Science

AIDE Technology Platform

Our proprietary Autologous Intracellular Drug Encapsulation, or AIDE, technology platform is an innovative drug/device combination platform that uses an automated process to encapsulate a drug into a patient’s own red blood cells.

Red blood cells have several characteristics that make them a potentially ideal vehicle for drug delivery, including potentially better tolerability, enhanced tissue biodistribution, reduced immunogenicity, and prolongation of circulating half-life. Our AIDE technology is designed to harness many of these benefits to allow for the chronic administration of drugs that have limitations due to toxicity, poor biodistribution, suboptimal pharmacokinetics, or immune response. In this way, the flexibility of our AIDE technology is believed to confer several benefits over conventional therapies and can be applied to a broad range of small or large molecule drugs and biologics. Additionally, the AIDE technology’s use of autologous red blood cells in the encapsulation process is different from standard cell therapies, such as synthetic or engineered cells, as well as distinct from typical blood transfusions that utilize donor red blood cells for drug administration to the patient. The use of autologous blood may minimize safety risks associated with the use of donor blood and may reduce the potential immunogenic risks associated with donor cells and synthetic cell therapies.

AIDE – Autologous Intracellular Drug Encapsulation

Our AIDE technology platform reflects more than 20 years of innovation and approximately $100 million of investment, which has resulted in innovation that creates high barriers to competitive entry. The AIDE technology drug/device combination consists of a proprietary CE marked non-invasive automated device called the RCL, along with a sterile, single-use treatment kit.

Potential Benefits of Red Blood Cell Encapsulated Drug Delivery

Many efficacious drugs have limited therapeutic potential because of toxicity, while other drugs may have efficacy limitations due to biodistribution, pharmacokinetics, and pharmacodynamics. Our proprietary AIDE technology uses an automated process designed to encapsulate a drug into the patient’s own red blood cells to deliver a therapy in a potentially more effective and safer method. Autologous red blood cells have several characteristics that make them an ideal vehicle for drug delivery:

Potential for improved biodistribution as encapsulated drug in autologous red blood cells is designed to enable the slow release of the drug from the red blood cells while circulating through various tissue beds.

Potential for altered pharmacokinetics and pharmacodynamics, including long circulating half-life, and altered or improved tissue biodistribution. The altered pharmacokinetics and pharmacodynamics of the encapsulated drug may significantly increase the desired therapeutic effect and improve the safety profile of the therapy.

Potential for the encapsulation of small or large molecules, peptides, and proteins inside of autologous red blood cells to limit biodegradability and immunogenicity..

Potential for avoiding issues with donor compatibility associated with heterologous cells.

Lead Asset eDSP and Addressing Limitations of Chronic Corticosteroid Administration

eDSP (previously referred to as EryDex) is the first product in development that leverages our AIDE technology and is composed of dexamethasone sodium phosphate (DSP) encapsulated in autologous red blood cells targeted for the treatment of patients with Ataxia-Telangiectasia, or A-T. DSP is a corticosteroid well described for its anti-inflammatory properties, but is coupled with serious adverse effects, including potential long-term adverse effects due to adrenal suppression. eDSP is designed to maintain the efficacy of corticosteroids while reducing or eliminating the significant adverse effects associated with corticosteroid treatment. Our AIDE technology is designed to encapsulate DSP in a patient’s own red blood cells and to alter the biodistribution, pharmacokinetics, and pharmacodynamics of the DSP to deliver a therapy in a potentially more effective and safer method.

The optimal efficacy of corticosteroids is the result of two pharmacokinetic characteristics: 1) an initial bolus to achieve a high Cmax that results in high levels of corticosteroid receptor occupation; and 2) sufficient sustained tissue concentrations that allow for continued receptor site occupancy over time.

In order for a conventional corticosteroid to achieve these characteristics, the drug must be dosed frequently, typically daily. Long-term daily dosing regimens sufficient to provide efficacy, lead to chronic adverse effects such as hyperglycemia, immunosuppression, and suppression of the HPA axis. Corticosteroid therapy without significant long-term safety liabilities would represent a major advancement in the treatment of many chronic diseases where corticosteroids are already known to be beneficial.

Pharmacokinetics of daily IV dexamethasone

Note: Pharmacokinetic (PK) curve from Population PK model (smoothed) based on company’s prior studies of eDSP. Information represented does not reflect a completed comparative study of eDSP versus oral/IV administration of dexamethasone, but rather provides a comparison of published corticosteroid pharmacokinetic information relative to company data regarding eDSP. IC50 and SC50 refer to pharmacodynamic parameters of which IC50 reflects drug concentration eliciting 50% of the maximum inhibition and SC50 reflects drug concentration eliciting 50% of the maximum stimulation. References: Montanha et al, Frontiers in Pharmacology (2022) 13: 814134; Krzyzanski et al, Journal of Pharmacokinetics and Pharmacodynamics (2021) 48: 411-438; Świerczek A, Jusko WJ., Clinical and Translational Science (2023) 16(9):1667-1679.

Highly Differentiated and Proprietary Drug/Device Combination

Our proprietary AIDE technology platform is a novel drug/device combination that uses an automated process designed to encapsulate a drug into the patient’s own red blood cells. The AIDE technology drug/device combination consists of a specialized automated equipment including the RCL and a sterile single-use treatment kit.

RCL Machine

Red Cell Loader (RCL)

The RCL is a proprietary CE marked non-invasive device that allows blood processing at the point of care. It automates the AIDE process technology by handling the blood, drug, and processing solutions with the use of the single-use treatment kit. The system has a user-friendly touch screen interface made up of three microprocessor circuit boards, two main boards, and an independent protective board as control.

Single-Use Treatment Kit

The single-use treatment kit is a CE marked medical device. It provides the essential single-use components for loading human red blood cells with variety of therapeutics, ranging from small to large molecules, as well as biologics, by using the RCL. The treatment kit contains a sterile, single use, pyrogen-free disposable blood tubing system equipped with a centrifuge, hemoconcentrator filter, bags, organizer cassette, and other accessories.

EryKit Consumables

AIDE Technology Fully Automated at Patient Point-of-Care

The automated AIDE process and treatment is designed to be completed at the point-of-care and includes a series of steps which take approximately two hours from start to finish. This process includes:

AIDE Technology at Point-of-Care

Collection of 50mL of a patient’s blood.

Loading the patient's collected blood in the RCL using the sterile, single-use treatment kit.

Autologous red blood cells in the RCL are swollen and their pores are “opened” using two hypotonic process solutions.

Drug is added to the RCL and enters into the opened red blood cells.

Physiological osmotic conditions are then restored by adding a hypertonic solution that “reseals” the red blood cells.

Drug that is not encapsulated during the process is removed by extensive washing.

Upon completion of the process, the drug encapsulated red blood cells are infused into the patient.