Pelage Pharmaceuticals Phase 2 Trials for PP405 Begin in June 2024

Update: May 6, 2024

Pelage Pharmaceuticals Phase 2 Clinical Trials Start in June 2024

Yesterday, a reader e-mailed a new link on Pelage Pharmaceuticals’ Phase 2 clinical trials for its PP405 inhibitor of mitochondrial pyruvate carrier (MPC). The Phase 2 trials are set to begin in June 2024 and will involve 60 participants. Half of these will take a PP405 0.05% topical gel once per day, and the other half will get a placebo vehicle  daily gel. The study primary completion date is December 2024, and actual completion date is February 2025.

Recruitment will likely start soon, and I assume it will be in the US based on the listed contact person and phone number. The contact e-mail is listed as clinicaltrials@pelagepharma.com. Please DO NOT call them now as the recruitment has not yet commenced and they might get annoyed.

If you are between the ages of 18-55 and have androgenetic alopecia, you can participate. However, the inclusion criteria for men and women is specific:

  • Males must have an AGA modified Norwood-Hamilton Classification score of Type III vertex, Type IV or Type V.
  • Females must have a Savin classification score of I-2, I-3 or I-4.

 

Pelage Pharmaceuticals
Pelage Pharmaceuticals Logo.

I previously wrote about Pelage Pharmaceuticals in my 2019 post related to the research of its President and co-founder Dr. William Lowry. The other co-founders are Dr. Heather Christofk and Michael Jung. I also covered the findings of Dr. Lowry and Dr. Christofk’s UCLA team in a 2017 post.

These UCLA researchers discovered two topical compounds (RCGD423) and (UK5099) that regrew hair in mice via different mechanisms. Both drugs involve an increase in lactate production. This in turn activates hair follicle stem cells and leads to increased and quicker hair growth.

Dr. Lowry’s patent can be found here. Patent and technology rights to both topical drugs have been exclusively licensed to Pelage Pharmaceuticals by UCLA.

Update: March 9, 2024

Earlier today, Pelage Pharmaceuticals gave a positive update on its novel small molecule PP405. Full summary can be read here. In Phase 1 clinical trials, PP405 reactivated dormant hair follicle stem cells and triggered hair growth. The company’s presentation was made by Dr. Christina Weng and titled: “Inhibition of pyruvate oxidation activates human hair follicle stem cells ex vivo”. Pelage will begin its multi-center Phase 2a trial of PP405 in mid-2024. It will recruit both men and women with androgenetic alopecia.

Their description of this unique hair growth molecule is as follows:

“PP405 is a potent topical mitochondrial pyruvate carrier (MPC) inhibitor that acts on the cellular metabolic pathway to upregulate lactate dehydrogenase (LDH).”

Stem cells are particularly sensitive to LDH, so this results in their activation and subsequent hair growth. PP405 demonstrates a statistically significant increase in Ki67 signaling in the hair follicle bulge. Ki67 is a well-established marker of stem cell proliferation.

February 27, 2024

Pelage Pharmaceuticals Raises $16.75 Million and Phase 2 Trials to Begin in 2024

Pelage Pharmaceuticals has raised $16.75 million in Series A Financing. More importantly, they will begin Phase 2 Clinical Trials for PP405 in mid-2024.

Phase I clinical data met primary safety endpoints. And they confirm that their was statistically significant stem cell activation in hair follicles after just one week of treatment with PP405.

Per CEO Daniel Gil, Ph.D.:

“Our scientific co-founders have uncovered a unique biological mechanism with the potential to reactivate hair growth in people with alopecia.”

The company will present translational data at the American Academy of Dermatology meeting in March 2024.

Recently, reader “Ben” made an very interesting discovery on Pelage Pharmaceuticals’ website. The following sentence at the bottom:

“Early Phase I clinical data shows statistically significant stem cell activation in the hair follicles after one week of treatment with PP405.”

This is super news. So their trials have started. I wonder if PP405 is RCGD423 or UK5099? I think it sounds like that latter. The company’s website homepage describes PP405 as:

“A novel, non-invasive, topical small molecule drug platform that activates stem cells in the hair follicles directly to stimulate robust hair growth. By targeting an intrinsic metabolic switch in hair follicles, Pelage’s platform is suitable for all genders, skin types, and hair types.”

In other recent news, Pelage appointed Dr. Qing Yu Christina Weng as Chief Medical Officer.

RCGD423

RCGD423 activates the JAK-STAT signaling pathway, which in turn leads to an increase in lactate production. This extra lactate activates hair follicle stem cells and results in quicker hair growth. The main 2017 study on RCGD423, lactate dehydrogenase activity and hair follicle stem cell activation can be read here. I also covered it in my earlier linked posts related to the work of Pelage co-founders Dr. William Lowry and Dr. Heather Christofk.

UK5099

UK5099, blocks pyruvate (a glucose metabolite) from entering cell mitochondria. This also results in an increase in lactate production in the hair follicle stem cells, and therefore accelerates hair growth. There is a 2015 study from China related to the application of mitochondrial pyruvate carrier blocker UK5099 and its effects on prostate cancer cells.

Bioengineering Approaches to Hair Regeneration: Kageyama

Earlier this week, Yokohama National University (Japan)’s Dr. Tatsuto Kageyama published a very lengthy and detailed paper in a Japanese scientific journal called Journal of the Society of Bioengineering. Dr. Kageyama works at the renowned Fukuda Lab in Japan, which is led by Dr. Junji Fukuda. The actual paper is in Japanese and is titled: “Bioengineering approaches for hair follicle regeneration.

I have translated it and will break out the main details in this post. Besides discussing his team’s scientific approach to hair regrowth, Mr. Kageyama also outlines their overall progress and future plans (though he gives on exact dates for clinical trials). Make sure to check out the diverse range of Google Scholar citations for Mr. Kagema. In most of his important hair growth related papers, he is a co-author with Dr. Fukuda and others.

Previously, I also mentioned that Ayaka Nanmo, Tatsuto Kageyama and Junji Fukuda are co-founders of a new company named TrichoSeeds. It aims to provide “hair regeneration medicine.”

Bioengineering Approaches for Hair Regeneration

To start off, Mr. Kageyama outlines the three main methods of hair regeneration that his team at Fukuda Lab is working on:

  1. Mesenchymal cell transplantation. Reactivates existing weakened hair follicles by injecting mesenchymal stem cells.
  2. Hair follicle primordium transplantion. See their pending patent on hair follicle primordia.
  3. Hair follicle regeneration. The creation of brand new hair follicles in those who have none left. See their January 2024 study on the large-scale preparation of hair follicle germs (HFGs). The transplantation of HFGs in mice resulted in highly efficient “de novo” hair follicle regeneration.
Bioengineering Approaches to Hair Regeneration
Bioengineering Approaches to Hair Regeneration. Journal of the Society of Bioengineering Volume 102, Issue 4 (2024). Tatsuto Kageyama.

I am most excited about the first method for now since it will come to market first. Especially in aging Japan, where autologous regenerative medicine treatments are going to be speed tracked to in-clinic use. In fact in my recent post titled “A Visit to Fukuda Lab“, Dr. Junji Fukuda had the following quote:

“Dermal papilla cell transplantation is about to begin in Japan.“

If you have a reasonable amount of your own scalp hair remaining, this mesenchymal stem cell injection treatment sounds very promising. The diagram below that Mr. Kageyma published in his new paper is extremely detailed.

Techniques for Culturing Dermal Papilla Cells

Mr. Kageyama discusses his team’s three unique approaches to culturing dermal papilla cells. I covered these methods in various posts and updates related to Dr. Junji Fukuda’s published papers over the past decade.

The conventional dermal papilla culturing method (number 1 below) is similar to Shiseido’s work, which Mr. Kageyama discusses briefly. He says that it has limited effectiveness, since the hair regeneration ability of the cells is reduced during the process of growing mesenchymal cells in a culture dish.

  1. Conventional culturing.
  2. Gel bead culture.
  3. Electrical stimulation culture.
  4. Startified culture.
Mesenchymal Stem Cell Culturing Hair Growth
Mesenchymal stem cell culturing and injection of derma papilla cells for hair growth. Journal of the Society of Bioengineering Volume 102, Issue 4 (2024). Tatsuto Kageyama.

Hair Regeneration by Transplantation of Hair Follicle Primordia

In this second key approach, the aim is to increase the total number of existing hairs. Dr. Kageyama also discusses the work of Dr. Takashi Tsuji and his team in this section of the paper.

The gist of this technology is the mixing of epithelial cells and mesenchymal cells into a single aggregate. This in turn results in the formation of hair follicle primordia (hair seeds), which can then be transplanted into thinning areas of the scalp. The Fukuda team has already succeeeded in the large-scale preparation of hair follicle
primordia.

At present, the team is conducting experiments in transplanting human hair follicle primordia into mice and improving the regeneration efficiency. At present, there is no guarantee that hair follicle will regenerate from the transplanted seeds. It is also difficult to control the direction of new hair growth with this approach.

Hair Follicle Regeneration

The third and final approach entails the creation of brand new hair follicles for transplantation. i.e., hair multiplication. The Fukuda Lab team has managed to develop a culturing technique for regenerating hair follicles in vitro. The discussion here is fairly technical, so I will just quote (and hope that the translation is accurate):

“Focusing on the self-organization process of epithelial cells and mesenchymal cells, we regenerate mature hair follicles with high efficiency (>99%) by controlling the spatial arrangement pattern of aggregates that form in the early stage of culture. Controlling the spatial arrangement of epithelial cells and mesenchymal cells in the aggregate on the second day of culture from a dumbbell shape to a core-shell shape was the key to in vitro hair regeneration. The production method is very simple, such as adding approximately 2% Matrigel to the culture medium when seeding epithelial cells and mesenchymal cells.”

Hair Follicle Regeneration In Vitro
Hair Follicle Regeneration In Vitro. Journal of the Society of Bioengineering Volume 102, Issue 4 (2024). Tatsuto Kageyama.

Future Plans

The team plans to continue its work in all three approaches to hair regeneration. i.e., transplantation of mesenchymal cells,
transplantation of hair follicle primordia, and transplantation of regenerated hair follicles. Moreover, they have succeeded in constructing microtweezers that can grasp, cryopreserve, and eject hair follicle primordia. They are also working with robotics experts to develop a fully automated transplantation robot.