PP405 is an investigational topical that works through a novel, non-hormonal mechanism. But does the new clinical data presented at the AAD 2026 Annual Meeting change the picture? We break down what Pelage Pharmaceuticals revealed, what it means for hair loss patients, and where our original analysis still stands.
Watch our original PP405 deep dive: I Spent Hours Researching PP405 and Here's the Honest Truth
What is PP405?
PP405 is an investigational topical treatment for androgenetic alopecia developed by Pelage Pharmaceuticals. It is currently in clinical trials and is not approved for clinical use.
PP405 inhibits the mitochondrial pyruvate carrier (MPC). This shifts cellular energy production away from oxidative phosphorylation and toward glycolysis, producing more lactate in the process. That lactate activates hair follicle stem cells, promoting new hair growth.
What makes PP405 novel is that it is the first topical for androgenetic alopecia that works through metabolic reprogramming of hair follicle stem cells. Unlike finasteride or dutasteride, it does not target the androgen pathway. And unlike minoxidil, which works primarily through opening potassium channels, PP405 operates through an entirely distinct mechanism. It represents a genuinely new mechanism of action in the AGA treatment landscape.
In our earlier video analysis of PP405, we raised several concerns about the drug based on the available data at the time. You can watch the full breakdown here: I Spent Hours Researching PP405 and Here's the Honest Truth
Our primary concern was the mechanism itself. PP405 forces hair follicle cells into glycolysis, a faster but less efficient way of producing energy. We compared this to chugging coffee versus getting a good night of sleep: glycolysis might produce a short-term burst of stem cell activation, but it is not necessarily the best long-term metabolic state for a hair follicle.
We also questioned whether PP405 was targeting the right part of the hair follicle. In androgenetic alopecia, the core pathology occurs in the dermal papilla, the signaling hub at the base of the follicle, not the bulge where the stem cells reside. While PP405 increases KI67 expression (a marker of cell proliferation) in the bulge, proliferation alone does not equal healthy, terminal hair growth. The hair follicle is a complex mini-organ with at least 33 cell subpopulations, and simply driving rapid cell division does not guarantee functional, cosmetically meaningful hair.
We were also skeptical of how Pelage reported their Phase 2 data. The headline, that 31% of men with severe alopecia saw greater than 20% hair density gains after 8 weeks, meant that only a small subset of the total trial was being highlighted, and the majority of patients potentially saw little to no benefit.
At the AAD 2026 Annual Meeting in Denver on March 28, 2026, Dr. Arash Mostaghimi (who is on Pelage's scientific advisory board) presented new exploratory imaging data from the Phase 2a trial.
The presentation introduced a relatively novel methodology: tracking individual follicular units over time using high-resolution clinical photography and dermatoscopy. While some prior work has explored hair-to-hair matching trichoscopy in AGA trials, this level of longitudinal follicular unit tracking is not commonly used in clinical research and allowed the team to observe changes at the level of individual follicular units rather than just counting total hairs.
The key finding was that PP405 appeared to activate previously dormant follicular units, groups of hair follicles that had completely stopped producing hairs. While existing treatments like minoxidil can promote telogen-to-anagen switching and some vellus-to-terminal transformation, the activation of entirely dormant follicular units that were producing no hairs at all would represent a distinct type of response if confirmed in larger studies.
One important caveat: the detailed follicular unit imaging data was presented for only 3 patients out of 78 enrolled in the trial. We were not shown aggregate data across the full cohort. Cherry-picking a handful of the best responders is a pattern we have seen before with PP405 data, and it makes it impossible to draw conclusions about how the average patient would respond.
A follicular unit is a natural grouping of one to five hair follicles that share a neurovascular bundle. Think of it as a family of hairs that live together in a community on the scalp.
When measuring hair loss treatment efficacy, most clinical trials use "total area hair count," the total number of individual hairs in a given area. But this metric doesn't distinguish between adding a third hair to an already-active two-hair follicular unit versus activating an entirely new follicular unit that was producing zero hairs.
The Pelage team argues that follicular unit count should be added alongside total area hair count to better understand how treatments are working. Activating a dormant follicular unit in a previously bald area is a fundamentally different, and potentially more cosmetically meaningful, outcome than adding one more hair to an existing group.
The AAD 2026 presentation identified three distinct patterns of response in PP405-treated patients, tracked from baseline through day 84 (after only 28 days of treatment):
More hairs in existing follicular units: Active follicular units that already had hairs grew additional hairs within the same unit.
Activation of dormant follicular units: Previously inactive follicular units, areas where no hairs were growing at all, began producing new hairs. This was the most notable finding.
Vellus-to-terminal transition: Existing thin, peach-fuzz vellus hairs became thicker and more terminal over time.
In placebo patients, some minor fluctuations in hair count were observed (which is normal, as hair naturally cycles), but the activation of dormant follicular units and vellus-to-terminal transition were essentially absent.
No. The Phase 2a was officially a study of "Safety, Pharmacokinetics and Efficacy of PP405 in Adults With AGA" (per the ClinicalTrials.gov listing, NCT06393452), but the primary endpoints were safety and pharmacokinetics. It included exploratory efficacy readouts, but was not designed or powered to prove that PP405 works. The imaging analysis presented at AAD was exploratory.
PP405 was applied for only 28 days, with follow-up through day 84. Most hair loss treatments require 6 to 12 months to show meaningful results. Minoxidil typically takes 4 to 6 months; finasteride often takes a full year.
The fact that any signal was detectable after just 28 days of treatment is notable, but the study was small and not powered for efficacy endpoints. Larger, properly powered Phase 3 trials are needed to confirm these findings.
The AAD 2026 data is more encouraging than the original Phase 2 headlines suggested. The follicular unit tracking methodology is novel and the observation of dormant follicular unit activation is genuinely interesting science.
However, our core mechanistic concerns remain, and if anything, the AAD 2026 presentation reinforced them. PP405 still works by forcing cells into glycolysis, an inefficient, stress-associated metabolic state. The question of whether this produces durable, long-term hair growth or just a temporary activation spike has not been answered.
Our concern about the dermal papilla is now even more pointed. The presentation framed the bulge stem cells as "dormant" and PP405 as "activating" them. But based on our reading of the literature and discussions with hair biology researchers, the dermal papilla (DP) may not be strictly required to activate upper bulge cells. Many signals can trigger that activation. What the DP appears to be critical for is promoting their differentiation, the process by which activated stem cells become functional, terminal hair. Without Wnt signals from the DP, the size and quality of the hair that grows out may still be limited by the size of the dermal papilla itself. (We should note that DP-stem cell crosstalk is an active area of research and the relationship is complex, but this framing is consistent with a significant body of published work.)
If this interpretation is correct, the implications are significant: activation does not equal differentiation. PP405 may be driving bulge cell proliferation, but proliferation of bulge cells likely cannot increase DP size. Only expansion of the hair germ can do that, as far as current science understands. You would still need to rescue whatever is blocking progenitor cell migration into the DP, whether that means expanding the hair germ to increase the flow of progenitor cells, or unblocking migratory cues within the DP that may be suppressed by factors like TGF-beta.
This is exactly what the AAD 2026 data itself suggests. Dr. Mostaghimi noted that many newly activated follicular units initially produce thin vellus hairs rather than cosmetically meaningful terminal hairs. That is consistent with bulge activation without adequate DP signaling: you get proliferation and some new growth, but not the robust terminal differentiation patients actually need.
In fairness, we should note that the treatment window was only 28 days, and the gold standard for hair loss clinical trials is typically 6 months of continuous use. It is possible that with longer treatment, the early vellus hairs could terminalize and the growth signal could become much stronger. That is a legitimate argument in Pelage's favor, and one reason Phase 3 data with a longer treatment duration will be critical.
However, we also need to acknowledge what was actually shown. The detailed imaging data was presented for only 3 patients out of 78 in the trial. Selecting a handful of best responders and presenting them as representative is not the same as demonstrating efficacy across a cohort. Until we see aggregate results from the full study population, the cherry-picking concern is valid.
Independent researchers in the hair loss community have echoed this concern. Hair biology researcher @hairypapasmurf noted after viewing the AAD 2026 presentation that while PP405 shows some signs of growth, there is no indication yet that it can compete with minoxidil, and that his base case expectation is JAK inhibitor-type growth at best.
It is also worth noting that Dr. Mostaghimi disclosed that he serves on Pelage's scientific advisory board. This does not invalidate the data, but it is relevant context.
Because PP405 works through a completely different mechanism than finasteride, dutasteride, or minoxidil, there is no known reason these treatments would interfere with each other.
In theory, a combination approach could be synergistic: one treatment preventing miniaturization (finasteride/dutasteride), another extending the growth phase (minoxidil), and PP405 activating dormant follicular units.
The Phase 3 program will initially study PP405 as monotherapy. Combination studies are reportedly part of the longer-term development plan.
PP405 passed its Phase 2a trial with no safety or tolerability concerns.
Based on public materials, Pelage appears to be moving directly from Phase 2a into Phase 3 (or possibly a combined 2b/3), without a standalone Phase 2b dose-finding efficacy trial. If that is the case, it would be unusual. A Phase 2b is typically where a company proves their drug works at a specific dose before committing to the much larger and more expensive Phase 3. Without that step, Pelage would be entering late-stage trials without ever having run a properly powered efficacy study for PP405.
The ClinicalTrials.gov registry (NCT06393452) shows that Part 1 of the study involved 28 days of blinded treatment. Part 2 was a three-month open-label extension (OLE) in which placebo patients were also eligible to receive PP405. This means the controlled, blinded data comes from only 28 days of treatment, and any longer-duration observations are from the unblinded extension.
Pelage Pharmaceuticals has raised $120 million in a Series B round backed by ARCH Venture Partners and Google Ventures. Their press release describes "positive Phase 2a results" and "initial efficacy observations" as justification for moving into Phase 3. But as we have discussed, the Phase 2a was primarily a safety and PK study with exploratory efficacy readouts, and the imaging data shown publicly comes from just 3 patients out of 78.
It is worth asking why a company would raise $120 million and move into late-stage trials without first running a rigorous dose-finding efficacy study. The cynical read is that a Phase 3 trial with an upcoming IPO is more valuable to investors than a Phase 2b that might produce underwhelming efficacy numbers. We are not saying that is what Pelage is doing, but the incentive structure is worth noting.
If Phase 3 is successful, FDA approval and commercial availability would still be several years away. A realistic timeline: Phase 3 enrollment, treatment, and follow-up will likely take 2 to 3 years (2026 to 2028/2029), followed by 12 to 18 months for NDA submission and FDA review. That puts the earliest possible approval around 2030, and more realistically 2031 or 2032. If Phase 3 fails or the FDA requests additional data, add another 3 to 4 years on top of that.
Our verdict remains cautious. The science is interesting and the AAD 2026 data adds meaningful new information, particularly around dormant follicular unit activation. This is a concept that existing treatments have not been shown to achieve.
But the activation-versus-differentiation gap is a real concern. Until Pelage can demonstrate that PP405-driven bulge activation translates into sustained terminal hair growth, not just vellus fuzz from proliferating stem cells without adequate DP signaling, the mechanism has a significant unanswered question at its core. The Phase 2a data is exploratory, from a very short treatment window, and we do not yet have properly powered efficacy data.
If you are currently experiencing hair loss, we would not recommend waiting on PP405. Proven treatments like finasteride, dutasteride, and minoxidil are available now and have decades of clinical evidence behind them.
That said, if PP405's Phase 3 results confirm dormant follicular unit activation with sustained terminal hair regrowth, it would represent a genuinely new class of hair loss treatment, and we will be first in line to report on it.
Mostaghimi A. PP405: Activating dormant follicular units in androgenetic alopecia. Presented at: AAD 2026 Annual Meeting; March 28, 2026; Denver, CO. Vimeo.
Pelage Pharmaceuticals. PP405 Phase 2a clinical trial results. 2025.
Verbinnen A. I Spent Hours Researching PP405 and Here's the Honest Truth. Anagen YouTube. YouTube
Olsen EA, et al. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol. 2002;47(3):377-385. PubMed
Kaufman KD, et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol. 1998;39(4 Pt 1):578-589. PubMed
PP405 is an investigational topical that works through a novel, non-hormonal mechanism. But does the new clinical data presented at the AAD 2026 Annual Meeting change the picture? We break down what Pelage Pharmaceuticals revealed, what it means for hair loss patients, and where our original analysis still stands.
Watch our original PP405 deep dive: I Spent Hours Researching PP405 and Here's the Honest Truth
What is PP405?
PP405 is an investigational topical treatment for androgenetic alopecia developed by Pelage Pharmaceuticals. It is currently in clinical trials and is not approved for clinical use.
PP405 inhibits the mitochondrial pyruvate carrier (MPC). This shifts cellular energy production away from oxidative phosphorylation and toward glycolysis, producing more lactate in the process. That lactate activates hair follicle stem cells, promoting new hair growth.
What makes PP405 novel is that it is the first topical for androgenetic alopecia that works through metabolic reprogramming of hair follicle stem cells. Unlike finasteride or dutasteride, it does not target the androgen pathway. And unlike minoxidil, which works primarily through opening potassium channels, PP405 operates through an entirely distinct mechanism. It represents a genuinely new mechanism of action in the AGA treatment landscape.
In our earlier video analysis of PP405, we raised several concerns about the drug based on the available data at the time. You can watch the full breakdown here: I Spent Hours Researching PP405 and Here's the Honest Truth
Our primary concern was the mechanism itself. PP405 forces hair follicle cells into glycolysis, a faster but less efficient way of producing energy. We compared this to chugging coffee versus getting a good night of sleep: glycolysis might produce a short-term burst of stem cell activation, but it is not necessarily the best long-term metabolic state for a hair follicle.
We also questioned whether PP405 was targeting the right part of the hair follicle. In androgenetic alopecia, the core pathology occurs in the dermal papilla, the signaling hub at the base of the follicle, not the bulge where the stem cells reside. While PP405 increases KI67 expression (a marker of cell proliferation) in the bulge, proliferation alone does not equal healthy, terminal hair growth. The hair follicle is a complex mini-organ with at least 33 cell subpopulations, and simply driving rapid cell division does not guarantee functional, cosmetically meaningful hair.
We were also skeptical of how Pelage reported their Phase 2 data. The headline, that 31% of men with severe alopecia saw greater than 20% hair density gains after 8 weeks, meant that only a small subset of the total trial was being highlighted, and the majority of patients potentially saw little to no benefit.
At the AAD 2026 Annual Meeting in Denver on March 28, 2026, Dr. Arash Mostaghimi (who is on Pelage's scientific advisory board) presented new exploratory imaging data from the Phase 2a trial.
The presentation introduced a relatively novel methodology: tracking individual follicular units over time using high-resolution clinical photography and dermatoscopy. While some prior work has explored hair-to-hair matching trichoscopy in AGA trials, this level of longitudinal follicular unit tracking is not commonly used in clinical research and allowed the team to observe changes at the level of individual follicular units rather than just counting total hairs.
The key finding was that PP405 appeared to activate previously dormant follicular units, groups of hair follicles that had completely stopped producing hairs. While existing treatments like minoxidil can promote telogen-to-anagen switching and some vellus-to-terminal transformation, the activation of entirely dormant follicular units that were producing no hairs at all would represent a distinct type of response if confirmed in larger studies.
One important caveat: the detailed follicular unit imaging data was presented for only 3 patients out of 78 enrolled in the trial. We were not shown aggregate data across the full cohort. Cherry-picking a handful of the best responders is a pattern we have seen before with PP405 data, and it makes it impossible to draw conclusions about how the average patient would respond.
A follicular unit is a natural grouping of one to five hair follicles that share a neurovascular bundle. Think of it as a family of hairs that live together in a community on the scalp.
When measuring hair loss treatment efficacy, most clinical trials use "total area hair count," the total number of individual hairs in a given area. But this metric doesn't distinguish between adding a third hair to an already-active two-hair follicular unit versus activating an entirely new follicular unit that was producing zero hairs.
The Pelage team argues that follicular unit count should be added alongside total area hair count to better understand how treatments are working. Activating a dormant follicular unit in a previously bald area is a fundamentally different, and potentially more cosmetically meaningful, outcome than adding one more hair to an existing group.
The AAD 2026 presentation identified three distinct patterns of response in PP405-treated patients, tracked from baseline through day 84 (after only 28 days of treatment):
More hairs in existing follicular units: Active follicular units that already had hairs grew additional hairs within the same unit.
Activation of dormant follicular units: Previously inactive follicular units, areas where no hairs were growing at all, began producing new hairs. This was the most notable finding.
Vellus-to-terminal transition: Existing thin, peach-fuzz vellus hairs became thicker and more terminal over time.
In placebo patients, some minor fluctuations in hair count were observed (which is normal, as hair naturally cycles), but the activation of dormant follicular units and vellus-to-terminal transition were essentially absent.
No. The Phase 2a was officially a study of "Safety, Pharmacokinetics and Efficacy of PP405 in Adults With AGA" (per the ClinicalTrials.gov listing, NCT06393452), but the primary endpoints were safety and pharmacokinetics. It included exploratory efficacy readouts, but was not designed or powered to prove that PP405 works. The imaging analysis presented at AAD was exploratory.
PP405 was applied for only 28 days, with follow-up through day 84. Most hair loss treatments require 6 to 12 months to show meaningful results. Minoxidil typically takes 4 to 6 months; finasteride often takes a full year.
The fact that any signal was detectable after just 28 days of treatment is notable, but the study was small and not powered for efficacy endpoints. Larger, properly powered Phase 3 trials are needed to confirm these findings.
The AAD 2026 data is more encouraging than the original Phase 2 headlines suggested. The follicular unit tracking methodology is novel and the observation of dormant follicular unit activation is genuinely interesting science.
However, our core mechanistic concerns remain, and if anything, the AAD 2026 presentation reinforced them. PP405 still works by forcing cells into glycolysis, an inefficient, stress-associated metabolic state. The question of whether this produces durable, long-term hair growth or just a temporary activation spike has not been answered.
Our concern about the dermal papilla is now even more pointed. The presentation framed the bulge stem cells as "dormant" and PP405 as "activating" them. But based on our reading of the literature and discussions with hair biology researchers, the dermal papilla (DP) may not be strictly required to activate upper bulge cells. Many signals can trigger that activation. What the DP appears to be critical for is promoting their differentiation, the process by which activated stem cells become functional, terminal hair. Without Wnt signals from the DP, the size and quality of the hair that grows out may still be limited by the size of the dermal papilla itself. (We should note that DP-stem cell crosstalk is an active area of research and the relationship is complex, but this framing is consistent with a significant body of published work.)
If this interpretation is correct, the implications are significant: activation does not equal differentiation. PP405 may be driving bulge cell proliferation, but proliferation of bulge cells likely cannot increase DP size. Only expansion of the hair germ can do that, as far as current science understands. You would still need to rescue whatever is blocking progenitor cell migration into the DP, whether that means expanding the hair germ to increase the flow of progenitor cells, or unblocking migratory cues within the DP that may be suppressed by factors like TGF-beta.
This is exactly what the AAD 2026 data itself suggests. Dr. Mostaghimi noted that many newly activated follicular units initially produce thin vellus hairs rather than cosmetically meaningful terminal hairs. That is consistent with bulge activation without adequate DP signaling: you get proliferation and some new growth, but not the robust terminal differentiation patients actually need.
In fairness, we should note that the treatment window was only 28 days, and the gold standard for hair loss clinical trials is typically 6 months of continuous use. It is possible that with longer treatment, the early vellus hairs could terminalize and the growth signal could become much stronger. That is a legitimate argument in Pelage's favor, and one reason Phase 3 data with a longer treatment duration will be critical.
However, we also need to acknowledge what was actually shown. The detailed imaging data was presented for only 3 patients out of 78 in the trial. Selecting a handful of best responders and presenting them as representative is not the same as demonstrating efficacy across a cohort. Until we see aggregate results from the full study population, the cherry-picking concern is valid.
Independent researchers in the hair loss community have echoed this concern. Hair biology researcher @hairypapasmurf noted after viewing the AAD 2026 presentation that while PP405 shows some signs of growth, there is no indication yet that it can compete with minoxidil, and that his base case expectation is JAK inhibitor-type growth at best.
It is also worth noting that Dr. Mostaghimi disclosed that he serves on Pelage's scientific advisory board. This does not invalidate the data, but it is relevant context.
Because PP405 works through a completely different mechanism than finasteride, dutasteride, or minoxidil, there is no known reason these treatments would interfere with each other.
In theory, a combination approach could be synergistic: one treatment preventing miniaturization (finasteride/dutasteride), another extending the growth phase (minoxidil), and PP405 activating dormant follicular units.
The Phase 3 program will initially study PP405 as monotherapy. Combination studies are reportedly part of the longer-term development plan.
PP405 passed its Phase 2a trial with no safety or tolerability concerns.
Based on public materials, Pelage appears to be moving directly from Phase 2a into Phase 3 (or possibly a combined 2b/3), without a standalone Phase 2b dose-finding efficacy trial. If that is the case, it would be unusual. A Phase 2b is typically where a company proves their drug works at a specific dose before committing to the much larger and more expensive Phase 3. Without that step, Pelage would be entering late-stage trials without ever having run a properly powered efficacy study for PP405.
The ClinicalTrials.gov registry (NCT06393452) shows that Part 1 of the study involved 28 days of blinded treatment. Part 2 was a three-month open-label extension (OLE) in which placebo patients were also eligible to receive PP405. This means the controlled, blinded data comes from only 28 days of treatment, and any longer-duration observations are from the unblinded extension.
Pelage Pharmaceuticals has raised $120 million in a Series B round backed by ARCH Venture Partners and Google Ventures. Their press release describes "positive Phase 2a results" and "initial efficacy observations" as justification for moving into Phase 3. But as we have discussed, the Phase 2a was primarily a safety and PK study with exploratory efficacy readouts, and the imaging data shown publicly comes from just 3 patients out of 78.
It is worth asking why a company would raise $120 million and move into late-stage trials without first running a rigorous dose-finding efficacy study. The cynical read is that a Phase 3 trial with an upcoming IPO is more valuable to investors than a Phase 2b that might produce underwhelming efficacy numbers. We are not saying that is what Pelage is doing, but the incentive structure is worth noting.
If Phase 3 is successful, FDA approval and commercial availability would still be several years away. A realistic timeline: Phase 3 enrollment, treatment, and follow-up will likely take 2 to 3 years (2026 to 2028/2029), followed by 12 to 18 months for NDA submission and FDA review. That puts the earliest possible approval around 2030, and more realistically 2031 or 2032. If Phase 3 fails or the FDA requests additional data, add another 3 to 4 years on top of that.
Our verdict remains cautious. The science is interesting and the AAD 2026 data adds meaningful new information, particularly around dormant follicular unit activation. This is a concept that existing treatments have not been shown to achieve.
But the activation-versus-differentiation gap is a real concern. Until Pelage can demonstrate that PP405-driven bulge activation translates into sustained terminal hair growth, not just vellus fuzz from proliferating stem cells without adequate DP signaling, the mechanism has a significant unanswered question at its core. The Phase 2a data is exploratory, from a very short treatment window, and we do not yet have properly powered efficacy data.
If you are currently experiencing hair loss, we would not recommend waiting on PP405. Proven treatments like finasteride, dutasteride, and minoxidil are available now and have decades of clinical evidence behind them.
That said, if PP405's Phase 3 results confirm dormant follicular unit activation with sustained terminal hair regrowth, it would represent a genuinely new class of hair loss treatment, and we will be first in line to report on it.
Mostaghimi A. PP405: Activating dormant follicular units in androgenetic alopecia. Presented at: AAD 2026 Annual Meeting; March 28, 2026; Denver, CO. Vimeo.
Pelage Pharmaceuticals. PP405 Phase 2a clinical trial results. 2025.
Verbinnen A. I Spent Hours Researching PP405 and Here's the Honest Truth. Anagen YouTube. YouTube
Olsen EA, et al. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol. 2002;47(3):377-385. PubMed
Kaufman KD, et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol. 1998;39(4 Pt 1):578-589. PubMed
