An Audience With in 2021

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.