CANbridge will seek FDA OK for human trials of new gene therapy

Therapy may be more potent, less toxic in SMA than Zolgensma

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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CANbridge Pharmaceuticals is planning to ask the U.S. Food and Drug Administration for permission to launch, by the end of 2024, clinical trials of its second-generation gene therapy candidate for spinal muscular atrophy (SMA).

That request — for clearance for first-in-human studies — will come in the form of an investigational new drug application to the U.S. regulatory body.

Preclinical studies have so far indicated that the SMA gene therapy candidate — which CANbridge acquired earlier this year — has the potential to be more potent and less toxic than Zolgensma (onasemnogene abeparvovec-xioi), the only gene therapy that’s now approved for the rare genetic disorder.

“We have made significant progress building CANbridge and advancing our pipeline,” James Xue, PhD, CANbridge’s founder, chairman and CEO, said in a press release detailing the company’s 2022 financial results and giving corporate updates.

“We are anticipating an exciting year ahead,” Xue said.

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An illustration of a mouse in a lab.

New Gene Therapy Shows Potential for Safety, Efficacy in Mouse Model

CANbridge aiming to launch trials of SMA gene therapy candidate in 2024

Mutations in the SMN1 gene, resulting in a lack of the survival motor neuron (SMN) protein, are the cause of the most common SMA types. The SMN protein is needed for the proper function of motor neurons, the specialized nerve cells that communicate with muscles to coordinate voluntary movement.

Zolgensma, marketed by Novartis,  is a gene therapy that provides patients with a healthy version of SMN1, allowing cells to produce their own functional SMN protein. It was approved in the U.S. in 2019 and granted conditional approval in the European Union in 2020.

The therapy is packaged into a viral vector, called adeno-associated virus serotype 9 (AAV9), that is modified so as not to cause disease. Still, the high dose that’s needed for the treatment to be effective can pose certain safety risks, including the potential for liver damage or other blood-related complications.

CANbridge’s second generation gene therapy involves certain modifications to the delivered gene that are intended to minimize these side effects. While all cells can still receive the contents from the AAV9 vector, only those where the SMN1 gene would normally be active in the body can produce the SMN protein.

The investigational treatment was initially developed at the Horae Gene Therapy Center at the University of Massachusetts Chan Medical School, where CANbridge-sponsored preclinical studies also were conducted.

Results from those studies indicated that a single into-the-vein (intravenous) infusion of the experimental therapy may be safer and less toxic than Zolgensma. Specifically, its infusion led to lesser accumulation in the liver compared with another gene therapy designed similarly to Zolgensma.

Moreover, the treatment significantly prolonged survival and resulted in greater motor function gains in a mouse SMA model. It also led to more substantial nerve cell innervation of muscles relative to the Zolgensma-like treatment in the mice. Female mice also attained a healthier body weight after receiving the second-generation therapy.

Based on the findings, CANbridge acquired exclusive global rights to develop, manufacture, and commercialize the experimental therapy for the treatment of SMA.

CANbridge last summer also opened its Next-Generation Innovation and Process Development Facility, an in-house gene therapy research and development facility. Its goal is to develop potentially curative gene therapies for rare genetic diseases, including SMA, Fabry disease, and Pompe disease.