Skip to main content
Go to the home page of the European Commission (opens in new window)
English en
CORDIS - EU research results
CORDIS

A First-in-Class MCL-1 degrader to promote apoptosis in therapy-resistant liquid and solid tumours

Project description

Targeted protein degradation for resistant cancers

Many cancers depend on MCL-1, a protein that prevents programmed cell death and drives resistance to therapy. Although blocking MCL-1 is an attractive strategy, conventional inhibitors have repeatedly failed due to severe cardiotoxicity. The EIC-funded CT-03 project applies targeted protein degradation to solve this challenge. Instead of inhibiting MCL-1, their small molecule CT-03 marks it for removal by the cell’s natural waste disposal machinery. Preclinical studies show strong MCL-1 degradation without cardiac side effects in non-human primates. The project will test CT-03 in patients with chemotherapy-resistant acute myeloid leukaemia, aiming to restore treatment sensitivity and validate safety. Positive results could enable out-licensing and accelerate next-generation treatments for oncology.

Objective

Captor Therapeutics is a biopharmaceutical company pioneering the development of therapeutics for unmet medical needs using Targeted Protein Degradation. We focus on high-value drug targets that are “undruggable” by conventional approaches.
One such target is MCL-1, a protein preventing programmed cell-death. MCL-1 is implicated in resistance to cancer treatments. Due to its broad applications, developing a safe therapy that could hamper MCL-1's effect in cancer cells, would be a gamechanger for oncology. Unfortunately, MCL-1 inhibitors give rise to cardiotoxicity, which has led to the termination of several clinical trials.
Our unique TPD technology platform allows us to apply a radically different approach. We have developed a small molecule able to tag MCL-1 for degradation using the cellular waste protein disposal system. CT-03, positioned to become a First-in-Class MCL-1 degrader, has shown potent degradation, with no signs of cardiotoxicity in Cynomolgus monkeys, the closest translational bridge to humans.
Our first indication – AML (Acute Myeloid Leukaemia) – has a market size of €3.6bn. Currently, Venclexta is commonly used in AML patients unable to undergo ablative chemotherapy or hematopoietic stem cell transplantation. Unfortunately, nearly all AML patients eventually acquire resistance to Venclexta, which leaves them with no further treatment options. By degrading MCL-1, CT-03 will make resistant cells susceptible to conventional therapies again.
The project’s goal is to demonstrate safety and lack of cardiotoxicity in humans. Successful results from a Phase Ia/Ib trial on Venclexta-resistant AML patients will constitute a crucial inflection point for securing a lucrative out-licensing deal with a large pharmaceutical company. Our future partner will take CT-03 forward in AML and other poorly-treated cancers. Revenues from the out-licensing deal will be invested into advancing our clinical pipeline of protein degraders in oncology & neurodegeneration.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-EIC-ACC - HORIZON EIC Accelerator

See all projects funded under this funding scheme

Call for proposal

(opens in new window) HORIZON-EIC-2024-ACCELERATOR-02

See all projects funded under this call

Coordinator

Captor Therapeutics Spolka Akcyjna
Net EU contribution
€ 2 499 875,00
Address
Dunska 11
54-427 Wroclaw
Poland
SME
Yes
Region
Makroregion południowo-zachodni Dolnośląskie Miasto Wrocław
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Links
Total cost
No data