ISB 1442 Lands FDA Orphan Drug Status for R/R Multiple Myeloma

The FDA has granted an orphan drug designation to ISB 1442, for the treatment of patients with relapsed/refractory multiple myeloma, according to Ichnos Sciences.¹

ISB 1442 is a 2+1 biparatopic bispecific antibody that has CD38 and CD47 targeting domains. The agent is based on the proprietary BEAT® multispecific antibody platform, by Ichnos, which allows for the development of immune cell engagers.²

Notably, ISB 1442, compared with daratumumab (Darzalex), binds to different CD38 epitopes and includes 2 fragment antigen–binding regions. With Fc domain engineering, the agent induces antibody-dependent cellular phagocytosis, complement-dependent cytotoxicity, and antibody-dependent cell-mediated cytotoxicity.

“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,” said Cyril Konto, MD, president and chief executive officer of Ichnos Sciences, in a press release.¹ “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.”

Previously, preclinical data have demonstrated that ISB 1442 has a higher killing potency of CD38 high- and low-expressing tumors compared with daratumumab. ISB 1442 also shows low on-target off-tumor binding and no red blood cell depletion compared with anti-CD47 monoclonal antibodies.²

Now, the agent is being evaluated in a first-in-human, multicenter, open-label, phase 1/2 study (NCT05427812). The trial began dosing ISB 1442 in patients with relapsed/refractory multiple myeloma in Australia in September 2022. Sites in the United States plan to open in the second quarter of 2023.

Enrollment in the trial is open to patients with relapsed/refractory multiple myeloma who have measurable disease after treatment with a minimum of 3 prior lines of therapy, including a CD38 antibody, immunomodulatory drugs, and proteasome inhibitors. Patients eligible for enrollment must also not be candidates for regimens that are known to provide clinical benefit.

The study will consist of a dose-escalation phase (phase 1), which will enroll approximately 46 patients who will be treated at escalating doses. This phase of the trial plans to assess accelerated and standard titrations using a 3+3 dose-escalation design.³

Then, phase 2 will enroll approximately 75 patients once the recommended phase 2 dose (RP2D) is established. This phase will split patients into 2 cohorts. In cohort A, up to 44 patients with R/R disease will be included while cohort B will consist of up to 34 patients with R/R disease after they have received chimeric antigen receptor T-cell therapy. Patients will continue to receive ISB 1442 until disease progression, unacceptable toxicity, or any other reason for stopping treatment with the study drug.

Investigators are assessing the primary end point of safety and tolerability in phase 1 and are also looking to determine the maximum tolerated dose and RP2D of ISB 1442. Phase 2 will evaluate the primary end point of efficacy. Secondary end points include evaluating pharmacokinetics and immunogenicity.

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://prn.to/42npZ8W

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-2022-15758

3. Phase 1/2 study of ISB 1442 in relapsed/refractory multiple myeloma. ClinicalTrials.gov Updated October 17, 2023. Accessed March 21, 2023. https://clinicaltrials.gov/ct2/show/NCT05427812