Olaratumab

MELBOURNE, Australia and BERLIN, Nov. 13, 2024 (GLOBE NEWSWIRE) -- Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) today announces that it has entered into a technology collaboration and licence agreement with Berlin-based Eckert & Ziegler SE (EZAG) for the use of EZAG’s cyclotron-based systems to produce the alpha-emitting isotope, actinium-225 (225Ac). This provides Telix with both an additional commercial source of 225Ac and access to a platform technology that enables highly efficient, scalable isotope production for use in the development of next generation targeted alpha therapies (TATs), a strategic focus for Telix. EZAG is one of the world’s largest providers of isotope technology for medical, scientific and industrial use and a long-term partner of Telix. By combining EZAG’s technology with Telix’s rapidly expanding global manufacturing footprint, the collaboration will enhance capacity to produce 225Ac, to accelerate the development of Telix’s alpha therapy candidates and support eventual commercial demand. “This new collaboration is a significant step in the implementation of our actinium strategy,” said Dr. Harald Hasselmann, Chief Executive Officer of Eckert & Ziegler. “Eckert & Ziegler and Telix have a long-standing and multi-faceted business relationship. Combining the strengths of two leading players in radiopharmaceuticals and isotopes will create a collaboration for the supply of actinium-225-based radiotherapeutics, that are of high interest worldwide.” Raphaël Ortiz, Chief Executive Officer, Telix International, added: “Targeted alpha therapy is regarded as the next frontier in the field of radiopharmaceuticals and is a priority R&D focus for Telix. This collaboration will enable us to unlock the early investment we have made in alpha therapy candidates and further leverage our manufacturing facilities worldwide, including in Brussels South, for the production of this important alpha emitting isotope.” Alpha emitters such as 225Ac have the potential to deliver high amounts of energy to cancer tissue, while their short range can reduce the risk of damage to surrounding healthy cells, increasing the selectivity and potency of radiation treatment. In contrast, beta emitters such as lutetium-177 (177Lu) and iodine-131 (131I) have a longer penetration, which may suit bulky metastatic disease. The development of TATs is a priority research and development focus area for Telix and is highly complementary to the Company’s existing late-stage therapeutic pipeline. Experts believe the demand for 225Ac will increase significantly over the next decade. Telix’s R&D commitment to TAT is demonstrated in an extensive clinical-stage TAT pipeline: TLX592, a PSMA1-targeting prostate cancer therapy candidate based on the Company’s proprietary RADmAb® engineered antibody technology;TLX252, a CAIX2-targeting radio antibody-drug conjugate (rADC) under development as a potential complement to the TLX250 (beta) program;TLX1023, a LAT14-targeting small molecule-based candidate under development as a potential complement to the TLX101 and TLX101-CDx brain cancer programs; andTLX300, a radiolabelled form of a naked antibody in-licensed from Eli Lilly & Company under investigation in soft tissue sarcoma5. In addition, the completed OPALESCENCE6 and PERTINENCE7 investigator-initiated trials have demonstrated CAIX-targeting and dosimetry proof-of-concept for alpha therapy in triple-negative breast cancer, and non-muscle-invasive bladder cancer, respectively, using TLX250-CDx PET8. About Eckert & Ziegler SE Eckert & Ziegler SE, with more than 1,000 employees, is a leading specialist in isotope-related components for nuclear medicine and radiation therapy. The company offers a broad range of services and products for the radiopharmaceutical industry, from early development work to contract manufacturing and distribution. Eckert & Ziegler shares (ISIN DE0005659700) are listed in the TecDAX index of Deutsche Börse. For more information visit: www.ezag.com Contributing to saving lives. About Telix Pharmaceuticals Limited Telix is a biopharmaceutical company focused on the development and commercialization 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)9, by the Australian Therapeutic Goods Administration (TGA) 10, and by Health Canada11. No other Telix product has received a marketing authorization 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 Legal Notices You should read this announcement together with our risk factors, as disclosed in our most recently filed reports with the Australian Securities Exchange (ASX) or on our website. The information contained in this announcement is not intended to be an offer for subscription, invitation or recommendation with respect to securities of Telix Pharmaceuticals Limited (Telix) in any jurisdiction, including the United States. The information and opinions contained in this announcement are subject to change without notification. To the maximum extent permitted by law, Telix disclaims any obligation or undertaking to update or revise any information or opinions contained in this announcement, including any forward-looking statements (as referred to below), whether as a result of new information, future developments, a change in expectations or assumptions, or otherwise. No representation or warranty, express or implied, is made in relation to the accuracy or completeness of the information contained or opinions expressed in the course of this announcement. This announcement may contain 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”, “believe”, “outlook”, “forecast” and “guidance”, or the negative of these words or other similar terms or expressions. 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 Telix’s good-faith assumptions as to the financial, market, regulatory and other risks and considerations that exist and affect Telix’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 trials, 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 for Telix’s product candidates, manufacturing activities and product marketing activities; Telix’s sales, marketing and distribution and manufacturing capabilities and strategies; the commercialisation of Telix’s product candidates, if or when they have been approved; Telix’s ability to obtain an adequate supply of raw materials at reasonable costs for its products and product candidates; 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. ©2024 Telix Pharmaceuticals Limited. The Telix Pharmaceuticals® and Illuccix® names and logos are trademarks of Telix Pharmaceuticals Limited and its affiliates – all rights reserved. _____________________________1 Prostate-specific membrane antigen.2 Carbonic anhydrase IX.3 TLX102 labelled with astatine-211. All other listed alpha therapies labelled with actinium-225.4 Large amino acid transporter 1.5 Telix ASX disclosure 17 April 2023.6 ClinicalTrials.gov ID NCT04758780. Positive topline results presented at SABCS in December 2023, Telix media release 7 December 2023. 7 ClinicalTrials.gov ID NCT04897763.8 Positron emission tomography.9 Telix ASX disclosure 20 December 2021.10 Telix ASX disclosure 2 November 2021.11 Telix ASX disclosure 14 October 2022.

This announcement contains inside information for the purposes of Article 7 of the UK version of Regulation (EU) No 596/2014 which is part of UK law by virtue of the European Union (Withdrawal) Act 2018, as amended ("MAR"). Upon the publication of this announcement via a Regulatory Information Service, this inside information is now considered to be in the public domain. 14 September 2024 Avacta Group plc (“Avacta” or “the Group” or “the Company”) Avacta Reports Updated Phase 1 Clinical Data of AVA6000 at the European Society for Medical Oncology (ESMO) Congress Demonstrating Multiple Ongoing, Durable Responses in Solid Tumors AVA6000 is safe and well-tolerated in both study arms: every three weeks (Q3W) and every two weeks (Q2W) dosing, with an early lack of serious cardiac safety signal and preliminary evidence of efficacy Multiple ongoing and durable RECIST responses observed in patients with FAPhigh and doxorubicin sensitive diseases including in patients with stroma-only expression of FAP pre|CISION-enabled doxorubicin (AVA6000) results in multiple fundamental changes in the pharmacokinetics of released doxorubicin in plasma and tumor versus conventional doxorubicin Avacta Group plc (AIM: AVCT), a life sciences company developing innovative, targeted cancer treatments and powerful diagnostics, is today presenting updated data from the ongoing Phase 1a trial of AVA6000 in patients with FAP-positive solid tumors at the 2024 European Society for Medical Oncology (ESMO) Congress, in Barcelona, Spain. The results demonstrate that AVA6000 is well-tolerated across the every 2 weeks and every 3 weeks dosing schedules with early evidence of efficacy supported by ongoing and durable RECIST responses in patients with FAPhigh disease. AVA6000 is the first peptide drug conjugate (PDC) in the Avacta pipeline and consists of doxorubicin conjugated with a peptide moiety that is specifically cleaved by Fibroblast Activation Protein (FAP) in the tumor microenvironment (TME). Professor Chris Twelves, Lead Investigator and Professor of Medicine, University of Leeds, commented: "The AVA6000 data presented at ESMO continue to demonstrate encouraging efficacy with several ongoing, durable responses. The observed efficacy aligns with a highly favorable safety profile including a lack of the significant cardiac toxicity that is often seen with doxorubicin treatment. “The mechanism of action of the pre|CISION™ peptide drug conjugates with the observed warhead release in tumors with lower FAP activity together speak to the potential of this platform to treat a broad range of solid tumor patient populations with clinical needs that are not being met. I am looking forward to working with the Company, colleagues and patients on the continued development of AVA6000." Christina Coughlin MD, PhD, Chief Executive Officer of Avacta, added: “With nearly six months of added follow-up, these compelling data strengthen the clinical validation for AVA6000 and the pre|CISIONTM drug delivery platform to challenge current drug delivery methods and expand the reach of highly potent therapeutics using peptide drug conjugates. “We believe our platform has the potential to revolutionize cancer treatment by enabling patients to achieve improved outcomes with fewer side effects by leveraging the tumor specific enzyme FAP to protect normal tissues from toxic drugs. The observation of warhead release in the tumor even in the setting of lower FAP activity is highly encouraging for our pipeline. We are excited to move our Company into the next stage of development, implementing these findings of this drug release mechanism across our innovative pipeline.” Trial Results Summary As at the latest data cut-off date, ten dose cohorts (n=57) have completed the Phase 1a trial under the Arm 1 dosing schedule of every three weeks (“Q3W”) and the Arm 2 dosing schedule of every two weeks (“Q2W”). In total, 57 patients were enrolled and are evaluable for safety (primary outcome measure) and 49 patients formed the efficacy evaluable dataset (secondary outcome measure). Efficacy data Cancer indications were categorized based on published data regarding both immunohistochemistry and FAPI-PET studies as FAPhigh (soft tissue sarcoma and salivary gland cancer) or FAPmid (pancreatic cancer, colorectal cancer, lung cancer and other malignancies). Patients with indications considered FAPlow were excluded from the trial. Patients had a median of two prior systemic cancer therapies (range 0-7) with 65% including cytotoxic exposure. Reduction in the sum of longest diameters (SLD) is used to measure response per RECIST 1.1 with partial responses of >30% reduction and minor responses of between >10% and <30% reduction. Among patients with FAPhigh cancers (n=23), three partial responses and four minor responses were observed, including: A durable, confirmed partial response at 12 weeks in a 79-year-old male patient with progressive salivary gland cancer (SGC). After an initial minor response (22% reduction in SLD), the observed durable PR is ongoing despite patient discontinuation due to lifetime maximum dosing (duration of response >18 weeks, with 46.2% reduction in SLD). Tumor histology demonstrates no expression of FAP in tumor cells with only stromal cell expression noted.A minor response (14.6% reduction in SLD at first 8-week scan) in a 65-year-old female patient with SGC who remains on the trial. This patient was dosed in the 250 mg/m2 Q2W cohort of the trial and had progression on a prior line of therapy. This patient continues on study. Similarly, the histology shows FAP-negative tumor cells and FAP expression only in the stromal compartment.A partial response (40.5% reduction in SLD) in a 55-year-old male patient with dedifferentiated liposarcoma who had progressed on two prior lines of therapy in the metastatic setting. After an initial minor response this patient experienced a partial response with SLD change of -40.6%. The patient experienced new lesions at their latest follow-up scan. Eight patients remain on study in the Phase 1a cohorts with a diagnosis of FAPhigh cancers Among patients with FAPmid cancers (n=26), two minor responses were observed. Safety and Pharmacokinetics Data Treatment with AVA6000 continues to be well-tolerated with the addition of the Q2W dosing regimen (Arm 2) with a favorable safety profile and reduction in severe and mild-to-moderate treatment-emergent toxicities as compared with conventional dose doxorubicin. A maximum tolerated dose has not been identified in either arm of the trial. Severe (CTCAE grade 3 or 4) neutropenia was observed in 14% of AVA6000 patients vs 49% treated with conventional dose doxorubicin (comparison made to a Ph III trial where doxorubicin monotherapy is the comparator arm in a similar patient population).1 There were no cases of febrile neutropenia in the AVA6000 trial compared to 16.5% of patients receiving conventional doxorubicin alone in a similar patient population1 The observed cardiac safety profile of AVA6000 compares favorably to conventional dose doxorubicin, with low incidence of left ventricular ejection fraction (LVEF) changes (LVEF dysfunction 12.3% v. 48.4% with conventional doxorubicin1,2) and no grade 3 or 4 severe cardiac events reportedReductions were observed in toxicities that impact quality of life including nausea, mouth sores, decreased appetite, constipation and vomiting and similar reductions were observed with both the Q3W and Q2W dosing schedules.as compared to conventional doxorubicin dosing1No new dose limiting toxicities were observed and neither arm has determined an MTD Treatment with AVA6000 results in multiple fundamental changes in the PK of released doxorubicin (compared to conventional doxorubicin administration3) including: Extension of the plasma half-life by ~40% Reduction of approximately 40-50% in both Cmax and the peripheral volume of distribution, suggesting AVA6000-released doxorubicin demonstrates a more limited distribution into normal tissues versus conventional doxorubicin4,5 Tumor biopsies taken 24 hours after the first dose of AVA6000 reveal additional insights regarding the role of FAP, in that the level of FAP positivity in the tumor appears not to correlate with the level of released doxorubicin in the TME (n=9). This lack of correlation indicates that lower levels of FAP activity are sufficient for warhead release. These data provide evidence for targeting of the FAPmid tumor types with novel warheads. pre|CISIONTM technology Many solid tumors have higher levels of FAP compared with healthy tissues. Avacta’s pre|CISIONTM technology is designed to leverage the tumor-specificity of FAP expression by rendering a therapeutic warhead inert with the bound peptide moiety attached to the warhead, until it encounters FAP and is cleaved, releasing active warhead into the TME. FAP targeted release of the warhead specifically in the TME aims to reduce damage to healthy tissues and systemic side effects, improving the tolerability for patients and allowing optimization of the dosing schedule to improve efficacy. References1Tap WD, et al. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA. 2020;323(13):1266-1276. doi: 10.1001/jama.2020.17072Jones, RL et al. Prospective evaluation of doxorubicin cardiotoxicity in patients with advanced soft tissue sarcoma in the ANNOUNCE Phase III randomized trial. Clin Ca Res 2021;27:3751-66. doi: 0.1158/1078-0432.CCR-20-4592 3Villalobos VM, et al. Pharmacokinetics of doxorubicin following concomitant intravenous administration of olaratumab (IMC-3G3) to patients with advanced soft tissue sarcoma. Cancer Med. 2020;9(3):882-893. doi: 10.1002/cam4.27284Kontny N et al, Population pharmacokinetics of doxorubicin: establishment of a NONMEM model for adults and children older than 3 years, Cancer Chemother Pharmacol 2013;71(3):749-63. doi: 10.1007/s00280-013-2069-15Pérez‐Blanco JS et al, Population pharmacokinetics of doxorubicin and doxorubicinol in patients diagnosed with non‐Hodgkin's lymphoma, Br J Clin Pharmacol. 2016; 82(6): 1517–1527 -Ends- For further information from Avacta Group plc, please contact: Avacta Group plcChristina Coughlin, CEOMichael Vinegrad, Group CommunicationsDirector Tel: +44 (0) 1904 21 7070www.avacta.com Peel Hunt (Nomad and Broker)James Steel / Chris Golden / Patrick Birkholm www.peelhunt.com ICR ConsiliumMary-Jane Elliott / Jessica Hodgson / Sukaina Virji avacta@consilium-comms.com About Avacta Group plc - www.avacta.com Avacta Group is a UK-based life sciences company focused on improving healthcare outcomes through targeted cancer treatments and diagnostics. Avacta Therapeutics: a clinical stage oncology biotech division harnessing proprietary therapeutic platforms to develop novel, highly targeted cancer drugs. Avacta Diagnostics focuses on supporting healthcare professionals and broadening access to diagnostics. Avacta has two proprietary platforms, pre|CISION™ and Affimer®. The pre|CISION™ platform is a highly specific substrate for fibroblast activation protein (FAP) which is upregulated in most solid tumors compared with healthy tissues. The pre|CISION™ platform harnesses this tumor specific protease to activate pre|CISION™ peptide drug conjugates and pre|CISION™ antibody/Affimer® drug conjugates in the tumor microenvironment, reducing systemic exposure and toxicity, allowing dosing to be optimised to deliver the best outcomes for patients. The lead pre|CISION™ program AVA6000, a peptide drug conjugate form of doxorubicin, is in Phase 1 studies. It has shown an improvement in safety and tolerability in clinical trials to date compared with standard doxorubicin and preliminary signs of clinical activity in multiple patients. To register for news alerts by email go to www.avacta.com/investor-news-email-alerts