The Society of the Immunotherapy of Cancer added an extra frisson to its annual meeting by inadvertently revealing full abstracts on its website yesterday, four weeks before the embargo on these was supposed to have lifted.
The mistake was soon rectified, but not before some investors took screenshots and acted on the information, resulting in Replimune surging 47%. Iovance was another early riser, and in common with Replimune it put its data into the public domain once the SITC mistake was noticed. For others the uncertainty will continue, with most of the market being aware only of the presentation titles.
Investors who were not so quick off the mark will argue that this situation is untenable, and Replimune and Iovance’s full disclosure seems the fairest course of action. On the other hand, both companies’ abstracts contain positive data, so it is in their interest to get these out.
This is not the case for Incyte, for instance. Its own SITC abstract, in the brief moment in which it was available, revealed zero responses in 16 patients given the oral, small-molecule PD-L1 inhibitor INCB86550; this was despite T-cell activation and signs of PD-1/PD-L1 interaction blockade. Incyte fell 4%.
Replimune’s 47% surge was triggered by three responses in six subjects given its oncolytic virus project RP2 as monotherapy. Oncolytic viruses are cumbersome and have a poor track record, being largely limited to niche use in melanoma; their remaining utility is in combination, which explains the excitement around Replimune.
Still, RP2 is no ordinary oncolytic virus – it additionally expresses an anti-CTLA-4 molecule. A separate Replimune virus, RP1, is the subject of another SITC presentation, this time in combination with Opdivo.
|Selected SITC 2020 abstracts|
|Company||Project||Mechanism||SITC 2020 abstract detail|
|Incyte||INCB086550||Oral anti-PD-L1||No mention of tumour responses in 16 patients|
|Alkermes||ALKS 4230||IL-2 fusion protein (SC)||Artistry-2 trial; needs to replicate IV efficacy|
|Replimune||RP2||Oncolytic virus expressing anti-CTLA-4||50% PR rate in 6 patients on monotherapy|
|Iovance||LN-145||TIL therapy||Keytruda combo: 1 CR & 3 PRs in 8 checkpoint-naive HNSCC pts|
|Xencor||XmAb20717||Anti-PD-1xCTLA-4 bispecific||1 CR & 2 PRs in melanoma, 2 PRs in NSCLC, 1 PR in ovarian cancer; 2 treatment-related deaths|
|Curis||CI-8993||Anti-Vista MAb||Prelim ph1 data|
|Biontech/Sanofi||SAR441000/BNT311||mRNA encoding IL-12sc, IFα2b, GM-CSF & IL-15sushi||Ph1 monotherapy & Libtayo combo data|
|Biontech/Genmab||GEN1046||Anti-PD-L1x4-1BB bispecific||First-in-human data|
|Imcheck||ICT01||Anti-BTN3A MAb||Data from Eviction trial|
|Roche||Selicrelumab||CD40 agonist MAb||Ph1/2 data with Tecentriq combo|
|Roche||RO7122290||4-1BB agonist||Solid tumour data|
|Merck KGaA||M9241||IL-12/Ab fusion protein||Bavencio combo in urothelial cancer|
|Silverback Therapeutics||SBT6050||Anti-Her2/TLR8 agonist conjugate||Likely trial design only|
|Seagen||Ladiratuzumab vedotin||Anti-ZIP6/LIV-1ADC||Monotherapy & Keytruda combo data|
|Alphamab/Sanofi||KN026 + KN046||Anti-Her2 + PD-L1xCTLA-4 bispecifics||Prelim data in Her2-mutated tumours|
|Amgen/Beigene||AMG 757||Anti-DLL3 bispecific||Ph1 in SCLC|
|Bioxcel||BXCL701||DPP VIII/IX & FAP inhibitor||Keytruda combo in prostate cancer|
|4D Pharma||MRx0518||Microbiome regulator||Keytruda combo in checkpoint-refractory pts|
|I-Mab||Lemzoparlimab||Anti-CD47 MAb||Ph1 monotherapy data|
|Bristol Myers Squibb||BMS-986218||Afucosylated anti-CTLA-4 MAb||Prelim monotherapy & Opdivo combo data|
|Scholar Rock||SRK-181||TGF-β1 inhibitor||Anti-PD-(L)1 combo in checkpoint-unresponsive pts|
Iovance closed up 7% yesterday as an SITC abstract revealed a 50% remission rate for its TIL project LN-145, in combination with Keytruda, in head and neck cancer. This might validate TILs in another tumour type, but the fact that patients were checkpoint inhibitor-naive and the lack of a Keytruda-only control limits their relevance.
Like Iovance, Xencor published the entire text of its SITC abstract in a US regulatory filing after the SITC snafu. This concerned the PD-1/CTLA-4 bispecific XmAb20717, and included a 21% ORR at the expansion dose in 29 subjects with prior checkpoint inhibitor exposure; however, there have been two treatment-related deaths among the 109 patients dosed.
Among the multitude of other early clinical results investors will note the large number of bispecifics. There might also be interest in such oddities as 4D Pharma’s microbiome regulator MRx0518 and ICT01, an antibody activating gamma-delta T cells in development by the private French company Imcheck.
However, the chaotic situation where some investors already know data in presentations but others do not looks set to continue until the formal abstract unveiling on November 8. That is unless, of course, the SITC decides that the damage already done warrants full disclosure now.