Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
This PowerPoint presentation shows the significance impact of medical and dermatological practice to answer the physical issues such as wrinkles, scars, and other signs of aging.
Pachyonychia congenita is an autosomal disorder which affects keratin. Manifestations of this disorder is most often seen on the skin and fingernails. This is just a short presentation which mostly focuses on its pathogenesis. Please see other references for more information.
This PowerPoint presentation shows the significance impact of medical and dermatological practice to answer the physical issues such as wrinkles, scars, and other signs of aging.
Pachyonychia congenita is an autosomal disorder which affects keratin. Manifestations of this disorder is most often seen on the skin and fingernails. This is just a short presentation which mostly focuses on its pathogenesis. Please see other references for more information.
This is a powerpoint presentation on the epidermal keratinization and its associated disorders, presented by Dr. Jerriton, Dermatology resident of SVMCH, Pondicherry.
This presentation includes -classification, biological in psoriasis,TNF alpha inbitors, T cell inhibitos, IL-12/23 inhibitors (indications,containdications,guidelines, adverse effects)
Subspecialty of dermatology and pathology focused on performing and interpreting tests on human tissue samples to provide scientific data and consultative opinions to referring clinicians
Dr. Natasha Mesinkovska, NAAF’s Chief Scientific Officer, shares the latest progress of NAAF’s Treatment Development Program, our efforts to build a stronger patient-centered research community and how your involvement is critical to developing treatments for alopecia areata. Dr. Mesinkovska is Director of Clinical Research in the Department of Dermatology at the University of California Irvine.
This is a powerpoint presentation on the epidermal keratinization and its associated disorders, presented by Dr. Jerriton, Dermatology resident of SVMCH, Pondicherry.
This presentation includes -classification, biological in psoriasis,TNF alpha inbitors, T cell inhibitos, IL-12/23 inhibitors (indications,containdications,guidelines, adverse effects)
Subspecialty of dermatology and pathology focused on performing and interpreting tests on human tissue samples to provide scientific data and consultative opinions to referring clinicians
Dr. Natasha Mesinkovska, NAAF’s Chief Scientific Officer, shares the latest progress of NAAF’s Treatment Development Program, our efforts to build a stronger patient-centered research community and how your involvement is critical to developing treatments for alopecia areata. Dr. Mesinkovska is Director of Clinical Research in the Department of Dermatology at the University of California Irvine.
Dr. Leslie Castelo-Soccio presented an overview of what parents need to know about alopecia areata in children and adolescents, including the differences between pediatric and adult patients, and the risks and benefits of current and evolving off-label treatment options. Dr. Castelo-Soccio is Assistant Professor of Pediatrics and Dermatology at the University of Pennsylvania School of Medicine and head of the Pediatric Hair Clinic and Director of Research in Pediatric Dermatology at the Children’s Hospital of Philadelphia. Her clinical and academic research focus is on pediatric hair disorders.
MANAGEMENT OF METASTATIC RENAL CELL CARCINOMA. please read and if you have anything to share/feedback, please mail me at farazrizvi.amu@gmail.com.
Since now this is paid membership on slideshare, if you want original slides, feel free to ask me on my email
While MIC is a good measure of antibiotic activity, it is static and reflects in vitro activity. PK and PD of the drug needs to be considered together with MIC if we wish to obtain an in vivo prediction of drug action and success.
•Recognize patients at risk for diabetic foot infections
•Design a diagnostic work-up for diabetic foot osteomyelitis
•State the principles of management of diabetic foot infections
Dr. Angela Christiano presented an update on genetic and immunological studies in alopecia areata. Her research is focused on defining the genetic basis of alopecia areata to clarify how the disease develops—a key initial step toward creating novel therapies. Dr. Christiano is the Richard and Mildred Rhodebeck Professor of Dermatology, Genetics and Development, Vice Chair for Basic Science Research in Dermatology, and Director of the Center for Human Genetics at Columbia University.
Dr. Maria Hordinsky presented an overview of key things adults need to know about alopecia areata, including the risks and benefits of current and evolving off-label treatment options. Dr. Hordinsky is Professor and Head of the Department of Dermatology at the University of Minnesota. She is recognized for her clinical expertise in alopecia areata and hair diseases.
Dr. Natasha Mesinkovska, NAAF’s Chief Scientific Officer, presented the latest progress of NAAF’s Treatment Development Program and how your involvement is critical to developing treatments for alopecia areata. In addition to overseeing NAAF’s research efforts, Dr. Mesinkovska is Director of Clinical Research in Dermatology at the University of California Irvine.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Discussion of the immune privilege collapse model of alopecia areata pathogenesis, available evidence to support this hypothetical scenario, and promising avenues for future investigation.
The FDA plans to prioritize improvements in the quality of demographic subgroup data collection, reporting and analysis, encourages greater participation of diverse patients, and supports the transparency of subgroup data. To this end, ways to recruit, engage, educate, and study those of diverse backgrounds to alopecia areata trials will be discussed.
Measuring willingness to pay in patients with alopecia areata to gauge their willingness to pay out of pocket for a cure or control of their condition.
While genome-wide association studies of common genetic variants in alopecia areata have highlighted etiological contributions from specific immune cells and pathways, exome studies of rare variants in patients and family members are implicating components of the hair follicle extracellular matrix, suggesting a crucial point of communication between the hair follicle and the immune system.
Novel induction of alopecia areata in C3H/HeJ mice shows a potential role of previously unrecognized endogenous SSEA-positive myeloid cells in driving inflammatory cascade and hair loss mechanisms.
Through in-depth interviews of key informant groups, Lilly developed a five-grade investigator global assessment (IGA) scale to measure clinically meaningful treatment response to alopecia areata treatment for patients with ≥ 50% scalp hair loss. Patient input was essential to the development of this content valid measure.
Report on the progress of NAAF’s Patient-Reported Outcome (PRO) Consortium to develop a single, consensus-defined PRO instrument that can be shared across industry partners and other ongoing initiatives to incorporate the voice of the patient in alopecia areata research.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Top 10 Best Ayurvedic Kidney Stone Syrups in India
The therapeutic landscape in atopic dermatitis
1. The Therapeutic Landscape in
Atopic Dermatitis
International Eczema Council 2019
Eric Simpson, MD, MCR
Professor, Dermatology
Oregon Health & Science University
El Greco,1596
John
Constable, 1821
Andrew
Wyeth, 1948
2. Disclosures
• Consultant and investigator for:
• Regeneron/Sanofi
• Genentech
• Medimmune
• GSK
• Leo
• Celgene
• Pfizer
• Chugai
• I will be talking about off-label use
• Dermira
• Lilly
• Tioga
• Incyte
• Abbvie
• Kiniksa
• Menlo
• Ortho Dermatologica
• Forte Biotech
4. Current Guideline-recommended or
Approved Therapies
Cyclosporine
Phototherapy
Methotrexate
Mycophenolate
Azathioprine
Dupilumab
Pimecrolimus
Corticosteroids
Crisaborole
Tacrolimus
5. Current Therapeutic Gaps
Topical
• Non-steroidal topical therapy with high efficacy AND without
significant burning or safety concerns
• Topical therapy that is infrequently dosed and easily applied
Systemic
• Systemic therapy with improved EASI 90s and lacks conjunctivitis
• Less frequent dosing
• Oral therapy option that is safe and effective
7. Microbiome as a Target
Commensal bacteria- BACTERiAD I/II Trial
• Gram neg present in flexures
• G neg bacteria reduced in AD
• Roseomonas mucosa from healthy volunteers
improved dermatitis in mice
• Strain-level differences in AD compared to NL
• Mono-methyl glutarate, histidinal
• Phosphatidylcholine (PC 37:2)
• Phosphatidylethanol and PE-ceramides
Myles IA, et al.. First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic
dermatitis. JCI Insight. 2018 May 3;3(9).
Roseomonas mucosa
8. Myles IA, et al. First-
in-human topical
microbiome
transplantation with
Roseomonas mucosa
for atopic dermatitis.
JCI Insight. 2018 May
3;3(9).
• 10 adults-
• 6 weeks
• Antecubitals
• 5 children
• 16 weeks
• All areas
• Decrease n S.
aureus
colonization
9. Microbiome as a Target
Commensal bacteria
• Coag- Staph make AMPs
• Reduced number in AD patients
• Screened for bacteria with anti-S. aureus
activity
• S.epidermidis and S. hominis
• Lantibiotics synergize with AMPs
• Clones identified and cultured and
applied to AD skin
S. Epidermidis
S. hominis
Nonsteroidal, no burning, less frequent dosing
11. Phase 2 study of topical delgocitinib (JTE-052) in adult AD
% change in EASI
• 327 Japanese 16-65 years
• Mod-severe AD
• 4 weeks of treatment
• 5g of treatment allowed-20%BSA
• Scalp excluded from treatment
• LOCF for rescued pts
• Sign reduction in itch
• No increase in AEs
• 1 case of burning
• 3 cases of EH (1.1%)
Nakagawa H, Nemoto O, Igarashi A, Nagata T. Efficacy and safety of topical JTE-052, a Janus kinase inhibitor, in
Japanese adult patients with moderate-to-severe atopic dermatitis: a phase II, multicentre, randomized, vehicle-
controlled clinical study. Br J Dermatol. 2018 Feb;178(2):424-432.
12. Ruxolitinib (JAK 1/2) -Phase 2 in Adult AD
• Primary endpoint: Mean % change from baseline in EASI score at Week 4 in ruxolitinib 1.5% bid group vs
vehicle
• Secondary and exploratory endpoints: IGA and EASI responder rates, itch NRS score and safety
• Kim B, et al. EADV 2018, FC03.01. Sponsored by Incyte
1:1:1:1:1:1
N=307
Double-blind
treatment period
Vehicle bid
Triamcinolone 0.1% bid
Ruxolitinib 0.15% qd
Ruxolitinib 0.5% qd
Ruxolitinib 1.5% qd
Ruxolitinib 1.5% bid
Week 1 4 8
Vehicle bid
Ruxolitinib 1.5% bid
12 16
Open-label
period
Safety
follow-up
Optional treatment
Key inclusion criteria:
• 18–70 years with active AD
• AD duration >2 years
• IGA 2/3
• BSA 3–20%
Key exclusion criteria:
• Active infections
• Use of other topical treatments
within 2 weeks of baseline
• Systemic drug use within 4 weeks
of baseline
R
13. 4.8
40
29.9
46.2
49.9
52.7
15.5
59.8
45.4
52.2
67
71.6
26.9
50.7
58.5
67
78.5
0
20
40
60
80
100
Vehicle bid
(n=52)
TAC 0.1% bid
(n=51)
0.15% qd
(n=51)
0.5% qd
(n=51)
1.5% qd
(n=52)
1.5% bid
(n=50)
Meanchange(%)
Week 2 Week 4 Week 8
Ruxolitinib cream
Improvement from baseline in EASI score
‡
‡
†
‡
‡
‡
‡
‡
‡
‡
‡
‡
*P<0.05; †P<0.01; ‡P<0.001 vs vehicle; Error bars represent 95% confidence intervals; TAC, triamcinolone
Kim B, et al. EADV 2018, FC03.01. Sponsored by Incyte
• No increase in AEs in treatment groups
• Rapid reduction in itch
• Highest doses similar to triamcinolone 0.1
Ruxolitinib (JAK 1/2) -Phase 2 in Adult AD
No significant burning, high efficacy
14. Dose-finding study of tapinarof (GSK2894512) cream for the
treatment of adults with moderate to severe AD
AhR, aryl hydrocarbon receptor
Peppers J, et al. EADV 2017, OP03.04 Sponsored by GlaxoSmithKline
Inclusion criteria:
• Age 12–65 years
• Diagnosis of AD with active
inflammation
• BSA ≥5–≤35% (excl scalp)
• IGA ≥3
• Primary efficacy analysis
– Patients with IGA 0/1 and ≥2 grade improvement in IGA from baseline at Week 12
Tapinarof (GSK2894512), a novel non-steroidal anti-inflammatory agent, is a
therapeutic AhR modulating agent cream
1:1:1:1:1:1
N=247
GSK2894512 cream 1.0% bid (n=40)
GSK2894512 cream 1.0% qd (n=41)
GSK2894512 cream 0.5% bid (n=43)
GSK2894512 cream 0.5% qd (n=41)
Vehicle cream bid (n=42)
Vehicle cream qd (n=40)
R
Screening
−4 BL 1 2 12
Double-blind treatment
16
Follow-up
4 148
Primary
endpoint
Week
• Bacterial-derived
• Polyphenol
• Binds AhR
• Anti-oxidant
15. Dose-finding study of tapinarof (GSK2894512) cream for the
treatment of adults with moderate to severe AD
IGA 0/1 and ≥2-point improvement
0.5% qd tapinarof
0.5% bid tapinarof
1% qd tapinarofVehicle qd
1% bid tapinarofVehicle bid
Week
16
60
50
40
30
20
10
0
70
80
90
100
Patientsa(%)
Follow-up
period
Treatment
period
1 2 4 8 12 14 Nonsteroidal, modest efficacy
Safety
• More AEs in treatment groups
• 10% with HA in highest dose
• Some LFT increases (not AEs)
• Some systemic effect at high doses?
Peppers J, Paller AS, et al. . A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for
the treatment of atopic dermatitis. J Am Acad Dermatol. 2019 Jan;80(1):89-98.e3.
17. Warning! Lack of standardization ahead!
EASI 50 EASI %Δ
EASI 75 SCORAD
Endpoints
None Run-in
As needed Mandatory
TCS Use
18. Standardization of Clinical Research in AD
Core Outcome
Sets for Trials
and Practice1
Guidance
Document for
Industry2
Endpoint
Training and
Standardization
Harmonizing Outcome
Measures for Eczema
1 Spuls PI,et al. Patient-Oriented Eczema Measure (POEM), a core instrument to measure symptoms in clinical trials: a Harmonising
Outcome Measures for Eczema (HOME) statement. Br J Dermatol. 2017 Apr;176(4):979-984.
2 Siegfried EC, et al.Developing drugs for treatment of atopic dermatitis in children (≥3 months to <18 years of age): Draft guidance for
industry. Pediatr Dermatol. 2018 May;35(3):303-322. doi: 10.1111/pde.13452. Epub 2018 Mar 30. PubMed PMID: 29600515.
20. • Epidermal “alarmin”
• IL-1 cytokine family
• Receptors on keratinocytes, Th2 cells, mast cells
• Activates NfKb
• Promotes type 2 inflammation (Th2 and ILC2)
Rationale for Targeting IL-33 in AD
IL-33
Inflammation
Keratinocytes
Cevikbas F, Steinhoff M. IL-33: a novel danger signal system in atopic dermatitis. J Invest Dermatol.
2012 May;132(5):1326-9.
21. Etokimab (anti-IL-33)
• Open-label phase 2a
• 12 adult patients
• Mod-severe AD
• Placebo at -7d
• 1X 300mg infusion
• Unclear TCS use
0
10
20
30
40
50
60
70
80
90
100
Day -21 Day 1 Day 15 Day 29 Day 57 Day 78 Day 113 Day 140
% patients achieving EASI-50 % patients achieving EASI-75* Average % EASI score reduction
High efficacy, infrequent dosing
22. • Produced by keratinocytes
• Upregulated in psoriasis and AD
• Initiates inflammatory cascade
Rationale for Targeting IL-17C
IL-17C
Inflammation
Keratinocytes
MOR106, an anti-IL-17C mAb, a potential new approach for treatment of moderate-to-severe atopic
dermatitis: Phase 1 study, AAD February 2018
23. MOR106 (anti-IL-17c mAB) Phase I Study
• N=25
• 4 weekly infusions
• Adults with mod-
severe AD
*Primary endpoint was safety; secondary endpoint was pharmacokinetics.
1. Thaçi D, et al. MOR106, an anti-IL-17c mAB, a potential new approach for treatment of moderate-to-severe atopic dermatitis: phase I study. Presented
at: 2018 American Academy of Dermatology Meeting; February 16-20, 2018; San Diego, CA.
9
EASI-50 score
% of patients with 50% EASI improvement
0
10
20
30
40
50
60
70
80
90
100
baseline 1 2 3 4
%ofsubjects
Weeks since start of treatment
Placebo
MOR106 1mg/kg
MOR106 4mg/kg
MOR106 10mg/kg
N = 7
N = 6
N = 6
N = 6
Infusion
24. • Produced by epithelium- lung and skin
• Promotes Th2 responses via dendritic cell binding
• Upregulated in skin in AD and lung in asthma
• Tezepelumab works in asthma
Rationale for Targeting TSLP
TSLP
Inflammation
Keratinocytes
25. Tezepelumab (Anti-TSLP)- Phase 2a
Alleviad
• 113 adult pts with AD
• 26 centers
• 2 weeks of TCS run-in
• Class 3 daily
• 12 weeks of dosing
• 280mg SQ q2 weeks
Simpson EL, Parnes JR, She D, Crouch S, Rees W, Mo M, van der Merwe R. Tezepelumab, an anti-TSLP monoclonal antibody, in the
treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial. J Am Acad Dermatol. 2018 Dec 11.
Percent Reduction in EASI
26. Tezepelumab (Anti-TSLP)- Phase 2a
Alleviad
• Some enhanced effects seen with
biomarker subgroups:
• DPP4-high
• Periostin-low
• TARC-low
• IgE high
• No significant AE signal
• Positive signal in asthma Phase 2 with
breakthrough status
• Another Phase 2 planned!
Simpson EL, Parnes JR, She D, Crouch S, Rees W, Mo M, van der Merwe R. Tezepelumab, an anti-TSLP monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized
phase 2a clinical trial. J Am Acad Dermatol. 2018 Dec 11. pii: S0190-9622(18)33050-0. doi: 10.1016/j.jaad.2018.11.059. [Epub ahead of print] PubMed PMID: 30550828.
Proportion of IGA 0/1
29. Rationale for Targeting OX40
• OX40L is a co-stimulatory molecule that promotes Th2 polarization of
naïve OX40-bearing T cells
• OX40 antagonism:
• Suppresses activated T cells (particularly atopic Th2 inflammation)
• Potentially increases T regulatory cells, which may achieve
immunologic tolerance disease modification?
Nygaard U, et al. Dermatol 2017;233:344–57; Dhingra N, et al. J Invest Dermatol 2013;133:2311–4
30. Anti-OX40 (KHK 4083)
• KHK4083 is a fully human, non-fucosylated
antagonistic anti-OX40 antibody
Study design
• A phase 1, single-center, open-label, three-dose study
• KHK4083 10 mg/kg iv administered every other week
(Weeks 0, 2, 4)
• TCS/TCI, oral immunosuppressants and phototherapy
were prohibited (Week –1 to Week 22)
• Rescue treatment for AD was permitted at
investigator’s discretion
• 22 patients received the 3 doses of treatment;
20 were evaluated
• 4 patients received rescue (documented as missing)
BL 2 4 6 10 14 18 22
−60
−40
−20
−80
0
20
40
60
Meanchangefrom
baseline(%)
KHK4083 (q2w)
• Nakagawa H, et al. EADV 2018, P0252. Sponsored by Kyowa Hakko Kirin
Percent Reduction in EASI
31. 1. Glenmark Pharmaceuticals SA. GBR 830 AD Phase 2a press release
Guttman-Yassky E, et al. AAD 2018, P7931 Sponsored by Glenmark Pharmaceuticals SA
Phase 2a study of GBR 830 (anti-OX40 mAb) in adults with
moderate to severe AD
• Clinical improvement was associated with a reduction in mRNA biomarkers for disease activity, indicating an effect
on acute and chronic stages of AD
• In the GBR 830 cohort, 17 of 23 patients (74%) achieved EASI 50 scores at Day 57 vs baseline, a key secondary
endpoint of the study1
Change in EASI score
n=8
n=15
-80
-60
-40
-20
0
Changefrombaseline(%)
DaysDose 1 Dose 2
Placebo
GBR 830
1 4 8 15 22 29 32 36 43 50 57 71 85
Infrequent dosing, disease modification?
35. 3
7
Example of a patient (48 years old; 8 years with AD) achieving EASI-50, NRS
≥ 3-point improvement and DLQI ≥ 4-point improvement (monotherapy)
Point
improvement
% improvement
EASI 34.7 72
NRS pruritus 6.1 61.4
DLQI 19 90
Baseline Week 16
4 IGA 2
58% BSA 22.5%
48 EASI 13.3
10 NRS pruritus 3.9
21 DLQI 2
36. Conjunctivitis at q2week dosing through Week 16:
SOLO Pooled data: 10% vs 2%
CHRONOS: 9% vs 5% (11.8 vs 6% at Week 52)
CAFÉ: 28% vs 11%
37. Bakker DS, Ariens LFM, Van Luijk C, van der Schaft J, Thijs JL, Schuttelaar MLA, Van Wijk F, Knol EF, Balak
DMW, van Dijk MR, the Bruin-Weller MS. Goblet cell scarcity and conjunctival inflammation during treatment
with dupilumab in patients with atopic dermatitis. Br J Dermatol. 2018 Dec 30. doi:10.1111 / bjd.17538.
[Epub ahead of print] PubMed PMID: 30597515.
38. Phase 2b Study of Tralokinumab (IL-13)
A randomized, double-blind, placebo-controlled, multicenter, multidose study1
40
• Concomitant Class 3 once daily TCS were administered throughout the study and run-in†
• Exploratory analyses: high serum DPP-4 levels and high periostin levels may be predictive of response
• Safety: acceptable safety and tolerability profile
• Did not meet asthma endpoints
*
Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, Moate R, van der Merwe R. Treatment of atopic
dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. 2019 Jan;143(1):135-141.
Percent IGA 0/1
39. Phase 2 Study of Lebrikizumab in Moderate-to-
Severe AD
TREBLE: a randomized controlled study
• Concomitant bid class 3 TCS were administered throughout the study†,1,2
• PRO endpoints: improvements in sleep loss VAS (125 mg, q4w and SD) and ADIQ (125 mg q4w)2
• Safety: rates of AEs were generally similar between treatment groups, and AEs were mostly mild or
moderate in severity2
41
18.9
21.2
28.3
33.3
0
5
10
15
20
25
30
35
Placebo Lebrikizumab
125 mg SD
Lebrikizumab
250 mg SD
Lebrikizumab
125 mg q4w
Proportionofpatients(%)
Primary Endpoint: Patients Achieving IGA 0/1
EASI: 53.1%
EASI: 58.5%
EASI: 57.7% EASI: 70.5%
40. Rationale for Biologics Targeting IL-31
• The itch cytokine
• Receptors on neurons
• Increased expression in AD lesions1,2
• Correlations with disease severity3
1. Nemoto O et al. Br J Dermatol 2016;174:296–304. 2. Cevikbas F et al. J Allergy Clin Immunol 2014;233:448–460.e7. 3. Bieber T,
D’Erme AM, Akdis CA et al. J Allergy Clin Immunol 2017;139:S58–S64.
42
IL-31
Th2
Itch1,2
Figure modified from Jones SA, et al. J Clin Investig 2011;121:3375–83
IL-31 receptor composition
OSMRβIL-31RA
41. Phase 2a Study of Nemolizumab in Moderate-to-Severe AD
“no imputation was performed for missing data. Data measured
during or after rescue therapy were included in the analyses.”
% reduction from baseline: NRS itch
42. Anti-OSM receptor β mAb (KPL-716)
Pruritus visual analog scale (VAS)a
Weeks
Meanchangefrom
baseline(%)
1 2 3 4
0
−20
−40
−60
−80
−100
−10.4%
−55.4%
EASI
1 2 3 4
Weeks
0
−20
−40
−60
−80
−100
−25%
−42.3%
Meanchangefrom
baseline(%)
Placebo (pooled iv)
KPL-716 (7.5 mg/kg iv)
• Phase 1b, dose-escalation study (AD patients): n=32
• Single IV infusion
• KPL-716 simultaneously inhibits IL-31 and oncostatin M (OSM) signaling
1. Mikhak Z, et al. EADV 2018, late breaking news D3T01.1F. Sponsored by Kiniksa Pharmaceuticals, Ltd
45. JAK Inhibition- The Good and The Bad
JAK1 Blockade
Good Bad
IL-4
IL-13
IL-22
IL-2
IL-6
IFN a/g
IL-15
JAK1/2 Blockade
Good Bad
IL-4 EPO
IL-13 TPO
IL-22 GM-CSF
IL-2
IL-6
IFN a/g
IL-15
IL-5
IL-12
IL-23
JAK1/2/3 Blockade
Good Bad
IL-2 EPO
IL-4 TPO
IL-13 GM-CSF
IL-6
IFN
IL-15
IL-22
IL-5
IL-12
IL-23
Disclaimer: All JAK inhibitors inhibit all JAK
signaling, just to greater or lesser extents. Dosing
as important for efficacy and side effect profile as
molecule.
?
?
?
?
46. Phase 2 study of baricitinib (JAK1/2) in
adults with moderate to severe AD
Change from baseline in EASI score over timea
• Steroid run-in X 4 weeks and TCS use during study
• Phase 3 studies underway
47. Phase 2b study of Abrocitinib (JAK1)
IGA response of 0/1 and ≥2-point improvementa
Week
41 2 6 8 12 13 14 16
100
80
60
40
20
0
LSmeanchangefrombaseline(%)
Mean change from baseline in EASI scoreb
PF-04965842 10 mg qd (n=49)
PF-04965842 30 mg qd (n=51)
PF-04965842 100 mg qd (n=56)
PF-04965842 200 mg qd (n=55)
Placebo (n=55)
Patients(%)
Dosing Follow-up
1 2 4 6 8 12 13 14 16
0
20
40
60
80
100
Week
27.8%
44.5%
6.3%
*
*
• No TCS use
• Phase 3 studies underway
50. 0
20
40
60
80
100
Day 1 Day 15 Day 29
ASN002 (JAK/SYK inhibitor) in Adult AD
• Guttman-Yassky E, et al. EADV 2018, Late-breaking news D3T01.1H. Sponsored by Asana
BioSciences
Patients(%)
*
*
‡
†
Patients achieving EASI 50
• Blocking Syk blocks IL-17 signaling
• 4 weeks study of 9 active, 2 placebo for each dose
• Blood and transcriptome improvements
• No TCS use
SYK JAK1 JAK2 JAK3 TYK2
5 46 4 11 8
ASN002 inhibition of kinase activity, IC50 (nM)
51. Summary of Adverse Events for JAKs
• Total AEs increase for all JAKs as doses increase
• Mainly driven by lab abnormalities
• Transient thrombocytopenia occurred with abrocitinib at highest dose
• Serious infections in AD populations are low and similar to placebo
for all JAKs at all doses
• Black box warning for infection and malignancy for all JAKs likely,
although AD data will likely be much safer than for RA
• If companies push doses for efficacy, will they get burned?
52. Summary and Conclusions
• Numerous targeted therapies being developed for AD with
early studies showing a promising signal
• Blockade of IL-4/IL-13 very effective and safe strategy
• Blockade of other extracellular targets appear to have
activity
• JAK inhibition promising, but efficacy will need careful
balancing with side effect profile
• Exciting and hopeful time for patients suffering from AD!
53. Thank you for listening!
Wanderer above the Sea of
Fog (1818) – Caspar David Friedrich