POLB 001 / Poolbeg Pharma - LARVOL DELTA

POLB 001, an Oral p38 MAPK Inhibitor for the Prevention of Cytokine Release Syndrome (IMS 2026) - "POLB 001 reduced key CRS-associated cytokines and clinical CRS scores in humanised mouse models without impairing BsAb anti-tumour efficacy in in vitro models and had no meaningful impact on T cell phenotype. A Phase I/II trial of POLB 001 in teclistamab-treated patients with multiple myeloma is now commencing."

Cytokine release syndrome • First-in-human • IO biomarker • Hematological Malignancies • Inflammation • Multiple Myeloma • CCL3 • CCR7 • CXCL8 • GZMB • IFNG • IL10 • IL2 • IL2RA • IL4 • IL6 • POLG2

POLB 001, an Oral p38 MAPK Inhibitor for the Prevention of Cytokine Release Syndrome (IMS 2026) - "POLB 001 reduced key CRS-associated cytokines and clinical CRS scores in humanised mouse models without impairing BsAb anti-tumour efficacy in in vitro models and had no meaningful impact on T cell phenotype. A Phase I/II trial of POLB 001 in teclistamab-treated patients with multiple myeloma is now commencing."

Cytokine release syndrome • First-in-human • IO biomarker • Hematological Malignancies • Inflammation • Multiple Myeloma • CCL3 • CCR7 • CXCL8 • GZMB • IFNG • IL10 • IL2 • IL2RA • IL4 • IL6 • POLG2

Poolbeg Pharma doses first patient in TOPICAL clinical trial (Proactiveinvestors) - "Poolbeg expects to enrol up to 30 patients and remains on track to deliver interim clinical data by the end of summer 2026. Skillington highlighted growing interest from additional UK investigators, which could accelerate enrolment as more sites come online."

P2a data • Trial status • Multiple Myeloma

TARGETING INFLAMMATION VIA P38MAPK INHIBITION TO IMPROVE AZACITIDINE EFFICACY IN AGED AML (EHA 2026) - "Background Acute myeloid leukaemia (AML) is a disease of elderly, with a median age at diagnosis > 65 years. Summary/Conclusion This non-conditioned aged AML model recapitulates key age-associated alterations in the BMM and immune landscape, providing a clinically relevant platform for therapeutic testing. Addition of the p38MAPK inhibitor POLB 001 to AZA enhances immunomodulatory effects and reduces leukaemic burden in aged AML, supporting its potential as a combinatorial strategy to improve outcomes in elderly patients."

Clinical • Acute Myelogenous Leukemia • Geriatric Disorders • Hematological Malignancies • Inflammation • Leukemia • CD8 • IFNG • POLG2

POLB 001, AN ORAL P38 MAPK INHIBITOR FOR THE PREVENTION OF CYTOKINE RELEASE SYNDROME (EHA 2026) - "POLB 001 is being investigated in a non-randomised, single-arm, multi-centre, open label Phase I/II trial in patients with multiple myeloma eligible to receive the bispecific t-cell engager antibody, teclistamab, within its licensed indication (Figure 1). Figure 1. Dosing schedule in single arm, multi-centre, open label Phase I/II trial in patients with multiple myeloma"

Cytokine release syndrome • First-in-human • IO biomarker • Hematological Malignancies • Inflammation • Multiple Myeloma • CCL3 • CCR7 • CXCL8 • GZMB • IFNG • IL10 • IL2 • IL2RA • IL4 • IL6 • POLG2

Poolbeg Pharma launches POLB 001 TOPICAL trial to tackle CAR-T side effects (Proactiveinvestors) - "Poolbeg Pharma PLC...to discuss the first site activation for Poolbeg's POLB 001 TOPICAL clinical trial, evaluating the drug as a preventative treatment for cytokine release syndrome (CRS), a serious side effect linked to CAR-T and bispecific antibody therapies. The UK study will enrol 30 multiple myeloma patients receiving teclistamab, with early readouts expected due to CRS typically occurring within the first two weeks of treatment...Tremble also highlighted new data presented at the EHA Congress showing POLB 001 reduced inflammatory cytokines without compromising tumour-killing activity, alongside early research suggesting potential applications in acute myeloid leukaemia (AMS)."

New trial • Preclinical • Acute Myelogenous Leukemia • Multiple Myeloma

Poolbeg Pharma reports positive FDA feedback for POLB 001 development pathway (Vox) - "The US Food and Drug Administration (FDA) has provided supportive feedback following a pre-Investigational New Drug (IND) meeting for POLB 001...The FDA feedback broadly aligned with its proposed development strategy for POLB 001, including agreement on the proposed primary endpoint for a future Phase 3 trial."

Cytokine release syndrome • FDA event • Immunology • Oncology

Poolbeg secures Canadian patent for POLB 001 in cancer immunotherapy‑induced CRS (PharmaTimes)

Patent • Oncology

Poolbeg Pharma PLC…has received clinical trial authorisation from the UK Medicines and Healthcare products Regulatory Agency for its TOPICAL trial, with interim data expected this summer. (Proactiveinvestors) - "The trial is investigating POLB 001, which is being developed as a potential first-approved preventative therapy for cytokine release syndrome (CRS), a serious immune reaction triggered by cancer immunotherapies, including CAR T-cell therapies and bispecific antibodies. The TOPICAL study will enrol around 30 patients with relapsed or refractory multiple myeloma receiving teclistamab, a bispecific antibody supplied by Johnson & Johnson at no cost to Poolbeg."

New trial • Multiple Myeloma

POLB 001, a p38 MAPK inhibitor, decreases local and systemic inflammatory responses following in vivo LPS administration in healthy volunteers: a randomised, double-blind, placebo-controlled study. (PubMed, Front Immunol) - "Pharmacodynamic findings confirm that POLB 001 inhibits LPS-induced local and systemic inflammation in vivo through inhibition of p38 MAPK. https://onderzoekmetmensen.nl/en/trial/51741, identifier NL81214.056.22."

Clinical • First-in-human • Journal • Preclinical • Dermatology • Immunology • Inflammation • Oncology • Systemic Inflammatory Response Syndrome • CXCL8 • IL6 • POLG2

Polb 001, an Oral Broad-Spectrum Anti-Inflammatory with the Potential to Prevent Cytokine Release Syndrome (CRS) (ASH 2023) - P1 | "Current treatments are dominated by reactive administration of tocilizumab, steroids or anakinra. POLB 001 is undergoing preclinical evaluation in humanized mouse models (NSG-(KbDb)null (IA)null) of T-cell engaging bispecific antibodies, CD19 CAR-T cell therapy for hematological malignancies and for CD28 induced cytokine storm. A Phase 2 trial of POLB 001 in Multiple Myeloma patients receiving T-cell engaging antibodies is planned."

Cytokine release syndrome • IO biomarker • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Influenza • Multiple Myeloma • Oncology • Respiratory Diseases • Systemic Inflammatory Response Syndrome • CRP • CXCL8 • IL10 • IL1B • IL6 • POLG2 • TNFA

Polb 001, an Oral p38 MAPK Inhibitor, Reduces Cytokine Release Syndrome (CRS) in a Mouse Model of Immunotherapy-Induced CRS (ASH 2024) - "Treatment of CRS includes anti-pyretic or anti-cytokine therapies such as tocilizumab (anti-IL-6R), anakinra (anti-IL-1RA), and corticosteroids...The positive control group was immediately dosed intraperitoneally with adalimumab (5 mg/kg)...POLB 001 significantly reduced peak serum levels of IL-4, IL-6, IL-8 and MIP1-α; all other cytokines tested, including IFN-γ, TNF, IL-10 and IL-2, showed trends of reduced peak serum levels. In combination with a previous successful trial in healthy human volunteers, the results of this animal study further support development of POLB 001 in a Phase 2 clinical study as a prophylactic for the prevention of immunotherapy-induced CRS."

Cytokine release syndrome • Preclinical • Hematological Malignancies • Inflammation • Oncology • CXCL8 • IFNG • IL10 • IL1R1 • IL2 • IL4 • POLG2

Poolbeg wins US backing for treatment aimed at serious cancer therapy side effects (Proactiveinvestors) - "Poolbeg Pharma PLC...has secured a key regulatory boost from the US authorities for a drug it is developing to prevent a dangerous complication linked to advanced cancer treatments. The London-listed biotech group said on Tuesday that the Food and Drug Administration had granted Orphan Drug Designation to POLB 001, an experimental treatment designed to protect patients from a condition known as cytokine release syndrome (CRS)....POLB 001 is a tablet designed to block a protein called p38 MAP kinase, which plays a key role in triggering the inflammatory response linked to CRS. The company is preparing to start a mid-stage clinical trial in the second half of this year, with early results expected in the first half of 2026 and headline data by the end of that year."

New trial • Orphan drug • Oncology

Effects of p38 MAPK Inhibitor POLB 001 on in Vivo LPS Challenge Responses (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Poolbeg Pharma plc | Recruiting ➔ Completed | Trial completion date: Apr 2023 ➔ Dec 2022

Trial completion • Trial completion date • Infectious Disease • Influenza • Respiratory Diseases • CXCL8 • IL10 • IL6 • POLG2