Non-clinical study findings published in the journal Molecular Cancer Therapeutics describing the characterization of the anti-CD205 antibody-drug conjugate (ADC) MEN1309/OBT076, being developed by the Italian pharmaceutical company Menarini Ricerche shows substantial in vitro activity resulting in durable responses and complete tumor regressions in triple negative breast cancer (TNBC), pancreatic, and bladder cancer cell-line derived and patient-derived xenograft (PDX) models, independent of antigen expression levels.[1]
CD205, a transmembrane glycoprotein and a member of the macrophage mannose receptor family of C-type lectins also known as lymphocyte antigen 75, LY75 and DEC-205, is robustly expressed in a variety of solid malignancies, such as pancreatic and bladder tumors, as well as triple negative breast cancer (TNBC). In these settings, MEN1309/OBT076 showed substantial in vitro antitumor activity.
These results were confirmed in vivo where MEN1309/OBT076 demonstrated potent antitumor activity in TNBC, pancreatic, and bladder xenografts and patient-derived PDX models, resulting in durable responses and complete tumor regressions.
Menarini Ricerche’s ADCMEN1309/OBT076, includes a fully human antibody targeting CD205, coupled to the DM4 toxin, a potent maytansinoid derivate, via a cleavable N-succinimidyl-4-(2-pyridyldithio) butanoate linker. MEN1309/OBT076 is in development for a number of CD205-driven tumors.
In a multicenter first-in-human clinical study in major European oncology centers in Italy, Spain, Belgium and UK, the investigational drug is evaluated in the treatment of metastatic solid cancers, including gastric cancer, triple-negative breast cancer, bladder cancer and pancreatic cancers as well as non-Hodgkin lymphoma (NHL). This clinical trial follows a precision oncology approach, key component of Menarini Ricerche’s strategy, recruiting only patients positive for the expression of the therapeutic target CD205.
A dose-Escalation phase I clinical trial is starting in the United States in highly experienced academic centers under the sponsorship of the company’s partner, Oxford BioTherapeutics.
Promissing
“The non-clinical data published in the journal Molecular Cancer Therapeutics confirm the promising activity of MEN1309/OBT076 in solid tumors expressing CD205. This supports the clinical development of MEN1309, which is being evaluated in the phase I SHUTTLE study,” noted Monica Binaschi, Ph.D, Director of the Preclinical and Translational Sciences Department of Menarini Ricerche.
“These results also provide a strong rationale for one of the key elements of the clinical development strategy of MEN1309/OBT076, represented by the specific targeting of patients with tumors expressing CD205 as confirmed by an appropriate assay developed in-house, Binaschi added.
“The published study represents an example of fruitful scientific collaboration between academic centers of excellence in oncology research and industry,” she concluded.
The collaboration in developing MEN1309/OBT076 includes a close cooperation with Joaquin Arribas, Ph.D, and his team at the Vall D’Hebron Institute of Oncology (VHIO) in Barcelona, Oxford BioTherapeutics.
Clinical trial
MEN1309 Intravenous Infusion in Patients With CD205-positive Metastatic Solid Tumors and Relapsed or Refractory Non-Hodgkin Lymphoma Phase I Study (CD205-SHUTTLE) – NCT03403725
Reference
[1] Merlino G, Fiascarelli A, Bigioni M, Bressan A, Carrisi C, Bellarosa D, Salerno M, et al. MEN1309/OBT076, a first-in-class Antibody-drug Conjugate (ADC) targeting CD205 in solid tumors. Mol Cancer Ther. 2019 Jun 21. pii: molcanther.0624.2018. doi: 10.1158/1535-7163.MCT-18-0624. [Epub ahead of print]
 MEN1309/OBT076, being developed by Menarini Ricerche shows substantial in vitro activity resulting in durable responses and complete tumor regressions){kind=link}