerative medicine approach, the treatment focuses on addressing the metabolic processes that regulate the activation and inactivation phases of hair follicle stem cells. Early results from a Phase 1 trial show that PP405 was well-tolerated and demonstrated statistically significant activation of hair follicle stem cells. In 2018, Pelage Pharmaceuticals licensed the intellectual property to PP405 and related topical small molecules from the UCLA Technology Development Group.

SOURCE Pelage Pharmaceuticals