NM-IL-12 (Recombinant Human Interleukin-12)

NM-IL-12 for Diffuse Large Cell B-cell lymphoma

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), an aggressive type of B-cell non-Hodgkin’s lymphoma (NHL), undergoing salvage chemotherapy face a poor prognosis. NM-IL-12 is being evaluated as an immunotherapeutic with concomitant hematopoietic regenerating properties for treatment of relapsed/refractory DLBCL. This clinical program seeks to show the benefits of combining the broad immunostimulatory effects of IL-12 with the existing efficacy of salvage chemotherapy regimens (R-ICE = rituximab plus ifosfamide-carboplatin-etoposide, R-DHAP = rituximab plus cytosine arabinoside-cisplatin-dexamethasone) for this patient population.

The company believes that if human trials show results similar to those seen in animal studies, NM-IL-12 could become an optimal adjuvant for these salvage chemotherapy regimens in DLBCL because:

  1. Animal studies have shown that NM-IL-12 effectively mitigates chemotherapeutic side effects,[9] [10]
  2. Animal studies conducted independently of Neumedicines have shown that IL-12 induces cytotoxicity against B cell lymphomas[11], and
  3. Very recent animal studies conducted independently of Neumedicines have suggested that IL-12, in combination with salvage chemotherapy may, similar to combination therapy with radiotherapy, immunize the body against its own tumors[12]. In the context of chemotherapy-induced immunogenic tumor cell death, NM-IL-12 is hypothesized to modulate the tumor microenvironment to potentiate tumor antigen uptake and presentation by APCs, and block activity of cells capable of immune suppression, resulting in a Th1-skewing and antitumor-stimulating immune environment. This could lead to long-lasting antitumor immunity via an endogenous vaccine effect.

    Therefore, the company believes that successful clinical development of NM-IL-12 could offer a new therapy for DLBCL patients, and is pursuing this regulatory goal, as a combination therapy with R-ICE or R-DHAP to expand the current treatment options.

9. Basile L, Gallaher T, Shibata D, et al. Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice.
J Transl Med. 2008;19:6-26.
10. Zagozdzon R, Golab J, Stoklosa T, et al. Effective chemo-immunotherapy of l1210 leukemia in vivo using interleukin-12 combined with doxorubicin but not with cyclophosphamide, paclitaxel or cisplatin. Int J Cancer. 1998;77:720–727.
11. Wajchman J, et. al. Interleukin-12-induced cytotoxicity against syngeneic B cell lymphomas of SJL/J mice. Leuk Res. 2002 Jun;26(6):577-90.
12. Jarosz-Biej M, et. al. Combined Tumor Cell-Based Vaccination and Interleukin-12 Gene Therapy Polarizes the Tumor Microenvironment in Mice. Arch Immunol Ther Exp (Warsz). 2015 Mar 24. [Epub ahead of print]

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