Replies to post #55065 on Biotech Values

[DewDiligence]

>i can't see an advantage that this [GenMab/GSK] product would have over 2H7, the 2nd gen fully human Rituxan. And it is about 1.5 years behind it in development.<

Between cancer and autoimmune diseases, the market for follow-ons to Rituxan is so big that there are multiple contenders. When the main CD20/Rituxan patent expires in 2014, GTCB hopes to come in with an FoB being co-developed with LFB of France.

[DewDiligence]

Biolex is yet another company in the anti-CD20 space,
although the program is in still in in vitro testing. The
company claims its mAb, which is produced in transgenic
plants, has greater ADCC and less CDC than Rituxan.

http://biz.yahoo.com/iw/071210/0337720.html

>>
Biolex Researchers Present Results of Anti-CD20 Antibody With Optimized Glycosylation at ASH Conference

Monday December 10, 9:00 am ET

Preclinical Results Demonstrate Potential for Improved Efficacy and Potency and Reduced Side Effects Compared to Rituxan(R)

PITTSBORO, NC--(MARKET WIRE)--Dec 10, 2007 -- Biolex Therapeutics today announced that preclinical results of an anti-CD20 antibody optimized in its proprietary LEX System(SM) were presented yesterday at the 49th Annual Meeting of the American Society of Hematology (ASH) in Atlanta, Georgia. The results highlight the ability of the LEX System to produce an anti-CD20 antibody with an optimized glycosylation structure with enhanced antibody dependent cellular cytotoxicity (ADCC), more potent B-cell depletion, and potentially lower side effects compared to Rituxan® (rituximab), the current standard of care for the treatment of non-Hodgkin's B-cell lymphoma. Biolex is developing BLX-301, a humanized anti-CD20 candidate incorporating the optimized glycosylation benefits of the LEX System.

"We are pleased with these results as they demonstrate the potential for a next-generation product that provides a therapeutic advantage while also addressing the relatively low potency and side-effect burden of the current standard of care," said Mr. Jan Turek, Biolex President and Chief Executive Officer. "Monoclonal antibodies are the fastest growing class of therapeutics in the pharmaceutical sector, and glycosylation can play a significant role in their therapeutic function. In addition to supporting the potential benefits of our BLX-301 candidate, these results also highlight the capability of the LEX System to improve the therapeutic benefits of a broad range of antibodies that can be enhanced through optimization of their glycosylation structures."

Anti-CD20 Results Presented at ASH Conference

The optimized rituximab included in the studies reported at the ASH conference was developed and produced in Biolex's LEX System, a next-generation platform for the production of biologic products. As reported in December 2006 in Nature Biotechnology, the LEX System has the ability to produce monoclonal antibodies with a fully human glycosylation structure without fucose. Research suggests that antibodies with a glycosylation structure that lacks fucose may improve therapeutic efficacy by enhancing ADCC, particularly in the treatment of cancer, autoimmune diseases, infectious diseases and inflammatory diseases. The LEX System can also produce monoclonal antibodies that have a fully G0 glycosylation structure, meaning they lack galactose. Research suggests that a G0 glycosylation structure provides the additional benefit of potentially reducing complement dependent cytotoxicity (CDC), thereby reducing side effects and the long infusion times associated with treatment with Rituxan and certain other antibodies.

As reported at the ASH conference, researchers evaluated an optimized version of rituximab produced in the LEX System to further support the potential benefits of developing an anti-CD20 antibody incorporating the LEX System optimization. Optimized rituximab produced in the LEX System demonstrated higher ADCC efficacy and 20 to 200 times higher potency than the current Rituxan. Furthermore, preliminary results suggest optimized rituximab was also more effective than Rituxan at causing B-cell depletion in whole blood. Lastly, the optimized rituximab produced in the LEX System with its G0 glycosylation structure had ten-fold lower CDC than Rituxan. Complement dependent cytotoxicity has been reported to be a key contributor to the serious side effects and long infusion times associated with Rituxan treatment.

Rituxan is approved for treatment of non-Hodgkin's B-cell lymphoma and rheumatoid arthritis. It is also being studied for use in other autoimmune diseases such as immune thrombocytopenic purpura, systemic lupus erythematosus, and multiple scelerosis. Biolex is developing BLX-301, a humanized anti-CD20 candidate incorporating the optimized glycosylation benefits of the LEX System, and currently expects that the first indication targeted for development will be non-Hodgkin's B-cell lymphoma.

About Biolex Therapeutics

Biolex is a clinical-stage biopharmaceutical company that uses its patented LEX System(SM) to develop hard-to-make therapeutic proteins and to optimize monoclonal antibodies. The LEX System is a novel technology that genetically transforms the aquatic plant Lemna to enable the production of biologic product candidates. The company's product candidates are designed to provide superior efficacy/tolerability profiles and to address large, proven pharmaceutical markets. Biolex's lead product candidate, Locteron®, under joint development with OctoPlus N.V., is in Phase 2 clinical trials and is the only controlled-release interferon alfa known to be currently in active clinical development for the treatment of chronic hepatitis C. Biolex has also developed two other product candidates that capitalize on the benefits of the LEX System, which it is advancing toward clinical trials: BLX-155, a direct-acting thrombolytic designed to dissolve blood clots in patients; and BLX-301, an anti-CD20 antibody it is optimizing for the treatment of non-Hodgkin's B-cell lymphoma and other diseases.
<<

[DewDiligence]

(GSK Genmab) Arzerra Succeeds in Phase-3 RA Study

[Arzerra (a/k/a/ ofatumumab) is a “second generation” knockoff of Rituxan that is being tested by in both cancer and autoimmune diseases. GSK licensed the drug from Genmab in 2006 in one of the largest-ever biotech deals (#msg-15652707).

The trial described here was in second-line RA following first-line failure on methotrexate; such second-line usage is the main setting for the immense RA sales of biologics (Enbrel, Remicade, Humira, Rituxan, Orencia, and the recently approved Simponi). The primary endpoint and all secondary endpoints were hit with impressive p-values—clearly, efficacy is not a problem.

The lead indication for Arzerra is CLL, where there is a BLA pending with a PDUFA date of Oct 31. An advisory panel for the CLL indication recommended approval in May by a 10-3 vote (#msg-38239069).

Second-generation CD20 compounds comprise a crowded class (#msg-32767969), but there is a lot of money to be made here. BMY stands to make a small royalty on Arzerra by way of its MEDX acquisition.

CC by Genmab on the phase-3 results in RA tomorrow at 9am ET.]

http://finance.yahoo.com/news/GlaxoSmithKline-and-Genmab-pz-2901212014.html?x=0&.v=1

›Wednesday July 29, 2009, 5:10 pm EDT

COPENHAGEN, Denmark, July 29, 2009 (GLOBE NEWSWIRE) -- GlaxoSmithKline (NYSE: GSK ) and Genmab A/S (Copenhagen:GEN announced today preliminary top-line results from a Phase III study of ofatumumab administered intravenously for the treatment of rheumatoid arthritis (RA) in patients who had an inadequate response to methotrexate. The study met the primary endpoint, ACR20 at 24 weeks [see definition below], which indicates a 20 percent or greater improvement in the number of swollen and tender joints, as well as improvements in other disease-activity measures.

In the study, 260 patients were treated and included in the analysis. At week 24, the ACR20 response rate was significantly greater for RA patients on ofatumumab (n=129) than on placebo (n=131) with a 50 percent response rate in the patients receiving ofatumumab, compared to 27 percent for patients on placebo (p-value less than 0.001). All key secondary endpoints were significant (p-value less than or equal to 0.001).

There were no unexpected safety findings. The most common adverse events in the ofatumumab treated patients (greater than 5 percent) were rash, urticaria, nasopharyngitis, pruritus, throat irritation and hypersensitivity. Other than nasopharyngitis, these events generally occurred within 24 hours of the first infusion. One death, judged by the investigator as unrelated to ofatumumab, was reported in the study during the 24-week study period.

"We have always believed in ofatumumab's potential to make a difference in patients' lives. We are pleased with the results of this study, supporting the further investigation of this antibody's promise in the treatment of RA," said Lisa N. Drakeman, Ph.D., Chief Executive Officer of Genmab.

"RA can be a highly debilitating disease. It is encouraging to see the reduction in disease symptoms achieved with intravenous ofatumumab, and we look forward to presenting the full study results," said Carlo Russo, M.D., Senior Vice President, Biopharm Development, GSK.

About the study

In this 24 week double-blind study, patients with active RA were randomized to receive two 700 mg doses of intravenous ofatumumab or placebo two weeks apart in addition to background methotrexate. Disease status was measured every 4 weeks. Patients for this non-IND study were recruited from Europe, South America and Australia.

The primary objective of the study was to determine the efficacy of intravenous ofatumumab in reducing the clinical signs and symptoms in RA patients after two 700 mg doses of ofatumumab compared to placebo. The primary endpoint of the study was ACR20 at 24 weeks. Other key secondary objectives included safety, patient reported outcomes, biomarkers and ACR 50 and ACR 70.

ACR Response

The ACR 20 response is defined as a 20 percent or greater improvement from baseline in tender and swollen joint counts, and 20 percent or greater improvement in 3 of the 5 following assessments: patient and physician global assessments, pain, disability, and an acute phase reactant (ESR or CRP).

About ofatumumab

Ofatumumab is a novel, investigational, fully human monoclonal antibody that targets a membrane-proximal (close to the cell surface) small loop epitope (a portion of a molecule to which an antibody binds) on the CD20 molecule of B-cells. This epitope is different from the binding sites targeted by other CD20 antibodies currently available.

Ofatumumab is being developed for other indications under a co-development and commercialization agreement between Genmab and GlaxoSmithKline. It is not yet approved in any country.

Conference Call

Genmab will hold a conference call to discuss the ofatumumab results Thursday, July 30, 2009, at

3:00 pm CEST
2:00 pm BST
9:00 am EDT

The conference call will be held in English.

The dial in numbers are as follows:

[phone] (in the US) and quote conference ID number 4129982
[phone] (outside the US) and quote conference ID number 4129982

To listen to a live webcast of the call please visit www.genmab.com.‹