Investigational Myeloma Treatment KP1237 Wins FDA Orphan Drug Status

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to Kleo Pharmaceuticals‘ KP1237, an investigational treatment for multiple myeloma.

The designation grants various development incentives to medications that address rare disorders affecting fewer than 200,000 people annually in the U.S. Incentives include regulatory support and financial benefits that will help accelerate the clinical development of KP1237, and seven years of marketing exclusivity if regulatory approval is ultimately granted.

“We are pleased to receive this orphan drug designation for KP1237, which is advancing to Phase 1 clinical testing in the fourth quarter of 2020,” Doug Manion, MD, CEO of Kleo, said in a press release.

KP1237 is an antibody recruiting molecule (ARM) that targets CD38, a molecule found on the surface of myeloma cells. Antibody therapies that target CD38 have shown efficacy, and been approved for use, in the treatment of multiple myeloma.

In these therapies, an antibody itself is the active drug, and the therapeutic effect is achieved by the antibody binding to CD38 on myeloma cells, which can kill these cells through several mechanisms. As an ARM, KP1237 achieves a similar end result, but through a different mechanism.

ARMs like KP1237 are able to bind to a particular molecule target — in this case, CD38 — and recruit antibodies that are already in the body to that target. This results in an antibody binding indirectly to CD38.

In theory, ARMs pose several advantages over antibody therapies: they are smaller than antibodies, which means they may be able to penetrate tumor tissue more effectively, and higher doses might be feasible without causing safety problems.

Additionally, while antibody therapies are almost always given by injection, ARMs might be suitable as oral therapies. Further, the molecular components used to make ARMs are more easily interchangeable than for antibody therapies, so the same ARM-based platform can be more easily tailored for different molecular targets.

Kleo is evaluating KP1237 as a systemic therapy in cases of multiple myeloma that either failed to respond (refractory) or returned after first responding (relapsed) to Darzalex (daratumumab), a CD38-targeting antibody that is FDA-approved to treat myeloma.

The investigational medication also is being evaluated in combination with patients’ own natural killer (NK) cells in people with newly diagnosed multiple myeloma who have minimal residual disease — the small number of cancer cells that remain after treatment — after undergoing a stem cell transplant.

Clinical trials for both of these programs are expected to begin before the end of this year.

Kleo also is planning to assess KP1237 in combination with donor-derived (off-the-shelf) NK cells.

“Based on compelling preclinical data, we will evaluate KP1237 in potentially three different clinical programs where KP1237 can have the greatest impact in patients whose options may be severely limited,” Manion said.