Aytu BioPharma Acquires License to Develop DB102 for vEDS

Aytu BioPharma has acquired the option to license DB102 (enzastaurin), an investigational anti-tumor therapy with the potential to treat vascular Ehlers-Danlos syndrome, or vEDS.

Denovo Biopharma, which holds worldwide rights to DB102 — originally developed as an oncology treatment — will continue to develop the oral therapy for certain cancers.

“DB102 has the potential to treat a variety of disorders, both inside and outside of the oncology field,” Michael F. Haller, PhD, Denovo’s chief business officer, said in a press release.

Also known as AR101, DB102 is an orally delivered, experimental small molecule that inhibits a type of enzyme called a serine-threonine kinase. Serine-threonine kinases are central to a number of cellular signaling pathways, some of which appear altered in vEDS. A signaling pathway works somewhat like an electrical circuit, where a signal at one end causes a reaction at the other end.

One recent study found that mice carrying vEDS-associated mutations in their equivalent of the COL3A1 gene had abnormal PKC beta signaling, resulting in the easily ruptured blood vessels characteristic of the disorder. The investigators behind that study determined that this signaling pathway represented “unanticipated therapeutic opportunities.”

Denovo had licensed DB102 to Rumpus Therapeutics for select medical indications. Rumpus had focused on applying it to vEDS.

“Rumpus Therapeutics has been actively pursuing development of DB102 in select rare genetic onset non-oncology indications, such as vEDS, since signing the option agreement,” Haller said, “and we welcome the interest of Aytu BioPharma in accelerating these efforts.”

Eli Lilly had originally developed DB102 because the PKC beta pathway, along with those related to the proteins PI3K and AKT, plays a central role in a range of cancers.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency have both given DB102 orphan drug status for the possible treatment of diffuse large B-cell lymphoma (DLBCL) and glioblastoma multiforme (GBM). The FDA also has given it fast track designation for these conditions.

Because the signaling pathways affected by DB102 are important for many cellular processes, the potential therapy could treat multiple conditions.

While Denovo focuses on its application to cancers, Rumpus has been working to develop DB102 for rare genetic disorders like vEDS. Under the terms of the current agreement, Aytu now holds an exclusive worldwide license to develop DB102 for rare genetic pediatric onset or congenital disorders outside of cancers.

“As these indications are outside Denovo’s core development areas for DB102 in DLBCL, GBM, and pulmonary arterial hypertension (PAH), this represents a validation of Denovo’s business model of acquiring drugs for all indications and developing them with newly-discovered biomarkers in parallel with out-licensing non-core indications,” Haller said.