First effective targeted therapy for T-cell acute lymphoblastic leukemia (T-ALL) and other NOTCH pathway driven cancers - CB-103

Programme(s)
H2020-EU.3. - PRIORITY 'Societal challenges
H2020-EU.2.3. - INDUSTRIAL LEADERSHIP - Innovation In SMEs
H2020-EU.2.1. - INDUSTRIAL LEADERSHIP - Leadership in enabling and industrial technologies

Topic(s) EIC-SMEInst-2018-2020 - SME instrument

Call for proposal H2020-SMEInst-2018-2020-1

Funding Scheme SME-1 - SME instrument phase 1

Grant agreement ID: 863225

Project description
Bringing a small molecule drug against leukemia to the clinic
T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive cancer with no effective cure yet. Chemotherapy is partially effective as a first-line treatment, but has significant side effects and cannot kill the cancer stem cells, leading eventually to relapse. The Swiss biopharma company Cellestia has developed a small molecule compound, CB-103, that targets the NOTCH pathway which is aberrantly activated in T-ALL. Preclinical data have shown that CB-103 has a high therapeutic index, significantly prolongs survival rate and has no toxicity. The EU-funded CB-103 project will undertake the necessary activities to plan clinical trials of the CB-103 small molecule in T-ALL patients. Successful development through clinical validation will advance CB-103 toward market approval.

Objective
T-cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive NOTCH-dependent cancer that affects the blood and bone marrow especially in children aged 0-14 years, and currently has no effective cure. T-ALL accounts for about 25% of the total cases of Lymphoblastic Leukemia (ALL); additionally, an estimated 250,000 people are afflicted by NOTCH-dependent cancers every year. Chemotherapy, the standard-of-care treatment for T-ALL, can reduce tumor growth, but it is ineffective at killing the cancer stem cells that drive tumor progression. Moreover, it can lead to adverse toxicological effects as a result of off-target toxicity, as the drug cannot discriminate between healthy and cancerous cells. Small molecule drugs help to solve this issue thanks to their high efficiency in targeting tumor cells. Cellestia may have found the answer. Its novel approach targets a tumor development pathway, the NOTCH, which play crucial oncogenic roles in tumorigenesis, tumor expansion and survival. By inhibiting the NOTCH signaling in its most downstream part, Cellestia’s small molecule compound, CB-103, blocks the problem at the roots (i.e. specifically at the level of the NOTCH transcription complex) stopping cancer cells growth and survival. Pre-clinical results show CB-103 to have a high therapeutic index relative to conventional cancer drugs. Most importantly, it significantly prolongs survival rates (median improvement of 75%) with no adverse side effects or dose-limiting toxicity (DLT). Results indicate it may have benefit for other cancers too – any in which NOTCH pathway is highly activated, including forms of leukemia and other cancers such as lung, breast and colorectal. The Phase 1 project will be focused on establishing a complete and scalable supply chain, verifying the business model and commercialization strategy, planning new collaborations and partnerships, including the ones to implement the next clinical trials stage.