LYT-500

Our programs 1
Discovery
Preclinical
Phase 1
Phase 2
Phase 3
LYT-500
Oral IL-22 +
Anti-inflammatory
IBD

Preclinical

Inflammatory bowel disease

~3M U.S.

Therapeutic candidate being advanced for the potential treatment of inflammatory bowel disease (IBD) that is designed with a dual mechanism of action to provide both mucosal repair and targeted resolution of tissue inflammation.
Phase completedPhase in progressRegistration-enabling development plans in progress

1 The FDA and corresponding regulatory authorities will ultimately review our clinical results and determine whether our wholly-owned therapeutic candidates are safe and effective. No regulatory agency has made any such determination that LYT-500 is safe or effective for use by the general public for any indication.

Oral biologic combination therapy for the potential treatment of inflammatory bowel disease

LYT-500 is an oral combination therapy in development for inflammatory bowel disease (IBD). Using our AlivioTM technology platform (see here), we have combined two active agents into a single therapeutic candidate for IBD that is designed to enhance the treatment of inflamed tissues while having the potential to minimally impact the rest of the body. Specifically, LYT-500 contains a unique combination of IL-22 and an anti-inflammatory drug, which is designed to address the two key underlying causes of IBD pathogenesis and progression, namely mucosal barrier disruption and inflammation.

  • Key Points of Innovation & Differentiation
    • Unlike many therapies in development for IBD, LYT-500 is designed with a dual mechanism of action to provide both mucosal repair and targeted resolution of tissue inflammation, which are critical for treating IBD.
    • Using our Alivio technology platform, a biologic agent and small molecule drug can be combined into a single oral dosage form that offers the potential to selectively act at the inflamed tissues to maximize efficacy, while reducing systemic exposure to minimize toxicity.
  • Program Discovery Process by the PureTech Team
    • A key challenge faced in developing new drugs for the treatment of autoimmune and inflammatory disease is that attractive drug targets are frequently expressed in both diseased and normal tissue. Consequently, we are interested in identifying ways to address autoimmune disease in a targeted manner. We have been inspired by a key observation, which is that pathologic inflammation, which is driven by dysfunctional immune signaling, frequently manifests at specific sites in tissues and organs. However, the current treatments and therapeutic approaches act broadly to suppress the immune system throughout the body. This mismatch substantially limits the potential targets that can be pursued and frequently results in narrow therapeutic windows. Moreover, it is quite challenging to combine therapies to address multiple aspects of the autoimmune diseases due to their systemic toxicity profiles and narrow therapeutic window. Working with leading scientists, we identified and in-licensed a technology platform in May 2016 that was created by Jeffrey Karp, Ph.D., Professor of Medicine at Harvard Medical School and Brigham and Women’s Hospital, and Robert Langer, Sc.D., David H Koch Institute Professor at MIT. As demonstrated in multiple publications, our Alivio technology platform can be used to develop therapeutic candidates that selectively target inflamed tissues and release drugs in proportion to the severity of inflammation.
  • Patient Need & Market Potential
    • IBD is estimated to affect approximately three million people in the United States.
    • Existing biologic therapies for IBD must be provided through multiple injections over time and are associated with several limitations including dose-limiting adverse events, loss of efficacy over time via anti-drug antibody development and the potential for opportunistic infections or malignancies.
    • We believe that the ideal solution for treating IBD could provide an oral drug therapy that targets multiple mechanisms of disease pathogenesis while minimizing the potential for systemic side effects. We believe LYT-500, developed from our Alivio technology platform, can potentially fulfill this goal.
  • Milestones Achieved & Development Status
    • We have developed an oral inflammation-targeting IL-22 composition with analytical data to support high IL-22 loading, high encapsulation efficiency, preservation of biologic activity, enzyme-mediated drug release and stability in simulated intestinal fluids. In addition, we have a comparable data set for oral inflammation-targeting composition that combine IL-22 with an anti-inflammatory drug.
    • We have completed initial preclinical evaluation of an inflammation-targeting IL-22 composition in a preclinical IBD model, where we demonstrated improvement in multiple endpoints related to mucosal healing.
    • We are currently developing oral dosage forms to enable testing of the inflammation-targeting IL-22 alone and in combination with an anti-inflammatory drug.
    • Upon successful completion of preclinical efficacy experiments, we expect to initiate IND enabling studies.
  • Expected Milestones
    • We expect preclinical proof-of-concept data for LYT-500 in the first half of 2022.
  • Intellectual Property
    • The intellectual property portfolio supporting LYT-500 consists of coverage around both the broader inflammation-targeting platform and the specific drug combination candidate. Platform intellectual property is supported by two patent families that have been exclusively licensed from the Brigham and Women’s Hospital, which includes three issued patents to date and several pending applications within and outside the U.S. Intellectual property specific to the LYT-500 candidate owned by Alivio consists of two patent families that contain several U.S. and international applications at various stages of prosecution.

LYT-500 enables highly targeted anti-inflammatory and mucosal healing effects while minimizing systemic toxicity as a potential treatment for IBD, such as ulcerative colitis. Our underlying Alivio technology platform has been described in five peer-reviewed articles published in journals such as Science Translational Medicine and Nature Communications, and has been validated in multiple labs using preclinical models for a range of different indications.