2014 Alopecia Areata Research Summit Highlights Recent Breakthroughs

Significant research progress occurred in 2014, offering new leads that are driving current research
efforts related to alopecia areata.

The fifth Alopecia Areata Research Summit, From Targets to Treatments: Bridging Autoimmune Research to
Advance Understanding of Alopecia Areata, brought together leading experts with new investigative partners to
discuss exciting new discoveries and identify opportunities to further advance alopecia areata research. This
meeting, held December 4 to 5 in Bethesda, Maryland, represented a pivotal moment for alopecia areata
research and treatment development with early stage clinical trials of drugs targeting autoimmune pathways
showing promising hair regrowth for the first time ever. Among the 90 participants were representatives from
five different branches of the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA),
the Patient-Centered Outcomes Research Institute (PCORI), and several biopharmaceutical companies with
relevant clinical initiatives, as well as experts in the fields of hair and skin disease research, clinical care, basic
science, immunology, and autoimmunity from more than 35 academic institutions and research centers across
the globe, and representatives of the patient community that any potential treatment would be designed to
serve.

Our three outstanding co-chairs, Drs. David Norris, Julian Mackay-Wiggan, and Jeff Frelinger, worked together to
develop a packed program focused on 1) autoimmune and immunological aspects of alopecia areata; 2) recent
genetic developments and new therapeutic targets; 3) emerging animal models; 4) new research technologies
and directions; and 5) clinical aspects, epidemiology and tools to advance research.

Immunology and Autoimmunity

Presentation Highlights
Dr. Raphael Clynes, Group Medical Director at Bristol-Myers Squibb, presented research on the
identification and targeting of cytotoxic CD8 T Cells in alopecia areata.

Dr. Marta Bertolini, from the University of Münster in Germany, discussed an ongoing project to
characterize the clonotypes of autoagressive CD8 T-cells that invade the hair follicles in alopecia areata.
She discussed the identification of CD8 T cells in situ in the hair follicle using laser capture
microdissection technology.

Dr. John Harris, from the University of Massachusetts, shared the commonalities between alopecia
areata and vitiligo including interferon-gamma (IFNg) gene expression and expression of CXCL9, CXCL10,
and CXCL11 chemokines. He noted that similarities in pathogenesis could lead to potential treatments.

Dr. Dan Kaplan, from the University of Minnesota, examined the diversity and phenotype of dendritic
cells found in the skin and their potential role(s) in alopecia areata.
 2014 Research Summit Summary
Page 2 of 8

Action Items for the Next Two Years

 Continue research to advance understanding of mechanisms of disease, including roles of dendritic cells,
antigen-presenting cells, macrophages and early innate immune response, which could lead to
discoveries for early intervention and prevention.
 Identify T-cell receptor antigens/epitopes driving the disease, which could be used as predictive
markers.
 Begin collecting more useful immunological samples (white blood cells, peripheral blood mononuclear
cells and swabs) for the Alopecia Areata Registry, Biobank and Clinical Trials Network and working with
the Immune Tolerance Network to develop a protocol for freezing and banking samples.
 Investigate the potential use of antibodies, cytokines or other molecules to serve as biomarkers for
alopecia areata and/or T-cell responses, responses to therapy, or predictive markers.
 Study regulatory T cells for potential use as predictors of hair regrowth or response to therapy.
 Investigate the role of chemokines regulating autoreactive homing in alopecia areata.
 Further study the relationship between other autoimmune diseases and alopecia areata.
 Further study the thyroid and thyroiditis in relationship to alopecia areata.
 Investigate the role of inflammasomes in alopecia areata.

Genetic Developments and Therapeutic Targets

Presentation Highlights
Dr. Angela Christiano, from Columbia University, provided an update on Genome-wide Association
Studies in alopecia areata, including resolution of human leukocyte antigen signal, identification of new
candidate GWAS loci, and regulation of autophagy, JAK-STAT signaling, and regulatory T cells.

Dr. Ali Jabbari, from Columbia University, shared preliminary results from a comprehensive gene
expression profile of skin and blood from patients with alopecia areata and the results correlate with
disease severity. Data suggests that alopecia universalis and alopecia totalis are extreme manifestations
of patchy alopecia areata at the gene expression level.

Dr. Rick Kittles, from the University of Arizona, presented the use of genetic ancestry in disease studies,
including genetic factors driving differences in disease susceptibility across populations and the use of
Ancestry-Informative Markers (AIMS) in the design of genetic studies.

Dr. Thomas Waldmann, Chief of the Lymphoid Malignancies Branch at the National Cancer Institute,
discussed JAK1-selective inhibitors and their role as a potential therapeutic agent for alopecia areata.

Dr. Massimo Gadina, Director of the Office of Science and Technology at NIAMS, reviewed studies of
Janus kinases (JAK) inhibitors in autoimmune and autoinflammatory diseases and related drugs now in
development.

Dr. Aziz Ghahary, from the University of British Columbia, presented a new cell therapy using IDO-
expressing fibroblasts to suppress the immune cells attacking hair follicles, resulting in regrowth of the
hairs.

Dr. Robert Gensure, from Albert Einstein College of Medicine, shared results of a trial of skin-targeted
parathyroid hormone agonists and antagonists in C3H/HeJ engrafted mice, including effects on hair
growth, immune response, and induction of the hair cycle.
 2014 Research Summit Summary
Page 3 of 8

Dr. Bill Levis, from New York and Rockefeller Universities, discussed a new delivery of diphencyprone
(DPCP) coupled with interference RNA (iRNA) targets in alopecia areata skin, enhancing DPCP efficacy
and response rates.

Dr. Scott Kachlany, from Rutgers School of Dental Medicine and Actinobac Biomed, Inc., presented an
experimental biologic that specifically targets active lymphocyte function associated antigen-1 (LFA-1)
on hyper-reactive immune cells. Leukothera is able to rapidly deplete activated immune white blood
cells that are involved in autoimmune and inflammatory conditions such as alopecia areata, resulting in
relief of disease symptoms.

Action Items for the Next Two Years

 Focus on expanding the Registry to 10,000+ DNA samples for deep sequence analysis to identify new
candidate genes and variants and determine the downstream impact.
 Study the epigenetics of alopecia areata and investigate the role of race and ethnicity.
 Undertake additional biomarker studies and determine a genotype risk score.
 Study gene expression of patchy alopecia areata and investigate parallels between regional beta cell
destruction in Type 1 diabetes.
 Investigate the role of epigenetics, environment, and triggers in discordant twins.
 Study the role of CD4 T cells in alopecia areata.
 Collaborate with international databases/repositories for the use of samples from diverse populations.
 Apply to NIH for funding of large-scale genetic sequencing studies.

Animal Models
Presentation Highlights
Dr. Michael Brehm, from the University of Massachusetts, provided an overview of humanized mouse
models that are currently available to study human immunobiology, discussing the advantages and
limitations of each model system and the possibility of future models for personalized medicine using
individual samples.

Dr. Lishan Su, from the University of North Carolina, presented an update of humanized mouse models
used in the study of human immunology, the recent progress in studying persistent human virus
infections, and the goal of generating disease-specific and patient-specific disease models.

Dr. John Sundberg, from The Jackson Laboratory, shared the International Knockout Mouse Project to
inactivate all known protein coding genes and analyze skin phenotypes in individual gene knockouts.
Systematically screening mice generated at The Jackson Laboratory and Sanger Center for skin diseases
will provide an enormous resource for dermatological research, including models for alopecia areata.

Action Items for the Next Two Years

 Expand research to identify better animal models to minimize graft-vs-host disease (GVHD) as current
models are often difficult to reproduce and accelerate.
 Develop a model that uses induced pluripotent stem (IPS) cells from patients to perform drug screening.
 Facilitate contracts between academics and industry and the coordination of resources.
 Develop standardized protocols for more reproducibility and begin pilot studies in basic and preclinical
trials.
 2014 Research Summit Summary
Page 4 of 8

New Technologies and Directions

Presentation Highlights
Dr. Vladimir Botchkarev, from the University of Bradford in the United Kingdom, shared how epigenetic
mechanisms play an important role in the control in the skin and hair follicle. Knowledge about how
epigenetic mechanisms are involved in pathogenesis of alopecia areata could lead to understanding how
to activate good genes and silence bad genes in skin cells.

Dr. Lita Proctor, Director of the Human Microbiome Project at the National Human Genome Research
Institute, discussed the human microbiome and its role in autoimmune diseases. The microbiome is an
integral, normal and necessary part of human physiology and new research suggests a loss in
microbiome diversity is associated with an increase in autoimmune diseases.

Dr. Annemieke de Jong, from Columbia University, explored the use of Next-Generation T-cell receptor
(TCR) sequencing in alopecia areata mice and humans to gain insight in the dynamics of the T-cell
repertoire during alopecia areata pathogenesis.

Dr. Heather Hickman, Staff Scientist at the NIAID Laboratory of Viral Diseases, described recent work
using intravital microscopy to track virus-infected cells and immune effectors in real time in vivo during
skin infection with vaccinia virus including intravital imaging of T-cell dynamics during skin infection.

Dr. Alessandro Sette, from the La Jolla Institute for Allergy and Immunology, presented the Immune
Epitope Database (IEDB), a searchable warehouse of published antibody and T-cell epitope data, as well
as new tools for antigen discovery and epitope prediction.

Dr. Stephen Miller, from Northwestern University, detailed the efficacy and mechanisms of using the
intravenous infusion antigen-encapsulated biodegradable PLG nanoparticles containing antigens to
induce immune tolerance including ongoing efforts to advance clinical translation of this novel therapy.

Action Items for the Next Two Years

 Perform a literature review and industry scan to identify the status of epitope and microbiome research
in alopecia areata and related diseases.
 Expand research into the scalp and hair follicle microbiome starting with a 16S Ribosomal DNA Sequence
Analysis comparing data from normal subjects to alopecia areata subjects.
 Analyze the regional and geographical pattern of alopecia areata to study the epidemiological,
ecological, and environmental factors related to microbiome diversity.
 Investigate differentially expressed proteins in hair follicles and nerves using proteomic approaches.
 Utilize the Immune Epitope Database (IEDB) analysis resource to generate predicted epitopes and sets
of specific predicted epitopes from proteins identified in point d) above for testing in alopecia areata.
 Leverage available technology in infectious diseases and allergies to generate targeted experimental
data using alopecia areata blood samples to screen the epitope sets described in point e) above.

Clinical Aspects, Epidemiology and Tools

Presentation Highlights
Dr. Maria Hordinsky, from the University of Minnesota, provided an overview of current treatment
practices in alopecia areata and examined the rationale for choosing one treatment over another,
including weighing the risk/benefit ratio of current and evolving choices.
 2014 Research Summit Summary
Page 5 of 8

Dr. Wilma Bergfeld, from the Cleveland Clinic, presented a retrospective study of 50 Cleveland Clinic
patients with alopecia areata that were treated with diphencyprone (DPCP) that revealed three
statistically significant predictors of poor treatment outcome: extent of hair loss, history of thyroid
disease, and extent of body hair involvement. Dr. Bergfeld also discussed Intralesional Kenalog (ILK) as
the first-line therapy in the treatment of alopecia areata and presented data suggesting that, in addition
to the immunosuppressive effect of intralesional steroids, the act of penetrating the skin may also be a
component of the therapeutic benefit of ILK injections.

Dr. Julian Mackay-Wiggan, from Columbia University, reported on the exciting preliminary results from
ongoing pilot trials at Columbia University Medical Center to test the efficacy of Jakafi (ruxolitinib, a Jak1
and 2 inhibitor) and Orencia (abatacept, the fusion protein CTLA4-Ig) to treat alopecia areata. Interim
results show promise and the incidence of adverse events are minimal. The design for the upcoming the
Xeljanz (tofacitinib, a Jak 3 inhibitor) study was also discussed. Early findings from the ruxolitinib study
were published in Nature Medicine in September.

Dr. Vera H. Price, from the University of California, San Francisco, shared the accomplishments and
current enrollment status of the Alopecia Areata Registry, Biobank and Clinical Trials Network (Registry)
including epidemiological data and tissue samples of patients with alopecia areata.

Dr. Melissa Piliang, from the Cleveland Clinic, discussed eosinophilic esophagitis as a potential trigger of
alopecia areata and the association of atopy and alopecia areata.

Dr. Natasha Mesinkovska, from the Cleveland Clinic, presented a retrospective cross-sectional study that
evaluated the prevalence of comorbid conditions among patients with alopecia areata over a 10-year
period and found no significant differences between alopecia areata and controls in sun induced skin
cancers.

Dr. William Russell, from Vanderbilt University, discussed the similarities between Type 1 diabetes and
alopecia areata, including the role of beta cells and prevention studies as well as enrolling alopecia
areata patients in a Type 1 Diabetes TrialNet prevention screening program.

Lindsay Boyers, medical student at Georgetown University, shared results of the Global Burden of
Disease Study; the burden of disease caused by alopecia areata is equivalent to 18.6 years of healthy life
lost despite the fact that mental health burdens are not considered. Data from this study is publicly
available on the Global Burden of Disease website: www.healthdata.org/gbd.

Dr. James Solomon, Director of Ameriderm Research, discussed the development of a Core Uniform
Protocol for alopecia areata to enhance and make it easier for pharmaceutical and device companies to
develop clinical trials, and to maintain consistent parameters to compare and contrast studies,
including: inclusion/exclusion; outcome assessment measures; and safety parameters.

Action Items for the Next Two Years

 Modify the Core Uniform Protocol to expand age ranges and duration of hair loss criteria for inclusion.
 Work with drug companies, both large and small, to supply therapies being tested and facilitate larger
trials with more patients.
 Estimate burden of disease and annual cost to payers to entice insurance companies for coverage as
well as pharmaceutical interest.
 2014 Research Summit Summary
Page 6 of 8

 Publicize information about disease burden and collaborate with the American Association of
Dermatologists to disseminate data quickly.
 Advocate for insurance coverage of systemic or topical JAK inhibitors and partner with PCORI for
comparative effectiveness research.
 Survey patients and medical professionals to capture clinical data about off-label use of JAK inhibitors
and other potential therapies.
 Encourage and support medical professionals in obtaining Institutional Review Board approval to
prospectively capture efficacy and safety data for alopecia areata patients treated off label with JAK
Inhibitors and other potential therapies.
 Study connections between alopecia areata and other systemic autoimmune diseases such as
hypothyroidism.
 Investigate response to therapy among different ethnic groups.
 Collaborate with investigators performing clinical studies and develop a unified database to capture
information.
 Improve communication between patients and caregivers, including sensitivity training about emotional
impacts, to facilitate information sharing.
 Improve privacy and emotional sensitivities of survey tools to validate potentially underestimated
prevalence and incidence statistics.

Funding and Partnership Opportunities

Presentation Highlights
Dr. Stephen Katz, Director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS), kicked off the meeting and discussed relevant NIH funding opportunities, including the
Accelerating Medicines Partnership, as well as a new initiative to share data about well-scored grants
that fall below the NIAMS pay-line with patient advocacy groups to provide important bridge funding.

“We are from the government, and we can really help!”—Dr. Stephen Katz

Dr. Ricardo Cibotti, Director of the Skin Immunobiology and Immune Mediated Diseases of Skin Program
at NIAMS, provided a comprehensive review of current funding opportunities to support clinical trials:
R21, R34 and U01 grants. He informed participants about common pitfalls to avoid, including insufficient
study premise documentation, inexperienced investigators, limited evidence for efficacy, poor study
design, sample size issues, and failing to address relationships between the principle investigator,
sponsor, and other parties.

Dr. Daniel Rotrosen, Director of the Division of Allergy, Immunology, and Transplantation at the National
Institute of Allergy and Infectious Diseases (NIAID), discussed funding opportunities and sponsored
research tools, reagents, and resources to facilitate basic and clinical research on autoimmune
disorders, including the Immune Tolerance Network (ITN) for clinical trials and ImmuneXpresso, a new
tool that filters literary data to create enrichment maps of network interactions between cells and
cytokines and gene expression for specific diseases.

Dr. Kara Odom Walker, Deputy Chief Science Officer at the Patient-Centered Outcomes Research
Institute (PCORI), introduced PCORI to participants, including comparative effectiveness research
(comparing two or more options for prevention diagnosis treatment), and patient-centered outcomes
research (including patient input throughout the development process). She presented funding
 2014 Research Summit Summary
Page 7 of 8

opportunities in five areas: prevention, diagnosis and treatment; improving healthcare; communication;
health disparities; and accelerating methodological research.

Dr. Anton Simeonov, Acting Deputy Scientific Director at the National Center for Advancing Translational
Sciences (NCATS), presented high-throughput screening opportunities, including the comprehensive
public-access screening collection of small molecule agents and a platform capable of testing thousands
of compounds in pairwise matrix blocks for the rapid and systematic identification of synergistic,
additive, and antagonistic drug combinations. He noted that it can take several years to establish good
cell-based assays for screening and is open to discussing projects with researchers

Dr. Theresa Mullin, Director of the Office of Strategic Programs at the U.S. Food and Drug Administration
(FDA) Center for Drug Evaluation and Research, discussed new FDA initiatives to help advance drug
development. She presented an overview of three key initiatives: structured benefit-risk assessment,
patient-focused drug development, and breakthrough therapy designation.

Amanda Wagner, Senior Director of Product Planning and Program Management at Concert
Pharmaceuticals, shared the business case for pursuing alopecia areata from the biotech industry
perspective. Important topics covered included how companies and investors think about drug
development and commercialization for alopecia areata; insurance reimbursement considerations for
novel therapies; and strategies to obtain approval for repurposing of existing drugs.

In addition to the scientific presentations, two patient advocates shared their stories. Maria Beckett, shared her
experiences as a young girl with hair loss and growing up with the stigma that the disease brought. She shared
how this disease affects more than just the hair and how the community must remember that while they are
looking for a cure they are also seeking to help improve a patient’s self-esteem and confidence. Guru Mathur
shared his perspective as a parent who struggles to weigh the pros and cons of toxic drugs to potentially treat
his young daughter. He stressed how difficult it is to not only watch your child suffer but to make the medical
decisions when there is no certainty the drugs will help to alleviate the burden. He encouraged researchers to
look outside the box for medical advances.

This two-day summit fostered innovation and collaboration across multiple disciplines with a series of key
research presentations followed by substantive question-and-answer sessions and discussions. Inclusion of
women, minorities, and people with disabilities is a NAAF priority and the meeting drew a diverse and balanced
group of knowledgeable attendees. Several early-career investigators brought fresh ideas and new talent, and
individuals with alopecia areata and family members provided an important bridge between those studying the
disease and those personally affected by it. The fruitful discussions had several common underlying themes,
including increased collaboration between existing researchers with common interests, increasing biopharma
interest and participation, expanding the Registry to include more diversity and more samples, amplifying the
NAAF message, and prioritizing research to learn more about how alopecia areata begins and how to stop its
progression. Participants left feeling excited about recent research progress and new possibilities. We are
working on preparing Summit Proceedings, which we hope will be accepted by the Journal of Investigative
Dermatology for publication next year.

Alopecia areata research summits are part of the National Alopecia Areata Foundation’s (NAAF) main strategic
initiative, the Alopecia Areata Treatment Development Program (TDP). Many of the research accomplishments
explained above have been part of this Program, with NAAF either providing direct funding or acting as a
concierge, leveraging all of our available research resources and clinical partnerships. Our strategic goal is to
 2014 Research Summit Summary
Page 8 of 8

produce a safe, effective, affordable treatment beneficial to the millions of people with alopecia areata. This
summit was another strategic step on the structured and focused path to that goal. Many of the Action Items
proposed and discussed are projects that have been in progress. NAAF has and will continue to provide the
support and leadership toward accomplishing these Action Items to enhance the understanding of alopecia
areata. We look forward to future discoveries.

Please contact us if you can help in any way or are interested in applying for funding to study any of the Action
Items mentioned above.

The National Alopecia Areata Foundation gratefully acknowledges the following

partners for generously supporting this meeting.

This meeting was made possible in part by funding received from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases and the National Center for Advancing Translational Sciences of the
National Institutes of Health under Award Number R13AR067088. The views expressed in written
conference materials or publications and by speakers and moderators do not necessarily reflect the official
policies of the Department of Health and Human Services; nor does mention of trade names, commercial
practices, or organizations imply endorsement by the U.S. Government.

Corporate Sponsors