Immunometabolic adjuvants are needed that can broadly and safely leverage the therapeutic benefits of chemotherapy, radiotherapy and immunotherapy in diverse advanced human cancers.
LIMR scientists have synthesized second-generation “combi” or “pan” inhibitors that block the catalytic activity of the IDO1, IDO2 and/or TDO2 enzymes. The large global market for cancer drugs is expected to increase from $85 billion in 2016 to $155.6 billion by 2025, according to the research and consulting firm Transparency Market Research.
Starting more than a decade ago, LIMR scientists pioneered the discovery of small molecule inhibitors of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO), several classes of which are being studied in ongoing Phase 2 oncology trials worldwide. These immunometabolic adjuvants have been observed in many studies to improve the response of cancer chemotherapy, radio-chemotherapy, radiotherapy and immunotherapy. As a result of ongoing research in the field, LIMR scientists have developed second-generation inhibitors that can coordinately block the TDO2 and IDO2 enzymes also implicated in cancer (which can mediate bypass to IDO1 blockade).
IDO/TDO inhibitors apply to the treatment of diverse cancers, with preclinical and emerging clinical evidence that they safely enhance the efficacy of chemotherapy, radiotherapy, radio-chemotherapy, immune checkpoint therapy and cancer vaccines.
Stage of development
Present work is at the preclinical proof-of-concept stage.
Multiple issued and pending patents claiming structure of matter and medicinal uses. Several classes of protected structure of matter is available for licensing, including the first pro-drug inhibitors for these enzymes.
Preclinical development of protected IDO inhibitor structures and novel combination drug therapies including IDO inhibitors to treat cancer.
Malachowski WP, Winters M, DuHadaway JB, Lewis-Ballester A, Badir S, Wai J, Rahman M, Sheikh E, LaLonde JM, Yeh S-R, Prendergast GC and Muller AJ. (2016) O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1. Eur J Med Chem 108: 564-576.
Prendergast GC, Malachowski WP, DuHadaway JB and Muller AJ. (2017). Discovery of IDO1 inhibitors: From bench to bedside. Cancer Res 77: 6795-6811.
Winters M, DuHadaway JB, Pham KN, Lewis-Ballester A, Badir S, Wai J, Sheikh E, Yeh S-R, Prendergast GC, Muller AJ and Malachowski WP. (2019) Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase. Eur J Med Chem 162:455-464.
Institutional contact: George C. Prendergast, PhD, LIMR President and CEO, 484.476.8475, [email protected]
IP manager contact: Heather Rose, PhD, JD, VP of Technology Licensing and Startups, Thomas Jefferson University, 215.503.0770, [email protected]