ProstACT SELECT Study of TLX591 Interim Readout: Positive Results Confirm Safety and Tolerability

• The study has achieved its primary objectives, confirming the safety and tolerability profile of TLX591 administered in two doses, two weeks apart in combination with standard of care (SoC)
• Preliminary activity demonstrates meaningful PSA^[1] reduction; monitoring of patients is ongoing, including for rPFS^[2]
• Findings reinforce the potential advantages of this first-in-class radio-antibody drug conjugate (rADC) investigational therapy, consistent with previous clinical studies of TLX591^[3]

MELBOURNE, Australia, Oct. 19, 2023 /PRNewswire/ -- Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) today announces positive preliminary results from the Phase I ProstACT SELECT study of its rADC therapy candidate TLX591 (Lutetium (¹⁷⁷Lu) rosopatamab tetraxetan) for prostate-specific membrane antigen (PSMA) positive metastatic castration-resistant prostate cancer (mCRPC).

The purpose of the SELECT study (ClinicalTrials.gov ID: NCT04786847) was to evaluate the utility of PSMA imaging to select patients for rADC-based PSMA therapy and to confirm the biodistribution of the rADC investigational therapy. The primary clinical objective was to determine whole body distribution and organ radiation and assess the safety and tolerability of TLX591, when administered in combination with SoC in second-line mCRPC.

The evaluable population was 28 patients (of a total 30 enrolled in the study). Patients received two (2) single intravenous (IV) infusions of TLX591, fourteen (14) days apart. Cohort 1 (5 patients) received a 27mCi dose followed by a 76 mCi dose for accuracy of biodistribution determination. Cohort 2 (23 patients) received two 76mCi doses.

The study achieved its primary objectives, confirming the safety and tolerability profile of TLX591 administered in two cycles,14 days apart (total cumulative dose 152mCi). The results reinforce the clinical utility of the short, fractionated dosing regimen.

Key results and observations

Dosimetry and biodistribution

• Consistent lesion delineation between TLX591 and ⁶⁸Ga-PSMA-11 imaging, within the detection sensitivity and resolution limits of SPECT^[4]
• Excellent uptake and retention in tumour and metastases up to 14 days post injection
• Radiation exposure to key organs is well within prescribed safety limits
• The highest absorbed dose was in the liver (clearance organ), with minimal uptake in exocrine (salivary) glands
• Long retention period is evidence of internalisation and ability to efficiently deliver payload to tumour

Hematologic profile and adverse events

• Grade 3 thrombocytopenia (25%) and neutropenia (38%) events in line with profile expected for this class of therapy. Similarly for Grade 4 hematologic events – thrombocytopenia (25%) and neutropenia (4%)
• Serious adverse events (SAEs) observed were generally lower than in earlier studies conducted at the same dose level, reflective of the SELECT study being conducted in a healthier patient population
• Hematologic events were transient and reversible
• Four patients (17%) received intervention in the form of platelets, growth factors or both
• All treatment related non-hematologic events were Grade 1 or Grade 2 and generally mild

Preliminary anti-tumour activity

• 64% of patients (baseline PSA and full dose) had a PSA reduction, with 27% demonstrating a 30% reduction and 18% demonstrating a 50% reduction. PSA and rPFS monitoring is ongoing

Scott T. Tagawa, MD, Professor of Medicine and Urology in New York said, "Preliminary results from the ProstACT SELECT study build on prior studies of TLX591 and underline the potential advantages of an antibody-based approach. Latest data provides further evidence of the long retention and internalisation of TLX591 in the tumour (and metastases), which may maximise the cell-killing effect of the ¹⁷⁷Lu radioisotope at the site of the tumour."

Nat Lenzo, MD, GenesisCare Group Clinical Director Theranostics and top recruiter onto the ProstACT SELECT study commented, "It is really exciting to see development of this next-generation PSMA-targeting radiotherapeutic progressing. This study confirms the suitability of the short, simple treatment duration with two doses administered two weeks apart which is attractive to physicians and patients. The safety and tolerability data also demonstrates the potential for this therapy to reduce undesirable side effects, while delivering a hematologic toxicity profile that is both tolerable and manageable."

Colin Hayward, Telix Chief Medical Officer, added, "TLX591 is being designed to integrate with current standard of care, demonstrative of Telix's continued innovation in prostate cancer treatment. The SELECT study provides further validation of the potential of TLX591, a first-in-class rADC therapy and the use of PSMA imaging with small molecules to select patients for antibody-based PSMA therapy."

Investigation of TLX591 is continuing in the Phase III ProstACT GLOBAL study (ClinicalTrials.gov ID NCT04876651), open for enrolment in Australia and expected to commence in the United States in 2024.

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-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).

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 LinkedIn.

TLX591 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),^[5] by the Australian Therapeutic Goods Administration (TGA),^[6] and by Health Canada.^[7] Telix is also progressing Marketing Authorisation Applications for ⁶⁸Ga-PSMA-11 in the United Kingdom, the European Union^[8] and Brazil.

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.

Legal Notices

This announcement is not intended as promotion or advertising directed to any healthcare professional or other audience in any country worldwide (including Australia, United States and the United Kingdom). This announcement may include forward-looking statements that relate to anticipated future events, financial performance, plans, strategies or business developments. Forward-looking statements can generally be identified by the use of words such as "may", "expect", "intend", "plan", "estimate", "anticipate", "outlook", "forecast" and "guidance", or other similar words. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. Forward-looking statements are based on the Company's good-faith assumptions as to the financial, market, regulatory and other risks and considerations that exist and affect the Company's business and operations in the future and there can be no assurance that any of the assumptions will prove to be correct. In the context of Telix's business, forward-looking statements may include, but are not limited to, statements about: the initiation, timing, progress and results of Telix's preclinical and clinical studies, and Telix's research and development programs; Telix's ability to advance product candidates into, enrol and successfully complete, clinical studies, including multi-national clinical trials; the timing or likelihood of regulatory filings and approvals, manufacturing activities and product marketing activities; the commercialisation of Telix's product candidates, if or when they have been approved; estimates of Telix's expenses, future revenues and capital requirements; Telix's financial performance; developments relating to Telix's competitors and industry; and the pricing and reimbursement of Telix's product candidates, if and after they have been approved. Telix's actual results, performance or achievements may be materially different from those which may be expressed or implied by such statements, and the differences may be adverse. Accordingly, you should not place undue reliance on these forward-looking statements.

Except as required by applicable laws or regulations, Telix does not undertake to publicly update or review any forward-looking statements. Past performance cannot be relied on as a guide to future performance. Readers should read this announcement together with our material risks, as disclosed in our most recently filed reports with the ASX and on our website.

©2023 Telix Pharmaceuticals Limited. The Telix Pharmaceuticals and Illuccix name and logo are trademarks of Telix Pharmaceuticals Limited and its affiliates (all rights reserved).

[1] Prostate-specific antigen.[2] Radiographic progression-free survival.[3] Bander et al. J Clin Oncol. 2005; Tagawa et al. Clin Cancer Res. 2013; Tagawa et al. Cancer. 2019; Batra et al. Urol Oncol. 2020; Niaz et al. Oncologist. 2020.[4] Single-photon emission computed tomography.[5] Telix ASX disclosure 20 December 2021.[6] Telix ASX disclosure 2 November 2021.[7] Telix ASX disclosure 14 October 2022.[8] Telix ASX disclosure 3 April 2023.