Pelage Embraces Diverse Patient Recruitment For Non-Hormonal Hair Loss Therapy

A conversation with Qing Yu Christina Weng, MD, chief medical officer, Pelage Pharmaceuticals

Around 50% of men and women are affected by androgenetic alopecia, or pattern baldness. While there are numerous types of alopecia, including chemotherapy-induced alopecia and autoimmune hair loss such as alopecia areata, androgenetic alopecia is by far the most common and something that most people will experience in their lifetime, says Pelage Pharmaceuticals’ CMO Qing Yu Christina Weng, MD.

Weng and her team at Pelage are embarking on a Phase 2a clinical trial for PP405 for the treatment of androgenetic alopecia.

In this interview, Weng discusses Pelage’s desire to buck the trend of the existing landscape of hair loss treatments, expand research to include patients of all skin and hair types, and incorporate decentralized elements in their trial design.

Help us explore the current landscape of androgenetic alopecia, first detailing the patient populations it affects, how it affects them, and then assessing currently available therapies. What is lacking in terms of treatment options?

While pattern baldness impacts all genders, hair loss manifests differently across men and women. In men, hair loss primarily affects the frontal temporal hairline and the vertex scalp, and in women, the most common sign is a widening part line. This is of course a generalization, and women and men with androgenetic alopecia also experience diffuse thinning of the hair.

Hair follicles normally cycle through periods of rest (telogen) and growth (anagen). This cycle can get disrupted due to a variety of factors, including age, hormones, stress, and genetics, and over time the stem cells in the follicle that initiate the growth of a new hair cycle can become quiescent.

While current treatment options may slow the progression of hair loss, most target secondary factors such as hormones. There are only two FDA-approved treatments for androgenetic alopecia — finasteride and minoxidil — with no new drugs approved in the last two decades. Both are limited in efficacy, and only a subset of users notices improvement in hair growth. There are also significant side effects, particularly with hormonal therapies such as finasteride.

Other options for androgenetic alopecia include over-the-counter supplements, red light treatments, platelet-rich plasma injections, and hair transplantation. These can be costly, time-consuming, and have limited efficacy, and most have not been tested in rigorous clinical trials.

Due to the shortcomings of the hair loss therapeutic landscape, the scientific cofounders of Pelage set out to create a new treatment option rooted in strong science that targets hair follicle stem cells directly. The hormone-free investigational treatment is designed to be noninvasive and is intended for all genders, hair types, and skin types.

What is the hope that PP405 achieves for patients?

With PP405, we aim to deliver a noninvasive, topical hair loss solution for all genders, skin types, and hair colors and textures grounded in stem cell biology. Unlike existing treatments that target indirect causes of hair loss, PP405 is designed to reactivate dormant hair follicle stem cells that can get stuck in the resting phase, triggering them to begin a new hair growth cycle.

Because of the mechanism of action, we expect this approach to work for women and men and across all hair types and skin types.

Pelage has just begun dosing patients with PP405 in its Phase 2a trial for safety and preliminary efficacy. When it came to enrollment, what was the reception and motivation to participate among patients with androgenic alopecia?

We are excited to see a lot of interest from people interested in participating in the Phase 2a study even before it began, which reflects how widespread androgenetic alopecia is and the excitement around a new mechanism of action. We are now actively enrolling across the United States.

Specifically, this trial has inclusion/exclusion criteria that welcome participants of both genders and various skin tones and hair textures. Historically, has that always been the case for trials exploring treatments for hair loss?

Unfortunately, hair loss trials have not always been inclusive of all genders and skin pigmentary types. This is a reflection of several factors, including the treatment mechanisms and the technology used to assess endpoints. For drugs with hormonal effects such as finasteride, many women may not be eligible due to its hormonal effects and risk of birth defects, and this automatically limits the population that can be enrolled. Additionally, the high-resolution imaging technology used to assess hair counts for clinical trial endpoints has evolved significantly — historically, darker hair against lighter skin is easier to photograph and evaluate, which has limited the inclusion of more pigmented skin in clinical trials. Thanks to continued innovation in this space, we are lucky to use imaging technology that allows for the quantification of hair density and other objective metrics across all hair types and skin pigmentary types. We were aware of an existing limitation in imaging technology and had early conversations with imaging providers to ensure this capacity was built in from the very beginning of the Phase 2a trial so that adults of all genders, hair types, and skin types could participate.

And so why is it important to include diverse patient genders and races in this type of trial? What do we know about various skin tones and hair textures as they relate to hair loss? Are there differences in disease prevalence or presentation?

We know that hair loss — in this case, androgenetic alopecia — affects people of all genders, hair types, and skin tones. We are lucky to have a potential therapeutic that targets the source of hair loss directly, at the level of hair follicle stem cells. Disruption of the natural hair cycle is consistent across everyone with androgenetic alopecia, no matter the gender or race. The components driving this disruption can be multifactorial — age, stress, hormones, genetics, nutrition, environmental factors, and even how you wear your hair. Those drivers vary across each patient, but we can bypass that and intervene at the level of the hair follicle stem cells. We are mindful of this unique opportunity to help patients of all genders, hair types, and skin types through a common mechanistic pathway, and we are designing our trials from the outset to reflect the diversity of the treatment population.

And what would the hazards be if more diverse patient groups were not included?

It’s hugely important to design clinical trials up front with a diverse population in mind. The earlier we can include a diverse range of patients, the more data we will have on the safety, tolerability, and efficacy of any particular treatment for all people. This will ultimately impact the population the drug is approved for and how the drug is used commercially, so it is in the interest of both the patients and the drug developers to include as diverse a population as early as possible.

Dermatological trials can sometimes require frequent in-person visits. How was this trial structured, as far as using in-person and digital/remote elements, to accommodate patients?

PP405 is a noninvasive topical designed to be applied by the patient. Patients in our trial can store and apply the treatment at home. As with most trials, they do have to go into the clinic at set times for monitoring visits, including assessment for safety and efficacy endpoints. However, for the majority of the trial, they can do the steps from home.

Given the prevalence of androgenetic alopecia, are there many competing trials for its treatment? And if so, what are some strategies Pelage used to raise awareness among HCPs and/or patients for PP405?

There is primarily incremental innovation in this space. Most treatments under development, including preclinical assets and those in Phase 1 studies and beyond, still use old mechanisms of action, and the landscape is dominated by reformulations and me-too products. We believe PP405’s novel mechanism that directly targets hair follicle stem cells, combined with a topical delivery approach, is unique and fulfills a large unmet need in the current treatment landscape for a safe and effective noninvasive product. It’s also supported by translational and clinical data from ex vivo facelift skin studies and our Phase 1 clinical trial.

The data, which was presented in a late-breaking session at the American Academy of Dermatology (AAD) 2024 Meeting, demonstrated proof of mechanism for PP405, which was consistent with preclinical data. Our co-founders, William Lowry, Professor of Molecular, Cell, and Developmental Biology, Heather Christofk, Professor of Biological Chemistry, and Michael Jung, Distinguished Professor of Chemistry, also have published extensively in this space.

Through our publications in peer-reviewed journals and data presentations at academic meetings to clinical and scientific colleagues, we can showcase this positive early-stage data, share our plans for continued clinical trials, and underscore the unique potential of PP405 in reversing the effects of hair loss for countless patients with androgenetic alopecia.

About The Expert:

Qing Yu Christina Weng, MD, is the chief medical officer of Pelage Pharmaceuticals. Weng is a physician-scientist and entrepreneur, board-certified dermatologist, and faculty member at Harvard Medical School. She is experienced in corporate-startup strategy in her previous roles as head of business development & strategy at Kira Pharma and CSO and cofounder of Mymiel Skincare. She is on the Advisory Board for Immunis, a regenerative medicine company developing secretomes for age-related dysfunction. She is on the Board of Directors for the Dermatology Innovation Forum and Dermatology Summit. Weng has an undergraduate degree from the California Institute of Technology, an MD from Harvard, and she completed a dermatology residency and fellowship at Harvard.