TLX250-CDx is a radiolabeled form of the antibody girentuximab, which binds to the tumor-specific 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. Telix developed a modernized production process for the manufacture of the antibody girentuximab.

TLX250-CDx (⁸⁹Zr-DFO-girentuximab) is an antibody radioactively labeled with zirconium-89 and has been tested by Telix in the ZIRCON study for imaging diagnostics of renal cancer using PET since August 2019. The study was carried out as a global multicenter Phase III trial at 36 study sites in Europe, Turkey, Australia, Canada, and the USA. 

Telix reported positive date of the ZIRCON study in November 2022. The study results delivered a sensitivity of 86% and specificity of 87%, thus exceeding the thresholds required to demonstrate the ability of TLX250-CDx to reliably detect the clear cell phenotype and provide a non-invasive method of diagnosing the presence and spread of ccRCC.

The study has also met the key secondary endpoint, achieving 85% sensitivity and 89% specificity in detecting ccRCC in tumors <4 cm (“T1a” classification), currently a significant clinical challenge in the diagnosis of ccRCC.

These highly positive results demonstrate that TLX250-CDx provides a way to non-invasively diagnose clear cell renal cancer – until now this could only be determined by invasive biopsy or surgery which presents a higher burden or danger for patients.

Telix had completed the submission of a rolling New Drug Application in the United States in June 2024. The company announced at the end of July that the FDA had not accepted the application for approval at that time because of a manufacturing issue. Evidence of adequate sterility assurance during filling of the substance must be provided. Telix plans to resubmit the revised application in the fourth quarter of 2024. The application for priority review remains unchanged.

Furthermore, Telix is preparing to launch an Expanded Access Program (EAP) to enable eligible patients to access TLX250-CDx to address unmet need and requests for access under the healthcare professional responsibility prior to marketing authorization.

Under Telix’s guidance a number of investigator-led studies of TLX250-CDx have been initiated, supporting the goal of indication expansion.

Telix is also planning the further development of a therapeutic radioimmunoconjugate (¹⁷⁷Lu-DOTA-girentuximab, TLX250) program based on the lutetium-177-labeled girentuximab antibody.

The IND application to conduct a Phase II (STARLITE 2) study was accepted by the FDA in September 2021. TLX250 is to be tested in the STARLITE 2 study as therapy for an estimated 29 patients with advanced clear cell renal cell carcinoma (ccRCC). The study will evaluate TLX250 in combination with the immunotherapy Opdivo® (nivolumab). The efficacy of combining immunotherapy with TLX250, as assessed by the number of tumors responding to the Telix therapy versus the current standard of care, will be tested. The first patient has been dosed in May 2022.

Developed by Heidelberg Pharma AG up to Phase II until 2014, upamostat is an oral serine protease inhibitor that is designed to block the activity of tumor-relevant serine proteases such as uPA, plasmin and thrombin to inhibit tumor growth and metastasis.

Since 2014, license agreements have been in place for the development and potential commercialization of upamostat with Link Health Co., Guangzhou, China, (Link Health), and RedHill Biopharma Ltd. (NASDAQ: RDHL), Tel Aviv, Israel, (RedHill).

Link Health informed Heidelberg Pharma that it will no longer continue development. Accordingly, Heidelberg Pharma does not expect any further progress from the collaboration with Link Health.

Heidelberg Pharma’s partner RedHill is developing upamostat (referred to as RHB-107 by RedHill) for treating COVID-19. RHB-107 has shown both antiviral and potential tissue-protective activity, with RHB-107 strongly inhibiting SARS-CoV-2 replication in a preclinical human bronchial tissue study. The drug candidate targets human serine proteases that are involved in the virus’s entry into target cells.

2023, a report on the Phase II clinical study in COVID-19 outpatients, that demonstrated preliminary evidence of efficacy with an excellent safety profile, and a review on properties of upamostat and potential indications in a variety of diseases were published.

In May 2023, RedHill announced that it will focus the company’s resources on the development of RHB-107. The company announced in December 2023 that non-dilutive external funding had been committed for the RHB-107 arm of a platform trial. In addition, the 300-patient Phase II RHB-107 arm of the PROTECT study received FDA clearance to start. The study is being conducted in the US, Thailand, Ivory Coast, South Africa and Uganda.

RHB-107 is also being tested in development programs against several viral diseases, including Ebola. 

RedHill announced in December 2023 that RHB-107 together with opaganib demonstrated synergistic effect when combined individually with remdesivir in a new in vitro Ebola virus study funded and conducted by the US Army, significantly improving efficacy while maintaining cell viability.