FirstWord Lists – Who, where and when – the race for supremacy in the $35 billion immuno-oncology race

If the immuno-oncology market lives up to commercial expectations, today’s strategising – both clinical and in terms of business development – will have profound implications over the next couple of decades and possibly beyond. FirstWord takes a brief look at what companies are pursuing which targets as the race to develop a broad portfolio of products capable of delivering multiple combination therapies heats up.

While a number of players lead the chase – primarily centred around possession of ‘backbone’ PD-1/PD-L1 antibodies – the clear leader in terms of access to other potentially complementary checkpoint inhibitors is Bristol-Myers Squibb; a status that stems from its 2009 acquisition of Medarex.

AstraZeneca has also sought to broaden its checkpoint inhibitor portfolio, while Roche benefits from other credentials, such as its leadership of the broader oncology market and a dominant position in personalised medicine.

Bristol-Myers Squibb

- Broadest clinical development programme (approximately 10,000 patients)
- Broadest portfolio of clinical stage immuno-oncology antibodies: PD-1(nivolumab), CTLA4 (Yervoy), PD-L1 and LAG-3 antibodies
- Leadership position stems from 2009 acquisition of Medarex - see In Focus: Bristol-Myers Squibb's R&D shake-up – A tale of two acquisitions
- Alliance with Innate Pharma also provides access to the costimulatory 4-1BB agonist urelumab and the NK cell anti-KIR checkpoint inhibitor lirilumab
- Nivolumab granted FDA fast track designation for melanoma, kidney and lung cancer
- Nivolumab most advanced PD-1 in development with Phase III studies under way in each of these indications

Merck & Co.

- Portfolio focused on the PD-1 antibody MK-3475
- MK-3475 integrated via 2009 acquisition of Schering-Plough
- Strategic position could be viewed as "tenuous," noted analysts at Leerink Swann recently, "but preclinical pipeline and strategic acquisitions could quickly change the story"
- MK-3475 being trialled across a wide range of tumours in preclinical setting; Merck expects to unveil new data prior to the ASCO annual meeting in 2014
- Phase II and III registrational studies under way in melanoma, with Phase III studies in lung cancer expected to initiate before end of year
- Running a 1000-patient plus Phase I study in melanoma for MK-3475; Merck has denied this is a first-to-market strategy, but MK-3475 has been granted FDA Breakthrough Therapy status where nivolumab has not


- Like Merck, Roche has one clinical stage immuno-oncology antibody – the PD-L1 inhibitor MPDL3280a
- Phase II studies in lung cancer under way; progression into Phase III studies imminent
- However, the Swiss pharma giant has access to a broad portfolio of immuno-oncology facilitators via its Genentech division and is viewed as being the global leader in personalised medicine
- Alongside Bristol-Myers Squibb, is the only player with active combination studies under way (MPDL3280a with Zelboraf and Avastin)
- Company recently disclosed two additional checkpoint inhibitors have emerged from pipeline - see Spotlight On: Roche's R&D day – The key takeaways

See also In Focus: The cancer immunotherapy race - Will Roche's breadth of portfolio prove decisive as Merck & Co. takes on a more streamlined approach to R&D?


- Leerink Swann analysts recently labelled AstraZeneca a ‘dark horse’ in the immuno-oncology race
- Focus primarily on the anti-PDL1 product MEDI4736
- However, CEO Pascal Soriot has talked up importance of multiple approaches and product combinations
- Acquisition of Amplimmune in August integrated the preclinical anti-PD-1 AMP-514 into AstraZeneca’s pipeline
- Recently confirmed initiation of Phase I study of MEDI4736 with its CTLA4 antibody tremelimumab (the only other clinical stage anti-CTLA4 product alongside Yervoy) - see ViewPoints: AstraZeneca initiates combination study as it looks to accelerate into cancer immunotherapy race
- Also expected to initiate combination study of MEDI4736 with Iressa in non-small-cell lung cancer
- Demonstrating breadth of approach, AstraZeneca also has an OX40 antibody in development, which stems from its 2011 partnership with AgonOx

See also Spotlight On: Oncology emerging as the key strategic narrative at AstraZeneca as Soriot looks to integrate antibody drug conjugate platform

...the rest of Big Pharma

- Analysts have suggested that the likes of Pfizer, Novartis and GlaxoSmithKline are "on the outside looking in" and appear to have effectively missed the boat on immuno-oncology development. That said, partnership opportunities remain and Novartis in particular has a broad position in oncology that could be leveraged in terms of immuno-oncology development.

See also ViewPoints: Will cancer immunotherapies drive the next wave of Big Pharma M&A?

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