FDA Grants Orphan Drug Designation to ISB 1442 for Relapsed/Refractory Multiple Myeloma

The FDA has granted an orphan drug designation to ISB 1442, the first-in-class biparatopic 2+1 BEAT®bispecific antibody targeting CD38 and CD47 for the treatment of patients with relapsed/refractory multiple myeloma, according to an announcement from Ichnos Sciences.¹

“Receiving orphan drug designation for ISB 1442 is an important milestone on Ichnos' journey to developing potentially curative therapies for patients with multiple myeloma. Reported new cases are on the rise year over year, making the potential clinical applications for ISB 1442 more relevant than ever before,” Cyril Konto, MD, president and chief executive officer of Ichnos Sciences, said in a press release. “It feels fitting to share this milestone during Multiple Myeloma Awareness Month, when our industry joins with patients and healthcare providers to highlight our shared commitment to curing this disease.”

ISB 1442 is based on Ichnos’ proprietary BEAT® multispecific antibody platform, which leads to the development of immune cell engagers. The agent is a 2+1 biparatopic bispecific antibody with CD38 and CD47 targeting domains.² Compared with daratumumab (Darzalex), the agent includes two fragment antigen–binding regions that can bind to distinct CD38 epitopes. Additionally, the agent is engineered with an Fc domain that enhances antibody-dependent cellular phagocytosis, complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC).

Previously presented preclinical data have shown that ISB 1442 leads to higher CDC and ADCC relative to daratumumab. Moreover, ISB 1442 demonstrated improved tumor growth inhibition compared with daratumumab in a xenograft model. ISB 1442 also led to more favorable on-target specificity with reduced binding on red blood cells, hemagglutination, and RBC depletion compared with an anti–CD47-directed monoclonal antibody.

The agent is now under study in a first-in-human phase 1/2 study (NCT05427812), which began dosing with the agent in Australia in September 2022, with United States sites planned to open in the second quarter of 2023.

To be eligible for enrollment in this trial, patients must have relapsed/refractory multiple myeloma with measurable disease following treatment with at least 3 prior lines of therapy, including a CD38 antibody, immunomodulatory drugs, and proteasome inhibitors, and who must not be candidates for regimens known to provide clinical benefit.

The phase 1 dose-escalation portion of the trial will enroll approximately 46 patients and evaluate accelerated and standard titrations in a 3+3 dose-escalation design. Phase 2 will enroll approximately 75 patients. Patients will be divided into 2 cohorts: cohort A will comprise up to 44 patients with relapsed/refractory disease and cohort B will include up to 34 patients with relapsed/refractory disease post CAR T-cell therapy.

The primary objective in phase 1 is to evaluate the safety and tolerability of the agent and determine the maximum tolerated dose and recommended phase 2 dose of the drug. In phase 2, efficacy will serve as the primary objective. Secondary objectives include pharmacokinetic and immunogenicity analysis.

References

1. Ichnos Sciences receives orphan drug designation for first-in-class bispecific (CD3 x CD47) antibody innate cell modulator, ISB 1442. News release. Ichnos Sciencies. March 21, 2023. Accessed March 21, 2023. https://www.prnewswire.com/news-releases/ichnos-sciences-receives-orphan-drug-designation-for-first-in-class-bispecific-cd38-x-cd47-antibody-innate-cell-modulator-isb-1442-301775354.html
2. Sia H, Tan PT, Richter J, et al. A phase 1/2, first-in-human, multicenter, open-label, dose escalation and dose-expansion study of single-agent ISB 1442 in patients with relapsed/refractory multiple myeloma. Blood. 2022;140(suppl 1):10182-10184. doi:10.1182/blood-2022-157585