Date: 2017-10-30
Type of information: Licensing agreement
Compound: AZD9668
Company: AstraZeneca (UK) Mereo Biopharma (UK)
Therapeutic area: Rare diseases - Genetic diseases - Respiratory diseases
Type agreement: licensing
Action mechanism:
- neutrophil elastase inhibitor. AZD9668 (alvelestat) is an orally available, potent and selective inhibitor of human neutrophil elastase that has potential utility as a therapeutic agent for inflammatory lung diseases, including COPD.
- AstraZeneca has conducted a number of Phase I and Phase II clinical studies with AZD9668 in respiratory conditions that share some common pathology with alpha-1 antitrypsin deficiency (AATD), specifically chronic obstructive pulmonary disease, cystic fibrosis and bronchiectasis. Approximately 1,000 patients have been treated with the drug in clinical studies to date. These studies have shown AZD9668 to be safe and well-tolerated. They have also generated signals of efficacy in lung function and biomarker data that are consistent with an elastase-mediated mechanism of action.
- AATD is a genetic disorder that affects approximately 100,000 patients in the United States and 120,000 patients in Europe. It can cause severe debilitating conditions such as chronic liver disease but, most notably, pulmonary emphysema, which is a life-threatening disease. Pulmonary emphysema results in irreversible destruction of the tissues supporting the function of the lungs and causing severe shortness of breath and wheeze. Patients typically present between the ages of 20 and 50 and have both a significantly reduced quality of life and a reduced life expectancy.
- The lung damage in AATD results from loss of the normal protective effect of alpha-1 antitrypsin against the damaging enzymes released during inflammation, specifically neutrophil elastase.
- Current standard of care for AATD varies from country to country. Protein replacement therapy, involving weekly infusions of plasma-derived alpha 1 antitrypsin is approved but is only reimbursed in the United States and some European countries. By suppressing neutrophil elastase through a more easily administered oral treatment, Mereo believes AZD9668 has significant differentiation from the current protein replacement therapy.
Disease: alpha-1 antitrypsin deficiency (AATD)
Details:
- • On October 30, 2017, Mereo BioPharma has reached an agreement with AstraZeneca for an exclusive license, including an option to acquire, AZD9668, an oral inhibitor of neutrophil elastase. Under the exclusive license Mereo plans to conduct a Phase II study for the treatment of alpha-1 antitrypsin deficiency (AATD), a congenital orphan condition. The company has the right to exercise its option to acquire AZD9668 after the initiation of pivotal studies. AstraZeneca has already generated a clinical data package on AZD9668 which includes extensive Phase II studies in several respiratory conditions that will inform the initial Phase II clinical study Mereo is planning for AATD.
- Mereo intends to initiate a Phase II study in AATD in 2018. This Phase II study is expected to be a 12-week randomized, placebo controlled, study that will evaluate two doses of AZD9668 in approximately 150 patients with the PiZZ and NULL genetic mutations. These mutations are seen in the more severely affected patients who have very low (PiZZ) or zero (NULL) alpha-1 antitrypsin levels. Mereo expects to leverage the internal expertise and respiratory disease key opinion leader network that it has assembled for the development of acumapimod to develop AZD9668.
Financial terms:
- Mereo has acquired the license and option to acquire AZD9668 for an initial upfront payment totalling $5 million, in a combination of $3 million in cash and the issue of 490,798 new ordinary shares in the capital of the company (“New Ordinary Shares”) to satisfy the balance of the upfront payment.
- Additional deferred payments in cash and in new ordinary shares would be payable on certain milestones based on completion and success of the proof of concept study in AATD and upon the initiation of a potentially pivotal study in this indication.
- Additional global filing and approval milestones are payable following successful pivotal data. Under the agreement, following product launch, if approved, Mereo will pay AstraZeneca commercial milestones, sales-related payments and royalties, each in line with rates for analogous licensing deals for drugs at this stage of development.
- The cash element of the upfront payment for the option purchase and the initial Phase II study will be funded from Mereo’s existing financial resources.
- Application will be made for the New Ordinary Shares to be admitted to trading on the AIM market operated by the London Stock Exchange and admission is expected to become effective and dealings in the New Ordinary Shares on the London Stock Exchange are expected to commence on or around 3 November 2017. The New Ordinary Shares, when issued, will rank pari passu with the existing ordinary shares in the capital of the Company.
- Following the issue of the New Ordinary Shares, the total number of shares in issue will be 71,094,974 ordinary shares, each with voting rights. Therefore, the total number of voting rights in the Company with effect from such date will be 71,094,974.
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