Pipeline

AlphaMedix^TM is a somatostatin receptor targeting peptide radiolabeled with ²¹²Pb for the treatment of somatostatin receptor expressing neuroendocrine tumors (NETs). Somatostatin receptors are overexpressed in most neuroendocrine tumors, a heterogeneous group of rare neoplasms that originate from neuroendocrine cells. These neoplasms occur mostly in the gastrointestinal tract and pancreas, but can also occur in other tissues including thymus, lung, and other uncommon sites such as ovaries, heart, and prostate.

AlphaMedix^TM obtained particularly promising results in the phase 1 trial launched in 2018. AlphaMedix has been evaluated in a non-randomized, open label, and single ascending dose (SAD) to Multiple Ascending Dose (MAD) trial. The treatment was well-tolerated and a response rate (ORR: objective response rate according to the RECIST 1.1 method) of 67% was observed. In addition, a supplementary cohort of patients already having received a radioligand therapy and in whom the disease had progressed was recruited. A response rate of 60% was measured in these patients.

AlphaMedix^TM entered Phase 2 clinical trials in 2021 to assess its safety and efficacy in the treatment of neuroendocrine tumors. AlphaMedix has been evaluated in a single arm, non-randomized, open-label trial that has enrolled 69 patients with somatostatin receptor expressing neuroendocrine tumors. After completing recruitment of patients who had never previously received radioligand therapy in 2023, recruitment of the second cohort of patients who progressed after receiving it was also completed in 2024. Once again, the treatment was generally well-tolerated, with a low rate of hematologic toxicity. The data has been presented in two oral sessions, at ASCO and NANETS in 2024. As of October 2024, the results presented at NANETS showed a response rate (ORR: objective response rate according to the RECIST 1.1 method) of 54.3%. These results remain preliminary, and data collection is ongoing.

In February 2024, the United States Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to AlphaMedix^TM (²¹²Pb-DOTAMTATE) for the treatment of adult patients with unresectable or metastatic, progressive somatostatin receptor expressing gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who are naïve to peptide receptor radionuclide therapy (PRRT). AlphaMedix^TM is the first Targeted Alpha Therapy to receive Breakthrough Therapy Designation.

In September 2024, Orano Med and RadioMedix entered into an exclusive licensing agreement with Sanofi for AlphaMedix™. Under this agreement, Sanofi assumes global responsibility for the commercialization of AlphaMedix™.

• More results on the AACR Journals site

Expanded access policy:

Currently, Orano Med, does not offer an expanded access program and is not accepting expanded access requests for AlphaMedix™. Our development resources are focused on conducting clinical trials that evaluate the safety and efficacy of our treatment. 

If you have additional questions about Orano Med’s expanded access policy, please email us at partner@oranomed.com.  

Find out more:

• www.clinicaltrials.gov
• Presentation of preliminary results of the phase 1 on the website of The Journal of Nuclear Medicine

• Side-by-Side Comparison of the In Vivo Performance of [²¹²Pb]Pb-DOTAMTATE and Other SSTR2-Targeting Compounds

Sanofi is an innovative global healthcare company, driven by one purpose: chasing the miracles of science to improve people’s lives. Across the world, its teams are dedicated to transforming the practice of medicine by working to turn the impossible into the possible. Sanofi provides potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of its ambitions. 

RadioMedix, Inc. is a clinical stage biotechnology company, based in Houston, Texas, focused on innovative targeted radiopharmaceuticals for diagnosis, monitoring, and therapy of cancer. The company is developing radiopharmaceuticals for PET imaging and therapeutic (alpha and beta-labeled) radiopharmaceuticals. RadioMedix has also established 21 CFR 211 compliant contract service facilities for academic and industrial partners: Full cGMP manufacturing and analytical suites for human clinical trials, and commercial phase manufacturing of the radiopharmaceuticals, in addition to small animal Molecular Imaging Center for the pre-clinical evaluation of new targets in vitro and in vivo.

²¹²Pb-GRPR is an anti-GRPR (Gastrin-Releasing Peptide Receptor) peptide radiolabeled with ²¹²Pb developed by Orano Med for the treatment of tumor types overexpressing GRPR, a G-protein-coupled receptor in the family of bombesin receptors. Its ligand, gastrin-releasing peptide (GRP) regulates numerous physiological functions of the gastrointestinal and central nervous systems including release of gastrointestinal hormones, smooth muscle cell contraction and epithelial cell proliferation. GRPR is overexpressed in many types of solid tumors.

Based on promising preclinical data published in JNM, Orano Med has obtained the FDA's approval to launch investigations of a new drug. The phase 1 clinical trial in the US includes patients with metastatic castration-resistant prostate cancer (mCRPC), HR+/HER2- breast cancer, Colorectal cancer, Cervical cancer, cutaneous melanoma and Non-small-cell lung cancer (NSCLC).

• Find out more : www.clinicaltrials.gov
• More results on the JNM website. 

²¹²Pb-PSMA is a peptide targetting PSMA (Prostate-Specific Membrane Antigen) radiolabeled with ²¹²Pb against prostate cancer developed by Orano Med. 

²¹²Pb-PRIT collaboration (pre-targeted radio immunotherapy) is a joint development with Roche to create a novel, advanced alpha radioimmunotherapy platform to target and kill cancer cells with a specific focus on cancer with a high unmet medical need. The first program targets carcinoembryonic antigen (CEA), a cell surface glycoprotein overexpressed in several cancers, including colorectal, pancreatic, gastric, and non-small cell lung cancer. Its restricted expression in normal tissues makes it an attractive target for antibody-based therapies and radioimmunotherapy.

A novel two-step PRIT clearing agent-independent PRIT regimen for carcinoembryonic antigen (CEA)-positive tumors, involving a complementary bispecific antibody pair and ²¹²Pb, has been developped. It showed excellent efficacy and safety in preclinical studies. The method achieved tumor uptake of 25–30% injected activity per gram (IA/g) at 24 hours post-injection, with minimal off-target retention in blood (<0.5% IA/g) and kidneys (<2% IA/g). The two-step regimen effectively enabled rapid excretion of unbound radioligand while maintaining high tumor specificity, comparable to the more complex three-step PRIT approach. It also significantly delayed tumor growth with only mild, transient weight loss observed. This optimized two-step PRIT approach simplifies logistics, eliminates the need for a clearing agent, and supports ongoing efforts to translate it into clinical trials, potentially enhancing the accessibility of PRIT for patients.

Preclinical Evaluation of a Novel Clearing Agent-Independent Approach for Pretargeted Alpha Therapy with ²¹²Pb

Roche is a Swiss pharmaceutical company and the world leader in the oncology field. Orano Med and Roche launched a strategic alliance in 2012 to develop a new platform. As part of this new alliance, Roche and Orano Med have built a research laboratory located in France dedicated to the co-development of targeted alpha therapy.

Orano Med has entered into a collaboration with Molecular Partners to develop a platform of Targeted Alpha Therapies using DARPIns radiolabeled with ²¹²Pb. DARPin therapeutics are a new class of custom-built protein therapeutics based on natural binding proteins capable of powerful and highly selective targeting of tumor cells.  The DARPin platform is a fast and cost-effective drug discovery engine, producing drug candidates with optimized properties for development and very high production yields.

In 2024, Orano Med and Molecular Partners announced  the debut of their lead Radio-DARPin therapy candidate MP0712, targeting DLL3 and radiolabeled with lead-212. 

. DLL3 is a highly relevant target for radiopharmaceutical therapy due to its abundant expression in tumors of patients with small cell lung cancer and other aggressive neuroendocrine tumors, while expression in healthy tissues is low.

The data presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2024 Annual Meeting and the European Associaton of Nuclear Medicine 2024 Annual Meeting provide strong support for MP0712’s clinical development in small-cell lung cancer  and other DLL3+ neuroendocrine tumors. 

The preclinical studies of MP0712 demonstrated compelling evidence of its efficacy and safety as a DLL3-targeting Radio-DARPin Therapeutic (RDT). ²¹²Pb-DLL3 RDT candidates were engineered by tuning their biophysical properties to achieve an optimal safety/antitumor activity profile in vivo. In vivo models showed strong, homogeneous tumor uptake with favorable tumor-to-kidney ratios exceeding 2, indicating effective targeting with minimal off-target effects. MP0712 exhibited significant and durable tumor growth inhibition at clinically relevant doses, with safety data confirming good tolerability across dosing levels.

Check out the presentations : 

• ²¹²Pb-DLL3 Radio-DARPin shows promising Preclinical Antitumor Efficacy in Small Cell Lung Cancer

• Preclinical Assessment of ²¹²Pb-Radio-DARPin Therapeutic (RDT) Targeting DLL3 in SCLC

• Preclinical Assessment of MP0712: ²¹²Pb Radio-DARPin Therapeutic Targeting DLL3 for SCLC

   

Molecular Partners AG is a clinical-stage biotech company developing DARPin (designed ankyrin repeat protein) therapeutics. The Company has formed partnerships with leading pharmaceutical companies to advance DARPin therapeutics in the areas of oncology and virology and has compounds in various stages of clinical and preclinical development across multiple therapeutic areas. Orano Med and Molecular Partners agreed on a partnership to develop up to 10 programs.

Orano Med has entered into a collaboration with Molecular Partners to develop a platform of Targeted Alpha Therapies using DARPIns radiolabeled with ²¹²Pb. DARPin therapeutics are a new class of custom-built protein therapeutics based on natural binding proteins capable of powerful and highly selective targeting of tumor cells. The DARPin platform is a fast and cost-effective drug discovery engine, producing drug candidates with optimized properties for development and very high production yields.

Following the promising results of MP0712, Molecular Partners and Orano Med have selected mesothelin (MSLN) as the target for the second program. Mesothelin is a cell surface glycoprotein overexpressed across several cancers with high unmet need, such as ovarian cancer, pancreatic cancer mesothelioma and other types, and largely absent from healthy tissues. The development of therapeutics against MSLN has been hampered by high shedding of MSLN. Molecular Partners has developed Radio-DARPins able to selectively bind to the membrane-proximal portion of MSLN present on cells and are therefore not impacted by shed MSLN.

Molecular Partners AG is a clinical-stage biotech company developing DARPin (designed ankyrin repeat protein) therapeutics. The Company has formed partnerships with leading pharmaceutical companies to advance DARPin therapeutics in the areas of oncology and virology and has compounds in various stages of clinical and preclinical development across multiple therapeutic areas. Orano Med and Molecular Partners agreed on a partnership to develop up to 10 programs.

Orano Med has entered into a collaboration with Molecular Partners to develop a platform of Targeted Alpha Therapies using DARPIns radiolabeled with ²¹²Pb. DARPin therapeutics are a new class of custom-built protein therapeutics based on natural binding proteins capable of powerful and highly selective targeting of tumor cells. The DARPin platform is a fast and cost-effective drug discovery engine, producing drug candidates with optimized properties for development and very high production yields.

Molecular Partners AG is a clinical-stage biotech company developing DARPin (designed ankyrin repeat protein) therapeutics. The Company has formed partnerships with leading pharmaceutical companies to advance DARPin therapeutics in the areas of oncology and virology and has compounds in various stages of clinical and preclinical development across multiple therapeutic areas. Orano Med and Molecular Partners agreed on a partnership to develop up to 10 programs.

Due to longer accumulation of antibodies targeting antigens expressed by solid tumors (usually several days), Orano Med is developing new approaches to label ²¹²Pb to peptides offering a more suitable pharmacokinetic profile for ²¹²Pb half-life. Orano Med is working on several targets expressed in various type of cancers. Orano Med uses biotechs developing phage display technologies to optimize the discovery of targeting peptides.

Phage display platform : 48Hour Discovery is a company with a dynamic peptide discovery platform that has revolutionized drug discovery through its innovative approaches to peptide design. Leveraging cutting-edge technologies, the platform accelerates the identification and optimization of peptides with therapeutic potential, offering a novel pathway to addressing unmet medical needs.

Due to longer accumulation of antibodies targeting antigens expressed by solid tumors (usually several days), Orano Med is developing new approaches to label ²¹²Pb to peptides offering a more suitable pharmacokinetic profile for ²¹²Pb half-life. Orano Med is working on several targets expressed in various type of cancers. Orano Med uses biotechs developing phage display technologies to optimize the discovery of targeting peptides.

Phage display platform : Biosynth secures life science supply chains with manufacture and supply of high-quality products thanks to its expertise and capability run across Complex Chemicals, Peptides and Key Biologics. Knowing of the importance of 3D conformation for many biological interactions, Biosynth’s peptide discovery chemists are experts in discovering and optimizing constrained peptides, using the proprietary CLIPS™ technology, that bind the target protein of interest.