Company of the Month: Achilles Therapeutics
Achilles Therapeutics is a biopharmaceutical company using DNA sequencing to develop personalised cancer treatments. We spoke to CEO Iraj Ali about Achilles’ innovative technology, as well as how ambitious funding plans and strategic relocations have fed into the company’s growth.
Iraj, with a PhD in Biochemistry from Cambridge University, was well-placed for a role in biotech, and has spent much of his career in the business side of the field. He spent six years in management consultancy with McKinsey and Company, before joining life sciences investment company Syncona Ltd.
It was through Syncona’s investment in the newly formed Achilles Therapeutics that Iraj came into contact with the company and its four founders Prof Karl Peggs, Prof Mark Lowdell, Prof Charles Swanton and Prof Sergio Quezada. In 2018, he left Syncona to join Achilles as its CEO.
The technology – a new concept for cancer treatment
Achilles’ origins are as a spinout of the Francis Crick Institute and University College London from work that was funded by Cancer Research UK. It was in this work that founder Prof Charles Swanton developed the theory that cancer tumours are clonal in origin, meaning that a single cell starts and seeds the entire tumour.
By using sequencing technology, the theory was that all the tumour cells could be mapped back, through mutations, to identify a single class of tumour antigens, which would be present on all tumour cells – clonal neoantigens.
“The ability to use cell therapy like this to target all tumour cells, while sparing all of the healthy tissue, is the game changer here for solid tumours. Treatments like chemotherapy and radiotherapy are effectively very blunt instruments that can do a lot of damage to healthy tissue. The advances in antibody treatments over the last 20 years have been terrific, but when you look at late stage, difficult-to-treat cancers, it’s only a cell therapy that has really shown convincing long-term disease control. We are helping refocus the immune system,” says Iraj.
And, so far, the results seem to be convincing. They have now progressed to clinical trial stage, with an open trial in small cell lung cancer, another in metastatic melanoma, and more in the pipeline.
In brief, the process involves comparing a sample of DNA from healthy tissue with a sample from a tumour. Using proprietary sequencing technology that has only recently become technically and financially viable, the DNA mutations that have occurred in the tumour cells can be mapped out.
Where the Achilles process becomes unique and differentiated from other precision immuno-oncology approaches such as CAR-T, TCR-T and TIL therapies, is with the introduction of dendritic cells into the manufacturing process of Achilles’ therapy. Dendritic cells are a crucial part of the body’s immune system. They act as messengers to the T cells in the body, presenting the information on tumour neoantigens, which the T cells can then attack.
The effect of using dendritic cells is that the resulting therapy delivers cells to the body that are designed to specifically target each patient’s tumour cells with precision. This, in turn, stimulates an extremely targeted immune response that doesn’t damage healthy tissue.
As Iraj explains:
“80% of people with cancer in the world have solid tumours. Of those, the most common – breast and prostate cancers – already have good outcomes from existing treatments. But lung cancer, for example, is almost as common but has very poor outcomes from existing treatments. For 200,000 lung cancer patients every year in Europe, the survival rate is only around 10%. That’s shockingly poor. But something like smoking-related lung cancer, which causes lots of mutations in the cells, is just the kind of cancer for which our therapy is most promising.”
Commitment and people
Two themes emerge when discussing the journey and growth of the company with Iraj: commitment and a recognition that a business is nothing without good people.
Although they took the decision to recruit a professional management team, including Iraj as CEO, all four scientific founders are still actively involved in the company. Two joined the company full-time, with Karl Peggs leaving a role as Head of Haematology at UCLH to become the Chief Medical Officer, and Sergio Quezada leaving his role as a professor at the UCL Cancer Institute to become the Chief Scientific Officer.
The decision to go ‘all in’ on early funding drives also informed the strong start the company made. Spearheaded by Syncona, the company was formed with an impressive £28million in Series A funding, which allowed them to set up labs, generate data and progress towards clinical trials. After Iraj joined as CEO, his approach to Series B funding was to maintain that ambition. At the time, they were the first UK pre-clinical biotech company to raise £100million in Series B funding, but, as Iraj explains, it was all about people:
“The attitude was: the more runway you have, the better the people. If you want to recruit the world leader in your field, she’s not going to join you if you only have three months of money. You need to be able to give people stability. At the start of the company, we managed to recruit really good people because of the strong funding position we were in and, as we grew, we wanted to maintain that.”
Moving from, and to, London
After initially relocating the company from its London origins to the Stevenage Bioscience Catalyst, the company has now moved back to London, and have fitted out their own premises in Hammersmith. While the move to Stevenage was driven by the availability of affordable lab space for smaller companies, the move back to London was driven, again, by people:
“We now have 200 employees and we’d reached a tipping point of needing to establish our own facilities. We looked at the home location of our existing staff, as well as those we’re expecting to hire. Two thirds of our staff already live in and around London. And looking at the talent in cell and gene therapy, they are all coming out of London universities. Institutions like UCL, King’s, the Francis Crick Institute and Imperial have really taken over in this space. Ultimately, we were looking for the least disruption for staff, so London was the clear favourite.”
The headquarters in Hammersmith isn’t the only investment in London. Achilles are also building a dedicating manufacturing facility in Hayes. When committing to this location (which will take two years+ to complete) again, access to talent was a feature, as well as the ability for staff to move between sites, and access to international logistics at Heathrow.
Ultimately, the goal now is to scale up and commercialise their process to make a product that can reach thousands of patients at an affordable price.
To that end, completing the infrastructure projects and trials in the UK are key, as is a strong commitment to collaborative research and development. They have a member of staff specifically dedicated to scanning the horizon for research funding and collaboration opportunities and in 2019/20 they took part in MedCity’s Collaborate to Innovate: Advanced Therapies programme. This provided funding for a collaboration with UCL on a research project that allowed them to be even more precise with the targeting of the T cells in their therapy.
The company also have their sights on the US market, of course. In July they recruited their first US patient in a trial for lung cancer. Iraj also credits their strong early performance in fundraising with being able to attract US investors. Earlier this year, they closed an IPO on the NASDAQ that raised approximately $175 million. Iraj is keen to point out that, contrary to popular belief, having no base in the US has not been a hindrance:
“Ultimately, that US investment has all come back to create jobs in the UK. We are now setting up a US R&D facility, but that wasn’t a factor in our IPO. I think sometimes we, in the UK, have a lack of confidence when it comes to raising money in the US. But we have science that is absolutely world class, we have an exceptional talent base, and we need to trust in that.”
Finally, Iraj has more words of encouragement for smaller companies that may be looking at Achilles’ new headquarters with envy:
“Having been involved in small companies for many years now, I’ve spent lots of time in one or two rooms, with no money and five people. That’s the hard reality for many biotechs. The nice building in Hammersmith we have now at Achilles is the sum of five years of work. Only a small percentage currently make it to that. But, you know, with good technology and good management, you can, and there can be a lot more companies in the UK achieving that and much more.”
Find out more: achillestx.com