Boehringer: what’s in and what’s out?

As a privately held pharma company Boehringer Ingelheim reveals relatively little about its R&D, but yesterday’s presentation of the state of play of its pipeline gave a good indication of where the group is heading in oncology. 

For instance the HER2 exon 20 inhibitor zongertinib, which recently started phase 3, was talked up, as were brigimadlin and the DLL3-targeting T-cell engager BI 764532. However, the update was equally notable for what it left out, and this revealed the quiet discontinuation or deprioritising of some early projects. And in KRAS, a space in which Boehringer has been active for a while, it appears that the company’s thinking is evolving.

Judging by Boehringer’s updated R&D listing the group’s KRAS focus is now on the multi-KRAS inhibitor BI 3706674, which is in phase 1/2 in gastric cancer, and which featured in a poster at the recent AACR conference. What wasn’t mentioned yesterday were the KRAS G12C inhibitor BI 1823911 or the pan-KRAS:SOS1 inhibitor BI 1701963.

Two studies of the latter have been terminated, but two continue, including one in combination with the former, and these are scheduled to end this year. The fact Boehringer’s pipeline no longer mentions these two projects doesn’t confirm their discontinuation, but it suggests that they’re no longer being prioritised.

Projects that do appear to have been discontinued include the MEK inhibitor BI 3011441. Boehringer licensed this from Lupin in 2019, but no active studies are listed on clinicaltrials.gov any more: three have been completed and one terminated.

A phase 1 breast cancer trial of the anti-IGF MAb xentuzumab, combined with Verzenio, ended a year ago, and with no data revealed and the asset no longer listed that seems likely to have disappointed. Also no longer in the pipeline is the BET inhibitor amredobresib; this mechanism is in focus given Novartis’s €2.7bn takeover of MorphoSys, driven by the latter’s BET inhibitor pelabresib.

Still in

Boehringer isn’t known as an oncology powerhouse, and its two approved cancer drugs, Gilotrif and Vargatef, are hardly big hitters. The group has long hoped to succeed here, but a $1.5bn bet on the ROR1 mechanism, for instance, recently ended in failure.

A 2023 acquisition, of Switzerland’s T3 Pharma for “up to” CHF450m, brought with it a modified yersinia project that features in Boehringer’s phase 1 pipeline. Phase 1 assets also include the anti-B7-H6 T-cell engager – a relatively unusual mechanism – and the 4-1BB x FAP agonist BI 765179; 4-1BB co-stimulation hasn’t had much success beyond Car-T therapy, however.

As for Boehringer’s most advanced oncology assets, zongertinib targets a lung cancer niche, having recently begun phase 3 in HER2-mutated disease, while brigimadlin is designed to address the so-called “guardian of the genome”, p53, a notoriously difficult target. Brigimadlin was already in pivotal development for dedifferentiated liposarcoma, and a phase 3 soft tissue sarcoma study has just been listed on clinicaltrials.gov.

The anti-DLL3 T-cell engager BI 764532 is playing catch-up with Amgen’s tarlatamab, which is already awaiting US approval. Meanwhile, the phase 1 pipeline also shows Boehringer taking multiple shots on goal in several areas, including oncolytic viruses, multi-antigen cancer “vaccines” and SIRPα blockade. 

After the recent selection of a second-generation Sting agonist over an earlier asset, Boehringer might soon have more prioritising to do.

Boehringer Ingelheim's oncology R&D summary

Source: company update & OncologyPipeline.