EAACI June 6 th -8 th Treatment of Severe Allergic Conjunctivitis with AK002 Indicated Improvement of Ocular Signs and Symptoms and Reduction of Severity of Comorbid Atopic Diseases in a Phase 1b Open-Label Study Andrea Leonardi 1 ; Stephen D. Anesi 2 ; Peter Y. Chang 2 ; Andrea M. Kantor 3 ; Alan T. Chang 3 ; Henrik S. Rasmussen 3 ; C. Stephen Foster 2 1 University of Padova, Padova, Italy; 2 Massachusetts Eye Research & Surgery Institution, Waltham, MA; 3 Allakos, Inc., Redwood City, CA EAACI 2020 London, UK June 6 th -8 th 2020
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Treatment of Severe Allergic Conjunctivitis with …...CurrOpinin Allergy Clinical Immunol. 2007, 7:429-435; TsubotaK. “Detection by brush cytology of mast cells and eosinophils
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EAACI June 6th-8th
Treatment of Severe Allergic Conjunctivitis with AK002 Indicated Improvement of Ocular Signs and Symptoms
and Reduction of Severity of Comorbid Atopic Diseases in a Phase 1b Open-Label Study
Andrea Leonardi1; Stephen D. Anesi2; Peter Y. Chang2; Andrea M. Kantor3; Alan T. Chang3; Henrik S. Rasmussen3;
C. Stephen Foster2
1University of Padova, Padova, Italy; 2Massachusetts Eye Research & Surgery Institution, Waltham, MA; 3Allakos, Inc., Redwood City, CA
EAACI 2020London, UK June 6th-8th 2020
EAACI June 6th-8th
Disclosures
• No financial conflicts to disclose
• AK002 is an investigational drug in clinical development as is not FDA or EMA approved
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EAACI June 6th-8th
AKC, PAC, & VKC Are Severe and Chronic Forms of Allergic Conjunctivitis
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CLINICAL FEATURES IMPACT
SymptomsExtreme Itching, Photophobia, Pain, Sensation of Foreign Body, Burning,
Common Atopic Comorbidities IncludeAtopic Dermatitis, Asthma, and Rhinitis
High Systemic Disease Burden, Poor Quality of Life
EAACI June 6th-8th
Severe Allergic Conjunctivitis
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Giant Papillae
Corneal Ulcer
(Vision Loss)
Redness, Chemosis
Photophobia, Watering, Periorbital Swelling
EAACI June 6th-8th
Mast Cells and Eosinophils are Key Effector Cells in Allergic Conjunctivitis
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PerennialAllergic Conjunctivitis
(PAC)
Vernal Keratoconjunctivitis
(VKC)
AtopicKeratoconjunctivitis
(AKC)
Mast Cells +++ +++ ++
Eosinophils ++ ++ +++
T and B cells + ++ +++
Fibroblasts ++ ++
Source: Leonardi A. “Immunopathogenesis of ocular allergy: a schematic approach to different clinical entities.” Curr Opin in Allergy Clinical Immunol. 2007, 7:429-435; Tsubota K. “Detection by brush cytology of mast cells and eosinophils in allergic and vernal conjunctivitis.” Cornea. 1991;10(6):525.
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Mast Cells and Eosinophils Are Key Drivers of Inflammatory Disease
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Tissue damage, fibrosisBronchoconstriction, increased GI motility, pain, itch
T Cell B Cell
ActivatedB Cell
IgE
ACTIVATION AND RECRUITMENT OF OTHERIMMUNE CELLS AND TISSUE INFLAMMATION
Smooth Muscle
Histamine, LTC4, PGD2 and proteases
IL- 4 IL-13
IL- 4 IL-13
HistamineNGF, Histamine
MacrophageEosinophil Neutrophil
IL-5 IL-8 IL-6, TNFa
Allergens
Epithelium
Mast CellNeuron
Sub P
IL-33 TSLP
ECP, MBP, elastase, MMP, TNFa , IL-1b, TGFb
Sub P
ACUTE AND CHRONIC INFLAMMATIONSENSITIZATION
EAACI June 6th-8th
AK002 Targets Siglec-8 on Eosinophils and Mast Cells
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ActivatingReceptors
Activation
Siglec-8
Mast cellEosinophil
Inflammatoryresponse
AK002
Inhibition
Mast cellEosinophil
InhibitionADCC/Apoptosis
AK002
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KRONOS: Phase 1b Study
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6 monthly doses of AK002 (mg/kg)
•Daily ACS questionnaire completion
•Baseline OSS assessment
•Screening and baseline assessments
Primary Objective – Safety and Tolerability: • Vital signs, physical exam, safety labs, ADA, and collection
• 53 year-old male with AKC, atopic dermatitis, asthma, and rhinitis
• Baseline normal peripheral blood eosinophils (120 eos/µL)
EAACI June 6th-8th
Case Study 2: Improvements in Ocular Signs and Symptoms and Comorbid Atopic Dermatitis, Asthma, and Rhinitis
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Sym
ptom
Sco
re
6.5
2.2
0
3
6
9
BL Wks21-22
Atopic Dermatitis
-67% 5.9
1.1
0
3
6
9
BL Wks21-22
Asthma
-82%
7.1
0.30
3
6
9
BL Wks21-22
Rhinitis
-96%
33.3
4.0
0
10
20
30
40
BL Wks21-22
Total ACS
-88%
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Conclusions/Discussion
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• Mast cells and eosinophils are key effector cells in the pathogenesis and perpetuation of allergic conjunctivitis
• AK002 is a novel anti-Siglec-8 antibody that has demonstrated selective and rapid depletion of eosinophils and inhibition of mast cells in preclinical and clinical studies
• Substantial and consistent improvements reported in symptoms by patients and investigators in multiple forms of severe AC
• Clinical activity observed in atopic comorbidities
• AK002 was generally well-tolerated
• AK002 may be a promising treatment for severe AC as well as atopic dermatitis, asthma and other atopic conditions