It is hard to believe that the Society for the Immunotherapy of Cancer was founded 31 years ago, back when immuno-oncology was a niche interest for just a handful of scientists. Of course in the past few years things have changed somewhat.
Now that the subject is the hottest thing in biotech the SITC’s annual meeting is watched closely. When this year’s instalment kicks off investors will be keen to see early data on Macrogenics’ little-appreciated asset enoblituzumab, as well as further work on Incyte’s IDO inhibitor and a combination CAR-T therapy from University of Pennsylvania, a partner of Novartis (see tables below).
All three are the subject of late-breaking presentations at the SITC meeting, which gets under way on November 4 at National Harbor, Maryland.
Macrogenics is quietly emerging as an early-stage immuno-oncology force to be reckoned with, licensing MGD011, a bispecific protein against CD19 and CD3, to Johnson & Johnson a year ago. A recent R&D day highlighted enoblituzumab, a first-in-class anti-B7-H3 MAb, and the stock closed up 13% on 19 October after sellside upgrades.
Its SITC late-breaker concerns an ongoing enoblituzumab monotherapy study, including data from the first three dose-expansion cohorts and additional results from five cohorts initiated a year ago. Leerink analysts say the opportunity in solid tumours is tremendous; Five Prime Therapeutics seems to have the only other anti-B7-H3 MAb.
IDO inhibition, meanwhile, one of the most interesting emerging immuno-oncology approaches, made a splash at last month’s European Cancer Congress courtesy of Incyte and Newlink Genetics.
The focus at SITC is on a combination of Incyte’s epacadostat with Merck & Co’s Keytruda, which could boost the former’s solid tumour potential. IDO deals with Newlink and Flexus respectively have been struck by Roche and Bristol-Myers Squibb – both non-exclusive Incyte partners; Iomet Pharma, a private UK biotech, is separately presenting its IDO and TDO inhibitors at SITC.
|General SITC sessions of interest|
|Epacadostat||Incyte||Phase I/II IDO + Keytruda combo, late-breaker||6 Nov|
|Opdivo||Bristol-Myers Squibb||Phase I/II study +/- Yervoy in SCLC||6 Nov|
|Axalimogene filolisbac||Advaxis||Phase I/II study of durvalumab combo in head & neck cancer||6 Nov|
|ADXS-PSA||Advaxis||Phase I/II study (Keynote-046) of Keytruda combo in mCRPC||6 Nov|
|APX005M||Apexigen||Immune stimulatory capabilities of CD40 MAb||6 Nov|
|IDO & TDO inhibitors||Iomet Pharma||Identification and optimisation||6 Nov|
|Enoblituzumab||Macrogenics||Phase I late-breaker, anti-H7-B3 MAb||7 Nov|
|GVAX Pancreas & CRS-207||Aduro Biotech||Phase II study in metastatic pancreatic cancer||7 Nov|
|Inlyta & Keytruda||Pfizer/Merck & Co||Phase I study of combo in advanced renal cell carcinoma||7 Nov|
|Varilumab||Celldex||CD27 agonist mechanism||7 Nov|
|Anti-ICOS MAb||Jounce||Preclinical efficacy||7 Nov|
|RO6927005||Roche/Aduro||Combining anti-CTLA4 with anti-mesothelin fusion protein||7 Nov|
|Various||Various||Biomarkers in cancer immunotherapy: oasis or mirage?||8 Nov|
Other studies of interest include Bristol’s Opdivo with or without Yervoy in small-cell lung cancer – a potential new use – as well as pancreatic cancer data from Aduro Biotech, a group that secured a Nasdaq IPO and huge Novartis deal this year.
Jounce Therapeutics, which pulled off a $56m series B round at around the same time, has early data on its anti-ICOS Mab. And Advaxis, which uses a related technology to Aduro, is presenting results of cancer vaccines combined with anti-PD-1/PD-L1 MAbs; the group’s ADXS-HPV project was recently hit with a clinical hold.
The SITC abstracts will not be unveiled until November 3, so for many sessions it is not yet clear what type of data will be revealed. Much is likely to be extremely early-stage, and this is certainly the case for several of the CAR-T approaches being profiled.
That said, Penn’s late-breaker is likely to attract significant interest, since it deals with patients who relapse on CD19-directed CAR-T therapy by including in the mix an anti-CD123 CAR. City of Hope/Fortress Biotech and Cellectis are also known to have CD123 CAR-T projects (Coronado’s latest opportunistic move: CAR-T therapy, March 19, 2015).
City of Hope itself is presenting early findings of two other CAR-T approaches at SITC, while the CD19 relapse theme is picked up by Baylor College's Her2 CMV bispecific CAR and Lentigen’s CD20/CD19 dual construct. Baylor has CAR-T alliances with Bluebird Bio and Celgene, while Lentigen has been renamed Opus Bio after selling its gene therapy assets to Miltenyi Biotec.
Also of interest will be a presentation by a little-known French firm, Theravectys, on lentiviral vector-delivered CARs. The private group reckons it can engineer an inducible and reversible “on/off” switch driving CAR expression, to reactivate CAR-T cells in cases of relapse and prevent cytokine release syndrome.
On November 9 the SITC will wind down with a discussion on biomarkers, featuring speakers from Kite Pharma, Roche, Bristol-Myers Squibb, AstraZeneca and Lilly. Given the problems of relying on tumours’ PD-L1 positivity, and pressure to cut drug costs, this should stimulate a lively debate.
|Selected SITC adoptive cell therapy sessions|
|CD123 & CD19 CAR-T||Uni of Penn||Leukaemia CD19 antigen loss relapses, late-breaker||6 Nov|
|IL13Ralpha2 CAR-T||City of Hope||Clinical development||6 Nov|
|Her2 CMV CAR-T||Baylor College||Bispecific CAR-T in phase I glioblastoma trial||6 Nov|
|MAGE-A10 TCR||Adaptimmune||Preclinical safety testing||6 Nov|
|NY-ESO TCR||Adaptimmune||Characterisation in myeloma patients||6 Nov|
|B7-H4 CAR-T||Novartis||Targeting B7-H4||6 Nov|
|Not specified||Novartis||CAR-T in ovarian cancer||6 Nov|
|PSCA CAR-T||City of Hope||Bone metastatic prostate cancer||7 Nov|
|BCMA CAR-T||Bluebird Bio||Multiple myeloma activity||7 Nov|
|EGFRvIII CAR-T||Kite Pharma||Glioblastoma||7 Nov|
|CD20/CD19 CAR-T||Lentigen||Dual CAR-T to minimise antigen escape||7 Nov|
|Not specified||Theravectys||Development of switchable CAR-T cells||7 Nov|