Exicure’s investigational small molecule succeeded in mobilizing key blood-forming cells in almost 90% of patients in a phase 2 multiple myeloma trial, paving the way for smoother and more effective autologous stem cell transplants.
The open-label study hit its main goal, with 17 of 19 patients (89.5%) collecting at least 2 × 10⁶ CD34+ cells/kg within two leukapheresis sessions, the California company announced in a Dec. 8 release. The remaining two patients hit the same level after another session, according to Exicure.
The midstage data were shared yesterday at this year’s American Society of Hematology annual meeting in Florida.
Exicure’s trial assessed burixafor, a small molecule the biotech picked up from GPCR Therapeutics via acquisition at the beginning of this year. The asset is designed to block CXCL12 binding to CXCR4 receptors on hematopoietic progenitor cells (HPCs), which are early versions of blood-forming cells used for stem cell transplants.
Before Exicure gained ownership of burixafor, GPCR Tx had been investigating the asset in the phase 2 trial in combination with the approved beta blocker propranolol and granulocyte colony-stimulating factor (G-CSF), a naturally occurring protein that helps produce white blood cells in the bone marrow.
At the time of the deal, GPCR Tx had seen interim data from 10 patients in the trial.
Now, Exicure has taken the baton and carried the study over the finish line, reporting a median time of 13 days to neutrophil engraftment for an undisclosed number of patients that advanced to transplant. Meanwhile, the median time to platelet engraftment was 17.5 days.
Peak peripheral levels of CD34+ cells were recorded within an hour after administration of the investigational treatment, according to Exicure.
Out of the 19 patients, 16 (84.2%) had prior exposure to daratumumab, an approved cancer therapy that targets the CD38 protein and is associated with decreased mobilization, Exicure said in the release. The two patients who did not meet the primary endpoint within two sessions were both participants with past daratumumab exposure.
On the safety side, the burixafor combination was well tolerated, with no burixafor-related adverse events higher than a grade 2 event occurring, according to Exicure.
“In this phase 2 study, the combination of burixafor, G-CSF and propranolol showed an excellent safety profile and supported reliable mobilization of hematopoietic progenitor cells, allowing all participants who elected to proceed with transplant to undergo AHCT and successfully engraft,” Jack Khouri, M.D., the study’s lead investigator and associate professor of medicine for the Case Western Reserve University School of Medicine, said in the release.
“We’re encouraged by these results, particularly given the high proportion of participants previously treated with daratumumab, an agent which may reduce stem cell yield,” Khouri explained. “The ability to achieve peak circulating HPC levels rapidly after burixafor administration for immediate leukapheresis also has the potential to meaningfully improve the patient experience by reducing the burden of the mobilization process.”
Since market open, Exicure’s stock has shot up 65%, rising from Friday’s close of $5.27 per share to $8.73 as of 10:10 a.m. ET today.
The phase 2 win represents a turnaround for Exicure, a biotech that had been stymied by several years of obstacles.
The company’s troubles kicked off in 2021, when an internal review found that former neuroscience group leader Grant Corbett, Ph.D., had misreported data on a preclinical Friedreich's ataxia program. That program was discarded, leaving the company holding on tight to a few Big Pharma partnerships and a new lead asset in SCN9A.
But, by the end of 2022, AbbVie and Ipsen had walked away from Exicure, and the company’s SCN9A program failed in preclinical studies.
By 2023, the biotech had laid off the majority of its workforce and halted all R&D work. By the time the summer of 2024 came around, Exicure only had $500,000 in the bank and warned that a cash infusion was desperately needed to survive.
Luckily for Exicure, that cash was delivered via South Korean telecommunications company HiTron Systems, which bought $10 million of Exicure’s equity near the end of last year. The purchase made HiTron the biotech’s majority shareholder and allowed it to install a new CEO in the form of Andy Yoo.
At the time, Exicure said part of its new funds would go toward “pursuing strategic transactions,” with plans for the GPCR deal unveiled soon after.