Merck takes a back seat on CAR-T, handing assets to Intrexon

Merck KGaA wants to get bigger in immuno-oncology, but from now on it won’t be taking a direct role in the drive to develop new CAR-T therapies.

The German drugmaker has reached an agreement to transfer all rights to its CAR-T technology and development programmes to US biotech company Intrexon in return for a $150 million equity stake in the Maryland-based firm, plus a note for another $25 million in stock.

Merck is also giving Intrexon $25 million in cash to help get the CAR-T programmes going, and says the handover will allow it to focus on its other R&D activities but still maintain an interest in the “rapidly advancing oncology field of CAR-T.”

CAR-T cells are genetically engineered T-cells with synthetic receptors that recognise a specific antigen expressed on tumour cells. When CAR-T cells bind to a target, an immunological attack against the cancer cells is triggered.

Intrexon, its wholly-owned subsidiary Precigen and Merck have been working together since 2015 on CAR-T, with the German firm’s Merck Serono division licensing various technologies used to engineer T-cells to target cancers, including its RheoSwitch platform for controlling gene expression and Sleeping Beauty, a non-viral approach to genetically modify CAR-T cells.

Shedding the CAR-T projects means Merck can concentrate on the development of its PD-L1 inhibitor Bavencio (avelumab) – partnered with Pfizer – as well as follow-up immuno-oncology candidates such as pan-av integrin inhibitor abituzumab and anti-PD-L1/TGF beta trap M7824, both in phase II.

The company’s decision may reflect the fact that it is playing catch-up in CAR-T, with Novartis and Gilead/Kite well out in front with products on the market and a sizeable number of candidates from them and other developers coming through the clinical pipeline.

While the first-generation products have used T cells harvested from patients, latterly there’s been a shift towards off-the-shelf CAR-Ts – from the likes of Allogene and Cellectis – that are designed to be quicker, easier and cheaper to administer.

Bavencio is approved for Merkel-cell carcinoma of the skin and bladder cancer (urothelial carcinoma) and in development for several other solid tumours as well as blood cancers but has yet to make any major inroads into the market with sales of just €19m in the third quarter of the year.

It has suffered some late-stage setbacks including a recent failure in ovarian cancer, but also some positive strides forward including solid results in first-line kidney cancer (renal cell carcinoma) for Bavencio in combination with Pfizer’s tyrosine kinase inhibitor Inlyta (axitinib).

“Strategically for Precigen, this evolution supports our vision and transition from an exclusive channel collaboration model to an agile R&D engine with full developmental autonomy over our portfolio of assets,” said Helen Sabzevari, Precigen’s president.

“We look forward to continued development of these promising CAR-T assets with the goal of delivering more cost-effective and precise therapies to patients in need.”