Telix Completes Proof-of-Concept Study of TLX592 Targeted Alpha Therapy in Prostate Cancer

• CUPID is a Phase I safety and dosimetry study of TLX592, Telix's investigational antibody-based targeted alpha therapy for prostate cancer.
• Establishes proof-of-concept for Telix's proprietary RADmAb® engineered antibody platform, currently under pre-clinical evaluation for multiple cancer targets.
• Initial results demonstrate rapid elimination from blood circulation compared to standard antibodies and hepatic (liver) clearance – both highly desirable characteristics for use with alpha emitting agents.
• Successful completion of mass dose escalation study establishes a baseline dosing schedule for future studies of TLX592 using actinium-225.
• Data is supportive of advancement to a therapeutic Phase I/II study in H2 2024.

MELBOURNE, Australia, May 21, 2024 /PRNewswire/ -- Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) today announces the successful completion of CUPID^[1], a first-in-human Phase I dose escalation study of TLX592 in patients with advanced prostate cancer.

TLX592 (²²⁵Ac-PSMA-RADmAb®) is Telix's investigational "next generation" targeted alpha therapy (TAT) for the treatment of prostate cancer and is the first clinical program to utilise Telix's proprietary RADmAb® engineered antibody technology. The RADmAb® approach accelerates blood clearance and reduces bone marrow residence time compared with standard monoclonal antibodies (mAbs), while retaining target selectivity, internalisation and retention. The RADmAb® platform is currently under pre-clinical and clinical evaluation for multiple cancer targets.

The CUPID (⁶⁴Cu PSMA Imaging and (Bio) Distribution) study is a 3+3 mass dose escalation study with four patient cohorts intended to evaluate the safety, tolerability, pharmacokinetics, biodistribution and radiation dosimetry of TLX592. The study utilises copper-64 (⁶⁴Cu) which is detectable by Positron Emission Tomography (PET) as a surrogate for actinium-225 (²²⁵Ac), enabling a successful proof-of-targeting study as well as predictive dosimetry calculations for future studies with ²²⁵Ac. Preliminary results in 11 evaluable patients enrolled in the study demonstrated accelerated blood kinetics compared to the standard antibody TLX591, while demonstrating similar (favourable) on-target and off-target biodistribution and hepatic clearance. There were no serious adverse events observed in the study.

Based on these encouraging results, Telix expects to advance TLX592 into a therapeutic Phase I/II study with ²²⁵Ac in the second half of 2024, subject to regulatory approval. TLX592 further deepens Telix's PSMA^[2]-targeting prostate cancer therapy portfolio and supplements its lead investigational radio antibody-drug conjugate (rADC) TLX591 (177Lu rosopatamab tetraxetan), currently being investigated in the ProstACT GLOBAL Phase III study. The Company intends to publish and present non-clinical and clinical data supporting these results at several upcoming symposia.  

Dr David N. Cade, Group Chief Medical Officer at Telix stated, "The CUPID study demonstrated clearly how theranostic approaches can be used to streamline novel radiopharmaceutical drug development. In this case, PET imaging was used to dose-find a targeting agent for future use with an alpha emitter, while establishing basic safety and utility parameters that will greatly inform ongoing development of this product candidate.

"There is a significant unmet need for novel targeting platforms that may be used with alpha emitting isotopes and avoid renal toxicity and other off-target effects, such as the exocrine gland uptake typical of PSMA small molecule agents. We are excited to progress TLX592 into therapeutic studies where our aim is to develop this agent for both early metastatic prostate cancer and late-stage patients who are no longer responding to lutetium therapy. We would like to thank all participants for their commitment to the CUPID study."

About Telix Pharmaceuticals Limited

Telix is a biopharmaceutical company focused on the development and commercialisation of diagnostic and therapeutic radiopharmaceuticals and associated medical devices. Telix is headquartered in Melbourne, Australia, with international operations in the United States, Europe (Belgium and Switzerland), and Japan. Telix is developing a portfolio of clinical and commercial stage products that aims to address significant unmet medical needs in oncology and rare diseases. Telix is listed on the Australian Securities Exchange (ASX: TLX).

Telix's lead imaging product, gallium-68 (⁶⁸Ga) gozetotide injection (also known as ⁶⁸Ga PSMA-11 and marketed under the brand name Illuccix®), has been approved by the U.S. Food and Drug Administration (FDA)^[3], by the Australian Therapeutic Goods Administration (TGA) ^[4], and by Health Canada^[5]. No other Telix product has received a marketing authorisation in any jurisdiction.

Visit www.telixpharma.com for further information about Telix, including details of the latest share price, announcements made to the ASX, investor and analyst presentations, news releases, event details and other publications that may be of interest. You can also follow Telix on X and LinkedIn.

Telix Investor Relations

Ms. Kyahn WilliamsonTelix Pharmaceuticals LimitedSVP Investor Relations and Corporate CommunicationsEmail: kyahn.williamson@telixpharma.com

This announcement has been authorised for release by the Telix Pharmaceuticals Limited Disclosure Committee on behalf of the Board.

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