Press Release

EME and ASKA Announce Collaboration Agreement on Creating Novel PharmaLogical®
VHH to address an unmet medical need in Obstetrics and Gynecology
TOKYO, February 7, 2023 - ASKA Pharmaceutical Co., Ltd. (Head Office: Minato-ku, Tokyo/President, Representative Director: Sohta Yamaguchi), a subsidiary of ASKA Pharmaceutical
Holdings Co., Ltd. (Head Office: Minato-ku, Tokyo/ President, Representative Director: Takashi
Yamaguchi), and Epsilon Molecular Engineering, Inc. (HQ: Saitama, Japan/ President & CEO:Naoto Nemoto; “EME”) announce that it entered into collaboration agreement on creating a novel
PharmaLogical® VHH(*1) for a target in the field of obstetrics and gynecology using EME’s
proprietary discovery platform” The Month”, and design platform for optimization.
The impact of this matter on the Company's financial results for the fiscal year ending March 31,
2023 will be immaterial.

Media Contacts

ASKA Pharmaceutical Holdings Co., Ltd.
Corporate Planning Department
Tel: +81-3-5484-8366
Email: kouhou@aska-pharma.co.jp

PRESS RELEASE
February 7, 2023
Epsilon Molecular Engineering, Inc
ASKA Pharmaceutical Co., Ltd.

EME and ASKA Announce Collaboration Agreement on Creating Novel PharmaLogical® VHH
to address an unmet medical need in Obstetrics and Gynecology

Japan – February 7, 2023 – Epsilon Molecular Engineering, Inc. (HQ: Saitama, Japan; President & CEO: Naoto Nemoto;“EME”) and ASKA Pharmaceutical Co., Ltd. (HQ: Tokyo, Japan; President, Representative Director: Sohta Yamaguchi;“ASKA”) announce that it entered into collaboration agreement on creating a novel PharmaLogical® VHH(*1) for a target
in the field of obstetrics and gynecology using EME’s proprietary discovery platform” The Month”, and design platform
for optimization.
”The Month”
EME’s proprietary technology enabling to identify druggable VHH, “PharmaLogical® VHH”(*2), by
combination of PharmaLogical® Library (*3) and cDNA display(*4).
EME will identify PharmaLogical® VHH with the platform and create drug candidates with the design platform. ASKA
will prepare antigen for a target and conduct in vitro and in vivo assay.
Under the term of this agreement, EME receive an undisclosed upfront payment this year and milestone payment inmeeting the criteria.
*1 VHH：Variable Domain of Heavy Chain of Heavy Chain Antibody found in camelids. Superior stability and easily
molecularly designed than conventional IgG*2 PharmaLogical® VHH：Druggable VHHs identified from PharmaLogicaｌ® Library*3 PharmaLogicaｌ® Library： EME’s proprietary humanized synthetic VHH library structurally based design with thepurpose of recognition for epitope that conventional IgG unable to recognize*4 cDNA display： Most stable and diverse genotype-phenotype coupling using cell-free translation system, enabling 101314 repertories of VHHs to be screened at once

【Key Features of PharmaLogical® Library】
Design based on crystal structure analysis data of VHH antibody
A humanized VHH library designed based on the structural characteristics resulting from the crystal structure
analysis data of the human sequence and VHH that have already been clinically applied to the antibody frameworkpart (FR). The three CDRs (Complementarity Determining Regions) that form the antigen recognition site aredesigned based on the structural property information obtained from the alpaca-derived VHH, and are known tocontribute most to antigen binding. By randomizing the CDR3s, large diversity is demonstrated.

Design to minimize the frequency on occurrence of amino acids that cause heterogeneity in formulation
Amino acids that are susceptible to modification and that can cause major structural changes, such as cysteine andproline residues, cause heterogeneity in the formulation process. By designing a CDR that minimizes the frequency
of appearance of these amino acids, it can be expected to minimize the problems that arise in the drug discovery
processInnovative VHH screening method by combining PharmaLogical® Library with cDNA display
The combination of PharmaLogical® Library which has a diverse library size of 1013-14 (10 trillion to 100 trillion),and a screening system based on the cDNA display technology enables an innovative VHH screening.

【About Epsilon Molecular Engineering】
EME is a biotech and pharmaceutical company specialized in VHH that has been developing as aninnovative modality and drugs based on evolutionary molecular engineering since 2016. Taking
advantage of our unique screening technology and molecular design method, we are engaged inresearch and development of diagnostic agents and reagents for regenerative medicine as well as drugdevelopment. With the corporate mission of "creating future biomolecules," we aim to contribute to awide range of society and people's lives.
Website：https://www.epsilon-mol.co.jp/eng/【About ASKA Pharmaceutical Co., Ltd. 】
Since its foundation in 1920, ASKA has concentrated its management resources in three core areas: internal medicine,obstetrics and gynecology, and urology, based on its corporate philosophy “Contribute toward the improvement ofpeople’s health and progress in medicine through the development of innovative products”. In addition, ASKA has been
actively engaged in the development of new drugs to solve medical needs.
Website： https://www.aska-pharma.co.jp/【Contact】
Epsilon Molecular Engineering, Inc.
Business Development Department
TEL：048-857-8880

E-mail : biz_dev@epsilon-mol.co.jp

ASKA Pharmaceutical Co., Ltd.
Corporate Planning Department
TEL：03-5484-8366

E-mail：kouhou@aska-pharma.co.jp