upamostat (formerly MESUPRON®) – Oral uPA Inhibitor
upamostat is an oral uPA/serine protease inhibitor, which has been developed by Heidelberg Pharma until Phase II. It is designed to block the activity of tumor-relevant serine proteases such as uPA, plasmin and thrombin to prevent tumor growth and metastasis.
In 2014, the development and commercialization rights for upamostat were out-licensed to Link Health Co., Guangzhou, China (Link Health) for China, Hong Kong, Taiwan and Macao, and RedHill Biopharma Ltd., Tel Aviv, Israel (RedHill) for the rest of the world.
In early January 2016, Link Health submitted an investigational new drug (IND) application to the China Food and Drug Administration (CFDA) for a Phase I dose-escalation study with upamostat. The application was approved at the end of 2018. Details of the planned trials are not yet available as the Chinese regulatory authorities have changed the trial regulations, as a result of which Link Health will have to revise the clinical development plan for upamostat. However, there is now a chance that a Phase II trial can begin immediately based on earlier data from the USA and Europe.
In recent years, RedHill has fled a number of patent applications and generated interesting data for new areas of application. In 2019, RedHill continued to conduct preclinical studies to evaluate patient populations and drug combinations for several indications. In March 2020, Heidelberg Pharma’s partner RedHill announced its plans to trial RHB-107 (upamostat) in combination with another development candidate, opaganib, as a third arm in a Phase I/IIa study in advanced cholangiocarcinoma, subject to talks with the FDA . On 20 April 2020, RedHill announced that it has entered into an agreement with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), to provide its investigational drug, RHB-107, for testing in non-clinical studies for activity against SARS-CoV-2, the virus that causes coronavirus disease (COVID-19).
TLX250-CDx (formerly REDECTANE®) – Diagnostic Antibody
TLX250-CDx is a radiolabeled form of the antibody Girentuximab, which binds to the tumor-specifc antigen CAIX on clear cell renal cell carcinoma. Accumulation of this antibody in tumor tissue can be visualized by positron emission tomography scans (PET). This could fundamentally change therapy planning for renal cancer patients and avoid potentially unnecessary surgery. The diagnostic agent may also prove suitable for monitoring response to treatment, detecting metastases and diagnosing other kinds of tumors.
Under the name REDECTANE®, the project was developed up to an initial Phase III trial (REDECT) at Heidelberg Pharma AG and licensed in 2017 to the Australian firm Telix Pharmaceuticals Limited, Melbourne, Australia, (Telix). The license agreement also covers the development of a therapeutic radioimmunoconjugate program. Last year Telix developed a modernized production process for the manufacture of the antibody Girentuximab.
Due to more favorable properties in terms of processing and diagnostics, Telix has decided to use zirconium-89 instead of iodine-124 for radiolabeling, and has defned 89Zr-DFO-Girentuximab (TLX250-CDx) as the product candidate. To ensure comparability with the earlier REDECT Phase III trial, the ZIRDOSE study was carried out and completed successfully.
Telix has been conducting a Phase III study (ZIRCON) with TLX250-CDx for diagnosing renal cancer since August 2019. The study is being carried out as a global multicenter Phase III trial at sites in Europe, Australia, Canada and the USA , and will enroll around 250 renal cancer patients who are to undergo kidney surgery. The study will determine the sensitivity and specificity of TLX250-CDx PET imaging to detect clear cell renal cell cancer (ccRCC) in comparison with histology as standard of truth determined from surgical resection specimens. Patient recruitment had to be suspended due to the COVID-19 lockdown but resumed in Europe in mid-June. The ZIRCON study is expected to complete recruitment in Q4 2020.
Telix is also planning the further development of a therapeutic radioimmunoconjugate (177Lu-DOTA-girentuximab, TLX250) program based on the lutetium-177-labeled girentuximab antibody. Due to the COVID-19 crisis, filing the study applications in the USA , which was planned for the first half of the year, is now expected to take place in Q3 2020.
Other ongoing activities to support the commercialization of TLX250 products include the adaptation of the girentuximab cell line to cell culture media based on non-animal-derived raw materials (ADRM), which meets the regulatory requirements of approval authorities worldwide.