177Lu-DOTATATE(The University of Chicago)

As radiopharmaceuticals continue their hot streak, one of the few players with a marketed product, ITM Isotope Technologies Munich, has pulled in additional funding to help advance its lead pipeline candidate. The firm has secured a new investment of €188 million ($204 million), led by previous backer Temasek, with participation from BlackRock, Qatar Investment Authority and ATHOS.ITM currently markets EndolucinBeta, which uses lutetium-177 (177Lu) for radiolabelling of other medicines, and TOCscan/Sogacin, which uses gallium (68Ga) edotreotide for diagnosing neuroendocrine tumours (NETs). While the two products are sold in a handful of European countries, ITM's pipeline has loftier ambitions and is stacked with a number of targeted radionuclide therapies based not only on 177Lu and 68Ga, but also on actinium-225 (225Ac), fluorine-18 and terbium-161.Phase III nearing completionIts lead asset, ITM-11 (177Lu-edotreotide), is nearing the end of Phase III testing in gastroenteropancreatic NETs (GEP-NETs). The late-stage COMPETE study is evaluating ITM-11 in patients with Grade 1 - 2 GEP-NETs, while the COMPOSE trial is for patients with well-differentiated high Grade 2 - 3 GEP-NETs. With this in mind, ITM will use some of the proceeds from the latest financing to “prepare commercial readiness” of ITM-11.“We have reached key milestones since our last financing round including advancing our pipeline with novel targets in multiple oncology indications,” remarked CEO Steffen Schuster. Almost exactly a year ago to the day, ITM announced a haul of €255 million – again led by Temasek – building on the €58 million it raised in 2022 and €114 million it secured in the prior year. Key supplier to NovartisAside from its internal pipeline, ITM recently launched a joint venture to produce 225Ac, while it has several supply agreements in place for 177Lu, including with Telix Pharmaceuticals and Endocyte, the latter now part of Novartis. In fact, the Swiss drugmaker is one of the key players in the radiopharmaceutical space, with its marketed products including Lutathera (177Lu dotatate) for GEP-NETs and the prostate cancer therapy Pluvicto (177Lu vipivotide tetraxetan). However, Novartis itself has faced production issues for Pluvicto, and only recently gained clearance for a new US radioligand manufacturing facility to help it keep up with demand.ITM plans to put some of the new funding toward ramping up its in-house manufacturing capacities for 177Lu and expand these to new radioisotopes including 225Ac. ITM said it will use the radioisotopes not only for its own pipeline, but also provide them to its global supply network. For related analysis, see Vital Signs: Mapping the slim pickings in radiopharmaceuticals.

Key data from the Phase III PSMAfore trial has been selected for a Presidential session; PSMAfore is investigating PluvictoTM (INN: lutetium (177Lu) vipivotide tetraxetan) in the pre-chemotherapy setting for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) New analysis of key subgroups of clinical interest from NATALEE reinforces the potential of Kisqali® (ribociclib) plus endocrine therapy (ET) to consistently reduce the risk of cancer recurrence across a broad population of patients with stage II and stage III HR+/HER2- early breast cancer, including those with no nodal involvement Basel, October 5, 2023 — Novartis will present new data from 29 Novartis and investigator-led abstracts at the European Society for Medical Oncology (ESMO) Congress 2023, highlighting latest developments from across its oncology portfolio and addressing unmet needs of patients diagnosed with some of the most prevalent cancers, including prostate and breast. Key data from the Phase III PSMAfore trial investigating PluvictoTM (INN: lutetium (177Lu) vipivotide tetraxetan) as an earlier line of treatment for patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have not been exposed to a taxane-containing regimen will be presented. PSMAfore met its primary endpoint of radiographic progression-free survival (rPFS) in December 2022, and data collection for the key secondary endpoint of overall survival (OS) is ongoing. Data from the primary rPFS analysis and the second interim OS analysis will be presented at ESMO. “Metastatic prostate cancer has a five-year survival rate of about 30 percent, and patients who progress despite taking androgen-receptor pathway inhibitor therapy need additional treatment options with reduced toxicity,” said Jeff Legos, Executive Vice President, Global Head of Oncology and Hematology Development at Novartis. “Pluvicto is the first and only approved, targeted radioligand therapy to significantly extend life in patients with mCRPC who have been treated with ARPI therapy and taxane-based chemotherapy. We look forward to sharing new data from the Phase III PSMAfore trial, which adds to the growing body of evidence demonstrating the potential of our radioligand therapy platform in earlier lines of therapy.” Key highlights of data accepted by ESMO include: Medicine Abstract title Presentation Number / Presentation Details Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) Phase 3 trial of [177Lu]Lu-PSMA-617 in taxane-naïve patients with metastatic castration-resistant prostate cancer (PSMAfore) Presentation Number #LBA13Presidential 3 (Proffered Paper session): Monday, October 23, 17:10 – 17:22 CEST Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) First real life data on [177Lu]Lu-PSMA-617: Descriptive analysis on the largest metastatic castration-resistant prostate cancer (mCRPC) cohort treated in early access in France Presentation Number #1814P Poster available: Sunday, October 22, 9:00 – 17:00 CEST Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) Enzalutamide and 177Lu-PSMA-617 in poor-risk metastatic, castration-resistant prostate cancer (mCRPC): a randomized phase 2 trial: ENZA-p (ANZUP 1901) Presentation Number #LBA84 Proffered Paper session: Friday, October 20, 16:40 – 16:50 CEST Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) Prognostic value of neutrophil-to-lymphocyte ratio and lymphopenia in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with [177Lu]Lu-PSMA-617: VISION post-hoc analysis Presentation Number #1838P Poster available: Sunday, October 22,9:00 – 17:00 CEST Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) Association of health-related quality of life with efficacy outcomes in the VISION study of patients with metastatic castration-resistant prostate cancer Presentation Number #1810P Poster available: Sunday, October 22,9:00 – 17:00 CEST Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) Molecular features of circulating tumour cells (CTCs) associate with response to 177Lu PSMA 617 plus pembrolizumab for metastatic castration resistant prostate cancer (mCRPC). Presentation Number #1825PPoster available: Sunday, October 22,9:00 – 17:00 CEST Kisqali® (ribociclib)* Invasive disease-free survival (iDFS) across key subgroups from the Phase III NATALEE study of ribociclib (RIB) + a nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2- early breast cancer (EBC) Presentation Number #LBA23 Mini oral session: Monday, October 23, 17:05 – 17:10 CEST Kisqali® (ribociclib)* First-line ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in aggressive HR+/HER2- advanced breast cancer (ABC): a subgroup analysis of patients (pts) with or without visceral crisis from the Phase II RIGHT Choice study Presentation Number #402P Poster available: Saturday, October 21, 9:00 – 17:00 CEST Kisqali® (ribociclib)* Quality of life (QOL) analysis from the Phase II RIGHT Choice study of first-line ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in aggressive HR+/HER2- advanced breast cancer (ABC) Presentation Number #456P Poster available: Saturday, October 21, 9:00 – 17:00 CEST Lutathera® (lutetium Lu 177 dotatate) A Prospective Phase II Single-Arm Trial on Neoadjuvant Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE Followed by Surgery for Pancreatic Neuroendocrine Tumors (NeoLuPaNET) Presentation Number #1186MO Mini oral session: Sunday, October 22, 17:25 – 17:30 CEST Product InformationFor full prescribing information, including approved indications and important safety information about marketed products, please visit https://www.novartis.com/about/products. 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