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Long-Term Safety & Efficacy of CTP-543,
an Oral JAK Inhibitor, for the Potential
Treatment of Alopecia Areata
2021 JAK Drug Development Summit
James V. Cassella, Ph.D.
Chief Development Officer
Disclosure
• Concert Pharmaceuticals, Inc.
‒ Employee:
• Salary Compensation
• Own stock and stock options
• No other disclosures
2
Presentation Outline
• Overview of alopecia areata
• Introduction to CTP-543: a deuterated JAK inhibitor
• Summary of Phase 2 dose-ranging study results in patients with alopecia areata
• Description of long-term, open label extension study
‒ Update on common adverse events to date
‒ Update on key hematology parameters through one year of continuous dosing with high dose CTP-543
‒ Update on efficacy through one year of continuous dosing with high dose CTP-543
3
Alopecia Areata: A Serious Medical Disease
• A devastating and poorly treated autoimmune disease
• Alopecia Areata occurs worldwide
‒ Prevalence of approx. 0.2% of the US population with a lifetime
risk of 1.7 – 2%*
• Chronic condition affecting women, men and children of
all ages
• Disease profoundly impacts patients; associated with
anxiety, depression and other autoimmune conditions
• No FDA-approved treatment options
‒ FDA PFDDI meeting (September 2017) on alopecia areata
highlighted patient experience and need for treatment
4*Safavi et al., 1995; Benigno et al., 2020
Burden of Illness in Alopecia Areata*
• Adult patients were recruited from the National Alopecia Areata Foundation (NAAF) database
• 216 patients completed the survey
‒ Most were female (83%), ≥45 years (59%), and White (78%)
‒ Data were analyzed descriptively
• 62% of respondents made different major life decisions (regarding relationships, education, or career)
due to alopecia areata
• 85% stated coping with alopecia areata is a daily challenge, citing mental health issues, concealing hair
loss and others’ reactions
‒ 47% reported anxiety/depression
• 75% persistently concealed hair loss (mean time spent: 10.3 hours/week)
• Significant expenditures included buying wigs/hairpieces and psychotherapy (mean ~$2,000/year each)
KEY FINDING: The impact of alopecia areata extends beyond cosmetic concerns
and carries a considerable psychosocial burden
5*Mesinkovska et al. Burden of Illness in Alopecia Areata: A Cross-Sectional Online Survey Study. J of Invest Derm Sym Proceed (2020) 20, S62eS68
Clinically Meaningful* Hair Regrowth
• Scalp-hair loss is the most bothersome alopecia areata sign/symptom for most patients
‒ Until very recently, patient perspectives on a success threshold for hair regrowth was unknown
• One of the objectives of this noninterventional, cross-sectional, qualitative interview study
was to understand clinicians’ and patients’ perspectives and expectations of a clinically
meaningful treatment outcome
‒ 25 adult and 5 adolescent alopecia areata patients and 10 expert clinicians participated in the study
• Perceived treatment success – short of 100% scalp hair – was the presence of ~70–90%
scalp hair with a median of 80% scalp coverage
KEY FINDING: Nearly all clinicians and patients in this study agreed that, for patients
with at least 50% scalp-hair loss, successful treatment would be hair regrowth
resulting in ≤ 20% scalp-hair loss
6*Wyrwich et al. The Alopecia Areata Investigator Global Assessment scale: A measure for evaluating clinically meaningful success in clinical trials. Br J Dermatol 2020; 183:609.
The Role of Janus Kinase (JAK) in Alopecia Areata
• JAK is a family of intracellular tyrosine kinases that play a central
role in the signaling of cytokine and growth factor receptors
‒ Therapies targeting downstream JAK effectors have shown efficacy in
autoimmune disorders such as atopic dermatitis, psoriasis, and RA
• Alopecia areata is an autoimmune disorder characterized by non-
scarring hair loss affecting scalp and body hair
• Proposed mechanism of hair loss in alopecia areata: cytotoxic T cell
attack of the hair follicle after loss of immune privilege, regulated by
JAK signaling
• Various JAK inhibitors are in clinical-stage testing and show
promise as a class in treating alopecia areata
7
CTP-543: Potential Oral Treatment for Alopecia Areata
• CTP-543 (deuruxolitinib) is deuterated JAK1/2 inhibitor
• Three Phase 2 trials, including definitive dose-ranging study, have
been completed
‒ Two effective doses have been identified
• Phase 3 THRIVE-AA Program underway
‒ 2 multinational Phase 3 trials (US, CAN, EU); approximately 1,100 patients
• A long-term, open label extension study is ongoing
‒ Initiated during the Phase 2 program; Phase 3 participants eligible
‒ Continued assessment of safety and efficacy
• CTP-543 granted Fast Track and Breakthrough Therapy Designation
by FDA
8
CTP-543 Phase 2 Trial: Baseline vs. Week 24
Opportunity to address important unmet medical need
CTP-543: Phase 2 Dose-Ranging Trial
• Randomized 149 adult patients with moderate to
severe alopecia areata
• Double-blind, randomized, placebo-controlled trial
‒ At least 50% hair loss as measured by Severity of Alopecia
Tool (SALT)
‒ Primary Endpoint: 50% relative reduction in SALT at Week
24 from baseline
‒ Sequentially randomized to receive one of three doses of
CTP-543 (4, 8,12 mg BID) or placebo for 24 weeks
• Primary endpoint met with statistical significance for
8 mg and 12 mg doses at Week 24
‒ 12 mg responders average 86% SALT improvement
‒ 8 mg responders average 78% SALT improvement
• Significant patient reported Global Impression of
Improvement 9
9 %
21%
47%
58%
0
10
20
30
40
50
60
4 mg BIDPlacebo 8 mg BID 12 mg BID
Patients with ≥ 50% Change in SALT Relative to Baseline
Responders at Week 24
*** P < 0.001 vs PBO
Response Over Treatment Period: 12 mg BID
Week 12 Week 24Baseline
Responders: ≥ 50% Change in SALT Relative to Baseline
10
21%
9 %
47%
58%
CTP-543 Phase 2: Patients Achieving a Clinically Meaningful SALT Score ≤ 20
11
0
10
20
30
40
50
60
Week 4 Week 8 Week 12 Week 16 Week 20 Week 24
% P
atie
nts
pe
r T
rea
tme
nt
Placebo 4 mg BID 8 mg BID 12 mg BID
***
+
7%
14%
26%
42%
*** P < 0.001 vs PBO
* P < 0.05 vs PBO
+ P < 0.05 vs 8 mg
Response Over Treatment Period: 12 mg BID
12
Baseline Week 12 Week 24
Response Over Treatment Period: 8 mg BID
13
Baseline Week 12 Week 24
Patient AASIS* Scores for Scalp Hair Loss
14
Patient Global Impression of Improvement: Responders
*** P < 0.001 vs PBO
***
***
% R
esp
on
de
rs
78%
58%
36%
21%
1515
Placebo(n = 44)
CTP-543
4 mg(n = 29)
CTP-543
8 mg(n = 38)
CTP-543
12 mg(n = 36)
Total # TEAEs 100 95 137 115
# Patients with TEAEs, n (%) 31 (70.5%) 25 (86.2%) 31 (81.6%) 30 (83.3%)
# Patients with Moderate or Severe
TEAEs, n (%)14 (31.8%) 9 (31.0%) 15 (39.5%) 7 (19.4%)
# Patients Discontinued, n (%) 9 (20.5%) 7 (23.3%) 8 (21.1%) 1 (2.7%)
Discontinued Due to AE, n (%) 3/9 (33.3%) 0/7 (0%) 2/8 (25%) 0/1 (0%)
Grade 3 or 4 Hematology:
Neutropenia, n (%)1 (2.3%)
(Pt discontinued)1 (3.6%) 1 (2.6%)
(Pt dose interrupted)0 (0%)
16
Phase 2 Dose-Ranging Trial Treatment Emergent AEs
Data from Study CP543.2001
Phase 2 Dose-Ranging Trial Common (≥ 10%) TEAEs (# Patients)
17
Preferred Term Placebo(n = 44)
CTP-543
4 mg(n = 28)
CTP-543
8 mg(n = 38)
CTP-543
12 mg(n = 36)
Headache 4 (9.1%) 5 (17.2%) 10 (26.3%) 7 (19.4%)
Nasopharyngitis 1 (2.3%) 3 (10.3%) 3 (7.9%) 9 (25.0%)
URI 7 (15.9%) 2 (6.9%) 2 (5.3%) 7 (19.4%)
Acne 2 (4.5%) 4 (13.8%) 4 (10.5%) 6 (16.7%)
Nausea 4 (9.1%) 4 (13.8%) 4 (10.5%) 1 (2.8%)
Cough 0 (0%) 4 (13.8%) 1 (2.6%) 2 (5.6%)
LDL increase 0 (0%) 0 (0%) 4 (10.5%) 0 (0%)
Diarrhea 3 (6.8%) 3 (10.3%) 1 (2.6%) 0 (0%)
Folliculitis 0 (0%) 3 (10.3%) 2 (5.3%) 1 (2.8%)
Blood CK (increase) 1 (2.3%) 3 (10.3%) 2 (5.3%) 1 (2.8%)
Oropharyngeal pain 1 (2.3%) 3 (10.3%) 1 (2.6%) 0 (0%)
Data from Study CP543.2001
Conclusion from Phase 2 Dose-Ranging Study
• The primary efficacy endpoint of ≥50% relative reduction in SALT at Week 24 was met for 8 mg BID
and 12 mg BID
• Dose-related improvements for 8 mg BID and 12 mg BID across all efficacy assessments
‒ Significant SALT improvement as early as Week 12
• At Week 24, 8 mg BID and 12 mg BID significantly different from placebo on percent of patients
achieving a clinically-meaningful SALT score ≤ 20
‒ Patients achieving a SALT score ≤ 20 is primary efficacy endpoint in Phase 3 program
• Good feedback through patient-reported outcome measures
• CTP-543 treatment was generally well-tolerated
‒ More than 90% of patients completing Phase 2 trials rolled into long-term extension study
18Data from Study CP543.2001
Study CP543.5001: Long-Term, Open Label Extension (OLE) Study
• Objective: Evaluate long-term safety and effects of CTP-543 on treating hair loss in adult patients with
moderate to severe alopecia areata.
‒ Study is ongoing; Current trial duration is 164 weeks
‒ Patients previously completing 24-weeks of treatment in a qualifying CTP-543 clinical trial are eligible
• Three qualifying Phase 2 studies to date; Phase 3 subjects also eligible and starting to roll in
• First patient enrolled in April 2019
• Treatment: Patients receive 8 mg BID or 12 mg BID
‒ Dose selection at the discretion of the Investigator, based on efficacy and tolerability from the previous study
‒ Dose adjustments allowed during study
• Assessments every 4 weeks for first 12 weeks; every 8 weeks thereafter
‒ Safety is evaluated by clinical laboratory measurements,
AEs and physical exams.
‒ Hair assessments performed using the Severity of Alopecia Tool (SALT)
19
SALT Scoring
Phase 2 Qualifying Studies: Patient Demographics and Alopecia Areata Baseline
Study CP543.2001(Aug 2017 – Jul 2019)
CP543.2002(Mar 2019 – Nov 2019)
CP543.2003(Jun 2019 – Mar 2020)
Phase 2 Demographics PlaceboCTP-543
12 mg BID
CTP-543
8 mg BID
CTP-543
16 mg QD
CTP-543
12 mg BID
CTP-543
24 mg QD
Efficacy Population, N 43 36 29 28 34 32
Age: Mean (SD) 38.0 (14) 36.0 (12) 40.4 (13) 39.8 (14) 38.8 (12) 40.4 (14)
Males, N (%) 15 (34%) 9 (24%) 9 (31%) 10 (36%) 13 (38%) 9 (28%)
Females, N (%) 29 (66%) 28 (76%) 20 (69%) 18 (64%) 21 (62%) 23 (72%)
White, N (%) 33 (75%) 30 (81%) 27 (93%) 23 (82%) 25 (74%) 23 (72%)
Black or African American, N (%) 7 (16%) 3 (8%) 0 3 (11%) 4 (12%) 4 (13%)
Phase 2 AA Baseline
AA Episode Duration: Mean 4.1 yr 3.5 yr 3.6 yr 3.8 yr 4.1 yr 3.1 yr
Baseline SALT Score, Mean (SD) 86.8 (18.4) 87.3 (18.7) 87.0 (17.2) 90.4 (17.5) 85.7 (19.5) 87.7 (17.3)20
OLE Study: Patient Entry and Disposition
21
OLE Patient Disposition to Date*
22*as of May 2021
0 0 510 13
21 2329 30 32 34 34 36 36 36 36
158
152
147
142139
131129
122 121119
95
73
52
29
22
50
25
50
75
100
125
150
175
BaselineVisit
Week 4 Week 8 Week 12 Week 20 Week 28 Week 36 Week 44 Week 52 Week 60 Week 68 Week 76 Week 84 Week 92 Week 100 Week 108
Num
ber
of
Subje
cts
Weeks in OLE Study
Discontinuations
Enrolled Subjects
1 yr. Cumulative Treatment
Most Common Adverse Events to Date*Consistent with Phase 2 Studies
23
*As of May 2021; >95% Patients on 12 mg BID
OLE Study* Qualifying Phase 2 Studies+
Preferred Term CP543.2001
(N=36)
CP543.2003(N=34)
Nasopharyngitis 25.0% 11.8%
Acne 16.7% 11.8%
Headache 19.4% 8.8%
Blood CK
(increase)2.8% 32.4%
URI 19.4% 11.8%
Lipase increased NA 11.8%
+AEs for 12 mg BID dose group from each study
% Patients with Adverse Event
Preferred Term CTP-543(N=154)
Nasopharyngitis 23%
Acne 20%
Headache 11%
Severity of AEs*:• 70% mild
• 27% moderate
• 2% severe
(CK = 6.5%; URI = 6%; Lipase increase = 1.9%)
Most common AEs defined as ≥ 10% occurrence in any dose group
Key Hematology Parameters Through 1 Year of Dosing
24
Study VisitPhase 2
Week 24
OLE
Week 4
OLE
Week 8
OLE
Week 12
OLE
Week 20
OLE
Week 28
Cumulative Time on
Treatment24 Weeks 28 Weeks 32 Weeks 36 Weeks 44 Weeks 52 Weeks
Hemoglobin(12-18 g/dL)
13.16(1.28)
13.10(1.31)
12.90(1.30)
12.84(1.41)
12.92(1.38)
12.98(1.17)
Platelets(140-400 x103/uL)
366.23(89.76)
355.40(84.87)
353.79(83.92)
346.24(79.34)
365.15(95.25)
376.80(86.98)
Neutrophils(1-8 x103/uL)
3.50(1.18)
3.46(1.19)
3.67(1.61)
3.39(1.18)
3.56(1.62)
3.68(1.23)
Combined* 12 mg BID Data
Mean (SD)
Only patients previously receiving 12 mg BID in Study CP543.2001 or CP543.2003 AND entered OLE are included;
Due to COVID restrictions or subject discontinuation, some assessments missing at certain visits;
N at each OLE visit between 50 and 58
(Normal Range)
Phase 2: Robust and Reliable 12 mg BID Treatment Response
25
Combined* 12 mg BID Data (N=70)
* Only patients previously receiving 12 mg BID in Study CP543.2001 or CP543.2003 are included
CTP-543 Maintains Hair Regrowth Through 1 Year of Dosing
26*Only patients previously receiving 12 mg BID in Study CP543.2001 or CP543.2003 AND entered OLE are included;
Due to COVID restrictions or subject discontinuation, some SALT assessments missing at certain visits; No imputation for missing data
Combined* 12 mg BID Data
Cumulative Time
on Treatment24 Wks 28 Wks 32 Wks 36 Wks 44 Wks 52 Wks
Response (SALT ≤ 20) Improvement Through 1 Year of Dosing
27* Only patients previously receiving 12 mg BID in Study CP543.2001 or CP543.2003 AND entered OLE are included;
Due to COVID restrictions or subject discontinuation, some SALT assessments missing at certain visits; No imputation for missing data
Combined* 12 mg BID Data
# Responders/N 26/63 28/60 29/54 30/53 29/55 29/51
41.3%
53.7%56.6%
52.7%
41.3%
56.9%
46.7%
Summary and Conclusion
• Hair regrowth assessed by SALT was sustained or improved in the vast majority of
patients relative to Phase 2 results with additional dosing in the OLE
‒ Majority of data based on 12 mg BID dosing
• Treatment with CTP-543 in the OLE study continues to be generally well tolerated
‒ Over 100 patients have been dosed cumulatively for > 1.5 years
‒ Adverse Events are consistent with those observed in the previous 24 week studies
‒ Clinical labs for hematology parameters (platelets, neutrophils, hemoglobin) appear stable across the
OLE relative to end of treatment in the Phase 2 studies
• Phase 3 THRIVE-AA program is underway; building data sets for NDA submission
• Overall safety and efficacy profile of CTP-543 and its potential to treat moderate to severe
alopecia areata is encouraging
28
A Special THANK YOU
• The patients with alopecia areata who volunteer to participate in clinical
studies
• The CTP-543 Clinical Study Teams and Investigators
• All Health Care Professionals for your service, especially during the
COVID-19 pandemic
29