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From: IRWIN JAMES FRANKEL	7/7/2011 1:37:52 PM
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YM by earnie: 306 SPA 7-Jul-11 09:36 am Right before ASCO, EXEL had its end of phase 2 meeting with FDA. Included in their description of this meeting was the statement that FDA senior management was well represented at this meeting. FDA followers know that in the Oncology Division, there is very little power sharing and most important decisions come directly from Dr. Pazdur. I cannot speak for EXEL, but I suspect that their statement was codespeak that Dr. Pazdur was in attendance. Throughout ASCO and the subsequent presentations EXEL has described the meeting as productive and said that FDA input at that meeting gave them a clear path going forward to craft an SPA for the 306 trial. They did not say that the FDA had accepted or embraced a bone scan resolution endpoint as an approvable criteria. They did say that FDA comments were incorporated into the submitted protocol. That is not quite the same thing as saying that all of the FDA's comments were incorporated. Make no mistake, this is a very high stakes game for EXEL. The sample size is large enough now to say unequivocally, the bone scan resolution phenomenon is real and unique. If a primary endpoint has a significant bone scan input, treatment arm efficacy will dwarf that of any imaginable drug treatment chosen as the control. Granting an SPA with a bone scan input that is a comparative criteria for Cabo vs control may be tantamount to approving a trial with a foregone conclusion. The devil could be in the details. The proposed 306 trial is described as employing "a combined endpoint of pain reduction and bone scan response." Does this mean that Cabo has to show superiority by both criteria separately or the single endpoint is made up of patients who show both a pain reduction and bone scan improvement? It may be that the drug approval is based on the pain reduction side and the bone scan response part is included so as to give a broader label description. Hopefully, when the SPA is finally agreed to, EXEL will provide enough clarity to be able to understand the exact makeup of the combined primary endpoint.

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From: IRWIN JAMES FRANKEL	7/7/2011 2:46:15 PM
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YM from voyagervx Piper Jaffray Note to Clients 7-Jul-11 10:33 am Piper Jaffray has an Overweight rating and a $13 price target on shares of Exelixis, Inc. (NASDAQ: EXEL). In a note to clients, Piper Jaffray writes, "Exelixis has extended the timeline to report pivotal Phase III data for Cabozantinib in metastatic thyroid cancer (MTC) until later this quarter. The push out is the result of having too few progressions to unblind the study, which we read as most likely positive, increasing our confidence that the Phase III trial will read positive. We believe EXEL shares should trade higher on this news. Exelixis expects to begin the 1st of 3 pivotal trials of Cabo in prostate cancer this year and could partner the drug overseas, generating non-dilutive financing." Shares of EXEL gained 9 cents yesterday to close at $9.19.

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From: IRWIN JAMES FRANKEL	7/7/2011 2:47:52 PM
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YM by earnie: Today's news 7-Jul-11 12:12 pm This did not directly answer your question, but it does indicate that the dropout rate was fairly low, 10% V arm and 5% placebo. I would expect similar numbers from the Cabo trial. Also, realize that trial entry was an ongoing process and the effect of dropouts on event accrual would be incorporated into the curve early on and perhaps would not only now be manifesting themselves. <<Also I wanted to ask you about your statement "it improves the chances that the trial will achieve its primary endpoint." Is this necessarily the case?>> If you assume that Cabo has any inherent efficacy, then yes, my statement is valid. The longer the trial continues and the longer the curves stay separated, the lower the resultant p value will be. <<And from the FDA's perspective is statistical signficance the only thing that is important?>> I think the Avastin experience told us emphatically that statistically significant PFS as an approval criteria has flaws. From a practical standpoint, as investors, all we will see this fall is topline data, a p value, a hazard ratio and perhaps median PFS for the 2 arms. The CRPC story will overtake the MTC data in terms of relative importance before the details of the MTC trial are revealed. <<Or is it the differential in survival between the two groups (i.e. the magnitude of the effect) that is important?>> Although they did not say so directly, yesterday EXEL was making the case that the trial had a good chance to show a survival advantage in addition to PFS. There will probably not be enough survival events this fall, but there is certainly a survival analysis built into the trial at a later date. <<does a delay in results have any implications for the latter-i.e. perhaps suggesting that the assumption of a 75% improved PFS might have been an overestimate?>> I would not dwell on the powering assumptions. Those are simply a tool to determine the needed size of a trial and are not a statement of what is the minimum clinically meaningful outcome. Some very large trials are powered based on the minimum clinically meaningful result, but such is not the case here.

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From: IRWIN JAMES FRANKEL	7/7/2011 2:51:03 PM
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YM by earnie: <<The SPA acceptance might just be anti-climactic now....>> Not at all. If they come back with an agreement that gives a Cabo arm an inherent advantage by incorporating a bone scan improvement component, it is back off to the races and we will see gains like those in last Dec and Jan. If this drags out into 2012, the market will register its disappointment. Just to reitierate, if the FDA agrees to a bone scan endpoint, that would be out of character for them. EXEL has created the expectation that it is a real possibility, perhaps even a likelihood. I hope they are not overpromising and when they do make the SPA announcement, I hope they are as transparent about revealing the details as they have claimed they would be. Biotech investing can be a real minefield when management gets selective about what they choose to reveal.

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From: IRWIN JAMES FRANKEL	7/14/2011 5:08:09 PM
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Form 8-K for EXELIXIS INC 14-Jul-2011 Termination of a Material Definitive Agreement Item 1.02. Termination of a Material Definitive Agreement. Termination of Collaboration Agreement with Bristol-Myers Squibb Company for XL281 On July 8, 2011, Exelixis, Inc. and one of its wholly-owned subsidiaries (collectively, the "Company") received written notification from Bristol-Myers Squibb Company of its decision to terminate the Amended and Restated Collaboration Agreement dated as of April 15, 2011 by and between the Company and Bristol-Myers Squibb, which amended and restated the Collaboration Agreement dated as of December 11, 2008 between Exelixis and Bristol-Myers Squibb (the "Agreement"), on a worldwide basis as to XL281. The termination is being made pursuant to the terms of the Agreement and will be effective as of the end of the day on October 8, 2011. Bristol-Myers Squibb informed the Company that the termination was based upon Bristol-Myers Squibb's review of XL281 in the context of Bristol-Myers Squibb's overall research and development priorities and pipeline products. Upon the effectiveness of the termination, Bristol-Myers Squibb's license relating to XL281 will terminate and rights to XL281 will revert to the Company, and the Company will be entitled to receive, subject to certain terms and conditions, licenses from Bristol-Myers Squibb to research, develop and commercialize XL281. The Company plans to wind down ongoing activities related to XL281 following the termination and does not currently expect to further research, develop or commercialize XL281 following the wind-down. Under the Agreement, the Company and Bristol-Myers Squibb originally had agreed to co-develop cabozantinib and Bristol-Myers Squibb also received an exclusive worldwide license to develop and commercialize XL281. On June 18, 2010, the Company received a notice from Bristol-Myers Squibb of its decision to terminate the Agreement solely as to cabozantinib, on a worldwide basis, pursuant to the terms of the Agreement. The Company continued to carry out certain clinical trials of XL281 under the Agreement, and Bristol-Myers Squibb was responsible for funding all future development of XL281, including the Company's activities. The Company was eligible for development and regulatory milestones of up to $315.0 million on XL281, sales performance milestones of up to $150.0 million and double-digit royalties on worldwide sales of XL281. For purposes of recognizing up-front license fees received under the Agreement, prior to receiving the notification the Company was recognizing revenue through April 2014. As a result of the termination, the estimated research term will now end as of the end of the day on October 8, 2011. Accordingly, the Company expects to accelerate the remaining deferred revenue balance and estimates that it will recognize an aggregate of approximately $109.9 million and $10.4 million in revenue in the third and fourth fiscal quarters of 2011, respectively, relating to the up-front license fees under the Agreement. In addition to the Agreement, the Company and Bristol-Myers Squibb are parties to the following: ? a collaboration agreement for the discovery, development and commercialization of novel therapies targeted against LXR, a nuclear hormone receptor implicated in a variety of cardiovascular and metabolic disorders, originally entered into in December 2005 and amended and restated as of April 15, 2011; ? a worldwide collaboration to discover, develop and commercialize novel targeted therapies for the treatment of cancer, originally entered into in December 2006 and amended in October 2010 to: (1) provide an exclusive license to Bristol-Myers Squibb of commercial and development rights and responsibilities to XL139, a Hedgehog inhibitor; (2) end the research term under the collaboration; and (3) terminate the Company's responsibility for conducting research activities or funding new development or commercialization activities under the collaboration, and amended and restated as of April 15, 2011; ? a global license agreement pursuant to which the Company granted to Bristol-Myers Squibb a license to its small-molecule TGR5 agonist program, including rights to the program's lead compound, XL475, as well as potential backups, originally entered into in October 2010 and amended and restated as of April 15, 2011; and ? a worldwide collaboration pursuant to which each party granted to the other certain intellectual property licenses to enable the parties to discover, optimize and characterize ROR antagonists that may subsequently be developed and commercialized by Bristol-Myers Squibb, originally entered into in October 2010 and amended and restated as of April 15, 2011.

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From: IRWIN JAMES FRANKEL	7/14/2011 6:30:03 PM
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YM from hbomb: Prostate Cancer Foundation Funds $4.2 Million in New Creativity Awards for Advanced Research * Reuters is not responsible for the content in this press release. Wed Jun 1, 2011 5:35pm EDT Prostate Cancer Foundation Funds $4.2 Million in New Creativity Awards for Advanced Research Initial Funding Launches 14 Innovative Projects For Accelerating Advances Against Prostate Cancer The Prostate Cancer Foundation (PCF) today announced that it has funded 14 new Creativity Awards for advanced prostate cancer research. These two-year awards are designed to support innovative research ideas that have the potential to achieve breakthroughs for improved prostate cancer diagnosis and treatment. PCF Creativity Awards aid the advancement of the world’s most imaginative, new research ideas that are not yet funded by any government or foundation sources. The funded projects represent a range of research areas including biomarkers for earlier and more precise detection and treatment, the development of new, nano-enabled therapeutics for patients with metastatic disease, and identifying new targets for drug development. “We were impressed with the unique ideas represented by the applicants. A rigorous process that included 71 peer reviewers vetted the 14 selected treatment sciences projects from a field of more than 200 applications representing leading institutions in 10 countries,” reports Howard Soule, PhD, executive vice president and chief science officer for PCF. “These awards fortify our pipeline of compelling ideas to cultivate new solutions for the prostate cancer problem. We believe that our investment in these projects will push scientific discovery and deliver better therapies for patients with advanced prostate cancer.” Historically, 70 percent of such PCF awards have gone on to attract additional multi-year funding from PCF and other sources within three years of their original funding by PCF. “Eight of the awards are going to investigators who have never before been funded by PCF and we are very excited to track the progress of these new ideas.” added Dr. Soule. “They have enormous potential to deliver breakthrough discoveries and ultimately enable physicians to cure more and overtreat less.” 2011 Creativity Award Recipients (* = First-time PCF Award Recipient) Steve Cho, MD Assistant Professor of Radiology The Johns Hopkins University School of Medicine Proposal Title: Evaluation of PSMA-based PET as Functional Imaging Biomarker of Primary Prostate Cancer A major unmet medical need in prostate cancer diagnosis and therapy is the ability to image small metastatic tumors. This proposal will develop a functional imaging biomarker specific to prostate cancer. This PET (positron emission tomography-a nuclear imaging technique) imaging tracer, already shown specific for prostate cancer by imaging studies in patients, will be tested for detection of bone and nodal metastases at time of original prostate cancer diagnosis. This imaging system has the potential to more specifically stage prostate cancer patients prior to initial therapy and determine those who might benefit from early aggressive therapy. Dr. Cho transitioned a 2007 PCF Young Investigator Award into this PCF grant. Potential patient benefit: The ability to detect early metastatic prostate cancer and to identify patients who will benefit from early aggressive treatment may prolong survival in an important subset of individuals. Samuel Denmeade, MD Professor, Pharmacology & Molecular Sciences The Johns Hopkins University School of Medicine Proposal Title: Evaluation of Bindarit, a Novel Inhibitor of the CCL2 Chemokine Axis, as Therapy for Metastatic Prostate Cancer Dr. Denmeade is testing a medication called Bindarit – an orally active compound already tested in over 500 patients. Bindarit affects a number of mediators of chemotherapy resistance, especially in bone. Preclinical studies will be performed to qualify Bindarit for testing in men with metastatic prostate cancer. Patient benefit: Bindarit may represent a new and novel tumor microenvironment therapy for men with metastatic prostate cancer and holds the potential to improve the efficacy of chemotherapy. * Peter B. Dervan, PhD Bren Professor of Chemistry California Institute of Technology The Susan and James Blair-PCF Creativity Award Proposal Title: DNA-binding Polyamides as Inhibitors of TMPRSS2-ERG Activity in Prostate Cancer The recent discovery of gene fusions in prostate cancer has established a new biological mechanism for expression of cancer causing genes (oncogenes). Dr. Dervan has developed a chemistry for producing oncogene inhibitors that is more creative and has higher potential than any pharmaceutical program in stopping oncogene activity. Oncogene inhibitors that block their interaction with specific genomic regions will represent a new class of medication for metastatic prostate cancer. Potential patient benefit: This work has the potential to discover new targeted therapies for metastatic prostate cancer with an entirely new type of chemistry. * Christian R. Gomez, PhD Research Associate The Mayo Clinic Facultad de Medicina, Universidad Diego Portales, Santiago, Chile Proposal Title: Hypoxia-Regulated DLG7 in Prostate Carcinogenesis and Prognosis An unmet medical need in prostate cancer diagnosis and therapy is the lack of highly-reliable progression biomarkers to monitor efficacy of therapy. Dr. Gomez’s research team has discovered a molecule called DLG7 which may serve as a reliable progression biomarker in prostate cancer. This research will test the ability of DLG7 and related molecules to predict an unfavorable outcome of prostate cancer by testing patient biopsy specimens that are well annotated with outcome data. Potential patient benefit: While PSA is a useful biomarker, it is prostate-specific and not prostate cancer-specific early in the prognostic process. DLG7 has the potential to be a prostate cancer-specific marker that may accurately predict the process of disease progression. Beatrice Knudsen, MD, PhD Medical Director of Biorepository and Translational Pathology Cedars-Sinai Medical Center Proposal Title: Biomarkers of Response to Treatment with XL184 in the Bone XL184 (caboxantanib) is a new experimental medication for metastatic prostate cancer with promising clinical results. To more effectively administer XL184 to patients with metastatic prostate cancer, Dr. Knudsen seeks to define the precise anti-cancer mechanism of action. She has assembled a team at Cedars-Sinai in Los Angeles and University of Washington/Fred Hutchinson Cancer Institute in Seattle to study the effects of XL184 in patient biopsies and will investigate the mechanism of action of this encouraging agent as a biomarker for response in patients. Potential patient benefit: An understanding of the mechanism of action of XL184 will accelerate the clinical development of this very encouraging agent by providing investigators with laboratory and imaging biomarkers of response. * Kit Lam, MD, PhD Professor of Medicine Chief, Division of Hematology/Oncology, Department of Internal Medicine UC Davis Medical Center Proposal Title: Smart Nanoparticles for Imaging and Treatment of Prostate Cancer Dr. Lam is an expert in the area of nanotechnology drug delivery systems. His research group has invented a nanoparticle that delivers chemotherapy only to prostate cancer cells. These targeted nanoparticles will be loaded with chemotherapy medications and will be tested for targeting in animal models of prostate cancer. It is hoped that these particles will deliver concentrations of chemotherapy directly to tumors that far exceed therapeutic levels that can be achieved by standard intravenous administration. Potential patient benefit: This delivery system could improve the efficacy of Docetaxel many-fold, thereby improving survival efficacy while reducing side effects. * Glenn Liu, MD Assistant Professor of Medicine University of Wisconsin School of Medicine and Public Health UW Carbone Cancer Center Proposal Title: Developing a Novel Quantitative Total Bone Imaging (QTBI) Methodology to Assess Treatment Response in Metastatic Prostate Cancer The lack of ability to measure tumor response in bone has greatly hindered prostate cancer drug development. This project will evaluate the role of functional, qualitative, total bone imaging to assess therapeutic response to new medicines in bone metastases. A PET/CT scan index will be established to estimate percent bone involvement and to determine total burden of disease in bone. Potential patient benefit: Development and measurement of this imaging biomarker will accelerate our ability to count cancer cells in patients and will speed the drug development process by more accurately and rapidly assessing tumor response in bone. The method may provide physicians with a better way to assess the progression and regression of prostate cancer. Peter Nelson, MD Full Member Fred Hutchinson Cancer Research Center Professor of Oncology, Adjunct Professor Genome Science and Pathology University of Washington Proposal Title: Targeting Therapy-Induced Resistance Mechanisms in the Prostate Tumor Microenvironment Dr. Nelson postulates that chemotherapy resistance originates in the tumor microenvironment in response to stress caused by chemotherapy. He has discovered that tumor cell repopulation accelerates during the intervals between courses of treatment causing resistance to further chemotherapy. This proposal seeks to understand the series of events occurring in the tumor microenvironment resulting in resistance to chemotherapy. Potential patient benefit: An understanding of the series of biologically programmed events in the tumor microenvironment that cause chemotherapy resistance will lead to resensitization strategies and improved efficacy of chemotherapy, the mainstay treatment for metastatic prostate cancer. * William Polkinghorn, MD Research Fellow Memorial Sloan-Kettering Cancer Center Proposal Title: Defining the role of AR Signaling in Promoting Prostate Cancer Radioresistance Dr. Polkinghorn postulates that androgen receptor signaling directly promotes prostate cancer resistance to radiation therapy (radioresistance). This work will determine which androgen receptor-dependent genes promote prostate cancer radioresistance. Medical inhibition of androgen pathway gene expression targets could increase efficacy of radiation therapy. Testing will be performed in prostate cancer cell lines as well as human prostate cancer tissue specimens from large clinical trials of androgen deprivation therapy during radiation treatment with known outcomes. Potential patient benefit: More effective radiation therapy of localized and locally advanced prostate cancer may result in the prevention of metastatic disease years, if not decades, later. * Ulrich Rodeck, MD, PhD Professor, Department of Dermatology & Cutaneous Biology Jefferson Medical College-Thomas Jefferson University The Ben Franklin-PCF Creativity Award Proposal Title: Improving the Therapeutic Window of Radiation Therapy for Prostate Cancer Radiation therapy of locally advanced prostate cancer is associated with severe toxicity limits. Dr. Rodeck will test the hypothesis that modulators of inflammation will preferentially protect normal tissues, but not tumor tissues against radiation-associated toxicity. A series of novel radioprotective compounds have been selected to test this hypothesis in models of prostate cancer and in patients. Potential patient benefit: This radiobiology proposal will allow higher doses of external beam radiation to be administered, resulting in improved cancer control with reduced side effects to normal adjacent tissue. * Marianne Sadar, PhD Senior Scientist, Michael Smith Genome Sciences Centre, BC Cancer Agency Honorary Associate Professor, Department of Pathology and Laboratory Medicine University of British Columbia Proposal Title: Niphatenones a Completely New Class of Androgen Receptor Antagonist Dr. Sadar has discovered and is developing compounds derived from undersea plant life for development of new treatments for metastatic prostate cancer. Some of these compounds block the activation of the androgen receptor and possess antitumor activity. These compounds, called niphatenones, will be thoroughly investigated as clinical therapeutic candidates for treatment of metastatic prostate cancer. Potential patient benefit: Niphatenones represent a new class of antineoplastic medication for treatment of metastatic prostate cancer. Matthew R. Smith, MD, PhD Associate Professor, Department of Medicine, Harvard Medical School Assistant in Medicine, Hematology/Oncology Massachusetts General Hospital Cancer Center Proposal Title: Prospective Translational Study of XL184, a Dual Inhibitor of VEGFR2 and MET, in Men with Castration-Resistant Prostate Cancer (CRPC) and Bone Metastases XL184 (caboxantanib), a new and highly encouraging medicine for the treatment of metastatic prostate cancer is in very early stages of clinical development. One significant goal of this proposal is to establish efficacy and safety of XL184 at lower doses to reduce toxicity and increase time on treatment. The rapid bone scan improvement in patients treated with XL184 will be examined with MR imaging technology to better define the significance of this unprecedented finding. Potential patient benefit: Determining the lowest effective dose of XL184 will establish a safer protocol for administering this very encouraging new treatment for metastatic prostate cancer. Owen Witte, MD Distinguished Professor of Microbiology, Immunology, and Molecular Genetics President's Chair in Developmental Immunology David Geffen School of Medicine University of California, Los Angeles Proposal Title: Target identification Combining In Vivo Tissue Transformation with Multi-parameter Profiling and “Surprisal Analysis” The goal of this highly creative proposal is to search for and discover new pathways and therapeutic targets in advanced prostate cancer for therapeutic destruction of disease. A “first-in-field” mathematical modeling and statistical tool has been invented and will be used to discover gene expression patterns and protein modification events that correlate with disease progression yielding new pathways and targets. Findings from this mathematical analysis will be tested in human prostate tumors, as well as in mouse models of prostate cancer. Potential patient benefit: Great progress has been made in development of new therapies for metastatic prostate cancer; however, the targets elucidated through this Creativity Award could provide an entirely new generation of medicines for metastatic prostate cancer. Bruce Zetter, PhD Professor of Cancer Biology, Department of Surgery Harvard Medical School Dana-Farber/Harvard Cancer Center Proposal Title: The Mesenchymal-to-Epithelial Transition (MET) as a Novel Target for Treatment of Disseminated (Metastatic) Prostate Cancer Epithelial-mesenchymal transition (EMT) is a programmed loss of cell adhesion accompanied by increased cell motility that is thought to be essential for tumor metastasis. However, this process is reversed (mesenchymal to epithelial transition--MET) over time in prostate cancer when disease is widely metastatic, making it adhesive once again. An animal model of prostate cancer MET will be used to obtain a genetic signature of this process. Methods will be established to block MET, which likely represents a lethal form of progressive prostate cancer. Potential patient benefit: This work will lead to an understanding of mechanisms of metastasis for which new drugs can be designed to inhibit this lethal process. About the Prostate Cancer Foundation The Prostate Cancer Foundation (PCF) is the world’s largest philanthropic source of support for accelerating the world’s most promising research for discovering better treatments and cures for prostate cancer. Founded in 1993, the PCF has raised more than $435 million and provided funding to more than 1,500 researchers at nearly 200 institutions worldwide. PCF advocates for greater awareness of prostate cancer and more efficient investment of governmental research funds for transformational cancer research. Its efforts have helped produce a 20-fold increase in government funding for prostate cancer. More information about the PCF can be found at www.pcf.org. Prostate Cancer Foundation Dan Zenka, APR Vice President, Communications 310-570-4714 (Direct) dzenka@pcf.org or Cara Lasala Senior Public Relations Specialist 310-570-4727 clasala@pcf.org Sponsored links

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