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Vital Signs Edition #6


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Vital Signs Edition #6

  1. 1. ONCOLOGY<br />Week of May 1st, 2011<br />By Scott Jordan, Partner --  <br />News & Events: Cancer Stem Cells<br />News Summary<br />News & Events: Cancer Stem Cells (CSCs)<br />CSC’s are a subset of cells found in tumors that have the ability to self-renew and differentiate (similar to embryonic and adult stem cells in healthy tissue) leading to tumor initiation and growth, recurrence and metastasis. However, in contrast to normal stem cells, CSC’s have oncogenic mutations resulting in the loss of normal limitations on growth. These mutations enable CSC’s to be resistant to both standard chemotherapy and radiotherapy and have an ability to migrate from the original tumor site increasing the probability of tumor recurrence. Current treatments may initially decrease the size of a tumor but they often leave behind an increased proportion of the most malignant cells. <br />Maintenance and migration of cancer stem cells is supported by EMT or Epithelial-Mesenchymal Transition. EMT is a program development of biological cells characterized by loss of cell adhesion, repression of E-cadherin expression, and increased cell mobility (characteristic feature of cells undergoing proliferation). The presence of EMT markers at the tumor-host interface provides strong evidence that EMT occurs during tumor development and that it regulates invasiveness and tumor aggressiveness. <br />Of interest is the ability of stromal cells (oftentimes comprising up to 50-70% of tumor masses) to induce EMT in tumor cells by stimulating mesenchmal cell growth and survival. Tumor cells having acquired a more mesenchymal like phenotype, have shown increased invasion and metastasis, resistance to chemotherapy and radiation induced DNA damage, increased interaction with stromal inflammatory mechanisms, and increased cell survival.<br />Company Profile: Immunocellular Cellular Therapeutics Ltd. (OTC: IMUC.OB) <br />ImmunoCellular, a Los Angeles based biotechnology company, is attempting to harness the native immune system to attack CSCs without harming healthy tissue. ImmunoCellular’s lead compound, ICT-107 is in a double blinded, placebo controlled, 2:1 randomized Phase 2 designed to evaluate the safety and efficacy of ICT-107 in patients newly diagnosed with GBM (brain cancer). The study will enroll approximately 100 patients and will be conducted at an estimated 15 clinical trial centers in the U.S. in collaboration with leading experts and opinion leaders in neuro-oncology.<br />ICT-107 is an autologous, or personalized, dendritic cell-based vaccine that works by activating a patient’s immune system against specific tumor-associated antigens. This is accomplished by extracting dendritic cells from a patient, loading them with the antigens, and reintroducing them to the patient’s body to trigger an immune response.<br />ICT-107’s Value Proposition: <br /><ul><li>Compelling Phase I/II Study Results</li></ul>ICT-107 increased overall survival and decreased cancer recurrence in a Phase1/2 study (Data presented at American Academy of Neurology Annual Meeting – April 2011)<br />16 newly-diagnosed patients with GBM enrolled between May 2007 and November 2009, 11 (69%) are still alive after a median time of 30 months<br />Six (38%) continue to show no tumor progression for more than two years without disease progression<br />Overall two-year survival for patients treated with ICT-107 was 80%, compared to historical rates for overall survival on standard treatment of 26% in all GBM and 38% in GBM patients whose tumor is completely resected (Stupp et al, NEJM 2005) <br />Median overall survival has not yet been reached<br />Median Progression-Free Survival (PFS) for patients receiving the cancer vaccine was 16.9 months, comparing favorably with historical PFS of 6.9 months for patients receiving standard treatment, and two-year estimated PFS for vaccine-treated patients was 44%<br /><ul><li>Multiple Antigen vs. Single Antigen vs. Whole Cancer Vaccines</li></ul>Multiple Antigens/Cancer Stem Cells (CSCs): Immunocellular <br />ICT-107 targets multiple antigens (gp100, Trp-2, Her-2/neu, MAGE-1, AIM-2, IL-13aR2). ImmunoCellular selected epitopes that stimulate dominate T-Cells including Trp-2 (high CSC Expression) and IL-13Ra2 (high expression in bulk tumor cells).<br />Platform Strength: Reduced ability of cancer cells to mutate (dendritic cells sensitized with multiple antigens targeting both cancer stem cells and bulk tumor cells).<br />Single Antigen: Celldex<br />Celldex’s APC Targeting Technology™ uses human monoclonal antibodies (mAbs) to deliver a disease target or antigen directly to APC (antigen presenting cells). mAbs are specific for receptors located on the surface of these APCs which are known to be entry portals for antigen processing pathways.<br />Lead clinical development program, CDX-110, is an immunotherapy that targets the tumor specific molecule called EGFRvIII, a functional variant of the epidermal growth factor receptor (EGFR), a protein that has been well validated as a target for cancer therapy. <br />Potential Platform Vulnerability: Cancer cell mutation <br />Whole Tumor Vaccines: Northwest Biotherapeutics<br />The Company’s platform technology, DCVax®, uses a patient’s own dendritic cells. The dendritic cells are extracted from the body, loaded with tumor biomarkers or ‘‘antigens’’, thereby creating a personalized therapeutic vaccine. <br />The company’s lead product candidate is DCVax®-Brain which targets GBM. DCVax®-Brain has entered a Phase II FDA-allowed clinical trial.<br />Potential Platform Vulnerability: Antigens not optimized; not powerful enough to maintain tumor response<br />Cost of Goods Sold (COGS)<br />Immunocellular generates 20 doses from one outpatient apheresis procedure (reduced cost of goods in comparison to Dendreon’s PROVENGE®) and employs cryopreservation technology to preserve product for several years.<br />Dendreon’s PROVENGE® requires 3 doses given at approximately 2-week intervals by intravenous infusion; each dose of PROVENGE® is preceded by a standard leukapheresis procedure approximately 2 to 3 days prior to the infusion date.<br />News Summary Clinical & Regulatory:<br />Caris Life Sciences, Inc. presented clinical data that validated the potential diagnostic impact of new biomarker profiles in combating breast cancer. These findings further support the diagnostic value of personalizing cancer treatment based on a tumor's unique genetic make-up. The data was derived by profiling cancer patients through the Caris Target Now(TM) evidence-based molecular profiling service, which examines a patient's tumor and provides a customized tumor-specific biomarker analysis, which is then matched with treatment guidance published by the world's most respected cancer researchers. The study also showed that equivocal HER2 results either by IHC or FISH cannot be resolved by microarray analysis due to poor inter-assay agreement. HER2 over-expression occurs in approximately 15-20% of patients with breast cancer and is associated with aggressive disease and decreased survival. The Caris Target Now molecular profiling service matches information from the individual tumor's genetic profile with data included in the nearly 100,000 published clinical studies reviewed by Caris' evidence team. Caris Target Now then provides a simple report indicating which available chemo, biologic, and hormone therapies are most likely to be effective and those that are likely to be ineffective. Caris Target Now emerged last year as the world's most comprehensive and actionable tumor profiling service, with nearly 20,000 patients profiled to date.<br />Roche Holding AG announced topline results of first randomized trial of trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer. The Phase II trial, known as TDM4450g, compar trastuzumab emtansine (T-DM1) single agent to the combination of Hercep (trastuzumab) and chemotherapy (docetaxel) in previously untreated patients. The results showed that patients treated with trastuzumab emtansine (T-DM1) in this study lived significantly longer with their disease under control (PFS) and experienced fewer side effects typical of chemotherapy. Data from the TDM4450g study will be submitted for presentation at a future medical congress. An earlier analysis of this study presented at the 35th Congress of the European Society of Medical Oncology (ESMO) in 2010 showed encouraging results in tumour shrinkage (overall response rate ORR) in patients with a minimum of 4 months of follow-up. In addition, the study showed that trastuzumab emtansine (T-DM1) significantly reduced the burden of typical side effects associated with conventional chemotherapy.<br />Precision Therapeutics, Inc. announced that the launch of a new product line, BioSpeciFx(R), will help further the personalization of cancer treatments. BioSpeciFx(R) is composed of carefully selected sets of well validated and clinically useful biomarker tests that identify critical molecular targets within a patient's cell. By using the information generated by BioSpeciFx(R) in combination with Precision's sophisticated drug response marker ChemoFx(R), physicians may gain a more complete understanding of a patient's tumor. When combined, both products offer a complementary sum of information which will enable physicians to look at both the relevant molecular targets as well as the synergistic activity of drug combinations on the entire cell. BioSpeciFx(R) provides proteomic and genomic information, while ChemoFx(R) takes into account all of the functional characteristics of a tumor including those not captured by biomarker testing, providing both sensitivity and resistance information.<br />CEL-SCI Corp. has received approval to begin enrollment of patients in its Phase III clinical trial of Multikine(R) in India from the Directorate General of Health Services Office of Drug Controller General (India). The global Phase III trial for Multikine was started in the United States in late December 2010. CEL-SCI expects to commence the trial in other countries around the world within the next 30-60 days. Multikine is the Company's flagship immunotherapy developed as a first-line standard of care in the treatment of head and neck cancer. CEL-SCI's Phase III clinical trial is an open-label, randomized, controlled, multi-center study designed to determine if Multikine administered prior to current standard of care (surgery plus radiotherapy or surgery plus concurrent chemo radiotherapy) in previously untreated subjects with Advanced Primary Squamous Cell Carcinoma of the Oral Cavity/Soft Palate (Head and Neck cancer) will result in an increased overall rate of survival, versus the subjects treated with standard of care only. CEL-SCI's 880 patient Phase III trial is expected to be the largest clinical study of head and neck cancer ever conducted. It is also the first trial in which immunotherapy will be administered before any other traditional means of care are attempted. This is significant because conventional cancer therapy weakens the immune system and likely compromises the benefits of immunotherapy. Phase II clinical trials of Multikine demonstrated that the product was safe and well-tolerated and eliminated tumors in 12% of the subjects less than a month into treatment. The Multikine treatment regimen was also shown to kill, on average, about half of the cancer cells in the subjects' tumors before the start of standard therapy. Follow-up studies of subjects enrolled in Phase II trials showed a 33% improvement in the survival rate of those treated with Multikine at a median of three and a half years following surgery. The U.S. Food and Drug Administration granted orphan drug status to Multikine in the neoadjuvant therapy of patients with squamous cell carcinoma of the head and neck.<br />Marina Biotech, Inc. announced the initiation of patient dosing in the Dose Escalation Phase of its START-FAP (Safety and Tolerability of An RNAi Therapeutic in Familial Adenomatous Polyposis) clinical trial with CEQ508. Marina Biotech's Phase 1b/2a trial is an open-label, escalating-dose study of single daily doses of CEQ508 and will be conducted as a single center study in Boston, Massachusetts. The first cohort comprised of three patients will be administered the starting dose of 1x10(8) colony forming units (cfu)/day. The study is primarily designed to evaluate the safety and tolerability of CEQ508 in patients with Familial Adenomatous Polyposis (FAP) after 28 days of daily, oral dosing. The trial is also intended to provide data on beta-catenin biomarker changes pre- and post-treatment and pharmacokinetic data related to the gastrointestinal coverage of CEQ508. The Dose Escalation Phase consists of 12 patients in four dose escalating cohorts; two patients in the first dosing group have been enrolled.<br />Progen Pharmaceuticals Limited announced that the PG11047 Phase Ib 7 arm, 172 patient combination study has completed patient enrolment. This Study (number 47-01-002) is entitled 'A Phase I Open label, Multicentre, Dose Escalation Study to determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT), Safety and Pharmacokinetics of PG11047 when used in Individual Combinations with Gemcitabine or Docetaxel or Bevacizumab or Erlotinib or Cisplatin or 5- Flurouracil or Sunitinib in Patients with Advanced Solid Tumours or Lymphoma. This is a significant study with 172 patients enrolled across 12 US Oncology sites. The Primary Objective of this study was to determine the MTD and DLT of PG11047 when used in combination with other approved anti-cancer products and also to establish the recommended dose for future studies. The Secondary Objective of the study was to establish the pharmacokinetics of PG11047 when used in each of the combinations assessed and to observe patients for any evidence of anti-tumour activity. The patient data will now be analysed and a Clinical Study Report is expected in Third Quarter 2011. PG11047 is a novel, conformationally restricted analog of the natural polyamine, spermine that lowers cellular endogenous polyamine levels and competitively inhibits natural polyamine functions leading to cancer cell growth inhibition. The company has previously announced that it is planning to divest the cell proliferation and epigenetic assets including PG11047 as they are not part of its core program or focus.<br />AstraZeneca PLC announced that the U.S. Food and Drug Administration (FDA) approved the orphan drug vandetanib for the treatment of medullary thyroid cancer that cannot be removed by surgery or that has spread to other parts of the body. Vandetanib is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable (non-operable) locally advanced or metastatic disease. The use of vandetanib in patients with indolent, asymptomatic or slowly progressing disease should be carefully considered because of the treatment-related risks. Vandetanib is the only medicine to receive FDA approval specifically for use in patients with advanced medullary thyroid cancer and is the first treatment that AstraZeneca has developed and brought to market under orphan drug designation in the US. The approval of vandetanib is based on the results of the ZETA study, a Phase III, double-blind trial that randomized 331 patients with unresectable locally advanced or metastatic medullary thyroid cancer to vandetanib 300 mg (n=231) or placebo (n=100). In the study, patients randomized to vandetanib showed a statistically significant improvement in progression-free survival (PFS) when compared to those randomized to placebo (Hazard Ratio [HR]=0.35; 95% Confidence Interval [CI]=0.24-0.53; p<0.0001). This difference reflects a 65% reduction in risk for disease progression. Median progression-free survival was 16.4 months in the placebo arm and at least 22.6 months in the vandetanib arm. At the primary PFS analysis, no significant overall survival difference was noted. QT prolongation, Torsades de pointes, and sudden death are included in the boxed warning for vandetanib. The most common adverse drug reactions (>20%) seen in the ZETA trial with vandetanib were diarrhea (57%), rash (53%), acne (35%), nausea (33%), hypertension (33%), headache (26%), fatigue (24%), decreased appetite (21%), and abdominal pain (21%). A Risk Evaluation and Mitigation Strategy (REMS) is required for vandetanib due to the risks of QT prolongation, Torsades de pointes, and sudden death. Only prescribers and pharmacies who are certified through the vandetanib REMS program, a restricted distribution program, will be able to prescribe and dispense vandetanib. AstraZeneca will work to make vandetanib available to patients as soon as possible. Vandetanib will be dispensed exclusively through the pharmacy business unit of Biologics Inc., an integrated oncology management company.<br />Seattle Genetics Inc. announced that data from a case series of Hodgkin lymphoma patients receiving brentuximab vedotin (SGN-35) following allogeneic stem cell transplant were presented in an oral session at the European Group for Blood and Marrow Transplantation (EBMT) Annual Meeting in Paris, France. Brentuximab vedotin is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of Hodgkin lymphoma. This is the first report of data from brentuximab vedotin in Hodgkin lymphoma patients who relapsed following allogeneic transplant. Patients in the company's pivotal Hodgkin lymphoma trial had all relapsed following autologous transplant, but none had received an allogeneic transplant. Patients relapsing following allogeneic transplant represent a particularly difficult therapeutic challenge. Key findings from this case series of 25 post-allogeneic transplant patients include: -- 50% of patients achieved an objective response including 38% complete remissions; an additional 42% of patients had stable disease. <br />-- Median progression-free survival (PFS) was 34 weeks; median overall survival had not been reached. -- The median time to objective response was 8.1 weeks and patients received a median of 8 cycles of therapy; five patients remain on treatment. -- Brentuximab vedotin administration was associated with manageable adverse events, with the most common being cough, fatigue, fever, nausea and peripheral sensory neuropathy. -- The most common Grade 3 or higher adverse events were neutropenia, anemia, fatigue and fever. The case series comprises data from Hodgkin lymphoma patients who relapsed following allogeneic stem cell transplant that were enrolled in one of three multicenter, open label clinical trials of brentuximab vedotin. Patients received 1.2 or 1.8 milligrams per kilogram of brentuximab vedotin every three weeks. The median age of patients was 32 years. Enrolled patients had received a median of five prior therapeutic regimens, including 76% who had a prior autologous stem cell transplant.<br />Asuragen, Inc. announced the launch of Inform(TM)Thyroid, a panel of molecular markers used on Fine Needle Aspirates (FNA) of thyroid nodules to aid physicians in the management of thyroid cancer. The FNAs are analyzed in Asuragen's CAP accredited CLIA Laboratory.<br />Avila Therapeutics, Inc. announced that it has successfully completed two Phase 1a clinical studies for AVL-292, its orally-available, selective inhibitor of Bruton's tyrosine kinase (Btk). Avila presented summary results from the first-in-human study, AVL-292-001, at the Keystone Symposium on Molecular and Cellular Biology: Evolving Approaches to Early-Stage Drug Discovery. The study AVL-292-001 was a double-blind, placebo-controlled, single ascending dose study in healthy volunteers and in this study AVL-292 demonstrated favorable safety, tolerability, and pharmacokinetics. In addition, the trial used Avila's unique covalent probe technology to assess the quantitative relationship among dose level, systemic exposure and occupancy of the target by AVL- 292. This combination of analyses provides a powerful and rigorous understanding of AVL-292 action at the molecular level and serves as a rational guide to future clinical development. Clinical development of AVL-292 has been supported, in part, through an alliance with The Leukemia & Lymphoma Society (LLS). AVL-292 is a novel, orally available, covalent drug that targets Bruton's tyrosine kinase (Btk). Inhibition of Btk is a promising new approach to treatment of diseases that are driven by B cells, including certain cancers and autoimmune diseases. AVL-292 selectively and covalently binds to Btk to inactivate and silence its activity. This unique mechanism of action confers greater target selectivity and a longer duration of action than is typical of conventional small molecule drugs. In preclinical studies, AVL-292 selectively and potently inhibited Btk and B cell receptor signaling in vitro and was efficacious in a variety of animal disease models. AVL-292 is in clinical development and has successfully completed two Phase 1a clinical studies to date. AVL-292 achieved statistically significant levels of target occupancy at all dose levels, with >80% Btk target site occupancy achieved at doses as low as 1.0 mg/kg. AVL-292 was well-absorbed with good systemic exposure and demonstrated a dose-proportional pharmacokinetic profile across all dose levels (ranging from 0.5 to 7.0 mg/kg) with low inter-subject variability. AVL-292 was shown to be generally safe and well tolerated.<br />Progen Pharmaceuticals Limited announced that it had presented new preclinical data on its dual angiogenesis and heparanase inhibitor, PG545, at the American Association for Cancer Research meeting being held in Oriando, Florida. The meeting brings together almost 20,000 participants from around the world to discuss new and significant advances in the causes, diagnosis, treatment and prevention of cancer. The data presented shows that PG545 slows solid tumour growth and potently inhibits the development of spontaneous lung metastasis in a model of breast cancer. Moreover, blockade of metastasis is linked with significantly improved overall survival. PG545 is currently being evaluated in cancer patients in a Phase I clinical trial in Australia.<br />Axelar AB announced positive results from the completed first part of the combined phase I/II clinical trial, evaluating AXL1717 as a new treatment for solid tumors. The study has successfully reached its primary endpoint, identifying the recommended phase II dose as well as provided evidence that AXL1717 is safe and tolerable. Furthermore, data also supports the company's strategy to target AXL1717 in patients with squamous non-small cell lung cancer. Results will be presented later 2011. In the ongoing study, AXL1717 has been tested in total of more than 45 patients. The now completed first part of the study with a total of 35 patients, consisted of a single-day dosing as well as a multi dosing part. The study has been amended to a phase II design. AXL1717 is now tested for 28 days BID (twice daily dosing) in two cycles with 14 days interval in order to confirm the phase II regimens and explore the possible anti-tumor effects. A phase II program is expected to start late 2011.<br />Circadian Technologies Ltd. announced its anti-cancer therapeutic, VGX-100, significantly inhibits tumour growth and spread in a variety of different mouse models of human cancer including lung, ovarian and prostate cancer. Subject to the successful completion of the animal safety/toxicology studies, Circadian intends to file an Investigational New Drug application with the US Food And Drug Administration in the third quarter of 2011 in order to begin human clinical trials of VGX-100.<br />Semafore Pharmaceuticals, Inc. announced encouraging preclinical results for its lead product candidate, SF1126, in certain B-cell malignancies. The data demonstrated that the therapeutic effects of SF1126 are superior to a delta isoform-selective PI3K inhibitor (CAL-101) both alone and in combination with rituximab in two diffuse large B-cell lymphoma (DLBCL) cell lines. These data, generated through a collaboration with Dr. Daruka Mahadevan of Arizona Cancer Center, were presented during a late-breaking poster session at the 102nd Annual Meeting of the American Association for Cancer Research (AACR) in Orlando, Florida. SF1126 is a novel peptidic prodrug that converts to LY294002, one of the most widely studied small molecule inhibitors of multiple, cancer-specific kinase targets, including all Class I phosphatidylinositol 3-kinase (PI3K) isoforms, mammalian target of rapamycin (mTOR), Pim-1, DNA-activated protein kinase (DNA-PK), and polo-like kinase 1 (PLK1).<br />TapImmune, Inc. anticipates that an IND for the first Phase I study in program to develop a vaccine against HER-2/neu breast cancer will be filed soon. The technology entering the clinic targets a novel set of HER-2/neu antigens discovered in breast cancer patients with pre-existent immunity to these antigens (Clinical Cancer Research 16[3]:825-34, 2010). This technology complements TapImmune's TAP technology that the company envision as part of a final vaccine product. This technology is currently completing preclinical development. Currently, Herceptin(R) (trastuzumab: an intravenously delivered monoclonal antibody) is used in the treatment of HER-2/neu breast cancer. Ongoing collaborative research, on a new smallpox vaccine, will select the most potent peptide antigens against the smallpox virus for combination with its TAP technology. In preclinical studies (Plos Pathogens 1: 289-98, 2005) TAP technology improved the efficacy of a vaccinia virus vaccine by over a hundred fold. TapImmune believes that this approach provides the potential for development of a vaccine against smallpox that has broader application, is more cost effective and has a better shelf-life than existing viral-based products. TapImmune plans to evaluate its TAP technology for improving the efficacy of vaccines designed to combat a range of additional viral threats in the biodefense and infectious disease field. To expand its technology platform TapImmune also plans to enter additional technology collaborations for the development of DNA plasmid expression vectors that can deliver TAP genes into target cells.<br />Keryx Biopharmaceuticals Inc. announced that two posters on KRX-0401 (perifosine) were presented at the 102nd annual meeting of the American Association for Cancer Research currently ongoing at the Orange County Convention Center in Orlando, Florida. Perifosine, the company's novel, potentially first-in-class, oral anti-cancer agent that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway, is currently in Phase 3 clinical trials for refractory advanced colorectal cancer and multiple myeloma. Both of these Phase 3 programs are being conducted under Special Protocol Assessment (SPA) agreements with the FDA, and with Fast Track designations obtained for both indications. Perifosine is also in Phase 1 and 2 clinical development for several other tumor types. Perifosine showed single agent anti-proliferative activity in a variety of gastric cancer cell lines. In 8/13 cell lines resistant to 5-FU, perifosine showed a synergistic antiproliferative activity with 5-FU. In 72% of cell lines, high basal levels of pAkt were detected. Treatment with perifosine reduced tumor growth in nude mice inoculated subcutaneously with the YCC 2 gastric cancer cell line. Finally, an MTT based microarray analysis was performed to identify pharmacogenomic classifiers for synergy in 5-FU resistant cell lines. Perifosine demonstrated antitumor activity in several gastric cancer cell lines. Furthermore, perifosine enhanced the antitumor activity of 5-FU including 5-FU resistant cell lines. 5-FU is the active metabolite of the pro-drug Xeloda(TM) (capecitabine), which is approved for the treatment of metastatic colorectal cancer and breast cancer in the U.S., as well as advanced gastric cancer in certain countries outside of the U.S. Pro-apoptotic TRAIL receptors present on tumor cells are known to represent a potential pharmaceutical target for cancer treatment. Perifosine stimulated the expression of pro-apoptotic TRAIL receptors on the multiple myeloma KMS-11 cell line, substantially reduced the levels of phosphorylated Akt and significantly enhanced the sensitivity of these cells for trail induced apoptosis. The same molecular effects were noted in the non-Hodgkin lymphoma cell line SU-DHL-4V. In this TRAIL resistant cell line, perifosine treatment substantially enhanced the cytotoxicity of TRAIL treatment to similar levels observed in the TRAIL sensitive multiple myeloma cell line. The synergistic activity was confirmed in NOD/SCID mice xenograft models, where perifosine induced a down-modulation of Akt expression as well as TRAIL receptor upregulation in tumor cells and tumor endothelial cells.<br />Telik Inc. presented data at the 102nd American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida on a group of second generation analogs of ezatiostat, the most clinically advanced product in development at Telik. Ezatiostat is the first inhibitor of glutathione-S-transferase P1-1 (GST P-1), a validated enzyme target in Myelodysplastic Syndrome (MDS), to successfully complete a Phase 2 clinical trial. The efficacy and tolerability observed with ezatiostat in several Phase 1 and Phase 2 clinical trials supported the initiation of the analog program to identify potential follow-on drug candidates. The structure-activity relationships for the most compelling of these analogs are presented in the AACR poster, entitled Synthesis and Biochemical Characterization of Novel Analogs of Ezatiostat Hydrochloride (TELINTRA(R), TLK199) by Danying Cai et al. A series of diacid ezatiostat analogs bearing different substituents on the cysteinyl sulfur were synthesized using computer aided drug design and TRAP(R), a proprietary drug discovery technology, to improve the inhibitory potency and selectivity for the target enzyme GST P1-1. Substitutions resulted in a 30- to 130-fold improvement in vitro potency against GST P1-1 and 3- to 10-fold higher selectivity relative to other isoforms. Select ezatiostat analogs were evaluated for toxicity as well as for acceleration of recovery of neutrophil levels in a standard preclinical model of 5-fluorouracil chemotherapy-induced neutropenia. The compounds were well-tolerated when administered at doses up to 200 mg/kg and, like ezatiostat, led to a significantly accelerated recovery in the 5-FU-induced neutropenia model. Ezatiostat treatment has been shown to cause a clinically significant and sustained reduction in red-blood-cell transfusions, transfusion independence and multilineage hematologic improvement responses in patients with MDS.<br />Oncothyreon Inc. announced enrollment of the first patient in a Phase 2 trial of PX-866 in patients with glioblastoma multiforme that has recurred during or following primary therapy. PX-866 is a small molecule compound designed to inhibit the activity of phosphatidylinositol-3-kinase (PI-3K), a component of an important cell survival signaling pathway. The Phase 2 trial is being conducted at 7 Canadian centers by the NCIC Clinical Trials Group (NCIC CTG), Queen's University in Kingston, Canada. The trial will enroll up to 30 patients whose brain tumor is in first relapse during or following primary therapy. The primary endpoint of this single-arm screening trial is a combination of objective response rate and early progression. PX-866 is an inhibitor of the PI-3K/PTEN/AKT pathway, a critical cell signaling pathway that is activated in many types of human cancer. Aberrant activation and regulation of PI-3K is implicated in a large proportion of human cancers, where it leads to increased proliferation and inhibition of apoptosis (programmed cell death). Results from a single-agent Phase 1 open-label, dose escalation study of PX-866 in patients with advanced metastatic cancer presented at the American Society of Clinical Oncology earlier this year demonstrated that PX-866 was well tolerated using both an intermittent and continuous (daily) dosing schedule. Additional data from the Phase 1 trial presented at the EORTC/NCI/AACR meeting in Berlin on November 18, 2010 demonstrated that 8 of 19 evaluable patients treated with continuous dosing achieved stable disease as their best response.<br />Ariad Pharmaceuticals Inc. announced results of preclinical studies on ponatinib, its investigational pan-BCR-ABL inhibitor, showing potent inhibition of all four members of the fibroblast growth factor receptor (FGFR) family of tyrosine kinases that are abnormally expressed in multiple cancers. Recent research has established that FGF receptors 1 to 4 are activated through multiple mechanisms in certain solid tumors and represent promising targets for antitumor therapy. The new data on ponatinib demonstrate potent activity against a broad range of tumor cells activated by all four FGFRs, in vitro and in vivo. In a panel of 14 cell lines representing multiple different tumor types including endometrial, bladder, gastric, breast, lung and colon cancer, ponatinib potently and selectively inhibited FGFR-mediated signaling and cell growth. Four other tyrosine kinase inhibitors with FGFR inhibitory activity that are in clinical development were substantially less active, and none potently blocked all four FGF receptors. In mouse models of FGFR-driven tumors, daily oral dosing of ponatinib reduced tumor growth and inhibited signaling in all 3 FGFR-driven models examined. Ponatinib reduced tumor growth by 80% in mouse models of bladder and endometrial cancers and induced tumor regression in a model of gastric cancer. Potency was similar to that previously observed in BCR-ABL-driven models of chronic myeloid leukemia (CML). Importantly, the Phase 1 trial of ponatinib in CML shows that plasma concentrations of ponatinib required for inhibition of all four FGFRs can be sustained at well-tolerated doses in patients.<br />Exiqon A/S announced positive results in the company's development of a diagnostic test for early detection of colorectal cancer in blood. The results were revealed during an oral presentation at the annual American Association for Cancer Research (AACR) meeting in Florida, USA. In a multicenter study, Exiqon has demonstrated the ability of the company's proprietary miRCURY LNA(TM) Universal RT microRNA PCR platform to robustly detect miRNA biomarkers associated with the presence of colorectal cancer based on less than 0.2 ml blood. The objective for the first phase of the early detection of colorectal cancer program was to identify candidate miRNA biomarkers in plasma samples from stage II/III colorectal cancer patients and age- and gender-matched colonoscopy-verified healthy controls. A genome wide screen in blood plasma profiled 730 individual miRNAs from 50 stage II cancers and 50 matched controls. The results were used to develop a candidate panel of miRNAs detectable in less than 0.1 ml plasma. In the second phase of the program, the candidate panel of miRNAs was profiled in a study set of 227 stage II/III colorectal cancer patients and matched controls. The results demonstrated that using a simple miRNA signature derived from plasma obtained under standard clinical conditions it is possible to detect colorectal cancer. In the study, including samples from patients with proven colorectal cancer and matched healthy subjects from five Danish hospitals, the biomarker signature had a sensitivity and specificity for cancer of 75% and 80%, respectively, easily fulfilling the requirement for a commercial test. Exiqon has begun the next phase which includes final assay development and validation of the biomarker signature in a larger study cohort of more than 3,000 patient/control samples. Exiqon plans to publish the results of the validation study before year end.<br />Eli Lilly & Co. announced results from two preclinical studies of molecules that target genetic mutations and disable specific signaling pathways that can lead to cancer. The studies evaluated two unique molecules a JAK2 inhibitor and a Hedgehog inhibitor with results presented during the American Association for Cancer Research (AACR) 102nd Annual Meeting in Orlando, Fla. Signaling pathways within cells regulate genes that underlie crucial biological processes including cell division, embryonic development and immunity. When these networks of proteins misfire, many types of cancer can result. The company showed how these pipeline molecules target out-of-control signaling pathways. The company is focused on developing therapies tailored for an individual patient's needs such as a cancer treatment that targets a specific genetic mutation. New Small Molecule Therapeutics mini-symposium suggested that the investigational compound LY2784544, a small-molecule JAK2 inhibitor, blocks a specific, difficult-to-isolate, signaling pathway that can lead to the development of cancer cells. Specifically, company's researchers chose to study inflammatory breast cancer (IBC) cells because these cells support their own survival by secreting chemicals known as growth factors, which allow them to break away from the primary tumor, multiply and then cluster together into tumor spheres ultimately metastasizing, or spreading. The company scientists focused on a growth factor called IL-6, which latches onto receptors on the surface of cells and triggers the IL-6--JAK--STAT3 signaling pathway, promoting formation of the deadly IBC cell clusters by activating the STAT3 protein, which then turns on the genes that encourage IBC cells to stick together. Researchers hypothesized that short-circuiting the IL-6--JAK--STAT3 pathway could prevent the formation of tumor cell clusters. The scientists first cultured the tumor spheres in medium containing IL-6. As expected, IL-6 activated STAT3, the cells proliferated, and the tumor spheres grew. Furthermore, expression of IL-6 by the spheres themselves increased by 50-fold; and secretion of intracellularly produced IL-6 activated STAT3, and prevented cell death in the tumor spheres. But when company's JAK2 inhibitor was added to the medium containing the tumor spheres, the scientists found that it inhibited STAT3 activation in a dose-dependent manner and that blocking this signaling pathway induced cell death in the tumor spheres. The IL-6--JAK--STAT3 pathway may serve as a 'molecular signature' of IBC and as a potential therapeutic target. The company's JAK2 inhibitor is currently being evaluated in Phase I clinical trials for the treatment of myeloproliferative neoplasms, or diseases of the blood and bone marrow, called polycythemia vera, essential thrombocythemia and myelofibrosis. Scientists have identified an orally administered anti-cancer agent, LY2940680, which, in preclinical studies, disrupted the abnormal signaling of a key regulator of embryonic cell development. This novel molecule has been shown to affect a cancer cell signaling pathway initiated by the Hedgehog (Hh) protein, which is essential for regulating normal cell differentiation and proliferation. Abnormal Hh signaling has been implicated in several types of cancer, including brain, lung, breast, prostate and skin cancers. Abnormal Hh pathway activation can result from genetic mutations in the pathway's protein components. One such protein component, known as Smoothened (Smo), is a key regulator of the Hh signaling pathway and is seen as a potential target for therapies aimed at treating cancer by halting abnormal Hh signaling. Scientists have identified that company's Hedgehog inhibitor is a small molecule antagonist of Smo, binding to it and inhibiting Hh signaling in a human medulloblastoma tumor cell. (Medulloblastoma is the most commonly diagnosed form of brain tumor in children, but is rare in adults. In addition, when the compound was orally administered to transgenic mice that spontaneously develop medulloblastoma, it improved animal survival. The company's Hedgehog inhibitor is currently being studied in Phase I clinical trials for solid tumors.<br />OncoGenex Pharmaceuticals, Inc. announced that preclinical data utilizing their pipeline compound OGX-427 was presented at the AACR 102nd Annual Meeting 2011. The study demonstrated the ability of OGX-427 to inhibit Heat Shock Protein 27 (Hsp27), a cell-survival protein believed to play an important role in the proliferation of castrate resistant prostate cancer (CRPC) and resistance to standard therapies. Hsp27, expressed in prostate cancer and a variety of other malignancies, can be induced by cell stress such as chemotherapy, radiation therapy, and hormone therapy. Molecular chaperones that are heat shock proteins such as Hsp27 act to repair the damage of misfolding of cell structures that can occur when a cell is stressed, thereby enhancing the ability of cancer cells to survive. The goal of this study was to test the ability of OGX-427, a second-generation antisense therapy, and other mechanisms (siRNA and proteasome inhibition MG132) in silencing the effects of Hsp27. The study showed that OGX-427 inhibits Hsp27 and therefore a cell survival process called autophagy, to increase intracellular unfolded protein burden and cause prostate cancer cell death. These pre-clinical data further support the current OGX-427 development plan in prostate and bladder cancers: An Investigator-sponsored Phase 1 clinical trial evaluating OGX-427 administered directly into the bladder in patients with superficial bladder cancer, which was initiated in August 2009; An investigator-sponsored, randomized Phase 2 clinical trial evaluating OGX-427 when administered as monotherapy to patients with castrate-resistant prostate cancer. This trial will enroll approximately 72 patients and was initiated in September 2010; A planned Phase 2 clinical trial of OGX-427 in approximately 180 patients with metastatic bladder cancer, which is planned to initiate in the second half of 2011.<br />Aeterna Zentaris Inc. announced that two posters on its lead anticancer agent, perifosine, were presented at the 102nd annual meeting of the American Association for Cancer Research currently held at the Orange County Convention Center in Orlando, Florida. Poster #1965: Entitled, "Antitumor activity of novel Akt inhibitor, perifosine in gastric cell lines",Tae Soo Kim, Hyo Song Kim, Bo Ram Kwan, Chan Hee Park, Hei-Cheul Jeung, Woo Ick Jang, Juergen Engel, Hyun Cheol Chung, Jae Kyung Roh, Sun Young Rha. Results: Perifosine showed single agent anti-proliferative activity in a variety of gastric cancer cell lines. In 8/13 cell lines resistant to 5-FU, perifosine showed a synergistic antiproliferative activity with 5-FU. In 72% of cell lines, high basal levels of pAkt were detected. Treatment with perifosine reduced tumor growth in nude mice inoculated subcutaneously with the YCC 2 gastric cancer cell line. Finally, an MTT based microarray analysis was performed to identify pharmacogenomic classifiers for synergy in 5-FU resistant cell lines. Conclusions: Perifosine demonstrated antitumor activity in several gastric cancer cell lines. Furthermore, perifosine enhanced the antitumor activity of 5-FU in parts of the cell lines - including 5-FU resistant cell lines. 5-FU is the active metabolite of the prodrug Xeloda, which is approved for the treatment of advanced gastric cancer in many countries including Japan and Korea. Poster #640: Entitled "The Akt inhibitor Perifosine strongly enhances the antitumor and antivascular activity of CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)", Arianna Giacomini, Silvia L. Locatelli, Marco Righi, Loredana Cleris, Paolo D. Longoni, Marco Milanesi, Maura Francolini, Michele Magni, Massimo Di Nicola, Alessandro M. Gianni, Carmelo Carlo-Stella. Results: Pro-apoptotic TRAIL receptors present on tumor cells are known to represent a potential pharmaceutical target for cancer treatment. Perifosine stimulated the expression of pro-apoptotic TRAIL receptors on the multiple myeloma KMS-11 cell line, substantially reduced the levels of phosphorylated Akt and significantly enhanced the sensitivity of these cells for trail induced apoptosis. The same molecular effects were noted in the non-Hodgkin lymphoma cell line SU-DHL-4V. In this TRAIL resistant cell line, perifosine treatment substantially enhanced the cytotoxicity of TRAIL treatment to similar levels observed in the TRAIL sensitive multiple myeloma cell line. The synergistic activity was confirmed in NOD/SCID mice xenograft models, where perifosine induced a down-modulation of Akt expression as well as TRAIL receptor upregulation in tumor cells and tumor endothelial cells. Conclusion: Perifosine markedly enhanced the antitumor activity of the cellular TRAIL based treatment and was able to overcome TRAIL resistance both in vitro and in vivo. The results are in line with other studies demonstrating the synergistic effects of perifosine with cytotoxic drugs, including bortezomib and 5-FU.<br />Lorus Therapeutics Inc. announced the presentation of new data for its lead small molecule anti-cancer drug candidate LOR-253 at the 102nd Annual Meeting of the American Association for Cancer Research (AACR), taking place April 2-6, 2011 in Orlando, Florida. The presentation includes preclinical results on the anticancer efficacy of LOR-253 in human lung cancer, as well as an overview of the ongoing Phase I clinical trial for LOR-253 in advanced or metastatic solid tumors. In the presentation, LOR-253 was shown to be a potent inhibitor of growth of non-small cell lung cancer (NSCLC), both in vitro and in animal models of human NSCLC. Anticancer activity of LOR-253 in lung cancer models was related to expression of the tumor suppressor gene KLF4, which is a cell growth regulator that is either turned off or expressed at very low levels in many cancer types. LOR-253 was highly active against NSCLC cells with low KLF4 levels, while normal lung cells and lung cancer cells with higher levels of KLF4 were less sensitive to LOR-253. Anticancer efficacy of LOR-253 in NSCLC models was associated with induction of KLF4 in a dose-response manner. The results demonstrate that KLF4 is an important mediator of LOR-253 anticancer activity in NSCLC, and suggest that KLF4 may be an important biomarker for antitumor response to LOR-253 in this cancer type. In addition, an overview of the design of the Phase I clinical study of LOR-253 in advanced or metastatic solid tumors was presented. This Phase I study is an open-label, dose-escalation investigation to determine the maximum tolerated dose and recommended Phase II clinical dose of LOR-253. Additional trial objectives include the safety profile, pharmacokinetics and antitumor activity of LOR-253. The Phase I clinical study, which is being conducted at Memorial Sloan-Kettering Cancer Center in New York, is currently enrolling patients.<br />Threshold Pharmaceuticals Inc. announced multiple preclinical presentations on its clinical stage hypoxia-activated prodrug, TH-302, at the American Association for Cancer Research (AACR) Annual Meeting, being held April 2 to 6, 2011, in Orlando, FL. Abstract 535, J.D.Sun et al., entitled Hypoxia-dependent in vivo activity of the hypoxia-activated prodrug (HAP) TH-302, demonstrates that TH-302 targets the hypoxic compartment of preclinical tumors selectively in vivo. Abstract 5054, J.D.Sun et al., entitled Hypoxia-activated prodrug TH-302 enhances antitumor activity of antiangiogenics in preclinical models, provides a translational rationale for combining TH-302 with antiangiogenics to increase the treatment benefit in not only the approved indications (RCC, HCC, GIST) but also other indications, such as NSCLC. Abstract 2648, F.Meng et al., entitled Pharmacological modulation of TH-302-mediated in vitro cytotoxicity, demonstrates that TH-302 activity may be modulated by pharmacological modulators of both select reductases and DNA damage and repair pathways.<br />ProStrakan Group plc announced the availability of ABSTRAL(R) (fentanyl) sublingual tablets as the first rapidly-disintegrating tablet placed under the tongue for breakthrough cancer pain. The U.S. Food and Drug Administration (F.D.A.) approved ABSTRAL, an opioid analgesic, in January 2011 specifically for the management of breakthrough pain in cancer patients, 18 years of age or older, who are already receiving, and who are tolerant to, opioid therapy for their underlying persistent cancer pain. ABSTRAL is available only through an F.D. A mandated program, ABSTRAL REMS (Risk Evaluation and Mitigation Strategy). ABSTRAL is the only available analgesic that disintegrates quickly under the tongue. It offers an alternative therapeutic choice to patients and clinicians with a simple, patient-friendly and predictable way of delivering fentanyl transmucosally, while retaining the individualized dose titration aspects required for optimal treatment of breakthrough pain.<br />Curis Inc. announced the presentation of interim Phase II clinical data on Hedgehog pathway inhibitor vismodegib in patients with basal cell nevus syndrome (BCNS), which is also commonly referred to as Gorlin syndrome. This data was presented at the 102(nd) Annual Meeting of the American Association for Cancer Research being held in Orlando, Florida, April 2-6, 2011. This Phase II double blind, randomized placebo-controlled, two arm multicenter clinical study of vismodegib has enrolled forty-one BCNS patients from September 2009 to January 2011. It is designed to assess the safety and efficacy of 150 mg of daily oral vismodegib versus placebo. A Data Safety Monitoring Board (DSMB), tasked with reviewing the unblinded results from an interim analysis of 29 patients who completed an average of 6 months of drug treatment, recently recommended to end the placebo arm of the trial due to statistically significant differences between the two groups, in order for all of the patients enrolled in the trial to receive vismodegib treatment. The DSMB's analysis revealed that vismodegib reduced the rate of new BCCs from an average of 1.74 BCCs per month in the placebo group to 0.07 in the vismodegib group (p=<0.0001). Vismodegib also reduced the size of existing BCCs (-24cm vs. -3cm placebo, cumulative diameter, p=0.006). Some patients achieved near complete remission with no BCC developing resistance during this period of time on trial.<br />Immunogen Inc. announced the reporting of the first data on the company's IMGN853 product candidate for the treatment of ovarian cancer and other types of solid tumors. The presentations are being given at the 102(nd) Annual Meeting of the American Association for Cancer Research (AACR) in Orlando, FL. IMGN853 is designed to selectively target and kill cancer cells expressing folate receptor 1 (FOLR1). This target is over-expressed on most cases of ovarian cancer as well as on other carcinomas including types of non-small cell lung cancers. IMGN853 was found to be highly effective against human ovarian cancer tumors in preclinical testing. The AACR's 2011 Program Committee recognized the abstract on the IMGN853 in vivo preclinical findings as scoring among the top 2% of abstracts for poster presentations. IMGN853 is a TAP compound, which means it consists of a tumor-targeting antibody with one of ImmunoGen's highly potent cell-killing agents attached via an engineered linker. The antibody serves to target the TAP compound specifically to cancer cells, and the cell-killing agent serves to destroy these cells. The target for IMGN853 -- FOLR1 - is robustly expressed on most ovarian cancers as well as on certain non-small cell lung cancers and other carcinomas. This is based on target quantification methods developed by ImmunoGen scientists; the design of IMGN853 has been optimized for its target - both in its antibody component and in the novel linker used to attach the highly potent payload to the antibody and control its release inside a cancer cell; and the IMGN853 product candidate has been found to be highly active against human ovarian cancer tumors in preclinical testing.<br />Immunogen Inc. disclosed the profile and first preclinical data for the Company's novel IMGN529 product candidate for the treatment of B-cell malignancies including non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). This disclosure was made in conjunction with the 102(nd) Annual Meeting of the American Association for Cancer Research (AACR) taking place in Orlando, FL. IMGN529 consists of a CD37-targeting antibody that has notable anticancer activity with the Company's potent cancer-cell killing agent, DM1, attached using its SMCC linker.<br />Currently, NHL is widely treated with the antibody product, rituximab (Rituxan(R)). A therapeutic or "functional" antibody, rituximab has anticancer activity and a favorable tolerability profile. To achieve better activity, however, rituximab often is used in combination with chemotherapy agents, which increases efficacy but can reduce tolerability. This has led a number of companies to try to develop more effective antibody therapies for the treatment of NHL that target CD20, like rituximab. ImmunoGen scientists sought to identify an alternative target which is as widely expressed on malignant B cells as CD20 and offers other beneficial properties. One advantage of this approach is that it allows a resulting product candidate to potentially be used both instead of CD20-targeting therapies and with them. CD37 met these criteria; however, it was known to be difficult to develop humanized antibodies to this target that also have potent anticancer activity. Numerous antibodies were successfully created by ImmunoGen scientists. These were then screened on multiple criteria, including intrinsic anticancer activity, to select the antibody used in IMGN529. The scientists also evaluated alternative ImmunoGen linkers and cancer-cell killing agents to select the SMCC-DM1 combination. This combination is best known for its use in trastuzumab-DM1 (T-DM1), which also contains a functional antibody.<br />Oncothyreon Inc. announced the presentation of preclinical data for ONT-10, a therapeutic vaccine directed at cancers expressing MUC1, and PX-866, its irreversible inhibitor of phosphatidylinositol 3-kinase (PI3K), at the American Association of Cancer Research meeting in Orlando, Florida. ONT-10 is a therapeutic vaccine targeting MUC1 which has been designed to stimulate both the humoral and cellular arms of the immune response. Results presented at the meeting demonstrated that administration of ONT-10 produced a robust antibody response in mice that was specific for human tumor MUC1. A strong cellular immune response directed to the target was also shown. ONT-10 blocked the growth of two different tumors expressing human MUC1 in murine models, with a high proportion of animals tumor free at the conclusion of the experiment. Additionally, the adjuvant component of ONT-10, PET-Lipid A, a fully synthetic toll like receptor 4 (TLR4) agonist discovered by Oncothyreon, was shown to have enhanced potency compared to the adjuvant monophosphoryl lipid A (MPL). PX-866 is an oral, small molecule compound designed to inhibit the activity of PI3K, a component of an important cell survival signaling pathway. Data presented at the meeting concerned the efficacy of PX-866 alone or in combination with either docetaxel or cetuximab in direct patient human tumor xenograft models (DPTM) of squamous cell carcinoma of the head and neck (SCCHN) developed by Dr. Antonio Jimeno's laboratory at University of Colorado School of Medicine. These models maintain the histology of the tumor and are particularly suited to preclinical evaluation of novel cancer therapeutics. PX-866 was equal or superior to docetaxel in slowing tumor growth in two of four DPTM and equal or superior to cetuximab in each of four DPTM. The combination of PX-866 plus docetaxel was superior to single agent therapy in three of four DPTM, while the combination with cetuximab was superior to single agent therapy in two of four DPTM. The data were presented by Daniel W. Bowles, M.D., University of Colorado School of Medicine, Aurora, Colorado. ONT-10 is a therapeutic vaccine targeting MUC1, a tumor-associated antigen present on many types of human malignant tumors, including lung, breast, colorectal, prostate and ovarian cancer. ONT-10 contains a forty three amino acid antigen which is glycosylated; the attached sugars are expected to contribute to the stimulation of an immune response to the vaccine. The adjuvant in ONT-10 is PET Lipid A, a fully synthetic TLR4 agonist developed at Oncothyreon. Oncothyreon currently expects to file an Investigational New Drug application for ONT-10 in the third quarter of 2011 and to begin a Phase 1 clinical trial by late 2011. ONT-10 and PET Lipid A are fully owned by Oncothyreon. PX-866 is a pan inhibitor of the PI-3K/PTEN/AKT pathway, a critical cell signaling pathway that is activated in many types of human cancer. Aberrant activation and regulation of PI-3K is implicated in a large proportion of human cancers, where it leads to increased proliferation and inhibition of apoptosis (programmed cell death). Results from a single-agent Phase 1 open-label, dose escalation study of PX-866 in patients with advanced metastatic cancer demonstrated that PX-866 was well tolerated using both an intermittent and continuous (daily) dosing schedule. Additional data from the Phase 1 trial presented at the EORTC/NCI/AACR meeting in Berlin on November 18, 2010 demonstrated that 8 of 19 evaluable patients treated with continuous dosing achieved stable disease as their best response.<br />Cell Therapeutics, Inc. announced that the April 2011 edition of the peer reviewed journal, Leukemia & Lymphoma (April 2011; 52(4): 620--628) published results of a phase I/II clinical trial evaluating the effect of cyclophosphamide, pixantrone, vincristine, and prednisone ("CPOP") in treating patients with aggressive non-Hodgkin's lymphoma ("NHL") who relapsed following initial therapy with cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone ("CHOP"). In the CPOP regimen, pixantrone substitutes for doxorubicin (H) in the CHOP regimen. The study enrolled 35 patients in the phase I portion of the trial and 30 patients in the phase II portion of the trial. A major tumor response was reported for 80% and 73% of patients in phase I and II respectively, with 57% and 47% of the patients achieving a complete or unconfirmed CR. Median overall survival in the phase II portion of the trial was 17.9 months with four patients achieving notable long-term disease-free survival ranging from 55 to 77 months, despite in some cases having failed multiple prior regimens including stem cell transplantation. High response rates were also observed in the 43% of patients who had received prior rituximab as part of their front-line regimen (CHOP-R), with an ORR rate of 77% and CR rate of 54%. Myelosuppression was the most common toxicity. Side effects (grade 3/4) in phase I of the trial included febrile neutropenia (11%), grade 3/4 infections (3%), and cardiac failure (6%). In phase II of the trial, side effects (grade 3/4) included febrile neutropenia (20%), and cardiac failure (3%).<br />Corporate Finance:<br />ProMetic Life Sciences Inc. reported consolidated financial results for the year ended December 31, 2010. For the year, the company generated revenues of CAD 11.4 million compared to CAD 13.6 million for the year ended 31 December 2009. Delays in programs caused by both the regulatory process and strategic deals for two of major customers, Octapharma and Abraxis, impacted significantly on revenues in the second half. The company returned a net loss of CAD 11.3 million or CAD 0.03 per share (basic and diluted), as compared to a net loss of CAD 9.3 million or CAD 0.03 per share (basic and diluted) for year ended December 31, 2009. Analysing the increase in the annual loss of CAD 1.9 million from the previous year, CAD 1.3 million can be explained by the PRDT gain in 2009 not being repeated in 2010 and CAD 0.2 million associated with lower exchange gains in 2010.<br />Advaxis Inc. has filed a Shelf Registration in the amount of $3.45 million.<br />ImmunoCellular Therapeutics, Ltd. has filed a Shelf Registration in the amount of $18.09 million.<br />Mergers & Acquisitions:<br />SuperGen Inc. (NasdaqGS: SUPG) entered into a definitive agreement to acquire Astex Therapeutics Limited from Cambridge Enterprise Seed Funds, Apax Partners Worldwide LLP, Abingworth Bioventures III, Abingworth Bioventures II, Abingworth LLP and other shareholders in cash and stock on April 6, 2011. Pursuant to the terms of the agreements, SuperGen will pay to Astex shareholders $25 million in cash, plus shares in SuperGen common stock representing 35% of the total post closing shares outstanding. Subsequently, SuperGen plans to pay deferred consideration in the amount of $30 million, to be paid in stock or cash at the discretion of the combined entity, over a period of 30 months. The combined entity will assume all outstanding incentive stock options of Astex Therapeutics Limited. SuperGen must pay Astex a termination fee of $6 million.<br />The combined entity to be named Astex Pharmaceuticals, Inc. The combined companyis expected to be listed on NASDAQ under the symbol ASTX. Under the new management structure, James S.J. Manuso, Chairman, Chief Executive Officer of SuperGen Inc., would become Chairman and Chief Executive Officer of Astex Pharmaceuticals, Inc., and Harren Jhoti, Chief Executive Officer of Astex Therapeutics Limited, would become President and a member of the Board of Directors of the combined entity. The Board of Directors of the combined entity would also include Peter Fellner as Vice Chairman, Walter Lack, Charles Casamento, Thomas Girardi, Allan Goldberg, Tim Haines and Ismail Kola. The transaction is subject to various customary closing conditions, including the approval of the issuance of the new SuperGen shares by the stockholders of SuperGen, U.S. and U.K. regulatory review clearance and shareholder approvals of SuperGen Inc. and Astex Therapeutics Limited, the absence of any order or injunction of a court of competent jurisdiction that prohibits the consummation of the transaction, the absence of certain governmental restraints, and the performance in all material respects by each party of its obligations under the implementation agreement. The proposed transaction is expected to close in July 2011.<br />Concurrently with the execution of the implementation agreement, Astex entered into support agreements with each Director of SuperGen, pursuant to which each such person agreed to vote his shares of SuperGen common stock. Melanie Toyne Sewell of College Hill (Europe) and Rebecca Skye Dietrich of College Hill (US) acted as public relation advisors to Astex Therapeutics. Michael Ares of Fleishman-Hillard and Alan Roemer of The Trout Group acted as public relation advisors to SuperGen Inc. Marc Recht of Cooley LLP and Kevin Jones of Wragge & Co LLP acted as legal advisors to Astex Therapeutics. Page Mailliard of Wilson Sonsini Goodrich & Rosati acted as a legal advisor to SuperGen Inc.<br />Millennium Pharmaceuticals, Inc. acquired two oncolgy assets from Biogen Idec Inc. (NasdaqGS: BIIB) effective April 5, 2011. The two assets are pan-Raf kinase inhibitor and one additional undisclosed kinase inhibitor program in oncology. <br />Sanofi-Aventis (ENXTPA: SAN) made a bid to acquire Genzyme Corp. (NasdaqGS: GENZ) from SV Life Sciences Advisers LLP, Relational Investors LLC, Carl Icahn and other investors for $17.6 billion in cash on July 29, 2010. Under the terms of the deal, Genzyme shareholders would receive $69 per Genzyme share in cash. BNP Paribas and JP Morgan will provide financing for the deal. The deal is fully financed and is not subject to a financing contingency. Genzyme's management and employees would play a key role within Sanofi-Aventis following the acquisition.<br />On August 11, 2010, the Board of Genzyme rejected the offer. At a meeting of financial advisors of Sanofi-Aventis held on August 24, 2010, Genzyme's Board was still unwilling to have constructive discussions. Sanofi secured financing from BNP Paribas and Société Générale in France, as well as J.P. Morgan Europe in the form of a term loan of upto $15 billion. The transaction is expected to close on December 10, 2010. The deal will be accretive to Sanofi-Aventis.<br />As of October 4, 2010, Sanofi-Aventis commenced the tender offer and it will expire on December 10, 2010. The transaction has been approved by Sanofi's Board and subject to regulatory, antitrust and minimum tender condition. The deal is also subject to approval by Board of Genzyme.<br />On October 7, 2010, Genzyme Board determined that the offer is inadequate and that the offer is not in the best interests of the company. As of October 20, 2010, the deal has been approved by U.S. antitrust regulators. The waiting period under the Hart-Scott Rodino Act has expired. As of December 13, 2010, the offer has been extended till January 21, 2011. Till December 13, 2010, 2.2 million shares have been tendered representing 0.9% of the outstanding shares on a fully-diluted basis. The deal has been approved by the European Commission on January 12, 2011.<br />The expiration date of the offer is extended to February 15, 2011.<br />Sanofi-Aventis (ENXTPA: SAN) entered into a definitive agreement to acquire Genzyme Corp. (NasdaqGS: GENZ) from SV Life Sciences Advisers LLP, Relational Investors LLC, Carl Icahn and other investors for $21.5 billion in cash on February 16, 2011. Under the terms of the deal, each shareholder will receive $74 and per share in cash. In addition to the cash payment, each Genzyme shareholder will receive one contingent value right for each share they own, entitling the holder to receive additional cash payments if specified milestones related to Lemtrada™ (alemtuzumab MS) are achieved over time or a milestone related to production volumes in 2011 for Cerezyme® and Fabrazyme® is achieved. The transaction is subject to customary closing conditions, listing of shares and registration statement effectiveness. The expiration date of the offer is extended to March 16, 2011. The transaction has been unanimously approved by the Boards of Directors of Sanofi-Aventis and Genzyme. Genzyme Corp will have to pay $575 million in case of termination. The transaction is expected to close early in the second quarter of 2011. The acquisition is expected to be accretive to sanofi-aventis' business net earnings per share in the first year following closing, and accretive to business net earnings per share.<br />Board of Directors of Genzyme Corp. unanimously recommended to the shareholders of Genzyme Corp. to tender their shares into the revised tender offer on March 7, 2011. On March 29, 2011, registration statement relating to the contingent value rights offered to Genzyme shareholders is declared effective by the U.S. Securities and Exchange Commission. On April $, 2011, Sanofi-Aventis acquired approximately 84.6% of Genzyme’s outstanding shares of common stock and to allow remaining Genzyme shareholders the opportunity to tender their shares, a subsequent offer period has been extended till April 7, 2011.<br />Thierry Arachtingi, Nikolaï Eatwell, Evan Cohen, Brian Hoffmann, Cécile Bourdonnas, Dominic Nadeau, Aaron Charney and Daniel Winick of Clifford Chance acted as legal advisors to BNP Paribas, JP Morgan Europe and Société Générale. François Maisonrouge of Evercore Partners and J.P. Morgan acted as financial advisors to Sanofi-Aventis. Kathryn Merryfield, Benjamin Vicentini and Lauren Hanley of Linklaters and Claude Serra, Michael Aiello, Agathe Soilleux, Warren Buhle, Emmanuel Ringeval, Jaclyn Cohen, Campbell Austin, Peter Milligan, Zillah Whittaker, Helene Jaffe, Douglas Nave, Roman Ferla, Greg Danilow, John Neuwirth, Michael Epstein, Jackie Cohen, Megan Pendleton, Andrew Gaines, Eric Schecter, Sarah Dale, Jared Rusman, Stephane Chaouat and Chayim Neubort of Weil, Gotshal & Manges LLP acted as legal advisor to Sanofi-Aventis. Credit Suisse Securities (USA) LLC and The Goldman Sachs Group acted as financial advisors to Genzyme Corp. and Paul M. Kinsella of Ropes & Gray LLP acted as legal advisor to Genzyme Corp. Axel Malkomes of SG Corporate & Investment Banking acted as financial advisor for Sanofi-Aventis. Andrew Brownstein, Greg Ostling and Donald P. Casey of Wachtell Lipton Rosen & Katz acted as legal advisors for Genzyme Corp. Computershare Trust Company, NA acted as depository and MacKenzie Partners acted as information agent to Sanofi-Aventis. Morgan Stanley (NYSE: MS) acted as a financial advisor to Sanofi-Aventis. Innisfree M&A acted as information agent to Genzyme. Kekst and Company Inc. acted as public relations advisor to Genzyme. Casey Cogut, Eric Swedenburg, Jason Breen and Ariel Oxman of Simpson Thacher acted as legal advisors to JPMorgan and Evercore.<br />Sanofi-Aventis (ENXTPA: SAN) completed the acquisition of Genzyme Corp. (NasdaqGS: GENZ) from SV Life Sciences Advisers LLP, Relational Investors LLC, Carl Icahn and other investors on April 8, 2011.<br />Adventrx Pharmaceuticals, Inc. (AMEX: ANX) entered into a definitive agreement to acquire SynthRx, Inc. for $35.5 million in stock on February 12, 2011. Under the terms, Adventrx will issue 1 million shares of Adventrx’s common stock, of which 0.2 million shares shall be deposited in escrow. The escrow amount will be held in escrow for 12 months following the closing of the merger. An additional 1.94 million shares of Adventrx’s common stock will be issued, which subject to vesting shares are subject to various repurchase rights by Adventrx and fully vest, subject to reduction upon certain events, upon achievement of the first milestone. Up to 1 million shares of Adventrx’s common stock will be issued upon achievement of the first milestone. In the event the first milestone is achieved prior to the first anniversary of the closing of the merger, twenty percent (20%) of the first milestone payment shall be deposited in escrow. 3.8 million and 8.6 million shares of Adventrx’s common stock will be issued upon achievement of the second and third milestone respectively.<br />SynthRx stakeholders would be entitled to receive these additional shares of common stock upon successful achievement of development milestones consisting of dosing the first patient in a phase 3 clinical study, acceptance by the U.S. Food and Drug Administration (FDA) of a New Drug Application (NDA) and approval by the FDA of an NDA. If Adventrx's stockholders do not approve the issuance of the milestone-related shares as required by NYSE Amex listing standards, Adventrx expects to pay SynthRx's stakeholders in cash the value of the shares it otherwise would have issued, with the NDA acceptance and NDA approval milestone payments payable based on net sales of 188 and all milestone payments payable in quarterly installments. Upon closing, SynthRx would become a wholly-owned subsidiary of Adventrx.<br />The consummation of the merger is subject to certain customary conditions, including, the approval by SynthRx’s stockholders; delivery of audited financial statements of SynthRx for fiscal years 2009 and 2010; obtaining required governmental consents; and Adventrx having obtained a waiver of participation rights under that certain Rights Agreement, dated July 27, 2005. The merger will be terminated if it has not been consummated on or prior to May 2, 2011. Canaccord Genuity Inc. acted as financial advisor for Adventrx Pharmaceuticals. Don Markley of Lippert/Heilshorn & Associates, Inc. acted PR advisor to Adventrx.<br />Adventrx Pharmaceuticals, Inc. (AMEX: ANX) completed the acquisition of SynthRx, Inc. on April 8, 2011. Beal Advisors LLC acted as the financial advisor for Synthrx, Inc.<br />Morphotek, Inc. acquired tumor targeting assets from TransMolecular, Inc. on April 4, 2011. The financial terms of the deal were not disclosed. The consideration included upfront payment and also includes payment on future development milestones. The transaction provides Morphotek and Eisai exclusive ownership of tumor-targeting peptide for therapeutic and diagnostic uses.<br />Morphotek, Inc. completed the acquisition of tumor targeting assets from TransMolecular, Inc. on April 4, 2011.<br />News & Events:<br />TopoTarget A/S announced the establishment of the Global Oncology Advisory Board. The members of the board are: Professor Jean-Louis Misset- Professor of Oncology at the University and at the St. Louis Hospital Oncology Division in Paris, France; Dr. Matti Aapro- Dean of the Multidisciplinary Oncology Institute, Genolier, Switzerland; Professor James Cassidy- Professor of Oncology and Head of Academic Unit, University of Glasgow, Scotland; Assistant Professor Alain Catalin Mita- Assistant Professor of Medicine at the University of Texas Health Science Center San Antonio, Texas, US; Professor Hans-Joachim Schmoll- Professor of Internal Medicine and Director of the Department of Haematology and Oncology at the Martin Luther University, Halle-Wittenberg, Germany Dr. Daniel D. Von Hoff- Physician in Chief, Senior Investigator and Director of Clinical Translational Research Division at TGen (Translational Genomics Research Institute) in Phoenix, Arizona, US.<br />Bradmer Pharmaceuticals Inc. announced that its license agreement with Duke University has been terminated. Pursuant to the license agreement, Bradmer licensed certain patent rights relating to a drug, termed Neuradiab(R), for the treatment of glioblastoma multiforme, the most common and advanced form of primary brain cancer. Bradmer's Phase III clinical trial for Neuradiab was suspended in March 2009 and Bradmer has not pursued any activities relating to the clinical development of Neuradiab since that date. Bradmer is continuing to negotiate with P1 Energy Corp. the terms of a definitive agreement in respect of their previously announced business combination. Completion of the Transaction remains subject to a number of conditions.<br />Strategy & Strategic Alliances:<br />Dainippon Sumitomo Pharma Co. Ltd. and Boston Biomedical, Inc. announced that they have signed a Product Option License Agreement for BBI608 for all oncology indications in Japan and exclusive right of negotiation for BBI608 for the United States and Canada. BBI608 is an orally administered, first-in-class, small molecule anti-cancer drug that targets highly malignant cancer stem cells as well as other heterogeneous cancer cells. In clinical trials to date, BBI608 has shown excellent safety, favorable pharmacokinetics, and encouraging signs of anticancer activity. BBI608 is under phase I extension clinical studies in colorectal cancer and phase Ib/II trials in multiple solid tumor types. Under the terms of the agreement, BBI will receive $15 million of upfront payment and clinical trial support upon signing. Based on the outcome of the clinical trials, DSP has the option to acquire exclusive rights for the development and commercialization for BBI608 in Japan. In addition, DSP has an exclusive negotiation right for the United States and Canada for a certain time. During this option agreement period, DSP will pay a maximum of $55million for part of the development costs of BBI608 and for continuation of the option. Assuming DSP exercise the option for Japan, upon successful clinical development and commercialization of BBI608 in Japan, BBI could receive a maximum of approximately $100million in aggregate, including milestone payments associated with successful development and commercialization, in addition to running royalties. BI608 is a first-in-class, cancer stem cell inhibitor, currently in clinical development. Cancer stem cells (CSCs), being refractory to current cancer therapies, represent an emerging approach for designing the next generation of oncology therapeutics. CSCs are considered to be fundamentally responsible for malignant growth, metastasis, and recurrence. These cells are a subpopulation of cancer cells that have self-renewal ability and can differentiate into the heterogeneous cancer cells that comprise the bulk of the tumor mass. CSCs have been isolated from almost every major type of cancer, and have been found to be intrinsically resistant to current cancer therapies. Targeting CSCs, therefore, holds great promise for fundamentally advancing cancer treatment. BBI608, through its undisclosed molecular target, simultaneously inhibits multiple key cancer cell stemness pathways. BBI608 targets highly malignant CSCs as well as heterogeneous cancer cells. In clinical trials to date, BBI608 has shown excellent safety, favorable pharmacokinetics, and encouraging signs of anticancer activity against a broad range of tumor types. BBI608 is currently in phase I extension in colorectal cancer and phase Ib/II trials for combination therapy with paclitaxel for selected solid tumor types.<br />Roche Holding AG announced that the David H. Koch Institute for Integrative Cancer Research at MIT will be using the Roche LightCycler 480 System, a real-time polymerase chain reaction system for the analysis of gene expression and genetic variation, in advanced cancer research. The Koch Institute plans to use the LightCycler 480 System to support several key areas of research it has identified as being critical for rapid progress toward controlling cancer, such as exploring the molecular and cellular basis of metastasis and engineering the immune system to fight cancer.<br />BioWa, Inc. and Oxford BioTherapeutics Limited announced that they have entered into a license agreement to provide OBT with access to BioWa's patented POTELLIGENT(R) Technology platform for the development of antibody dependent cellular cytotoxicity (ADCC) enhanced antibodies. OBT intends to use POTELLIGENT(R) Technology to develop, manufacture and commercialize selected ADCC programs from its pipeline of preclinical antibodies for oncology which it has built based upon novel targets identified using its OGAP(R) proteomic database. In return for the license, OBT will pay to BioWa undisclosed license fees, development and commercialization milestones and royalties on sales of any products that it commercializes.<br />Myriad Genetics Inc. signed an agreement with BioMarin Pharmaceutical Inc. to conduct BRCA1 and BRCA2 mutation testing on patients to be enrolled in BioMarin's Phase I/II clinical study of BMN 673, a novel PARP-inhibitor drug candidate in patients with advanced or recurrent tumors. Under the agreement, Myriad will perform Comprehensive BRACAnalysis(R) with large rearrangement testing to identify the presence of germline mutations in the patients prior to enrolling in the study and provide standard test reports to the clinicians. This is the third agreement between Myriad and pharmaceutical companies developing PARP-inhibitors and is consistent with one of the Company's goals of becoming a leader in companion diagnostics.<br />ProMetic Life Sciences Inc. announced that it had entered into an agreement with Celgene Corporation for the worldwide rights to a commercial application of ProMetic's Protein Technologies. Under the terms of this agreement, Abraxis BioScience Inc. will forgive a $10 million long-term debt entered into with ProMetic on February 9, 2010, effectively terminating said loan agreement four years prior to its original term in return for intellectual property rights for specific commercial application of its Protein Technologies within restricted fields of use. This agreement is subject to certain conditions relating to the completion of relevant intellectual property transfer documentation.<br />AlCana Technologies, Inc, University Of British Columbia, and Alnylam Pharmaceuticals, Inc. announced that Alnylam has elected to extend the companies' RNAi therapeutics research collaboration for a third year. The research collaboration was initiated in August 2009 and focused on the discovery of novel cationic lipids employed in lipid nanoparticles for the systemic delivery of RNAi therapeutics. The research collaboration is funded by Alnylam and the work will be conducted by scientists at UBC and AlCana. Under the terms of the research agreement, Alnylam retains exclusive rights to all new inventions in the RNAi field as well as rights to sublicense any resulting intellectual property to Alnylam's current and future partners. As part of the original 2009 agreement, Tekmira Pharmaceuticals Corporation receives rights to use any new AlCana/UBC inventions for their own RNAi therapeutic programs licensed under Alnylam intellectual property through its InterfeRx(TM) program.<br />Definiens AG and Cernostics Inc. announced a partnership to develop a multiplexed assay tool for the diagnosis of cancer. Cernostics Inc. will apply Definiens AG' image analysis technology to develop new molecular diagnostic tests for the treatment of a variety of cancer types. Cernostics Inc. is using Definiens Tissue Studio to develop its cancer diagnostic test, which relies on highly multiplexed panels of fluorescence biomarkers, with the final goal to deploy the solution in the clinical routine. Definiens Tissue Studio enables pathologists to analyze cancers on the cellular and sub-cellular level. Rapid and accurate quantification of cancer characteristics will provide the Cernostics Inc. research team with data on which to build and deploy cancer diagnostic tests. The collaboration with Definiens AG will enable Cernostics Inc. to accelerate development of its pipeline of systems biology-based diagnostic, prognostic and predictive tests.<br />Caliper Life Sciences, Inc. announced that its Caliper Discovery Alliances and Services (CDAS) unit has formed a research collaboration with Catholic Health Initiatives (CHI). The health care system's Center for Translational Research (CTR), which is part of CHI's Institute for Research and Innovation, will work with Caliper to develop improved methods for evaluating and predicting the efficacy of new cancer drugs. Under this program, CTR will provide fresh human tumor samples to CDAS for CDAS to perform biomarker and standard-of-care drug resistance/sensitivity studies on these samples. CDAS will grow the CTR samples under various experimental conditions, including traditional two-dimensional cell culture, three-dimensional (3-D) in vitro culture, and in vivo culture in mice, and the CTR will supply key treatment history and diagnostic data for these tumor sources. The drug discovery industry demands better, more clinically relevant drug screening services utilizing cellular models that mimic the function of living tissues to reduce the drug candidate attrition rate between the stages of in vitro and in vivo experimentation. Optimized 3D cell assays or assays performed on human tumor cells maintained in a similar tumor microenvironment under the skin of mice, may provide valuable information to better predict drug efficacy in humans. CDAS provides oncology drug discovery assays based on a variety of biological output parameters such as proliferation, viability, apoptosis or specific biomarkers applied under conventional monolayer cell culture conditions. This new collaboration allows these testing methods to be extended to fresh tumor cells maintained under potentially more natural and disease-relevant conditions.<br />Eisai Co., Ltd. has entered into an option agreement with PRISM BioLab Co., Ltd. Under the terms of the agreement, PRISM shall grant Eisai the option to acquire the exclusive worldwide rights (excluding some countries) to develop and commercialize analogous compounds of the CBP/beta-catenin inhibitor and pharmaceutical products that contain analogous compounds as an active ingredient for the treatment of solid tumors and leukemia, with the right to sublicense. Simultaneously, Eisai has also entered into a license and collaborative research and development agreement with PRISM under which PRISM shall grant Eisai the exclusive worldwide rights (excluding some countries) to develop and commercialize CBP/beta-catenin inhibitor as well as pharmaceutical products that contain CBP/beta-catenin inhibitor as an active ingredient for the treatment of solid tumors and leukemia, with the right to sublicense.<br />Algeta ASA has entered research collaboration with Genzyme Corporation to evaluate the potential of its Thorium platform. Under the terms of the collaboration, Genzyme will provide access to a novel and proprietary tumor-targeting antibody and Algeta will provide access to its Thorium platform to attach the alpha emitting payload thorium-227. Both companies will contribute resources towards the collaboration, which is expected to last for up to a year initially. Thorium-227 is an element (radionuclide) that emits high-energy alpha particles. Such elements are of considerable interest in the treatment of cancer as they are potent at killing tumor cells and have a highly localized effect as a result of the very short range of the alpha particle (2-10 cell diameters). Thorium-227 is linked to tumor-targeting carrier molecules, such as monoclonal antibodies, to reach its target. By conjugating thorium-227 to a number of such molecules, each with a different tumor target, Algeta is exploring the potential to create a pipeline of new-generation alpha-pharmaceuticals to specifically seek and destroy cancers while minimizing damage to surrounding healthy tissues.<br />