Denovo Biopharma recently entered an exclusive global license agreement with Stanford University School of Medicine to further develop and market its lead compound, DB102 (formerly called enzastaurin), as a potential treatment for pulmonary arterial hypertension (PAH) and emphysema.
In research in preclinical models at Stanford, DB102 was found to prevent and even reverse the progression of experimental pulmonary hypertension.
An oral small molecule, DB102 — a serine/threonine kinase inhibitor of the PKC beta and AKT protein-signaling pathways — has been studied in clinical trials, including ongoing trials, for its potential against a range of solid and hematological cancers.
“We are now able to expand DB102 development beyond oncology and into PAH which is a significant unmet medical need,” Wen Lou, PhD, chief executive officer and chief scientific officer of Denovo Biopharma, said in a press release.
“This new development allows DB102 to expand into unexpected new indications through traditional drug repurposing efforts” and the use of biomarker identification — a focus and point of specialty for Denovo, Lou added. “We will evaluate DB102’s activity in patients with PAH in the near future.”
DB102 has anti-tumor activity; it is thought that the medication decreases blood supply to cancer cells, preventing tumor growth. The company acquired rights to the compound from Lilly, which investigated its efficacy in Phase 3 studies in diffuse large B cell lymphoma(DLBCL) and glioblastoma patients, Denovo reports on its website.
At Stanford, DB102 was found to also modulate a therapeutically promising pathway through a previously unknown drug target, distinct from the candidate therapy’s targets for cancer patients. An international patent request has been filed related to this discovery.
Denovo is also conducting a Phase 3 study, ENGINE (NCT03263026), of DB102 in about 235 treatment-naïve patients with high-risk diffuse large B-cell lymphoma (DLBCL) identified by a biomarker as possibly responsive to the treatment. Patients are to be randomized to treatment or placebo plus R-CHOP chemotherapy across 39 clinical sites in the U.S. and China.
This trial’s primary goal is to determine if adding DB102 to R-CHOP extends the lives of patients positive for the biomarker DGM1, which seems to predict treatment response.
R-CHOP chemotherapy was granted orphan drug status by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to treat DLBCL and glioblastoma multiforme.
The company has two other late stage therapy programs: DB103 as a potential treatment for schizophrenia, and DB104 for depression.