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 and systemic lupus erythematosus (SLE).  Our radiolabeled antibodies have an isotope attached to them, and are being tested in certain solid tumors.  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 four 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 and other B-cell mediated autoimmune diseases, as well as in children with acute lymphoblastic leukemia, and in non-Hodgkin’s lymphoma (NHL), which are types of blood cancer.  Our humanized CD20 antibody, veltuzumab, is currently in clinical trials for the therapy of non-Hodgkin’s lymphoma and immune thrombocytopenic purpura ITP, an autoimmune disease.  Phase I/II trials with our humanized CD74, milatuzumab, is currently enrolling patients with multiple myeloma.  For solid tumor therapy, we are advancing yttrium labeled PAM4 antibody for the treatment of patients with pancreatic cancer. 

We have licensed our lead product candidate, epratuzumab, to UCB, S.A. for the treatment of all autoimmune disease indications worldwide.  We have retained the rights for epratuzumab 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 disease indication, systemic lupus erythematosus, or SLE, UCB has recently announced that analyses of recently closed trials for epratuzumab in the treatment of SLE suggest a favorable efficacy and tolerability profile.  The US open-label extension study for those patients benefiting from treatment during the initial studies is still ongoing.  A Phase IIb dose ranging study with epratuzumab for SLE is scheduled to commence in the first quarter of 2008 with results anticipated in the first half of 2009.

In oncology, there are three studies that are ongoing with epratuzumab.  The first one is a Phase 2 trial sponsored by the North Central Cancer Treatment Group of the National Cancer Institute evaluating epratuzumab in combination with rituximab and CHOP chemotherapy for patients with previously untreated diffuse large B-cell lymphoma.  Preliminary results from this study have recently been published on-line in the journal Cancer.  The second study, led by the Children’s Oncology Group of the National Cancer Institute, is testing chemotherapy plus epratuzumab in children with relapsed acute lymphoblastic leukemia.  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.

A second naked humanized B-cell antibody, called veltuzumab, was constructed using the same human framework as our CD22 antibody.  Preclinical testing demonstrated this antibody is similar to rituximab’s affinity and mechanism of action, but we are observing potential potency differences pre-clinically and, most importantly, clinically, with our humanized CD20 antibody in patients with NHL. Specifically, we observe a shortened infusion time with less adverse events, and initial impressive efficacy results at low doses. We believe these are important points, which could potentially differentiate veltuzumab from rituximab.  Phase I/II clinical trials in the United States and Europe to evaluate various doses and dosing schedules in patients with NHL are completed.  We have observed activities at the low doses of 80 and 120 mg/m2. 

These effective doses are considerably lower than the approved 375 mg/m2 dose of rituximab.  A new study evaluating this antibody in ITP, an autoimmune disease indication has begun.  Simultaneously, we are developing a subcutaneous formulation which could be very attractive in the NHL and autoimmune disease setting.  Our initial studies in primates with our subcutaneous formulation have been completed, providing us with PK, immunogenicity and B-cell depletion data. We are evaluating the subcutaneous formulation in patients with NHL or CLL.

We are focused on a yttrium-labeled antibodies for solid tumor therapy.  PAM4, which reacts with about 85% of pancreatic cancers, has shown a high specificity for pancreatic cancer and minimal activity with normal tissues, including normal pancreas.  We have completed patient enrollment for our Phase I dose escalation clinical trials, which have shown early evidence of efficacy in patients who have failed prior therapy. Future plans include a Phase I/II dose escalation study using fractionated yttrium-labeled PAM4 in combination with gemcitabine, a drug approved for pancreatic cancer therapy and known to potentiate radiation.  In preclinical studies, survival curves in animals with transplanted human pancreatic cancer demonstrated that the combination of yttrium-90-labeled PAM4 antibody and radiosensitizing gemcitabine was superior to the yttrium-labeled PAM4 antibody by itself, and to the 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 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 profiles in patients with multiple myeloma.  Patients who have failed at least 2 prior therapies are being administered twice weekly for 4 weeks in a dose-escalating scheme to determine the maximum tolerated dose and assess initial efficacy.  Weill Cornell Medical is also conducting a Phase I study in patients with NHL or CLL, which is sponsored by the NCI.