INV724 Earns FDA Rare Pediatric Disease, Orphan Drug Designations for Neuroblastoma

FDA

The FDA has awarded rare pediatric disease designation and orphan drug designation to INV724 for the treatment of patients with neuroblastoma.¹

Developed in collaboration with Carbone Cancer Center of the University of Wisconsin, INV724 is a novel antibody designed to target GD2 and B7-H3 tumor antigens, and the agent is intended to mitigate the pain associated with GD2-targeted therapies. In preclinical studies, the agent displayed therapeutic potential and robust developability, according to the agent’s developer, Invenra.

“Anti-GD2 antibodies are a key component in treating neuroblastoma, but their use is often limited by severe pain due to nerve binding. Our studies indicate that INV724 binds effectively to neuroblastoma cells while sparing nerves, offering a significant advantage over existing therapies,” Paul Sondel, MD, PhD, professor of pediatrics and human oncology at the University of Wisconsin, stated in a news release. “Our next goal is to transition from laboratory research to clinical trials, aiming to provide effective treatment with fewer [adverse] effects [AEs].”

Rare pediatric disease designation and orphan drug designation allow for potential benefits in drug development, including transferrable priority review, extended market exclusivity, and eligibility for grants and research support.

“Invenra’s work with INV724 opens the door to developing a new agent that may offer enhanced antitumor activity with reduced AEs,” Julie R. Park, MD, chair of the Department of Oncology at St. Jude Children’s Research Hospital and Scientific Chair of NANT, added in a news release.

INV724 was developed using Inverna’s B-Body platform, which is designed to overcome the challenges in discovery and manufacturing of bispecific antibodies. The platform has yielded products in the range of 6 g/L to 11 g/L, topping known bispecific antibody platforms.² The platform is also intended to address other issues in the production of bispecific antibodies, such as validated production, proper assembly, purity, and compatibility.

GD2 is overexpressed in certain cancers, including melanoma and neuroblastoma, making it a potential actionable target. However, IgG antibodies designed to target GD2 have been limited by the co-expression of GD2 on nerves, leading to toxicities such as severe neuropathic pain.³

In order to overcome the off-target effects of targeting GD2, researchers developed a next-generation bispecific antibody targeting both GD2 and B7-H3 to improve tumor selectivity.

In a preclinical study, investigators transduced B7-H3 into GD2-positive murine melanoma cells. Findings showed that the bispecific antibody bound to GD2-positive, B7-H3–positive B78 cells with high avidity; however, this avidity was not observed with GD2-positive, B7-H3–negative cells.

With higher selectivity for cells expressing both GD2 and B7-H3, researchers concluded that this form of treatment could help reduce the toxicities associated with targeting GD2 by reducing off-target GD2 binding in nerves.

“Invenra is deeply committed to advancing INV724 as a potentially transformative treatment for children with neuroblastoma. The FDA's rare pediatric disease and orphan drug designations not only validate our innovative approach but also give us the critical support to fast track its development in collaboration with potential partners. We are eager to bring this therapy to patients who need it most,” Roland Green, chief executive officer or Invenra, added in a news release.¹

References

1. Invenra’s novel antibody INV724 receives rare pediatric disease and orphan drug designations from the US FDA for neuroblastoma treatment. News release. August 23, 2024. Accessed August 23, 2024. https://www.businesswire.com/news/home/20240823081052/en
2. B-Body: The Premier Bispecific Antibody Platform. Inverna. Accessed August 23, 2024. https://invenra.com/our-science/
3. Rosenkrans ZT, Erbe AK, Clemons NB, et al. Targeting both GD2 and B7-H3 using bispecific antibody improves tumor selectivity for GD2-positive tumors. bioRxiv [Preprint]. Published online May 30, 2024. doi:10.1101/2024.05.23.595624.