Immusoft of CA has achieved what the company calls a "historic achievement" in gene therapy: the safe and well-tolerated re-dosing of a patient with a gene-modified therapeutic product candidate. The patient in Immusoft's first-in-human clinical study has now received two doses of ISP-001 to treat mucopolysaccharidosis type I (MPS I), separated by 18 months, with an excellent safety and tolerability profile to date.
This milestone addresses a longstanding challenge in gene therapy, where the vast majority of treatments are not re-dosable with current technologies. "There have long been questions about lifelong durability of one-and-done gene therapies and the ability to safely re-dose has been a much sought after feature in advanced therapeutics," stated Sean Ainsworth, CEO of Immusoft. "In more recent times, we are seeing that it's difficult for many of these approaches to be safely dosed a first time, let alone a second time."
Engineered B Cells Overcome Traditional Gene Therapy Limitations
The breakthrough stems from Immusoft's engineered B cell approach, which differs fundamentally from conventional viral gene therapeutics and gene-modified stem cell approaches. Based on clinical data generated to date, engineered B cells do not elicit the dangerous immune response associated with systemically delivered viral gene therapeutics, avoiding the burdensome immunosuppression regimens required by viral approaches.
Unlike gene-modified stem cell approaches that require toxic chemotherapy regimens typically involving several-week hospital stays and substantial morbidity, B cells naturally migrate to and engraft in the bone marrow without chemotherapy. This chemotherapy regimen is sometimes associated with mortality, making re-treatment impractical and unsafe with traditional approaches.
When engineered B cells engraft in bone marrow, they act as living biofactories, continuously secreting therapeutic proteins into circulation. The ability to safely re-dose provides the opportunity to extend potential treatment effects, enabling around-the-clock therapeutic protein delivery possibly for the life of the patient.
Clinical Results Show Sustained Benefits
The first patient treated with ISP-001 initially received the lowest dose specified for the trial and saw durable benefits beyond a year. They were subsequently re-dosed with double the initial dose with the objective of titrating to effect. This patient has continued to show positive outcomes since their initial treatment, including pharmacodynamic, functional, and quality-of-life improvements.
Dr. Paul Orchard, Professor of Pediatrics, Division of Blood and Marrow Transplant & Cellular Therapy at the University of Minnesota Medical School and Principal Investigator of the ISP-001 clinical trial, commented: "The ability to re-dose is something that the gene therapy field has been striving toward for decades. The results we've seen so far in the Immusoft clinical trial are very encouraging, particularly given the absence of myeloablation or immunosuppression. The engineered B cell approach, if successful, could dramatically change how we treat many genetic diseases like MPS I."
Expanding Patient Enrollment
Immusoft recently dosed a second patient in the clinical trial, who has also exhibited a very clean safety and tolerability profile to date. This patient received the mid dose specified for the trial, approximately three times the first patient's first dose. Initial pharmacodynamic results are encouraging.
The trial is supported by an $8 million award from the California Institute for Regenerative Medicine (CIRM), which funds cell and gene therapy research and clinical trials in California.
Technology Platform and Future Implications
Immusoft has developed a technology platform called Immune System Programming (ISP™), which modifies a patient's B cells and instructs the cells to produce gene-encoded medicines. The B cells that are reprogrammed using ISP become miniature protein therapeutic biofactories that are expected to persist for many years.
The company positions itself as a clinical-stage next-generation, advanced therapeutics company focused on developing novel therapies for rare diseases using sustained delivery of protein therapeutics from a patient's own cells. The successful re-dosing capability could have broad implications for treating various genetic diseases beyond MPS I.
