Phases of the Project

REDDSTAR consists of two Preclinical Phases (PP1 and PP2) and two Clinical Phases (CP1 and CP2). PP1 and CP1 will progress in parallel, followed by PP2 and CP2, also in parallel.

 

 

Preclinical Phase 1 (PP1)

PP1 will assess the safety and efficacy of the SSC populations in alleviating nephropathy, retinopathy, cardiomyopathy, neuropathy, impaired bone repair and wound ulceration associated with diabetes.  In PP1, the novel ORB1 antibody will be used to isolate ORB1+SSC and ORB1-SSC from human, rabbit, rat and murine bone marrow.  These SSC populations will be isolated, expanded and prepared for adoptive transfer into models of diabetic complication.

In this first preclinical phase, adoptive transfer experiments will focus on determining the optimal SSC dose and optimal route of SSC administration. Thus, PP1 will discern if ORB1+, ORB1- or PA-SSC can safely and effectively attenuate/limit progression of each diabetic complication. As SSC delivery has been shown to improve glycemic control, the impact of SSC transplantation upon blood glucose will also be assessed in each model. The preclinical safety and efficacy data from PP1 will be reviewed and the complication which responded most favourably to SSC treatment will be prioritised for First in Human (FIH) clinical studies by REDDSTAR partners.  PP1 will culminate in an Investigator Brochure (IB) that will comprise the relevant SSC efficacy and risk data in the selected indication and will support a clinical trial application in CP2 below.

Clinical Phase 1 (CP1)

In CP1, cGMP protocols governing the isolation, expansion and cryopreservation of ORB1+, ORB1- and PA-SSC will be developed.  The Nanosorter® [1] will be customised for REDDSTAR clinical studies to sort ORB1+ and ORB1- SSC from human bone marrow.  An Investigational Medicinal Product Dossier (IMPD) will be produced describing the ORB1-SSC therapeutic for submission as part of a clinical trial application in CP2 below.  In addition, clinical doses of GMP-compliant ORB1-SSC will be produced for administration in the REDDSTAR Phase Ib Clinical Trial.

Preclinical Phase 2 (PP2)

PP2 will investigate the mechanism of action for SSC therapeutic alleviation of complications.

The preclinical mechanism of action data will be collated for review using a novel cloud-based software technology. The output of PP2 will be mechanism of action data that will be used to develop SSC potency/bioassays [2] that will be required for the IMPD and IB in any subsequent Phase-2 clinical trial.

Clinical Phase 2 (CP2)

In CP2, REDDSTAR clinical partners will prepare a Clinical Trial Application to the Danish Medicines Agency to undertake a Phase Ib, dose escalation study that will assess the safety of ORB1-SSC in diabetic patients with the indication chosen at the end of PP1. The application to the DMA will combine the safety and efficacy data compiled in the IB in PP1, the IMPD from CP1 and a Clinical Trial Protocol. The primary endpoint of the REDDSTAR Phase Ib trial will be safety at all 3 doses.  It should be noted that if more than one indication emerges with promising data from PP1 and CP2 provides robust clinical safety data, REDDSTAR may lead to two or more Phase-2 efficacy studies in patients with diabetic complications.

 


[1] The Nanosorter® is the world’s first MEMS-based bench-top FACS, which will be used to support the large-scale high-speed stem cell sorting that is a critical element of the REDDSTAR technical platform. The Owl Nanosorter® enables sterile, high-speed, scalable isolation of highly specific cells using a cGMP-compliant and fully enclosed disposable, sterilized sort cartridge.   The Nanosorter® permits sequential sorting to be performed to generate different sub-populations, enabling cGMP scale up of novel therapies such as ORB1-SSC.

[2] Bioassays are measurements of the concentration or potency of a substance by its effect on living cells or tissues.

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