Agreements

Date: 2016-12-29

Type of information: Pipeline acquisition

Compound: remetinostat, birinapant and all intellectual property and data associated with Tetralogic’s HDAC inhibitor and SMAC mimetic projects.

Company: Medivir (Sweden) Tetralogic Pharmaceuticals Corporation (USA - PA)

Therapeutic area: Cancer - Oncology

Type agreement: pipeline acquisition

Action mechanism:

• HDAC inhibitor/SMAC mimetic. Remetinostat is a topical, skin-directed inhibitor of histone deacetylases (HDACs). The compound was designed to effectively inhibit HDACs within cutaneous lesions, but to be rapidly broken down in the bloodstream, preventing the side effects associated with systemically administered HDAC inhibitors.
• Birinapant is a bivalent, second mitochondrial activator of caspases (SMAC) mimetic that binds cellular inhibitor of apoptosis proteins (cIAPs) and induces their degradation. cIAPs are part of the ubiquitin proteasome system, and birinapant therefore ties in well to Medivir’s existing interests in modulators of protein ubiquitination.

Disease: early stage cutaneous T-cell lymphoma, solid tumours, High-grade serous carcinomas

Details:

• • On December 29, 2016, Medivir announced that the acquisitions of the two clinical stage oncology programs from TetraLogic Pharmaceuticals have been completed. In connection with the closing, Medivir has paid the upfront payment of $12 million to TetraLogic.
• • On November 2, 2016, Medivir  announcds that it has entered into an agreement to acquire two clinical stage oncology programs from Tetralogic Pharmaceuticals Corporation, advancing and expanding its clinical pipeline. The acquisition includes remetinostat, a skin-directed HDAC inhibitor, and birinapant, a bivalent SMAC mimetic, and all intellectual property and data associated with Tetralogic’s HDAC inhibitor and SMAC mimetic projects. Remetinostat is currently in a late phase II program aimed to treat early stage cutaneous T-cell lymphoma. Medivir currently plans to start a phase III trial with remetinostat in the second half of 2017. The company also plans to start two different clinical studies with birinapant. The first study is a phase I study in combination with Keytruda® (pembrolizumab), a PD-1 inhibitor from Merck&Co, in patients with solid tumours, subject to transfer to Medivir of the clinical trial agreement between Tetralogic and Merck&Co and receipt of Keytruda® supply. Preclinical studies have shown that SMAC mimetics such as birinapant are able to enhance the response of T-cells to tumour antigens, and the objective of the planned phase I study is to investigate the safety of the combination and the potential of birinapant to enhance response rates seen with Keytruda® alone.
• The second study is a phase II program, to investigate birinapant in combination with platinum-based chemotherapy for the treatment for high-grade serous carcinomas (HGSCs), including ovarian cancer, in collaboration with clinical investigators at UCLA. The UCLA team have identified that platinum-resistant cells in HGSCs are highly susceptible to birinapant-platinum co-therapy in approximately half of patients, and have developed a bioassay to enable patient selection. High-grade serous carcinomas are tumours that are believed to be derived from cells in the fallopian tube and can present as ovarian, endometrial, tubal or peritoneal cancer. The majority of ovarian cancer cases are high-grade serous carcinomas and these patients have a very poor survival rate.
• The transaction is an important strategic move for Medivir that is currently expanding its pipeline with programs in later stage clinical phases, shifting the balance from research to clinical development.  The transaction is subject to confirmation by Merck&Co of agreement transfer to Medivir, the consent of the Tetralogic Senior Noteholders, approval of the Tetralogic shareholders and other customary closing conditions. Medivir expects the transaction to close by year end 2016.

Financial terms:

• The acquisition has been structured to provide an upfront cash payment, but with the majority of financial consideration tied to successful clinical development, regulatory approvals and sales milestones. Medivir will also assume agreements or certain obligations with other third parties, including the Merck&Co agreement regarding Keytruda®, subject to confirmation from Merck&Co.
• The acquisition includes the following potential payments to Tetralogic and other third party licensees: - Upfront cash consideration of $ 12m; - Remetinostat development milestones through regulatory filings of up to $ 20m; - Remetinostat regulatory approval milestones of up to $ 45m; - Remetinostat tiered royalties capped at an aggregate of 13%; - Additional remetinostat commercialization milestones of up to $ 31m, primarily based on substantial sales achievement levels; - Birinapant development milestones and research support of up to $ 20m; - Birinapant tiered royalties capped at an aggregate of 10%; and - Additional birinapant commercialization milestones of up to $ 110m, primarily based on substantial sales achievement levels.

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