PhaseBio Inks European Licensing Agreement with Alfasigma S.p.A for Commercialization of Bentracimab
17 June 2021 - - US-based biopharmaceutical company PhaseBio Pharmaceuticals, Inc. (NASDAQ: PHAS) has entered into an exclusive licensing agreement with Italian specialty pharmaceutical company Alfasigma S.p.A. for the commercialization of bentracimab, the company said.

The agreement covers countries in the European Union and European Economic Area, as well as the United Kingdom, Russia, Ukraine and other countries within the Commonwealth of Independent States.

Bentracimab is a novel, human monoclonal antibody fragment that in earlier clinical trials has shown immediate and sustained reversal of the antiplatelet effects of Brilinta/Brilique (ticagrelor).

Under the terms of the license agreement, PhaseBio will receive a USD 20m upfront payment and will be eligible to receive up to USD 35m in pre-revenue regulatory milestones and up to USD 190m in payments contingent upon the achievement of certain sales milestones.

PhaseBio will also receive tiered royalties on net sales, with %ages starting in the low double digits and escalating up to the mid-twenties.

PhaseBio will be responsible for developing bentracimab and securing approval with the European Medicines Agency and the Medicines and Healthcare Products Regulatory Agency, after which marketing authorization will be assigned to Alfasigma.

Alfasigma will be responsible for securing regulatory approval in other territories not covered by EMA or MHRA approvals, and for obtaining and maintaining regulatory approvals necessary to market and sell the product, including pricing approvals and post-marketing commitments.

Bentracimab is currently in late-stage clinical development in the REVERSE-IT (Rapid and SustainEd ReVERSal of TicagrElor Intervention Trial) trial.

REVERSE-IT is a Phase 3, multi-center, open-label, prospective single-arm trial designed to study reversal of the antiplatelet effects of ticagrelor with bentracimab in patients who present with uncontrolled major or life-threatening bleeding or who require urgent surgery or an invasive procedure.

The company expects to complete enrollment of the first 100 patients in the REVERSE-IT trial in mid-2021 and is targeting to submit its Biologics License Application for bentracimab in mid-2022, although those timelines could be impacted by the continued scope and duration of the COVID-19 pandemic.

To date, nearly all of the patients enrolled have required urgent surgery or an invasive procedure.

Previously, bentracimab has been studied in Phase 1 and Phase 2 clinical trials and has demonstrated the potential to bring life-saving therapeutic benefit through immediate and sustained reversal of the antiplatelet activity of ticagrelor, potentially mitigating concerns regarding bleeding risks associated with the use of this antiplatelet drug.

Additionally, in a translational study, bentracimab achieved equivalent reversal of branded ticagrelor and multiple ticagrelor generics.

Bentracimab is a novel, recombinant, human monoclonal antibody antigen-binding fragment designed to reverse the antiplatelet activity of ticagrelor in major bleeding and urgent surgery situations.

In a Phase 1 clinical trial, bentracimab demonstrated the potential to bring life-saving therapeutic benefit through immediate and sustained reversal of ticagrelor's antiplatelet activity, mitigating concerns regarding bleeding risks associated with the use of this antiplatelet drug.

The Phase 1 clinical trial of bentracimab in healthy volunteers was published in the New England Journal of Medicine in March 2019.

In April 2019, bentracimab received Breakthrough Therapy Designation from the Food and Drug Administration.

Breakthrough Therapy Designation may be granted by the FDA when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapy.

In September 2019, PhaseBio completed a Phase 2a trial in which bentracimab was investigated in older and elderly subjects on dual antiplatelet therapy of ticagrelor and low-dose aspirin.

Additionally, the Phase 2a trial investigated a bentracimab regimen for the reversal of supratherapeutic doses of ticagrelor in healthy younger subjects.

In both arms of the trial, bentracimab achieved immediate and sustained reversal of the antiplatelet effects of ticagrelor and was generally well-tolerated, with only minor adverse events reported.

These results are consistent with the results observed in healthy younger subjects treated with ticagrelor in the previously published Phase 1 trial.

PhaseBio initiated the REVERSE-IT trial, a pivotal Phase 3 clinical trial of bentracimab, in March 2020 to support a Biologics License Application for bentracimab in both major bleeding and urgent surgery indications. There are currently no approved reversal agents for ticagrelor or any other antiplatelet drugs.

PhaseBio Pharmaceuticals is a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies for cardiovascular and cardiopulmonary diseases.

The company's pipeline includes: bentracimab (PB2452), a novel reversal agent for the antiplatelet therapy ticagrelor; pemziviptadil (PB1046), a once-weekly VIP receptor agonist for the treatment of pulmonary arterial hypertension; and PB6440, an oral agent for the treatment of resistant hypertension.

PhaseBio's proprietary elastin-like polypeptide technology platform enables the development of therapies with potential for less-frequent dosing and improved pharmacokinetics, including pemziviptadil, and drives both internal and partnership drug-development opportunities.

PhaseBio is located in Malvern, PA, and San Diego, CA.

Privately owned, Alfasigma is an Italy based multinational pharmaceutical company, present in over 90 countries, through distributors and subsidiaries.

The company employs a workforce of around 3,000 people, has in-house R and D capabilities, and several production plants. Alfasigma is known for its strong focus on Gastroenterology and Vascular.