CUE-221 / United BioPharma, Cue Biopharma, Ascendant Health Sciences - LARVOL DELTA

Cue Biopharma Announces Positive Topline Results from CUE-221 Phase 2 Study in Chronic Spontaneous Urticaria (GlobeNewswire) - "The trial enrolled 145 participants with moderate to severe chronic spontaneous urticaria (CSU), a disease resulting in chronic hives, that remained inadequately controlled despite treatment with H1 antihistamines...The primary endpoint of percentage of patients with HSS7=0 at week 12 was dose-responsive and met at all dose levels. The key secondary endpoint of percentage of patients with UAS7=0 at week 12 was dose responsive and met statistical significance at the 4 mg/kg highest dose level...The percentage of participants who achieved HSS7=0 further increased beyond the Week 12 primary endpoint, peaking at Week 22 across all CUE-221 dose groups. After a last dose was administered for all groups at Week 16, clinically meaningful benefit was maintained for up to 12 weeks off treatment (through week 28) at the 4 mg/kg dose level."

P2 data • Chronic Spontaneous Urticaria

Business, Financial and Leadership Highlights (The Manila Times) - "CUE-221...Phase 2 data readout in Chronic Spontaneous Urticaria anticipated by the end of the third quarter of 2026...CUE-401: Company anticipates submitting an IND to the FDA and initiating a Phase 1 clinical study by year-end 2026."

IND • New P1 trial • P2 data • Chronic Spontaneous Urticaria • Food Hypersensitivity • Immunology

Veteran biotech finance executive joins Cue to support the Company’s next phase of clinical and corporate growth as the company advances regulatory filing for food allergy (GlobeNewswire) - "Mr. Ahlers joins Cue at a pivotal point in the Company's evolution with a recent Investigational New Drug (IND) submission to the FDA for CUE-221 in food allergy and anticipated Phase 2 CSU data readout for the program by the end of the quarter."

IND • P2 data • Chronic Spontaneous Urticaria • Food Hypersensitivity

Biologics in IgE-mediated food allergy: where are we know? (PubMed, Curr Opin Allergy Clin Immunol) - "Biologics offer a meaningful advance in food allergy treatment by targeting key immune pathways with an agnostic approach, therefore, independent on the specific antigen-specificity. This may offer the benefit of targeting multiple food allergies and also, eventually, further co-morbidities. There is broad evidence for an excellent safety profile for omalizumab. Studies are ongoing on other biologicals to explore the efficacy alongside the safety. A new era is also opened by the introduction of biosimilar on the market, by dramatically amortizing the economic burden. With the availability of multiple therapeutic options, the challenge for clinicians is to provide a personalized approach, shaped on the specific patient's need."

Journal • Allergy • Food Hypersensitivity • Immunology • IL33 • IL4

UB-221, an antibody that neutralizes IgE and downregulates the CD23 receptor: a potential treatment for the alpha-gal syndrome. (PubMed, Ticks Tick Borne Dis) - No abstract available

Journal • FCER2

Therapies for Chronic Spontaneous Urticaria: Present and Future Developments. (PubMed, Pharmaceuticals (Basel)) - "If symptoms persist despite this adjustment, the next step involves the use of omalizumab, a monoclonal anti-IgE antibody, which has shown efficacy in the majority of cases. However, a subset of patients remains refractory, necessitating alternative treatments such as immunosuppressive agents like cyclosporine or azathioprine...Among them, significant attention is being given to drugs that block Bruton's tyrosine kinase (BTK), such as remibrutinib, which reduces mast cell activation. Therapies like dupilumab, which target the interleukin-4 (IL-4) and IL-13 pathways, are also under investigation. Additionally, molecules targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2), and those inhibiting the tyrosine kinase receptor Kit, such as barzolvolimab, show promise in clinical studies...Further research is essential to better elucidate the pathophysiology of CSU and optimize treatment protocols to achieve long-term benefits in managing this condition...."

Journal • Review • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • BTK • IL13 • IL4

New biologics for food allergy. (PubMed, Curr Opin Allergy Clin Immunol) - "Biologics hold promising potential for food allergy treatment. Tailoring therapeutic approaches based on shared decision-making becomes pivotal. While omalizumab remains a significant option, next-generation anti-IgE antibodies and agents targeting alarmins exhibit unique strengths. Dupilumab, despite limited success as monotherapy, shows promise as an adjunct for OIT. Careful consideration of treatment goals, patient preferences, and the evolving landscape of biologics will shape future clinical practice, offering allergists an expanded toolbox for personalized food allergy management."

Journal • Allergy • Food Hypersensitivity • Immunology • IL33 • IL4 • IL4R

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases. (PubMed, Allergy) - "In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID."

Journal • Review • Immunology

A Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety, and Efficacy of UB-221 IV Infusion as an add-on Therapy in Patients With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: United BioPharma | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety, and Efficacy of UB-221 IV Infusion as an add-on Therapy in Patients With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: United BioPharma | Trial completion date: Mar 2023 ➔ Dec 2023 | Initiation date: Jun 2022 ➔ Oct 2022 | Trial primary completion date: Mar 2023 ➔ Dec 2023

Trial completion date • Trial initiation date • Trial primary completion date • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Evaluating the Safety and Tolerability and Determining the PK and PD of Single Dose UB-221 in Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: United BioPharma | Trial completion date: Jan 2024 ➔ Jan 2026 | Trial primary completion date: Nov 2022 ➔ Nov 2024

Trial completion date • Trial primary completion date • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms. (PubMed, J Clin Invest) - "A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level."

Journal • Allergy • Asthma • Atopic Dermatitis • Chronic Spontaneous Urticaria • Dermatitis • Dermatology • Immunology • Pulmonary Disease • Respiratory Diseases • Urticaria • FCER2

Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of UB-221 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: UBP Greater China (Shanghai) Co., Ltd | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2022 ➔ Jun 2024

Trial completion date • Trial primary completion date • Chronic Spontaneous Urticaria • Dermatology • Urticaria

Emerging treatments for chronic urticaria. (PubMed, Expert Opin Investig Drugs) - "While three omalizumab biosimilars are investigated, the assumed early approval of ligelizumab will expand the effective and safe anti-IgE approach observed with omalizumab. For other anti-IgEs like UB-221, the development is behind. Data are too limited so far to clearly define the role of anti-cytokine and anti-cytokine receptor biologics such as dupilumab, tezepelumab, mepolizumab, benralizumab, and CDX-0159, of which only dupilumab is actually investigated in phase 3. Among three selective oral BTK inhibitors, remibrutinib, rilzabrutinib, and fenebrutinib, the development of remibrutinib is most advanced (phase 3). As the pipeline addresses different targets, study results will give deeper insights into the pathomechanisms of CU. Hopefully, in the next future additional approved and also more targeted approaches will be available."

Clinical • Journal • Review • Chronic Spontaneous Urticaria • Dermatology • Urticaria

A Phase II, Double-blind, Randomized, Parallel Group, Placebo-controlled Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety, and Efficacy of UB-221 IV Infusion as an add-on Therapy in Patients With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: United BioPharma

New P2 trial • Chronic Spontaneous Urticaria • Dermatology • Urticaria

Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of UB-221 in Healthy Volunteers (clinicaltrials.gov) - P1; N=15; Not yet recruiting; Sponsor: UBP Greater China (Shanghai) Co., Ltd; Initiation date: Jun 2020 ➔ Dec 2021

Clinical • Trial initiation date • Chronic Spontaneous Urticaria • Dermatology • Urticaria

Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of UB-221 as an Add-on Therapy in CSU Patients (clinicaltrials.gov) - P1; N=15; Completed; Sponsor: United BioPharma; Recruiting ➔ Completed

Trial completion • Chronic Spontaneous Urticaria • Dermatology • Urticaria

Anti-IgE for the Treatment of Chronic Urticaria. (PubMed, Immunotargets Ther) - "Phase 2 b results of ligelizumab have not only demonstrated efficacy and safety but also superiority to omalizumab. Whereas further development of quilizumab was discontinued, other approaches, eg UB-221 or DARPins are under investigation. Anti-IgE treatment with omalizumab represents a landmark in the treatment of chronic urticaria, with and without angioedema, and there is light on the horizon suggesting success may come with various next-generation anti-IgE approaches."

Clinical • Journal • Review • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Urticaria

Evaluating the Safety and Tolerability and Determining the PK and PD of Single Dose UB-221 in Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1; N=32; Not yet recruiting; Sponsor: United BioPharma; Trial completion date: Jan 2023 ➔ Jan 2024; Trial primary completion date: Nov 2020 ➔ Nov 2022

Clinical • Trial completion date • Trial primary completion date • Dermatology • Urticaria

New treatments for chronic urticaria. (PubMed, Ann Allergy Asthma Immunol) - "Novel and better treatments for CU are very much needed. Some are in clinical trials already, and additional ones should be developed, making use of the many promising targets recently identified and characterized."

Journal • Review • Dermatology • Dermatopathology • Immunology • Urticaria

Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of UB-221 in Healthy Volunteers (clinicaltrials.gov) - P1; N=15; Not yet recruiting; Sponsor: UBP Greater China (Shanghai) Co., Ltd

Clinical • New P1 trial • Dermatology • Dermatopathology • Immunology • Urticaria

Evaluating the Safety and Tolerability and Determining the PK and PD of Single Dose UB-221 in Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1; N=32; Not yet recruiting; Sponsor: United BioPharma; Initiation date: Jan 2020 ➔ May 2020; Trial primary completion date: Jun 2020 ➔ Nov 2020

Clinical • Trial initiation date • Trial primary completion date

Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of UB-221 as an Add-on Therapy in CSU Patients (clinicaltrials.gov) - P1; N=15; Recruiting; Sponsor: United BioPharma; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Dec 2019 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date

Evaluating the Safety and Tolerability and Determining the PK and PD of Single Dose UB-221 in Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1; N=32; Not yet recruiting; Sponsor: United BioPharma; N=48 ➔ 32

Clinical • Enrollment change

Evaluating the Safety and Tolerability and Determining the PK and PD of Single Dose UB-221 in Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1; N=48; Not yet recruiting; Sponsor: United BioPharma

Clinical • New P1 trial