Roche dumps Oryzon’s epigenetic AML, solid tumor drug 

The Roche Tower
The Roche Tower in Basel (Taxiarchos228)

Roche has jettisoned Oryzon’s treatment for acute myeloid leukemia (AML) and solid tumors from its pipeline. The decision to dump lysine-specific demethylase-1 (LSD1) inhibitor ORY-1001 wiped as much as 30% off Oryzon’s stock price as investors digested the loss of the $500 million-plus deal.

Oryzon landed the validatory deal and accompanying $21 million in upfront and near-term payouts in 2014. Roche extended the initial two-year collaboration by 12 months in 2016, reportedly to buy more time to transfer technology and knowledge that would help it in clinical trials. But the Swiss Big Pharma has now called time on the collaboration, stripping Oryzon of the chance to bag most of the $500 million in milestones tied to the agreement.

Investors responded to the setback to Oryzon’s most advanced and only partnered drug by taking a chunk out of its stock price. Oryzon CEO Carlos Buesa admitted the decision was disappointing. But he sought to limit the damage by framing Roche’s action as being unrelated to data generated to date. 

“We have been informed that the decision was not data driven but a consequence of internal reprioritization of Roche’s pipeline. During the next weeks, Oryzon will focus its efforts to regain the control of the asset as soon as possible to ensure the continuation of the clinical development plan without interruptions,” Buesa said in a statement.

The spearhead of the clinical development plan is a trial in patients with AML. Oryzon brought the LSD1 inhibitor through an early-phase safety study last year, after which it transitioned into a phase 2a to get an early glimpse of efficacy. Among the 14 evaluable participants, Oryzon saw an objective response rate of 36%. Evidence of morphologic blast differentiation was seen in two-thirds of the evaluable patients.

Oryzon thought the data showed ORY-1001 had a future in AML, at least in a subset of patients. The idea behind ORY-1001 is to disrupt the activity of LSD1, a histone-modifying enzyme that acts on leukemic stem cells by regulating gene expression. LSD1 expression is also upregulated in some solid tumors.

The link between LSD1 and cancer is compelling enough to attract the interest of Roche and GlaxoSmithKline, which is testing its own inhibitor of the enzyme in patients with AML, small cell lung cancer and myelodysplastic syndrome.  

Responsibility for keeping pace with GSK will now fall on Oryzon, although it will retain the support of Roche in the near term. Roche is committed to finalizing an ongoing phase 1 trial of the drug in small cell lung cancer. Beyond that, Oryzon is on its own.