Avid Bioservices Inc (CDMO)

[cjgaddy]

FTM, a bit more (from iBox) on 'NHS-IL2-LT (EMD 521873)', (aka "Selectikine"), which Merck KGaA licensed from Peregrine in 2000. In 2009, Merck-KGaA added a 2nd Ph.1 trial for this compound: Selectikine+RAD vs. NSCLC in The Netherlands. Recall that “SELECTIKINE” is the brand name for the TNT-based immunocytokine fusion protein NHS-IL12 . In Dec.2006, Merck began its 1st Ph.1 trial (Selectikine+Chemo vs. Solids-Tumors or NHL) at 2 sites in Switzerland…

Eur. Licensee Merck-KGaA's TNT/Cytokine Fusion Protein Ph.1 Trials:
4-2009: 2nd SELECTIKINE Ph.1 trial added: SELECTIKINE+RAD/NSCLC: http://tinyurl.com/pzl9j8
5-2007: 2nd SELECTIKINE Ph.1 site added, Univ. of Lausanne, Switz: http://tinyurl.com/2l933s
Ph.1 Trial Protocol (Merck KGaA/Germany, PI=Dr. R.Stupp): http://tinyurl.com/2f4u2t
2-22-07: TNT-based European Cancer Trial initiated by 'Licensee': http://tinyurl.com/2zcjqr
Clearly, it's Merck-KGaA's 'SELECTIKINE' (NHS-IL2-LT/EMD521873): http://tinyurl.com/yud7pw

Quick Google shows Selectikine was presented at AACR’11 as well:

4-2011/AACR: “A Low-Toxicity IL-2–Based Immunocytokine Retains Antitumor Activity Despite Its High Degree of IL-2 Receptor Selectivity”
Stephen D. Gillies 1, Yan Lan 1, Thore Hettmann 1, Beatrice Brunkhorst 1, Yaping Sun 1,
Stefan O. Mueller 2,3, and Kin-Ming Lo 1
1 EMD Serono Research Institute, Middlesex, MA
2 Merck Serono, Darmstadt, Germany
3 Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany
“CONCLUSIONS: The qualities of low toxicity and single-agent efficacy shown suggest that NHS-IL2LT is a good candidate for therapeutic approaches combining standard cytotoxic and immune therapies. In fact, this molecule (also known as Selectikine or EMD 521873) is currently in phase I clinical trial.”
http://clincancerres.aacrjournals.org/content/early/2011/05/17/1078-0432.CCR-10-2921

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AACR’12 ABSTRACT BY MERCK-KGAA/ EMD SERONO ABOUT “SELECTIKINE”…
…about the TNT Fusion Protein “Selectikine”, (NHS-IL2-LT/EMD521873), which Merck-KGaA licensed from Peregrine in 4-2001 (now in Ph.1 trials in Eur. – see below):
Mon., Apr 2, 2012, 8:00am-12pm
AACR’12 #1536: ”A Novel Immunocytokine Generates a CD8+ T Cell-Mediated Anti-Tumor Response In Vivo”
Jonathan K. Fallon 1, Robert Tighe 2, Wolfgang Strittmatter 2, Helen Sabzevari 2, Jeffrey Schlom 1, John W. Greiner 1
1 LTIB, National Cancer Institute, Bethesda, MD
2 EMD Serono, Billerica, MA
ABSTRACT:
Interleukin-12 (IL-12) is a potent TH1 cytokine produced by dendritic cells and macrophages to activate NK cells and T cells. Data from preclinical studies in mice indicate that this cytokine may be useful for the treatment of cancer. However, cases of severe toxicity in human trials have impeded its successful clinical development. Targeting delivery of IL-12 to a tumor while reducing systemic IL-12 exposure could make this a safer, more effective cancer therapeutic agent. One strategy is to conjugate IL-12 to a tumor-binding antibody, as antibody conjugates have previously been used to deliver radioisotopes, other cytokines, and small molecule therapeutics to tumors in vivo. NHS-IL12 is a novel immunocytokine consisting of two molecules of the IL-12 heterodimer covalently fused to a fully humanized antibody (NHS76). This antibody targets necrotic portions of tumors because of its high affinity for single- and double-stranded DNA, which are often exposed as tumors outgrow their blood supply. NHS-IL12 may therefore be useful against a wide range of solid tumors, and mouse models can be used to study its mechanisms of action.
Initial imaging studies clearly showed superior in vivo localization of IL-12 to mouse tumors following subcutaneous NHS-IL12 injection as compared to administration of recombinant IL-12 (rIL-12) or IL-12 fused to a control antibody (BC1). In the MC38/CEA+ colorectal carcinoma model in CEA.Tg mice, treatment with NHS-IL12 significantly delayed subcutaneous tumor growth more effectively than treatment with rIL-12. NHS-IL12 did not inhibit MC38/CEA+ tumor cell growth in vitro, suggesting that NHS-IL12 acts indirectly on tumors in vivo most probably via an immune-mediated mechanism. Subsequent findings revealed that tumor-bearing mice treated with NHS-IL12 developed a strong CD8+ T cell response directed against the endogenous p15E tumor antigen. In one study, a subset of mice bearing MC38/CEA+ tumors had complete tumor regression following NHS-IL12 treatment. Each of these mice still had a strong p15E-specific CTL response more than two months after tumor rejection, indicating that p15E may be the major tumor rejection antigen for this in vivo tumor model. Subsequent in vivo depletion studies are planned to investigate which immune cell subsets contribute to the anti-tumor efficacy of this agent. Taken together, these data show that targeted delivery of IL-12 to tumors can overcome the immunosuppressive tumor microenvironment and prime a robust CD8+ T cell response. These findings suggest that NHS-IL12 may be a promising cancer therapeutic as a single agent and/or as a potent vaccine adjuvant.