PP405

Last updated
PP405
Clinical data
Other namesPP-405
Routes of
administration 		Topical administration as a gel to the scalp [1] [2]
Drug class Mitochondrial pyruvate carrier (MPC) inhibitor; Indirect lactate dehydrogenase (LDH) stimulant [1] [2]

PP405, or PP-405, is a drug acting as a mitochondrial pyruvate carrier (MPC) inhibitor which is under development for the treatment of alopecia (hair loss), specifically androgenic alopecia (pattern hair loss). [1] [3] [2] [4] It is used topically as a 0.05% concentration gel on the scalp once-daily. [1] [2] [5] [6] PP405 is a possible first-in-class drug with a novel mechanism of action in the potential treatment of hair loss. [7] [4]

Contents

Pharmacology

Pharmacodynamics

PP405 is listed as a dual mitochondrial pyruvate carrier (MPC) MPC1 and MPC2 inhibitor. [3] It is thought to work by causing pyruvate accumulation, which in turn results in stimulation of lactate dehydrogenase (LDH) activity in hair follicle stem cells (HFSCs). [2] [8] As a result of this, lactic acid levels and glycolysis increase within the cells and more energy for cellular growth becomes available. [8] [9] It appears that changes in intracellular lactate availability may be a key mediator of the hair growth cycle, with low lactate levels resulting in dormancy or the telogen stage and high lactate levels resulting in active growth or the anagen stage. [10] [11] [12] [9] [8] In the case of androgenic alopecia, hair follicles have miniaturized and permanently entered the telogen phase. [5] [13] According to its developers, PP405 acts differently than existing hair loss drugs like minoxidil and finasteride in that it works via reactivating dormant hair follicles by altering HFSC metabolism. [2] [4] MPC inhibitors like UK-5099 (JXL001) and PP405 have been found to stimulate hair growth in genetically modified mice in vivo and in excised human skin ex vivo . [2] [14] [15] Another related approach to promoting hair growth is application of deoxyribose sugar gel, which was also effective in stimulating hair growth in mice. [16] [17]

Pharmacokinetics

PP405 is used topically on the scalp instead of orally for potential safety and tolerability reasons. [2] [6] As an example, MPCs and pyruvate availability also prominently regulate stem cells and cellular growth in the intestines. [10] The drug is said to be unstable in blood, which limits the risk of systemic absorption and side effects. [2] [8] It is said to have been engineered to be 1,000 times more effective at "penetrating" skin than blood. [4] No PP405 was detected in circulation with topical administration to the scalp in clinical studies. [2] [6]

Chemistry

Chemical structure of the related drug JXL069. JXL069 structure.png
Chemical structure of the related drug JXL069.

The chemical structure of PP405 has not yet been disclosed. [1] The drug has been patented and its structure is said to be known only to Pelage Pharmaceuticals. [2] The company has also patented and published on other MPC inhibitors such as JXL069 and JXL082. [2] [14] [18] [19] [20] They are (E)-2-cyano-3-(1H-indol-3-yl)acrylic acids and related analogues. [14] [18] [21] PP405 is said to be neither JXL069 nor JXL082. [2] The drug-related properties of certain related MPC inhibitors like UK-5099 (JXL001) are said to be incompatible with therapeutic use. [18]

History

UK-5099 (JXL001), the earlier MPC inhibitor from which PP405 was derived, was first described in the scientific literature by 1975. [22] [23] PP405 is under development by Pelage Pharmaceuticals. [1] [2] In 2025, it was reported that lab work on the drug had been ongoing for almost a decade. [24] It originated at the University of California, Los Angeles (UCLA), with Pelage Pharmaceuticals being founded and spunt out of UCLA in 2018 by three scientists at the university. [1] [2] [8] [5] These academics included Bill Lowry, Heather Christofk, and Michael Jung. [1] [8] [5] The chief medical officer (CMO) of the company is Qing Yu Christina Weng. [4] Pelage Pharmaceuticals was named after the French word for "coat of fur" and PP405 was named after the company and the 405 freeway that goes through Los Angeles. [2] [8] The first human clinical trials of PP405 started in 2023 in Orange County. [2] [24]

Society and culture

Grey market use

PP405 has attracted an unusual amount of attention for an investigational drug, such as in the r/Tressless subreddit about hair loss on Reddit. [2] A large group of r/Tressless members, having believed that JXL069 is PP405, are known to have sourced JXL069 from China in 2025 in an effort to treat their hair loss. [2] This included sending a sample to an analytical testing lab to confirm the compound's authenticity. [2] Pelage Pharmaceuticals says that it does not endorse such use and has explicitly stated that PP405 is not JXL069. [2] PP405 is also said to not be JXL082. [2]

Research

As of June 2025, PP405 is in phase 2 clinical trials for treatment of alopecia. [1] Two clinical trials have been completed, including a phase 1 trial and a phase 2a trial. [8] [5] [25] [1] [3] There were initial concerns that PP405 might actually kill all hair follicles rather than promote hair growth, but its developers were pleased to find that this was not the case. [24] [26] [27]

The effectiveness data for a phase 2a trial was released in June 2025. [1] [2] In this preliminary trial, 31% of men with "advanced baldness" or "a higher degree of hair loss" experienced an increase in hair density of 20% or more at the 8-week follow-up point subsequent to 4 weeks of PP405 treatment, whereas none of the men in the placebo group showed improvement. [2] [7] Existing hair-loss drugs like minoxidil and finasteride are said to require months to produce any visible difference. [2] [4] The new hair growth was described as not being vellus hair, peach fuzz, or baby hair, but as being proper and thick terminal hair, and to have grown in previously bald areas. [2] [6] [7] [4] However, Pelage Pharmaceuticals declined to share before-and-after photos, citing regulations preventing them from doing so. [2] Moreover, the trial was a short-term study that was primarily designed to assess safety and not efficacy. [2] A three-month open-label extension of the phase 2a trial was subsequently completed and these data will be shared in 2026. [7] [6]

Phase 3 trials of PP405 for alopecia are being planned for 2026. [2] [7] [4] It has been estimated that if PP405 is successful in clinical trials and passes regulatory scrutiny, the drug could be approved for the treatment of hair loss sometime between 2027 and 2029 at the earliest. [2] [4]

PP405 is currently Pelage Pharmaceuticals's only official drug candidate. [2] [28] However, the company is also investigating reactivation of dormant stem cells for treatment of other medical conditions. [2] Pelage Pharmaceuticals had raised more than $30 million by August 2025, with investment being led by Google Ventures of Alphabet. [2] In October 2025, it was announced that the company had raised $120 million. [7] In 2019, Pelage Pharmaceuticals had reached an agreement that granted Allergan (now AbbVie) an option to acquire the startup company, but this deal was terminated in 2020. [5]

PP405 may also have applications in the treatment of other forms of hair loss besides androgenic alopecia. [4] [8] [25]

In October 2025, Time magazine named PP405 one of the best inventions of 2025. [29] However, the magazine also disclosed, via communication with Pelage Pharmaceuticals, that PP405 may not be effective in the end stages of balding if the hair follicle is "scarred". [29] In general, drugs like PP405 are only thought to have potential effectiveness for a given follicle if it is still intact, undamaged, and merely dormant. [29] [2]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "PP 405". AdisInsight. 20 June 2025. Retrieved 23 October 2025.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 Brown, Lane (12 August 2025). "The Great Unbalding Draws Nearer". Intelligencer. Retrieved 23 October 2025.
  3. 1 2 3 "Delving into the Latest Updates on PP-405(Pelage Pharmaceuticals) with Synapse". Synapse. 20 October 2025. Retrieved 23 October 2025.
  4. 1 2 3 4 5 6 7 8 9 10 "Topical Agent Targets Dormant Follicles in Alopecia". Medscape. 4 September 2025. Retrieved 23 October 2025.
  5. 1 2 3 4 5 6 Vinluan, Frank (29 February 2024). "Roots Start to Show for Hair Loss Startup Pelage With a Peek at First Clinical Data". MedCity News. Retrieved 23 October 2025.
  6. 1 2 3 4 5 Meara, Killian (23 June 2025). "Pelage's PP405 Demonstrates Efficacy in Phase 2a Trial for Androgenetic Alopecia". Dermatology Times. Retrieved 23 October 2025.
  7. 1 2 3 4 5 6 Becker, Zoey (15 October 2025). "Pelage Pharma raises $120M series B to untangle roots of hair loss with regenerative med". Fierce Biotech. Retrieved 23 October 2025.
  8. 1 2 3 4 5 6 7 8 9 Chang, Connie (3 September 2025). "Experimental Drug PP405 May Wake Up Dormant Follicles to Regrow Hair". Popular Mechanics. Archived from the original on 22 October 2025. Retrieved 23 October 2025.
  9. 1 2 Flores A, Schell J, Krall AS, Jelinek D, Miranda M, Grigorian M, Braas D, White AC, Zhou JL, Graham NA, Graeber T, Seth P, Evseenko D, Coller HA, Rutter J, Christofk HR, Lowry WE (September 2017). "Lactate dehydrogenase activity drives hair follicle stem cell activation". Nat Cell Biol. 19 (9): 1017–1026. doi:10.1038/ncb3575. PMC   5657543 . PMID   28812580.
  10. 1 2 Shapira SN, Christofk HR (July 2020). "Metabolic Regulation of Tissue Stem Cells". Trends Cell Biol. 30 (7): 566–576. doi:10.1016/j.tcb.2020.04.004. PMC   8059102 . PMID   32359707.
  11. ↑ Lee JH, Choi S (February 2024). "Deciphering the molecular mechanisms of stem cell dynamics in hair follicle regeneration". Exp Mol Med. 56 (1): 110–117. doi:10.1038/s12276-023-01151-5. PMC   10834421 . PMID   38182654. The importance of several metabolic pathways in HFSC activation has also been revealed (e.g., lactate production is potentially essential for HFSC activation)117.
  12. ↑ Liu Y, Yang S, Zeng Y, Tang Z, Zong X, Li X, Yang C, Liu L, Tong X, Zhou L, Wang D (July 2022). "Dysregulated behaviour of hair follicle stem cells triggers alopecia and provides potential therapeutic targets". Exp Dermatol. 31 (7): 986–992. doi:10.1111/exd.14600. PMID   35524394.
  13. ↑ Lolli F, Pallotti F, Rossi A, Fortuna MC, Caro G, Lenzi A, Sansone A, Lombardo F (July 2017). "Androgenetic alopecia: a review". Endocrine. 57 (1): 9–17. doi:10.1007/s12020-017-1280-y. hdl:2108/272636. PMID   28349362. AGA features a progressive miniaturization of the hair follicle leading to vellus transformation of terminal hair. This results from an alteration in hair cycle dynamics: anagen phase duration gradually decreases and that of the telogen phase increases. As the anagen phase duration determines hair length, the new anagen hair becomes shorter, eventually leading to bald appearance [5, 6].
  14. 1 2 3 Liu X, Flores AA, Situ L, Gu W, Ding H, Christofk HR, Lowry WE, Jung ME (February 2021). "Development of Novel Mitochondrial Pyruvate Carrier Inhibitors to Treat Hair Loss". J Med Chem. 64 (4): 2046–2063. doi:10.1021/acs.jmedchem.0c01570. PMC   8939290 . PMID   33534563.
  15. ↑ Flores, A.A.; McDaniel, T.; Sun, D.; Christofk, H.; Jung, M.; Weng, Q.; Gil, D.; Lowry, W. (2024). "LB1045 Inhibition of pyruvate oxidation activates human hair follicle stem cells ex vivo". Journal of Investigative Dermatology. 144 (8): S186. doi:10.1016/j.jid.2024.06.1215 . Retrieved 23 October 2025.
  16. ↑ Anjum MA, Zulfiqar S, Chaudhary AA, Rehman IU, Bullock AJ, Yar M, MacNeil S (2024). "Stimulation of hair regrowth in an animal model of androgenic alopecia using 2-deoxy-D-ribose". Front Pharmacol. 15 1370833. doi: 10.3389/fphar.2024.1370833 . PMC   11180715 . PMID   38887556.
  17. ↑ Cassella, Carly (21 March 2025). "A Surprise Hair Loss Breakthrough: Sugar Gel Triggers Robust Regrowth". ScienceAlert. Retrieved 23 October 2025.
  18. 1 2 3 Tavoulari S, Sichrovsky M, Kunji ER (August 2023). "Fifty years of the mitochondrial pyruvate carrier: New insights into its structure, function, and inhibition". Acta Physiol (Oxf). 238 (4) e14016. doi:10.1111/apha.14016. PMC   10909473 . PMID   37366179.
  19. ↑ WO 2019/006359,Lowry WE, et al.,"Compositions and methods for modulating hair growth.",published 3 January 2019, assigned to The Regents Of The University Of California
  20. ↑ WO 2023/129854,Sun DL, et al.,"Compounds for treatment of hair loss.",published 6 July 2023, assigned to Pelage Pharmaceuticals, Inc.
  21. ↑ Huang Y, Peng X, Zhang H, Pan M, Su X, Li G, Zhang Q (November 2024). "Design, synthesis and biological evaluation of novel cyano-cinnamate derivatives as mitochondrial pyruvate carrier inhibitors". Bioorg Med Chem Lett. 112 129923. doi:10.1016/j.bmcl.2024.129923. PMID   39134097.
  22. ↑ Halestrap AP (April 1975). "The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors". Biochem J. 148 (1): 85–96. doi:10.1042/bj1480085. PMC   1165509 . PMID   1156402.
  23. ↑ Halestrap AP, Denton RM (April 1975). "The specificity and metabolic implications of the inhibition of pyruvate transport in isolated mitochondria and intact tissue preparations by alpha-Cyano-4-hydroxycinnamate and related compounds". Biochem J. 148 (1): 97–106. doi:10.1042/bj1480097. PMC   1165510 . PMID   1171687.
  24. 1 2 3 Harlow, John (4 February 2025). "Did UCLA Just Cure Baldness?". UCLA. Retrieved 23 October 2025.
  25. 1 2 Olmstead, Susan C. (28 February 2024). "New Topical Agent for Alopecia to Enter Phase 2 Trials". Dermatology Times. Retrieved 23 October 2025.
  26. ↑ Pye D, Scholey R, Ung S, Dawson M, Shahmalak A, Purba TS (2024). "Activation of the integrated stress response in human hair follicles". PLOS ONE. 19 (6) e0303742. Bibcode:2024PLoSO..1903742P. doi: 10.1371/journal.pone.0303742 . PMC   11189182 . PMID   38900734.
  27. ↑ Gomez, Shirley (11 August 2025). "Hair loss treatment: New cream could end balding for good". HOLA! USA. Initial concerns that PP405 might overactivate or damage follicles were quickly replaced with cautious optimism.
  28. ↑ "Delving into the Latest Updates on Pelage Pharmaceuticals, Inc. with Synapse". Synapse. 20 October 2025. Retrieved 23 October 2025.
  29. 1 2 3 Akhtar, Allana (9 October 2025). "Pelage Pharmaceuticals PP405: The Best Inventions of 2025". TIME. Retrieved 23 October 2025. Correction, Oct. 9 The original version of this story misstated the limited of the drug's efficacy. It may not work in the end stages of balding if the follicle is scarred, but it doesn't only work in the early stages of balding.
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