Value Proposition
· Kinase inhibition is a highly effective, targeted therapy that is standard of care for many cancers.
· Aurora kinase inhibition is a promising class of these therapeutics demonstrated to successfully inhibit tumor growth and promote patient survival in various cancer indications. However, current oral administration requires high doses, leading to significant side effects and adverse events.
· The disclosed technology is an antibody-drug conjugate (ADC) platform that delivers Aurora kinase inhibitors directly to tumor cells using a novel click chemistry-based linker, enabling a 200-fold lower dose than conventional administration.
· In preclinical mouse models of prostate cancer, just two doses of this modified drug over 21 days resulted in significantly improved tumor suppression with no observed toxicity to major organs.
Unmet Need
· Aurora kinase inhibitors are serine/threonine kinase inhibitors that block cellular mitosis and promote apoptosis in rapidly dividing cancer cells. However, current formulations require high systemic doses, leading to significant toxicity and adverse side effects.
· MLN8237 (Alisertib) is an orally available selective aurora A kinase inhibitor in development for over 50 forms of cancer. Clinical trial results of high dose MLN8237 showed improved patient survival and tumor stabilization in a variety of indications, but with significant side effects such as fatigue, anorexia, nausea, neutropenia, and thrombocytopenia, resulting in elevated infection risk, frequent dose reduction, and/or medication noncompliance.
· Therefore, there is an urgent need for targeted delivery systems that achieve therapeutic benefits at significantly lower doses, minimizing systemic toxicity and improving patient tolerability and treatment compliance.
Technology Description
· Researchers at Johns Hopkins have developed a drug delivery platform that allows for precise targeting of effective anti-cancer drugs directly to tumor cells at significantly lower doses than conventional delivery, reducing toxicity and improving drug efficacy.
· This approach was demonstrated in mouse models of prostate cancer using MLN8237 (Alistertib), a commercially available aurora kinase inhibitor, and is adaptable to other therapeutics and targeting systems.
Stage of Development
· Preclinical proof-of-concept has been demonstrated in human prostate cancer xenograft mouse models, with further development planned for additional delivery platforms and cancer indications.
· Inventors are currently testing this drug delivery platform with a variety of other cancer therapeutics and targeting molecules in mouse xenograft models.
Data Availability
· Data available on request.
Publication
Liatsou I, Assefa B, Liyanage W, Surasinghe S, Nováková Z, Bařinka C, Gabrielson K, Raman V, Artemov D, Hapuarachchige S. Development and therapeutic evaluation of 5D3(CC-MLN8237)3.2 antibody-theranostic conjugates for PSMA-positive prostate cancer therapy. Front Pharmacol. 2024 May 1;15:1385598. doi: 10.3389/fphar.2024.1385598. PMID: 38751786; PMCID: PMC11094276.
