IPAX-1 Study of TLX101 Investigational Glioblastoma Therapy Published in Neuro-Oncology Advances

MELBOURNE, Australia, Sept. 4, 2024 /PRNewswire/ -- Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) today announces that the Company's IPAX-1 Phase I study has been published in Neuro-Oncology Advances, confirming the safety and tolerability profile, and early efficacy of TLX101 therapy, in combination with external beam radiation therapy (EBRT) in recurrent glioblastoma (GBM), the most common and aggressive form of primary brain cancer.

TLX101 (4-L-[ ¹³¹I] iodo-phenylalanine, or ¹³¹I-IPA) is a systemically administered targeted radiation therapy that targets L-type amino acid transporter 1 (LAT1), which is typically over-expressed in GBM.

In the first peer-reviewed publication of the IPAX-1 study, Professor Josef Pichler and colleagues report that single or fractionated doses of TLX101 plus EBRT were associated with acceptable tolerability and specific tumour-targeting in patients with recurrent GBM. Authors explain that the study delivered encouraging preliminary efficacy data, demonstrating a median overall survival (OS) of 13 months from the initiation of treatment, or 23 months from initial diagnosis. Given that GBM has a median survival from initial diagnosis of 12-15 months, authors conclude that findings from the IPAX-1 study "support further investigation into the use of TLX101 plus EBRT, including its potential as a first line treatment".

Key findings of the IPAX-1 study, outlined in the paper, include:

• All dosing regimens were well tolerated.
• Organ-absorbed radiation doses in the red bone marrow (0.38 Gy) and kidney (1.28 Gy) confirmed no radiation-based toxicity.
• Stable disease with MRI^[1] assessment was observed in 4 of 9 patients at 3 months post-treatment (3-month follow-up, 1 patient did not reach protocol-mandated end of study), yielding a response rate of 44.4%.
• At the 3-month follow-up, 6 patients demonstrated metabolic stable disease with ¹⁸F-FET PET imaging.
• Median progression-free survival was 4.3 months (95% confidence interval, 3.3–4.5), while median OS was 13 months from the initiation of treatment (95% confidence interval, 7.1–27), or 23 months from initial diagnosis.

Metabolic tumour responses were determined using Telix's investigational PET^[2] agent for glioma imaging, TLX101-CDx (Pixclara®^[3], ¹⁸F-floretyrosine or ¹⁸F-FET).

Professor Josef Pichler, Kepler University Hospital, Austria, Principal Investigator in the IPAX-1, IPAX-2 and IPAX-Linz studies, and lead author, commented, "A significant unmet need exists for well-tolerated and efficacious treatments for patients with glioblastoma. The results from this Phase I study demonstrate the favourable safety and tolerability profile and preliminary efficacy of TLX101 in combination with second-line EBRT, in patients with recurrent glioblastoma. Following treatment with TLX101 plus EBRT, stable disease was observed in 44% of patients at 3 months post-treatment and median progression-free survival was 4.3 months, with no confirmed radiation toxicity. The overall survival improvement trend seen in this patient population clearly warrants further investigation into the use of TLX101 plus EBRT, including its potential as a first-line treatment. These studies are now well advanced."

Dr David N Cade, Chief Medical Officer at Telix said, "We believe that TLX101 has significant potential to improve outcomes for patients living with glioblastoma – a disease in urgent need of new treatment options. In the front-line setting, the standard of care has not advanced materially in almost two decades, and in recurrent disease, no standard treatment exists. We are encouraged by these data, which show that TLX101, in combination with EBRT, is well tolerated at the doses tested, with preliminary clinical evidence demonstrating an anti-tumour effect and disease stabilisation - outcomes that are very important for this advanced patient population. Telix is pleased to be at the forefront of developing a new therapy for glioblastoma, and we welcome the excellent work conducted by Professor Pichler and his colleagues to progress this."

The IPAX-2 and IPAX-Linz studies in the front-line and recurrent settings continue to progress well in combination with standard of care, and using Telix's Pixclara®³ investigational PET agent as companion diagnostic. Data from IPAX-1, together with these studies, will inform the design of Telix's future registration-enabling trial for TLX101.

The Neuro-Oncology Advances publication is available online at: https://academic.oup.com/noa/article/6/1/vdae130/7723438

About TLX101

TLX101 is Telix's LAT1-targeting investigational therapy for patients with brain cancer. TLX101 therapy utilises a small molecule approach due to the need to cross the blood brain barrier, the normal protective barrier that prevents many potential drug candidates entering the brain. TLX101 has received orphan drug designation in the U.S. and Europe for the treatment of glioma.

About the IPAX series of studies

• IPAX-1 was a multicenter, open-label, single-arm Phase I study to evaluate TLX101 plus EBRT in patients with recurrent GBM. The primary objective of the IPAX-1 study was to evaluate the safety and tolerability profile of intravenous TLX101 administered concurrently with second line EBRT. Secondary objectives were to determine optimal dosing, biodistribution and radiation absorption into the tumour, as well as assess preliminary efficacy through clinical and imaging-based assessment of tumour response. ClinicalTrials.gov ID: NCT03849105.
• IPAX-2 is a Phase I study of TLX101 in combination with post-surgical standard of care treatment in patients with newly diagnosed GBM. Active, dosing patients. ClinicalTrials.gov ID: NCT05450744.
• IPAX-Linz is a Phase II investigator-initiated trial of TLX101 in combination with EBRT in patients with recurrent high-grade gliomas (HGG), including GBM. Active, dosing patients.

About Telix Pharmaceuticals Limited

Telix is a biopharmaceutical company focused on the development and commercialisation of therapeutic and diagnostic 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)^[4], by the Australian Therapeutic Goods Administration (TGA) ^[5], and by Health Canada^[6]. 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

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