German 'immunotherapy powerhouse' BioNTech sees the potential of the drug, which is in Phase 1/2 trials, both in being used alone or in combination with the personalized immunotherapies it is developing.
Rockville, Maryland’s OncoC4 will receive a $200m upfront payment and will be eligible to receive development, regulatory and commercial milestone payments (of undisclosed amounts) as well as double-digit tiered royalties.
'Targeting CTLA-4 has not reached its full potential in cancer immunotherapy'
CTLA-4 is a molecule that inhibits the activity of immune cells. OncoC4’s CTLA-4 antibody candidate ONC-392 aims to delete immunosuppressive T cells (regulatory T cells, “Tregs”) in the tumor microenvironment, but spare Tregs in healthy tissues.
“With a potentially differentiated safety profile, ONC-392 may be able to achieve a more effective dosing regimen in the clinic and more successful tumor killing,” say the two companies as they announced the partnership.
The immune checkpoint receptor CTLA-4 inhibits T cell immune response and reduces the activity of T cells in recognizing and eliminating cancer cells. Blocking CTLA-4 preserves T cell activity and enhances anti-tumor activity. OncoC4’s next-generation anti-CTLA-4 antibody candidate ONC-392 was designed to preserve CTLA-4 recycling and thus Treg function in the peripheral tissues. This aims to give rise to fewer immune-related adverse effects and a positive safety profile.
Data from the ongoing Phase 1/2 trial in patients with advanced solid tumors were presented at SITC in 2022 and 2021, where ONC-392 showed 'encouraging clinical activity, either as single agent or in combination with pembrolizumab in patients with metastases, particularly those who progressed on immunotherapies targeting PD-1 and CTLA-4.'
ONC-392 has already received Fast Track designation from the US Food and Drug Administration (FDA) as a monotherapy for immunotherapy-resistant non-small cell lung cancer (NSCLC).
A randomized Phase 3 trial is set to evaluate ONC-392 as monotherapy against the current standard of care in PD-1-resistant NSCLC.
The candidate is currently also being evaluated in an additional Phase 2 trial as a combination therapy with pembrolizumab in platinum-resistant ovarian cancer (NCT05446298).
“Despite being a prime target for more than a decade, we believe that targeting CTLA-4 has not reached its full potential in cancer immunotherapy," said Prof. Ugur Sahin, M.D., CEO and co-founder of BioNTech.
"The data presented by OncoC4 on their ONC-392 antibody indicate a differentiated safety profile and encouraging clinical activity in various types of tumors. We believe that this antibody is a valuable addition to our immuno-oncology portfolio, whether used alone or in combination with our personalized immunotherapies.”
BioNTech and OncoC4 will jointly develop and share costs for ONC-392 as monotherapy and in combination with anti-PD-(L)-1 antibodies in a range of solid tumor indications, including NSCLC, until approval.
All combinations outside of PD-1 inhibition, in particular all combinations with a compound in BioNTech’s pipeline, will be solely developed by BioNTech.
The transaction is expected to close in the first half of 2023, subject to customary closing conditions and regulatory clearances.