The U.S. Food and Drug Administration (FDA) has given the designation of orphan drug to Immune-Onc Therapeutics’ investigational antibody-based therapy IO-202 for the treatment of acute myeloid leukemia (AML).
Orphan drug status is given to experimental therapies that aim to treat rare diseases — those affecting fewer than 200,000 people in the U.S. — to support their development. The designation provides certain benefits to treatment manufacturers, including financial incentives for clinical development and commercialization, fee and tax exemptions, and seven-year market exclusivity in the U.S. upon approval.
“Receiving orphan drug designation for IO-202 in AML is another important milestone for Immune-Onc and underscores the need for effective new treatments for this aggressive and hard-to-treat cancer,” Charlene Liao, PhD, CEO of Immune-Onc, said in a press release.
IO-202 is a man-made antibody that is designed to target and inhibit LILRB4 (also known as ILT3), a protein that normally promotes immune tolerance by preventing antigen-presenting cells (APCs) from being active and priming killer T-cells for action. Of note, APCs are specialized immune cells that can control the activity of killer T-cells, as well as redirect them toward their targets.
This natural immune tolerance mechanism is sometimes exploited by cancer cells to avoid being targeted and destroyed by T-cells. By inhibiting LILRB4, IO-202 is expected to boost T-cell activity toward malignant cancer cells.
In preclinical studies, IO-202 was found to promote T-cells’ immune reactivity toward AML cells cultured in a lab dish and to successfully eliminate them. Moreover, in mouse models, the antibody-based therapy inhibited AML tumor growth and prevented cancer cells from infiltrating into other tissues. Finally, experiments in primate models demonstrated IO-202 had a favorable pharmacological and safety profile.
Immune-Onc recently launched a Phase 1 trial (NCT04372433) to assess the safety and tolerability of increasing doses of IO-202 in adults with relapsed or refractory AML or chronic myelomonocytic leukemia (CMML).
The trial, underway at City of Hope, in California, and at the MD Anderson Cancer Center, in Texas, is currently recruiting participants. Up to 44 patients, ages 18 and older, will be enrolled; more information can be found here.
The study’s detailed design will be presented in a poster, titled “A First-in-Human (FIH) Phase 1 Study of the Anti-LILRB4 Antibody IO-202 in Relapsed/Refractory (R/R) Myelomonocytic and Monocytic Acute Myeloid Leukemia (AML) and R/R Chronic Myelomonocytic Leukemia (CMML),” at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, to be held online Dec. 5–8.
In the poster’s abstract, recently accepted for inclusion in the “Trials in Progress” session of the meeting, investigators at Immune-Onc and their collaborators listed the major inclusion and exclusion criteria of the trial, as well as its primary and secondary goals.
The main goal is to assess the safety and tolerability of increasing doses of IO-202, to determine its maximum tolerated dose, and the recommended dose to be used in future studies.
Secondary goals include assessing the therapy’s pharmacological properties and preliminary anti-cancer activity. Changes in the levels of LILRB4 and certain immune cell biomarkers also will be evaluated.
After determining IO-202’s recommended dose during the dose-escalation phase of the study — which will use an accelerated dose increment scheme to reduce patient exposure to low therapy doses — the investigators will administer the treatment’s optimal dose to an expansion group to assess its preliminary efficacy.
While IO-202 was originally designed to be given alone as a monotherapy, the trial also includes a protocol amendment that will allow the investigators to administer IO-202 in combination with other therapies, including Vidaza (azacitidine).
“As outlined in our ASH poster presentation, IO-202 holds promise for AML patients because it demonstrates novel mechanisms of action in overcoming immune suppression,” Liao said.
“IO-202 is one of several programs in our pipeline that target the LILRB family of immune inhibitory receptors. We are excited to continue our momentum in evaluating IO-202 and Immune-Onc’s preclinical candidates in other cancers, including solid tumors, in the near future,” Liao said.
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