FDA Grants Orphan Drug Designation to Novel Fusion Peptide in Multiple Myeloma

The FDA has granted orphan drug designation to the investigational compound OM-301 for the treatment of patients with multiple myeloma, according to a press release from Oncolyze.¹

Investigators will initiate a phase 1/2 trial evaluating OM-301 in 2023.

OM-301 has previously demonstrated efficacy against multiple myeloma in preclinical models. According to findings published in Blood, OM-301, although designed for p53-selective cells, may interact with Bcl-2, which effectively induces mitochondrial dysfunction and cell death regardless of TP53 status.² Overall, investigators concluded that the agent may be a novel and effective therapeutic option for managing multiple myeloma.

At an intraperitoneal dose of 20 mg/kg twice a day, OM-301 significantly reduced tumor size in preclinical in-vivo models with respect to vehicle control, suggesting the agent’s stability without any loss of activity (P <.0001). Additionally, the agent significantly increased survival in a disseminated model (P <.0001).

Cells treated with OM-301 also demonstrated alterations in genes including those involved in inflammatory responses, fatty acid metabolism, glucose metabolism, and oxidative phosphorylation. Investigators also dissected the compound’s underlying mechanism by dual-tagging it with fluorophores to evaluate its localization and stability in multiple myeloma cells. Through this process, OM-301 was deemed stable and primarily localized in the cytosol.

In an evaluation of the impact of OM-301 on mitochondrial function and physiology, treatment with the agent decreased mitochondrial membrane potential in different multiple myeloma cell lines. Additionally, the agent increased production of mitochondrial superoxide, inducing mitophagy, and mitochondrial fission was observed through electron microscopy.

The investigational fusion peptide OM-301 binds to HDM2 that is expressed on the surface of cancer cells, selectively creating pores in these cells to induce their death.³ Manufacturers of OM-301 describe the process as a “molecular icepick,” as the process of poking holes in cancer cells causes extracellular fluid to rapidly enter the cell through an osmotic mechanism.⁴ The cell then rapidly enlarges and experiences increased tension in the stretched membrane until it pops open.

Investigators are evaluating OM-301 in multiple hematologic and solid cancer types, envisioning the agent being administered as an intravenous infusion once a day. According to its manufacturers, results from upcoming clinical trials will help determine a specific dosing schedule for the agent.

Investigators plan to advance OM-301 through Good Manufacturing Practices toxicology, submit an investigational new drug application to the FDA, and initiate a first-in-human phase 1/2 clinical trial evaluating the agent in 2023.

The FDA previously granted orphan drug designation to OM-301 for the management of acute myeloid leukemia (AML) in January 2022.⁵

“The orphan drug designation is an important milestone that further validates our efforts to investigate the value of OM-301 as a potentially groundbreaking therapy for patients with AML and other cancers,” Steven Evans, MD, co-founder and chief executive officer of Oncolyze, said in a press release on the orphan drug designation in AML.

References

1. Oncolyze announces FDA orphan drug designation for OM-301 for the treatment of multiple myeloma. News release. Oncolyze. April 11, 2023. Accessed April 14, 2023. bit.ly/3MHLSug
2. Nigam L, Zhu Y, Troadec E, et al. OM301, a synthetic polypeptide containing the p53TA (transactivation) domain, impairs mitochondrial activity and survival of myeloma cells. Blood. 2021;138(1):2661. doi:10.1182/blood-2021-151506
3. Pipeline. Oncolyze. Accessed April 14, 2023. bit.ly/404cHM9
4. “Not your grandfather’s HDM2.” Oncolyze. Accessed April 14, 2023. bit.ly/41vmHza
5. Oncolyze announces FDA orphan drug designation for OM-301 for the treatment of acute myeloid leukemia. News release. Oncolyze. January 5, 2022. Accessed April 14, 2023. bit.ly/3KEifHw