Oncology Pipeline

For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. In 2019 Lilly created Loxo Oncology at Lilly, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new medicines that work in early clinical development and will matter to patients.

IDH1 Inhibitor

LY3410738

IDH1 Inhibitor

Waitkus MS, et al1

Target
The enzyme isocitrate dehydrogenase (IDH1) is mutated in a variety of cancers, including acute myeloid leukemia (AML), cholangiocarcinoma, chondrosarcoma, and glioma.2-5 These mutations are typically somatic gain-of-function mutations located in arginine 132 (R132) that grant IDH1 the ability to produce 2-hydroxyglutarate (2-HG).6 2-HG is an oncometabolite that promotes tumor development by inhibiting enzymes that maintain normal DNA and histone methylation, leading to hypermethylation associated with transcriptional dysregulation.6,7 As a result, IDH1-mutated cells become blocked in a progenitor-like state and contribute to tumor development both directly through cellular self-renewal and indirectly through cooperation with other oncogenic drivers.7
Molecule
LY3410738 is a potent, selective, and covalent inhibitor of mutant IDH1 that has been shown in vitro and in vivo to rapidly inactivate mutant IDH1 and inhibit 2-HG production without impacting wild-type IDH1.8
Clinical Development
​​​​LY3410738 is being investigated in clinical trials in patients with advanced hematologic malignancies or advanced solid tumors.

References

  1. Waitkus MS, et al. Cancer Cell. 2018;34(2):186-195. 2. Gross S, et al. J Exp Med. 2010;207(2):339-344. 3. Borger DR, et al. Oncologist. 2012;17(1):72-79. 4. Amary MF, et al. J Pathol. 2011;224(3):334-343. 5Yan H, et al. N Engl J Med. 2009;360(8):765-773. 6. Losman JA, et al. Science. 2013;339(6127):1621-1625. 7. Lu C, et al. Nature. 2012;483(7390):474-478. 8. Brooks N, et al. AACR Annual Meeting; March 29-April 3, 2019; Atlanta, GA. Abstract LB274.

The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.

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