Novel Immunotherapy QXL138AM Wins Orphan Drug Status in US
The first-in-class therapy is designed to kill targeted cancer cells without the “significant toxicities” of other treatments also based on the interferon-alpha (INF-alpha) protein, Nammi said in a press release.
“By reducing systemic activation of the immune system, Nammi expects to improve safety and enhance the ability to combine multiple immune modulators,” the company said.
Orphan drug status is given to treatment candidates that may be safe and effective for rare, life-threatening, or chronically debilitating conditions that have no approved treatments, or where an experimental therapy shows the potential for significant benefit over existing treatments.
This designation is meant to expedite QXL138AM’s clinical development and review by providing regulatory support and financial benefits, as well as a seven-year marketing exclusivity period upon regulatory approval, if granted.
Nammi said it expects to file an application to the FDA later this year asking to test the therapy in clinical trials.
Myeloma is a rare type of blood cancer characterized by the excessive growth of a type of immune cell called a plasma cell. Malignant plasma cells are dubbed myeloma cells.
Therapies based on INF-alpha, an immune-regulating signaling protein involved in the fight against pathogens and cancer, have been shown to have anti-tumor effects in clinical trials. However, these treatments are not commonly used because they are highly toxic.
This is mainly due to the fact that the receptor protein of INF-alpha is located at the surface of most cell types in the body. Administering an INF-alpha-based therapy activates its receptor and its signaling cascade throughout the body.
QXL138AM, a new type of masked immunocytokine (MIC), was designed to overcome this toxicity issue by promoting interferon-alpha signaling activation only in tumor cells.
It comprises an antibody that specifically binds to CD138 — a protein present at the surface of plasma cells, but at higher levels in myeloma cells — and that is fused with a masked INF-alpha 2b.
This INF-alpha 2b molecule is masked with small proteins that prevent its binding to IFN receptors and that can be broken down by enzymes located at the surface of tumor cells. This means that the antibody-fused IFN-alpha 2b is activated only once bound to malignant plasma cells, allowing interaction with its receptor proteins.
This binding is thought to promote the death of myeloma cells not only directly, but also by boosting anti-tumor immunity.
In previous preclinical tumor models, treatment with QXL138AM alone was shown to be associated with durable complete responses that lasted for months after treatment discontinuation.
This type of approach is expected to improve safety and increase the ability to combine it with other immunomodulating therapies without significantly increasing safety risks.
Nammi is an immunotherapy company based in Los Angeles that is focused on the development of platforms and products that selectively activate anti-tumor immunity within the tumor microenvironment, while minimizing whole-body immune activation.
In addition to the MCI platform, the company has also developed a nanoparticle-based platform, called nammisome, that may be effective in fighting solid tumors.