Telix Pharmaceuticals Limited announced a strategy update for the TLX591 (prostate therapy) program. Concurrent with the completion of the acquisition of Atlab Pharma SAS Telix engaged a third-party Clinical Research Organization (CRO) to audit and monitor the clinical data acquired by Weill Cornell Medical Centre (WCMC)1 for 177Lu (lutetium)-huJ591. HuJ591 is a humanized anti-PSMA 2 monoclonal antibody (mAb) that has been extensively studied as a targeting agent in several hundred patients, including 217 patients for targeted radionuclide therapy in multiple Phase I and II studies. HuJ591 is one of the most widely studied targeting agents in radionuclide therapy for prostate cancer. Via the acquisition of Atlab, Telix has certain commercial radiotherapy rights to huJ591. The focus of the audit was prior clinical experience with fractionated (repeat dosing) of 177Lu-huJ591. Fractionated dosing enables the hematologic (blood/marrow) toxicity typically associated with antibody-directed radiotherapy to be ameliorated. A high-level summary of this data has been previously published in a peer-reviewed setting3 but the clinical detail remains largely undisclosed. HuJ591 Fractionated Data: Analysis: The analysis of the audited WCMC huJ591, which includes extensive patient follow-up (to Dec '18) and survival analysis, has confirmed several key findings. An interim analysis report has been issued to Telix with a fully monitored (quality assured) database due at the end of March `19. Impact on Program Decision-Making: Considering the highly promising analysis results for the fractionated huJ591 dose escalation data, Telix's management (in consultation with advisors) have formed the view that: The huJ591 fractionated data supports progressing to a Phase III study in an expedited fashion, particularly given the significant level of commercial interest in PSMA-based therapeutics. This decision accelerates the commencement of a Phase III trial by approximately 2 years, subject to regulatory approval. Telix's proprietary engineered huJ591 (previously denoted as TLX591) will continue to be developed as a "second generation" program for use with an alpha-emitting radionuclide (225Ac ­ actinium). Actinium is a promising fit for the kinetics and product profile of this antibody and further extends the depth of Telix's therapeutic pipeline. Manufacture of huJ591 and TLX591: Telix has previously disclosed that it is manufacturing both a proprietary huJ591 variant and the "original" huJ591 for clinical use. Telix elected to manufacture clinical grade huJ591 to support comparability studies and several important ongoing collaborations, including with WCMC and BZL Biologics LLC. As such the Company has an existing manufacturing plan that is supportive of this strategic pivot. Indicative Timelines. March 19: submission of an information package to the US Food and Drug Administration (FDA), summarizing the entirety of the clinical data for 177Lu-huJ591. Request for an "end of Phase II meeting" to formally review the existing data and establish a Phase III roadmap. May/June `19: FDA meeting request to obtain guidance on proposed Phase III clinical trial protocol (currently under development with Telix's medical advisors). The Company envisages also recruiting patients in Australia and therefore this trial will also require registration with the Therapeutic Goods Administration (TGA). August/September `19: Release of radiolabeled material suitable to potentially support early patient recruitment in Australia. Fourth Quarter '19: Filing of Phase III Investigational New Drug (IND) application based on FDA guidance. Impact on Capital Requirements: The Company's budgeted activity includes completion of manufacturing of huJ591. The Company had also budgeted for a US-based Phase II study of the re-engineered huJ591 in approximately 120 patients (planned start mid-2019). This expenditure will be now deferred until the start of a Phase III trial in late 2019 /early 2020 in order to prioritize huJ591. Telix has adequate funding to prepare the necessary documentation to engage with the relevant regulatory authorities. Telix does not currently have sufficient capital to execute a Phase III trial. However, further capital would not be sought for such a study until the Company had agreement from the FDA to proceed (late 2019 /early 2020). Potential commercial partnerships may also offset future capital needs.