From Xconomy Newsline...—Seattle Genetics. The Bothell, WA-based biotech company (NASDAQ: SGEN) said it plans to present data at the ASCO meeting from an early-stage clinical trial on how well its SGN-35 drug candidate (for lymphomas) performs when given on a weekly basis, instead of a less frequent schedule of once every three weeks. This drug—which combines the tumor-targeting capability of an antibody with a potent toxin designed to give it extra killing power—has already shown stellar results when it is given once every three weeks. The previous trial was in 44 patients with relapsed forms of Hodgkin’s disease and related lymphomas who got the drug in that less-frequent dose. It showed that 17 of the 44, or about 38 percent, had their tumors completely wiped out. The results with more frequent, weekly dosing are still quite preliminary, but they look even better. At the time the abstract was submitted, preliminary data showed that of the 15 patients taking low weekly doses, seven of them had a complete disappearance of their tumors, and one had more than 25 percent tumor shrinkage, Seattle Genetics said. Tumors stabilized in five patients, and just two had their disease spread or get worse. The drug was generally well-tolerated with the more intense weekly dosing, with some mild to moderate reports of rash, nausea, and nerve damage in the fingers and toes, the company said. More details will be presented at the conference on June 1............BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq: SGEN - News) announced today that data from a phase I clinical trial evaluating weekly dosing of SGN-35 will be reported during an oral presentation at the American Society of Clinical Oncology (ASCO) 2009 Annual Meeting being held May 29 to June 2, 2009 in Orlando, Florida. Related Quotes Symbol Price Change SGEN 9.14 -0.19 {"s" : "sgen","k" : "c10,l10,p20,t10","o" : "","j" : ""} The abstract, titled “Complete remissions with weekly dosing of SGN-35, a novel antibody-drug conjugate (ADC) targeting CD30, in a phase I dose-escalation study in patients with relapsed or refractory Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL)” (Abstract #8500), is available on the ASCO website at www.asco.org. Updated data, including tolerability and objective responses in additional patients treated with SGN-35, will be presented during a Clinical Science Symposium on Monday, June 1, 2009. At the time of abstract submission, preliminary data were available for 17 patients from this dose-escalation trial, including 13 with Hodgkin lymphoma and four with systemic anaplastic large cell lymphoma. SGN-35 dose levels ranged from 0.4 to 1.0 milligrams per kilogram. Out of 15 patients evaluable for response, seven achieved a complete response and one had a partial response. All of the complete responses were at the two highest dose levels. Stable disease was observed in five patients and two patients had progressive disease. SGN-35 was generally well-tolerated. The most common related adverse events were Grade 1 and 2 rash, nausea and peripheral neuropathy. Seattle Genetics is advancing SGN-35 in an ongoing pivotal trial for relapsed and refractory Hodgkin lymphoma and a planned phase II trial for systemic anaplastic large cell lymphoma. The pivotal trial is being conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). SGN-35 has also received Fast Track designation from the FDA for Hodgkin lymphoma. SGN-35 is an ADC comprising an anti-CD30 antibody attached by an enzyme cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE), using Seattle Genetics’ proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into CD30-expressing tumor cells, resulting in targeted cell-killing.....From Seeking Alpha...Seattle Genetics – Another step towards approval Seattle Genetics (SGEN) will present results from a phase I trial of SGN-35 in two rare blood cancers. This agent is important not only because it represents Seattle Genetics’ first opportunity for commercial revenue, but also because it serves as a proof of concept for the company’s antibody- drug conjugate (ADC) technology. The drug already generated impressive data when given every three weeks, and this year it will probably show even stronger activity in a weekly regimen. The company wanted to use a more frequent dosing in order to increase the overall amount of SGN-35 it can give and see whether it leads to higher efficacy without increasing side effects. At the time of abstract submission, the study still did not reach the maximum tolerated dose. Nevertheless, the weekly schedule led to a spectacular response rate in the two highest dose groups. Of the 8 evaluable patients in these groups, 7 (87.5%) achieved a complete response (CR). Although the sample size is too small for definitive conclusions, it seems that the weekly schedule is more potent in comparison to the every three weeks trial, where response rate in the three highest doses was 54%, including a 32% CR rate. At ASCO, Seattle Genetics will probably present a more mature data set that will include higher doses as well as a follow up on response duration. The company is enrolling a pivotal Phase II trial of SGN-35 in relapsed/refractory Hodgkin’s lymphoma. At the moment, the company uses the every three weeks schedule, but if updated results from the weekly trial are as promising as the abstract, Seattle Genetics could amend the schedule in order to achieve better efficacy. Given the pronounced efficacy SGN-35 had in two distinct trials, Seattle Genetics is now closer than ever to its first product launch, towards the end of 2011. A rich licensing deal is also likely by year end, although the company has set a fairly strict starting point for ongoing negotiations. Seattle Genetics’ shareholders can also be encouraged by the apparent superiority SGN-35 has over competing antibodies that also hit CD30. Both Medarex (MEDX) and Xencor are evaluating anti-CD30 antibodies (MDX-1401 and XmAb2513, respectively) in a similar patient population. These antibodies are not conventional antibodies, as both are members of a new class of modified antibodies called “non-fucosylated" antibodies. These antibodies lack a certain component on their surface and as a consequence are believed to be more efficient in recruiting the body’s immune system against cancer cells. Although results for the two antibodies, as well as SGN-35 are from distinct fairly small trials, SGN-35’s activity is far superior over Medarex’s and Xencor’s antibodies. This is another validation for Seattle Genetics’ ADC technology which proves once again that the strong potency observed is due to the drug payload conjugated to the antibody rather than the antibody itself. Next ASCO, there could be data for several other ADCs powered by Seattle Genetics, including agents under development by Genentech, Progenics (PGNX) and Takeda. Just two days after ASCO, Seattle Genetics will present results for another candidate, lintuzumab (SGN-33) at the EHA annual meeting in Berlin. In contrast to SGN-35, lintuzumab is a “naked” antibody which is not conjugated to a drug payload. Lintuzumab demonstrated remarkable activity as a single agent in elderly patient with a Acute myeloid leukemia (AML).It is being evaluated in an 80 patient phase I study as well as a larger registration trial with expected read out in the first half of next year. Preliminary results from the phase I trial back in December of 2007 were so impressive that the company decided to immediately launch a registration randomized study of lintuzumab in combination with standard chemotherapy. In parallel to the registration trial, Seattle Genetics decided to expand the phase I single agent study to validate the drug’s activity. At the EHA meeting, Seattle Genetics will provide a long anticipated update from this trial. As I discussed in a previous article, lintuzumab represents an immediate commercial opportunity of almost $1B with potential approval as early as next year. Seattle Genetics intends to license international rights for the drug, but the timing for such a deal is vague. The company could wait for results from the registration trial in order to get better deal terms , but it might choose to monetize the drug beforehand as a risk mitigation step. In this case, results from the phase I are crucial for securing a deal. It seems that results from the phase I study are positive, but less impressive than the preliminary results, so Seattle Genetics might choose not to partner lintuzumab until data from the registration trial is available. Another company which is expected to generate important news at the EHA meeting is Micromet (MITI) which will present results from two trials of its leading agent blinatumomab (MT-103). Based on preliminary data the company shared at its annual R&D day, the EHA meeting could position Micromet’s technology as one of the most promising platforms in the biotech industry. Hopefully, the results will also prove once and for all that Medimmune’s recent decision to opt out of the blinatumomab program was not data driven. Immunogen – High expectations Genentech/Roche (RHHBY.PK) will present data from a phase II evaluating T-DM1 in breast cancer. T-DM1 is an ADC version of the blockbuster breast cancer drug, Herceptin, powered by Immunogen’s (IMGN) ADC technology. Preliminary results from the study were presented 6 months ago and included strong clinical activity in patients who had progressed on Herceptin (second line patients). 60% of the patients in this trial had also progressed while on Tykerb (third line patients), which is approved for the treatment of Herceptin resistant patients. The confirmed objective response rate for the entire trial was 27%, however, this analysis included patients who did not have sufficient follow up to achieve a confirmed response. The confirmed response rate of 76 patients with longer term follow up, including those who discontinued treatment, was 38%, which is more in line with previous studies. At ASCO, Genentech will provide final response data for the entire trial (107 patients), which will probably be somewhere in the middle. T-DM1 is currently being evaluated in two registration studies: A phase II single arm study in patients who progressed on Herceptin and Tykerb (third line study)) and a phase III trial that compares T-DM1 to Tykerb+Xeloda in Herceptin resistant patients (second line study). The primary endpoint for the single arm third line study is response rate, whereas the primary endpoint for the second line study is progression free survival. As noted, the study to be presented at ASCO includes both second line and third line patients, so investors will try to get a sense with respect to T-DM1’s chances of succeeding in the two registration trials. Among the third line patients, investors will be looking at response rate, whereas among the second line patients, the important parameter will be progression free survival. Although the third line study has no predefined threshold for response rate, the bar is usually set at 25%, so anything above that value in third line patients will be considered positive. In the second line phase III, T-DM1 will be compared against an approved regimen, with an estimated PFS of approximately 6.5 months. Since larger, randomized studies usually result in lower efficacy, compared to single arm studies, T-DM1 will have to show a higher PFS in the second line subgroup in order to be considered as a worthy opponent for Tykerb+Xeloda. Therefore, anything above 8.5 months should be seen as a good indication. Needless to say, there is no guarantee that the results at ASCO will be reproduced in the registration studies, but hopefully, they will give investors a sense regarding the likelihood of seeing T-DM1 approved in the future. Another study that might indirectly affect Immunogen is a phase III trial of Herceptin in gastric cancer. As previously discussed here, if Herceptin is approved for gastric cancer, it could open an entirely new market for T-DM1 as well. Additional agents Exelixis (EXEL) and its new partner, BMS (BMY), are expected to present very strong data of XL184 in brain cancer. If actual activity is as strong as described in the abstract, this agent could find itself in a pivotal trial already this year. Exelixis will also present data for two early stage compounds XL147 and XL765. The abstracts for the two drugs include only minor signs of activity such as prolonged disease stabilization, however, based on management remarks, actual results at ASCO might include stronger efficacy data. Exelixis is in advanced stage discussions to out license the drugs to a large pharmaceutical company, and according to the company’s recent earnings call, a deal is expected to be finalized in the coming weeks. Arqule will present updated results for its MET inhibitor as a single agent in a group of rare cancers called MiT tumors as well as a combination trial with Tarceva in NSCLC. Roche will present results from a phase I trial of PLX4032, a RAF inhibitor it licensed from Plexxikon. The trial is intriguing because it shows a strong correlation between prolonged tumor shrinkage and a specific mutation in melanoma patients. According to Roche, the drug could enter registration trials for melanoma patients with the specific mutation already this year. Other interesting agents are OSI Pharmaceuticals’ (OSIP) OSI-906 with single agent activity in a phase I trial and Infinity (INFI) Pharmaceuticals’ IPI-504 which showed impressive preliminary results in advanced stage NSCLC patients. Portfolio updates We are adding another position in Curagen (CRGN) ahead of ASCO due to the initial signs of activity and the huge commercial potential of CR011. With a market cap of $61 million, the market assigns little to no value to CR011, but if the ASCO presentation shows additional signs of activity, this could change instantly.

—Seattle-based Trubion Pharmaceuticals (NASDAQ: TRBN) reported that it plans to give a presentation on a clinical trial of its experimental cancer drug, TRU-016, at ASCO.........Evaluation of the effect of TRU-016, an anti-CD37 directed SMIP in combination with other therapeutic drugs in models of non-Hodgkin's lymphoma. Sub-category: Lymphoma Category: Lymphoma and Plasma Cell Disorders Meeting: 2009 ASCO Annual Meeting Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 8571) Abstract No: 8571 Attend this session at the ASCO Annual Meeting! Session: Lymphoma and Plasma Cell Disorders Type: General Poster Session Time: Saturday May 30, 8:00 AM to 12:00 PM Location: Level 2, West Hall C Personalize your Annual Meeting experience with a suggested or customized itinerary! Author(s): P. R. Baum, C. Cerveny, B. Gordon, C. Nilsson, J. Wiens, S. Rafiq, R. Lapalombella, N. Muthusamy, J. C. Byrd, A. Wahl; Trubion Pharmaceuticals Inc, Seattle, WA; The Ohio State University, Columbus, OH Abstract: Background: TRU-016, a single chain anti-CD37 Fc fusion molecule has been shown to display pro-apoptotic and Fc-dependent cellular cytotoxicity activities against primary CLL cells and NHL cell lines. The pro-apoptotic signal generated by TRU-016 binding to CD37 on CLL cells has been shown to be caspase-independent and distinct from the signal generated by many other therapeutics including rituximab. We have tested drug combinations using the mantle cell lymphoma line Rec-1 and diffuse large B-cell lymphoma line SU-DHL-6 in vitro and extended these results to in vivo settings using the follicular lymphoma cell line DOHH2 treated with the combination of TRU-016 and bendamustine. Methods: To determine TRU-016 interactions with the established therapeutics rituximab, doxorubicin, rapamycin, and bendamustine, drugs were tested alone or in combination with TRU-016 and the anti-proliferative effects on cell lines measured after 96 hours. Combination index analysis was performed for drug combinations over the 20-90% effect levels using the Calcusyn software package. To determine if in vitro synergy could be recapitulated in vivo, SCID mice were implanted with DOHH2 cells and therapeutic treatment was initiated when tumor volumes reached 200 mm3. Treatments consisted of TRU-016, bendamustine, or the combination of TRU-016 and bendamustine. Results: Combination index analyses determined that TRU-016 is synergistic with rituximab, bendamustine, or rapamycin and additive with doxorubicin in NHL models. In vivo results show that treatment with the combination of TRU-016 and bendamustine resulted in increased efficacy compared to the efficacy attained with the individual drugs. This demonstrates that the in vitro synergy results were extendable to a more complex in vivo disease model. Conclusions: TRU-016 in combination with rituximab, rapamycin, or bendamustine increases cell killing of NHL cells. Furthermore, the combination of TRU-016 and bendamustine displayed greater in vivo anti-tumor activity than either agent alone against a follicular lymphoma tumor model. The drug is made through Trubion’s technology for targeting cells like an antibody, but using a smaller, lighter molecule that is supposed to be better at penetrating bulky tissues than larger antibody drugs. This trial looked at 10 patients with chronic lymphocytic leukemia who took an escalating series of doses of TRU-016. Researchers reported patients had decreasing counts of cancer cells in the blood after taking the drug, and it reduced their lymph nodes and spleen size. There were no serious adverse events, the company said. “The data to be presented at ASCO expands our pre-clinical experience and reinforces our belief that TRU-016 has the potential to improve treatment options for patients with B-cell malignancies like chronic lymphocytic leukemia and non-Hodgkin’s lymphoma,” said Peter Thompson, Trubion’s CEO, in a statement.

—Seattle-based ZymoGenetics (NASDAQ: ZGEN) will present detailed results at ASCO on a mid-stage clinical trial of its experimental drug, IL-21, in combination with Bayer and Onyx Pharmaceuticals’ sorafenib (Nexavar). ZymoGenetics is hopeful that its drug, which is supposed to stimulate T cells and Natural Killer cells of the immune system to fight tumors, will add to the effect of sorafenib, which is made to cut off blood supply to tumors, and block pathways that allow those cells to proliferate. The study, according to the abstract, enrolled 33 patients in the U.S. and Canada who failed to respond to one or two prior rounds of therapy for kidney cancer that has spread through the body. Six of the 23 evaluable patients (26 percent) had at least partial tumor shrinkage. Six patients dropped out of the study because of drug toxicity, and the regimen is clearly a rough one. One-third of patients reported moderate to severe side effects, including low phosphate levels, rash, and deficiencies of white blood cells and platelets in the blood. Researchers termed the safety profile “acceptable.” “We see encouraging anti-tumor activity with IL-21 combined with Nexavar,” said Nicole Onetto, ZymoGenetics’ chief medical officer, in a statement. “We believe the combination of IL-21 and Nexavar could be more effective than Nexavar alone.” ZymoGenetics is looking to out-license this drug, because it is getting out of cancer research as part of the sweeping cost cuts it announced a couple weeks ago.

—OncoGenex Pharmaceuticals, a Bothell, WA-based developer of cancer drugs, will finally relieve the suspense about its prostate cancer drug at the ASCO meeting. The company (NASDAQ: OGXI) made waves back in December when it reported results from a clinical trial of 82 men. The trial suggested the OncoGenex drug, OGX-011, had an unprecedented ability to help men live longer with the disease, a median time of 27.5 months on the company’s experimental drug in combination with a chemo treatment and immune suppressor, compared with 16.9 months for those on the latter two treatments alone. But skeptics now have some ammunition to shoot holes in this result. The company never disclosed in its press release back in December whether the survival finding reached the FDA’s threshold to show it was statistically significant, and therefore unlikely to be due to chance. That threshold is a p-value of 0.05 or lower. The OGX-011 study, as you can see in this abstract, had a p-value higher than that, 0.07. OncoGenex is hoping that investors and partners won’t be scared away by that uncertainty, pointing out that the study’s primary goal wasn’t to show improved survival times, and it is extremely difficult, in a mathematical sense, to achieve statistical significance in a small study of 82 patients, said Jason Spark, a spokesman for the company. Plus, this isn’t the final word on the study, because the abstract uses relatively old data from November, while the formal presentation at ASCO will provide more follow-up data needed for the final analysis—which may produce a different p-value, Spark says. The drug is interesting to scientists because it uses “antisense” technology, essentially designed to serve like a genetic mirror image that shuts down the production of clusterin, a protein associated with helping tumors resist chemotherapy. The original work was done by Martin Gleave, a urologist at the Prostate Centre Vancouver General Hospital. OncoGenex hopes the ASCO presentation will generate enough interest from potential partners, and investors, to raise enough money to complete a pair of pivotal clinical trials, with more than 700 men, which it will need to win FDA approval of the product.......BOTHELL, WA and VANCOUVER, May 27 /PRNewswire-FirstCall/ - OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today that the Company will hold a live webcast and conference call of presentations made at an OncoGenex hosted reception during the 2009 American Society of Clinical Oncology Annual Meeting (ASCO) on Saturday, May 30, 2009. The webcast will begin at 7:10 p.m. EDT. During the reception, OncoGenex management and guest speakers will provide a comprehensive review of the final results of a randomized Phase 2 trial presented during an oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting, as well as discuss the treatment landscape and the relevance of clinical trial endpoints for prostate cancer. Guest speakers include: Dr. Kim Chi, OGX-011 Principal Investigator, BC Cancer Agency Dr. Oliver Sartor, Medical Oncologist, Tulane Medical School Dr. Tomasz Beer, Medical Oncologist, Oregon Health & Science University Dr. Brent Blumenstein, Independent Statistician, Trial Architecture Consulting Dr. Martin Gleave, Distinguished Professor, Department of Urologic Sciences, University of British Columbia and Chief Scientific Officer, OncoGenex Pharmaceuticals, Inc. To access the webcast, log on to the Investor Relations page of the OncoGenex Web site at www.oncogenex.com. Alternatively, you may access the live conference call by dialing 877-627-6544 (U.S. & Canada) or 719-325-4857 (International). A webcast replay will be available approximately two hours after the call and will be archived at www.oncogenex.com. About OncoGenex Pharmaceuticals OncoGenex Pharmaceuticals is a biopharmaceutical company committed to the development and commercialization of new therapies that address unmet needs in the treatment of cancer. OncoGenex has a deep oncology pipeline, with each product candidate having a distinct mechanism of action and representing a unique opportunity for cancer drug development. OGX-011, the lead candidate currently completing five Phase 2 clinical studies in prostate, lung and breast cancers, is designed to inhibit the production of a specific protein associated with treatment resistance; OGX-427 is in Phase 1 clinical development; SN2310 has completed enrollment in a Phase 1 clinical trial; and CSP-9222 and OGX-225 are currently in pre-clinical development. More information is available at www.oncogenex.com. SOURCE OncoGenex Pharmaceuticals, Inc.

—Cell Therapeutics (NASDAQ: CTIC) will present data on its experimental drug for non-Hodgkin’s lymphoma, pixantrone. Nothing much new appears in the abstract—the Seattle-based company repeated that a study called PIX-301 of 140 patients found that 20 percent of those randomly assigned to get the drug had their tumors completely disappear, compared with 5.7 percent who did that well in a control group. These patients were quite sick, having failed to respond to at least two prior rounds of therapy. Pixantrone is modified to be less toxic to the heart than other drugs in the anthracycline class of chemotherapies. The trial was originally designed to enroll 320 patients, but was cut down to 140 because of slow enrollment. The company disclosed in its annual report that there were more “severe cardiac events” among patients who got the drug, than in the control group. —

—ImmunoGen (NASDAQ: IMGN), the Waltham,MA-based company with technology to make a “souped-up” version of Herceptin for breast cancer, will have one of the highly anticipated presentations. This drug, called trastuzumab DM1, or TDM1, has been developed in collaboration with Genentech, now owned by Swiss drug giant Roche. It takes the hit antibody drug for breast cancer, marketed as Herceptin, and aims to make it more potent by attaching a potent toxin to it. Preliminary results presented in December from 107 patients in a mid-stage clinical trial showed that about 40 percent had partial or complete tumor shrinkage after taking the drug. This happened even after their disease had spread through the body and they had stopped responding to traditional treatment combinations of Herceptin, chemotherapy, or another targeted drug, GlaxoSmithKline’s lapatinib (Tykerb). Just two patients quit taking infusions of the drug because of side effects that were possibly drug-related, researchers said in December. The abstract on the ASCO site doesn’t appear to say much more than the December presentation, but ImmunoGen noted that final results of this trial will be presented on May 30. This presentation will include important measurements on tumor shrinkage, how long the drug kept tumors from spreading, and how long the patients’ remissions lasted, ImmunoGen said in a statement.............ImmunoGen, Inc. (Nasdaq: IMGN) has a number of oral and poster presentations for its Antibody-maytansinoid conjugates with hydrophilic linkers and others.

—Infinity Pharmaceuticals (NASDAQ: INFI), the Cambridge, MA-based cancer drug developer, suffered a big setback last month when it halted a pivotal trial of patients with a rare form of cancer known as GIST, for gastrointestinal stromal tumors, after trial monitors saw a higher death rate among patients taking the treatment. This drug, IPI-504, is made to block a target on cells known as heat shock protein90, which operates like a chaperone for cells that help cancer cells survive and resist chemotherapies. This trial, called RING, was closed, but Infinity is continuing to test it for other tumors, like non small-cell lung cancer, and in combination with Roche’s trastuzumab for breast cancer patients. One abstract of data to be presented at ASCO shows IPI-504 was able to shrink tumors on its own in a study of 24 patients with non small-cell lung cancer that failed to respond to prior therapies. Two of the 24 had their tumors shrink by at least 25 percent, while seven patients had more modest reduction in their tumor volume, researchers said. The drug was considered well-tolerated, and was related to fatigue, nausea, and diarrhea. —Cambridge, MA-based Synta Pharmaceuticals (NASDAQ: SNTA) suffered a devastating setback in February when a clinical trial of 630 patients was shut down. The company pulled the plug after patients who were randomly assigned to get its novel drug for melanoma that has spread through the body showed a higher risk of death than those in a control group. Full results of this study weren’t made available in an abstract form on the ASCO site, although the final version will be made available on Saturday, May 30 at noon eastern time..........Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) is on deck tpo present data, but we’d advide to look into recent news about a trial for cancer being halted this week.

—Cambridge, MA-based Biogen Idec (NASDAQ: BIIB) had some discouraging news to report from a mid-stage clinical trial of an antibody drug for ovarian cancer. The company reported on a clinical trial of 127 women who were randomly assigned to get Biogen’s experimental antibody drug, volociximab, in combination with a form of doxorubicin chemotherapy, or the chemo alone. The new drug didn’t appear to add any safety concerns, although it was halted early after researchers saw it had a low probability of keeping tumors from spreading any more than the standard treatment...................Biogen Idec Inc. (NASDAQ: BIIB) will be presenting data on protease inhibitors. Keep in mind that this one just gave earnings yesterday and has been under pressure from Carl Icahn.