Innovent revives its US checkpoint plan
The plan to get the anti-PD-1 MAb sintilimab approved in the US hit a terminal roadblock in 2022, but its originator, Innovent, hasn’t been put off. The Chinese group’s latest plan is to advance IBI363, a fusion protein that combines PD-1 activity with IL-2, and today this received the FDA’s fast-track designation. Of course, such an accolade says nothing about the project’s approvability in the US, and with Innovent primarily targeting melanoma the likeliest development pathway would seem to be to study it in post-checkpoint patients in the relapsed setting, and as part of a Keytruda or Opdivo combo in the front line. At an ESMO virtual plenary in June Innovent reported a 17% ORR among 300 evaluable patients with various cancers given IBI363 ≥0.1mg/kg in a phase 1 trial. Mechanistically IBI363 is unusual; while most other IL-2 projects aim to avoid activity at the 2α subunit, to avoid activating T regulatory cells, IBI363 retains activity for IL-2Rα but has weakened binding to IL-2Rβ and IL-2Rγ, which Innovent says reduces toxicity. Innovent retains full rights to IBI363, so perhaps the FDA’s blessing will tempt a US partner.
Innovent's work on molecules with PD-(L)1 activity
Project | Mechanism | Deals | Status |
---|---|---|---|
Tyvyt (sintilimab) | Anti-PD-1 MAb | 2015 development deal with Lilly, which handed back ex-China rights in Oct 2022 | Approved in China in 7 cancer settings; US development deprioritsed after 2022 CRL |
IBI363 | Anti-PD-1/IL-2α-biased fusion protein | None | Ph2 trial in melanoma |
IBI322 | Anti-PD-L1 x CD47 bispecific MAb | None | Ph2 trials in NSCLC |
IBI321 | Anti-PD-1 x TIGIT bispecific MAb | 2015 development deal with Lilly | Ph1 trial in solid tumours |
IBI319 | Anti-PD-1 x 4-1BB bispecific MAb | 2015 development deal with Lilly | Ph1 trial in unspecified tumours |
Fidasimtamab (IBI315) | Anti-PD-1 x HER2 bispecific MAb | 2017 co-promotion deal with Hanmi | Ph1 trial in solid tumours |
IBI323 | Anti-PD-L1 x Lag3 bispecific MAb | None | Ph1 trial in unspecified tumours |
IBI327 | Anti-PD-L1 x Ox40 bispecific MAb | None | Preclinical |
Source: OncologyPipeline.
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