Periodic Reporting for period 4 - Anti-L1CAM (Anti-L1CAM antibody: A novel efficacious immunotherapy for pancreatic and ovarian cancer patients)
Periodo di rendicontazione: 2023-03-01 al 2024-02-29
The Elthera project addresses the issues of present cancer therapy especially in ovarian and pancreatic cancers.
Over 170’000 people in Europe and more than 570’000 people worldwide are affected by pancreatic and ovarian cancer. In pancreatic cancer neither conventional chemotherapies nor combinations thereof nor novel checkpoint inhibitors have led to significant therapeutic benefits in recent years, and survival times are still measured in months for the vast majority of patients. In ovarian cancer, first line therapy with platinum-based drugs usually leads to good response rates, however tumors recur in 80-90% of patients and usually develop resistance to chemotherapy. As a consequence, the 5-year survival rate for this type of tumor remains low with only 40%.
Therefore, innovative treatment modalities with alternative modes of action and therapeutics aiming at novel targets are eagerly awaited to improve patient prognosis.
Elthera has developed a proprietary mouse antibody against L1CAM, which inhibits the cancer-promoting effects of L1CAM, such as tumor cell proliferation and migration. The antibody has been humanized and optimized for affinity and stability. Since the submission of the grant application Elthera have performed studies to further characterize the pharmacological properties of the clinical candidate molecule in various mouse tumor models.
The goal of the Elthera project is to demonstrate the efficacy of the antibody in prolonging patient survival in pancreatic and ovarian cancer and partner the further development steps and commercialization with a large pharma company.
Over 170’000 people in Europe and more than 570’000 people worldwide are affected by pancreatic and ovarian cancer. In pancreatic cancer neither conventional chemotherapies nor combinations thereof nor novel checkpoint inhibitors have led to significant therapeutic benefits in recent years, and survival times are still measured in months for the vast majority of patients. In ovarian cancer, first line therapy with platinum-based drugs usually leads to good response rates, however tumors recur in 80-90% of patients and usually develop resistance to chemotherapy. As a consequence, the 5-year survival rate for this type of tumor remains low with only 40%.
Therefore, innovative treatment modalities with alternative modes of action and therapeutics aiming at novel targets are eagerly awaited to improve patient prognosis.
Elthera has developed a proprietary mouse antibody against L1CAM, which inhibits the cancer-promoting effects of L1CAM, such as tumor cell proliferation and migration. The antibody has been humanized and optimized for affinity and stability. Since the submission of the grant application Elthera have performed studies to further characterize the pharmacological properties of the clinical candidate molecule in various mouse tumor models.
The goal of the Elthera project is to demonstrate the efficacy of the antibody in prolonging patient survival in pancreatic and ovarian cancer and partner the further development steps and commercialization with a large pharma company.
During the entire 1st year of the project, Elthera worked on the optimization of the drug-like properties of an L1CAM-targeting bispecific antibody, involving several rounds of protein engineering, biophysical and pharmacological characterization. The second year was dedicated to the development of an anti-L1CAM antibody drug conjugate (ADC). By the end of 27 months, Elthera had identified an anti-L1CAM ADC with good biophysical and pharmacokinetic properties and excellent anti-tumor efficacy both in vitro and in vivo. This ADC was nominated the clinical development candidate (“ELT048”) and was tested in an exploratory safety and tolerability study in cynomolgus monkeys. In RP3, the gross pathology analysis and full histopathology analysis of all organs was conducted. ELT048 was found to be well tolerated and no treatment-related macroscopic or microscopic changes were observed in any of the examined tissues/organs, whereas good exposure and pharmacodynamic activity of ELT048 was confirmed in PK/PD assays. Additional in vitro and in vivo pharmacological studies indicated that ELT048 had an acceptable therapeutic index, thus supporting its clinical developability. Fund raising and business development activities took place during the whole duration of the project and were further intensified during the third reporting period to finance or partner further development. As a result of these endeavours, Elthera entered into a license agreement with LegoChem Biosciences on 13th Feb 2023. Under the terms of the agreement, Elthera grants LegoChem a worldwide exclusive license to further develop and commercialize the anti-L1CAM ADC and any other products containing Elthera’s proprietary anti-L1CAM antibodies. By closing this license agreement, Elthera has met the ultimate goal of the project.
The project has led to the development of a first-in-class anti-L1CAM antibody drug conjugate (ADC) with preclinically demonstrated efficacy and safety. By entering into the license agreement with LegoChem Biosciences, a specialized ADC company, Elthera has ensured that this ADC can seamlessly proceed to the next stages of development, which include large scale manufacturing and clinical testing. It can be expected that within approximately two years from now the ADC will become available for the first clinical tests in pancreatic and ovarian cancer patients. If the preclinical results translate well into the clinical setting, the anti-L1CAM ADC has the potential to provide significant benefit in terms of increased progression-free and overall survival for pancreatic and ovarian cancer patients, but also for patients affected by other L1CAM-expressing cancer types.