New data at EHA backs Sanofi, Innate’s NK cell engager

One of the lead candidates in Sanofi natural killer (NK) cell engager alliance with Innate Pharma has shown encouraging and durable efficacy in various haematological cancers, according to a phase 1/2 study presented at the EHA congress.

SAR443579 (also known as IPH6101) is a tri-functional NKp46/CD16-based anti-CD123 NK cell engager – described as a first-in-class therapy – that has now advanced into a phase 2 programme. It was the first candidate taken forward by Sanofi after it signed its first partnership with Innate in 2016.

The phase 1/2 trial presented at EHA tested SAR443579 as a monotherapy for the treatment of a basket of blood cancers with high unmet needs, including relapsed or refractory acute myeloid leukaemia (AML), B‑cell acute lymphoblastic leukaemia (B-ALL), and high-risk myelodysplastic syndromes (HR-MDS).

The latest data comes from a group of 59 patients all with AML, other than one subject who had HR-MDS, and looked at a range of doses of the drug, given as a monotherapy by intravenous infusion between 0.01 and 6.0 mg/kg. The patients had received an average of two prior therapies, although the range extended from one to 10.

The best response rate was seen with the 1.0 mg/kg dose group, with five AML patients achieving either complete remission (CR) or CR with incomplete haematological recovery. The median treatment duration was 7.9 weeks, with durable CR – of 10 months or more - seen in three patients, with two remaining on maintenance therapy as of the data cut-off.

“Ongoing studies are focused on further demonstrating the potential of the NK cell engager in patients with leukaemia,” said Peter Adamson, Sanofi’s global development head for oncology. “We look forward to sharing data from these trials at future scientific meetings.”

The results are a further endorsement of the potential of Innate’s antibody-based NK cell engager therapeutics (ANKET) platform, which attracted a €400 million partnership with Sanofi in 2016 that focused on a pair of NKp46 programmes. The other candidate from that agreement is SAR445514, a tri-functional anti-BCMA NK cell engager in phase 1 testing for relapsed, refractory multiple myeloma.

The alliance was extended in 2022 to allow Sanofi to take additional candidates, with a €25m upfront payment and a potential €1.35 billion in developmental, regulatory, and commercial milestones. As part of the deal, Sanofi licensed a programme targeting the immune checkpoint protein B7H3. Then, last December, Sanofi picked up a fourth candidate for another €15 million upfront fee.

NKs are involved in the body’s first line of immune defence, which can recognise and destroy cancer cells. Other companies operating in the NK cell engager area include Affimed – which signed a $5 billion partnership with Roche in 2018 – as well as Gilead/Dragonfly.