PP405

What is PP405?#

PP405 is a first-in-class topical small molecule therapeutic developed by Pelage Pharmaceuticals for the treatment of androgenetic alopecia (pattern hair loss) in both men and women. Unlike currently available hair loss treatments that primarily target secondary causes such as hormones (finasteride) or vasodilation (minoxidil), PP405 acts on the primary biological pathway driving the natural hair follicle cycle by targeting hair follicle stem cells directly.

PP405 was discovered at UCLA by researchers in the Lowry and Christofk laboratories and subsequently licensed to Pelage Pharmaceuticals for clinical development. It is classified as a small molecule rather than a peptide, but its mechanism centers on cellular signaling in hair follicle stem cells.

Mechanism of Action#

PP405 inhibits the mitochondrial pyruvate carrier (MPC), a protein complex consisting of MPC1 and MPC2 subunits that transports pyruvate from the cytoplasm into the mitochondrial matrix for oxidative phosphorylation.

By blocking MPC, PP405 prevents pyruvate from entering the mitochondria. This causes pyruvate to accumulate in the cytoplasm, where it is converted to lactate by lactate dehydrogenase (LDH). The resulting increase in lactate and glycolytic flux serves as a metabolic signal that drives hair follicle stem cells from their quiescent (telogen) state into the active growth (anagen) phase.

This mechanism is based on the discovery that hair follicle stem cells preferentially use glycolytic metabolism and produce significantly more lactate than other epidermal cells when in their activated state. When these stem cells rest in the telogen phase, they rely on mitochondrial oxidative phosphorylation. PP405 exploits this metabolic switch to force activation.

Clinical Development#

PP405 is currently in Phase 2 clinical development:

• Phase 1: Demonstrated safety with no systemic absorption and showed activation of human hair follicle stem cells both ex vivo and in vivo
• Phase 2a (NCT06393452): Randomized, double-blind, vehicle-controlled trial in 78 patients with androgenetic alopecia showed statistically significant hair regrowth
• Phase 3: Planned for 2026, supported by $120 million Series B financing

Important Considerations#

PP405 is an investigational drug that is not yet approved by any regulatory authority. It is not commercially available and cannot be prescribed or purchased. The promising Phase 2a results require confirmation in larger Phase 3 trials before regulatory submission.

Key Research Findings#

Lactate dehydrogenase activity drives hair follicle stem cell activation, published in Nature Cell Biology (Flores A et al., 2017; PMID: 28812580):

Foundational study from UCLA demonstrating that hair follicle stem cells rely on lactate production via LDHA for activation, and that MPC1 deletion or pharmacological MPC inhibition accelerates the hair cycle.

• Hair follicle stem cells use glycolytic metabolism and produce more lactate than other epidermal cells
• Deletion of LDHA prevented hair follicle stem cell activation
• MPC1 deletion accelerated hair follicle stem cell activation and the hair cycle

Phase 2a Randomized, Double-Blind, Vehicle-Controlled Study of PP405 in Adults With Androgenetic Alopecia, published in ClinicalTrials.gov (NCT06393452) (Pelage Pharmaceuticals (company press release), 2025):

Phase 2a randomized controlled trial evaluating 0.05% PP405 topical gel versus vehicle in 78 patients with androgenetic alopecia. Once-daily application for 4 weeks with follow-up to 12 weeks.

• Met primary safety endpoint with no serious adverse events
• No systemic absorption of PP405 detected in blood plasma
• 31% of men with advanced hair loss achieved greater than 20% increase in hair density at 8 weeks versus 0% in placebo

Related Reading#

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