Androgenetic alopecia (AGA) is the most common type of hair loss in men and women, affecting an estimated 50 million men and 30 million women in the U.S.1

  • It is characterized by varying degrees of hair thinning that occurs as terminal (mature) hairs are gradually “miniaturized” to vellus (fine/wispy) hairs.2
  • AGA generally presents in a characteristic pattern and varies by age and race.
  • It is most prevalent in Caucasians, with approximately half of men developing hair loss by age 50 and one third of women developing some form of loss as age increases.2-4

Healthy hair follicles follow a cycle, progressing through the anagen (growth) phase followed by the catagen (regression) phase, the telogen (quiescent) phase, and then back into an anagen phase.5 In AGA, this cycle is disrupted and hair follicles miniaturize and stop growing. There are many molecular pathways involved in this process of hair follicle formation and maturation, including6,7:

  • Sonic hedgehog (SHH)
  • Bone morphogenetic protein (BMP)
  • TGF-β
  • Notch
  • Wnt

In particular, activation of the Wnt signaling pathway has been shown to be required for the initiation of hair follicle development8, and epithelial β-catenin signaling is required for maintenance of proliferation in the anagen phase.9


    1. NIH Genetics Home Reference. https// Accessed Oct. 4, 2016.
    2. Sinclair R. Male pattern androgenetic alopecia. BMJ. 1998;317(7162):865-9.
    3. Sinclair R, Patel M, Dawson TL Jr, et al. Hair loss in women: medical and cosmetic approaches to increase scalp hair fullness. Br J Dermatol. 2011;165(suppl 3):12-8.
    4. Norwood OT. Incidence of female androgenetic alopecia (female pattern alopecia). Dermatol Surg. 2001;27(1):53-4.
    5. Hardy MH. The secret life of the hair follicle. Trends Genet. 1992;8;55-61.
    6. Paus R & Cotsarelis G. The Biology of Hair Follicles. NEJM. 1999;341(7):491–97.
    7. Krause K & Foitzik K. Biology of the Hair Follicle: The Basics. Semin Cutan Med Surg. 2006;25(1):2–10.
    8. Andl T, Reddy ST, Gaddapara T, Millar SE. Wnt signals are required for the initiation of hair follicle development. Dev Cell. 2002;2(5):643-53.
    9. Choi YS, Zhang Y, Xu M, et al. Distinct functions for the Wnt/β-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell Stem Cell. 2013;13(6):720-33.

Dalosirvat (SM04554)


Biosplice Therapeutics has developed dalosirvat, a topical, small-molecule Wnt pathway modulator, in Phase 2/3 clinical trials for the treatment of androgenetic alopecia (AGA).

Mechanism of Action

Wnt signaling in the skin has been shown to be a pivotal pathway in hair growth and development, specifically in the transition of follicles from telogen to anagen and in anagen phase hair growth. Additionally, increased levels of Prostaglandin D2 (PGD2) have been observed in bald scalp and shown to drive the process of follicle miniaturization and hair loss.

Through an iterative phenotypic screening and design optimization campaign, Biosplice Therapeutics nominated dalosirvat as a lead clinical candidate to address androgenetic alopecia (male pattern baldness). Dalosirvat is a topically-applied modulator of follicular Wnt signaling, which increases expression of Wnt pathway genes (Axin2, Lef1, and TCF7), decreases PGD2 production and increases follicular proliferation (increased Ki-67) compared to vehicle. In preclinical, placebo-controlled models, dalosirvat decreased the duration of telogen phase and increased the number of follicles entering anagen phase, which accelerated anagen hair growth.


Data to Date

Biosplice Therapeutics has completed two phase 1 safety studies and two phase 2 studies, testing various concentrations of dalosirvat. Across all clinical trials, dalosirvat appeared safe and well tolerated with similar rates of adverse events compared to placebo.

In AGA-02, a phase 2 study testing two different concentrations of dalosirvat and placebo with 90 days of daily dosing in 302 subjects, the 0.15% concentration of dalosirvat led to statistically significant increases in non-vellus (i.e., mature) hair count versus placebo, as measured by macrophotography at day 135 of the study.

In AGA-04, a phase 2 study testing two different concentrations of dalosirvat and placebo with 90 days of daily dosing in 49 subjects, 0.15% and 0.25% concentrations of dalosirvat led to statistically significant increases in total follicle counts versus placebo, as measured by histological quantification of hair counts at day 135 of the study.

Biosplice is currently conducting a 52-week phase 2/3 clinical trial of dalosirvat. The ongoing phase 2/3 study is fully enrolled with data availability expected in 2021.