JAKs are responsible for transducing a signal to initiate a cascade that ultimately affects responsive genes, such as those associated with the expression of several inflammatory molecules3

TEC family of non-receptor tyrosine kinases are key regulators of immune cells that can impact cytokine production and inflammation.30,31

Based on the pathophysiology of alopecia areata, Crohn’s disease, non-segmental vitiligo, rheumatoid arthritis, and ulcerative colitis, JAK3 and TEC family of non-receptor tyrosine kinases may be therapeutic targets in each of these conditions4-10,29-33

PF-06651600 is a once-daily oral JAK3/TEC inhibitor under investigation in subjects with alopecia areata, Crohn’s disease, non-segmental vitiligo, rheumatoid arthritis, or ulcerative colitis.22-27

JAK PATHWAY

JAK inhibition may be a factor in a number of inflammatory diseases, including alopecia areata, atopic dermatitis, Crohn's disease, non-segmental vitiligo, plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus, and ulcerative colitis.3,7-16

Figure adapted from Paller AS et al. J Allergy Clin Immunol. 2017;140(3):633-643.

  • Chronic idiopathic inflammatory diseases of the skin and gut are characterized by a hyperactive immune milieu containing upregulated chemokines, proinflammatory cytokines, and infiltration of an assortment of innate and adaptive immune cells3,17-20
  • The Janus kinase-signal transducer and activator of transcription (JAK-STAT) is a signaling pathway by which a number of proinflammatory cytokines (eg, IL-4, IL-13) may transduce their pathophysiologic functions and contribute to immune hyperactivity3,17
  • The binding of a cytokine to its receptor leads to JAK activation, which in turn phosphorylates STATs. STATs then dimerize and translocate to the nucleus, where they may direct expression of a number of genes affecting differentiation of immune cells and lead to upregulated cytokines3,17

Now enrolling in Crohn’s Disease

For adults with moderate to severe active Crohn’s disease and an inadequate
response, loss of response, or intolerance to ≥1 prior conventional therapy22

PF-06700841 is an investigational oral TYK2/JAK1 inhibitor.1
PF-06651600 is an investigational oral JAK3/TEC inhibitor.1,29

The kinase activity of Janus kinases (JAK1, JAK3, and TYK2) and TEC family of non-receptor tyrosine kinases may play a role in the pathophysiology of several autoimmune diseases.7-12,21,30-33

This is a phase 2a, randomized, double-blind, parallel-group, placebo-controlled study to assess the efficacy and safety profile of oral PF-06700841 and PF-06651600 as induction and open-label extension treatment in subjects with moderate to severe active Crohn's disease with an inadequate response, loss of response, or intolerance to ≥1 prior conventional therapy.22

Planned countries for recruitment include: Australia, Austria, Belgium, Bosnia-Herzegovina, Canada, Croatia, Czech Republic, Georgia, Germany, Hungary, Italy, Lebanon, Poland, Russia, Saudi Arabia, Serbia, Slovakia, South Africa, South Korea, Spain, Switzerland, Tunisia, Turkey, Ukraine, the United Arab Emirates, and the United States.22

VIEW STUDY DESIGN22

VIEW ENDPOINTS

PRIMARY ENDPOINT22

  • Proportion of subjects achieving clinically meaningful endoscopic improvement, defined as a reduction of ≥3 points from baseline in Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) at week 12

KEY SELECTED SECONDARY ENDPOINTS22

  • Number of subjects with potentially clinically important findings for serious infections at week 64
  • Proportion of subjects achieving SES-CD 25 and SES-CD 50 at week 12
  • Proportion of subjects achieving endoscopic remission (defined as SES-CD 2) at week 12
  • Proportion of subjects achieving mucosal healing at week 12

VIEW ELIGIBILITY CRITERIA

KEY SELECTED INCLUSION CRITERIA22

  • 18 to 75 years of age at the time of informed consent
  • Diagnosis of Crohn’s disease for ≥3 months
  • Active endoscopic disease (SES‑CD ≥7; isolated ileal disease, SES‑CD ≥4)
  • Average daily stool frequency ≥2.5 or daily abdominal pain ≥2.0
  • Inadequate response, loss of response, or intolerance to at least ≥1 conventional therapy for Crohn’s disease

KEY SELECTED EXCLUSION CRITERIA22

  • Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, diverticular disease, ulcerative colitis, or clinical findings suggestive of ulcerative colitis
  • Presence of active (draining) fistulae, or intra-abdominal or perineal abscesses
  • Strictures with obstructive symptoms

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NOW ENROLLING IN ULCERATIVE COLITIS

For adults with moderate to severe active ulcerative colitis and an inadequate
response, loss of response, or intolerance to ≥1 prior conventional therapy23

PF-06700841 is an investigational oral TYK2/JAK1 inhibitor.1
PF-06651600 is an investigational oral JAK3/TEC inhibitor.1,29

The kinase activity of Janus kinases (JAK1, JAK3, and TYK2) and TEC family of non-receptor tyrosine kinases may play a role in the pathophysiology of several autoimmune diseases.7-12,21,30-33

This is a phase 2b, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of oral PF-06651600 and oral PF-06700841 as induction and chronic therapy in subjects with moderate to severe ulcerative colitis and an inadequate response to, loss of response to, or intolerance to ≥1 conventional therapy.23

Planned countries for recruitment include: Austria, Bulgaria, Canada, Czech Republic, Denmark, Georgia, Germany, Hungary, Israel, Italy, Netherlands, Poland, Romania, Russia, Serbia, Slovakia, South Korea, Spain, Turkey, Ukraine, and the United States.23

VIEW STUDY DESIGN23,28

VIEW ENDPOINTS

PRIMARY ENDPOINT23

  • Change from baseline in total Mayo score at week 8

KEY SELECTED SECONDARY ENDPOINTS23

  • Proportion of subjects achieving endoscopic remissiona at week 8
  • Proportion of subjects achieving symptomatic remissionb at week 8

aEndoscopic remission is defined as an endoscopic subscore of 0.

bSymptomatic remission is defined as a total Mayo Score of 2 points or lower, with no individual subscore >1 point, and both rectal bleeding and stool frequency subscores of 0.

VIEW ELIGIBILITY CRITERIA

KEY SELECTED INCLUSION CRITERIA23

  • 18 to 75 years of age at the time of informed consent
  • Diagnosis of ulcerative colitis for ≥3 months
  • Moderate to severe active ulcerative colitis
  • Inadequate response, loss of response, or intolerance to ≥1 conventional therapy for ulcerative colitis

KEY SELECTED EXCLUSION CRITERIA23

  • Women who are pregnant or breastfeeding
  • Clinical findings suggestive of Crohn's disease
  • Subjects who have a history of bowel surgery within 6 months prior to baseline

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NOW ENROLLING IN ALOPECIA AREATA

For adults and adolescents with alopecia areata and 50% or greater scalp hair loss24

PF-06651600 is an investigational oral JAK3/TEC inhibitor with FDA Breakthrough
Therapya designation for alopecia areata.1,29

The kinase activity of JAK3 and TEC family of non-receptor tyrosine kinases may play a role in the pathophysiology of several autoimmune diseases.7,10,30-33

This is a phase 2b/3, randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy and safety of PF-06651600 in the treatment of subjects aged 12 years and older with alopecia areata and 50% or greater scalp hair loss.24

Planned countries for recruitment include: Australia, Canada, Japan, and the United States.24

aBreakthrough designation is defined as a drug under investigation with preliminary clinical evidence that indicates the drug may demonstrate
substantial improvement over existing therapies on one or more clinically significant endpoints.2

VIEW STUDY DESIGN24

VIEW ENDPOINTS

PRIMARY ENDPOINT24

  • Percentage of subjects achieving an absolute Severity of Alopecia Tool (SALT) score ≤10 at week 24

KEY SELECTED SECONDARY ENDPOINTS24

  • Characterize exposure response based on the percentage of subjects achieving an absolute SALT score ≤10 at week 24
  • Percentage of subjects achieving a SALT score of ≤10 at weeks 4, 8, 12, 18, 28, 34, 40, and 48
  • Percentage of subjects achieving 50%, 75%, and 90% improvements in SALT score from baseline at weeks 4, 8, 12, 18, 24, 28, 34, 40, and 48
  • Absolute SALT scores at weeks 4, 8, 12, 18, 24, 28, 34, 40, and 48
  • Percentage of subjects achieving ≥2 grade improvement or a score of 3 in Eyebrow Assessment (EBA) and Eyelash Assessment (ELA) scores at weeks 4, 8, 12, 18, 24, 28, 34, 40, and 48

VIEW ELIGIBILITY CRITERIA

KEY SELECTED INCLUSION CRITERIA24

  • 12 years of age and older
  • Clinical diagnosis of alopecia areata with no other cause of hair loss
  • ≥50% hair loss of the scalp, including alopecia totalis and alopecia universalis, without evidence of terminal hair regrowth within 6 months
  • Current episode of hair loss ≤10 years

KEY SELECTED EXCLUSION CRITERIA24

  • Other types of alopecia or other diseases that can cause hair loss
  • Other scalp diseases that could interfere with assessment of hair loss/regrowth
  • Subjects with shaved heads (may enter the study once hair has grown back and is considered stable by the investigator)
  • Prior treatment with JAK inhibitors

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NOW ENROLLING IN VITILIGO

For adults with active non-segmental vitiligo25

PF-06700841 is an investigational oral TYK2/JAK1 inhibitor.1
PF-06651600 is an investigational oral JAK3/TEC inhibitor.1,29

The kinase activity of Janus kinases (JAK1, JAK3, and TYK2) and TEC family of non-receptor tyrosine kinases may play a role in the pathophysiology of several autoimmune diseases.7-12,21,30-33

This is a phase 2b, randomized, double-blind, placebo-controlled, multicenter, dose-ranging study evaluating the efficacy and safety profile of PF-06651600 with a partially blinded extension period to evaluate the efficacy and safety of PF-06651600 and oral PF-06700841 in the treatment of subjects with active non-segmental vitiligo.25

Planned countries for recruitment include: Canada, Japan, and the United States.25

VIEW STUDY DESIGN25

I=induction; M=maintenance; NBUVB=narrowband UVB.

VIEW ENDPOINTS

PRIMARY ENDPOINT25

  • Percent change from baseline of Vitiligo Area Scoring Index (VASI) at week 24
  • Number of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) from baseline to week 56
  • Number of subjects with change from baseline in laboratory test results to week 56
  • Number of subjects reporting TEAEs and TESAEs from baseline to week 56
  • Number of specific clinical laboratory abnormalities from baseline to week 56

KEY SELECTED SECONDARY ENDPOINTS25

  • Percentage of subjects achieving ≥50% improvement in VASI from baseline (VASI50) at week 24
  • Percent change from baseline in VASI at week 20
  • Percent change from baseline in facial VASI at week 24
  • Percent change from baseline in Vitiligo Extent Score (VES) at week 24
  • Percent change from baseline in self-assessment VES (SA-VES) at week 24
  • Percentage of subjects achieving VASI50 at week 20

VIEW ELIGIBILITY CRITERIA

KEY SELECTED INCLUSION CRITERIA25

  • 18 to 65 years of age at the time of informed consent with moderate to severe active non-segmental vitiligo

KEY SELECTED EXCLUSION CRITERIA25

  • History of HIV or positive HIV serology at screening
  • Infected with hepatitis B or hepatitis C viruses
  • Evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)

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