Rubius scraps lead drug after seeing 'uninterpretable' data

Rubius CEO Pablo Cagnoni (Business Wire)

Rubius Therapeutics has pulled the plug on its lead drug after its first use in a phase 1b generated “uninterpretable” data. The data capped off a series of setbacks for the phenylketonuria (PKU) asset, leading Rubius to stop the trial and focus instead on its oncology and autoimmunity prospects. 

When Rubius emerged from Flagship Ventures’ incubator late in 2015, it listed rare metabolic disease PKU as an early indication of interest. Oncology came to play a more prominent role in Rubius’ public discussions of its plans in subsequent years, but the PKU program was the first to enter the clinic, making it an important early test case for the biotech’s plans to weaponize red blood cells.  

Now, the stuttering progress of the PKU asset, RTX-134, has come to a stop. In disclosing the news, Rubius shared a snapshot of what it learned from the first patient dosed in a phase 1b earlier this year.

“While there were no reported adverse events and RTX-134 administration was well tolerated, the results from the first patient were uninterpretable possibly due, in part, to the low dose of cells administered and the sensitivity of the flow cytometry assay used to detect circulating cells,” Rubius wrote.

RTX-134 took a bumpy path into the clinic. In explaining the decision to “deprioritize” the candidate, Rubius ran through some of the difficulties the drug has faced, including “continued manufacturing challenges” at a contract service provider that delayed progress. Rubius also cited “the anticipated high cost associated with producing chronic, high-dose therapy for enzyme deficiencies.”

While the travails of the PKU program had already led some analysts to shift their focus to Rubius’ oncology assets, they still see downsides to the discontinuation of the PKU study. Jefferies analyst Michael Yee set out his concerns in a note to investors.

“The fundamental issue is we were supposed to have data in PKU by now which would de-risk the platform. But because of various issues, we still don't yet have proof of concept going into 2020 to know if it 'works,'” Yee wrote.

Without RTX-134 spearheading its pipeline, Rubius is left reliant on solid tumor cell therapy RTX-240 to provide early clinical validation of its platform. The FDA recently cleared an IND of the candidate, which expresses 4-1BBL and IL-15TP, but Rubius is yet to dose a patient.