Verastem, Inc., a biopharmaceutical company, and Infinity Pharmaceuticals, Inc., an innovative biopharmaceutical company, announced that the companies entered into a license agreement under which Verastem licensed exclusive worldwide rights to develop and commercialize Infinity’s oncology product candidate duvelisib.

Duvelisib is an oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma being investigated for the treatment of haematologic cancers, including chronic lymphocytic leukaemia (CLL), indolent non-Hodgkin lymphoma (iNHL) and T cell lymphomas.

Verastem will pay to Infinity up to $28 million in milestones, with positive data from DUO, a phase 3, randomized monotherapy study of duvelisib in patients with relapsed/refractory CLL, triggering the first milestone payment, and royalties on net sales.

“Duvelisib is a clinically validated, late-stage product candidate with a proven mechanism of action. This transaction has an attractive risk/reward profile given the modest financial investment prior to obtaining topline data from the DUO study, currently anticipated in the first half of 2017, as well as the potential applications for a variety of other lymphoid malignancies,” said Robert Forrester, president and chief executive officer of Verastem. “Duvelisib complements Verastem’s oncology pipeline by augmenting our strategic focus of developing small molecule agents that target malignant cells both directly and through modulation of the tumour microenvironment. This transaction represents a positive step toward our goal of bringing new treatment options to patients with cancer. We are working closely with Infinity to ensure a smooth transition of the duvelisib programme.”

“The potential of duvelisib is supported by clinical data demonstrating anti-cancer activity and a manageable safety profile in a wide range of lymphoid malignancies, including relapsed/refractory iNHL, CLL and T cell lymphomas,” said Gregory I. Berk, MD, Chief Medical Officer of Verastem. “While there have been significant advances recently in the treatment of lymphoid malignancies, not all patients experience benefits or can tolerate these treatments. There remains a need for new oral medicines, and the targeted inhibition of PI3K-delta and PI3K-gamma brings a unique approach designed to address both the malignant B cell and its supportive microenvironment. We look forward to reporting data from the DUO study, which could enable a submission for regulatory approval.”

“Infinity has always been committed to finding innovative ways to develop novel medicines which hold significant promise for people living with cancer. Verastem provides duvelisib the best opportunity to advance toward regulatory filings and potential commercialization given their oncology-focused capabilities and deep knowledge of the tumor microenvironment,” stated Adelene Perkins, president and chief executive officer of Infinity. “Additionally, the license of duvelisib fulfills an important strategic goal for Infinity by preserving cash while enabling our shareholders to participate in the value of the duvelisib program through potential milestone payments and royalties to Infinity.”

Under the terms of the license agreement, Verastem is obligated to pay to Infinity up to $28 million in milestones. Infinity is entitled to receive two milestone payments, $6 million upon positive data from the DUO study and $22 million upon the first regulatory approval inside or outside of the US. Verastem will also pay Infinity tiered mid-to-high single-digit royalties on net sales and will be responsible for the single-digit-royalty on net sales of duvelisib owed by Infinity to MundiPharma International Corporation Limited and Purdue Pharmaceutical Products L.P.

In addition to duvelisib, Verastem also holds worldwide rights to the tumour microenvironment-targeting focal adhesion kinase (FAK) inhibitors defactinib (VS-6063) and VS-4718. Verastem’s lead FAK inhibitor, defactinib, is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types, including pancreatic, ovarian, non-small cell lung cancer, and mesothelioma. These studies are combination clinical trials with pembrolizumab or avelumab from Merck & Co. and Pfizer/Merck KGaA, respectively. Verastem also owns rights to the FAK inhibitor VS-4718 and the dual PI3K and mTORC1/2 inhibitor VS-5584 which are both currently being evaluated in phase 1 clinical studies.

Based on current operating plans including duvelisib, Verastem expects to have sufficient cash, cash equivalents and short-term investments to fund its research and development programs and operations into 2018.

The tumour microenvironment encompasses various cellular populations and extracellular matrices within the tumor or cancer niche that support cancer cell survival. This includes immunosuppressive cell populations such as regulatory T cells, myeloid-derived suppressor cells, M2 tumour-associated macrophages, as well as tumour-associated fibroblasts and extracellular matrix proteins which can hamper the entry and therapeutic benefit of cytotoxic immune cells and anti-cancer drugs. In addition to targeting the proliferative and survival signalling of cancer cells, Verastem’s compounds duvelisib, defactinib, VS-4718 and VS-5584 also target the tumour microenvironment as a mechanism of action to potentially improve a patient’s response to therapy.

Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes that are known to help support the growth and survival of malignant B cells and T cells. PI3K signalling may lead to the proliferation of malignant B cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment. Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO, a randomized, phase 3 monotherapy study in patients with relapsed/refractory chronic lymphocytic leukaemia (CLL), and DYNAMO, a single-arm, phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL) that achieved its primary endpoint of overall response rate upon topline analysis of efficacy data. Duvelisib is also being evaluated for the treatment of haematologic malignancies through investigator-sponsored studies, including T cell lymphoma.

Defactinib (VS-6063) is an investigational inhibitor of Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase encoded by the PTK-2 gene that mediates oncogenic signalling in response to cellular adhesion and growth factors. Based on the multi-faceted roles of FAK, defactinib is used to treat cancer through modulation of the tumour microenvironment, enhancement of anti-tumour immunity, and reduction of cancer stem cells. Defactinib is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types including pancreatic, ovarian, non-small cell lung cancer, and mesothelioma. These studies are combination clinical trials with pembrolizumab and avelumab from Merck & Co. and Pfizer/Merck KGaA, respectively.