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woman using eye drops

New spinout Healome Therapeutics to speed development for eye therapeutics

Written by Louise Stanley on . Posted in Experimental medicine.

BHP founder-member the University of Birmingham has created a new spinout, Healome Therapeutics Ltd, to commercially deploy a platform that delivers a ‘pro-healing’ microenvironment for the leading causes of preventable blindness.

The company’s leading application will be in ocular surface diseases, which are notoriously challenging conditions to treat, and have progressively larger impacts on quality of life as the diseases run their course.

The Healome technology is a novel fluid-gel material that flows like a liquid, and self-structures into a thin, clear, protective layer over the surface of the eye which is gradually dispersed and cleared away by blinking over 2-8 hours (customisable depending on application).

The gel can be used alone, or as a ‘carrier molecule’ to deliver other therapeutics.

Studies have already shown that one of Healome’s formulations has anti-fibrotic (anti-scarring) activity and these healing properties are augmented by combining it with other therapeutics.

The technology was developed by a team led by Professor Liam Grover who is Director of the University’s Healthcare Technologies Institute (HTI).  It is envisaged that treatments developed from this platform will come in the form of clear degradable ‘ocular bandages’ that can be applied like normal eye drops.

Professor Grover, who is also a co-founder of Healome Therapeutics, commented: “There are many cutting edge drugs on the market or in development for diseases that affect the surface of the eye. One of the biggest challenges is to keep therapeutics on the surface of the eye for sufficient time for them to have an effect and more generally to regain or replace all the functions of the tear film.”

The company’s founding directors already have prior experience in commercialisation and advancing therapies towards Phase I-III clinical trials and include Professor Anthony Metcalfe, Industrial Professor of Wound Healing, formulation engineer Dr Richard Moakes, and Dr Richard Williams, whose work at the HTI involves translating healthcare technology concepts to finished products ready to enter clinical trials.

Although Healome will initially concentrate on Dry Eye Disease, in the long-term the company aims to partner with healthcare companies to co-develop new therapeutics for delivery to the surface of the eye.

The gels respond to shear stress, which allows it to change back and forth from a liquid to a soft-solid consistency according to the physical forces applied to it, such as extrusion from a container, or blinking.

Its mechanical and drug diffusion properties can be ‘tuned’ by physical rather than chemical changes to the base polymers.  These attributes mean that pre-clinical or early clinical safety studies for new formulations will not need to be repeated and will reduce the time and cost to bring new products to market.

CEO of Healome, Dr Richard Williams, commented: “Ocular surface diseases leading to Dry Eye have a disproportionately large impact on health, well-being and the ability to enjoy life. These conditions can also be very expensive for patients to manage. There are many unmet patient, clinical and industrial needs in this area, which Healome Therapeutics is well-placed to address. Pre-clinical safety of the platform is well-established, GMP manufacturing has been set up to supply planned phase 1 trials and we have brought in significant executive experience in eye care to accelerate plans.”

The researchers behind Healome have already raised £2.8m grant funding from the Medical Research Council (MRC) to progress the original concept from lab bench to completing phase 1 human trials. The developed platform and supply chain was then applied to help tackle challenges in ocular surface diseases via a £1.3m grant from the National Institute of Health and Care Research (NIHR) Invention for Innovation programme. The platform has also shown early promise in dermal and orthopaedic applications.

Healome Therapeutics has already raised £400k funding from Innovate UK and SFC Capital, and is now establishing its own laboratories at the Birmingham Research Park, which has been nurturing high-growth biomedical companies since 1986.

Phase I human trials to test the core technology in combination with therapeutics known to prevent corneal scarring and manage severe dry eye will commence in Q2 2022, supported by the University of Birmingham GMP manufacturing facility.

Brave little girl having blood collection for tests

Continuation of funding secures Birmingham’s Clinical Research Facility

Written by Louise Stanley on . Posted in Experimental medicine.

The Birmingham Health Partners NIHR Wellcome Trust Clinical Research Facility (CRF) has been successful in its renewal funding bid from the National Institute for Health Research.music

The NIHR Wellcome Trust CRF was established in 2000 as one of the original 5 ‘millennium’ facilities, based at Queen Elizabeth Hospital Birmingham. It incorporated a facility at Birmingham Women’s and Children’s hospital in 2008.  This new award of £12.9million will continue to allow BHP founder-members UHB and BWC NHS Foundation Trusts to provide patients with opportunities to participate in experimental medicine research projects alongside their routine clinical care, in our ageless approach to care – from newborns through childhood, adulthood, maternity to old age.  In addition to this, the CRF is a vital facility enabling healthy volunteer studies and first in human trials for the advancement of new treatments and will continue to deliver this important work over the next five years.

The CRF supports both research and education, ensuring it maximises opportunities for staff development including all learners whether students on placement or healthcare professionals pursuing a clinical academic career.

Joanne Gray, CRF Clinical Manager said: “This is fantastic news for UHB and BWC patients and staff, allowing continuation of an established research facility leading to direct patient benefits and new technologies supporting patient care pathways.

“I am so happy to have received this news following our bid for funding at a time of such challenging times for the NHS.  It is great news for not only the CRF team but for the whole of the Birmingham region as we continue to offer research to Birmingham patients in an area the size of Scotland with the diversity of the world.”

Dr Dhruv Parekh, Programme Director, explained: “Experimental research is crucial and the stepping-stone to finding new treatments that may benefit patients. We are grateful for the on-going funding from the NIHR for the next 5 years to ensure the Birmingham Clinical Research Facility continues its excellent track record of ensuring new discoveries are translated to benefit our diverse populations across a wide range of diseases and ages.”

Professor Jeremy Kirk, Research and Innovation Director at Birmingham Children’s Hospital, said:

“We are delighted that the funding of the Birmingham Clinical Research Facilities has been renewed. This continued funding is a reflection of the very high-quality research being performed within Birmingham, including at the Children’s Hospital, the first paediatric unit of its kind in the UK.

“The early phase studies being performed within the CRF will ensure that our patients have access to the best and most promising therapies both now and in the future.”

Prof Simon Ball, UHB Chief Medical Officer added: “We are delighted to receive ongoing support for the Birmingham Clinical Research Facility from NIHR. It is a testament to our world-class facilities and professionals, the strength of the Birmingham Health Partners strategic alliance, and the relationship we have with our patients and population. We look forward to ensuring early phase clinical research is accessible to all the communities we serve.”

Matthew Boazman, Chief Officer for Strategy and Innovation at BWC said: “We are absolutely delighted to have received confirmation of funding and the ongoing support of the NIHR for the Birmingham Clinical Research Facility.

“This recognition is testament to the outstanding track record and expertise we have across the whole of our partnership for the delivery of early phase clinical trials and will enable us to continue to support experimental medicine and the advancement of new treatments from childhood through to old age over the next five years.”

Professor Lorraine Harper, Director of the CRF, added: “We are absolutely delighted to receive this funding award which reflects the world-class staff and facilities we have within our CRF.

We now look forward to offering opportunities to take part in early phase clinical research to a broader range of our diverse communities reflected within our Birmingham Health partnership”

Christopher Hodson, CRF patient/public representative, commented: “The CRF is a centre of excellence, providing vital input into early clinical and medical trials from a wide range of disciplines both from UHB and Birmingham Children’s Hospital. It is supported by a first class medical, nursing and laboratory team with a can-do ethic.  It is a privilege to be associated with it.”

Sandra Haynes, also a patient representative, added: “Involvement in the CRF and the funding means that patients get the very real opportunity to influence how research impacts on them, and make it relevant for all of us without medical backgrounds to have a say. We are the voice of those with lived experience, helping to guide researchers and experts to put patients at the centre of all they do.”

New study explores unique approach to treat a rare liver disease

Written by Louise Stanley on . Posted in Clinical trials, Experimental medicine.

A UK research study looking into a new approach to treat primary sclerosing cholangitis (PSC), a rare disease where the body’s immune attacks its own liver, has been given the green light thanks to vital funding from LifeArc and the patient-led organisation PSC Support.

The FARGO trial, led by Dr Palak Trivedi at the University of Birmingham, will find out if a new treatment can slow PSC progression and improve quality of life for patients.

What is PSC?

PSC is a rare liver disease which affects around 3,600 people in the UK. People can develop the condition at any age, but most commonly those under the age of 40.

In PSC, the body’s immune system attacks the liver, causing inflammation and scarring of the bile ducts. This causes bile to stop flowing properly, and patients experience repeated infections, develop liver failure and, in some cases, cancer. In four out of five people, the body’s immune system will also attack the bowel, leading to inflammatory bowel disease (IBD) as well as liver disease. The combination of PSC and IBD can lead to around a third of all patients developing bowel cancer and patients require a colonoscopy every year to screen for it.

Currently, doctors treat PSC by managing symptoms only. We don’t fully understand what causes PSC, and there is no cure. A liver transplant is the only life-saving treatment. Although a very rare disease, PSC accounts for 1 in 10 of all liver transplants in the UK and is now the leading reason for liver transplantation in several European countries.

While it is life saving, liver transplantation is also risky and costly to the NHS. People who have had a transplant must take a cocktail of drugs to prevent their new liver being rejected. PSC can still return in around a third of people who have had a liver transplant.

Imbalance of gut microorganisms – and a new approach

We know that the microbes present in the gut of people with PSC are different to those in people without liver and bowel inflammation. This gut microbe imbalance is linked with many abnormal immune functions, which may drive development of the condition.

In the FARGO study, the research team will find out if taking stools containing natural microbes from the gut of healthy donors, refining it in a lab, and transferring it to the bowel of people with PSC, could reverse the imbalance of gut microorganisms. This treatment is called faecal microbiota transplantation, or FMT. Early research has also shown that it can treat IBD.

Bespoke clinical trial

The Birmingham team, together with teams at the Royal Free London, St Mark’s Hospital, Imperial College London, and Norfolk and Norwich University Hospitals NHS Foundation Trust, will carry out a clinical trial to test this new treatment approach. People with PSC taking part in the study will receive either FMT once a week for eight weeks, or placebo (an inactive FMT equivalent). Each group will continue to receive their usual routine standard of care for their IBD.

The teams will observe both groups for another 40 weeks. The team will then measure how successful the treatment has been in improving liver blood tests, reduce scarring of the liver, lessen the severity of their IBD, and improving symptoms and quality of life.

Dr Palak, who is leading the trial at the NIHR Birmingham Biomedical Research Centre, said: “I am delighted that LifeArc has chosen to support such a novel, bespoke and distinctive clinical trial, and to enable us to the necessary ground work needed to better understand how PSC develops and progresses.

“This study will really help us to understand which gut microbes are most important, and how this potential treatment could be scaled up to treat more people.

“Our study will lay the foundation for future work on a larger scale, with a view to making FMT available across the world.

“Should our trial show that FMT works well, PSC Support will be advocating for patients to access FMT as early as possible. We hope this means it will be making a difference to patients within five years after we’ve completed this work.”

LifeArc’s Dr Catriona Crombie said: “Our approach to funding is to work with others, to uncover the potential of promising research that could solve complex healthcare problems that patients face.”

She continued: “We’re delighted to be jointly funding this project with PSC Support, where Dr Trivedi’s team aim to reveal more information about PSC and help to translate this experimental treatment, from lab idea towards the clinic, where it could offer hope to patients with PSC.”

Martine Walmsley, Chair of Trustees at PSC Support, said: “Although we welcome clinical trials that test brand new drugs for PSC, progress is painfully slow. People with PSC don’t have the luxury of time and we must look at quicker medicine development routes.”

3d rendering of red blood cells in vein

New blood cancer gene defect can be treated with existing drugs

Written by Louise Stanley on . Posted in Cancer outcomes, Experimental medicine.

A defective gene normally found in blood cancers could be treated with drugs already available for cancers with similar gene defects, scientists at BHP founder-member the University of Birmingham and Queen’s University Belfast have revealed.

The research team, funded mainly by Cancer Research UK and the Medical Research Council, found that tumours with mutations in the SF3B1 gene respond to PARP inhibitors – a type of drug used to treat cancers which have similar mutations in the BRCA1 and BRCA2 genes.

The researchers believe that PARP inhibitors could be used to treat patients with tumours carrying the defective SF3B1 gene. This mutation is most often found in blood cancers, including chronic lymphocytic leukaemia, as well as some rare cancers like uveal melanoma.

Co-author Professor Grant Stewart, of the University of Birmingham, said: “Our work demonstrates that a molecular understanding of how a specific gene mutation affects a cancer cell’s ability to repair damaged DNA can be exploited clinically to specifically tailor the anti-cancer therapy used to treat an individual’s tumour. This will increase the effectiveness of the therapy and hopefully, reduce the chances of re-occurrence.”

Dr Kienan Savage, lead author and Reader at Queen’s University Belfast, said: “Our findings have clinical implications for the treatment of many cancers. We specifically focused on this genetic mutation as it is found in several difficult to treat leukaemias and other cancers, and it affects so many cancer patients. By deepening our understanding of this gene mutation, we have identified new ways of treating these cancers that could improve survival rates.”

PARP inhibitors, which include olaparib and rucaparib, are used to treat some patients with ovarian, breast, prostate and pancreatic cancers – usually patients who have inherited a faulty BRCA1 or BRCA2 gene. Around 1 in 400 people have a faulty BRCA1 or BRCA2 gene.

The research – published in Cancer Research, a journal of the American Association for Cancer Research – found that the SF3B1 mutation produces similar effects to the faulty BRCA1 gene by damaging DNA, preventing it from being repaired properly, and stopping it from making normal copies of itself. PARP inhibitors target the cell’s DNA repair tools by locking them in place on the DNA. This stops DNA repair, causing the cancer cells to die.

The scientists found that cancer cells with the SF3B1 mutation were sensitive to olaparib, the most common PARP inhibitor, some specific chemotherapies and to radiotherapy. The scientists believe that the SF3B1 mutation disrupts the cell’s ability to make DNA repair proteins, leaving it vulnerable to drugs which target these proteins.

The SF3B1 mutation occurs in up to 30% of blood cancers called myelodysplastic syndromes, where blood cells don’t form properly. They are difficult to treat as they occur predominantly in older patients who may not be considered fit for treatment. The mutation is also common among uveal melanoma or cancers of the eye, which currently have limited treatment options.

Dr Katrina Lappin, of Queen’s Univesity Belfast and first author of the study, added: “Our research shows that cancers with these specific mutations, may be treated effectively with PARP inhibitor therapy drugs, which are less toxic, better at killing cancer cells with these mutations and can be taken at home in tablet form. This could have huge implications for improving outcomes and quality of life of people with these cancers. This work will pave the way for clinical trials using PARP inhibitors for the treatment of patients with this commonly associated cancer mutation, allowing a more personalised approach to the treatment of these cancers.”

The researchers now want to test PARP inhibitors in clinical trials with patients who have the SF3B1 mutation to see if they can stop their cancer from spreading.

Michelle Mitchell, Chief Executive of Cancer Research UK, said: “Our scientists helped to discover the BRCA gene over 25 years ago and since then we’ve led the way in developing PARP inhibitors to treat cancers with BRCA gene faults. It’s really exciting to hear about a new mutation, which behaves like the BRCA1 mutation and could in the future be treated in the same way. With PARP inhibitors already widely available, there is huge potential to help people with some of the rarest and most difficult-to-treat cancers known to us. Over the past two decades, PARP inhibitors have saved thousands of lives worldwide, and it will be interesting to see if this research in the future could lead to a similar impact for people with rarer cancers.”

The research was funded by the UK Medical Research Council, Cancer Research UK, Blood Cancer UK, Leukaemia and Lymphoma NI and Great Ormond Street Hospital Children’s Charity.

tablets

Triple-drug combo could prove key weapon in fight against cancer

Written by Louise Stanley on . Posted in Cancer outcomes, Clinical trials, Experimental medicine.

Combining three existing drugs – a commonly-used anti-epileptic, a contraceptive steroid and a cholesterol-lowering agent – could form an effective and non-toxic treatment for a range of aggressive blood cancers, a new study reveals.

The discovery by University of Birmingham scientists has led to a £1 million funding award from Blood Cancer UK to run a randomised clinical trial to test the new drug combo against another experimental agent (Danazol) in patients living with Myelodysplastic Syndromes (MDS).

Over 7,000 people in the UK have MDS and many patients die because their disease transforms into acute myeloid leukaemia (AML) – an even more aggressive blood cancer. The general outlook for AML is poor, but when AML arises from MDS it is worse.

Left untreated, AML kills patients quickly by crippling production of normal blood cells. AML is most prevalent in elderly people – many of whom cannot tolerate ‘traditional’ treatment of intensive chemotherapy because of their age and frailty.

Scientists at the University of Birmingham had already discovered that mixing bezafibrate (BEZ – cholesterol-lowering) with medroxyprogesterone acetate (MPA – contraceptive steroid) eased a range of blood cancers including AML, chronic lymphocytic leukaemia (CLL) and non-Hodgkins lymphoma.

Now clinical trials show that adding valproic acid to a low-dose combination of the other two drugs offers enhanced killing of AML cells – giving the low-dose triple-drug combo (VBaP) a cancer-busting impact similar to a high dose of BEZ and MPA (BaP).

Researchers from the University of Birmingham have published their findings in British Journal of Cancer.

Co-author Professor Chris Bunce, commented: Using existing drugs to treat conditions outside of their approved indications is a proven approach to generate effective low-toxicity therapies. We believe that treating patients earlier with low toxicity therapies is the most effective clinical strategy for improving patient outcomes.”

Earlier clinical trials had shown that low-doses of BaP given to patients who could not have chemotherapy produced no toxic side effects and helped patients to boost their production of blood cells.

However high doses of the dual combo were not well tolerated, due to the frail nature of the patients caused by their age, poor kidney function, disease and, in some cases, prior chemotherapy treatments.

Co-author Dr Farhat Khanim commented: “A major challenge in our previous BaP trials has been the focus on elderly patients for whom more intensive therapies were not option.

“For many of these patients there are very few treatment options other than regular transfusions to combat life-threatening deficits in red cells and platelets and antibiotic control of frequent life threatening infections.

“It is therefore an attractive option to consider testing VBaP in MDS patients. As the drug combination may have profound impact on quality of life and survival of these patients.”

Birmingham leads the way in delivery of a new advanced therapy in uveal melanoma

Written by Louise Stanley on . Posted in Cancer outcomes, Experimental medicine.

BHP founder-member University Hospitals Birmingham is the first site in the UK to treat a uveal melanoma patient with the new therapy Tebentafusp outside a clinical trial. Uveal melanoma is a rare cancer situated within the eye. This initiative is being led by Dr Leila Khoja, Immunotherapy lead for the Birmingham Experimental Cancer Medicine Centre (ECMC) and senior clinical lecturer at another of BHP’s founder members, the University of Birmingham.

Developed by Immunocore PLC, Tebentafusp is a bispecific immunotherapy drug, a type of advanced therapy. Immunotherapies harness the body’s immune system to fight cancer, helping it to attack it and to prevent tumours from growing. However, in some tumours the immune response is inadequate to control the tumour and, even in tumours that respond, resistance to treatment can develop. Tebentafusp’s mechanism of action enables it to attach to the tumour and simultaneously to T-cell immune cells. This means that it is able to pull in and activate tumour specific T-cells in hard to treat tumours.

Birmingham participated in the phase II study of Tebentafusp, and the results were published in Clinical Cancer Research. This led to a phase III trial, where it was shown to offer patients better outcomes in terms of survival, when compared with standard drugs offered by their clinical teams.  It is the first drug of this type for a solid tumour that has been proven to offer this benefit to patients. Regulatory approval for Tebentafusp is in process, but the drug is currently available through a compassionate use programme.

Transferring Tebentafusp into standard clinical care for patients with solid tumours is challenging, as specialist pharmacy, nursing and junior doctor skills are required. Hospitals also need to have sufficient capacity to deliver infusions of the drug on an inpatient basis, as the dose is increased over a three week period, before it can be provided on an outpatient basis. The development of this programme will create a model for similar therapies in the future, and Birmingham ECMC is currently facilitating the setup of clinical trials in this field.

These initiatives underline the importance of the Birmingham ECMC and Midlands Wales Advanced Therapy Treatment Centre (MW-ATTC) networks in supporting the delivery of the innovative therapies of the future, training staff and providing the infrastructure required.