Briggs Morrison trades lead role in AstraZeneca R&D for the helm of tiny Syndax

Briggs Morrison

Last week, Briggs Morrison was the head of late-stage development and chief medical officer at AstraZeneca ($AZN) with responsibility for leading the turnaround at one of the world's biggest pharma pipelines with thousands of staffers, dozens of clinical-stage programs and a budget that's in the billions. This week, he's moving to a new job as CEO of Syndax Pharmaceuticals, a small biotech based in Waltham, MA, that has a staff of 20, counts its research budget in the millions and has a pipeline with one drug, the histone deacetylase (HDAC) inhibitor entinostat.

Morrison is still in transition from his old Big Pharma job to the new one in biotech and isn't free yet to publicly discuss his career leap. But it's a clear coup for Syndax and its venture backers. Morrison's high-profile transition will turn a bright spotlight on entinostat, a promising Phase III anticancer drug armed with a breakthrough drug designation at the FDA and a partnership with Merck ($MRK) developing an immuno-oncology combo. Syndax was named a Fierce 15 company in 2007.

"Bringing somebody like Briggs to the team allows us to build out a pipeline" and create a foundation for the company, says Michael Metzger, who's joining Morrison to shake things up at Syndax as the new president and COO. "This is a leadership team that's completely scalable."

Morrison has spent the last 20 years in Big Pharma R&D after starting out at Merck, moving to Pfizer ($PFE) and then landing a top job at AstraZeneca. When Pascal Soriot took over the pharma giant in 2012 he promoted Morrison to executive vice president in charge of late-stage development. Morrison played a big role in persuading investors to stick with the company and back its R&D strategy as it wrestled its way out of Pfizer's takeover attempt last year. Metzger's last job was at Regado, which was gutted after its big drug failed in Phase III and was then used as a shell company for a reverse merger, which he helped complete.

Morrison and Metzger have some big challenges ahead. Syndax can now evaluate the best way, and the best timing, for raising a crossover round and taking a second stab at an IPO that would position the company to grow its pipeline, says Metzger, adding new partnerships for a lead program with multiple cancer targets and adding new molecules to build the company further. Syndax's first shot at an IPO under CEO Arlene Morris was shelved earlier this year.

A few years ago, someone of Morrison's stature in the industry would be expected to stay put or look for an even better job in Big Pharma. But with the public markets for biotech sizzling with record valuations for single-asset companies, particularly in the cancer field, biotech can be a particularly alluring field these days. In making this leap, Morrison joins the likes of Tony Coles, the ex-CEO at Onyx who's now starting up a new biotech venture from scratch; Annalisa Jenkins, who now runs Dimension Therapeutics after a stint in charge of R&D at Merck Serono; and Jose-Carlos Gutierrez-Ramos, who recently handed in his leadership role at Pfizer's new R&D center in Cambridge, MA, for an upstart of his own.

Today, with the giants grappling with an onslaught of generic competition and demands to cut or keep the lid on expenses, moving up in pharma can mean moving out to the biotech industry, where investors have been pouring in billions for a piece of equity in the dream that these small developers are in charge of experimental therapies with game-changing potential. Gaining that kind of economic freedom to pursue game-changing technology can be tempting.

"The robustness of the capital market allows smaller companies to do things they've never been able to do before," says Metzger.

In this case, the bulk of the money has come from Domain and MPM. As of the first 9 months of 2014, according to its S-1, the company had burned through $155 million to advance entinostat into a Phase III study for breast cancer with 600 patients. Working closely with the National Cancer Institute, Syndax has a successful Phase IIb study behind it, with improvements in overall survival as well as progression-free survival. A second program for non-small cell lung cancer is not far behind. And Syndax is partnered with Kyowa Hakko Kirin in Asia, but still has a free hand in the U.S. and Europe.

Entinostat was in-licensed from Bayer in 2007 in a $150 million deal. And the science behind it is straightforward. The epigenetics program is aimed at HDAC, an enzyme that modifies histone in DNA as well as nonhistone proteins involved in cell survival, proliferation and immunity. Levels of HDAC are abnormally raised in cancer cells, triggering genes that accelerate the growth of cancer cells. Not surprisingly, HDAC is a well understood target in oncology, leading to the approval of two HDAC inhibitors--Zolinza (vorinostat) and Istodax (romidepsin). But Syndax believes, with some major validation from the FDA, that entinostat is a prospective first-in-class therapy, offering an oral therapeutic approach that can hit the best HDAC target with a longer half-life for less frequent dosing. The company also believes that this drug can work not only for hematological malignancies but also for solid tumors, greatly expanding its market potential.

The drug has also demonstrated an ability to thwart host immune cells that can set up obstacles to checkpoint inhibitors, making it an ideal combination candidate for the likes of Merck's PD-1 drug Keytruda. That's a field that Morrison understands well from his post at AstraZeneca, which has made immuno-oncology a cornerstone of its planned comeback.

Entinostat succeeded in registering a 27% reduction in the risk of death for breast cancer patients in a Phase IIb study, hitting the mark for statistical significance for progression-free as well as overall survival, with patients hitting a median OS of 28.1 months compared to the control arm's 19.8-month rate. That's a success that Syndax is now looking to confirm in Phase III, which should read out in mid-2017.

Their Phase IIb study for non-small cell lung cancer, though, failed to hit either the primary or the secondary endpoints. But Syndax reported that in a subset of 26 patients with elevated levels of E-cadherin, the median overall survival for patients hit 9.4 months in the entinostat-erlotinib arm compared to 5.4 months in the erlotinib plus placebo arm. In addition, the median PFS was 3.7 months in the entinostat-erlotinib arm compared to 1.9 months in the control arm.

As a result, Syndax has been busily hunting down new biomarkers that can link their drug with specific groups that are likely to benefit from it.

At the time the company filed its S-1, Domain Associates owned 34.3% of the company's shares, with MPM in charge of 29.4%, RMI Investments at 13.2%, Forward Ventures at 8.2% and Eddingpharm at 5.7%.

Source