Hanmi Pharmaceutical confirms possibility of combined use of HM16390 for melanoma and breast cancer

Long-acting IL-2 SC once a week Non-clinical results
Survival and CRR increase with PD-1·CTLA4 combination

Hanmi Pharmaceutical SITC 2024

Hanmi PharmaceuticalAnimal testing results showed that the long-acting anticancer immunotherapy candidate has a high cancer killing effect when administered together with PD-1 and CTLA4 immunotherapy agents. The researchers assessed that there was a high possibility of developing a combination treatment.

According to the American Society of Immuno-Oncology (SITC 2024) on the 10th, the previous day (local time), Hanmi Pharmaceutical researchers presented a poster of the results of animal testing of ‘HM16390’, a long-acting interleukin (IL)-2 candidate substance. SITC 2024, which started on the 6th, will be held in Houston, USA until the 10th.

HM16390 is a new anticancer drug candidate that combines Hanmi Pharmaceutical’s long-lasting platform, Labscovery technology. At this conference, Hanmi Pharmaceutical disclosed research results proving the effectiveness of HM16390 using a cold tumor animal model that no longer responds to immunotherapy drugs.

HM16390 acts on the CD8 T cell receptor to help the immune system attack cancer cells. The company predicts that the analogue with an increased IL2 half-life can reduce the number of administrations and that it will be developed as a subcutaneous injection (SC) formulation to increase patient convenience.

Basic research was conducted by administering a control group, existing IL-2 drug (aldesleukin), and HM16390 to a melanoma-inducing animal model (B16F10) to check the ratio of immune cells such as tumor infiltrating lymphocytes (TIL) for 8 days. Done. HM16390 was administered once and aldesleukin was administered five times to compare the effects.

As a result, the percentage of CD8 cells in TIL in the aldesleukin treatment group decreased from 25% on the first day of treatment to 12% on the 8th day of treatment, but the percentage of cells in the HM16390 treatment group increased from 22% to 41% during the same period.

In a study in which anti-PD-1 immunosuppressant, anti-CTLA4 immunosuppressant and HM16390 were administered together, the cancer killing effect of the combined administration model was more pronounced than that of single administration.

Using a triple-negative breast cancer orthotopic transplant animal model (4T1), an additional study was conducted to compare the effects of existing immunosuppressants twice a week and HM16390 and the chemotherapy drug paclitaxel once a week in combination or singly administered for 4 weeks.

In a comparative study of PD-1 immunosuppressants, the animal model administered paclitaxel alone did not survive, but the group administered high-dose HM16390 alone achieved a complete response (CR) of 14.3%, and all animal models survived.

When a high dose of HM16390 was administered in combination with a PD-1 immunosuppressant, the complete response rate (CRR), in which the cancer completely disappeared, was confirmed to be 57.1% and the survival rate was 85.7%. The survival rate in the PD-1 alone group was 14.3%, and there was no CR.

The effect was also confirmed with CTLA4 combined administration. When CTLA4 immunosuppressants and high doses of HM16390 were administered together to triple-negative breast cancer animal models, all animal models survived with a 100% survival rate. CRR was 42.9%. The survival rate in the group administered CTLA4 alone was 14.3%, and in the group administered high-dose HM16390 alone was 57.1%.

The researchers evaluated that HM16390 is effective in suppressing excessive immune responses while increasing cancer cell toxicity. It was also analyzed that HM16390 acts broadly on CTLA4, which helps the initial activation of T cells, and PD-1, which reaches cancer cells after an immune response occurs and helps T cells attack cancer.

Through this, the researchers predicted, “HM16390 may have the potential as an ideal combination therapy to increase immune responses at various stages of fighting cancer by acting on the tumor microenvironment (TME).”

Reporter Lee Ji-hyeon bluesky@hankyung.com