FDA Greenlights IND for MPS Type 1 Cell Therapy


Immusoft plans to begin the phase 1 clinical trial of ISP-001 before the end of 2022.

The FDA has cleared an investigational new drug application (IND) for Immusoft’s ISP-001, an investigational engineered autologous B-cell therapy intended for the treatment of mucopolysaccharidosis type I (MPS I), allowing the company to initiate a phase 1 clinical trial.1

The treatment involves reprogramming a patient’s B-cells outside the body using the company’s proprietary Immune System Programming (ISP) technology platform, which results in the B-cells producing therapeutic proteins in vivo.1,2 Immusoft expects that this approach will allow the treatment to bypass issues with immunogenicity typically seen in virus-delivered gene therapies as well as the chemotherapy preconditioning typically necessary for stem cell-mediated gene therapies. Furthermore, the company expects that the B-cells will persist for years and that re-dosing will be possible. Immusoft sees ISP-001 as a potentially favorable alternative to enzyme replacement therapy, a currently available treatment for MPS I, in terms of cost and frequency of dosing.2

“There is a clear need for additional therapies for MPS I, as current interventions are not curative and significant disease related morbidity still exists,” Paul Orchard, MD, professor, Division of Pediatric Bone Marrow Transplantation, University of Minnesota Medical Center, and principal investigator on the ISP-001 phase 1 clinical trial, said in a statement.1 “A non-viral gene delivery method such as ISP-001 holds great promise with the potential to provide definitive therapy.”

ISP-001 previously received orphan drug designation from the FDA in May of 2018, and was granted rare pediatric disease designation by the FDA in October of 2018.2,3 Immusoft plans to begin the phase 1 clinical trial of ISP-001 before the end of 2022.1

“We are pleased with the FDA’s clearance of our IND application for our lead candidate ISP-001 in MPS I. This is a huge achievement for the Company and a historic moment in the field of cell and gene therapies,” Sean Ainsworth, chief executive officer and chairman, Immusoft, added to the statement.1 “I look forward to working with our team and investigators to initiate our Phase I clinical trial later this year and to continue our commitment to the development of our engineered B-cell platform for patients in need.”

Several other companies are also developing treatments for MPS I. Orchard Therapeutics is developing OTL-203, an ex-vivo autologous hematopoietic stem cell (HSC) gene therapy, in collaboration with the San Raffaele-Telethon Institute for Gene Therapy.4,5 It is designed to deliver a functional copy of the IDUA gene and has also been granted rare pediatric disease designation by the FDA. It is currently under investigation in a proof-of-concept clinical trial.

Meanwhile, REGENXBIO is developing RGX-111, a gene therapy designed to deliver IDUA directly to the central nervous system via an AAV9 vector.6 The FDA has granted it orphan drug designation, rare pediatric disease designation, and fast track designation, and it is currently under investigation in a phase 1/2 clinical trial (NCT03580083).

Sangamo Therapeutics had been investigating SB-318, a zinc finger nuclease gene editing therapy, in a phase 1/2 clinical trial (NCT02702115). However, the clinical trial was terminated in November of 2021 after less than impressive interim results were posted in early 2019.7 A long-term follow-up investigation (NCT04628871) of the therapy’s safety for the patients treated remains on-going, however.

1. Immusoft announces FDA clearance of IND application for ISP-001 for MPS I, the first engineered B cell therapy toenter into clinical trials. News release. Immusoft. September 1, 2022. https://www.immusoft.com/2022/09/01/immusoft-announces-fda-clearance-of-ind-application-for-isp-001-for-mps-i-the-first-engineered-b-cell-therapy-to-enter-into-clinical-trials/ 
2. Immusoft granted orphan drug designation for treatment of rare childhood disease. News release. Immusoft. May 2, 2018. https://www.immusoft.com/2018/05/02/immusoft-granted-orphan-drug-designation-for-treatment-of-rare-childhood-disease/ 
3. Immusoft receives rare pediatric disease designation for treatment of MPS I. News release. Immusoft. October 17, 2018. https://www.immusoft.com/2018/10/17/immusoft-receives-rare-pediatric-disease-designation/ 
4. Pipeline. Website. Orchard Therapeutics. https://www.orchard-tx.com/approach/pipeline/ 
5. Orchard Therapeutics announces multiple presentations at 2022 SSIEM annual symposium highlighting neurometabolic disease portfolio. News release. Orchard Therapeutics. August 29, 2022. https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-announces-multiple-presentations-2022-ssiem 
6. MPS I: Developing life-changing gene therapies. Website. REGENXBIO. https://www.regenxbio.com/mps-i/ 
7. Sangamo Announces Interim Results Of Phase 1/2 EMPOWERS Study Evaluating SB-318 Zinc Finger Nuclease (ZFN) In Vivo Genome Editing Demonstrating Increased Leukocyte IDUA Activity In Patients With MPS I. News release. Sangamo Therapeutics. February 7, 2019. https://investor.sangamo.com/news-releases/news-release-details/sangamo-announces-interim-results-phase-12-empowers-study
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