RMC-035

RMC-035

RMC-035 is a so-called biological drug candidate designed to mimic the endogenous (human) protein A1M in its intact form. It is currently in clinical development to prevent and treat acute kidney injury that leads to permanent loss of kidney function, initially in patients undergoing open-heart surgery.

RMC-035 has received an IND (Investigational New Drug) clearance from the U.S. Food and Drug Administration (FDA), which means that RMC-035 can be administered to patients in clinical studies in the U.S.

Furthermore, RMC-035 has been granted Fast Track Designation by the FDA to reduce the risk of irreversible loss of kidney function, the need for dialysis, or death after open-heart surgery in patients at high risk for acute kidney injury.

RMC-035 is administered through intravenous infusion over a short treatment period, typically lasting a few days. The treatment is hospital-based and intended for patients at high risk of acute kidney injury, such as those undergoing open-heart surgery, kidney transplantation, or suffering from sepsis. The goal of the treatment is to prevent permanent loss of kidney function, thereby reducing the risk of end-stage renal disease (ESRD) requiring dialysis or kidney transplantation.

Due to its size and characteristics, RMC-035 is produced using recombinant technology in bacteria. The drug has been modified compared to the naturally occurring protein to make it suitable for use as a medication.

Intellectual property rights for RMC-035 are secured until 2037, with approved patents in major regions such as the U.S., EU, Japan, and China.

Kidney Injuries in Open-Heart Surgery

Open-heart surgery performed with the use of a heart-lung machine mainly involves coronary artery bypass grafting (CABG), with or without valve or aortic root surgery (the first part of the body's main artery). This type of surgery often causes significant kidney injury.

A major reason for this is reduced blood flow and oxygen supply to the kidneys (known as ischemia-reperfusion injury). Another contributing factor to kidney injury during surgery is hemolysis, where red blood cells are damaged, leading to kidney injury due to harmful breakdown products from hemoglobin, the oxygen-carrying substance. Hemolysis occurs when blood circulates outside the body via the heart-lung machine and during blood transfusions, which are often administered during the procedure.

In addition to oxygen deficiency and hemolysis, secondary inflammation often arises, contributing to ongoing kidney injury, increasing the risk of scarring and permanent loss of kidney function.

Clinical Studies of RMC-035 in Open-Heart Surgery

RMC-035 has been evaluated in a comprehensive Phase 1 program and a global Phase 2a study (proof-of-concept), known as the AKITA study. The subsequent Phase 2b study, POINTER, began in the third quarter of 2024.

About the AKITA Study (Phase 2a)

AKITA is a global, randomized, double-blind, placebo-controlled Phase 2a study aimed at evaluating the kidney-protective effect of RMC-035 in patients at increased risk of developing kidney injury during open-heart surgery.

The study included a total of 177 patients, and the results showed a clinically meaningful and statistically significant improvement in kidney function with RMC-035 compared to placebo 90 days post-surgery. Positive treatment effects were observed based on two different efficacy measures: changes in kidney function (estimated glomerular filtration rate, eGFR) and a reduction in the number of major adverse kidney events (MAKE), a composite endpoint which include either death, dialysis, or ≥ 25% loss of kidney function.

Akita

About the POINTER Study (Phase 2b)

POINTER is a randomized, double-blind, placebo-controlled Phase 2b study aimed at determining an optimal dosing regimen and the exact target population for RMC-035 treatment prior to subsequent pivotal Phase 3 study.

The study is expected to enroll approximately 160 patients, divided into two dosing arms of RMC-035 (60 mg and 30 mg) and a control arm (placebo). An independent Data Monitoring Committee (DMC) will perform pre-defined interim safety evaluations based on data from approximately one third and two thirds of the planned number of patients. Results of these analyses will be blinded to Guard Therapeutics.

Patient recruitment began in the third quarter of 2024 and is expected to continue for about a year, with overall study results anticipated approximately six months after the completion of patient recruitment.

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Clinical Studies of RMC-035 in Kidney Transplantation

RMC-035 has been evaluated in a Phase 1b clinical study of patients undergoing kidney transplantation to assess its safety profile and pharmacokinetics in this patient group. The next steps in the clinical program for kidney transplantation will be evaluated after the POINTER study.