A new balance

2 August 2021 | BioPharm

T-cell

Immunotherapies, which harness the power of the body’s own cellular defences to attack selected targets, have been enabling huge clinical advances in areas like oncology. Scientists have successfully used CAR T-cells to stimulate patients’ immune systems to destroy tumours. But now the same techniques are being used to help transplant patients and people with autoimmune diseases, by suppressing immune responses when healthy cells are under attack.

London-based biopharmaceutical company Quell Therapeutics is using T regulatory cells (Tregs), a group of cells which provide a natural balance within the immune system, to develop new treatments for liver transplant patients, as well as people with ALS (motor neurone disease) and Type 1 diabetes. These pioneering therapies offer the prospect of single-dose treatments which could radically improve patients’ quality of life and slow disease progression.

Combined efforts

Founded by life sciences VC company Syncona, Quell unites leading academics from UCL, Kings College London and Hannover Medical School. The founders, Professors Emma Morris and Hans Stauss from UCL, Professor Giovanna Lombardi, Dr Marc Martinez-Llordella and Professor Alberto Sánchez-Fueyo from King’s and Dr Elmar Jaeckel from Hannover, combine unrivalled knowledge of the biology of Tregs as well as deep clinical and translational expertise. Their scientific credentials are complemented by an executive team with significant commercial and industry experience.

Bringing together so many institutional partners to create the company wasn’t an easy process. UCLB, along with the technology transfer organisation of King’s, was responsible for licensing the IP to the fledgling business. Barny Cox is Senior Business Manager for UCLB, and previously a board member at Quell:

“The company benefits from the expertise of some of the world’s leading immunologists. Working collaboratively across multiple organisations made the task of formalising the contracts required for company incorporation all the more complex. All parties involved were driven by a united desire to rapidly progress these innovative treatments towards the clinic for the benefit of patients.”

Pioneering engineered Treg therapy

Quell are creating multi-modular engineered Treg cell therapies. Cells are taken from a patient, before being activated and expanded in the lab, and then reinfused. The manufacturing process is the first key component of the technology, ensuring that cells are maintained in the right state. The second component is engineering the Tregs for different features, directing them to different targets within the body – for example liver tissue for liver transplant patients.

The therapies are highly innovative, as Luke Henry, Quell’s Chief Business Officer, explains: “No-one has yet dosed a patient with an engineered Treg, so Quell will be one of the first companies to do that when our liver transplant programme goes into the clinic early next year.”

Selective targeting will create an immunosuppressant ‘bubble’ around the liver, allowing the body to tolerate the transplant, without the need for suppressants in the rest of the body.

In addition to targeting, Quell’s process engineers in further modules, including a ‘phenotype lock’ which ensures that the Tregs don’t change their suppressive function, and also enhances their potency. Because the technology is so new, the final feature is a safety switch, which will allow the system to be turned off in the event of unexpected effects.

Single-dose treatments with lasting effects

Pre-clinical data suggests that a single dose of Tregs activated at the site of disease can effectively ‘reset’ the immune system, and induce a durable response even beyond the time that the CAR Tregs are active in a patient’s system. The implications are momentous. Currently, people undergoing transplant surgery have significantly reduced life-expectancy and suffer side-effects from the drugs used to stop transplanted organs being rejected.

“Patients who require liver transplants live on a cocktail of immunosuppressants for the rest of their lives,” explains Luke. “Because the drugs are suppressing the entire immune system, over time that leads to increased rates of cancer and opportunistic infections, as well as cardiovascular issues and kidney problems associated with side effects of the immunosuppressant drugs themselves.”

With Treg therapy, systemic suppressants may no longer be needed, creating the prospect of a lasting cure.

Building a product pipeline

Unsurprisingly, the potential for patients to permanently come off immunosuppressants is attracting a lot of attention. Quell achieved the biggest ever Series A investment in the field, with an initial financing round in March 2019 that was extended in February 2021 which brought total investment to $84 million. Excitingly, Quell’s platform has the potential to control both immunity and inflammation across a number of diseases, and the funding was used to build out the company’s pipeline, which includes two further indications, in ALS (motor neurone disease) and Type 1 diabetes.

These targeted treatments are progressing through pre-clinical proof-of-concept development. The hope is that they will slow disease progression, and in the case of Type 1 diabetes, reduce the co-morbidities which reduce long-term survival for patients with the condition. Luke outlines a fast-paced approach, which has seen the company grow rapidly, creating 75 highly-skilled jobs to date:

“We’ve come a long way in two years, from selecting the first clinical candidate, to building out our manufacturing capability, getting the investment needed to grow the company and now being on the cusp of filing for regulatory approval to go into the clinic with our first programme.”

Leading the field

As an early mover in a highly innovative space, the ongoing strategic relationship with academic partners has been critical. Quell is learning first in a cutting-edge field, says Luke: “You’re connecting the dots between the technology requirements, the manufacturing, embedding therapies into clinical practice, and running trials and so on. Working with an institution like UCL that just understands cell therapies makes that work seamlessly.”

With a broad and ambitious programme of future development mapped out, Quell looks set to continue leading the field, and to make a transformative impact on patients’ lives.

Further information: 

Quell Therapeutics