OX40L blocking monoclonal antibody KY1005 strongly suppresses thedelayed-type hypersensitivity skin response to KLH in healthy volunteersM. Saghari1 MD, J. Powell2 MBChB FFPM, R. Wilson2 PhD, S. Gilbert2 PhD, R. Rissmann1 PhD, M. Moerland1 PhD, M.B.A. vanDoorn3, MD, PhD, P. Gal1 MD PhD, N. Brennan2 BSc, B. Porter-Brown2 MBBS FFPM, S. Quaratino2 MD PhD and J. Burggraaf1,4

MD PhD

• KY1005 is a human non-depleting monoclonal antibody blockingOX40L interaction with OX40, inhibiting Teff response and maintainingTreg activity.

• In a phase 1 healthy volunteer study, skin delayed typehypersensitivity (DTH) assessment was implemented to assesspharmacodynamic activity of KY1005.

• OX40/OX40L expression is upregulated in AD skin.

Introduction

1 Centre for Human Drug Research, Leiden, the Netherlands; 2 Kymab Ltd, Cambridge, United Kingdom; 3 Department of Dermatology, Erasmus Medical Centre, Rotterdam, the Netherlands; 4 Leiden Academic Centre for Drug Research, Leiden, the Netherlands; Correspondence; ben.porter-brown@kymab.com Kymab Ltc, Babraham Research Campus, Cambridge, UK CB22 3AT

Objective

Materials and Methods

Results

Conclusions

Affiliations

To explore the DTH immune response after KY1005 treatment followed by immunization challenges with a neo-antigen (keyholelimpet hemocyanin, KLH).

• Five multiple dose cohorts of 8 male subjects each in a 6:2active vs. placebo ratio received three doses of KY1005 at 4-week intervals at ascending doses.

• Subjects were vaccinated with 0.1mg KLH seven days after thethird dose. Twenty-one days later, subjects received 0.001mgKLH intradermally in the left forearm and saline control in theright forearm.

• Forty-eight hours after intradermal KLH administration, the DTHresponse was quantified by multispectral imaging (Antera 3D,Miravex, Dublin, Ireland) and laser speckle contrast imaging(LSCI, PeriCam PSI System, Perimed AB, Järfälla, Sweden)recordings.

KY1005 treatment suppressed KLH-induced dermalerythema quantified by multispectral imaging in; 0.45mg/kg, 4 mg/kg, and 12 mg/kg cohorts compared toplacebo reaching P<0.05 (estimated differences: 0.20AU (95% CI 0.09 – 0.31, effect size (estimateddifference/SD) 1.95), 0.15 AU (95% CI 0.04 – 0.26, effectsize 1.46), and 0.22 AU (95% CI 0.11 – 0.33, effect size2.14), respectively) and the cutaneous blood flow byLSCI in 0.45 mg/kg and 4 mg/kg treatment groupscompared to placebo reaching P<0.05 (estimateddifferences: 11.6 AU (95% CI 3.1 – 20.0, effect size1.62), and 10.2 AU (95% CI 2.1 – 18.3, effect size 1.43),respectively).

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• The anti-OX40L monoclonal antibody KY1005 suppressed the T-cell mediated delayed type hypersensitivity response quantifiedby multispectral and laser speckle contrast imaging.

• KY1005 shows potential to serve as a novel treatment modality in cutaneous T-cell dependent disorders.• A phase 2a study in moderate to severe atopic dermatitis is ongoing (NCT03754309)

Effect of KY1005 on DTH in Arbitrary Units (AU) compared to Placebo between day 85 and day 87 as measured by Antera 3D and LSCI (Per Protocol Pop#)

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Day 87

PlaceboExample single subject LSCI images across the dose range

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Nominal P values: *<0.05 **<0.01 ***<0.001#Per Protocol Population: subjects who received all 3 doses of Placebo or KY1005