A Novel Human IL-22-

Secreting Synthetic Biotic

Medicine for the Treatment of

Inflammatory Bowel Disease

Anna Sokolovska, Ning Li, Starsha Kolodziej, JR Gao, Christopher

Bergeron, Jillian Means, Caroline Kurtz, David Hava and Mylene

Perreault.

Digestive Disease Week (DDW)

May 23, 2021

© 2021 SYNLOGIC. ALL RIGHTS RESERVED.

Disclosures

All authors were Synlogic employees and shareholders at the time the work was

performed.

© 2021 SYNLOGIC. ALL RIGHTS RESERVED.

Intestinal Homeostasis is Disrupted in IBD

Disease pathophysiology in IBD linked to compromised barrier function and increased inflammation

Mucosal healing is the next therapeutic goal to achieve stable remission in IBD patients

Zhang 2017, Neurath 2014, Bourma and Strober 2003

© 2021 SYNLOGIC. ALL RIGHTS RESERVED.

Adapted from Keir et al., 2020

IL-22 as a Therapeutic Effector

Promotes barrier function and mucosal healing

  • IL-22promotes epithelial barrier functions and mucosal healing.
  • Extensive pre-clinical evidence supports a critical role for IL-22 in IBD.
  • Many IL-22 associated molecules are encoded by IBD susceptibility genes and patients with ulcerative colitis have evidence of IL-22 dysfunction.
  • Systemically administered hIL-22-Fc results in pharmacodynamic responses but is associated with dose-dependent skin adverse effects.

Can local delivery of IL-22 in the gut promote epithelial barrier healing in IBD patients without systemic toxicity?

Rutz 2014, Chi 2014, Wang 2014 , Stefanich 2018, Sugimoto 2008, Rothenberg 2018

© 2021 SYNLOGIC. ALL RIGHTS RESERVED.

Synthetic Biotics: A Novel Approach to Immune Diseases

Exploiting the Interaction Between Bacteria and the Immune System

Bacteria and Immune System are Intimately

Linked

  • Immune system has evolved to recognize bacteria
  • Bacteria have evolved mechanisms to control the immune response

Synthetic Biotics Enable Unique Therapeutic

Opportunities

- Bacteria has evolved to survive the gastrointestinal tract

- Local delivery to the site of disease

Synthetic Biotics Enable Multiple Therapeutic

Modalities

- Ability to deploy multiple pathways

- Broad expression of bacterial and mammalian effectors

© 2021 SYNLOGIC. ALL RIGHTS RESERVED.

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Synlogic Inc. published this content on 21 May 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 24 May 2021 07:48:07 UTC.