Kleo’s KP1237 Therapy Soon Will Enter Clinical Testing, Following FDA’s Grant of New Drug Status

KP1237, an experimental therapy by Kleo Pharmaceutical that harnesses the body’s natural antibodies to fight cancers, will soon enter clinical testing for multiple myeloma, now that the U.S. Food and Drug Administration has granted it investigational new drug status.

The upcoming, single-arm trial will investigate the safety and tolerability of KP1237, working together with the body’s own natural killer (NK) cells, in 25 to 30 people who have received an autologous stem cell transplant — a transplant using their own blood-making stem cells that were treated in the lab and returned to their bodies. NK cells are a type of immune cell so named because they have the ability to kill tumor cells without any priming or prior activation.

Exploratory measures also include assessments of minimal residual disease (MRD) status — the small number of cancer cells that remain in the body after treatment —  about 90 to 100 days after the transplant. That evaluation will determine the proportion of patients who became negative for the very low number of remaining myeloma cells, which might cause the cancer to reappear.

Enrollment is planned to begin in the next months in the U.S., and topline results are expected by the end of 2021.

“We are excited to have clearance to initiate a clinical trial in the US that addresses a significant unmet medical need in newly diagnosed, post-transplant multiple myeloma patients,” Doug Manion, MD, Kleo’s CEO, said in a press release.

“Approximately 30,000 individuals are diagnosed with multiple myeloma in the United States each year, with at least 1/3 of those patients undergoing autologous stem cell transplants,” Manion noted.

KP1237 belongs to a class of therapies called antibody recruiting molecules (ARMs), which are small molecules that bind simultaneously to a target protein in cancer cells and to antibodies already present in the patient’s blood, regardless of their primary target.

These antibodies are then able to recruit immune cells, inducing the death of cancer cells. This is done through immune-mediated mechanisms, specifically one known as antibody-dependent cellular cytotoxicity (ADCC).

The experimental therapy is an ARM that recognizes and binds to CD38, a protein found at high levels on the surface of multiple myeloma cells. But unlike other CD38-targeting therapies, which also eliminate NK cells and other immune cells that produce the CD38 factor, KP1237 leaves these cells unharmed.

This allows researchers to couple KP1237 with NK cell therapies, which are expected to enhance the immune-mediated mechanisms that kill cancer cells.

Data presented at the 2019 American Society of Hematology (ASH) annual meeting in December showed that the small molecule effectively binds its cancer target and induces cell death by antibody-dependent mechanisms. The treatment needed higher doses to achieve the same anti-tumor activity as the approved CD38 antibody Darzalex (daratumumab).

However, the researchers found no signs of NK cell death nor complement-dependent cytotoxicity with KP1237. This was seen both in human cells and tumors cultured in the lab and in animal models of myeloma and lymphoma.

“By leveraging endogenous antibodies, ARMs can exploit the validate antitumor mechanisms mediated by IgG antibodies without any of the know pitfalls of recombinant, infused antibodies,” the researchers said in one of the posters presented at the meeting. “Based on this in vitro data and the in vivo efficacy data presented elsewhere, Kleo Pharmaceuticals is advancing a CD38-ARM program to the clinics for the treatment of multiple myeloma.”