It targets enzymes (pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase) in the mitochondria of cancer cells that affect cancer cell energy metabolism, resulting in cell apoptosis and/or necrosis.
Trials are currently recruiting in R/R Burkitt lymphoma/leukemia or high-grade B-cell lymphoma with high-risk translocations [1], high risk myelodysplastic syndrome [2], locally advanced pancreatic [3], R/R AML [4] and metastatic pancreatic [5]. Also, ones are planned in R/R T-cell NHL [6], advanced unresectable biliary tract [7], and the company has a compassionate use program [8].
Refs:
1 https://clinicaltrials.gov/ct2/show/NCT03793140
2 https://clinicaltrials.gov/ct2/show/NCT03929211
3 https://clinicaltrials.gov/ct2/show/NCT03699319
4 https://clinicaltrials.gov/ct2/show/NCT03504410
5 https://clinicaltrials.gov/ct2/show/NCT03504423
6 https://clinicaltrials.gov/ct2/show/NCT04217317
The drug with gemcitabine and nab-paclitaxel [1], fully enrolled in one pivotal trial [2], and past the midpoint in another (again, pivotal) [3].
Refs:
1 https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.4635
An oral form of devimistat (RFL-618) is in development, as are three second generation compounds (RFL-5800/5990/6520). INDs are expected to be filed either this and/or next year.
In the first PhIII (metastatic pancreatic) the company is expecting a data readout by Q3. In the second PhIII (R/R AML), an IA will be conducted by Q2.
Four PhII trials are planned in first-line metastatic pancreatic (dev plus gemcitabine and nab-paclitaxel), metastatic CRC (dev plus FOLFOXIRI and bevacizumab), R/R MDS (dev plus hydroxychloroquine) and R/R TCL (dev plus bendamustine), also a PhI/II in R/R ccSTS (dev plus hydroxychloronquine).
