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.