Orbsen Therapeutics announces encouraging interim results from the NEPHSTROM proof of concept clinical study evaluating ORBCEL™ cell therapy in patients with diabetes and advanced chronic kidney disease

GALWAY, Ireland, Jan. 26, 2023 /PRNewswire/ -- Orbsen Therapeutics Limited ("Orbsen"), a global leader in stromal cell immunotherapies, today announces encouraging headline interim results from the EU Horizon 2020-funded NEPHSTROM clinical trial for Diabetic Kidney Disease (NEPHSTROM). NEPHSTROM is a randomized, double-blind, placebo-controlled Phase 1/2a, trial evaluating the safety, tolerability and preliminary efficacy of an off-the-shelf allogeneic bone marrow-derived mesenchymal stromal cell immunotherapy, ORBCEL™, in adult study subjects with type 2 diabetes and progressive diabetic kidney disease (DKD). ORBCEL is a proprietary formulation of highly purified immunomodulatory stromal cells. This investigator-sponsored, multi-centre study was led by the Mario Negri Institute for Pharmacological Research IRCCS (Bergamo, Italy).

Interim results highlights

• These interim results are from the lowest dose patient cohort who were administered 80 million cells of ORBCEL (n=12) or placebo (n=4).
• The safety and tolerability profile of ORBCEL was found to be similar to placebo
  - No treatment-related adverse effects due to the stromal cell infusions were observed

• A single infusion of intravenously delivered, ORBCEL was associated with statistically significant preservation of kidney function over baseline compared to a placebo treatment over 18 months (study end).
  - Based on serial measurements of changes in serum creatinine-based estimated glomerular filtration rate (CKD-EPI, p=0.034; MDRD, p=0.034)
  - Monitored blood markers suggest ORBCEL treatment was associated with evidence of stabilisation in the proportion of regulatory T cells in blood, which tended to decline in placebo-treated patients, and by a reduction in inflammatory monocytes

• The results from this study are consistent with preclinical data previously generated with ORBCEL.
• Enrolment in the second dose level patient cohort (160 million cells or placebo (n=13)) was completed late last year and interim results are expected to be available in the second half of 2023.
• The consortium is preparing to submit these first-cohort interim results for publication in a peer-reviewed journal.

These results were recently presented on 4^th November 2022 at the prestigious American Society of Nephrology's Kidney Week meeting held in Orlando, Florida.

Orbsen Therapeutics will now seek input from the US Food and Drugs Administration (FDA) and the European Medicines Agency (EMA) for the design of an adaptive phase 2b clinical study that, if successful, could potentially result in the conditional approval of ORBCEL of patients with progressive DKD, a significant unmet medical need where patients progress to end-stage kidney disease despite current standard of care therapy.

DKD affects 30-40 percent of adults living with type 2 diabetes. and accounts for about 40 per cent of all people with end-stage kidney disease (kidney failure) and greatly increases the risk for heart and blood vessel disease. An important aspect of DKD is an imbalance between inflammatory and anti-inflammatory immune cells.

Dr. Larry A. Couture, Chief Executive Officer of Orbsen Therapeutics Ltd said:

"We are pleased to announce the promising interim results from the NEPHSTROM first-in-patients clinical study, providing early-stage validation of the ORBCEL platform and confirming our belief that this novel cell immunotherapy has the potential to bring significant value to patients with DKD. At Orbsen Therapeutics, we are excited to be working with some of Europe's leading researchers and institutions through NEPHSTROM. Orbsen Therapeutics is at an exciting point in its journey to redefine cell therapy and look forward to progressing ORBCEL through clinical development and commercialisation."

Commenting on these results Professor Guiseppe Remuzzi, Director of the Mario Negri Institute for Pharmacological Research IRCCS, Bergamo, Italy commented: 

"The current standard of care for DKD patients includes multiple types of drug therapy, such as renin-angiotensin-aldosterone system inhibitors and the more recently approved drug class known as sodium-glucose transporter 2 (SGLT2) inhibitors, which have a proven ability to slow the decline of kidney function. However, these medication classes are not tolerated by all patients and are not always effective to fully halt or reverse the progression of kidney injury in DKD. ORBCEL cell therapy might be particularly useful as an additional treatment in patients with rapidly progressive kidney disease caused by diabetes."

Dr Stephen Elliman, Chief Scientific Officer of Orbsen Therapeutics Ltd said: 

"We're very encouraged by the safety profile and the preliminary efficacy signal that we have seen with our allogeneic cell therapy in patients with diabetes and chronic kidney disease. Our goal with ORBCEL is to resolve systemic inflammation and improve kidney function, so that these patients will not require dialysis or a kidney transplant. The growing burden of DKD and its impact on healthcare make this an important disease target for Orbsen and our technology."

Study Details

The NEPHSTROM for Diabetic Kidney Disease clinical trial[1] is a double-blind, randomized, placebo-controlled, dose-escalating Phase 1b/2a trial prospectively designed to enrol 48 adult patients with type 2 diabetes and established chronic kidney disease (CKD), already receiving standard of care therapy for DKD, who will receive a fixed dose of ORBCEL (80 million, 160 million, or 240 million cells), or placebo. The primary objective of the study is an evaluation of the number and severity of all pre-specified infusion-associated events and the overall number and frequency of adverse events, up to 18 months after cell or placebo infusion. Secondary objectives of the study included changes over baseline, compared to placebo, of glomerular filtration rate, urinary albumin/creatinine ration, urinary albumin excretion and prospectively defined blood markers. The results presented above are from the cohort of 16 patients who received either the 80 million cell dose of ORBCEL or placebo. Interim Results from patients treated in the second patient cohort (ORBCEL 160 million cells or placebo) are expected to be reported in the second half of 2023. 

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About Diabetic Kidney Disease

Type 2 diabetes is the single leading cause of end-stage kidney disease, accounting for nearly half of all end-stage kidney disease cases and over 40 per cent of new patients entering dialysis treatment. There are approximately 2 million cases of advanced DKD every year. With the current global diabetes population exceeding 450 million, over 6 million new patients are expected to develop DKD in the United States alone. For patients with end-stage kidney disease, the only treatment option is renal replacement therapy (dialysis or kidney transplantation) which incurs high medical costs and substantial disruptions to a normal lifestyle. For those with diabetes who require dialysis, the mortality rate is high with a 30-50% per cent fatality rate within three years. While kidney transplantation offers superior life expectancy for some people with end-stage kidney disease, including those with DKD, the availability of donor kidneys falls far short of the demand. As a result, approximately 50,000 persons in the United States have died while waiting on the transplant list. The current standard of care for CKD in type 2 diabetes includes multiple types of drug therapy, such as renin aldosterone angiotensin system inhibitions and SGLT2 inhibitors, with proven ability to slow the decline of kidney function. However, these medication classes are not tolerated by all patients and do not fully halt or reverse the progression of kidney injury. This leaves a large residual risk for end-stage kidney disease among persons with type 2 diabetes and a continued need for new therapeutic options.

About The NEPHSTROM EU Horizon 2020 Consortium (nephstrom.eu)

The research described above has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 634086, 'NEPHSTROM'. 

The NEPHSTROM project is a 12-partner pan-European consortium including four leading clinical Nephrology Centres of Excellence and four Cell Therapy GMP manufacturing facilities located in Ireland, Italy, the Netherlands and the UK. These partners have successfully collaborated over 7 years, including the development of a scalable Hub & Spoke network of GMP manufacturing facilities to locally manufacture and deliver Orbsen's ORBCEL cell therapy to 4 clinical centres for the NEPHSTROM clinical trial. The participating clinical sites are Bergamo, University of Galway, University Hospitals Birmingham NHS Foundation Trust and Belfast Health and Social Care Trust.

About Orbsen Therapeutics Limited

Orbsen Therapeutics is a global leader in stromal cell immunotherapy. The Company has leveraged its proprietary technology platform, which is based on highly purified stromal stem cells, to establish a specific portfolio of early-stage product candidates. Orbsen's allogeneic or 'off-the-shelf' cell product candidates target significantly advanced stages of diseases where there are high unmet medical needs, including moderate-severe acute respiratory distress syndrome (ARDS), autoimmune disease and Stage 3 DKD.

[1] ClinicalTrials.gov Identifier: NCT02585622

SOURCE Orbsen Therapeutics