SYT13 Antisense Oligonucleotide for Gastric Cancer Peritoneal Metastasis

Near-term first-in-human ready optimized drug candidate

Advantage and Core Benefit

  • First in class medicine for peritoneal dissemination, highly unmet medical needs
  • Topical administration through peritoneal implantable port reduces delivery issues of ASOs
  • SYT13 expression measurement in tissue or peritoneal lavage can be companion diagnostics

Background and Technology

Gastric cancer is the 5th most common cancer in the world and 1 million patients are currently affected. Peritoneal metastasis (PM) is the most common case when diagnosed as stage IV gastric cancer (GC) in Asian countries, as well as the most common recurrence after resection with poor effect of resection, radiation, systemic anti-cancer drug.

We identified therapeutic target Synaptotagmin13 (SYT13) among selectively expressed molecules in human samples from GC patients with PM. Since small molecules or antibodies are not a suitable approach for SYT13, we synthesized nuclease resistant amido-bridged nucleic acids (AmNA)-modified antisense oligonucleotides (ASOs), and selected ASO-4733 as a candidate.

Effective delivery to the target tissue, as well as costs and toxicity is the most important challenge for clinical use of ASOs. We confirmed administration through peritoneal implantable port solves them.

Data

  • ASO-4733 was selected among 71 SYT13 ASOs through analysis of in-vitro, in-vivo activity, hepatotoxicity, off-target risk.
  • Intraperitoneal administration of ASO-4733 significantly reduced tumor growth and prolonged survival of GC PM model mice (fig: ASO 01).
  • SYT13 expressions in GC patient’s tissues and peritoneal lavage fluid strongly corelated with present and future PM.

Patents and Publications

Patent
PCT/JP2020/32270,  JP6803572B2

Molecular Therapy -Nucleic Acids, VOLUME 22, P791-802, DECEMBER 04, 2020
https://doi.org/10.1016/j.omtn.2020.10.001

British Journal of Surgery, Volume 105, Issue 10, September 2018, Pages 1349–1358
https://doi.org/10.1002/bjs.10876

Gastric Cancer volume 22, pages1143–1152 (2019)
https://doi.org/10.1007/s10120-019-00967-3

Researcher

Lecturer, Mitsuro Kanda, MD, PhD, Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Japan.

Development Plans and Expectations

Nagoya Univ. is seeking a partner who will succeed or support the project.

  • GLP preclinical safety study with monkey and rat is scheduled in 2023.
  • First-in-human study will be ready with future funding support in 2024.
  • AmNA, artificial nucleic acid technology is licensable as a package.

Product No: KJ-04010

Inquiry Form

    Your name (*required)

    E-mail address (*required)

    Company name

    Message (*required)

    Following submission of your inquiry

    We will contact you shortly to discuss confidentiality, materials transfer, evaluation steps, and licensing opportunities.

    <Notice>


    Our support is provided free of charge.
    The information submitted on this form is for business development use only.


    By clicking "Send", you are agreeing to our Privacy Policy.
    If you have questions please reach out to info (at) tech-manage.co.jp.

    About Bionauts.jp Tech Manage Corp.
    Copyright © Tech Manage Corp. All Rights Reserved.
    This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.