POLB 001 : Tackling Cancer Therapy’s Elephant in the Room – CRS
“…This means we could potentially prevent CRS before it starts. Patients could take POLB 001, then receive their cancer immunotherapy, then go home, without the hospital stay…”
Cancer treatment is entering its next phase of transformative change. That was the message of keynote speakers at a recent Investor Summit, who shed light from the perspectives of finance, science and business on the breakthroughs making possible the next generation of cancer immunotherapies, and the barriers that remain.
Oncology is making increasing use of immunotherapies that harness the body’s own immune system to target and destroy cancer cells, moving beyond non-selective therapies such as chemotherapy and radiotherapy.
Summit participant Dr Jeremy Skillington, CEO of Poolbeg Pharma (AIM:POLB), highlighted the company’s POLB 001, a p38 MAP Kinase inhibitor that has the potential to take cancer immunotherapies to the next level, promising to preserve the power of current treatments while radically reducing the threat of life-threatening side effects. Safer administration would allow treatment at community hospitals, reducing dependence on a handful of specialist cancer centres, ultimately opening access for many more patients.
Dr Skillington was speaking at last month’s Immunotherapy and the Future of Oncology Investor Summit alongside Dr Brian White, Healthcare Analyst at Shore Capital, and Professor Martin Kaiser, Consultant Haemato-Oncologist at The Institute of Cancer Research and The Royal Marsden Hospital.
Building on today’s immunotherapies
The panel emphasised the extraordinary advances in cancer care made possible by the rapid adoption of cancer immunotherapies, which have moved from experimental concepts to mainstream treatments in the space of a decade.
The panel discussed a major concern with the current generation of cancer immunotherapies: their significant side effects. The powerful stimulation of the immune system that makes them such efficient therapies can unleash inflammatory storms inside the body, a phenomenon known as Cytokine Release Syndrome (CRS).
Symptoms range from fever and fatigue to life-threatening complications like organ failure. Around 70pc of patients treated with certain cancer immunotherapies develop CRS, which requires extended hospitalisation in specialist cancer centres. Doctors can intervene with steroids or cytokine inhibitors, but these treatments tend to dampen the immune system and risk undermining the cancer therapy itself as well as increasing the risk of developing infections.
The risk of CRS
The risk of CRS confines the administration of cancer immunotherapies to a handful of specialist centres, limiting their potential reach to patients. As Dr Skillington put it: ‘CRS is the elephant in the room. Unless we address it effectively, the broader rollout of cancer immunotherapies will be restricted.’ Poolbeg is presenting POLB 001 as an elegant solution: a treatment that could reduce or even prevent CRS while ensuring current cancer immunotherapies retain their effectiveness, and that can be administered easily, at home and in the form of a simple pill.
POLB 001: a preventative therapy targeting cancer immunotherapy-induced CRS
POLB 001’s technology has the potential to act as a preventative therapy to target cancer immunotherapy-induced CRS. The company has achieved positive data from a human LPS challenge trial and will be entering a Phase 2a in-patient trial to clinically assess its potential. ‘In healthy volunteer studies, when we gave our drug and then triggered the immune system with LPS, their inflammatory response was significantly dampened,’ said Dr Skillington. ‘This means we could potentially prevent CRS before it starts. Patients could take POLB 001, then receive their cancer immunotherapy, then go home, without the hospital stay.’
And unlike current CRS management it is proactive rather than reactive. Today’s treatments oblige doctors to monitor patients in hospital for CRS symptoms. But by administering POLB 001 they would be able to allow patients to go home, safe in the knowledge that the risk of CRS had been adequately addressed. Hospitals would no longer need to dedicate scarce beds in specialist cancer centres for round-the-clock monitoring, allowing clinicians to oversee cancer immunotherapy programmes in community hospitals. That means much greater convenience for patients and lower costs for healthcare centres. Dr Skillington said: ‘Preventing CRS doesn’t just benefit patients – it removes a bottleneck in the entire system. That’s why big pharma has been so interested in our work.’ Poolbeg has already secured an approved bispecific antibody from a pharma partner for the forthcoming Phase 2a trial.
Professor Kaiser agreed: ‘If development continues as it is, specialists may be able to manage many more patients with fewer resources. It won’t put doctors out of work, but it will change the model of care – similar to rheumatology, which moved from inpatient chemotherapy to outpatient injections that patients can even self-administer at home.’ POLB 001 would make it safer to combine cancer immunotherapies with chemo, radiation, or targeted drugs. By reducing the risk of side-effects like CRS, powerful therapies could be given sooner in treatment, not just as a last resort. ‘In five years,’ said Professor Kaiser, ‘almost no patient will receive a single-modality immunotherapy. Combination regimens will be the rule, not the exception.’
Market potential
Discussing the market opportunity, the panel noted that immunotherapies already generate more than US$60bn annually. The current wave of drugs such as Merck’s Keytruda and Bristol Myers Squibb’s Opdivo have generated billions of dollars in sales. Analysts estimate that POLB 001’s potential for pairing with multiple immunotherapies across different cancers suggests the potential for peak annual sales of around $10bn, Poolbeg taking its share through strategic partnerships.
Poolbeg has also secured an Orphan Drug Designation for POLB 001 from the US Food and Drug Administration, which on approval would open seven years of US market exclusivity, as well as regulatory and tax advantages.
‘Our strategy is to generate proof-of-concept human data in multiple myeloma,’ said Dr Skillington. ‘If successful, we’ll seek a pharma partner to take it forward. That’s when pharma really engages – once there’s human patient data’ and discussions have already taken place to lay the groundwork. He believes Poolbeg has ‘first-mover advantage and strong Intellectual Property protection if others try to move into this space.’ The company is confident its short treatment window will reduce safety risks, and its broad anti-cytokine action may prove more effective than the single-target approaches currently used.
Summing up the POLB 001’s potential, Dr Skillington said: ‘We know cancer immunotherapy works. The question is how to make it work better, safer, and available for everyone who needs it.’ POLB 001 has the potential to make powerful cancer immunotherapy treatments safer and more widely available, reduce strain on hospitals and healthcare budgets, and unlock the next wave of innovation in oncology: the missing piece that will allow today’s cancer immunotherapies to fulfil their promise.
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