Fresh disappointment for Innate’s Astra lifeline
With Lumoxiti confirmed as commercially unviable monalizumab fails its phase 3 trial in head and neck cancer.
The October 2018 cross-licence with Astrazeneca had seemed like a fresh start for Innate Pharma after the failure of the Bristol Myers Squibb-partnered lirilumab. But progress has been mixed, and today the deal’s key asset, monalizumab, crashed out of its first pivotal trial.
This is not to say that the Astra/Innate deal is dead; earlier-stage molecules remain in play while the monalizumab can is kicked down the road to a post-2023 phase 3 readout in a different use. But with the other end of the tie-up, Lumoxiti, confirmed as a commercial disaster, the premise behind the move today is on shaky ground.
The idea was that Innate got an injection of capital, fresh big pharma endorsement, and the immediate chance to sell a rare cancer drug of its own. Astra got rights to monalizumab for $100m, while giving Innate its newly approved hairy cell leukaemia drug Lumoxiti for $50m.
Just two years later Lumoxiti, an anti-CD22 ADC, was dead: blaming lower than expected sales and the Covid pandemic Innate handed rights back to Astra. In February 2021 Lumoxiti got EU approval, but in July the marketing authorisation was withdrawn at the request of Astra, which appears no longer to promote the drug in the US either.
Many will see in Lumoxiti yet another example of a small biotech attempting a solo drug launch, and failing miserably. At least Innate will not have been the first or last biotech to fall at the commercialisation hurdle.
With a share price 70% below where it had stood when the Astra deal was struck Innate today added monalizumab to its disappointments.
The anti-NKG2A MAb had shown promise in an early study in head and neck cancer, but success in the pivotal setting proved elusive. Today Innate said Astra’s Interlink-1 trial, comparing monalizumab plus Erbitux against Erbitux monotherapy in second-line patients, had failed an interim futility analysis and would be wound down.
Any remaining value in monalizumab, which carries 2028 sellside consensus revenue forecasts of $150m according to Evaluate Pharma, now lies in stage III non-small cell lung cancer, courtesy of Astra’s Pacific-9 study putting it on top of Imfinzi. The blueprint for Pacific-9 is the smaller Coast trial, which at last year’s Esmo conference showed the combo to boost response rates and PFS versus Imfinzi alone.
However, Pacific-9 has only just started dosing patients, and data are not due until after 2023. A separate part of the 2018 deal saw Astra take on rights to the anti-CD39 MAb IPH5201, and this should yield phase 1 solid tumour data this year.
True, having Astra develop monalizumab has allowed Innate to fund other pipeline projects, but the transformation of Innate into an independent, self-financing entity seems just as distant today as it did in 2018.
|Selected monalizumab studies|
|Coast||Stage III NSCLC||Imfinzi + oleclumab or monalizumab, vs Imfinzi||Esmo 2021: ORR 35.5% vs 17.9% for Imfinzi, mPFS 15.1mth vs 6.3mth|
|Neocoast||Neoadjuvant stage III NSCLC||Imfinzi + oleclumab or monalizumab or danvatirsen, vs Imfinzi||AACR 2022: major pathological response 33.3% vs 12.5% for Imfinzi|
|Interlink-1*||2nd-line head & neck||Monalizumab + Erbitux, vs Erbitux||Failed interim futility analysis mid-2022|
|Neocoast-2||Neoadj & adj stage II-IIIA NSCLC||Imfinzi + oleclumab or monalizumab||Ends 2026|
|Pacific-9*||Stage III NSCLC**||Imfinzi + oleclumab or monalizumab, vs Imfinzi||Ends 2026|
|Note: *phase 3; **not progressed after chemoradiation. Source: clinicaltrials.gov.|