ASCO 2019 preview: Big Pharmas looking for cancer R&D revival as we hit next-gen crossroads

ASCO
It’s that time of year again, when the big and the small come together to shout about (or try to quietly hide) their latest cancer data at the American Society of Clinical Oncology annual meeting. (ASCO)

It’s that time of year again, when the big and the small come together to shout about (or try to quietly hide) their latest cancer data at the American Society of Clinical Oncology (ASCO) annual meeting.

The last few years, if we’re honest, have not created the most exciting sets of oncology data we’ve ever seen. We’re at something of a crossroads: A few years back, we had the late-stage results from checkpoint inhibitors showing us their promise, and then we had the rise of cell therapies in the form of Gilead Sciences' (nee Kite Pharma) and Novartis’ chimeric antigen receptor T-cell (CAR-T) therapies.

These drugs are now approved, and what we will see next as a "new way" will be CRISPR, but that’s only just getting clinic time, and we’re some way off from getting any major data sets. Now, we’re caught in a realm of combos, notably with checkpoint inhibitors such as Merck’s Keytruda (now with more than 1,000 trials) and a focus on next-generation T cell therapies, including those that are off-the-shelf or able to combat solid tumors—something many have struggled to do, with nearly all successes coming from blood cancers.

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As they say in the publishing world, you’re only as good as your last book, and us in the media especially can be guilty of wanting "the next big thing" and not seeing the promise of newer versions of marketed drugs or effective combinations.

Atara Biotherapeutics

There is genuine excitement (though the caveat remains heavy and constant throughout about how early these data are, and how small the patient populations remain) about one of these next-gen treatments, namely California biotech Atara Biotherapeutics' work on mesothelin-targeted CAR-T.

This therapy, being researched with the Memorial Sloan Kettering Cancer Center, has shown glimpses of promise in a hard-to-treat form of lung cancer and will be posting updated data at ASCO this coming week.

Celgene/BMS

Celgene, in the middle of being subsumed by Bristol-Myers Squibb, also has new data out from a next-gen CAR-T. JCAR-017 (bought from its $9 billion deal with biotech Juno last year), is being tested specifically in chronic lymphocytic leukemia, where the phase 2 data follow last year's American Society of Hematology update on hitting 65% to 83% complete response rates and improved safety in heavily treated patients.

This continues to be a phoenix from the flames story for Juno/Celgene and a big pipeline catalyst for the BMS deal, after Celgene had to stop work on a different version of a CAR-T therapy, known as JCAR-015, when it caused major safety concerns and a string of deaths, leading it to be axed, and focus on 017.

Then there is the story of Big Pharma: Sanofi and AstraZeneca to be exact, which are both posting new updates to their experimental cancer drugs and combos in the hopes they are not overshadowed by the smaller biotechs.

Sanofi and AstraZeneca both have long histories in cancer, but have both in recent months shaken up their R&D teams and are looking to the future of oncology research with renewed vigor.

Sanofi

Sanofi just this very week poached Atara’s R&D chief Dietmar Berger as its new head of development. The appointment also reunites Berger with John Reed, now Sanofi’s global head of R&D. Reed spent six years running the pRED unit at Roche, during which time Berger held senior positions in the oncology and hematology global clinical development teams at Genentech.

Berger arrives at a time when Reed, who joined Sanofi in July 2018, is starting to reshape the R&D group in line with his plans for the company. In February, Sanofi punted 38 projects and is still considering further, albeit smaller, revisions to its focus.

“We're continuing to review the portfolio and, in fact, are in the process now of refreshing our disease area strategies and looking at one of the places where we will prioritize and focus. So, while I don't expect major changes of the type you saw last year, I think we'll continue to see an effort to focus the R&D organization that will involve some prioritization,” Reed told investors last month.

If all goes to plan, a growing portion of the assets prioritized and advanced by Reed and Berger will originate at Sanofi. Having long relied on partners such as Regeneron for innovation, Sanofi now aims to derive about two-thirds of its pipeline from internal research.

One of these assets is anti-CD38 antibody isatuximab, which is being tested in combination with pomalidomide and dexamethasone. The latest data showed this cocktail led to about a 40% improvement in progression-free survival, 11.6 months vs. 6.5 months for pomalidomide and dexamethasone alone (p=0.001), in certain forms of multiple myeloma.

The drug is hoping to be a rival to the $500 million-IPO-seeking Genmab and its multiple myeloma therapy Darzalex. Whatever the financial impact of isatuximab, the drug will have symbolic importance to Sanofi if it comes to market.

Through a period in which partnerships have been critical to Sanofi, isatuximab was one of the in-house assets management pointed to as evidence that internal R&D was firing again. Sanofi’s researchers developed isatuximab with ImmunoGen but were heavily involved as far back as preclinical. With Sanofi looking internally for innovation, it needs isatuximab to be an R&D lodestar. 

AstraZeneca

The British-based Big Pharma has also been rejigging its R&D structure after a continued exodus of research executives left over the past two years; it created a new unit focused on cancer to be led by scientist José Baselga, M.D., Ph.D.

AstraZeneca has been leaning heavily on the approval of checkpoint inhibitor Imfinzi as evidence of its cancer success. But coming after a host of similar drugs were approved before it, and with its continual struggles to gain success in combo tests for the drug, it’s no surprise that it’s tacitly looking elsewhere for future innovation.

In the build-up to ASCO, Baselga spoke with The Wall Street Journal, saying under his leadership AZ would seek out assets and trials that focused on hitting cancer at an earlier stage. It also recently opened a near $7 billion biobucks deal with Japanese pharma Daiichi Sankyo for its next-gen breast cancer therapy.

At ASCO, the focus will be on AKT inhibitor capivasertib, a fairly under-the-radar drug, which analysts at Jefferies describe in its pre-ASCO note to clients as previously showing “encouraging efficacy." AZ says data will be presented from the phase 2 FAKTION trial, sponsored by Velindre NHS Trust, combining capivasertib plus its older drug Faslodex in relapsed metastatic oestrogen receptor-positive breast cancer.

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