Olaratumab Antibody Licensed from Lilly Demonstrates Proof of Concept as a Theranostic Radiopharmaceutical

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Apr 16, 2023, 18:35 ET

MELBOURNE, Australia, April 16, 2023 /PRNewswire/ -- Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) today announces successful preclinical development of radiolabelled olaratumab, an antibody licensed from Eli Lilly and Company (Lilly). Telix has demonstrated proof-of-concept (PoC) of using olaratumab to selectively deliver both diagnostic and therapeutic radiation to tumours as a radiopharmaceutical moiety and has produced a candidate for clinical translation. Telix will now progress to first-in-human clinical studies based on these highly encouraging results.

In April 2022, Telix secured the exclusive worldwide rights to develop and commercialise radiolabelled forms of olaratumab for the diagnosis and treatment of human cancers.^[1] Olaratumab was originally developed as a naked (non-radiolabelled) monoclonal antibody targeting Platelet Derived Growth Factor Receptor Alpha (PDGFRα), a target expressed in multiple tumour types. Olaratumab has a well-established clinical safety profile, a favourable toxicology dataset and advanced manufacturing package in relation to Lilly's development program, which Telix expects to be able to leverage for future development as a radiopharmaceutical drug product.

Telix's initial development PoC has focused on a rare type of cancer known as Soft Tissue Sarcoma (STS). External beam radiation is a key part of the standard of care for STS, which may therefore be a suitable clinical target for novel radionuclide therapy, particularly for alpha-emitting radionuclides. The ability of olaratumab to target PDGFRα in the STS tumour microenvironment makes it a highly novel and high-potential radiopharmaceutical candidate.

Telix has now completed its preclinical evaluation, with results sufficiently encouraging to advance development toward initial human clinical trials, in line with planned R&D expenditure for 2023/24. The agent has been assigned formal candidate status in Telix's development pipeline (to be denoted as TLX300-CDx/TLX300 for the diagnostic/patient selection tool and therapeutic, respectively). Specifically, these studies have shown that olaratumab can be bioconjugated with multiple chelators (including Telix's proprietary DFO-squaramide chelator), radiolabelled with zirconium-89 (⁸⁹Zr) for imaging by Positron Emission Tomography (PET) and used to demonstrate specific delivery of radiation to STS cancer cells to show proof of concept in xenograft tumour mouse models. Furthermore, olaratumab radiolabelled with therapeutic radionuclide payloads has demonstrated in vivo efficacy with significant reduction in tumour volumes in relevant disease models, even after administration of a single dose. The Company is preparing to publish preliminary findings.

Telix Chief Scientist, Dr Michael Wheatcroft stated, "Building on Telix's proven track record in acquiring and developing novel radiopharmaceutical assets, it is extremely pleasing to demonstrate the adaptation of this traditional biologic agent for future potential use as a targeted radiopharmaceutical. TLX300 will initially be evaluated in a first-in-human clinical study that is designed to inform both the potential efficacy (dosimetry) and safety profile of this research candidate as a therapeutic, demonstrating the development advantage of a theranostic approach."

About Soft Tissue Sarcoma (STS)

Soft tissue sarcoma is a complex disease that encompasses a diverse group of relatively rare cancers, with more than 50 histological subtypes. In the United States (U.S.), it is estimated that 13,040 new cases and 5,150 deaths were caused by STS in 2019, representing 0.75% of overall cancer incidence and 0.84% of overall cancer mortality.^[2] In Europe, nearly 23,600 new STS cases rose annually, and the crude incidence rate was 4.7 per 100,000.^[3] Approximately 39,900 new STS cases occurred nationwide in China in 2019, accounting for 1.05% of overall cancer incidence.^[4]The crude incidence rate was 2.91/100,000 and generally increased with age. Standard treatment for soft tissue sarcoma includes surgery, radiation therapy and/or chemotherapy. For patients with advanced, unresectable, or metastatic disease, treatment typically involves chemotherapy with single agents (e.g., doxorubicin) or anthracycline-based combination regimens. However, the prognosis for these patients remains poor, with treated patients with metastatic disease having a median overall survival of around 12–18 months.^[5]

About olaratumab

Olaratumab (previously marketed under the brand name, Lartruvo^®) was originally developed as a monoclonal antibody targeting PDGFRα. Olaratumab was granted "Accelerated Approval" in the U.S. and "Conditional Approval" in the EU based on Phase II trial data which showed a 1-year survival benefit in patients with STS, when given in combination with standard chemotherapy. Olaratumab was voluntarily withdrawn from the market by Lilly following the failure of the Phase III ANNOUNCE clinical trial, in which olaratumab did not improve survival for patients.

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 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 (@TelixPharma) and LinkedIn.

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),^[6] and by the Australian Therapeutic Goods Administration (TGA),^[7]and by Health Canada.^{^[8]} Telix is also progressing a marketing authorisation application for this investigational candidate in the United Kingdom.^[9]

Telix Investor Relations

Ms. Kyahn Williamson
Telix Pharmaceuticals Limited
SVP Corporate Communications and Investor Relations
Email: [email protected]

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

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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.

[1] Telix ASX disclosure 11 April 2022.

[2] American Cancer Society 2020.

[3] RARECARE Project 2013.

[4] Yang et al. Cancer Biol Med. 2019.

[5] In et al. Ther Adv Med Oncol. 2017.

[6] Telix ASX disclosure 20 December 2021.

[7] Telix ASX disclosure 2 November 2021.

[8] Telix ASX disclosure 14 October 2022.

[9] Telix ASX disclosure 3 April 2023.

SOURCE Telix Pharmaceuticals Limited