(Health Korea News / Lee Chung-man) Hanmi Pharmaceutical is beginning full-scale clinical trials of its new immunotherapy drug candidate ‘HM16390’. This drug is attracting extraordinary attention as it has been shown to be effective in non-immune tumors in animal tests.
Hanmi Pharmaceutical received approval for the Phase 1 Clinical Trial (IND) for ‘HM16390’ from the Ministry of Food and Drug Safety on the 7th. The test is to evaluate dose increase and expansion of ‘HM16390’ in patients with advanced or metastatic solid cancer.
‘HM16390’ is effective by applying Hanmi Pharmaceutical’s proprietary platform technology ‘Labscovery’, which dramatically increases the efficacy of IL-2 (interleukin-2) biopharmaceuticals known to regulate the differentiation, survival and function of immune cells. It is a new drug candidate that maximizes safety and sustainability.
This drug is expected to amplify the therapeutic effect when used in combination with immune checkpoint inhibitors, which are currently widely used around the world.
IL-2 immunotherapy, such as ‘HM16390’, has recently emerged as a combination therapy that can overcome the limitations of immune checkpoint inhibitors. The idea is to convert non-immune tumors (cold tumors) that do not respond to immune checkpoint inhibitors into immune tumors (hot tumors) through IL-2 immunotherapy.
Non-immune tumors refer to carcinomas in which T cells do not exist or are distributed extremely rarely in tissues in the tumor microenvironment. Immune checkpoint inhibitors do not respond well to non-immune tumors because there are no available T cells. Representative non-immune tumors include breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, brain cancer (glioblastoma), and melanoma.
IL-2 is a cytokine that regulates immune responses and is regulated through binding to downstream receptors such as alpha and beta. Alpha receptors induce regulatory T cells (Treg) that suppress immune responses, and beta receptors induce T cell activity.
IL-2 agonists are drugs that increase the immune response by acting on IL-2. In non-immune tumor treatment, the approach is to intentionally induce an inflammatory response in the tumor microenvironment through IL-2 agonists to attract T cells and then treat with immune checkpoint inhibitors.
The representative currently approved IL-2 agonist is Novartis’ Proleukin (ingredient name: adesleukin). The U.S. Food and Drug Administration (FDA) approved ‘Proleukin’ as a treatment for melanoma and renal cell cancer in January 1998. Korea’s Ministry of Food and Drug Safety approved the product as a treatment for renal cell carcinoma in March 2007.
However, the disadvantage of ‘Proleukin’ is that it has a short half-life in vivo. However, it is not possible to increase the dose to extend the half-life. If the dose is increased, the binding force of alpha and beta receptors also increases, causing serious side effects such as vascular leak syndrome, and the level of regulatory T cells also increases, which strengthens immune suppression.
As a result, ‘Proleukin’ was not widely used, and Novartis transferred all rights to ‘Proleukin’ to the UK’s Clinigen in February 2019.
To meet these unmet medical needs, Hanmi Pharmaceutical has begun developing new and improved drugs that can overcome the limitations of existing IL-2 agonists.
‘HM16390’ is a long-acting IL-2 conjugate that improves the binding power of the IL-2 beta receptor and optimizes the binding power of the IL-2 alpha receptor to increase anticancer activity and reduce side effects. It can also be administered by subcutaneous injection, increasing patient convenience.
In fact, ‘HM16390’ has proven significant effectiveness in preclinical experiments. The experiment compared and evaluated subcutaneous injection of IL-2 conjugate and intravenous injection of ‘Proleukin’ in mice, and the results showed a higher level of blood distribution than the ‘Proleukin’ administration group even though it was administered subcutaneously.
Therefore, ‘HM16390’ is expected to not only provide medication convenience to patients and medical staff, but also become a new alternative for non-immune tumor patients who are currently suffering from very limited treatment options. Of course, this is assuming that clinical trials are successful.
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