ASP1531
NON-CONFIDENTIAL SUMMARYASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

DISCLAIMER

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This material includes forward-looking statements based on assumptions and beliefs in lightof information currently available to the Astellas and subject to significant risks anduncertainties.
This material contains information on pharmaceuticals (including compounds in research orunder development) and other matters. Notwithstanding the foregoing, Astellas makes norepresentations, warranties, assurances or guarantees of any kind or nature whatsoever,whether expressed or implied, regarding the information in the materials (including, withoutlimitation, no representations, warranties, assurances or guarantees as to the accuracy,
sufficiency or completeness of any information, as to whether Astellas has rights to any suchinformation or pharmaceuticals/compounds, as to whether any third party has or does nothave any rights to any of such information or pharmaceuticals/compounds, as to the safety,efficacy, or effectiveness of any preparations described in this material, as to the regulatory
status of or potential for regulatory agency action regarding any pharmaceuticals/compounds described in this material, or as to any uses, including unapproved uses, of any
such preparations in any fashion). This material does not provide medical advice of any kind.
Astellas undertakes no obligation or duty to change, remove, add, clarify, correct or update
any information in the materials at any time.

ASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

ASP1531 SUMMARY

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Note

Product name

ASP1531

Mechanism of Action

Block binding of Fn14 1) to its ligand TWEAK 2)

Target Indications

Cancer Cachexia and Solid tumorsLatest development phase

Pre-IND stage1)
2)

Fn14: Fibroblast growth factor-inducible 14, TNFRSF12A
TWEAK: Tumor necrosis factor-like weak inducer of apoptosis, TNFSF12

ASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

BACKGROUNDASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

PHARMACOLOGICAL CONCEPT OF ASP1531
Fn14 is a cell-surface receptor for TWEAK andupregulated in injured tissue and solid tumor. Fn14
overexpression itself can activate the down-stream
signals and induce multiple gene expressions.

5Skeletal muscle specific TWEAK-T.g. mice
exhibited muscle atrophy in association withvisceral obesity, insulin resistance andmetabolic dysfunction.

TWEAK

ASP1531

Fn14

NF-kB

MAPKfatmuscleetc.

MuRF1↑, cytokines↑, GLUT4↓ etc.

Muscle atrophy
Tissue inflammation
Metabolic disorder

ASP1531 is a novel anti-Fn14 fully human monoclonal antibody which is expectedto block Fn14 signals in tumors and muscles.
Nat Rev Drug Discov. 2008;7:411-25

FASEB J. 2015;29:988-1002

ASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

PREVALENCE OF CANCER CACHEXIA AND FN14 EXPRESSIONBY TUMOR TYPEHigh prevalence of cancer cachexia• Pancreatic cancer• Gasto-esophageal cancer• Lung cancer

Nat Rev Dis Primers. 2018;4:17105.

Fn14 overexpression (IHC)• NSCLC• Pancreatic cancer

Clin Cancer Res 2010.16.497-6

ASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

ANTI-FN14 ANTIBODY PREVENTED COLON 26 (C26)-TUMORINDUCED BODY WEIGHT LOSS IN MICEOS7

Body weightanti-Fn14 antibody

Cell 2015. 162. 1365-

ASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

TWEAK/FN14 PATHWAY AS A TARGET FOR SOLID TUMORSACHN xenograft models
Tumor growth

Yin X et.al., Clin Cancer Res. 2013;19(20):5686-98

Gene expression

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ASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

EXPERIMENTAL DATAASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

ASP1531 CHARACTERIZATION FOR CACHEXIA AND SOLID
TUMOR TREATMENT

10• Astellas discovered a novel anti-Fn14 fully human monoclonal antibody(ASP1531) which can block Fn14 activation.

• ASP1531 is an anti-Fn14 antagonistic antibody with mutations to avoid
antibody-dependent cellular cytotoxicity (ADCC).
For cachexia•

ASP1531 improved muscle wasting and function in C26-induced cancer cachexia modelmice.

•ASP1531 in combination with gemcitabine prolonged survival with no additional antitumor
efficacy compared to each monotherapy group in C26 xenografted mice.

•ASP1531 reduced cytokines in C26 tumors and proteolysis enzymes in muscles.

For solid tumors•

ASP1531 blocked TWEAK mediated upregulation of Fn14 downstream genes in NSCLC celllines.

•ASP1531-surrogate elicited antitumor effect as monotherapy in syngeneic tumor models.

ASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

ADME AND TOXICOLOGICAL STUDIES WITH ASP1531• IND-enabling studies completed• No issues found toward IND

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ASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

INTELLECTUAL PROPERTYASP1531 NON-CONFIDENTIAL SUMMARY -- Version dated July 6, 2022

INTELLECTUAL PROPERTY
Patent covering ASP1531•WO2020/090892 (filed on Oct. 30, 2019) for the substance•This patent family is maintained in Argentina, Australia, Brazil, Canada, China, Colombia,
Europe, Gulf Cooperation Council, Hong Kong, India, Indonesia, Israel, Japan, Jordan, Korea,Malaysia, Mexico, Philippines, Russian Federation, Singapore, South Africa, Taiwan, Thailand,
Ukraine, USA, Vietnam.

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