Roche licenses Innovent ADC that could challenge Amgen drug

In a deal valued at up to $1 billion, Roche has licensed rights to a DLL3-directed antibody-drug conjugate (ADC) from China's Innovent Biologics, hoping to bring a competitor to Amgen's recently approved Imdelltra to market.

The deal – which includes an upfront payment of $80 million – grants Roche exclusive global rights to develop, manufacture, and commercialise IBI3009, which has just started clinical testing and has potential as a treatment for small cell lung cancer (SCLC) and other neuroendocrine tumours (NETs).

Amgen brought the first DLL3-targeting drug to market earlier this year after it got US approval for bispecific T-cell engager (BiTE) Imdelltra (tarlatamab) for adults with advanced, extensive-stage SCLC with disease progression on or after platinum-based chemotherapy.

DLL3 is an antigen with low expression in normal tissues, but is significantly overexpressed in certain solid tumours, making it an attractive drug target. Early drug development attempts ran into problems, however, most notably when AbbVie abandoned the development of Rova-T, an anti-DLL3 ADC acquired as part of a $5.8 billion takeover of Stemcentrx, after a phase 3 failure as a post-chemo maintenance therapy in SCLC.

According to Innovent, IBI3009 has shown encouraging anti-tumour activity in multiple animal models, particularly in chemo-resistant cancer types, and has also demonstrated a "favourable safety profile."

Tolerability could be an important differentiator for the drug, as Imdelltra does have safety issues, with its FDA-approved label, including a boxed warning for cytokine release syndrome and neurologic toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS).

Despite that, analysts have suggested that Imdelltra could reach annual sales of $2 billion if it also gets approval for patients with limited-stage SCLC who have not progressed following chemoradiation therapy, a follow-up indication. Amgen priced its drug at $166,500 per patient course.

There's a long way to go before Roche can see if IBI3009 will be a contender that can take on Imdelltra, but it has been cleared for clinical testing in China, the US, and Australia, with the first patient dosed in December. The two companies will work together on the early-stage development of the ADC, after which Roche will take over full development if it passes muster.

Other companies with DLL3 programmes in clinical testing include Boehringer Ingelheim with BI 764532, a CD3xDLL3 bispecific in phase 2 development for advanced or metastatic DLL3-expressing large-cell neuroendocrine carcinoma (NEC) of the lung, and MSD's MK-6070, a DLL3-targeting T-cell engager acquired as part of its takeover of Harpoon Therapeutics, which is in a phase 1/2 study.