Immunomedics has several potential therapeutic agents in clinical trials and in preclinical development for more than 90% of all human cancers and for autoimmune diseases.  Our product candidates involve humanized antibodies that we are developing in three different forms.  The naked antibody therapeutic program evaluates just the antibody by itself in certain blood cancers and autoimmune diseases, such as NHL, immune thrombocytopenic purpura (ITP) and systemic lupus erythematosus (SLE).  Our radiolabeled antibodies have an isotope attached to them, and are being tested in certain solid tumors and in NHL.  Finally, in preclinical development, we are testing our first antibody with a drug attached to it.

In order to effectively develop our extensive product pipeline, and address diseases with unmet medical needs, we have prioritized our clinical development efforts with the development of five product candidates for the therapy of cancer and autoimmune disease.  Three of these products are different naked humanized antibodies, which recognize antigens on B-cells, called CD22 and CD20, while CD74 is also present on a variety of hematological tumors and even on some solid cancers.  Epratuzumab (anti-CD22 antibody) is being evaluated in patients with lupus, as well as in children with acute lymphoblastic leukemia (ALL), and in non-Hodgkin’s lymphoma (NHL).  Our humanized anti-CD20 antibody, veltuzumab, is currently in clinical trials for the therapy of NHL, chronic lymphocytic leukemia (CLL), and immune thrombocytopenic purpura (ITP), an autoimmune disease.  Phase I/II trials with our humanized anti-CD74, milatuzumab, is currently enrolling patients with multiple myeloma.  New studies in patients with NHL/CLL are open to enrollment.  For solid tumor therapy, we are advancing our clinical trials with the yttrium-90-labeled PAM4 antibody for pancreatic cancer therapy and iodine-131 labeled labetuzumab for colorectal cancer with liver metastases.

We have licensed the subcutaneous formulation of veltuzumab to Nycomed for all non-cancer indications worldwide, with rheumatoid arthritis as the primary indication. We will continue to conduct the ongoing Phase I/II trial in patients with ITP and will be reimbursed by Nycomed for all such expenses.  The agreement also provides us with an option to co-promote veltuzumab for the ITP indication in the United States.  We retain the rights to veltuzumab in cancer indications.  Under the terms of the agreement, Nycomed will be responsible for all costs associated with current and future clinical development, manufacturing and commercialization of veltuzumab in subcutaneous formulation for all non-cancer indications.  Nycomed will purchase clinical trial materials from us at cost-plus and will source a third party contract manufacturing organization for commercial scale manufacturing of veltuzumab.

In oncology, we have completed a Phase II study of veltuzumab in patients with recurrent NHL and reported data at the 2008 annual meeting of ASCO.  Patients were infused once weekly for four consecutive weeks with 80, 120, 200, 375 or 750 mg/m2 of veltuzumab.  Of the 82 patients reported at the meeting, 73 had received at least one prior rituximab-containing regimen.  No rituximab resistant patients nor patients who had received radioimmunotherapy were enrolled into the study.  Updated results in 81 NHL patients showed an objective response rate of 41% for all patients and 44% for follicular NHL patients, across all dose levels.  More importantly, an impressive complete response rate of 21% for all NHL patients and 27% for follicular NHL patients across all dose levels was observed.  These responses have been found to be durable.  

Veltuzumab is currently being studied in two Phase I/II trials.  The first is for the treatment of ITP.  Approximately 60 adult patients with chronic ITP who failed at least one standard therapy will be given veltuzumab once every 2 weeks for a total of 2 infusions at one of 3 dose levels.  An early result was encouraging with the first patient having a complete response after a single intravenous infusion of 80 mg of veltuzumab.  This study has now been transitioned to the subcutaneous formulation.  The second study also involves the subcutaneous formulation and is in patients with NHL or CLL.  After receiving only a single subcutaneous injection of a low dose of 80 mg of veltuzumab, circulatory B-cell levels were reduced to less than 1% compared to baseline, indicating that veltuzumab, administered subcutaneously, is distributed in the body similar to the intravenous formulation and was well tolerated.  Approximately 72 adult patients with documented CD20-positive NHL or CLL are planned for this open-label, multicenter study.  We plan to submit preliminary results from these two studies to the 2008 annual meeting of the American Society of Hematology for presentation.

For epratuzumab, we granted UCB the exclusive worldwide rights to develop, market and sell epratuzumab for all autoimmune disease indications.  We have retained the rights in oncology indications for which UCB has been granted a buy-in option.  UCB has development, manufacture and commercialization rights, and is responsible for all clinical trials evaluating epratuzumab for the treatment of patients with moderate and severe lupus.  At present, there is no cure for lupus and no new lupus drug has been approved in the U.S. in the last 40 years.  The U.S. Food and Drug Administration (FDA) granted its Fast Track Product designation to epratuzumab for the treatment of patients with lupus.

For the first autoimmune indication, SLE, UCB recently reported at the annual European Congress of Rheumatology results from the ALLEVIATE trials, which showed that epratuzumab treatment demonstrated in 90 moderate and severe flaring SLE patients clinically meaningful improvements compared to placebo.  Both the 360 and 720 mg/m2 doses of epratuzumab resulted in reductions in disease activity as measured by the total BILAG scores and reduced steroid use.  Additionally, epratuzumab was shown to be well-tolerated with a similar safety profile as placebo.

UCB has initiated a new phase IIb clinical study program for epratuzumab.  The primary objective of this program is to assess the dose response and the dose frequency for epratuzumab.  The new randomized, double-blind, placebo controlled study is expected to enroll about 210 lupus patients with moderate or severe disease activity.  Primary endpoint is efficacy as measured by the responder rate according to a combined response indexed evaluated at week 12 incorporating BILAG assessment, SLEDAI, a physician’s global assessment and treatment failure.  UCB has stated that first results from this study are anticipated in the first half of 2009.

In oncology, epratuzumab is currently being investigated in three National Cancer Institute-sponsored clinical trials.  The North Cancer Center Treatment Group is evaluating, for the first time, the addition of epratuzumab to rituximab and chemotherapy to treat patients with newly diagnosed diffuse large B-cell lymphoma.  This study has completed enrolling all 86 patients.  The Children’s Oncology Group is testing epratuzumab in combination with standard chemotherapy in children with acute lymphoblastic leukemia.  Results from the feasibility phase of this study have shown that this regimen is safe and efficacious, and were published in the Journal of Clinical Oncology.   A third trial has recently been added and is sponsored by the Cancer and Leukemia Group B to study the combination of epratuzumab and rituximab in patients with previously untreated follicular non-Hodgkin’s lymphoma.

At the 2008 annual meeting of ASCO, the North Central Cancer Treatment Group reported interim results from their study combining epratuzumab with rituximab and CHOP for patients with previously untreated diffuse large B-cell lymphoma.  A total of 78 patients were eligible to participate in this open-label study which has a primary endpoint of event-free survival at 12 months.  At the time of reporting, 95% of patients responded to the treatment regimen, and 62% of patients had a complete response.  Event-free survival for the 34 interim analysis patients was 85%.  Final analysis on all patients is expected to be completed by the end of 2008. If the results remain promising, the group may launch a randomized phase III trial to definitely assess whether ER-CHOP is more effective than R-CHOP.

Our solid tumor therapeutic, humanized PAM4 antibody, reacts with about 85% of pancreatic cancers and has shown a high specificity for pancreatic cancer and minimal activity with normal tissue, including normal pancreas.   We have completed our Phase I single dose escalation clinical trials, which have shown early evidence of efficacy in patients who have failed prior therapy.  A new Phase Ib dose escalation study using fractionated yttrium-labeled PAM4 in combination with gemcitabine, a drug approved for pancreatic cancer therapy and known to potentiate radiation, has begun patient enrollment.  In preclinical studies, survival curves in animals with transplanted human pancreatic cancer demonstrate that the combination of yttrium-90-labeled PAM4 antibody and the radiosensitizing gemcitabine was superior to the yttrium-labeled PAM4 antibody by itself, or of gemcitabine alone.

CD74 is present on a variety of hematological tumors and even on some solid cancers, with restricted expression by normal tissues.  It is an attractive target for a drug conjugate because of its rapid internalizing property.  In preclinical studies, both naked milatuzumab antibody and milatuzumab conjugated with doxorubicin have demonstrated in-vivo anti-lymphoma activity.  The naked antibody is currently in Phase I/II clinical trials to evaluate safety and tolerability in patients with multiple myeloma, and has received orphan drug designation from the FDA for this indication.  Patients who have failed at least 2 prior therapies are being administered milatuzumab twice weekly for 4 weeks in a dose-escalating scheme to determine the maximum tolerated dose and assess initial efficacy.  Milatuzumab has also received orphan drug status for the treatment of CLL in the U.S.  Weill Cornell Medical Center is currently conducting a Phase I study in patients with NHL or CLL, which is sponsored by the NCI.  We have initiated our own study in patients with NHL or CLL using different doses and dosing schedules of milatuzumab.

Finally, German clinical investigators have been studying the safety and efficacy of 131I-labetuzumab (anti-CEACAM5 humanized antibody) in colorectal cancer patients given salvage resection of their liver metastases.  One Phase II trial has been completed and published in the Journal of Clinical Oncology, and a second article in Annals of Surgical Oncology.  A second Phase II trial is also being completed and the organization of a multicenter, randomized trial is in progress because of the encouraging single-center Phase II results indicating an improved survival of patients given post-operative 131I-labetuzumab.