Here are the latest clinical developments from the 49th Annual Meeting of the American Society of Hematology in Atlanta.

• Aldagen Inc., of Durham, N.C., said results demonstrating that the potent adult stem cell population isolated using the firm's ALDH cells can regenerate vascular function and repair liver damage in preclinical models. Researchers from the Robarts Research Institute, Washington University School of Medicine and the University of California Davis Medical Center presented results demonstrating that ALDH cells can initiate regeneration of functional blood vessels in a preclinical model of ischemic injury.

• Ariad Pharmaceuticals Inc., of Cambridge, Mass., presented positive data on its multitargeted kinase inhibitor, AP24534, showing efficacy and oral dosing flexibility in animal models of chronic myeloid leukemia (CML), including forms of CML caused by clinically relevant variants of the target protein, Bcr-Abl. AP24534 also demonstrated potent inhibition of selected additional kinase targets - the receptors for vascular endothelial growth factors, fibroblast growth factors and angiopoietin that control angiogenesis and Flt3 kinase that plays a role in acute myeloid leukemia. The company said the findings supported the broad potential of AP24534 not only in drug-resistant CML, but also in other hematological cancers, such as AML, and various solid tumors.

• Bayer Healthcare AG, of Leverkusen, Germany, and Johnson & Johnson Pharmaceutical Research & Development LLC, of New Brunswick, N.J., said Phase III clinical trial results underscored that rivaroxaban, the oral, once-daily, investigational anticoagulant, was significantly more effective than enoxaparin, the standard of care, in preventing venous thromboembolism in patients undergoing total hip or knee replacement surgery. Rivaroxaban-treated patients consistently experienced lower rates of VTE events compared to enoxaparin-treated patients across three large studies as well as demonstrating a similar rate of major bleeding events.

• Celgene International Sarl, of Boudry, Switzerland, said clinical data from two ongoing Revlimid (lenalidomide) studies in relapsed/refractory aggressive non-Hodgkins lymphoma showed activity in the initial analysis of the first 46 patients of a 200-patient Phase II multicenter, open-label clinical study, NHL-003. Described as encouraging, the results are consistent with those of the earlier NHL-002 trial. The company is a wholly owned subsidiary of Celgene Corp.

• Cell Therapeutics Inc., of Seattle, said preliminary data from a Phase II/III trial showed patients with aggressive non-Hodgkin's lymphoma who received pixantrone experienced less severe toxicities than those treated with standard doxorubicin-based therapy.

• ChemGenex Pharmaceuticals, of Melbourne, Australia, presented preclinical data characterizing the mechanism of action of omacetaxine mepesuccinate (formerly known as Ceflatonin). Study results demonstrated that omacetaxine, down-regulating the key protein Mcl-1, had a direct anticancer effect on leukemic stem cells that was not exhibited by the tyrosine kinase inhibitor imatinib. Omacetaxine reduced the number of leukemic stem cells in the bone marrow by more than 80 percent in an animal model of CML (mice with BCR-ABL-induced CML disease). In contrast, the tyrosine kinase inhibitor imatinib mesylate (Gleevec) did not reduce the number of leukemic stem cells in the bone marrow.

• CSL Behring, of Melbourne, Australia, reported the results of a preclinical study it said showed that it's feasible to genetically fuse Factor VIIa (FVIIa) to human albumin, in prolonging the half-life of while retaining its biologic activity. In the proof-of-principle study, rVIIa-FP was generated by genetic engineering, expressed in mammalian cell culture, purified and characterized. The rVIIa-FP displayed full biological activity and sixfold to ninefold extended half-life compared to either Novoseven, a recombinant FVIIa, or rVIIa control protein in a preclinical rat model. The pharmacological properties of the rVIIa-FP could facilitate a single dosing regimen of one injection per bleeding event for treatment of hemophilia inhibitor patients, the company said.

• CuraGen Corp., of Branford, Conn., and TopoTarget A/S, of Copenhagen, Denmark, reported updated trial results with intravenous belinostat for peripheral T-cell lymphomas, and said results have been submitted to the FDA as part of an end-of-Phase-II meeting in late November. CuraGen plans to submit a clinical trial protocol to the FDA under a special protocol assessment and expects to start a registrational trial for PTCL during the second half of 2008.

• Exelixis Inc., of South San Francisco, reported Phase I data from an ongoing trial of XL019 in patients with myelofibrosis, a myeloproliferative disorder. XL019 is an investigational small molecule that selectively inhibits the tyrosine kinase JAK2. Preliminary clinical activity observed in most subjects, including: reduction in spleen size of 33 percent to 100 percent in five of six patients evaluated; reduction in erythropoietin-independent colony formation of up to 39 percent and up to 100 percent in two patients; relief of constitutional symptoms, including pruritus, fatigue, back pain and abdominal fullness; and reduction in the number of cells with the JAK2 V617F mutation.

• F. Hoffmann-La Roche Ltd., of Basel, Switzerland, reported positive results from two Phase II trials tracking the outcome of patients with chronic lymphocytic leukaemia (CLL) who were treated with MabThera (rituximab). In one trial, 92 percent of patients with previously untreated CLL achieved a response to treatment when treated with MabThera in combination with chemotherapy. That improvement confirmed similar results from earlier studies. Further results from the second part of the study are expected in 2008. A second trial focused on patients with relapsed CLL and demonstrated a better response for patients treated with MabThera in combination with chemotherapy than with chemotherapy alone, 70 percent to 57 percent.

• Gloucester Pharmaceuticals Inc., of Cambridge, Mass., announced encouraging interim results from an investigator-sponsored Phase I/II dose-escalation study investigating the use of the company's lead product, romidepsin, in combination with bortezomib (Velcade) and dexamethasone for patients with relapsed/refractory multiple myeloma. An overall response rate of 80 percent was reported, with one complete response, six partial responses and one minor response. The most common adverse events reported included nausea, fatigue, constipation/diarrhea and neuropathy. The most common grade 3/4 event was thrombocytopenia. The Phase I dose-escalation portion of the trial has been completed and the maximum tolerated dose was determined to be 1.3 mg/m2 of bortezomib, 20 mg of dexamethasone and 10 mg/m2 of romidepsin. Additional patients are being accrued at the maximum tolerated dose to assess clinical activity.

• Incyte Corp., of Wilmington, Del., presented data from a Phase I/II trial of INCB18424, its orally available janus-associated kinase inhibitor, showing it provides rapid benefits for myelofibrosis patients. Data included results from 11 patients in the study, and demonstrated that mean reduction in spleen size reached 52 percent in the first month and 86 percent in the third. Six patients treated for longer than three months all achieved improvement as defined by the International Working Group. It also was well-tolerated and that no patients discontinued the study.

• MGI Pharma Inc., of Minneapolis, provided a summary of the Dacogen (decitabine) for injection presentations, including five oral presentations, 11 poster presentations, and four publications. A survival analysis of the five-day outpatient regimen of Dacogen in patients with myelodysplastic syndromes and preliminary results from a multicenter, Phase II study evaluating the five-day regimen of Dacogen in patients with de novo or secondary MDS were among the data presented, as were results from a Phase II trial evaluating Dacogen in older patients with acute myelogenous leukemia.

• Pharmion Corp., of Boulder, Colo., announced interim data from a Phase II clinical trial evaluating three alternative five-day dosing schedules for Vidaza (azacitidine for injection) that demonstrated safety and response profiles consistent with those achieved with the FDA-approved seven-day regimen, as reflected in rates of hematologic improvement and red blood cell (RBC) transfusion independence. The company said the data suggested that a five-day schedule is as effective as the currently approved seven-day schedule at achieving RBC transfusion independence and hematologic improvement in MDS patients.

• ProMetic Life Sciences Inc., of Montreal, said a Phase II trial of its investigational compound PBI-1402 induced a significant increase in red blood cell count and hemoglobin level in patients with chemotherapy-induced anemia. No significant adverse events were observed. PBI-1402 is a novel, orally active low molecular weight synthetic compound with erythropoiesis-stimulating activity via a mechanism of action distinct from erythropoietin.

• Sanofi-Aventis, of Paris, released a study showing that low-molecular weight heparin (LMWH) was associated with reduced hospital costs of venous thromboembolism (VTE) treatment compared with unfractioned heparin (UFH). The study shows that total hospital direct medical costs associated with the treatment were reduced $550 per patient. The analysis included 38,664 patient discharges, with 53 percent receiving LMWH and 47 percent receiving UFH. The average length of hospital stay for the UFH group was 1.1 days longer (5.7 days vs. 4.6) days. After adjustments for co-variates, the average total direct hospital costs were $3,618 for UFH and $3,068 for LMWH.

• S*BIO Pte Ltd., of Singapore, presented data on three compounds. It said SB1518, an ATP-competitive inhibitor of both JAK2 kinase, and its JAK2V617F mutant, demonstrated therapeutic potential for the treatment of myeloproliferative disorders caused by aberrant JAK2 signaling; SB939, a histone deacetylase HDAC inhibitor it said has improved metabolic, pharmacokinetic and pharmacological properties compared to other HDAC inhibitors; and SB1317, a potent inhibitor of FLT3 kinase and CDKs 1, 2 and 9, which it said demonstrated therapeutic potential for the treatment of hematological malignancies.

• ThromboGenics NV, of Leuven, Belgium, unveiled results of the first Phase I trial of TB-402, a recombinant human monoclonal antibody, which has shown a beneficial partial inhibition of the blood coagulation Factor VIII. The randomized, single-dose, placebo-controlled, dose-escalation trial in healthy male volunteers showed that TB-402 is both safe and well-tolerated and no serious adverse events were reported. In addition, there were no major bleeding complications, with the overall incidence being similar in both the TB-402 treated group and the patients who received placebo. The compound now will move into Phase II development.

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