Trial Information

A Phase Ib, Pharmacokinetic, Multiple Center, Open Label Study Evaluating the Safety and Efficacy of Mycograb Administered IV in Combination With Docetaxel in Metastatic or Recurrent Breast Cancer Patients

Combination therapies that incorporate new agents have demonstrated the potential to improve
outcome for patients with metastatic breast carcinoma. Docetaxel has been shown to be a
very active drug in breast cancer, and anthracycline-based chemotherapy combinations
represent the most active form of therapy generating objective response rates of between
40-70%. Mycograb® was most effective in breast carcinoma cell lines in combination with
cisplatin, docetaxel and anthracyclines (doxorubicin, daunorubicin).

We propose that Mycograb® binds to hsp90, inhibiting hsp90 chaperone functioning and
resulting in the destabilization of key proteins including estrogen/steroid receptors,
nitric oxide synthase, ras1, MAP (Mitogen-activated protein) kinase, Src,
Erb-B2,(erythroblastic leukemia viral oncogene homolog 2) HER(human estrogen receptor)
kinases and EGFR (epidermal grown factor receptor). Over expression of HER2 receptors are
observed in malignancies such as breast cancer and reportedly have been associated with
resistance to chemotherapeutic agents. Both maturing and fully mature forms of the receptor
depend on hsp90 association for stability. Inhibition of hsp90 function down regulates AKT
kinase and Src kinase which are non-receptor kinase. Therefore, Mycograb® may be of use in
estrogen dependent and hormone independent breast cancers.

Mycograb® has been demonstrated to have anti-tumor activity in cell culture. The 50%
cytotoxicity of Mycograb® on its own is 50 Combination therapies that incorporate new agents
have demonstrated the potential to improve outcome for patients with metastatic breast
carcinoma. Docetaxel has been shown to be a very active drug in breast cancer, and
anthracycline-based chemotherapy combinations represent the most active form of therapy
generating objective response rates of between 40-70%. Mycograb® was most effective in
breast carcinoma cell lines in combination with cisplatin, docetaxel and anthracyclines
(doxorubicin, daunorubicin).

We propose that Mycograb® binds to hsp90, inhibiting hsp90 chaperone functioning and
resulting in the destabilization of key proteins including estrogen/steroid receptors,
nitric oxide synthase, ras1, MAP kinase, Src, Erb-B2, HER kinases and EGFR. Overexpression
of HER2 receptors are observed in malignancies such as breast cancer and reportedly have
been associated with resistance to chemotherapeutic agents. Both maturing and fully mature
forms of the receptor depend on hsp90 association for stability. Inhibition of hsp90
function down regulates AKT kinase and Src kinase which are non-receptor kinase. Therefore,
Mycograb® may be of use in estrogen dependent and hormone independent breast cancers.

Mycograb® has been demonstrated to have anti-tumor activity in cell culture. The 50%
cytotoxicity of Mycograb® on its own is 50 µg/ml (MCF7 [Breast cancer cell line
designation]). Mycograb® in combination with docetaxel, doxorubicin and cisplatin and
Herceptin increased the cytotoxicity in breast cancer cells.

It is appropriate to evaluate the apparent tumor response and survivor benefits resulting
from the addition of Mycograb® to a docetaxel containing chemotherapy regimen in metastatic
or recurrent breast cancer patients.

(MCF7). Mycograb® in combination with docetaxel, doxorubicin and cisplatin and Herceptin
increased the cytotoxicity in breast cancer cells.

It is appropriate to evaluate the apparent tumor response and survivor benefits resulting
from the addition of Mycograb® to a docetaxel containing chemotherapy regimen in metastatic
or recurrent breast cancer patients.