An Audience With

Fouad Namouni, head of R&D at Blueprint Medicines, discusses how dual blockade of a single target could push the tyrosine kinase inhibitor envelope.

As Galvani Bioelectronics advances its first ‘electroceutical’ candidate for a chronic disease into the clinic, company president Kristoffer Famm discusses the bioelectronic medicines R&D roadmap.

Ellen Sigal, the founder of Friends of Cancer Research, discusses the origins and future of the FDA’s breakthrough therapy designation as well as the changing patient advocacy landscape.

Ray Deshaies, head of discovery research at Amgen, discusses the role of PROTACs, RIBOTACs, molecular glues, multispecific biologics and DNA-encoded libraries in industry’s future.

John Maraganore, departing CEO of Alnylam Pharmaceuticals, discusses 20 years of RNAi drug development, new public health opportunities, remaining delivery challenges and his post-Alnylam plans.

Susan Galbraith, head of Oncology Research & Development at AstraZeneca, discusses the opportunities oncologists can’t walk away from, including HER2, antibody–drug conjugates and earlier intervention.

Feng Zhang discusses the expanding gene-editing toolkit, the need for better delivery systems and the reprogrammable biological technologies that remain to be discovered.

William Kaelin, a researcher at the Dana-Farber Cancer Institute, discusses how his research into the mechanisms of oxygen sensing paved the way for two new drugs, and how to improve the calibre of preclinical research.

Dean Li, the recently appointed President of Merck Research Laboratories, discusses his immuno-oncology ambitions, emerging antiviral opportunities and the changing pace of technological cycle times.

Luisa Salter-Cid, the Chief Scientific Officer of Pioneering Medicines, will build a portfolio of programmes by tapping technologies on offer at dozens of companies founded by venture capital firm Flagship.

Uğur Şahin, an oncologist and mRNA pioneer, discusses his firm’s development plans for cancer vaccines, mRNA-encoded proteins and more.

Mind-altering drugs such as psilocybin and MDMA could transform the treatment paradigm for mental health disorders, says neuroscientist David Nutt. But trial design considerations, regulatory hurdles and economics still pose problems for psychedelic-assisted therapies.

Peter Horby, co-lead on the RECOVERY platform trial, discusses the origins, lessons learned and future plans for one of the most informative studies of COVID-19 therapeutics.

Large pharmaceutical firms typically turn to clinician scientists to head up their R&D and early development operations. When Roche hired Aviv Regev last year to lead Genentech Research and Early Development (gRED), the company instead opted for a computational and systems biologist. Regev was one of the most prolific researchers at the Broad Institute of MIT prior to taking on her new role, with diverse interests spanning the life sciences and their interface with technology and computation. With projects like Perturb-seq, combining single-cell RNA profiling with CRISPR-based genetic perturbations, she showed how computational approaches could be used to dissect the molecular circuitry of the cell. With The Human Cell Atlas, she set out to collaboratively and comprehensively characterize all of the cell types in the human body. Now, she brings this big picture mindset to Roche’s Genentech. Advances in human biology, massively parallel high-resolution methods, modalities, and computation and mathematics are on track to change the nature of drug discovery, she told Asher Mullard.

When Kathy High started working on haemophilia in her academic lab at the University of North Carolina in the 1980s, she never imagined that she’d go on to co-create the company that would usher in the era of gene therapies. But, as founding President and Chief Scientific Officer of Spark Therapeutics, her work helped to validate the emergent modality. And since the FDA’s landmark 2017 approval for Spark Therapeutics’s voretigene neparvovec, for the treatment of an inherited retinal disease, the field of gene therapy has been booming. After Roche acquired Spark for US$4.8 billion in 2019, High decided it was time to return to the research lab. But the COVID-19 pandemic quickly put a damper on those plans, and High started thinking about returning to industry. Now, she has joined Asklepios BioPharmaceutical (AskBio) — recently acquired by Bayer for $2 billion upfront and up to $2 billion in milestones — as President of Therapeutics. High spoke with Asher Mullard about her career path, gene therapy manufacturing innovations and the field’s changing clinical focus.

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.