Clovis Oncology announced today that it has acquired EOS (Ethical Oncology Science) S.p.A., a privately-held Italian biopharmaceutical company developing a novel targeted therapy to treat cancer. EOS owns the exclusive global (excluding China) development and commercialization rights for lucitanib, an oral, dual-selective inhibitor of the tyrosine kinase activity of fibroblast growth factor (FGF) receptors 1 and 2 (FGFR1/2) and vascular endothelial growth factor (VEGF) receptors 1-3 (VEGFR1-3). In 2012, EOS sublicensed lucitanib rights in Europe and the rest-of-world (ROW) markets, excluding China, to Les Laboratoires Servier (Servier). Clovis holds exclusive rights for lucitanib in the U.S. and Japan, and will collaborate with Servier on the global clinical development of lucitanib.
In an ongoing Phase I/IIa clinical study, lucitanib has demonstrated multiple objective responses in FGF-aberrant breast cancer patients, and objective responses have also been observed in patients with tumors often sensitive to angiogenesis inhibitors, such as renal cell and thyroid cancer. FGF-aberrations include amplification of the FGFR1 gene as well as amplification of a region of chromosome 11q that contains several FGF ligands, specifically FGF-3, -4 and -19.The initial development program for lucitanib will focus on the approximately 25 percent of women with breast cancer who have FGF-aberrant disease.
FGFs and VEGFs each play a role in tumor growth and angiogenesis and both are validated targets in oncology. Clovis believes lucitanib is unique in its pattern of clinical inhibition of both FGFR and VEGFR tyrosine kinases. As a result, lucitanib has potential to provide benefit to cancer patients by simultaneously targeting two relevant tumor growth pathways in selected patients identified by FGF aberrations. In particular, Clovis believes FGF-aberrant tumors are driven by both FGF and VEGF pathways, and that by inhibiting both, lucitanib can provide more meaningful benefit than single pathway inhibitors.
“We have been interested in lucitanib for some time and are pleased to have acquired EOS to add this program to our portfolio,” said Patrick J. Mahaffy, Clovis Oncology’s president and CEO. “It is highly consistent with our focus on developing targeted therapies that provide meaningful benefit to specific patient populations. We are extremely encouraged with lucitanib’s 50 percent response rate seen to date in heavily pre-treated targeted patients and we intend to develop it aggressively, in collaboration with our partner Servier.”
Lucitanib Clinical Development
The first clinical trial of lucitanib was initiated in Europe in July 2010 and is currently ongoing at Institute Gustave-Roussy in Paris with Professor Jean-Charles Soria and at Vall d’Hebron Institute of Oncology in Barcelona with Professor Josep Tabernero. This trial is an open-label, dose-escalation, Phase I/IIa study to determine the maximum tolerated dose (MTD), recommended Phase II dose, efficacy, pharmacokinetics and pharmacodynamics of lucitanib in adult patients with advanced solid tumors.
Doses evaluated in the study ranged from 5mg to 30mg given once per day. Twenty milligrams once per day was identified as the MTD. Overall, the toxicity profile observed to date is consistent with what was expected from preclinical studies and with VEGF inhibitors generally, with hypertension, proteinuria, asthenia and subclinical hypothyroidism being commonly observed. Other common treatment-related adverse events include gastrointestinal symptoms such as diarrhea, abdominal pain, nausea and vomiting.
Subsequent to MTD identification, a dose expansion phase was initiated in defined populations expected to derive benefit from lucitanib, and initial data show encouraging activity in patients who were either FGF-aberrant or angiogenesis inhibitor-sensitive. Six of 12 evaluable FGF-aberrant breast cancer patients achieved RECIST partial responses and the median progression-free survival was 9.4 months in these 12 patients. These patients were heavily pre-treated, with at least three or as many as 14 prior treatment regimens. Importantly, two of the responders had previously failed to achieve a response with a selective FGFR inhibitor. Responses were also observed in other tumor types.
A broad Phase II program is being initiated to explore lucitanib in multiple indications including a U.S. study in patients with treatment-refractory FGF-aberrant breast cancer and a global study in patients with metastatic squamous NSCLC. In parallel with these planned Clovis-sponsored studies, a Servier-sponsored Phase II study of lucitanib monotherapy in patients with advanced breast cancer will begin enrolling this month. This ex-US study is expected to enroll approximately 120 patients and will seek to determine whether the activity of lucitanib is limited to a defined population of breast cancer tumors with FGF-aberrations or if a more broadly defined population may benefit as well.
If these Phase II monotherapy studies in breast cancer are successfully completed, Clovis and Servier intend to pursue future development of lucitanib as monotherapy and/or in combination with estrogen antagonists. Other potential indications that may be considered for development include squamous NSCLC, bladder, head and neck cancer, and other solid tumors with FGF-aberrancies.
Clinical development of lucitanib in patients with FGF-aberrant tumors will be accompanied by development of a diagnostic test designed to identify a selected patient population most likely to benefit.
Composition of matter patent protection for lucitanib and a group of structurally related compounds is issued in the United States and is pending in Japan. In the United States, the composition of matter patent will expire in 2030.
Under the terms of the deal, Clovis is acquiring EOS for an up-front payment of $200 million, which includes $190 million in Clovis common stock (3,713,731 shares) and $10 million in cash. Clovis will pay an additional $65 million in cash upon the initial approval of lucitanib by the U.S. Food and Drug Association (FDA). Pursuant to the license agreement with Servier, Clovis is entitled to receive up to €350 million (approximately $470 million) upon the achievement of development and commercial milestones, as well as royalties on sales of lucitanib in the Servier territories. Clovis will also pay the EOS shareholders up to an additional €115 million in cash (approximately $155 million) upon the receipt by Clovis of certain of the milestone payments pursuant to the Servier license agreement.
Clovis and Servier will collaborate on the development of lucitanib pursuant to a mutually-agreed upon global development plan. Servier is responsible for the initial €80 million (approximately $108 million) of costs under the global development plan and costs above €80 million will be shared equally between the companies.
Clovis intends to host an R&D Day and webcast for institutional investors and analysts to detail its clinical development programs for CO-1686, lucitanib and rucaparib next January in New York City.
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