GP (HK) Entered into an Exclusive Product Licensing Agreement with ITM in Germany, Strategically Plans Three Global Innovative RDC Drugs, Significant Milestone in the Field of Radionuclide Drugs

GP (HK) Entered into an Exclusive Product Licensing Agreement with ITM in Germany, Strategically Plans Three Global Innovative RDC Drugs, Significant Milestone in the Field of Radionuclide Drugs

(December 27, 2021 - Hong Kong) Grand Pharmaceutical Group Limited (“GP (HK)” or the “Company”, together with its subsidiaries, the “Group”, stock code: 00512) is pleased to announce that the Group has reached a product strategic cooperation with ITM Isotope Technologies Munich SE in Germany ("ITM" company). According to the products approval and sales situation, the Group will pay a signing fee as well as milestone payments in aggregate no more than EUR 520 million to obtain the exclusive development, production and commercialization rights of 3 global innovative radionuclide-drug conjugates (the “RDC”) candidates developed by ITM company in Greater China region (Mainland China, Hong Kong, Macau, Taiwan), including: (1) TOCscan® (68Ga-Edotreotide) for the diagnosis of gastroenteropancreatic neuroendocrine tumors ("GEP-NETs"); (2) ITM-11 (n.c.a.177Lu-Edotreotide) for the treatment of GEP-NETs (3) ITM-41 (n.c.a.177Lu- Zoledronate) for the treatment of malignant tumors with bone metastases.

The Group’s strategic plan of the three RDC drugs from ITM, TOCscan®, ITM-11 and ITM-41, will further enriches the product pipeline of the Group’s radiopharmaceuticals diagnosis and treatment platform and lays a solid foundation for the mid- and long-term strategic development of the Group. The Group will actively promote the clinical registration of these three newly introduced RDC products in China.

Radionuclide diagnosis and treatment drug is one of the strategic directions of the Group in anti-tumor field, and now the company has achieved a comprehensive layout in the fields of research, production and commercialization worldwide. The Group will cooperate with its associate company Sirtex Medical Pty Ltd, its invested company Telix Pharmaceuticals Limited (ASX: TLX) and ITM company to increase investment and development of global innovative products in the field of radiopharmaceuticals diagnosis and treatment drugs for unmet clinical needs, enrich and improve product pipelines and industrial layout, constantly enhance the Group's global R&D strength in this field, make contribution to the development of radiopharmaceutical industry in China and strive to build an international leading radionuclide drugs diagnosis and treatment platform. 

ITM company was established in Munich, Germany in 2004. It is a biotechnology company that focuses on R&D, production and global supply of radionuclide drugs for targeted diagnosis and treatment of tumors. ITM company is also one of the largest manufacturers of medical isotopes in the world and its R&D team has gathered senior experts in the fields of mechanical engineering, radiopharmaceutical chemistry, nuclear physics and medicine, and it has been deeply engaged in the production and development of radionuclide drugs for more than 10 years. ITM company is committed to developing a new generation of tumor-targeted radionuclide therapy to significantly improve the treatment effect and quality of life of tumor patients.

ITM-11 is a therapeutic RDC drug based on radionuclide conjugated technology that targets GEP-NETs, and TOCscan® is a diagnostic RDC drug for GEP-NETs. ITM-11 uses peptide receptor radionuclide therapy (PRRT) that conjugates no-carrier-added 177Lu with somatostatin analogs, and targeted killing of tumor cells by binding to the somatostatin receptor ("SSTR") that highly expressed on the surface of GEP-NETs. It is one of the RDC drug treatments. Compared with the commonly used carrier-added 177Lu radioisotope products, the no-carrier-added 177Lu has higher specific activity and purity, and produces less long half-life impurities during the production process and has less radioactive pollution. ITM-11 has been granted orphan drug designation by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The clinical study of ITM-11 versus everoliumus for GEP-Nets has entered Phase III clinical trials overseas. TOCscan® uses somatostatin receptor imaging ("SRI") with Gallium-68 (68Ga) labelled somatostatin analogues to assess tumor receptor expression and response to treatment by PET. TOCscan® has been approved in Germany, Austria, and France in 2018.

The incidence of GEP-NETs is increasing every year. According to “Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up (2020)”, the global incidence of neuroendocrine neoplasms increased by nearly 6 times from 1997 to 2012. SRI imaging has now become an important imaging method recommended by the standard diagnosis and treatment guidelines for the clinical diagnosis of GEP-Nets. According to related studies, 68Ga-SRI diagnostic sensitivity, specificity and accuracy are significantly better than traditional imaging methods. It can accurately perform disease staging and potentially monitor the tumor response to treatment. The guidelines also recommend PRRT therapy for SRI-positive patients with advanced midgut and pancreatic neuroendocrine tumors. The “Guidelines of Chinese Society of Clinical Oncology (CSCO) for Neuroendocrine Neoplasms (2021)” indicated that PRRT treatment based on 177Lu is superior to the high-dose octreotide (somatostatin analogue) that is currently used in the first-line clinical treatment in terms of progression-free survival time (PFS) and objective response rate (ORR) and it bring significant benefits to the patients. The combination of ITM-11 and TOCscan® integrates the imaging and treatment of GEP-NETs, providing a new diagnosis and treatment option for the patients with GEP-NETs.

ITM-41 is a therapeutic radiopharmaceutical drug based on radionuclide conjugated technology that conjugates carrier-free 177Lu and zoledronic acid to target bone metastases of malignant tumors. Zoledronic acid is a first-line drug for the treatment of bone metastases of malignant tumors, which can reduce the occurrence of skeletal-related events (SRE) in patients with bone metastases. The combination of carrier-free 177Lu with high specific activity and purity and zoledronic acid has an anti-proliferative effect on bone metastases, greatly improves the quality of life of patients, with the potential to further reduce severe SRE. The treatment is specifically targeted to bone hydroxyapatite in osteogenic bone metastases, thus minimising the background irradiation of normal tissues. At present, the candidate is in clinical Phase I clinical study overseas.

Bone metastasis is a common complication of advanced cancer, especially breast cancer and prostate cancer. Patients with bone metastasis often have a poor prognosis. The overall strategy for the treatment of bone metastases is palliative treatment, with the main goal of relieving pain and improving the quality of life of patients. According to "Management of Bone Metastases: A Multidisciplinary Guide", the combination of radionuclides and bisphosphonates can be used to target bone metastases and the course of disease can be really changed by adjusting the palliative dose of radiotherapy to the radical dose. The ITM-41 candidate obtained by the Group will provide a new treatment option for patients with bone metastases of malignant tumors in China.

At present, the group has 16 global innovative products in the field of anti-tumor, covering 13 cancer types including liver cancer, prostate cancer, colorectal cancer and etc, involving three directions of tumor intervention, RDC drugs and immunotherapy. Among them, the platform of radionuclide drug diagnosis and treatment platform is a high-end technology platform built by the Group in the field of anti-tumor. Currently, the platform reserved 9 innovative products, covering 6 nuclides including 68Ga, 177Lu, 131I, 90Y, 89Zr and 99mTc. In terms of product pipeline, SIR-Spheres® Y-90 resin microspheres, a tumor intervention product, is the first radioactive microspheres product approved by FDA and now it is in the final stage of new drug application review in China. Thermosensitive embolic agent, another product in tumor intervention direction, has been awarded as innovative medical device by the National Medical Products Administration of China (the “NMPA”). In terms of RDC drugs, TLX591-CDx for the diagnosis of prostate cancer was recently approved in the United States and Australia. TLX591-CDx also obtained special authorization in Brazil to allow sales before formal approval; TLX250-CDx for the diagnosis of clear cell renal cell carcinoma has been approved by the FDA for breakthrough therapy and completed the first patient administration of Phase I clinical study in Australia; TLX101 for the treatment of glioblastoma has been granted orphan drug designation by FDA; TLX591 for the treatment of prostate cancer has been approved for Phase III clinical studies in Australia. The registration of several RDC drugs in China is also in progress. Among them, TLX591-CDX is expected to submit an investigational new drug application (IND) to NMPA in the first quarter of 2022.

Product pipeline and development stage in the anti-tumor field are as below

The Board of Grand Pharmaceutical Group Limited, commented, “The Group always put a high value on the R&D of innovative products and advanced technologies. The cooperation with ITM company an important milestone in the Group's development in the field of radionuclide drugs, and further improved the Group’s product pipeline strategic plan of RDC. Looking ahead, the Group will continue to adopts the strategy of ‘global expansion and dual-cycle operation’ continuously increase the investment and development of global innovative products in the field of radiopharmaceuticals, enrich and improve product pipelines and industrial strategic plan, and strive to build an international leading radiopharmaceutical diagnosis and treatment platform."