Debiopharm International, a Swiss biopharmaceutical company, has confirmed that it has acquired ImmunoGen‘s IMGN529, also known as Debio 1562 or naratuximab emtansine, a clinical-stage anti-CD37 antibody-drug conjugate or ADC offering a potential new treatment for for the treatment of patients with Diffuse Large B-cell Lymphoma (DLBCL) and other B-cell malignancies, including non-Hodgkin lymphomas (NHL) subtypes.

The investigational drug comprises an antibody that targets CD37, a member of the tetraspanin superfamily of cell surface antigens found on B-cell malignancies, with the potent cancer cell-killing agent, DM1, attached. The antibody serves to deliver the DM1 specifically to B cells to kill them and, based on preclinical research, also contributes anticancer activity.

The tetraspanin CD37, which is a heavily glycosylated 40- to 52-kDa glycoprotein, belongs to a family of transmembrane proteins which play a major role in the organization of the plasma membrane. Given the potential role of CD37 in supporting tumor survival and immune evasion, an improved understanding of tetraspanin activity may be clinically valuable.[1]

An early attempts to develop a tetraspanin-targeted therapy for the treatment of hematological malignancies included a murine anti-CD37 monoclonal antibody (MoAb) MB-1 labeled with iodine 131 or 131I for the treatment of patients with advanced-, low- or intermediate-grade non-Hodgkin lymphoma (NHL) who failed conventional treatment. [2] Although these initial approaches were promising, targeting CD20 became a more favored approach.  As result, the potential of CD37 as a target was, for many years, neglected. Recently, anti-CD37 therapies, including IMGN529, have seen a resurgence and are now actively investigated.[1]

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non-Hodgkin lymphoma
More than 70,000 people were diagnosed with non-Hodgkin lymphoma (NHL) in the United States in 2014. DLBCL is an aggressive lymphoma that represents approximately one third of the new NHL cases diagnosed annually. This represents a major unmet medical need and much research is needed to find a potential treatment option. [3]

IMGN529/Debio 1562 demonstrated evidence of anticancer activity in NHL in a Phase I monotherapy trial and successfully completed a safety run-in study in combination with rituximab (Rituxan®; Biogen and Genentech/Roche) which indication for treatment includes low-grade or follicular CD20+ non-Hodgkin’s lymphoma and CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma. [4]

Treatment with an CD37 targeting agent may be useful the treatment of patients resistant or refractory to anti-CD20 mAb therapy or relapsing after such treatment. [5]

Used as a single agent in patients with heavily pre-treated relapsed/refractory DLBCL, IMGN529 has demonstrated encouraging evidence of activity.[6]

The investigational agent is now ready to move forward into a Phase II trial in NHL, and particularly in DLBCL for which it has Orphan Drug status.

Under the terms of the agreement, ImmunoGen received a US $ 25 million upfront payment for IMGN529/Debio 1562.  The company is also entitled to a US $ 5 million milestone payment to be paid after completion of the transfer of all technologies related to the asset, which the parties expect to achieve by the end of 2017. In addition, ImmunoGen is eligible for a second success-based milestone payment of US $ 25 million upon IMGN529/Debio 1562 entering a Phase III clinical trial.

Compelling data of combination with rituximab
Transaction adds innovative clinical-stage program to expanding Debiopharm portfolio and broadens its clinical development expertise

“The purchase of IMGN529/Debio 1562 from a pioneer in the field of ADCs represents a strategic investment leveraging our expertise and track record in oncology and supports our strong commitment to deliver targeted therapies and precision medicines to help patients suffering from severe diseases,” noted Bertrand Ducrey, CEO of Debiopharm.

Researchers found that the preclinical assessment are consistent with in vitro findings and research data in which the combination of IMGN529 and rituximab was highly active against DLBCL models in vivo. The synergy was also seen in vitro in a model representative of “double hit” lymphoma, a particularly difficult-to-treat type of DLBCL characterized by deregulation of two different genes, BCL2 (or BCL6) and MYC. Researchers noted that both IMGN529’s antibody component and its DM1 payload contributed to its synergistic activity with rituximab.

“IMGN529/Debio 1562 has [also] generated compelling clinical data and we look forward to further exploring it in combination with rituximab, which could provide an attractive alternative to conventional chemotherapies for patients with NHL such as diffuse large-cell B-cell lymphoma,” explained Chris Freitag, Vice President of Clinical Research & Development of Debiopharm.

Strategic focus
The divestiture aligns with ImmunoGen’s focus on strategic growth initiatives and generates near-term value.

“With a strong history of developing and bringing oncology drugs to market, Debiopharm offers the right mix of resources and capabilities to advance IMGN529/Debio 1562 through its next phase of development,” stated Mark Enyedy, President and Chief Executive Officer of ImmunoGen.

“Consistent with the strategic review of our portfolio undertaken last fall, this transaction further enables us to prioritize our development efforts on mirvetuximab soravtansine and our IGN programs, while generating near-term value from IMGN529/Debio 1562,” Enyedy added.

Mirvetuximab soravtansine is in a Phase III trial for FRα-positive platinum-resistant ovarian cancer, and is in Phase Ib/II testing in combination regimens for earlier-stage disease.

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