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Biotech / Medical : MEDX ... anybody following? -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (791)	3/19/2004 2:01:33 PM
From: Icebrg	Read Replies (1) \| Respond to of 2240

Genmab's Pipeline. (source: DZ Bank AG) I came across the following which might be of interest to Medarex-watchers. HuMax-IL15: The antibody binds to the cytokine IL-15, which leads to proliferation of Tcells. IL-15 up to now is no clinically validated target, but there are reports about increased levels of IL-15 in autoimmune diseases like rheumatoid arthritis. Therefore, blocking IL-15 is a promising approach to treat patients suffering from autoimmune diseases. Moreover, IL-15 probably regulates both the cytokines TNF and IL-1, the former one being targeted by FDA approved drugs like Humira, Enbrel and Kineret. In Juli 2003, Amgen exercised for an upfront payment of USD 10m plus USD 136m in milestones the option to licence HuMax- IL15 ahead of schedule. Amgen will carry out the further clinical development of the antibody in rheumatoid arthritis, which validates the target at least through a partner, that has a strong expertise in developing Biologicals for rheumatoid arthritis. The successful clinical development could help Amgen to secure its revenues in rheumatoid arthritis, as Enbrel is facing increasing competition coming from a phalanx of newly approved and expected anti-TNF-biologicals. Currently, HuMax-IL15 is in phase II clinical trials, but instead of unblinding the trial end of 2003, Amgen decided to increase the number of patients for the trial which underlines Amgen’s commitment. HuMax-CD4: The antibody binds to the surface protein CD4, which is present on certain white blood cells (the T-cells) and was originally developed for the treatment of autoimmune diseases. The clinical development for the treatment of rheumatoid arthritis was not successful and stopped in 2002. Also the Phase II trial for the treatment of psoriasis did not show efficacy, which surprised us, as Biogen’s Amevive works by a similar mechanism as HuMax-CD4 by depleting T-cells. However, it is possible that Amevive also depletes a subset of T-cells (CD8 positive) which might be also important for efficacy of the drug. These cells are not depleted by HuMax-CD4. As the antibody clearly showed its efficacy in depleting CD4 positive cells in patients, Genmab started a Phase II open label trial for the treatment of cutaneous T-cell lymphoma (CTCL) at the beginning of 2003. CTCL is a blood cancer where T-cells bearing the CD4 molecule proliferate in an uncontrolled way. At the beginning the disease is “low malignant” and develops about 10-15 years with symptoms that resemble moderate-tosevere psoriasis, as the T-cells invade the skin and lead to chronic inflammation. After the low malignant phase, around 20% of these develop a high grade malignancy with worldwide about 10.000 patients being affected. Current treatment options are limited to photodynamic therapy for early stages of the disease. After that, only short lasting treatment options with severe side effects remain like methotrexate, interferon and the only approved drugs Ontak and Targretin (Ligand Pharmaceuticals). Although not approved for the indication, some physicians recommend the antibody Campath (Schering) which is targeting the CD-52 molecule on the surface of T-and B-cells. All these drugs, esp. Ligand’s, have severe side effects. On Feb 18th, 2004 Genmab presented promising results with 36 patients using the validated CA-score (Composite Assessment of Index lesion severity index) as an endpoint. The data for HuMax-CD4 presented showed a dose depending efficacy that was better than for Ontak and Targretin, however with less side-effects. Genmab is planning a pivotal Phase III trial in the indication with 50-80 patients to start in 2004. In case of a successful outcome of the trial, the antibody could get to the market as soon as 2006. HuMax-EGFR: This antibody targets the EGF-receptor (EGFR), that is overexpressed in many tumours. The EGFR is a clinically validated target, as the antibody Erbitux (Imclone) directed against it has been approved by the FDA for the treatment of colorectal cancer on Feb.13th, 2004. In addition, the small molecule Iressa (AstraZeneca) inhibiting EGFR has been approved by the FDA in lung cancer and further results of Phase III trials for Tarceva (Genentech) showing a similar efficacy are expected. Genmab initiated a clinical trial in patients suffering form head and neck Cancer in Q3 2003. Although the field of anti EGFR antibodies is highly competitive, as also Abgenix’ ABX-EGFR is in Phase II, it may turn out as an advantage, that HuMax-EGFR binds to EGFR with a higher affinity to the EGFR-receptor and may therefore be more efficient. HuMax-CD20: The antibody has been filed for IND in Q4 2003 for treatment of patients with Non-Hodgkin Lymphoma (NHL). The antibody targets the CD20 protein, that is present on the surface of malignant B-cells. The “Threrapeutic Gold Standard” is Genentech’s antibody Rituxan, that also targets CD20, which generated sales of USD 1.5bn in 2003. In 2003, Genmab presented promising preclinical data. HuMax-CD20 was able to deplete Bcells in primates much more efficiently than Rituxan. In addition, Gemab’s antibody is able to kill tumour cell lines that are resistant to Rituxan. This resistance is also seen in NHL patients as 50% do not respond to Rituxan. The resistance is likely due to an increased amount of complement cascade inactivating proteins CD59 and CD55 on the surface of the B-cells. The complement cascade is a process leading to the destruction of the cells which starts with the binding of an antibody. Genmab showed that HuMax-CD20 is a more potent activator of complement than Rituxan and could therefore work in NHL-patients that do not respond to Rituxan. To our knowledge, currently there is no other CD20 antibody in clinical development. Although the radioactively labeled antibodies BEXXAR (Corixa) and Zevalin (Biogen-Idec) are on the market to treat Rituxan refractory patients, they are more difficult to market than “naked” antibodies like Rituxan or eventually HuMax-CD20, due to the need of a special education for physicians dealing with radioactivity and the more complicated disposal of contaminated waste.