LYT-510

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Discovery
Preclinical
Phase 1
Phase 2
Phase 3
LYT-510
Oral Immunosuppressant
IBD/chronic pouchitis

Preclinical

Inflammatory bowel disease and chronic pouchitis

~3.9M U.S.


Oral inflammation-targeting formulation of tacrolimus, a potent immunosuppressant drug, in development for the potential treatment of inflammatory bowel disease (IBD) and chronic pouchitis. Tacrolimus is approved for certain indications, however its approval for IBD and chronic pouchitis has been hampered by systemic toxicities, narrow therapeutic window of activity and opportunistic infections that can arise from systemic immunosuppression. There is clinical data demonstrating that tacrolimus is effective in addressing IBD indications, but adverse events have held it back.

Phase completedPhase in progressRegistration-enabling studies to begin in 1H2022

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-510 is safe or effective for use by the general public for any indication.

Oral immunosuppressant molecule in development for the potential treatment of inflammatory bowel disease and chronic pouchitis

LYT-510 is our lead candidate generated from our Alivio™ technology platform (see here) and is an oral inflammation-targeting formulation of tacrolimus, a potent immunosuppressant drug, in development to treat inflammatory bowel disease (IBD) and chronic pouchitis. While tacrolimus is FDA-approved for certain indications, it has been evaluated in several clinical studies as a potential treatment for IBD, where it has demonstrated strong efficacy with high response and remission rates. However, despite the compelling efficacy, IBD patients are at risk for significant side effects due to systemic exposure, which has prevented tacrolimus’ advancement for these indications. We believe that our oral formulation that targets tacrolimus to inflamed tissue, with minimal systemic exposure to healthy tissues, can overcome these limitations to potentially provide a safe and effective oral treatment for IBD patients. More broadly, this approach offers a path to unlocking the full therapeutic potential of multiple immunosuppressant and anti-inflammatory drugs that have well established clinical efficacy in a way that matches the chronic, variable expression of autoimmune diseases.

  • Key Points of Innovation & Differentiation
    • Using our Alivio technology platform, a biologic agent and/or small molecule drug can be administered in an oral dosage form that offers the potential to selectively act at the inflamed tissues locally to maximize efficacy, while minimizing toxicity by reducing systemic exposure of the drugs.
    • LYT-510 is an oral inflammation-targeting formulation of tacrolimus in development to treat IBD and chronic pouchitis. Tacrolimus is a potent immunosuppressant drug that is FDA approved for prophylaxis of organ rejection in patients receiving allogeneic kidney, liver or heart transplants and topically for the treatment of atopic dermatitis. Clinical studies have demonstrated that tacrolimus can be an effective agent to induce remission in IBD patients following a short-term treatment regimen. However, the current tacrolimus products have found limited use because of a narrow therapeutic window, which has the potential to cause various systemic side effects including hypertension, paresthesia, neuropathy, renal impairment, and opportunistic infections. We believe that LYT-510 can overcome these clinical challenges by targeting tacrolimus to inflamed intestinal tissue and minimizing systemic exposure. With this enhanced PK profile, we believe that LYT-510 has the potential to be the first tacrolimus treatment approved for IBD in the U.S.
  • 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 more targeted manner. We have been inspired by the key observation that pathologic inflammation 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 due to narrow therapeutic windows. Moreover, combining therapies to address multiple aspects of the autoimmune diseases is quite challenging due to both distinct and overlapping drug toxicity profiles. 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 3.9 million people in the U.S.2, with monoclonal antibody therapies being the preferred treatment option for patients with moderate-to-severe disease. However, these therapies must be provided through multiple injections over time and are associated with several limitations including a lack of efficacy for some patients, dose-limiting AEs, loss of efficacy over time via anti-drug antibody development and the potential for opportunistic infections or malignancies.
    • We believe that an ideal solution for treating IBD and chronic pouchitis would be an oral drug therapy that targets multiple mechanisms of disease pathogenesis while minimizing the potential for systemic side effects. We believe LYT-510, developed from our Alivio technology platform, can potentially fulfill this goal.
  • Milestones Achieved & Development Status
    • In multiple preclinical IBD models, LYT-510 showed significant improvements in several efficacy endpoints compared to untreated controls. Furthermore, the inflammation-targeting properties were shown to result in very low systemic blood levels compared to the current immunosuppressant formulations, which minimizes the potential for systemic side effects.
    • In 2020, the U.S. Department of Defense (DOD) Technology/Therapeutic Development awarded $3.3 million to support the advancement of LYT-510 into the clinic.
  • Expected Milestones
    • We intend to file for regulatory approval to initiate first-in-human studies at year end 2022 and initiate a clinical study evaluating LYT-510 as a single agent for the potential treatment of IBD and chronic pouchitis in early 2023.
  • Intellectual Property
    • The intellectual property portfolio supporting LYT-510 consists of coverage around both the broader inflammation-targeting platform and the specific drug combination candidate. Platform intellectual property is supported by one patent family that has been exclusively licensed from the Brigham and Women’s Hospital, which includes seven issued patents to date and five pending applications within and outside the U.S. In addition, intellectual property specific to LYT-510 includes one patent family which is owned by Alivio that consists of eight patent applications within and outside the U.S.

2 Inflammatory Bowel Disease (IBD) in the United States. (2021, November 09). https://www.cdc.gov/ibd/data-statistics.htm

We are developing LYT-510 as an oral inflammation-targeting formulation of tacrolimus, a potent immunosuppressant drug, to treat IBD and chronic pouchitis. Tacrolimus is approved for certain indications, however its approval for IBD and chronic pouchitis has been hampered by systemic toxicities, narrow therapeutic window of activity and opportunistic infections that can arise from systemic immunosuppression. There is clinical data demonstrating that tacrolimus is effective in addressing IBD indications, but adverse events (AEs) have held it back. We believe that LYT-510 can overcome these clinical challenges with targeted drug delivery to the intestines, with the potential to be the first tacrolimus treatment approved for IBD in the U.S. In multiple preclinical IBD models, LYT-510 showed significant improvements in several efficacy endpoints compared to untreated controls. Furthermore, the inflammation-targeting properties were shown to result in very low systemic blood levels compared to the current immunosuppressant formulations, which minimizes the potential for systemic side effects.