CANbridge Acquires Possibly Safer, More Effective SMA Gene Therapy

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by Lindsey Shapiro PhD |

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An illustration of three laboratory vials, two containing DNA and one with a liquid compound.

CANbridge Pharmaceuticals has acquired exclusive global rights to develop, manufacture, and commercialize a second-generation gene therapy for spinal muscular atrophy (SMA).

The company had completed preclinical studies of the investigational gene therapy in collaboration with the Horae Gene Therapy Center at the University of Massachusetts (UMass) Chan Medical School, where the therapy was initially developed.

This research in mouse models of SMA indicated that the therapy may be more potent and less toxic in intravenous use than Zolgensma (onasemnogene abeparvovec-xioi), the only gene therapy approved for the disease.

“The gene therapy we developed with UMass Chan, and to which we now have global rights in the field, holds promise as a potential best in class therapeutic for SMA,” James Xue, PhD, founder, chairman, and CEO of CANbridge, said in a company press release.

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Lesser accumulation seen in liver of mice given investigative SMA gene therapy

The most common forms of SMA are caused by mutations in the SMN1 gene, leading to insufficient production of the survival motor neuron (SMN) protein that’s important for the health of cells involved in voluntary movement.

Approved SMA treatments are designed to raise SMN levels in cells. Zolgensma, marketed by Novartis, is a gene therapy that aims to deliver a healthy copy of SMN1 to cells, allowing them to produce their own functional SMN protein.

It relies on a viral vector, or carrier, that helps the therapy reach its target cells and be taken up by them. While the vector is modified so as not to cause disease, the high dose required for a therapeutic effect can lead to liver damage and other blood-related complications.

The second-generation gene therapy was designed to minimize these side effects through certain alterations to the viral vector. One of the most prominent changes is the expression of the healthy SMN1 gene in the same tissues as the endogenous (original) gene, rather than in all cell types.

CANbridge-sponsored preclinical studies were conducted to compare the experimental therapy with another designed similarly to Zolgensma, called a benchmark therapy, in healthy mice.

Results showed that the second-generation therapy, injected directly into the bloodstream, had lesser accumulation in the liver compared with the benchmark, suggesting it could be safer and less toxic.

In an SMA mouse model, the treatment significantly prolonged survival compared with the benchmark. Specifically, while mice receiving the benchmark therapy survived for a median of 60 days in the 90-day study, those treated at high dose with the experimental therapy survived for the entire study period.

Moreover, mice given the second-generation treatment showed greater gains in motor function, less tissue death around the ears, and a more complete restoration of nerve cells’ innervation of muscles, which is lost in SMA.

Female mice also reached a healthier body weight after receiving the new gene therapy than those given the benchmark, although no weight differences were seen in male mice.

This investigational gene therapy “has a remarkably improved potency and safety profile as compared to the benchmark vector, holding great promise for further clinical development,” said Guangping Gao, PhD, director of the Horae Gene Therapy Center and co-director of the Li Weibo Institute for Rare Diseases Research, also part of UMass.

“We feel confident in CANbridge’s ability to develop this gene therapy for spinal muscular atrophy, which could help more patients and families suffering from this devastating disease,” Gao said.

In addition to the potential SMA gene therapy, CANbridge has acquired the rights to gene therapy candidates for Fabry and Pompe disease developed by LogicBio Therapeutics.

“We look forward to developing potential best-in-class gene therapies for these three rare diseases which currently have limited treatment options,” Xue said.

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