The founders of Astex Pharmaceuticals recalled its humble beginnings as the company celebrated its 20th anniversary in style with a garden party at Longstowe Hall.

A contortionist, strongmen, jugglers and a magician were among the performers entertaining guests at the July 7 event, at which Dr Harren Jhoti, president and CEO of the Cambridge Science Park-based company, paid tribute to the staff.

Recalling how the company was launched in 1999, he told guests: “I don’t think in any moment of madness I imagined I would be standing here 20 years later with the company still going, so that’s a real tribute to all of the fantastic people who have worked with us over the years and been on this journey.”

And he recalled a key moment from 2005, when Astex had generated its first drug candidate.

“We had a report that a patient on an early clinical trial in the US had responded. I had a request to go and visit this patient, by her husband. Using our drug we had been able to slow down the progression of her tumour by at least a year. What he wanted to do was thank me because they were then able to enjoy a special wedding anniversary together.

“That was a real emotional moment for me that emphasised what we are actually doing with this company,” he said.

Dr Jhoti was one of three scientific founders of Astex, along with noted biochemist and structural biologist Sir Tom Blundell and Chris Abell, who is now pro-vice chancellor for research, and professor of biological chemistry at the University of Cambridge.

“Dr Roberto Solari and I were at Glaxo Wellcome when we started to think about setting up a company,” Dr Jhoti told the Cambridge Independent.

“Tom and Chris were independently coming up with an idea looking at antimicrobials.

“We all started talking to the same investor, Abingworth Management.

“We were focused on developing a new approach to small molecule drug discovery now called fragment-based drug discovery. We were one of the first, if not the first, to form the phrase. This is now generally accepted as a very interesting approach to generating small molecule drugs in a much more efficient way than was possible at the time.”

The method involves screening much smaller compounds than usual. Biophysical techniques are used in the process to detect the binding of these tiny fragments to target proteins.

It is an approach that has borne fruit: Astex has two approved cancer drugs to its name, developed with partners, and a healthy looking internal pipeline.

It is a far cry from the company’s humble beginnings in a two-person office above Andrew Webster’s accountancy firm in Wellington Street, Cambridge.

“The first acquisition was some office chairs from Argos,” recalled Dr Solari. There were not even enough of them, however, to accommodate guests from Janssen when the company struck its first deal.

“They’d heard that Tom had set up a company and he had been consulting with them for many years,” said Dr Jhoti. “They had to visit the company premises – a two-person office, so we grabbed some people from Tom and Chris’ labs, but we only had two chairs… people were standing up when they arrived!

“But we got the deal done – they knew the experimental work was being done in the university.

“After three or four months, we got our first premises on Cambridge Science Park at the same time that we raised significant amounts of funding.

“We had three rounds of venture capital financing, of approximately £50million. We were the most well-funded life science company in Europe at the time.”

Sir Tom, who has played key roles in restructuring British research councils, said the board realised that to be successful they would need to work with pharma partners.

“We knew we had to collaborate, because as soon as you get to the end of the pre-clinical phase, things get incredibly expensive. All we could do on venture capital was to get drugs into phase one. Harren has been brilliant,” he said.

The success of Astex comes not only from its pioneering science, but its visionary approach to the business.

“From day one, we wanted to run a hybrid business model by building a new platform technology for the fragment-based approach and seek, early on, to establish partnerships,” recalled Dr Jhoti. “We were also mindful we didn’t want to sell all the value in the company, so we wanted to develop our internal pipeline as well.

Sir Tom, who turned 77 on Sunday, noted: “We had a good selection of people who came in on the board like Simon Campbell, whom I started working with at Pfizer in 1980. He was impressed and stayed with us on the board. It was an incredible period.”

“We also established very good collaborations with academic groups,” added Dr Jhoti. “It’s a really good mix of big pharma, which some of us had experience of, and academic backgrounds.”

Among those on the scientific advisory board is Prof Herbie Newell, emeritus professor at the Northern Institute for Cancer Research at Newcastle University.

“He was instrumental in the latest BALVERSA drug, which has just been approved in the US,” said Dr Jhoti.

Astex’s success is all the more remarkable when you consider how drugs are typically developed today.

“The amazing thing we managed to do was drug discovery in a small company. The trick was in the technology. Combine it with structure and it’s just amazing,” said Sir Tom, acknowledging the benefits of screening much smaller fragments.

Dr Jhoti said: “It was obvious to us, but it wasn’t to many people at the time. People thought we were really out there,”

For Prof Abell, one of the most remarkable facts about Astex, and a key reason for its success, is its ability to retain talented staff – aided by the kind of camaraderie in evidence at Sunday’s garden party, organised by its social committee.

“There have been people in this company for 17, 18, 19 years, which has been instrumental to the company,” said Prof Abell.

Sir Tom suggested: “What Harren has managed to do is to keep that culture where everybody shares and everybody interacts. It’s not divided. It’s multi-disciplinary and that’s been hugely successful.”

The team’s efforts really came to fruition in 2017, when Kisqali, a first-line treatment for HR+/HER2-advanced breast cancer, used in combination with an aromatase inhibitor, was approved for Astex’s partner Novartis by the US Food and Drug Administration (FDA) and also by NICE in the UK.

Then in April this year, Erdafitinib, marketed as BALVERSA, was approved for another partner, Janssen Pharmaceutical, by the FDA to treat certain cases of locally advanced or metastatic urothelial carcinoma.

Astex was acquired in 2013 for $886million by the Japanese company Otsuka Pharmaceutical.

“It was the seventh largest M&A deal that year in biotech, which underlines the value they place on biotech and the technology,” said Dr Jhoti. “Otsuka have been incredibly supportive. What they’ve allowed us to do is carry on running the business.

“Just last week, we were informed by another partner, AstraZeneca, that our drug capivasertib, which is a small molecule that inhibits AKT, a kinase in oncology, has formally entered phase III trials.

“Then we have a whole range of proprietary internal programmes, ranging from phase III to phase I. We’re in a very good position.”

But what, exactly, does ‘Astex’ mean?

“Roberto and I came up with the name in the pub. We got rather drunk,” said Dr Jhoti. “It’s an acronym and only a few people know it, but it adds some mystique. The real answer is rather dull…!”

Thankfully, the company’s life story – like its partying – is anything but.

Read more

How Astex founder Dr Harren Jhoti has changed the drug discovery process

Astex welcomes positive results for Kisqali breast cancer treatment

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