LIfT Biosciences is an advanced therapies SME that is developing the world’s first cell bank of cancer-killing neutrophils. Recently a runner up in the European Institute for Innovation and Technology (EIT) Accelerator programme, the company is an alumnus of the first round of the Collaborate to Innovate programme, which is managed by MedCity.

Unlike traditional targeted cancer treatments, the approach taken by LIfT Biosciences focusses on the innate immune system and the transferal of immunity from those who can successfully fight cancer. By extracting stem cells from these ‘exceptional donors’, the company plans to create a bank of neutrophils that will be stored to treat cancer patients and effectively switch on their immune system. This innate immunity platform is known as Neutrophil only Leukocyte Infusion Therapy (N-LIfT). Not only can it potentially produce a safer and more effective approach, but one that can be used across different types of cancers.

Here LIfT Biosciences CEO Alex Blyth talks about the experience of working with a research team from King’s College London as part of Collaborate to Innovate, the challenges faced by an advanced therapies SME and the next steps for the company.

A different approach to treat all types of solid tumours

Having worked in the pharmaceutical industry for over 15 years, LIfT Biosciences CEO Alex Blyth saw that cancer treatments were dominated by targeted approaches and that, although these have benefits in terms of selectivity and tolerability, they are limited in their success to provide sustained remission. “Put very simply the problem is that tumours adapt and targeted therapies do not,” says Blyth. “So I started to think about why so many people don’t get cancer and what is it that makes them different.”

When he saw those targeted treatments fail to save his mother from pancreatic cancer he was determined to find a different approach and it was this motivation that led to the formation of LIfT Biosciences. Through his search for a broad spectrum living cell therapy, Blyth found the work of Professor Zheng Cui from Wake Forest University in the US, which had identified a ‘super mouse’ with innate cancer immunity and then transferred its neutrophils to other mice to enable them to fight cancer.

“From the research it was clear that this approach could work,” says Blyth. “But I know from my experience in industry that consistency and predictability are key, so I approached Professor Cui to see if we could use stem cells to mass produce the neutrophils. This had never been done before and many believed that stem cells could not be used ex vivo to produce neutrophils as they are notoriously vulnerable.”

Collaborate to Innovate

It was at this stage in the company’s development that Blyth applied to Collaborate to Innovate and won funding to work with a research team at King’s College London that was run by Professor Farzin Farzaneh. “The team were cell experts which was exactly what we needed,” says Blyth. “So, for the first time, we were able to produce these special neutrophils with cancer killing ability ex vivo from stem cells and we found that not only could we get them to survive but that they could destroy 90 – 95% of pancreatic cancer cells in 30 hours which is astounding.

“The partnering with King’s at this stage meant a lot more than just the money to us. As an SME it is very difficult to get a university like King’s College on board and to give you access to their facilities. But having MedCity behind us really meant that we could get the necessary research done and, with a concerted effort, we got the data to support our patent filing. The patent was what the whole technology hinged on as well as the company’s chances of raising investment to get N-LIfT to patients and together we did it. MedCity also gave us support in getting media coverage of our findings which was very helpful in raising the profile of the company to attract partners and investment.”

Challenges of the advanced therapies sector

LIfT Biosciences is now at the stage of scaling up the process and they continue to work with the research team at King’s College London. However, they are increasingly aware that, as they get closer to their ultimate goal of using the therapy to cure cancer, they will need their own laboratory space and finding this is a challenge.

“At the moment we are doing critical experiments on cell production and it is really hard to find the right lab space in London that is also affordable,” says Blyth. “In advanced therapies we have very specific requirements in terms of handling the cells and the use of cryogenics to freeze them, which means a shared space can be difficult but it is also very expensive to set up our own laboratory to meet our specific needs.”

Alongside the issue of finding a lab there are also challenges in terms of negotiating the regulatory space and finding talent with regulation experience and an in-depth knowledge of Advanced Therapies Medicinal Products (ATMPs). “I’ve worked hard to get the right people in the team and I am very happy with the level of expertise,” Blyth says. “But it has been difficult to get experts in the area as it is still relatively new so finding someone who has worked for a long time in the regulatory space but also understands the very specific requirements for ATMPs is hard.”

Looking to the future: clinical trials

Whilst working on the scale-up process for the platform, the team at LIfT Biosciences are also raising money to conduct its first in-human clinical trial by 2021.

“We have all the protocols for the trial laid out,” Blyth explains. “The plan is to screen up to 300 donors and from this we expect to get 20 super donors. We will then run a process that will stimulate the release of stem cells into their blood so we can extract them and differentiate them into neutrophils. Once we have produced the neutrophils we are then planning to trial the therapy on a range of cancer patients.”

Reflecting the journey so far

Looking back on the journey of LIfT Biosciences, Blyth believes there are some places where he could have trusted his instinct more. “My biggest mistake was not going to the Medicines and Healthcare products Regulatory Agency (MHRA) right up front,” he says. “We deliberated for some time because those who were more accustomed to the traditional MHRA formalised procedures didn’t think we were ready. But when I decided to follow my instinct and just meet with the MHRA innovation team they gave us really clear guidance on what we needed.

“I also think it’s important to recognise that to be truly innovative you will need to shake up the system,” says Blyth “Often the most difficult people to convince about the potential of our work are immunologists as they tend to have been taught that treatments must be targeted and this is what they believe. Whereas when I talk to biologists, physicians or even the public they totally get it: they understand that some people get cancer and some people don’t and that you can transfer immunity. So you do need to change some people’s mindset, especially in academia, but once they are on board we find they tend to be absolute advocates.”

Remaining unique: Occam’s Razor

LIfT Biosciences is now in its third year of trading and, during that time, the advanced therapies sector, and more recently allogeneic innate cell therapies in particular, have grown and received more mainstream recognition. As the company moves towards completing its next round of funding, Blyth is certain that the sheer simplicity of the concept behind LIfT Biosciences will continue to contribute to its uniqueness and its success.

“There is clearly something missing from the current approach to fighting cancer and we believe that, until now, the role of the innate immunosurveillance system has been totally overlooked. Neutrophils are the most abundant white cell so it’s almost like ‘the elephant in the body’ to misuse a well-known phrase.

“There are 4 billion people on this planet who will never get cancer because they have effective innate immune cells within their body stopping cell mutations before they develop into tumours, and we believe we know how to unlock the potential of this innate immunity to totally destroy all solid tumours in those cancer patients who have not been so fortunate.

“I am a big believer in the philosophical principle of Occam’s razor which proposes that if there are two competing hypotheses, the simpler one with less compounding variables wins. I apply this when I compare all the heavily engineered therapies to N-LIfT which is just so beautifully simple. We mass produce N1a neutrophils from stem cells to give the exceptional innate immunity originally found in exceptionally healthy donors to cancer patients. The simple answer to cancer being ‘one another’.”

LIfT Biosciences are currently completing their next round for £6 million and seeking other investors to join the syndicate.

Alex Blyth will be talking at the next Advanced Therapies Network event on 14 May 2019 which is focussed on investment.