IM-3050 / Immunome - LARVOL DELTA

Immunome Reports Full Year 2024 Financial Results and Provides Business Update (Businesswire) - "Pipeline Highlights:...IM-3050: Immunome recently submitted an IND for IM-3050 and expects to initiate a clinical trial for the program in the second half of 2025."

IND • New trial • Solid Tumor

Immunome Provides Pipeline Update in Advance of Presentation at the 43rd Annual J.P. Morgan Healthcare Conference (Businesswire) - "The presentation will cover Immunome’s pipeline of targeted therapeutics, including varegacestat (formerly known as AL102), a once-daily oral gamma secretase inhibitor in the Phase 3 RINGSIDE clinical trial for the treatment of desmoid tumors. Immunome expects to report topline data in the second half of 2025....Immunome also announced the FDA clearance of its IND submission for IM-1021, a ROR1-targeted ADC. Immunome anticipates submitting an IND for IM-3050, its FAP-targeted radioligand therapy, by the end of the first quarter of 2025."

IND • P3 data: top line • Desmoid Tumors

Immunome Reports Third Quarter 2024 Financial Results and Provides Business Update (Businesswire) - "Immunome expects to report topline data for RINGSIDE Part B in the second half of 2025. In parallel, Immunome is performing additional manufacturing and pharmacology work required to support a new drug application filing for AL102. Immunome also anticipates submitting INDs for IM-1021 and IM-3050 in the first quarter of 2025, as previously disclosed."

IND • P3 data • Desmoid Tumors

Prolonged disease-free survival and bladder preservation in a patient with chemotherapy-resistant Muscle Invasive Bladder Cancer (MIBC) after first-in-human 177Lu-FAP radioligand treatment - the RadioMolecularIncubator Experience within the Bladder BRIDGister. (EANM 2024) - "Three cycles Gemcitabin/Cisplatin chemotherapy were applied; however, the patient denied planned cystectomy...The second PTRT in 05/23 included intravesical application via transurethral catheter of 2.9 GB 177Lu-3BP-3940 followed by i.v. application of 3.9 GBq 177Lu-3BP-3940 plus 200 mg Pembrolizumab infusion as radiosensitizer 3h after radioligand therapy... To the best of our knowledge this is the first molecularly stratified, theranostic application of FAP radioligand therapy (RLT) by transurethral intravesical instillation plus systemic administration in combination with immune checkpoint inhibitor therapy after initial immune-sensitizing RLT. Remarkably, complete response of chemotherapy-resistant MIBC was achieved. A phase I/II study is currently initiated."

Clinical • IO biomarker • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • FAP • KRT20 • KRT5 • NECTIN4 • PPARG

Impact of molar mass of FAPI on 68Ga/177Lu-FAPI PET imaging and radiotherapy for targeting murine FAP in wildtype tumor cell line derived xenograft (EANM 2024) - "The administration molar mass of 68Ga/177Lu-FAPI-04 shall apparently influence FAP-targeted imaging results and therapeutic effect. It's never careful enough to take it in consideration when apply radiolabeled FAP ligands to FAP-targeted PET imaging and radiotherapy in preclinical situation."

Preclinical • Tumor cell • Oncology • FAP

The first case of 99m Tc-FAPI Uptake in Optic Nerve sheath Meningioma (EANM 2024) - "Nonetheless, FAPI avidity may offer hope for future treatment planning with 177Lu-FAPI in patients who are refractory to 177Lu-Dotatate treatment. Overall, this study highlights the potential use of FAPI-ligand uptake as a diagnostic and therapeutic tool for optic nerve sheath meningioma patients who have not responded well to traditional treatments. Further research is needed to explore this potential further and optimize treatment strategies using FAPI-ligands."

Clinical • Brain Cancer • CNS Tumor • Meningioma • Oncology • Solid Tumor

Enhanced Diagnostic and Therapeutic Potentials of 68Ga-LNC1013 and 177Lu-LNC1013 in Cancer Imaging and Radionuclide Therapy: A Comparative and Preclinical Study (EANM 2024) - "This tracer demonstrated superior tumor growth inhibition compared to 177Lu-FAPI-46 and control groups in CDXs, suggesting effective radionuclide therapy potential. 68Ga-LNC1013 outperforms 18F-FDG in the diagnostic imaging of diverse cancer types, providing higher contrast and detection sensitivity. The theranostic potential of this tracer series is further highlighted by the promising therapeutic outcomes of 177Lu-LNC1013 in preclinical models, setting the stage for advanced FAP-targeted theranostics in oncology."

Preclinical • Oncology

Localized in vivo prodrug activation using radionuclides. (PubMed, bioRxiv) - "RAiDER was evaluated in syngeneic mouse models of cancer using fibroblast activation protein inhibitor (FAPI) agents 99m Tc-FAPI-34 and 177 Lu-FAPI-04, the prostate-specific membrane antigen (PSMA) agent 177 Lu-PSMA-617, combined with caged-MMAE or caged-exatecan. This proof-of-concept study shows that RAiDER is compatible with multiple radionuclides commonly used in nuclear medicine and has the potential to improve the efficacy of radiopharmaceutical therapies to treat cancer safely. RAiDER thus shows promise as an effective strategy to treat disseminated malignancies and broadens the capability of radiopharmaceuticals to trigger diverse biological and therapeutic responses."

Journal • Preclinical • Oncology

Immunome Reports Second Quarter 2024 Financial Results and Provides Business Update (Businesswire) - "...Immunome continues to expect to report topline data for RINGSIDE Part B in the second half of 2025. In parallel, Immunome is performing additional manufacturing and pharmacology work required to support a new drug application filing for AL102. Immunome also anticipates submitting INDs for IM-1021 and IM-3050 in the first quarter of 2025, as previously disclosed."

Commercial • IND • P3 data • Desmoid Tumors

Clinical translation of a novel FAPI dimer [68Ga]Ga-LNC1013 (SNMMI 2024) - "The lead compound, 68Ga -LNC1013, was then labeled with 177Lu in a biodistribution study against the FAPI monomer, 177Lu-FAPI-46, measured with a γ-counter. Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over their monomeric counterparts. We demonstrated that LNC1013, the lead compound without piperazine moiety, had superior diagnostic potential when labeled with 68Ga over 68Ga-FAPI-46 and 18F-FDG. A preliminary experiment with 177Lu suggests extended retention of dimer in HT-1080 tumor-bearing mice model and implies its potential for radioligand therapy of FAP-positive cancers."

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • FAP

Clinical translation of a novel FAPI dimer [68Ga]Ga-LNC1013 (SNMMI 2024) - "The lead compound, 68Ga -LNC1013, was then labeled with 177Lu in a biodistribution study against the FAPI monomer, 177Lu-FAPI-46, measured with a γ-counter. Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over their monomeric counterparts. We demonstrated that LNC1013, the lead compound without piperazine moiety, had superior diagnostic potential when labeled with 68Ga over 68Ga-FAPI-46 and 18F-FDG. A preliminary experiment with 177Lu suggests extended retention of dimer in HT-1080 tumor-bearing mice model and implies its potential for radioligand therapy of FAP-positive cancers."

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • FAP

Clinical translation of a novel FAPI dimer [68Ga]Ga-LNC1013 (SNMMI 2024) - "The lead compound, 68Ga -LNC1013, was then labeled with 177Lu in a biodistribution study against the FAPI monomer, 177Lu-FAPI-46, measured with a γ-counter. Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over their monomeric counterparts. We demonstrated that LNC1013, the lead compound without piperazine moiety, had superior diagnostic potential when labeled with 68Ga over 68Ga-FAPI-46 and 18F-FDG. A preliminary experiment with 177Lu suggests extended retention of dimer in HT-1080 tumor-bearing mice model and implies its potential for radioligand therapy of FAP-positive cancers."

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • FAP

Clinical translation of a novel FAPI dimer [68Ga]Ga-LNC1013 (SNMMI 2024) - "The lead compound, 68Ga -LNC1013, was then labeled with 177Lu in a biodistribution study against the FAPI monomer, 177Lu-FAPI-46, measured with a γ-counter. Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over their monomeric counterparts. We demonstrated that LNC1013, the lead compound without piperazine moiety, had superior diagnostic potential when labeled with 68Ga over 68Ga-FAPI-46 and 18F-FDG. A preliminary experiment with 177Lu suggests extended retention of dimer in HT-1080 tumor-bearing mice model and implies its potential for radioligand therapy of FAP-positive cancers."

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • FAP

Preclinical Evaluation of 68Ga/177Lu labeled novel FAP-targeted peptide for tumor radionuclide imaging and therapy (SNMMI 2024) - "In therapeutic studies, 177Lu-FAP-HXN showed significant antitumor activity in HEK-293-FAP tumors at well-tolerated doses, which also exhibited longer tumor retention and better tumor growth delay in comparison to FAP-2286. Preclinical studies show that radiolabeled FAP-HXN had high tumor uptake and retention, as well as potent efficiency in HEK-293-FAP tumors. FAP-HXN has the potential as a novel theranostic tracer for clinical translation in FAP-positive tumors."

Preclinical • Oncology • FAP

68Ga-FAPI-RGD PET/CT Detected Skull Metastasis Better Than 18F-FDG in a Patient With Radioiodine-Refractory Differentiated Thyroid Cancer. (PubMed, Clin Nucl Med) - "68Ga-FAPI-RGD PET/CT demonstrated higher tracer uptake and clearer lesion boundaries compared with 18F-FDG PET/CT. This suggests that 177Lu-FAPI-RGD could potentially serve as a treatment option for radioiodine-refractory differentiated thyroid cancer."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

First Experience of Radionuclide Therapy With 177Lu-FAPI-2286 in a Patient With Metastatic Mediastinal Sarcoma. (PubMed, Clin Nucl Med) - "FAP inhibitors (FAPIs) labeled with 177Lu could be potentially a therapeutic radiopharmaceutical. Here, we presented the experience of 4 cycles of 177Lu-FAPI in a 67-year-old man with an unresectable mediastinal sarcoma."

Journal • Metastases • Oncology • Sarcoma • Solid Tumor

Immunome Reports First Quarter 2024 Financial Results and Provides Business Update (Businesswire) - "Immunome expects to report topline data for RINGSIDE Part B in the second half of 2025...Immunome anticipates submitting INDs for two preclinical candidates in the first quarter of 2025: IM-1021, a ROR1 ADC, and IM-3050, a FAP-targeted RLT....In-process research and development expenses for the quarter ended March 31, 2024 were $112.0 million. These expenses were related to Immunome’s acquisition of AL101 and AL102 from Ayala Pharmaceuticals, Inc. and the exclusive license of IM-1021 and related ADC platform technology from Zentalis Pharmaceuticals, Inc., both of which closed in the quarter ended March 31, 2024."

Commercial • IND • P2/3 data • Desmoid Tumors • Oncology • Solid Tumor

The Synergy of 177Lu-FAPI-046 with Tyrosine Kinase Inhibitor in a Sarcoma Patient-Derived Xenograft Mouse Model. (PubMed, Biomed J) - "This study successfully demonstrated the reduction in FAP expression and suppression of tumor volume in sarcoma PDX following the combination therapy of 177Lu-FAPI-46 with Pazopanib."

Journal • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CASP3 • FAP

A novel lutetium-177 radioligand therapy targeting FAP has potent antitumor activity in xenograft cancer model (AACR 2024) - "Screening this library for binding, biodistribution and pharmacology properties identified a 177Lu-FAP RLT lead molecule...The treatment was well-tolerated, with no significant weight loss or deaths. The outstanding antitumor activity and high selectivity for FAP support further evaluation of this investigational RLT in patients with solid tumors."

Preclinical • Oncology • Solid Tumor

Novel fibroblast activation protein targeting radioligand for imaging and radiotherapy of solid tumors (AACR 2024) - "Finally, analysis of tumor inhibiting activity demonstrated that 177Lu-FAP8-IP-DOTA suppressed tumor growth between 60% and 100% in all xenograft models tested (HT29, MDA-MB-231, KB and 4T1), with remarkably improved overall survival rates compared to untreated groups. Based on these promising results, we suggest that FAP8-IP-DOTA warrants further evaluation for possible translation into human clinical trials."

Oncology • Solid Tumor • CAFs

Immunome Reports Full Year 2023 Financial Results and Provides Update on Recently Acquired Assets (Businesswire) - "Topline data for Phase 3 RINGSIDE trial of AL102 expected in first quarter of 2025; IM-1021 and IM-3050 IND filings expected in first quarter of 2025; Current cash expected to fund activities into 2026."

IND • P3 data: top line • Desmoid Tumors • Oncology • Solid Tumor

Immunome to Present Preclinical Data for IM-3050, Its Lead Radioligand Therapy Candidate, at 2024 American Association for Cancer Research (AACR) Annual Meeting (Businesswire) - "Immunome...announced that it will present preclinical data for IM-3050, the company’s lead lutetium-177 radioligand therapy (RLT) targeting fibroblast activation protein (FAP). Jack Higgins, PhD, Chief Scientific Officer at Immunome, will present the data in a poster at the American Association for Cancer Research (AACR) Annual Meeting 2024....Immunome expects to submit an Investigational New Drug application to the U.S. Food & Drug Administration for IM-3050 in the first quarter of 2025."

IND • Preclinical • Oncology

Theranostic imaging and treatment of chemotherapy resistant muscle invasive bladder cancer by targeting FAP and CXCR4: The Bladder BRIDGister experience. (ASCO-GU 2024) - "PET/CT Imaging by CXCR4 and/or FAP instillation was performed in selected patients followed by systemic radioligand application after completion of cisplatinum based NACT to enable improved staging...Theranostic instillation imaging revealed strong uptake into the invading MIBC and subsequent instillation therapy with 177Lu-FAP led to partial remission and increased immune cell infiltration indicating initial effectivity... Expression of the radioligand targets CXCR4 and FAP are associated with aggressive stromal and basal like tumors being resistant to NACT. This could be validated by selecting patients for FAP & CXCR4 PET/CT imaging. Instillation of radioligands into the bladder revealed to be safe with first signs of effectivity justifying clinical approaches as part of phase 1 / 2 clinical trials."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CXCR4 • FAP • FGFR3 • HER-2

Immunome Reports Third Quarter 2023 Financial Results (Businesswire) - "Highlights: (i) IMM-ONC-01: We expect to provide guidance in Q1 2024 regarding our timeline to submit to the FDA an IND for IMM-ONC-01; (ii) 177Lu-FAP: We anticipate an IND submission with the FDA in Q1 2025."

IND • Oncology