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

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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

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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

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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

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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

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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%)

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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)

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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

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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

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*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

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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

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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

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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

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