First Patient Dosed in STARSTRUCK Study of TLX250 Targeted Radiation Therapy in Combination with Merck Investigational DNA-PK Inhibitor, Peposertib

MELBOURNE, Australia, July 19, 2023 /PRNewswire/ -- Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) today announces that the first patient has been dosed in a Phase I study of the Company's investigational targeted radiation therapy, TLX250, in combination with a Merck KGaA, Darmstadt, Germany (Merck) DNA-dependent protein kinase (DNA-PK) inhibitor candidate, peposertib (M3814). The study is being conducted in patients with solid tumours expressing carbonic-anhydrase IX (CAIX), a potential pan-cancer target.

STARSTRUCK (ClinicalTrials.gov Identifier: NCT05868174^[1]) is a Phase Ib, open label, single-arm, multicentre dose escalation and dose expansion study to evaluate the safety profile, dosing and activity of TLX250 (¹⁷⁷Lu-DOTA-girentuximab) in combination with the DNA damage response inhibitor (DDRi) peposertib, which is an inhibitor of DNA-PK. The target population is patients with CAIX-expressing solid tumours that are relapsed or refractory to standard therapies. Up to 80 patients will be assessed in this study in Australian sites.

The clinical hypothesis is that the combination of TLX250 and a DNA-PK inhibitor provides an enhancement in potency through their synergistic action on cancer cells. Targeted radiation effectively induces DNA damage in targeted cancer cells and the DNA-PK inhibitor may act to prevent the cell from repairing this damage, resulting in higher potency at lower doses. This hypothesis was confirmed in preclinical studies, conducted under a strategic research collaboration between Merck and Telix announced in 2019,^[1] and provided evidence that the combined effect of Merck's investigational DNA-PK inhibitor peposertib with Telix's targeted radiation candidate has potential to significantly improve efficacy and reduce the required radiation dose for tumour reduction and remission, compared to targeted radiation alone.

Principal Investigator for the STARSTRUCK study, Professor Nat Lenzo, GenesisCare Group Clinical Director Theranostics said, "The treatment of advanced cancer can be extremely challenging. We are pleased to support the commencement of this study with Telix to help determine if there is a potential future clinical benefit regarding the combination of molecular targeted radiation and DNA-PK inhibitors."

Telix Chief Medical Officer, Dr. Colin Hayward stated, "Preclinical data has shown excellent combination response, which has potential to translate to additional response or more tolerable treatment regimens in patients. We would like to thank Prof. Lenzo and his clinical team at GenesisCare Murdoch, as well as the patients who will contribute to this important study."

Merck and Telix are continuing the initial scientific collaboration to further explore and optimise the combination of TLX250 or other next-generation targeted radiation therapy candidates with Merck's DDRi compounds in preclinical studies.

About TLX250

TLX250 (¹⁷⁷Lu-DOTA-girentuximab) is an antibody-based therapeutic platform that targets CAIX, a cell surface protein that is highly expressed in several human cancers, and is currently the subject of the STARLITE-1 (ClinicalTrials.gov Identifier: NCT05663710^[2]) and STARLITE-2 (NCT05239533^[3]) studies in combination with immunotherapy.^[2] High CAIX tumour expression is generally correlated with poor prognosis.

Telix's companion investigational diagnostic imaging agent TLX250-CDx (⁸⁹Zr-DFO-girentuximab) was the subject of a successful global Phase III trial (ZIRCON trial, NCT03849118), which completed enrolment and reported positive top-line data during 2022.^[3] Analyses of primary endpoints and key secondary endpoints of the ZIRCON trial were presented to the medical community for the first time at ASCO GU on 18 February 2023.^[4] TLX250-CDx is currently being investigated in the Phase II STARBURST study (ClinicalTrials.gov Identifier: NCT05563272) exploring CAIX expression in patients with a diverse range of solid tumours for potential diagnostic and therapeutic applications.^[5][4][5]

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).

Visit www.telixpharma.com^[6] 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 Twitter^[7] (@TelixPharma) and LinkedIn^[8].

TLX250 and TLX250-CDx have not received a marketing authorisation in any jurisdiction. Telix's lead product, Illuccix^® (gallium-68 (⁶⁸Ga) gozetotide (also known as ⁶⁸Ga PSMA-11) injection), has been approved by the U.S. Food and Drug Administration (FDA),^[6] and by the Australian Therapeutic Goods Administration (TGA),^[7] and by Health Canada.^[8] Telix is also progressing marketing authorisation applications for this investigational candidate in the United Kingdom and the European Union.^[9]

Telix Investor Relations

Ms. Kyahn WilliamsonTelix Pharmaceuticals LimitedSVP Investor Relations and Corporate CommunicationsEmail: kyahn.williamson@telixpharma.com^[9]

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).

References

1. ^{^} NCT05868174 (clinicaltrials.gov)
2. ^{^} NCT05663710 (clinicaltrials.gov)
3. ^{^} NCT05239533 (clinicaltrials.gov)
4. ^{^} NCT03849118 (clinicaltrials.gov)
5. ^{^} NCT05563272 (clinicaltrials.gov)
6. ^{^} www.telixpharma.com (www.telixpharma.com)
7. ^{^} Twitter (twitter.com)
8. ^{^} LinkedIn (www.linkedin.com)
9. ^{^} kyahn.williamson@telixpharma.com (www.prnasia.com)