Agreements

Date: 2017-03-22

Type of information: Milestone

Compound: novel potentiator and combination therapies in cystic fibrosis

Company: Galapagos (Belgium) AbbVie (USA - IL)

Therapeutic area: Rare diseases - Genetic diseases

Type agreement: R&D development commercialisation

Action mechanism:

Disease: cystic fibrosis

Details:

• • On September 24, 2013,  Galapagos and AbbVie have announced that they have entered into a global alliance to discover, develop and commercialize novel potentiator and combination therapies in cystic fibrosis. AbbVie and Galapagos will work collaboratively to contribute technologies and resources in order to develop and commercialize oral drugs that address the main mutations in CF patients, including F508del and G551D.  The goal of the collaboration is to identify compounds that correct defects in expression of (corrector) and/or increase the activity (potentiator) of the main mutations in the cystic fibrosis transmembrane regulator (CFTR) protein, including the F508del mutation, which is the most common with 90 percent prevalence among patients with CF.
• In the alliance, AbbVie and Galapagos will develop potentiators and correctors discovered by Galapagos and expand the range of molecules, with the aim to initiate Phase 1 clinical studies at the end of 2014.  Following successful clinical development and regulatory approval, AbbVie will be responsible for commercial activities, with Galapagos retaining exclusive rights in China and South Korea and co-promotion rights in Belgium, the Netherlands, and Luxembourg.
• Galapagos initiated its research in CF in 2005 as part of a collaboration with the Cystic Fibrosis Foundation.  In 2010, Galapagos decided to pursue CF as the first orphan disease in which the company is attempting to discover, develop and launch its own medicines.  Galapagos has developed small molecule therapies that can restore the function of the defective CF protein (CFTR).  The first pre-clinical candidate is expected to be nominated this year, with the first clinical trials starting at the end of 2014.

Financial terms: Under the terms of the agreement, AbbVie will make an initial upfront payment of $45 million to Galapagos for rights related to the global alliance.  Upon successful completion of pre-determined success milestones, AbbVie and Galapagos will share responsibility and funding for Phase III clinical development. Galapagos is eligible to receive up to $360 million in total additional payments for developmental and regulatory milestones, sales milestones upon the achievement of minimum annual net sales thresholds and additional double-digit royalty payments on net sales.

Latest news:

• • On March 22, 2017, Galapagos announced initiation of a Phase 1 study with novel potentiator GLPG3067 for cystic fibrosis  in a Phase 1 study. Galapagos is to receive a $7.5 million milestone payment from its collaboration partner AbbVie for this achievement.
• • On February 1, 2017, Galapagos announced dosing of the first patient with cystic fibrosis Class III (F508del and a gating mutation like G551D) with novel CF corrector GLPG2222 as an add-on to Kalydeco® in a Phase 2a study. Galapagos further announced the opening of an Investigational New Drug (IND) file with the FDA for GLPG2222, triggering a $10 million milestone payment. • On May 9, 2016, Galapagos announced the start of a Phase 1 trial with potentiator GLPG2451 for cystic fibrosis. Following GLPG1837, GLPG2451 is the second potentiator compound in Galapagos' extended CF-portfolio to enter clinical trials. Galapagos is conducting a randomized, double-blind, placebo-controlled study over a range of doses of GLPG2451 in healthy volunteers in Belgium and the Netherlands and expects topline results in Q4 2016. The start of this Phase 1 study triggers a $10 million milestone payment from AbbVie under the recently expanded global collaboration agreement.
• • On April 29, 2016, Galapagos and AbbVie  announced that they have expanded their agreement in cystic fibrosis (CF) to reflect the successful expansion of their cystic fibrosis portfolio. Companies have agreed to increase the potential milestones to Galapagos for Phase 1 and 2 achievements, bringing the remaining total milestones in the cystic fibrosis alliance up to approximately $600 million, from $350 million. Other key collaboration terms remain in place: tiered royalty payments on net sales, ranging from mid-teens to twenty percent. Galapagos retains commercial rights to China and South Korea, and has an option to co-promote in Belgium, Netherlands, and Luxembourg. Galapagos and AbbVie aim to develop a triple CFTR combination therapy to address 90% of patients with cystic fibrosis. In order to bring a more effective therapy to patients, the companies have developed multiple candidates and backups for each of the three components of a potential triple combination. Triple combinations of cystic fibrosis compounds in the portfolio have consistently shown restoration of healthy activity levels in in vitro assays with human bronchial epithelial (HBE) cells of patients with the F508del mutation. These combinations result in a statistically significant increase in chloride transport over Orkambi[1] in HBE cells with the homozygous F508del mutation. It is expected that a triple combination therapy from this collaboration will be tested in patients having the F508del mutation in 2017.
• • On January 19, 2016, Galapagos has provided an update on progress made in the cystic fibrosis (CF) programs. Galapagos and AbbVie  aim to develop a triple CFTR combination therapy to address 90% of patients with CF. In order to bring a more effective therapy to patients, the companies plan to develop multiple candidates and backups for each of the three components (1st generation correctors, next generation correctors, and potentiators) with the goal of identifying a potential triple combination. In addition to Galapagos' potentiator and corrector that are being tested in the clinic, a total of four additional compounds have the potential to reach clinical development in the CF program this year. Dosing to humans of GLPG2222, the first 1st generation corrector in Galapagos' portfolio, started earlier this month. This achievement earns Galapagos a $10 million milestone payment in connection with the global collaboration agreement with AbbVie. Galapagos is conducting a randomized, double-blind, placebo-controlled study over a range of doses of GLPG2222 in healthy volunteers in Belgium and expects topline results in Q2 2016. Galapagos further announces the selection of preclinical candidate GLPG2851, an additional 1st generation corrector, aiming to initiate Phase 1 with this compound by the end of 2016. Galapagos also announced selection of an additional next-generation corrector GLPG2737, expected to enter Phase 1 in healthy volunteers by Q4 2016. Galapagos and AbbVie are also developing an alternative series of next-generation correctors with different activity and expect to nominate candidates and additional compounds from that series later in 2016. • On October 15, 2015, Galapagos announced that GLPG2665 has been selected as the first next generation corrector compound candidate. Galapagos discovered multiple C2 corrector compound series, each with a different chemical scaffold and corresponding unique and complementary mode of action. GLPG2665 is the first candidate to complete the potential triple combination therapy for the delta F508 (class II) mutation in cystic fibrosis. GLPG2665 will now enter pre-clinical development, and is expected to enter Phase 1 studies by mid 2016. GLPG2665 in combination with corrector GLPG2222 and potentiator GLPG1837 consistently have shown restoration of healthy activity level in human bronchial epithelial (HBE) cells of patients with the Class II F508del mutation. The combination resulted in chloride transport up to six-fold greater than Orkambi in HBE cells with the homozygous F508del mutation. Poor functioning of the CFTR channel is the major deficit in patients with cystic fibrosis. Advancement of the third component of the triple combination therapy into development brings the Galapagos-AbbVie collaboration closer to its goal of bringing disease-modifying therapies to CF patients. Galapagos expects to enter Phase 2 studies with potentiator GLPG1837 in Class III mutation patients and a Phase 1 study with corrector GLPG2222 in healthy volunteers by filing before year-end.
• • On December 19, 2014, Galapagos announced the initiation of the first Phase 1 study with GLPG1837. This novel potentiator is designed as a CFTR targeted therapy for cystic fibrosis patients who carry class III/IV mutations (e.g., G551D). This achievement triggers a milestone payment of $10 million from AbbVie.
• • On December 16, 2013, Galapagos has announced that it nominated a pre-clinical candidate potentiator for clinical development in its cystic fibrosis program. Galapagos has developed multiple, novel potentiators that, in pre-clinical research, show high potency and superior efficacy in comparison to Kalydeco® (ivacaftor),the only approved disease-modifying cystic fibrosis drug on the market today. The Galapagos compounds show good drug-like properties, which support further pre-clinical development. The clean safety profile of these compounds should allow the combination with antibiotics frequently prescribed for CF patients. From these series, Galapagos selected GLPG1837 as pre-clinical candidate and expects to start the first clinical trial before end 2014. Galapagos recently filed a patent application covering GLPG1837, with the expected patent life until at least 2034. Galapagos initiated its research in cystic fibrosis in 2005 as part of a collaboration with the Cystic Fibrosis Foundation. In September 2013 Galapagos signed an agreement with AbbVie in which they will work collaboratively to develop and commercialize oral drugs that address the main mutations in cystic fibrosis patients, including F508del and G551D. Under the terms of the agreement, AbbVie made an upfront payment of $45 million to Galapagos. Upon successful completion of pre-determined success milestones, AbbVie and Galapagos will share responsibility and funding for Phase III clinical development. Galapagos is eligible to receive up to $360 million in total additional payments for developmental and regulatory milestones, sales milestones upon the achievement of minimum annual net sales thresholds and additional double-digit royalty payments on net sales.

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