OPN-6602 Granted Orphan Drug Designation in R/R Multiple Myeloma

Data from a multiple myeloma mouse xenograft model demonstrated promising tumor regression activity from OPN-6602 monotherapy and in combination with standard of care agents.

OPN-6602, an oral, small molecule inhibitor of the E1A binding protein and CREB-binding protein, has been granted orphan drug designation (ODD) by the FDA for the treatment of patients with relapsed/refractory multiple myeloma, according to a press release from the developer, Opna Bio.¹

The agent is currently being evaluated in a dose escalation/dose expansion, open-label phase 1b trial (NCT06433947). The trial is assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OPN-6602 monotherapy and when it’s administered with dexamethasone in those with relapsed/refractory multiple myeloma.

In December 2024, data from the trial that investigated the efficacy in multiple myeloma mouse xenograft models was presented at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH).²

We are pleased to have received ODD for OPN-6602 for the treatment of multiple myeloma, a further validation of the drug’s therapeutic potential in patients with this disease who have limited treatment options once they have relapsed,” Gideon Bollag, PhD, chief scientific officer at Opna Bio, stated in the press release.¹

In multiple myeloma mouse xenograft models, OPN-6602 monotherapy demonstrated 71% tumor suppression vs 100% tumor regression when used in combination with dexamethasone, pomalidomide (Pomalyst), or mezigdomide.² OPN-6602 and mezigdomide also generated a substantially increased duration of response. Key multiple myeloma drivers and signature genes were also downregulated by OPN-6602, as was made clear by RNA sequencing of treated tumors.

The BCL2, CCND2, ETV6, IRF4, MEF2D, MYB, MYC, and PIM2 genes demonstrated reduced expression due to OPN-6602 treatment, which was enhanced, then the agent was combined with pomalidomide or mezigdomide.

The phase 1b trial will consist of 3 parts: part 1a, an OPN-6602 monotherapy dose escalation phase; part 1b, an OPN-6602 with dexamethasone dose escalation phase; and part 2, a dose expansion of the preferred regimen phase.³ Part 2 is intended to select and optimize the dosage with 1:1 randomization between at least 2 dose levels with 20 patients at each level. The trial will enroll up to 130 patients.

Eligible patients have a confirmed diagnosis of multiple myeloma; are relapsed or refractory to 3 or more prior lines of therapy for multiple myeloma that included immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies who are not eligible for established therapies known to provide clinical benefit; and have adequate hematologic, renal, liver, and cardiac function.⁴

Exclusion criteria include monoclonal gammopathy of undetermined significance, smoldering myeloma, Waldenstrom’s macroglobulinemia, or IgM myeloma; active plasma cell leukemia; prior Stevens Johnson syndrome; localized radiation therapy to disease sites within 2 weeks of first dose; prior chemotherapy, targeted anticancer or radiation therapy within 2 weeks prior to first dose; prior allogenic stem cell transplantation or solid organ transplantation within 12 months of screening; known central nervous system involvement my multiple myeloma; and poorly controlled type 2 diabetes.

Trial end points include number and type of dose-limiting toxicities; number and type of treatment-emergent adverse events; and number of participants with clinical laboratory test abnormalities.

In the mouse xenograft model, lead study author Bernice Matusow, MS, director of preclinical development at Opna Bio, and coinvestigators wrote, “In preclinical human derived multiple myeloma models, OPN-6602 suppresses tumor growth with synergistic effects observed in combination with dexamethasone, pomalidomide, and mezigdomide. Further development of OPN-6602 in combination with other standard of care agents in multiple myeloma is planned.”²

Additional development of OPN-6602 with other standard of care agents in multiple myeloma is planned.

Reference

1. Opna Bio receives orphan drug designation for OPN-6602, an oral EP300/CBP bromodomain inhibitor, for multiple myeloma. News release. Opna Bio. February 12, 2025. Accessed February 13, 2025. https://tinyurl.com/4a46e9zs
2. Matusow B, Saghafinia S, Li PP, et al. OPN-6602, an orally bioavailable EP300/CBP bromodomain inhibitor, targets multiple myeloma through suppression of IRF4 and MYC. Blood. 2024;144(Suppl 1):1908. doi:10.1182/blood-2024-208181
3. Walling JM, Matusow B, Nichols C, et al. A phase 1b, dose escalation/dose expansion, multicenter, open-label study to assess the safety and tolerability of OPN-6602 monotherapy and in combination with dexamethasone in subjects with relapsed and/or refractory multiple myeloma. Blood. 2024;144(suppl 1):7022. doi:10.1182/blood-2024-205626
4. Study to assess safety and tolerability of OPN-6602 in subjects with relapsed and/​or refractory multiple myeloma. ClinicalTrials.gov. Updated December 10, 2024. Accessed February 13, 2025. https://tinyurl.com/4yzzmhdf