Amphista Therapeutics has consolidated its move from Scotland to Cambridge with such aplomb that it would be easy to overlook the logistical triumph it represents.
Prof Alessio Ciulli, a world leader in the field of targeted protein degradation based at the University of Dundee, cuts the cake with CEO Nicki Thompson at the opening of Amphista Therapeutics’ new Cori Building base in September. Picture: Tim Steele Photography
The team of 50 – and growing fast – is now installed at Granta Park’s Cori Building, with the result is that the Cambridge region now has something of a targeted protein degradation (TPD) jewel in its crown.
Amphista is a global leader in the discovery and development of next-generation TPD therapeutics. The TPD field is poised to pursue targets previously considered ‘undruggable’. The emerging strategy tackles disease-causing proteins that have historically been very challenging to target with conventional small molecules.
Using TPD, disease-causing proteins within cells are targeted and removed using the body’s natural waste removal mechanisms. Amphista’s technology identifies disease-causing proteins and flags them up as waste which the body then eliminates.
CEO Nicki Thompson is a cell biologist by training. Picture: Keith Heppell
Amphista was founded in 2017 by Advent Life Sciences with the groundbreaking science emerging from the laboratory of Professor Alessio Ciulli at the University of Dundee.
“The company’s roots are in the University of Dundee, though Prof Ciulli was also an academic in Cambridge at one time,” Amphista Therapeutics’ CEO Nicki Thompson explains.
Indeed Prof Ciulli, a world leader in the field of targeted protein degradation, was awarded a Gates Cambridge Scholarship to study at the University of Cambridge under the supervision of Professor Chris Abell and was a BBSRC David Phillips fellow at the University of Cambridge within the Department of Chemistry and a fellow of Christ’s College, before moving to Dundee in 2013.
Amphista takes its name from the mythical serpent the Amphisbaena (also known as an Amphista), which had a head at each end and was said to possess health-giving qualities.
In the lab at the Cori Building. Picture: Keith Heppell
The Greek name is apt: in 2015, Ciulli developed one of the first ever non-peptidic two-headed PROTAC (proteolysis-targeting chimeras) approaches. PROTACs are designed as a two-headed molecule where one end binds an enzyme and the other binds the disease protein, bringing the two into close proximity.
Since then, Amphista has developed its proprietary Eclipsys drug development platform to deploy mechanistic insights and novel chemistry approaches for new protein-degrading therapeutics with superior levels of efficacy and broad therapeutic applicability.
The science – and the move – have progressed rapidly under Nicki’s watchful eye since she took on the role in June 2019.
“I started my career at Glaxo,” Nicki says. “I’m a cell biologist by training. Then I decided I wanted to learn more about business development, then I was approached by Roche.”
Amphista Therapeutics enjoys new facilities on Granta Park. Picture: Keith Heppell
Nicki moved into Roche’s leadership team in Basel as VP, global head, office of external drug discovery, where she helped develop the company’s portfolio. After Roche her CV is Cambridge-centric, first as CBO at Phico Therapeutics, then as CBO at Nanna Therapeutics.
“While I was at Nanna I was approached by Advent Life Sciences. Advent had incubated Amphista in Alessio’s lab. I went up to look at the technology and found it incredibly exciting; it was everything you’d look for in a start-up, so I stayed at Nanna as chair until it was acquired by Astellas [in 2020]. I stepped back after the acquisition.”
The elegance of the TBD mechanism being developed was irresistible.
“TPD is a new therapeutic modality which is moving very rapidly,” Nicki says. “Amphista had something novel, and a world-leading lab, and very knowledgeable founders.
“I’d worked in that space and understood the unmet need to use the body’s own cells to remove proteins involved in disease, or that are faulty and need to be removed. We’re not changing the protein’s function, we link up to it and drag it to the cell’s waste disposal. We target it for destruction but this is a natural process.”
Amphista Therapeutics has a team of 50 on Granta Park. Picture: Keith Heppell
First up is cancer.
“We started focusing on cancer but we believe we’ve made such progress we’re moving out to immunology and there are also indications in the central nervous system, for instance neuro-degeneration.”
With the first molecule due to go into pre-clinical development in 2023, Amphista’s science is in a great place, underpinned by the appointment of leading protein degradation pioneer Ian Churcher in May 2020.
Meanwhile, a very solid financial position has been secured by Nicki and her team. A Series A round raised $7.5m in April 2020. An oversubscribed Series B round raised $53m in March 2021, for which Amphista won a Financial Deal of the Year at the Scrips Awards this year. In May this year Amphista entered into a strategic collaboration with Merck for the discovery and development of targeted protein degradation therapeutics.
The Amphista Therapeutics trophy for winning Financial Deal of the Year at the Scrips Awards this year. Picture: Keith Heppell
Amphista and Merck will collaborate to leverage the Eclipsys TPD platform and generate novel protein degrading therapeutics in oncology and immunology. The collaboration includes up to $45m in combined upfront and R&D funding payments for an initial three programmes: Amphista will potentially receive up to $1bn in total payments.
Also in May, Amphista announced a collaboration with Bristol Myers Squibb which included an upfront payment of $30m, the potential for up to $1.25bn in performance-based milestone payments and payments for a limited expansion of the collaboration, including royalties.
In October, shortly after being named a member of the Fierce 15 for 2022 by Fierce Biotech, Amphista selected Cambridge-based Domainex as one of its trusted partners to support its research programmes. Domainex, a leading, multi-award winning integrated medicines research services partner, will provide expertise in protein production, assay biology and medicinal chemistry.
Nicki Thompson, CEO at Amphista Therapeutics. Picture: Keith Heppell
Nicki concluded: “Amphista is expanding rapidly at our Granta Park research hub as we advance our growing internal TPD portfolio and our recently signed strategic partnerships with Bristol Myers Squibb and Merck.”
The low-key tone is part of Amphista’s modus operandi. I put it to Nicki that the fact that the consolidation from Scotland to Cambridge was achieved in less than a year, while a similar shift into the UK’s life sciences powerhouse took AstraZeneca eight years.
“Yes, but they had a lot more staff,” she instantly demurs in an understated tone that belies the sheer scale of the success that she and the Amphista team have already delivered – and there’s more, so much more, to come.
Business News Mike Scialom