An Audience With in 2019

With Takeda’s US$62 billion acquisition of Shire in 2018, the Japanese firm scored a spot as a top 10 pharmaceutical firm. But well before the deal was even on the radar, President of R&D Andy Plump and CEO Christophe Weber were already working to transform the company. Once a small-molecule specialist, it is now embracing new modalities to be better positioned to follow the biology of disease. Once internally focused, it is now partnering whenever possible both to bring compelling new projects in and to let promising assets out. And Plump, now celebrating 5 years at the firm, is ready to showcase Takeda’s new look. He spoke with Asher Mullard about Takeda’s plans to leapfrog competitors in immuno-oncology, cellular therapy, rare diseases, gene therapy and more.

Vertex’s goal over much of the past decade has been on treating cystic fibrosis, targeting the dysfunctional CFTR chloride channel at the root of the disease. Following the speedy approval in October of its triple combination therapy Trikafta, nearly 90% of people with cystic fibrosis now stand to benefit from the firm’s CFTR potentiators and correctors. With this landmark success in hand — and the lucrative market it has opened up — the company is now in the process of broadening its horizons. In April 2020, current CMO Reshma Kewalramani will step up to the CEO role to oversee the transition. She spoke with Asher Mullard about the lessons the company has learned from cystic fibrosis drug development and its future R&D plans.

In 2009, Merck & Co.’s PD1-blocking antibody pembrolizumab was in development limbo. A decade on, the immuno-oncology drug is Merck’s crown jewel, with more than 20 approvals in 15 tumour types and revenues that are expected to reach US$10 billion this year. For Roger Perlmutter — an immunologist, president of Merck Research Laboratories and executive vice-president of Merck & Co. — this success was not always a sure thing. On the fifth anniversary of the FDA’s approval of pembrolizumab, he spoke with Asher Mullard about remaining immuno-oncology opportunities and questions.

In 1989, Stanley Crooke left his job heading up R&D at Smith Kline Beckman, a predecessor of the pharmaceutical giant GlaxoSmithKline, to found and run the antisense-oligonucleotide start-up Ionis Pharmaceuticals (initially called Isis Pharmaceuticals). With just over US$5 million funding at the time, Crooke’s ambitious plan was not just to develop a new RNA-targeted modality that could lower protein expression, but also to tackle industry’s productivity crisis while delinking drug development from commercialization. As broader interest in antisense technologies waxed and waned, Ionis faced some tough years. But it now has three antisense products on the market with partners, three products including a pioneering treatment for Huntington disease in phase III trials and more than ten candidates that could enter phase III trials by the end of 2020. After 30 years at the helm of Ionis as CEO, Crooke will transition to the executive chairman role in January. He spoke with Asher Mullard about Ionis’s long road to success, and the future of antisense drug technology.

Clinical trials can be big, cumbersome and unpredictable. Patients can be hard to recruit, and then their care has to be carefully coordinated through complex health-care systems, all while an ever-growing amount of data is collected and analysed. But if you could build a clinical trial operating system from the ground up, could you tame these beasts? Cardiologist Jessica Mega was running 10,000-plus patient trials at Harvard before jumping at the opportunity to take this task on at Google X in 2015. As chief medical and scientific officer at Verily, Alphabet’s resulting life sciences subsidiary, she now oversees a stable of projects that include immune profilers, wearable sensors and bioelectronic medicines. In May, Verily partnered with four large pharmaceutical firms to put its evolving clinical trial operating system to the test. She spoke with Asher Mullard about how her team is working to bring clinical trials to heel by optimizing patient recruitment and re-imagining health-care data.

Daphne Koller didn’t anticipate becoming a drug hunter when she joined Stanford University as a professor of machine learning in 1995. But after stumbling into biology a few years later because of the novelty of the small but diverse data sets it offered, the field quickly drew her in. By 2016, she was the chief computing officer at Alphabet’s ageing-focused biotech Calico. She then founded the biotech insitro in 2018 to explicitly generate high-quality biological data sets at high throughput to enable the application of machine learning to drug discovery. She spoke with Asher Mullard about her vision for machine learning in drug discovery, the need to view data as a core asset of a business rather than a byproduct and how to foster computational excellence in biopharma.

Merck & Co. set up its Exploratory Science Center in Cambridge, Massachusetts, to keep a finger on the pulse of emerging biological science, with a disease-agnostic scope and nimble mindset. Headed up by Daria Hazuda, CSO of the centre and vice president of infectious diseases and vaccine discovery at Merck, for now it focuses on the interaction between the microbiome and human immunity. Hazuda spoke with Asher Mullard about the firm’s exploratory science agenda, its interest in the microbiome and its continued focus on antibiotics and HIV drugs.

As a child, John Tsai used to take apart his older brother’s toys to see how they were made. This curiosity propelled him into a career first as an electrical engineer, and then on to medical school and into drug development. Last year he joined Novartis as head of global drug development and Chief Medical Officer, after nearly 20 years at Pfizer, Bristol-Myers Squibb and Amgen. At Novartis he is now overseeing, amongst other things, the company’s embrace of advanced therapies — including its gene therapy Zolgensma for spinal muscular atrophy. He spoke with Asher Mullard about applying an engineering mindset to drug development, the opportunities for operational efficiencies in clinical science and the future of advanced therapies at Novartis.

If drug discovery is the art of taking smart risks, then David Liu is a virtuoso. A Harvard chemical biologist who has been kicked out of casinos for winning too much money with a blackjack card-counting system of his own creation, Liu has developed genome-editing tools that may one day be turned into therapeutics and DNA-encoded libraries that can help in the hunt for small-molecule drug leads. His attitude towards risk — and its minimization — has also led him to become a serial biotech entrepreneur, setting up six biotech firms, including Ensemble Therapeutics, Editas Medicine, Beam Therapeutics and another company that is in the works. He spoke with Asher Mullard about the future of genome editing, the influence of DNA-encoded libraries and how company creation has influenced his career.

Bahija Jallal knows biologics, having spent the past 11 years working in and overseeing R&D at AstraZeneca’s biologics organization MedImmune. So when the opportunity came along to steward the development of what could be a new biologics modality, Jallal couldn’t resist. In January, she stepped down as president of MedImmune — just months before AstraZeneca retired its biologics brand — to instead take up the CEO role at the biotech firm Immunocore. Immunocore’s focus is on T cell receptors (TCRs), the cell-surface molecules that help T cells to hunt down pathogenic cells. While other companies are engineering TCRs on T cells ex vivo to develop cellular therapies, Immunocore has figured out how to engineer TCRs for use as soluble, bispecific biologics. Jallal spoke with Asher Mullard about the opportunities for TCRs in cancer immunotherapy, infectious disease and autoimmunity.

Hal Barron feels like he has been training his whole life to run R&D at GlaxoSmithKline, even if he didn’t know it at the time. His broad set of experiences — including an undergraduate degree in physics, a medical degree in cardiology, a professorship in epidemiology and biostatistics, as well as time spent steering R&D at Genentech and Roche and helping to build the Google-backed biotech Calico from scratch — will come in handy as he tackles the challenges of drug discovery and development at scale, he told Asher Mullard. After over a year on the job, he talks about doubling down on genetically validated targets, functional genomics, machine learning, immunology and more.