Hammer Stock Blog

Regardless of IMGN901’s specific case, the impression I am getting from all the scientific material I come across that deals with Immunogen’s (IMGN) technology, is that IMGN901 will probably be the last ADC (antibody-drug conjugate) powered by the cleavable DM1 linker. There are currently no ADC programs, except from IMGN901, that utilize this specific linker. As I mentioned in one of my SGEN’s (SGEN) pieces, Genentech seems to prefer a noncleavable linker for the majority of its ADCs. Another example may be, Centocor, who licensed Immunogen’s technology for arming a antibodies targeted against alpha integrin and evaluated both DM1 and DM4 cleavable linkers with the same antibody. Results from several animal experiments showed that the cleavable DM4 version was much more stable in the bloodstream and active in inhibiting tumor growth than the cleavable DM1 version.

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There are currently 2 ongoing and one planned clinical trials for the evaluation of SGN-33.

The first clinical trial is the extension of the phase I trial, but this time all patients are to receive the highest dose tested in the original phase I (8mg/kg). The company expects to have data from this trial by the beginning of 2009. Typically, these types of trials should result in better performance than the first dose escalation trial, since the highest dose is expected to achieve better results than lower doses. In this case, since clinical activity in the highest dose and in the lower doses was similar, I wouldn’t expect to see a substantial improvement in the rate of CR in the ongoing trial. This can be explained by the fact that even lower doses ( 4 and 2.5 mg/kg) lead to the saturation of the vast majority of CD33 in the bone marrow, so any additional antibodies that enter the bone marrow has no targets left to bind. This is also why the dose was not escalated beyond 8 mg/kg even though there were no dose limiting toxicities.  

The second trial (and the more important one) is a randomized double-blind trial where SGN-33 is combined with low-dose araC, the standard therapy for older AML patients. Half of the patients are to receive araC+ placebo with the other half  receiving araC+ SGN33. This trial will hopefully shed some light on two crucial issues.

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Seattle Genetics (SGEN) recently published clinical data from a phase I which evaluated SGN-33 for the treatment of elderly AML (Acute Myelogenous Leukemia) patients. AML is a common type of blood cancer, with around 13,000 new cases and 9000 deaths expected to occur during 2007 in the US alone. Prognosis of the disease is very poor, especially among elderly patients (over 60 years old), who have a long term survival rate of 5%, compared to 20% in the case of patients who are under 60. The dismal prognosis elderly AML patients have can be attributed to their inability to tolerate aggressive chemotherapy or stem cell transplant. Moreover, AML among elderly patients is inherently more resistant to standard chemotherapy due to several factors. Therefore, there is a unique challenge in developing better treatments for elderly AML patients, because these treatments must be very safe in addition to being effective. Antibodies, as well as other targeted therapies are regarded as excellent candidates, as they have an excellent safety profile and can be usually co-administered with other treatments. The market opportunity for such treatments is substantial, due to the high incidence of AML among elderly patients, so naturally there are multiple treatments currently being evaluated. The majority of these treatments are chemo agents but there are several targeted therapies, the most promising of which is SGN-33.

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