Rubius Therapeutics Exits Rare Disease to Focus on Cancer

Rare Daily Staff

Rubius Therapeutics said it is halting development of its experimental therapy for the rare metabolic condition phenylketonuria, as well as other rare disease programs to focus its resources on its cancer programs.

Phenylketonuria (PKU) is a rare, inherited metabolic disorder that is caused by mutations in the phenylalanine hydroxylase (PAH) gene. Patients with mutations in the PAH gene inefficiently metabolize phenylalanine (Phe) leading to potentially toxic levels of Phe in the blood that can cause severe intellectual disabilities. Newborn screening is available for this disorder.

Rubius experimental therapy RTX-134 is an off-the-shelf cellular therapy for the potential treatment of PKU. The cells are genetically engineered to express the enzyme phenylalanine ammonia lyase, or PAL, inside the cell. RTX-134 is designed to circulate in the blood stream and degrade toxic levels of phenylalanine that accumulate due to a deficiency in the PAH enzyme.   

Rubius suffered unanticipated delays in the RTX-134 program, primarily due to continued manufacturing challenges at the company’s contract manufacturing organization. It also said it was deprioritizing the program because of the anticipated high cost associated with producing chronic, high-dose therapy for enzyme deficiencies and the continued momentum of the company’s oncology pipeline.

It said future capital investments and improvements in manufacturing efficiency, together with enhancements to its platform technology may enable it to revisit chronic, high dose-dependent conditions in the future.

Rubius dosed its first patient with RTX-134 in January 2020 in a phase 1b clinical trial in PKU. The company said there were no reported adverse events and RTX-134 administration was well tolerated, but the results from the first patient were uninterpretable. It said this may be due in part to the low dose of cells administered and the sensitivity of the assay used to detect circulating cells.

Rubius is putting its resources into advancing Red Cell Therapeutics to stimulate the immune system in a fight against certain cancers. The company said it is on track to file by year-end an application to begin clinical testing of its experimental therapy RTX-321, its first artificial antigen-presenting cell for the treatment of HPV-positive cancers.

“Over the past two years, we have generated exciting oncology preclinical data, demonstrating the ability of our Red Cell Therapeutics to both broadly activate the immune system, and induce tumor-specific responses by activating and expanding antigen-specific T cells with our artificial antigen-presenting cells,” said Pablo Cagnoni, president and CEO of Rubius Therapeutics. “By focusing on the development of our oncology and autoimmune pipeline, we believe we will have the greatest opportunity to bring life-saving therapies to patients, enhance shareholder value and extend our cash runway into 2022.”

Photo: Pablo Cagnoni, president and CEO of Rubius Therapeutics