SITC preview – All eyes on Incyte and Infinity

A deal Incyte struck yesterday with Macrogenics, handing across $150m up front to get access to the latter’s anti-PD-1 MAb MGA012, immediately promoted a clinical trial of this little-known asset up the list of important presentations at the upcoming SITC meeting.

This ramps up the pressure on Incyte, which will also be subjected to scrutiny when Bristol-Myers Squibb reports data on BMS-986205, an IDO inhibitor that rivals Incyte’s epacadostat, in an SITC late-breaker. Among other recently revealed late-breakers the spotlight will also fall on Infinity, an early beneficiary of SITC-related investor exuberance (see table below).

The BMS-986205 study had been rumoured earlier to have made it into the SITC (Society for the Immunotherapy of Cancer) late-breakers. It is seen as important because, according to Evercore ISI’s Umer Raffat, this compound causes a structural change in the IDO enzyme’s binding site, rendering its effect irreversible.

In contrast, Incyte’s epacadostat appears simply to inhibit the interaction of IDO with its substrate, and this reversible interaction might be less potent than an irreversible one. The title of the Bristol late-breaker promises to reveal preliminary antitumor and immunomodulatory activity of the once-daily IDO inhibitor – epacadostat is twice-daily – combined with Opdivo.

Full texts of the meeting’s late-breakers will be available on November 7, a day before SITC kicks off (World Lung and SITC – two more doses of oncology, October 11, 2017).

We have a winner

Infinity is one company that has benefited disproportionately from the late-breaker titles being revealed: its stock surged 122% on October 12 with news that IPI-549, a follow-up PI3k inhibitor to the highly disappointing duvelisib, would feature.

Still, this dataset was already presented at April’s AACR meeting with no market repercussions, so a lot is riding on Infinity’s update.

Meanwhile, Incyte’s newly acquired anti-PD-1, MGA012, features in standard SITC presentations, in abstracts detailing a clinical trial and preclinical characterisation; Leerink has for some time seen the monotherapy clinical trial as an important Macrogenics catalyst – though it is currently listed only in SITC’s “trials in progress” category – and now it will become one for Incyte.

Interestingly, Incyte already has an anti-PD-1, SHR-1210, now known as INCSHR1210, licensed from Jiangsu Hengrui Medicine two years ago, so yesterday’s Macrogenics deal suggests that INCSHR1210 is not progressing well. It is not clear what impact the group thinks it can make given the dozens of PD-(L)1 agents already in development, but its $150m up front suggests that a decent in-house asset is key to its combo strategy.

Selected late-breaking abstracts to be presented at SITC meeting, National Harbor, MD, Nov 8-12
Project Mechanism Company Title Trial ID (assumed) Abstract
APX005M CD40 agonist MAb Apexigen First-in-human solid tumour study NCT02482168 O36
Opdivo + Yervoy Anti-PD-1 & anti-CTLA4 MAbs Bristol-Myers Squibb 1st-line renal cell carcinoma study Checkmate-214, including OS by subgroups NCT02231749 O38
E7046 PGE2 receptor type 4 inhibitor Eisai Phase I study in advanced solid tumors with high myeloid infiltrate NCT02540291 O39
BMS-986205 IDO1 inhibitor Bristol-Myers Squibb/Flexus Combination with Opdivo in advanced cancers NCT03192943 O41
Cabiralizumab Anti–CSF-1 receptor MAb Five Prime/Bristol-Myers Squibb First-in-human phase I study of Opdivo combo in advanced solid tumours NCT03158272 O42
IPI-549 PI3K-gamma inhibitor Infinity Pharmaceuticals Monotherapy dose-escalation first-in-human study in advanced solid tumours NCT02637531 O43
DPV-001 Cancer vaccine Ubivac Evaluating immune responses NCT01909752 P511
MEDI0457/INO-3112 HPV16/18 vaccine Astrazeneca/Inovio CR to Opdivo in HPV16 +ve head and neck cancer patient treated with MEDI0457 NCT02163057 P513
LN-144 TIL therapy Iovance Biotherapeutics Efficacy and tolerability in phase II metastatic melanoma trial NCT02360579 P515
TILs TIL therapy Ubivac TIL generation from head and neck squamous cell cancers ? P516
MB-103 Anti-Her2 CAR-T Mustang/Fortress Bio Regional intraventricular delivery targets breast cancer metastasis to the brain ? P517
Imprime PGG Beta-D glucan Biothera Pharmaceuticals Enhancement of checkpoint inhibitors & suppression of IDO expression NCT02981303 P521

Among other late-breaking presentations, investors will be interested in an update of Bristol’s Checkmate-214 study of the Opdivo/Yervoy combo in renal cell carcinoma. The trial caused controversy at Esmo, given the way negative analyses were played down, and SITC should shed more light on subgroup data.

There are also two first-in-human studies of novel immune therapies from Apexigen’s APX005M, and cabiralizumab, an asset Bristol picked up from Five Prime two years ago. Another licensed asset, MEDI0457, an HPV vaccine Astrazeneca got from Inovio, features in a study detailing a complete remission on subsequent treatment with Opdivo.

And cell therapies make their mark in presentations from Iovance and the private group Ubivac, which has also scored a late-breaker slot for its cancer vaccine DPV-001. Given the abysmal track record of cancer vaccines, however, it is probably a safe bet that expectations here will be low.

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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