Clinically approved mesenchymal stromal cell preparation for treatment of inflammatory diseases, such as osteonecrosis, ARDS, and prediabetes

Challenge

Mesenchymal stromal cells (MSC) possess a high immunosuppressive and immunomodulatory potential. A novel MSC product provides effective treatment of steroid and therapy-refractory acute graft-versus-host disease. We are looking for partners to develop our clinical approved MSC product for further specific indications, such as osteonecrosis, ARDS or prediabetes.

Technology

Scientists from University Children’s Hospital of Goethe University and the German Red Cross Blood Center of Frankfurt/Main developed a novel method for preparing clinical scale mesenchymal stromal cell (MSC) by pooling bone marrow from several third-party donors. Typically, MSCs are isolated from a single bone marrow donor causing marked variations in the therapeutic potency from donor to donor. Additionally, intrapopulation heterogeneity at the clonal level enhances these variations.

A novel three-step technique overcomes the described problem of quality and potency variations. In a first step bone marrow mononuclear cells (BM-MNCs) are isolated from multiple third-party, healthy donors. Then MSCs are generated from the pooled BM-MNCs after thawing and cryopreservation in vials. Finally, MSCs are serum-free expanded to obtain clinical-scale doses. The novel method allows for the generation of MSCs with an equivalent therapeutic potency, thus minimizing inter-donor variability of allosuppressive potential, thus, ensuring consistency, reproducibility, and reliability in immunosuppressive performance. The novel MSC preparation is characterized by a stable proliferative capability and an increased immunosuppressive potential when compared to individual donor MSC preparations.

Administration of MSCs to 69 patients with severe steroid-resistant acute GvHD in 7 stem cell transplant centers who were refractory to many lines of treatment, induced a 83% overall response at the primary end point (day 28). Remarkably, although the cohort of patients was highly challenging (36% grade III and 59% IV, and only 4% grade II GvHD), after treatment with MSC end-products the overall survival rate at two years follow up was 71±11% for the entire patient cohort, compared to 51.4±9.0% in GvHD clinical studies, in which MSCs were derived from single donors.

Commercial Opportunity

Due to their immunomodulating properties MSCs are currently tested in various clinical trials. Preclinical and clinical data support osteonecrosis as promising indication for use of MSCs. Osteonecrosis is newly diagnosed each year in an estimated 20,000 to 30,000 patients in the United States, with even larger numbers worldwide, and it is the underlying diagnosis in approximately 10 percent of all total hip replacements (THR) in the United States. Osteonecrosis affects about 15,000 patients per year in the United State. There is no effective therapeutic treatment yet. Most of the time surgery is eventually required which include osteotomy or joint replacement .

Development Status

The novel MSC preparation received national authorization according to § 4b Abs. 3 AMG (German Medicines Act) for treatment for GvHD patients in 2016.

Patent Situation

A Priority Patent Application on the MSC preparation method and product was filed on July 16, 2014 (EP 14 177 312.7); and a European Patent is issued (EP 2 975 118). A corresponding International PCT Patent Application was filed on July 14, 2015 (PCT/EP2015/066083). Patent applications are pending in AU, BR, CA, CN, EP, IL, IN, JP, KR, MX, NZ, SA, SG UA, US.

Further Reading

Bader et al., Bone Marrow Transplantation,53(7):852-862, 2018.

Elgaz et al., Transfus Med Hemother 2019.

Jones et al., Biol Blood Marrow Transplant 14: 1081-1087, 2008.