A cancer pipeline cull from AbbVie

AbbVie might be determined to become a player in the hot area of antibody-drug conjugates, but some projects still don’t make the grade. A look at the group’s oncology pipeline, spurred by its fourth-quarter results release on Friday, shows a slew of early-stage assets that have apparently hit the buffers.

This includes two ADCs using the company’s novel Bcl-XL inhibitor payload, so perhaps AbbVie is tidying up its pipeline ahead of its acquisition of ImmunoGen, set to close mid-year. Outside ADCs, a BET inhibitor seems to have fallen out of favour, as has a Jacobio-partnered SHP2 inhibitor JAB-3312 – both are mechanisms that have disappointed more broadly.

The projects in the table below didn’t appear in AbbVie’s latest pipeline update on Friday. The company has previously noted that these updates are not a comprehensive look at its R&D portfolio; however, the projects in question are also no longer listed on AbbVie’s website. It is probably safe to say that, at best, they’ve been deprioritised.

Missing in action: assets no longer listed on AbbVie’s website pipeline

Note: partnered with *Pfizer; **Jacobio. Source: company presentations.

The writing had already been on the wall for a couple of these molecules. Pfizer had disclosed the discontinuation of cofetuzumab pelidotin in November, and AbbVie is apparently not interested in taking this project forward alone.

CytomX disclosed last year that AbbVie had walked away from its CD71-targeting probody-drug conjugate ABBV-CX-202 in March 2023; the originator deprioritised the asset in November.

Meanwhile, reports of the demise of the Stemcentrx-originated ABBV-011 emerged in August; the SEZ6-targeting ADC used a calicheamicin payload and had early data at ASCO last year. AbbVie must have seen more promise in its other SEZ6 ADC, ABBV-706, which has a more conventional payload, a topoisomerase inhibitor, and is currently in phase 1.

Bcl-XL payload

Unimpressive early clinical results also emerged last year on mirzotamab clezutoclax and ABBV-637, two ADCs using the Bcl-XL inhibitor payload. With plenty of competition in B7-H3 and EGFR, it seems sensible for AbbVie to step back here.

CD40, the target of the monoclonal antibody giloralimab, is also fairly crowded; however, this isn’t the case for TRAIL agonism, where AbbVie was the only clinical-stage proponent, according to OncologyPipeline.

BET inhibition, meanwhile, has produced lacklustre data as a class, although MorphoSys still hopes that this will be enough to get its contender pelabresib approved. Indeed, MorphoSys stock surged 40% this morning on a Reuters report that Novartis was in advanced discussions over a takeover; pelabresib is a combo partner for Incyte's Jakafi, over which Novartis has rights.

AbbVie might have jettisoned ABBV-744 to focus on its late-stage myelofibrosis asset, the Bcl-2/Bcl-XL inhibitor navitoclax; however, the latter, also on top of Jakafi, didn’t impress at ASH 2023.

And the SHP inhibitor JAB-3312, originated by Jacobio, no longer appears in AbbVie's pipeline highlights slide or list of partnered assets, but does still feature on Jacobio's website.

AbbVie’s oncology pipeline could do with a boost: its late-stage highlights consist largely of new uses for approved products, as well as the aforementioned navitoclax and the cMet-targeting ADC telisotuzumab vedotin, on which the jury is still out.

The group will have to hope that the ImmunoGen deal fills some holes. On Friday, AbbVie said it was focused on smaller deals; it cited bi- and multispecific immuno-oncology agents as an area of interest, and highlighted a recent agreement with Umoja in the field of in vivo Car-T.

After this story was published Novartis announced that it was taking over MorphoSys.