AACR – Combinations, oncolytic viruses and more

With all the abstract titles for the American Association for Cancer Research meeting now available, as well as the texts of the non-clinical presentations, biotech investors have a good idea what to expect when the meeting kicks off tomorrow.

Much focus could fall on combinatorial approaches, especially that of Lilly’s abemaciclib, while with the recent approval of Merck KGaA/Pfizer’s Bavencio investors will be keen to pick apart the Merkel cell cancer study due for presentation on Monday. There is even a supporting role for oncolytic virus approaches, which also hold most promise in combination (see table below).

The most important oncolytic virus presentation seems to be on Viralytics’ Cavatak, with results of a phase I study combining it with Yervoy due on Tuesday. Response durability will be analysed to see if the melanoma study backs the theory that virus-infected cells increase a tumour’s immunogenicity, making it liable to immune checkpoint blockade.

Transgene is presenting a preclinical poster on its own oncolytic virus that also seems to support combination with PD-1 or CTLA-4 blockade.

Immuno-oncology combos

That said, other combinatorial approaches might get more attention, especially those involving IDO inhibition, with Bristol-Myers Squibb investors looking for read-across from a trial of BMS-986205 with Opdivo to back the company’s recent acquisition of Flexus, which has given it an alternative IDO inhibitor to combine (AACR – Rags to riches to rags again, March 3, 2017).

Beyond IDO three presentations investigate combining abemaciclib with a PD-L1 blocker, anti-ERK1/2 or Mek inhibitor – the last in a clinical study. Abemaciclib most recently improved progression-free survival in the Monarch-2 trial in HR-positive, Her2-negative breast cancer, and is expected to be launched in 2018.

Bavencio, as Merck KGaA/Pfizer’s avelumab is now known, recently became the fourth MAb targeting the PD-1/PD-L1 interaction to be approved, getting the US green light for the orphan indication of Merkel cell carcinoma. Its Merkel cell trial might thus be of academic interest, though safety will be scrutinised as investors await progress in more lucrative cancer types.

The texts of AACR abstracts detailing clinical trials do not become available until 4:30pm Eastern time tonight. Accordingly, investors are still none the wiser about some studies, including that of Corvus’s A2a antagonist – an approach more commonly associated with failing to deliver in Parkinson’s disease.

A separate clinical trial, due for unveiling at AACR on Sunday, concerns Novocure’s wearable Optune device, which delivers low-intensity electric fields. Investors will look for the magnitude of the benefit Optune shows in final results of a trial whose interim data were good enough for US approval in glioma (Interview – Novocure plays the fields, February 9, 2016).

Selected abstracts for 2017 AACR meeting
Project Company Abstract detail Abstract no
Abemaciclib + anti-PD-L1 Lilly Anti-PD-L1 combo 583/17
Abemaciclib + LY3214996 Lilly Anti-ERK1/2 combo 317/3
Abemaciclib + PD-0325901 Lilly Embargoed clinical trial - Mek inhibitor combo CT046
Opdivo Bristol-Myers Squibb Embargoed clinical trial - 5yr follow-up from CA209-003 NSCLC study CT077
Opdivo + Yervoy Bristol-Myers Squibb Embargoed clinical trial - 2yr OS update from Checkmate-067 CT075
BION-1301 Aduro First-in-class fully blocking anti-April MAb 2645/4
Cabiralizumab  Five Prime Anti-CSF-1R approach 1599/7
COM701 Compugen Anti-PVRIG approach 581/15
FPA154 Five Prime Anti-GITR approach 613/17
INCAGN1876 Agenus Anti-GITR approach 3643
Cavatak + Yervoy Viralytics Embargoed clinical trial - oncolytic virus combination CT114
NKTR-214 Nektar CD122-biased cytokine agonist synergistic with radiotherapy 1604/12
Avelumab Merck KGaA/Pfizer Embargoed clinical trial - Merkel cell carcinoma CT079
STRO-001 Sutro Biopharma CD74-targeting antibody-drug conjugate 67/18
Optune Novocure Embargoed clinical trial - wearable device in GBM CT007
on/off CAR switch tech Bellicum Use in activating or ablating CAR-T cells LB-184/7
BPX-701 Bellicum Go-switch activated anti-PRAME engineered TCR 3745
UCART22 Cellectis Allogeneic anti-CD22 CAR in relapsed leukaemia 3763/19
Self-deliverable siRNA Mirimmune (RXI Pharmaceuticals) Suppression of PD-1 to improve CAR-T cell activity 5650/4
mRNA administration Moderna mRNAs encoding IL-36γ, IL-23 and Ox40L 1607/15
CA4948  Curis IRAK4 inhibitor  127/23
TG6002 Transgene Armed oncolytic virus boosted by checkpoint blockade 4563/8

With clinical data still under wraps numerous preclinical presentations have caught the attention of analysts and physicians.

For instance, early data on Aduro’s BION-1301 will be important since this project is a first-in-class MAb fully blocking April, a ligand associated with BCMA, with potential in multiple myeloma. For signs of activity against novel immune targets early data will be discussed on PVRIG, courtesy of Compugen’s COM701, and GITR (Five Prime’s FPA154 and Agenus’s INCAGN1876).

And, as before, novel adoptive cell therapy approaches will play an important role, with Bellicum’s on/off switch technologies featuring in two AACR presentations. At a recent investor webinar Dr Marcela Maus, a prominent cell therapy specialist at Massachusetts General Hospital, cast doubt on the utility of these suicide genes.

Be that as it may, all the leading CAR-T players are on the lookout for novel technologies of this type, and AACR is bound to provide plenty of food for thought.

This story was amended to correct the Transgene entry. The AACR meeting this year takes place in Washington, DC, and begins on April 1.

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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