- Those waiting for the first look at human data from Rubius will have to be patient for a few more months. On Thursday, the Cambridge, Massachusetts-based biotech delayed the timeline for its first clinical readout to early 2020, admitting the trial has yet to dose its first patient.
- The study is testing Rubius' lead therapeutic candidate, RTX-134, in adult patients with phenylketonuria, or PKU. Several other companies, including BioMarin Pharmaceutical, Homology Medicines and Moderna, are also developing therapies to treat the rare inherited disorder.
- Rubius was one of biopharma's largest IPOs in 2018, going public last July at a $2 billion valuation. Shares have fallen more than 60% since, as the company disclosed manufacturing setbacks this summer, while other biotechs have advanced rival therapies. Rubius' stock fell as much as 8% Thursday morning.
Rubius has failed to deliver on its first clinical timeline, after setting the expectation throughout 2019 for a readout by year's end.
Even after disclosing problems with a contract manufacturer in August, Rubius executives said the situation was under control and reaffirmed the 2019 timeline for data. They lowered expectations for the readout to include just four patients instead of the previously planned five to 10.
Rubius now expects to report early Phase 1 results in the first three months of 2020, the company said in reporting its third quarter financial results. Rubius stated it will announce when the first patient is treated, implying the study has yet to dose a patient despite actively recruiting since late September, according to clinicaltrials.gov.
The RTX-134 data will focus on preliminary safety, durability and phenylalanine levels, as well as a biomarker tracking the drug's mechanism of action. The plan is this early-stage trial will determine dosing and scheduling for a multi-dose Phase 2 study focused on efficacy.
If the Phase 2 study brings positive results, Rubius would launch a registrational trial for the adult population and also start a study in children with PKU.
That's a long road to market in a rapidly-evolving disease space, crowded with formidable competition.
BioMarin already has marketed PKU drugs in Palynziq (pegvaliase) and Kuvan (sapropterin dihydrochloride) and is seeking to expand its franchise with a gene therapy option. That program is set to soon enter the clinic, as the big biotech submitted a U.K. clinical trial application in September.
Homology is even further along with its gene therapy approach of HMI-102. On Tuesday, company executives said it remains on track to present initial clinical data from a Phase 1/2 study by year's end.
Beyond gene therapy, Synlogic and Codexis have also presented early clinical data for their respective PKU treatments, putting them further along in development than Rubius. And Moderna and Agios Pharmaceuticals have both said they are doing preclinical work on the disorder.
The PKU space may look radically different by the time Rubius gets to later-stage testing let alone commercialization.
The gene therapies, in particular, could present a compelling option for patients if they normalize phenylalanine after a single dose. Baird analyst Madhu Kumar, who holds a sell rating on Rubius, believes it would be "game over" for RTX-134 if that happens, he said in a recent interview with BioPharma Dive.
Rubius pushes back against this opinion, saying PKU patients will need options and not every patient can or will want to undergo such a treatment for a non-fatal disease.
The biotech also plans to move beyond PKU, with plans to submit its first Investigational New Drug application in oncology in early 2020. The company anticipates filing four or five INDs in the next two years.