News & Comment

With multiple COVID-19 vaccines approaching the finish line, and dozens of COVID-19 drugs in development, more eyes are on the European Medicines Agency (EMA)’s decisions than ever before. Emer Cooke, who started as Executive Director of the EMA in November, is ready. Cooke, a pharmacist by training, has more than 30 years’ experience in pharmaceutical regulation. During this time, she has seen the system transform: the typewriters and carbon copy are gone, replaced by unprecedented volumes of data and complexity. With prior roles that have included oversight of the regulation of medical products at the World Health Organization, Head of Inspections at the EMA and Head of International Affairs at the EMA, she is prepared for the multidisciplinary nature of the challenges ahead. She spoke with Asher Mullard about the speed of progress with COVID-19 vaccines, the potential longer-term impacts of the pandemic on regulatory affairs and her goals for the EMA once the world returns to business as usual.

The sugars that coat the surface of the cell have long fascinated Carolyn Bertozzi, a Professor of Chemistry at Stanford University. But her study of these complex carbohydrates has had much further reaching implications. Her pioneering work on bioorthogonal chemistry — reactions that can be run in living systems, without damaging them — has opened up basic drug discovery and therapeutic applications alike, for example. In her hands, these chemical tools have led to the creation of new therapeutic modalities including antibody–enzyme conjugates that can reshape the glycocalyx and lysosome-targeting chimaeras (LYTACs) that can degrade membrane-bound and extracellular targets. These, in turn, are helping her to further unravel the role of sugars in biology and in immuno-oncology. Bertozzi has already founded eight companies to advance these and other approaches. More are on the way. Speaking with Asher Mullard, she discussed her work and why drug developers have been so slow to see the sugars on the surface of the cell.

Between 2000 and 2010, Pfizer racked up three of the ten largest biopharmaceutical deals of all time, with a US$90 billion acquisition of Warner-Lambert, a $60 billion merger with Pharmacia and a $68 billion acquisition of Wyeth. The last deal, especially, was aimed at bolstering Pfizer’s flagging pipeline and protecting its revenue base from an upcoming patent cliff. More than a decade on — having walked away from an attempted takeover of AstraZeneca and a merger with Allergan — the company is celebrating an R&D turnaround. Pfizer CSO Mikael Dolsten has overhauled the firm’s scientific approach, focusing on five therapeutic areas, halving the number of candidates the company has in the clinic, and expanding its modality capabilities beyond the small molecules it used to focus on. And he believes the results are in: Pfizer’s phase II success rate has tripled in recent years, he said at a recent investor day. Dolsten spoke with Asher Mullard about Pfizer’s clinical success rate, its focus on speedy drug development and its approach to modality expansion in recent years.

Computational chemistry is already embedded in the drug discovery process. Schrödinger — a company that was founded more than 30 years ago to develop chemical simulation software for biopharmaceutical partners — believes that it should be more foundational still. Having co-founded several biotechs in the past decade, including Nimbus Therapeutics and Morphic Therapeutics, Schrödinger launched its own drug discovery pipeline in 2018 to expand this model. Heading up that effort is Schrödinger Chief Biomedical Scientist Karen Akinsanya. A pharmacologist by training, Akinsanya has more than 20 years industry experience working at the bench, the bedside and then in the boardroom. She now goes back to her research roots, leading the screening of hundreds of billions of compounds against targets of interest. She spoke with Asher Mullard about Schrödinger’s physics-based approach to computational chemistry, the bottlenecks in this approach, and the new opportunities it can open up.

When Tillman Gerngross co-founded Adimab in 2007, his goal was to build a one-stop antibody-discovery shop for biopharma partners in need of biologic therapeutics. In the years since, the company has worked on over 350 programmes from more than 70 partners, helping advance 41 antibodies into the clinic — without ever being tempted into drug development programmes of its own. The onset of COVID-19 has changed that. Although dozens of biopharma firms are already working on therapeutic antibodies that might help keep the SARS-CoV-2 virus at bay, Gerngross and his co-founders of the Adimab spin-out Adagio Therapeutics see an opportunity to use antibodies to tackle coronaviruses more broadly. And, while much of the drug discovery world is laser-focused on the current pandemic, perhaps now is the time to also start preparing for the next outbreak. Gerngross spoke with Asher Mullard about broadly neutralizing antibodies for the prevention of coronaviral infections, and more.

Leena Gandhi, a thoracic oncologist, started working with cancer immunotherapies in 2008 in one of the first trials of the PD1 inhibitor nivolumab and has been hooked on the field ever since. In the subsequent decade, she coordinated dozens of immuno-oncology trials — first at Dana Farber Cancer Institute, then at New York University’s Perlmutter Cancer Center — including a seminal study defining the use of PDL1 as a biomarker for PD1 inhibition in lung cancer. After a 2-year stint overseeing immuno-oncology at Eli Lilly, Gandhi is now returning to the Dana Farber Cancer Institute as Director of its new Center for Therapeutic Innovation. She spoke with Asher Mullard about the appeal of immunotherapies, how they have impacted academic drug development, and the hunt for better biomarkers that can unravel their complicated biological effects.

Last year, Pfizer joined the growing ranks of pharmaceutical firms with a digital strategy leader on their executive management teams. Lidia Fonseca, Pfizer’s first Chief Digital & Technology Officer, stepped into this role with a broad remit to set the company’s digital goals in drug discovery and development, operational processes and manufacturing, product sales, patient-facing experiences and more. No small task before COVID-19, the global pandemic has now forced companies to embrace digital tactics more than ever. Fonseca spoke with Asher Mullard about Pfizer’s pre-COVID-19 digital priorities, and how the pandemic has changed things.

CRISPR–Cas gene editors are now both moving into the clinic and being embraced as a means to find and validate drug targets. But for Jennifer Doudna, who helped pioneer this promise with her work at UC Berkeley, the full potential of these tools will only be unleashed when they can be used at scale. To this end, Doudna and colleagues partnered last year with GlaxoSmithKline to launch the Laboratory for Genomic Research (LGR), a US$67 million effort aimed at industrializing the CRISPR–Cas workflow for the detailed exploration of human genetics. One year on, she spoke with Asher Mullard about her hopes for CRISPR–Cas editors as drug discovery tools, the types of projects the LGR is working on and the challenges they face.

Over 180 clinical trials of proposed COVID-19 drugs are already recruiting patients, and another 150 are registered to start recruiting patients soon. But many of these trials are small and not designed to identify the best treatment strategies for the COVID-19 pandemic. For Chief Executive of the Research Council of Norway John-Arne Røttingen, a more collaborative approach is now needed. And as Chair of the Executive Group and the International Steering Committee of the WHO’s recently launched Solidarity trial, he hopes this mega-trial can provide a blueprint, he told Asher Mullard.

In 2013, Ted W. Love — a former drug developer at Onyx, Genentech and elsewhere and cardiologist by training — came out of retirement to take on sickle cell disease. This inherited blood disorder, in which sickled red blood cells clump together, blocking blood flow and the delivery of oxygen through the body, afflicts nearly 100,000 people in the USA and millions more throughout the world. And yet, until recently, these patients have had few therapeutic options for preventing the organ damage, risk of stroke and severe pain associated with disease. Last year, as CEO of Global Blood Therapeutics, Love secured an FDA approval for his company’s voxelotor, a first-in-class anti-sickling agent that at last takes aim at the underlying pathophysiology of the disease. He spoke with Asher Mullard about the science of voxelotor, his hopes of being able to turn sickle cell disease into a quiescent condition and the FDA’s embrace of surrogate end points in more and more indications.

Roche is the world’s top oncology company by sales, earning nearly US$28 billion in 2018 just from its anticancer drugs. And oncologist Sandra Horning has been instrumental in making that possible, shaping the company’s development priorities for the past decade. An oncologist by training, Horning served as Global Head of Clinical Science for Oncology and Hematology at Genentech/Roche from 2009 to 2014, and then as Chief Medical Officer and Head of Global Product Development at the company from 2014 to 2019. In December she retired from this role. She spoke with Asher Mullard about how she has thought about Roche’s cancer pipeline, real-world evidence and more.