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发帖数: 125 | 1 IMMU is breaking out. Anyone familiar with its pipeline and prospects? | f**********g
发帖数: 2252 | 2 Ask Biofish?
Immunomedics Reports Progress on Development of Antibody-SN-38 Conjugates at
Cancer Meeting
4 hours 6 minutes ago - PMZ via Comtex
GlobeNewswireImmunomedics, Inc. (Nasdaq:IMMU), a biopharmaceutical company
primarily focused on the development of monoclonal antibody-based products
for the targeted treatment of cancer, autoimmune and other serious diseases,
today announced at the 102nd Annual Meeting of the American Association for
Cancer Research results from 2 studies on the development of antibody-SN-38
conjugates for targeted drug therapy of cancer.
SN-38 is the active metabolite of irinotecan, an FDA-approved drug for
metastatic colorectal cancer treatment. SN-38 cannot be administered
systemically to patients because of its toxicity and poor solubility. By
conjugating SN-38 to monoclonal antibodies, the potent drug can be delivered
selectively to tumors, thereby increasing the amount reaching the tumors
and minimizing the damage to normal tissues and organs. This is the
rationale behind Immunomedics' efforts to developing antibodies conjugated
with SN-38 for improved selective therapy of cancer.
The first study focused on the tolerability and dose-limiting toxicity of SN
-38 conjugates of labetuzumab, the Company's proprietary humanized antibody
targeting the CEACAM5 cancer marker, and hRS7, an anti-TROP-2 humanized
antibody, in a number of animal models. Both antibody-drug conjugates (ADCs)
were found to be well tolerated.
In addition, labetuzumab-SN-38 was shown in a mouse model of human colonic
cancer to be efficacious at a dose of 0.5 mg given twice a week for 2 weeks,
whereas hRS7-SN-38 was efficacious at 0.25 mg/dose, administered twice
weekly for 4 weeks, in a human pancreatic cancer model.
Earlier at the same conference, strong anti-lymphoma and anti-leukemia
activity for the SN-38 conjugate of epratuzumab, the Company's humanized
anti-CD22 antibody, was reported in a separate poster presentation.
Epratuzumab, as a naked antibody, has shown to be potentially safe and
efficacious in a number of clinical studies in cancer and autoimmune
diseases. It is an ideal candidate for ADC development, because it is an
internalizing antibody. The potential therapeutic activity of epratuzumab-SN
-38 may lie in the combined effect of both the antibody and the drug.
Epratuzumab-SN-38 demonstrated potency at the nanomolar level against a
number of human NHL and acute lymphoblastic leukemia (ALL) cell lines. The
ADC also produced significant antitumor activity in mice bearing human
lymphoma cells. At a dose of 75 μg twice weekly for 4 weeks, the SN-38
conjugate of epratuzumab extended the median time to progression (TTP) from
1 week in animals treated with an irrelevant ADC to 4 weeks. Increasing the
epratuzumab-SN-38 dose to 250 μg improved TTP to more than 12 weeks, with
7 of 10 animals cured, while the irrelevant conjugate's TTP was just 3.5
weeks.
Additionally, the therapeutic response to epratuzumab-SN-38 was enhanced by
co-treating animals with veltuzumab, the Company's proprietary humanized
anti-CD20 antibody that has completed Phase I/II clinical trials in NHL. In
another animal lymphoma model, median survivals in animals treated twice
weekly for 4 weeks with 300 μg of the conjugate alone or 5 μg
veltuzumab alone were 63 and 91 days, respectively, compared with 42 days in
untreated animals, while combining epratuzumab-SN-38 with veltuzumab
prolonged survival significantly to more than 161 days. Importantly, these
treatments were tolerated without toxicity. These data suggest that
epratuzumab-SN-38 is a potent, minimally-toxic therapeutic in both NHL and
ALL, with the added value when combined with anti-CD20 antibody therapy for
enhanced responses.
"SN-38 is an important drug in our ADC program, as shown in these two poster
presentations," remarked Cynthia L. Sullivan, President and Chief Executive
Officer. "The first SN-38 conjugate we are bringing into the clinic is
labetuzumab-SN-38, which is planned to be evaluated in a Phase I dose-
escalation study for the therapy of patients with colorectal cancer later
this year," Ms. Sullivan added.
The development of antibody-SN-38 conjugates has previously been reported by
the Company. (For more information, please refer to the Company's press
release at www.immunomedics.com/news_pdf/2010_PDF/PR04192010a.pdf). |
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