Hammer Stock Blog

A lot of clinical data was published at the American Society of Hematology (ASH) meeting, some of it quite impressive. Naturally, established drugs such as Millennium Pharmaceuticals‘ (MLNM) Velcade, Genentech’s (DNA) Rituxan and Celgene’s (CELG) Revlimid got most of the attention. In my opinion, the real star of the conference is MT-103 which is being co-developed by Micromet (MITI) and MedImmune, the biologics division of AstraZeneca (AZN). I won’t go too deep into describing the mechanism of action and the platform based on which MT-103 is built (I intend to do that in a review I hope to publish next week). However, the clinical data presented by Micromet is so impressive and so groundbreaking from several perspectives, that it must not be ignored.

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CD70 program

CD70 is a receptor expressed on many types of blood cancers as well as the majority of renal cancer cases. The expression profile of this target is highly restricted to cancer cells, which, combined with its ability to internalize antibodies, makes it a desirable target for ADCs. Seattle Genetics is evaluating a naked antibody as well as an ADC that target CD70, both candidates are based on the same antibody, which was licensed from CLB-Research and Development. The naked antibody, SGN-70, is evaluated for certain blood cancers and is expected to enter phase I during 2008. Another possible use for SGN-70 is for autoimmune diseases, as it is expressed on white blood cells that are involved in the disease, but not on “resting” cells.

SGN-75 is an ADC based on SGN-70, which is currently evaluated pre-clinically for Renal cell carcinoma. This disease, although not as common as prostate and lung cancers, represents a large market opportunity with over 43,000 new cases and almost 13,000 deaths expected in 2007 in the US alone. Although surgical resection of the kidney has high chances to prevent the disease from spreading, nearly one third of patients are diagnosed at advanced stage, where the cancer has spread to additional organs. In addition, more than 30% of patients who undergo resection will eventually develop metastatic disease, for which very few therapeutic options exist. SGN-75 is expected to enter the clinic only in 2009.

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Seattle Genetics’ lead product is SGN-40, an antibody targeting CD40 which is a very common receptor expressed on various hematological malignancies such as non-Hodgkin lymphoma [NHL], chronic lymphoid leukemia [CLL] and Multiple myeloma [MM]. Surprisingly, CD40 is also expressed on solid tumors such as breast and ovarian cancers, which may broaden SGN-40’s spectrum of application. Although everybody is smiling at the moment, the company has undergone quite a rollercoaster with this candidate, lasting more than 8 years and involving 3 different names for the same antibody.

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Antibodies have been proven as excellent tools for specifically targeting cancer cells, however, the damage they inflict upon cancer cells is minimal, especially when compared with chemotherapy drugs. (more…)

Metaphorically, antibodies can be described as unarmed guided missiles, which have extraordinary precision and targeting abilities, but once they hit the target, they inflict minimal damage. Chemotherapy and radiotherapy can be described as artillery, very powerful, but unguided. In order to optimally use the two, the most logical step is arming those unarmed missiles with a variety of explosives. Using the same reasoning, there is a true need to develop anti-cancer therapies which have an antibody-like specificity as well as chemo/radio-therapy-like potency. Doing so enables us to take advantage of the selectivity of antibodies and the potent toxic activity of chemo/radio-therapy, thus creating superior cancer treatments. The antibody binds the target on the tumor, delivers its payload and kills the cell. Arming antibodies with effector molecules like chemotherapy agents and radio-isotopes results in a hybrid agent referred to as an Immunoconjugate. An antibody which is not conjugated to an effector is referred to as “naked” antibody.

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