ESMO Asia 2025 – Oric’s first-line gamble
Relapsed data are uncompetitive, but the front-line PACC-mutant space offers hope.
Relapsed data are uncompetitive, but the front-line PACC-mutant space offers hope.
Oric Pharmaceuticals has presented results involving the EGFR/HER2 inhibitor enozertinib that back its decision to abandon this molecule’s development in second-line lung cancer. The data, revealed at the ESMO Asia conference, show response rates that look uncompetitive versus figures put up in broadly similar settings by two recently approved drugs.
Instead, the company has pivoted to first-line lung cancer with a PACC (P-loop alpha-c helix compressing) mutation, revealing preliminary data that do appear to offer some backing. However, this space already features two more advanced players, ArriVent and Black Diamond, and Oric’s dataset amounts to just 10 efficacy-evaluable patients.
Among these 10 patients, who all had previously untreated EGFR PACC-mutant NSCLC, Oric on Thursday claimed an 80% preliminary response rate. It’s not clear whether this number, announced by press release, includes unconfirmed responses, but these and other nuances are important given that Oric is sitting on a valuation above $1bn.
PACC-mutant NSCLC is a battleground featuring ArriVent’s firmonertinib and Black Diamond’s silevertinib. These two molecules have put up respective 68% and 56% ORRs, and – with the caveat that those responses are confirmed and involve more patients – enozertinib might be in with a chance; Oric plans to update the first-line results in mid-2026.
Relapsed less promising
If enozertinib, a molecule previously coded ORIC-114 that Oric licensed from Voronoi for just $13m, now has a future in PACC and other non-classical EGFR lung cancer mutations that could offer fresh hope. Such hope is important given enozertinib’s poor performance in relapsed lung cancer.
An ESMO Asia poster concerning relapsed NSCLC harbouring HER2 exon 20 insertions revealed confirmed ORRs of 26% and 27% for 80mg and 120mg doses respectively. In a similar setting Boehringer Ingelheim’s Hernexeos and Bayer’s Hyrnuo were approved this year on the back of ORRs of 75% and 71% respectively in the Beamion Lung-1 and Soho-01 studies.
While Boehringer recently revealed that it’s now shooting for first-line approval, Oric says it has abandoned enozertinib’s development in the HER2 exon 20 insertion population entirely.
Selected cross-trial response rates in NSCLC
| Project (company) | 1st-line PACCm | 2nd-line PACCm | 2nd-line HER2 exon 20 |
|---|---|---|---|
| Enozertinib (Oric) | 80% (n=10)* | 36% (n=22) | 27% (n=45) |
| Firmonertinib (ArriVent) | 56% (n=25) | NA | NA |
| Silevertinib (Black Diamond) | 68% (n=22) | 44% (n=9) | NA |
| Hernexeos (Boehringer Ingelheim) | NA | NA | 75% (n=71)** |
| Hyrnuo (Bayer) | NA | NA | 71% (n=70)^ |
Notes: *might include unconfirmed responses; **any HER2 mutations, not just exon 20; ^any HER2 mutations, 70% of which were exon 20. Source: OncologyPipeline, ESMO & US prescribing information.
Oric earlier discontinued enozertinib’s development in all relapsed lung cancer serttings, citing the front line’s relatively bigger commercial opportunity.
The abandoned settings include relapsed PACC-mutant NSCLC, where a separate ESMO Asia presentation has shown a confirmed 36% ORR for enozertinib among a 22-patient subgroup. One comparator is the 44% ORR Black Diamond earlier generated in the relapsed PACC-mutant setting for silevertinib, but this involved just nine patients.
Oric’s other pipeline hope is the PRC2 inhibitor ORIC-944, whose prostate cancer dataset appears to be deteriorating.
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