Trial met primary and secondary endpoints and confirmed favourable safety and tolerability profile, indicating TLX250-CDx has the potential to become a new clinical standard in the identification and characterisation of clear cell renal cell carcinoma (ccRCC):

• Primary endpoint met: Sensitivity of ≥84% and specificity of ≥84% in all three readers (86% / 87% overall)
• Considerably exceeds confirmatory trial sensitivity and specificity success targets
• Key secondary endpoints met, achieving ≥85% sensitivity and ≥89% specificity in small renal masses (cT1a ≤4cm)
• Full data set: 93% positive predictive value; 75% negative predictive value; 86% accuracy (secondary endpoints)
• cT1a masses: 93% positive predictive value; 78% negative predictive value; 87% accuracy
• Case study presented on a 1cm mass, demonstrating potential for clinical decision making with renal masses ≤2cm
• Favourable safety and tolerability profile of TLX250-CDx also confirmed

MELBOURNE, Australia, Feb. 20, 2023 /PRNewswire/ -- Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) today announces detailed positive results from its completed pivotal Phase III ZIRCON trial (ClinicalTrials.gov Identifier: NCT03849118)^[1]. The study met primary and secondary endpoints, with TLX250-CDx demonstrating the ability to reliably characterise and detect the clear cell phenotype and provide a non-invasive method of diagnosing the presence and spread of ccRCC, delivering on an unmet medical need in this disease setting.

The results were featured in an oral presentation delivered by Associate Professor Brian Shuch, MD, Director, Kidney Cancer Program, UCLA Institute of Urologic Oncology (Los Angeles, California) and a Principal Investigator in the Phase III ZIRCON study, at the American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium (ASCO GU), on Saturday, 18 February 2023. This marks the first time that detailed analyses of the primary endpoints and key secondary endpoints from the ZIRCON study have been presented to the medical community.

A total of 300 patients were dosed with TLX250-CDx resulting in 284 evaluable patients (those patients with central histology reading and evaluable TLX250-CDx PET scan at central review). Each patient received a single dose of TLX250-CDx and a tumour sample from surgical resection (centrally reviewed) was used as the standard of truth comparator.

The study delivered highly consistent results across three readers of an average 86% sensitivity and 87% specificity (see Figure 1), exceeding the pre-determined threshold required to demonstrate the ability of TLX250-CDx to reliably detect the clear cell phenotype and provide an accurate and non-invasive method for identifying the presence and spread of ccRCC. Confidence intervals (CIs) exceeded expectations in all three readers showing high accuracy and consistency of interpretation.

The study also met the key secondary endpoint, achieving 85% sensitivity and 89% specificity in detecting ccRCC in tumours ≤4cm ("T1a" classification), currently a significant clinical challenge in the diagnosis of ccRCC. See Figure 2.

Figure 1: Co-primary endpoints (full analysis set)

Sensitivity and specificity thresholds exceeded by all three independent readers^[2] 

	Reader 1	Reader 2	Reader 3	Overall %  (95% CI)
Sensitivity, %	84.13	85.19	87.30	85.5
Lowest bounds, Wilson 95% CI	78.24	79.42	81.80	(79.8; 89.8)
Specificity, %	88.42	88.42	84.21	87
Lowest bounds, Wilson 95% CI	80.45	80.45	75.57 %	(78.8; 92.3)
Positive predictive value, %	93.53	93.60	91.67	93 (88; 96)
Negative predictive value, %	73.68	75.00	76.92	75 (66; 82)
Accuracy, %	85.56	86.27	86.27	86 (81.5; 89.6)

Figure 2: Key secondary endpoints (small lesions, cT1a ≤4cm)

Sensitivity and specificity thresholds were met by all three independent readers (full analysis set)

	Reader 1	Reader 2	Reader 3	Overall %   (95% CI)
Sensitivity, %	84.05	86.17	86.17	85.5
Lowest bounds, Wilson 95% CI	75.33	77.76	77.76	(77; 91.2)
Specificity, %	90.74	90.74	87.04	89.5
Lowest bounds, Wilson 95% CI	80.09	80.09	75.58	(78.6; 95.2)
Positive predictive value, %	94.05	94.19	92.05	93.4 (86.1; 97)
Negative predictive value, %	76.56	79.03	78.33	78 (66.2; 86.5)
Accuracy, %	86.5	87.8	86.5	87 (80.6; 91.4)

A clinical case study example was presented, demonstrating the potential for clinical decision making and accurately identifying clear cell renal cancer even in very small renal masses, smaller than 2cm (Figure 3).

Figure 3: ZIRCON clinical case in a 1cm mass^[3]

Potential support for clinical decision making

For such cases the high sensitivity and PPV shows that this patient is highly likely to have a ccRCC diagnosis, confirming that they should have this malignant tumour removed. The image could help understand the stage of the disease as well as the location, defining the surgical plan. In such a patient a biopsy would be avoided and they would likely move to surgery with confidence in the diagnosis.

The favourable safety and tolerability profile of TLX250-CDx was also confirmed, with the majority of adverse events (AEs) being post-surgical complications and not study treatment related. No unexpected safety signals were observed and tolerability profile was consistent with experience of girentuximab in previous therapeutic and imaging studies.

A/Prof Brian Shuch, MD, Director, Kidney Cancer Program, UCLA Institute of Urologic Oncology (Los Angeles, California) said, "On behalf of Telix and all of the investigators and clinical sites that contributed towards the successful ZIRCON study, it is a privilege to present at ASCO GU. Since the news of positive top line data in November there has been tremendous interest from peers in the medical community and it's great to be able to dig a little deeper into the clinical impact of these excellent results, including in particular patient sub-sets. The high sensitivity and specificity will allow us to change patient management accurately identifying which patients do or don't have ccRCC."

Dr Colin Hayward, Chief Medical Officer at Telix said: "We are pleased to share these key Phase III ZIRCON study results with the urologic oncology community for the first time at ASCO GU, the leading specialised event for GU cancer care worldwide. The consistency of results and accuracy of the test in both larger and smaller renal masses is especially encouraging. Telix would like to thank Dr Shuch for his personal commitment to this study, as well as all of the patients and clinical teams who participated worldwide."

Telix is also pleased to inform shareholders that the ZIRCON study has been accepted for presentation at the 38^th Annual European Association of Urology (EAU) Congress taking place in Milan, Italy, from 10 – 13 March 2023. Professor Peter Mulders, Head of Urology at Radboud University Nijmegen Medical Centre and a Principal Investigator in the ZIRCON study will present further analyses in a "game-changing" oral presentation on 11 March. Further details on this and other Telix presentations at EAU to follow. 

Investor Briefing

Telix is hosting an investor briefing with A/Prof Brian Shuch and Dr Colin Hayward, Telix Group Chief Medical Officer tomorrow, Tuesday 21 February at 8.30am AEDT (Monday 20 February at 4.30pm EST).

The briefing provides an opportunity for investors to hear Dr Shuch's ASCO GU presentation and a clinician's perspective on the clinical utility of this investigational imaging agent. This will be followed by a Q&A session.

Please register at the following link to access the investor briefing:
https://s1.c-conf.com/diamondpass/10028731-hd94t2.html

Dr Shuch's presentation can be viewed or downloaded from the Telix corporate website here.

About Telix Pharmaceuticals Limited

Telix is a biopharmaceutical company focused on the development and commercialisation of diagnostic and therapeutic radiopharmaceuticals. 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-stage products that aims to address significant unmet medical need in oncology and rare diseases. Telix is listed on the Australian Securities Exchange (ASX: TLX). For more information visit www.telixpharma.com and follow Telix on Twitter (@TelixPharma) and LinkedIn.

TLX250-CDx has not received a marketing authorisation in any jurisdiction. Telix's lead product, gallium-68 (⁶⁸Ga) gozetotide (also known as ⁶⁸Ga PSMA-11) injection, has been approved by the U.S. Food and Drug Administration (FDA),^[4] and by the Australian Therapeutic Goods Administration (TGA),^[5] and by Health Canada.^[6]

^[1] Top line data released to ASX on 7 November 2022.  
^[2] 95% CI had to be >0.7 for sensitivity and >0.68 for specificity, for ≥2 independent readers to declare the study positive.
^[3] Note: representative patient response only, may not be representative for all patients.
^[4] ASX disclosure 20 December 2021.
^[5] ASX disclosure 2 November 2021.
^[6] ASX disclosure 14 October 2022.

Telix Investor Relations

Ms. Kyahn Williamson
Telix Pharmaceuticals Limited
SVP Corporate Communications and Investor Relations
Email: kyahn.williamson@telixpharma.com

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