Periodic Reporting for period 1 - ImmunoNet (Inhibiting resistance to immunotherapy in Oncology by targeting Netrin-1)
Okres sprawozdawczy: 2022-09-01 do 2023-09-30
Immune Checkpoint Inhibitors (ICPIs) have recently revolutionized the treatment and management of cancer. Yet, progress recorded and impact on long-term survival affect only a limited fraction of patients, as most cancer patients do not or incompletely respond to ICPIs due to primary or secondary resistance to these treatments. NETRIS Pharma is an innovative biotech company based in Lyon that has developed NP137, a humanized monoclonal antibody targeting Netrin-1. This therapeutic antibody has shown promising results in preclinical pharmacological models with a demonstrated effect on tumor growth inhibition and the potential to alleviate resistance to ICPIs. The mode of action of this drug has been recently published in 2 back-to-back papers in Nature® in August 2023, significantly raising the profile of the Company and the interest in its unique approach. These publications present the role of NP137 in reversing a critical process in cancer progression and metastases development. Hence, the administration of NP137 drives tumor cells reepithelization, increasing the potential for better efficacy of existing cancer treatments, namely chemotherapy and immunotherapy, by reducing the resistance to these treatments.
The objective of the ImmunoNet project is to conduct a proof-of-concept of the efficacy in clinical trials assessing the benefit of NP137 on top of immunotherapy to alleviate suspected resistance to ICPIs in patients. The increased response rate to ICPIs with NP137 would have a major impact on patients having limited treatment options beyond immunotherapies and create significant growth opportunities for the European company NETRIS Pharma.
The objective of the ImmunoNet project is to conduct a proof-of-concept of the efficacy in clinical trials assessing the benefit of NP137 on top of immunotherapy to alleviate suspected resistance to ICPIs in patients. The increased response rate to ICPIs with NP137 would have a major impact on patients having limited treatment options beyond immunotherapies and create significant growth opportunities for the European company NETRIS Pharma.
The major achievements so far include, as projected, the approval and launch of 3 clinical trials, Immunonet, Lapnet and Livernet, currently enrolling patients. These trials targets have been designed to measure the incremental benefit of NP137 on top of standards of care. As presented in clinicaltrials.gov
- Immunonet is enrolling patients based on their response to immunotherapy with 3 cohorts with i) stable disease patients, ii) primary refractory patients and iii) secondary refractory patients. This trial expects to recruit patients with tumor types harboring a strong upregulation of Netrin-1, including Head & Neck, melanoma, Lung and others.
- Lapnet is measuring the activity of NP137 over the standard of care in pancreatic cancer patients being Folfirinox
- Livernet is measuring the activity of NP137 over the standard of care in hepatocellular carcinoma patients being the combination of Atezolizumab and Bevacizumab.
All trials are currently recruiting patients and the pace of recruitment should accelerate with the opening of new centers in France in each trial.
Along such recruitment, the company is collecting patients' biological material before and after treatment and will analyze the samples to identify elements of response.
The objective of this project and all ongoing clinical activities is also to prepare for a registration study that will position NP137 as a blockbuster drug. A communication plan has been designed targeting :
- the scientific community, with our Nature® publications and other publications from collaborations to sustain the interest in this first-in-class medicine
- the pharma industry, which has the capacity not only to finance a registration study, but also to prepare for the marketing of the drug
- the investment community as NETRIS Pharma is currently in a fundraising mode to cover all its expenses to 2026,
- and ultimately the patients, when the first results shall be confirmed.
Beyond this communication plan, which includes 7 press releases since the approval by EIC of the ImmunoNet project, the company has also started its strategic thinking on market access.
- Immunonet is enrolling patients based on their response to immunotherapy with 3 cohorts with i) stable disease patients, ii) primary refractory patients and iii) secondary refractory patients. This trial expects to recruit patients with tumor types harboring a strong upregulation of Netrin-1, including Head & Neck, melanoma, Lung and others.
- Lapnet is measuring the activity of NP137 over the standard of care in pancreatic cancer patients being Folfirinox
- Livernet is measuring the activity of NP137 over the standard of care in hepatocellular carcinoma patients being the combination of Atezolizumab and Bevacizumab.
All trials are currently recruiting patients and the pace of recruitment should accelerate with the opening of new centers in France in each trial.
Along such recruitment, the company is collecting patients' biological material before and after treatment and will analyze the samples to identify elements of response.
The objective of this project and all ongoing clinical activities is also to prepare for a registration study that will position NP137 as a blockbuster drug. A communication plan has been designed targeting :
- the scientific community, with our Nature® publications and other publications from collaborations to sustain the interest in this first-in-class medicine
- the pharma industry, which has the capacity not only to finance a registration study, but also to prepare for the marketing of the drug
- the investment community as NETRIS Pharma is currently in a fundraising mode to cover all its expenses to 2026,
- and ultimately the patients, when the first results shall be confirmed.
Beyond this communication plan, which includes 7 press releases since the approval by EIC of the ImmunoNet project, the company has also started its strategic thinking on market access.
In the ImmunoNet project, patients with diverse cancers not responding to ICIs treatments are being treated with the anti-netrin-1 therapeutic antibody (NP137) in combination with immunotherapy (anti-PD1, Pembrolizumab or other approved drugs). To date, more than 10 patients have been recruited for this trial but it is premature to make any announcement on preliminary outcomes. These shall take place in the course of 2024, along with analysis, including bulk RNAseq and spatial transcriptomic, or immune infiltrate characterization by multiplex immunofluorescence. The ultimate objective of such studies will be to correlate a clinical response with a specific immunological signature and observe a potentiation of the effectiveness of immunotherapy when combined with NP137.