January 29, 2021 – 3D Medicines Inc. announced that the National Medical Products Administration (NMPA) has granted the IND approval for 3D011, a Class 1 innovative drug self-developed by 3D Medicines for the treatment of advanced solid tumors. The approval signifies the in-house R&D ability of 3D Medicines to independently develop innovative drugs with global intellectual property rights, laying a solid foundation for realizing the strategic goal of long-term sustainable development for the company.

IND approval for 3D011

Candidate compound screening

The R&D process of 3D011 began at the end of 2016. After a comprehensive and detailed investigation of dozens of anti-cancer drugs in development or those had failed phase III clinical trials, the R&D team of 3D Medicines selected a high-efficacy oral anti-cancer drug as the original compound, and then started the systematic process of development and optimization.

The selected parent drug could significantly inhibit the activity of relevant kinases, and its favorable anti-cancer efficacy had been fully demonstrated in clinical trials, with the time to progression (TTP) at 5.4 months, p = 0.001 and the overall response rate (ORR) at 10.1%, p = 0.018. However, the parent drug had the drawback of relatively high systemic toxicity, so the R&D team of 3D Medicines decided to improve its pharmacokinetic characteristics through prodrug design, thereby reducing its systemic toxicity.

Compound design and optimization

During rounds and rounds of exploration from design, optimization and synthesis to examination and re-optimization, the R&D team of 3D Medicines fully considered and verified how different combinations affected the activity and toxicity of the compound, and finally obtained a candidate molecule with perfect balance. In July, 2017, the R&D team of 3D Medicines filed international Patent Cooperation Treaty (PCT) applications for the series of compounds including 3D011, and the patent applications in many countries and regions are currently under review.

With a relatively large molecular weight, many chiral structures and polar groups, 3D011 was extremely hard to be synthesized and purified in the early stages, and the yield had been hovering around the milligrams. In September, 2019, the R&D team of 3D Medicines finally made a major breakthrough by transforming it into a salt compound, significantly improving the water solubility, breaking the bottleneck of synthesis and purification, obtaining the compound at the gram level and enabling the following key experiments. In the subsequent process of amplification, the R&D team of 3D Medicines overcame the difficulties one after another, and finally succeeded in producing the Active Pharmaceutical Ingredient (API) for the clinical samples.

Pre-clinical studies

3D011 has demonstrated significant inhibition of tumor growth in efficacy pharmacology studies, and no inhibition of hERG pathway in safety pharmacology studies. No obvious abnormalities were seen in the central nervous system of mice, or the cardiovascular system and the respiratory system of dogs. No obvious drug-related toxic reactions were seen in toxicology studies on mice and dogs.

John Gong, M.D., Ph.D., Chairman and Chief Executive Officer of 3D Medicines, commented, “The clinical trial approval for 3D011 is a significant milestone in the innovative drug R&D process of 3D Medicines, a sign of our innovative abilities at the source of innovative drug R&D, and an important step in expanding and improving our pipeline. In the future, 3D Medicines will keep devoting itself to developing differentiated products with clinical value, providing tumor patients with more and better treatment options and realizing our vision of ‘helping people with cancer live longer and better’.”

About 3D Medicines

3D Medicines, Inc. is a clinical-stage biopharmaceutical company with a mission to help people with cancer live longer and better. Envisioning a future when cancer is managed as a chronic disease, 3D Medicines focuses on the development of differentiatedimmuno-oncology drugs, helping cancer patients live with prolonged survival time and a better quality of life. 3D Medicines has established a pipeline with both biological macromolecule and chemotherapeutic small-molecule drugs, as well as a professional team capable of global development, registration and commercialization operation.

For more information, please visit: www.3d-medicines.com

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