Upcoming Events Message from the Founder...Vardy’s Jewelers is a family business in Cupertino, California, run by Vardy Shtein and his daughter, Fanya Hull, and son, Misha Shtein

In this issue

Copyright © 2008 Canary Foundation. All rights reserved.

Upcoming Events

> July 14: OSH Golf Tournament benefiting Canary - Blackhawk Country Club, Danville, CA.

> September 5: Stand Up to Cancer

> September 13: Cabana gala - Woodside, CA.

> September 21: Canary Derby - Gastown, Vancouver, British Columbia, Canada.

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Share your personal story on how early detection of cancer has affected you or your loved one.

Message from the FounderJuly 2008

Momentum continues to build in the realm of early cancer detection. Canary’s second quarter featured the addition of new projects to each disease-specific team to complete the initial program portfolios of research in discovery, validation, and imaging. Canary Canada was officially established, and we benefited from two fundraising events—Canary Cancer Bash and the Canary Derby—that raised CAD$140,000 for Canary efforts in Canada. We had a superb scientific symposium and signed a new agreement with Stanford University to build the Canary Early Detection Center at Stanford.

On the scientific front, we added molecular imaging projects to the prostate and pancreatic programs. A new molecular imaging target called F-ACBC is being developed to “light up” prostate cancer. We have also added an imaging project for pancreatic cancer using a novel approach, molecular ultrasound, which we are also exploring for imaging ovarian cancer. This is an important milestone as it completes the project structures for our ovarian, lung, pancreatic, and prostate early detection programs.

The Arrillaga Alumni Center at Stanford was the scene of our fourth annual Early Detection Symposium. It was our best meeting yet and featured a keynote address by Dr. John Niederhuber, Director of the National Cancer Institute (NCI). The 200 participants were Canary researchers and affiliates and included four new American Cancer Society (ACS) postdoctoral fellows whose research is focused on early detection. Dr. Ian Jacobs, a world-renowned ovarian cancer researcher, joined us from the United Kingdom to deliver a keynote speech and share knowledge gained from his decades-long ovarian cancer screening studies.

New projects were added to the Canary Foundation network this quarter. Twenty novel targets have been identified for pancreatic cancer, and antibodies and assays (tests) will be developed for all of them. This work will be done largely in British Columbia. On that note, we also became official as a nonprofit in Canada and enjoyed two fundraising events in Victoria, BC, which raised CAD$140,000 for our programs on the island.

And, finally, we are excited to announce that we are expanding our relationship with Stanford University and are in the final phases of negotiating an agreement to build the Canary Early Detection Center at Stanford. This new facility will be led by Dr. Sanjiv (Sam) Gambhir and is located on California Avenue in Palo Alto. It will be the first of its kind in the world, bring-ing together both blood-based and imaging biomarker programs. We have recruited our first team member, Dr. Bonnie King, as deputy director and anticipate a phased occupa-tion beginning in fall of this year, moving towards full operation in 2009. Canary is most grateful to Dr. Phil Pizzo, dean of Stanford School of Medicine; Dr. Gary Glazer, head of Radiology; and Dr. Beverly Mitchell, deputy director of the Comprehensive Cancer Center, for their support.

Page 1 Message From the FounderPage 3 Vardy’s Jewelers—From Miniature Art to Big PhilanthropyPage 5 Taking Flight in CanadaPage 7 Collaboration UpdatePage 10 Summer Science Update

In this issue Share your personal story on how early detection of cancer has affected you or your loved one.


Message from the Founder (continued)

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Progress is tangible in science, partnerships, affiliates, fundraising, and infrastructure. We continue to drive towards our goal of early detection tests for all solid tumors by 2015. Thank you for your continuing support.




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Vardy’s Jewelers—From Miniature Art to Big PhilanthropyJuly 2008

Vardy’s Jewelers is a family business in Cupertino, California, run by Vardy Shtein and his daughter, Fanya Hull, and son, Misha Shtein. One of the first things they will tell you about their business is that many customers end up like family. They are also philanthropic and feel strongly about supporting nonprofits. “It is important to give to the community,” says Vardy Shtein. Last year, they decided to get involved with Canary Foundation and became top sponsor of the Cabana gala by donating, along with Hearts on Fire, a stunning set of diamond earrings and a brilliant diamond necklace. This year, they will again be top sponsor of the Cabana gala.

Vardy Shtein and his family are from Estonia, part of the former Soviet Union. He relates that as a young man he had the good fortune to apprentice under two master Fabergé craftsmen, for whom perfection was the goal. He immigrated to the United States 27 years ago, when his daughter was seven and his son four. The family believes that jewelry is miniature art. Often when asked to find a certain style pendant or bracelet for a customer, they will instead work to create a unique piece, using modern tools such as CAD—a computerized design to wax casting process—combined with old-world methods to create a piece of perfection and beauty.

Hull answered the following questions to help elucidate the family’s reasons for partnering with Canary Foundation:

Canary: How did your partnership with Canary Foundation develop?

Hull: We were introduced to Canary Foundation through our public relations person, Dan Orloff, who was impressed with Canary Foundation’s mission and leadership. He knows it is important to our family that we give to our community and thought this would be a good match.

(L-R) Misha Shtein, Vardy Shtein, Fanya Hull




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Vardy’s Jewelers—From Miniature Art to Big Philanthropy (continued)

Canary: What criteria did your family use for choosing a nonprofit with which to become involved?

Hull: The key factors for us were that we believed in the importance of Canary Foundation’s mission and also that it was locally based.

Canary: In what ways do you see the mission of Canary Foundation and your goals for Vardy’s Jewelers coming together?

Hull: Canary Foundation’s mission to eradicate cancer before it spreads and its efforts to excite people and organizations into getting involved provides Vardy’s Jewelers with a unique opportunity to be involved with an organization in which important work is being accomplished that will really help people.

Canary: What, if any, are your personal interests and goals in this partnership?

Hull: Our family and many of our customers have been affected by cancer. There can be no more important heath care goal than to beat cancer before it takes hold.




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Dr. Brad Nelson receives a check for CAD$12,500, raised at the Canary Cancer Bash, from Grant Olson, co-owner of the Strathcona Hotel.

Taking Flight in CanadaJuly 2008

It’s official: Canary Foundation of Canada has been recognized as a charitable organization by the Canada Revenue Agency! What better way to celebrate the launch of Canary Canada than by watching sleek soapbox derby racers flying down the Vancouver Island Technology Park course at the third annual Canary Derby in Victoria, BC? The derby continues to expand. This year’s hot new event—the Canary Cancer Bash and DJ Spinoff at the Strathcona Hotel’s Clubhouse and Elements Nightclubs—as well as the fundraising and awareness raising activities of each participating company, such as founder GenoLogics, all added up to a lot of canary yellow flying around Vancouver Island.

Spectators and competitors gathered under fairly sunny skies on June 14 to watch 14 teams race their cars in the third annual Canary Derby and enjoy the food and activities during the community picnic. These teams are getting their car design and strategies down to a fine art. The GenoLogics car won the Canary Style category, but in the end it was the Schneider Electric aerodynamically designed car cruising to the finish line at 51 km/h that posted the winning time of 68.16 seconds.

Young spectators surround the Canary Derby Speed Award–winning Schneider Electric car.




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Taking Flight in Canada (continued)

The race wasn’t just about the fastest car though. This year, everyone was working hard to raise the funds needed to purchase needed equipment for Dr. Brad Nelson’s lab at BC Cancer Agency’s Trev & Joyce Deeley Research Centre in Victoria, BC. This equipment will further improvements in the efficiency of assay development, in addition to the gains made through last year’s derby, which also raised funds for valuable cost- and time-saving equipment. Dr. Nelson’s group has recently added two new employees and now comprises six full-time staff dedicated to developing blood tests to measure novel candidate biomarkers for ovarian, prostate, pancreatic, and lung cancers.

GenoLogics took home the largest trophy of the day when their team placed first in the fundraising category by raising a whopping CAD$20,044. Well, almost the largest trophy. Evidently, derby organizers saved a remnant of Aspreva’s 2006 derby car wreck and created the Bent Wheel Trophy. Caorda Solutions was the distinguished recipient this year after their close encounter with a straw bale. Everyone gave one last cheer at the end of the day as the final total of CAD$140,000 was posted on the board.

This event was a tremendous success, thanks to Michael Ball of GenoLogics, Heather Jones of BC Cancer Foundation, Walt Nicholson, Tami Tate, the entire Canary Derby committee, and the Island’s vibrant technology community, including the many corporate sponsors. We can’t wait to see what next year brings as the momentum continues to build.

Third Annual Canary Derby trophies, including the infamous Bent Wheel Trophy, on display at the Canary Foundation booth.




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Collaboration Update July 2008

Canary Foundation Early Detection Symposium The fourth annual Canary Foundation Early Detection Symposium was held from May 20–22 at the Arrillaga Alumni Center at Stanford University, and feedback was unanimously positive. One hundred ninety-two scientists, doctors, administrators, industrialists, and philanthropists heard inspiring keynotes and cutting-edge scientific talks. The agenda focused on ovarian cancer as a model program, covering biomarker discovery, validation, and translation. At the end of day one, Randy Scott, CEO of Genomic Health, shared the challenges and successes of driving diagnostic tests to market, providing a valuable outlook on Canary’s mission to place effective cancer early detection tests into clinical practice. Symposium day two included overviews and progress updates on all of Canary’s programs: ovarian, lung, prostate, pancreatic, and baseline. Attendees enjoyed ample opportunities to mingle and mix with the best minds from a broad range of fields, all with a common passion for early detection of cancer.

On the second day of the symposium, disease-specific teams held breakout meetings, in which they shared the latest progress and pushed forward the planning of their research agendas. An additional breakout focused on bioinformatics was arranged to bring together recipients of our CPAS software installation grants. The group discussed the current status of bioinformatics tools and next steps, specifically in the area of products and standards to annotate and share data among labs.

As is always the case at the Canary symposium, a highlight for many attendees was the opportunity to build new collaborations and deepen existing ones in the generous time between sessions. Attendees enjoyed good food before and between sessions and exquisite wine, donated by Ross Bott, in the evenings. The symposium included a poster session for the second year, and again it was a great success, despite a last-minute move indoors due to the uncharacteristically windy California weather. Scientists presented 50 posters featuring research from major Canary-supported labs, ACS/Canary fellowship recipients, and others.

Dr. John Niederhuber, director of the National Cancer Institute, delivers the symposium keynote address.

Canary Foundation Early Detection Symposium

American Cancer Society/Canary Foundation Joint Fellowships

Canary Journal




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Collaboration Update (continued)

We are especially grateful to our symposium sponsors that underwrote the cost of the event. GenoLogics has been a supporter of Canary for several years and continued that tradition by acting as our main sponsor again this year. We were also fortunate to have four additional supporting sponsors for 2008: Hamamatsu, Applied Biosystems, Rules-Based Medicine, and Varian Medical Systems. Thanks to all of our sponsors for supporting Canary and the Early Detection Symposium.

American Cancer Society/Canary Foundation Joint FellowshipsThe American Cancer Society (ACS) and Canary announced at the Early Detection Symposium the recipients of the Canary Foundation and American Cancer Society Early Detection Postdoctoral Fellowship Program for 2008. The program selected four awardees this year, each fellow is awarded US$138,000 over three years to support research directed towards early cancer detection. The program reached a milestone this year and recognized the graduation of the first class of postdoctorals, all of whom attended the symposium.

The fellowship program continues to be very successful. In addition to the four latest awardees, Canary Foundation and the ACS are currently supporting six postdoctoral fellows at a number of institutions across the United States. These fellows have reported a number of collaborations leading to new and accelerated research progress and an impressive number of academic publications.

The 2008 recipients are:

• David J. Gorin, Harvard University: DNA-Encoded Libraries for Biomarker Identification

• Christopher A. Maher, University of Michigan Medical Center: The Role of Noncoding RNAs in Early Detection of Prostate Cancer.

• Joe Shuga, University of California, Berkeley: High Throughput Detection of Mutations as Biomarkers of Hematologic Cancer

• Robert W. Sprung, Vanderbilt Ingram Cancer Center: Medical Center Proteomics of Formalin-Fixed Paraffin-Embedded Colon Adenomas




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Collaboration Update (continued)

“These fellows represent some of our best and brightest researchers in early cancer detection today,” said Canary Foundation CEO and founder Don Listwin. “With the American Cancer Society, we are committed to cultivating future leaders in this field and ensuring that institutions conducting early detection research will have the talent they need through this fellowship program.”

Canary and ACS both remain committed to this program and expect to announce the 2009 fellowship application dates shortly.

Canary JournalThe Canary Journal was officially launched at the Early Detection Symposium. Canary Journal is a new web resource from Canary that serves as an aggregator of scientific papers and news articles on early detection of cancer. It provides a single point where scientists and laypeople alike can go to see the state of the field and members can participate with comments and recommendations. The journal offers the capability to record and display comments and recommendations so that viewers can read not only the papers but also responses from other leaders in the field. As time goes on, we expect that input from the early detection community will become a real value-add to the papers and news items featured on the site. Advanced search and sort options enable users to view papers according to topic, recommendation, or date. Take a look.




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Summer Science UpdateJuly 2008

Ovarian Cancer Program Canary Foundation’s Ovarian Cancer Program, with its impressive breadth and depth, was featured as a model at this year’s Early Detection Symposium. This program has well-developed projects directed towards both blood and imaging tests, each of which includes targeted efforts in biomarker discovery and validation. We continue to make progress on all fronts and to refine our strategy as we learn and move forward.

One of the themes that emerged from this year’s symposium is the potentially great value of “pathognomonic” biomarkers—biomarkers that are only found in cancer; this is in contrast to many biomarkers (for example, CA125) that are found in healthy patients but are simply elevated under disease conditions. Pathognomonic biomarkers are ideal for detecting very small tumors in the blood or other fluids because they have no background level, and thus only small amounts are diagnostic of cancer. Such biomarkers are especially challenging to identify because many traditional discovery methods rely on knowing in advance what you are looking for. Dr. Martin McIntosh presented some encouraging preliminary results from his early efforts in this area, in which he used mass spectrometry to profile ovarian cancer cells derived from ascites (tumor fluids) and identified a number of potentially novel protein variants. These candidates require much more vetting but provide a great proof-of-principle of this approach and a starting point for further develop-ment of experimental techniques and analytical methods. Additional discovery efforts are planned using emerging high-throughput DNA sequencing methods, which allow efficient discovery of previously unseen DNA sequence variants arising from tumorigenic DNA rearrangements.

Our efforts in the validation of blood biomarkers continue to shift towards evaluation of specimens collected prior to the diagnosis of disease, instead of the more commonly used (and readily available) clinical specimens obtained following diagnosis. Such preclinical specimens are essential to assessing a biomarker’s utility in early detection, yet they are extremely hard to come by as they rely on large cohort studies that follow many healthy women over time, repeatedly sampling and banking their blood, until some of them

Ovarian Cancer Program

Lung Cancer Program

Prostate Cancer Program

Pancreatic Cancer Program

Baseline Program

Symposium attendees prepare for informal presentations and discussions at the poster session.




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develop ovarian cancer. Fortunately, through our rich network of collaborations, we have been able to access a number of these large cohort studies and have begun to evaluate some of our lead blood biomarkers in these specimens. Initial studies with such specimens have clearly demonstrated that biomarkers that appear to be equally promising in specimens obtained in women with acute ovarian cancer vary greatly in how early in the disease course they are elevated. We continue to reach out and build collaborations to assess our lead candidates in greater numbers of preclinical biospecimens and to push our novel candidates through progressively more challenging specimen sets.

Our ovarian cancer imaging program, led by Dr. Sanjiv Gambhir, encompasses two strategies: PET imaging and molecular ultrasound. Our PET imaging program is focused on engineering tiny, labeled peptide probes to light up tumors by binding to targets that are specific to ovarian cancer tumor cells. Recently, lead peptides (imaging probes) were identified for all three of our PET imaging candidates through successive screening of large sets of candidate peptides, and fluorescent versions of these peptides have been successfully synthesized. These fluorescent probes will soon be tested in cell culture studies and subsequently in small animal optical imaging studies. Our molecular ultrasound program involves engineering microbubbles to bind to specific biomarkers found in the blood vessels that feed tumors and using ultrasound to image the labeled vessels. Dr. Gambhir recently shared encouraging results showing that small tumors (several millimeters) can be detected in mouse models of ovarian cancer using customized microbubbles that can target multiple biomarkers at once.

Lung Cancer ProgramThe Canary Lung Cancer Program continues to build on this year’s strong start. The lung cancer team has launched multiple research projects while continuing to enrich the program with projects under development. At the lung cancer meeting following the Early Detection Symposium, the team shared early insights from their research in progress. Dr. Sylvia Plevritis of Stanford University reported on a model for predicting the size at which lung tumors make the transition that will lead them to spread and become lethal. In order to effectively screen for lung cancer to save lives, we must be able to catch tumors before this fatal transition. Incorporating data from the U.S. Surveillance Epidemiology and End Results (SEER) program, her team’s model predicts that most tumors are not extremely small when they reach the fatal transition. These preliminary data are encouraging because they suggest that otherwise lethal lung tumors can be found within feasible limits of detection, whether by imaging or by blood tests. Dr. Plevritis’s Canary project also takes advantage of her association with the Cancer Intervention and Surveillance Modeling Network, a consortium of National Cancer Institute–sponsored investigators. As a member of this group, Dr. Plevritis brings knowledge and expertise from the entire collective effort using a comparative modeling approach to understand and predict screening effectiveness for lung cancer.

Summer Science Update (continued)




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Following up on their commitment to identify biomarkers for lung cancer among never smokers, the team also enthusiastically received a new project proposal from Dr. Jason Chien of the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, Washington. By leveraging the research infrastructure and faculty expertise of the Women’s Health Initiative (WHI) and the FHCRC, Canary funding for this project will enable one of the largest comprehensive epidemiologic studies of lung cancer risk among women who have never smoked. The Canary project will take advantage of the many years and depth of data available from the WHI—a multimillion-dollar, 15-year project sponsored by the National Institutes of Health involving over 161,000 women ages 50–79. WHI is one of the most comprehensive studies of postmenopausal women’s health ever undertaken in the world. The Canary study will address the need to identify genetic and environmental risk factors for lung cancer among never smokers, which are largely unknown. Surprisingly, only a small percentage of cases of never-smoker lung cancer are due to known environmental risk factors such as environmental tobacco smoke. The study will examine demographic, dietary, lifestyle, medical, family history, and reproductive risk factors in relation to risk of lung cancer and will comprehensively compare lung cancer risk factors among never, former, and current smokers. Knowing which people might be at high risk for lung cancer will aid in designing screening strategies for never smokers and may also lead to the identification of candidate lung cancer biomarkers for blood and imaging tests.

Prostate Cancer Program Canary Foundation’s Prostate Cancer Program continues to advance swiftly, as the team prepares to launch enrollment in the multi-institutional Canary Prostate Active Surveillance Study (PASS). This study will enroll and follow men who have been diagnosed with early-stage prostate cancer and opt to be actively monitored rather than prematurely undergo radical treatment. Following site initiation in June, patients will be accepted at the following six participating institutions: Stanford University; University of California, San Francisco; University of Washington; Veterans Affairs Puget Sound Health Care System (Seattle); University of Texas Health Science Center; and the University of British Columbia (Canada).

The retrospective component of the Prostate Cancer Program, which will use existing archived tissue samples to evaluate candidate biomarkers, has also made significant progress. As part of our partnership with the Early Detection Research Network (EDRN), Canary has employed the statistical expertise of the EDRN to design tissue microarray studies. These studies will allow us to rigorously assess candidate tissue-based biomarkers for their potential to distinguish lethal from nonlethal cases of prostate cancer as a filter prior to accessing precious specimens from our prospective study (PASS). Canary has also leveraged EDRN resources as a data management and coordinating center for creating standardized annotations, allowing tissue microarray data to be combined across institutions.





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On the assay development front, our dedicated team in Victoria continues to develop antibody-based assays that can be used to measure levels of candidate biomarkers in the blood. Several of our leading candidates have now progressed beyond the protein production stage into the lengthy stage of antibody production. We are also finalizing the design and cross-institutional transfer of several sets of blood samples that can be used to test readily available commercial assays as well as future in-house assays.

Pancreatic Cancer ProgramThe Canary Pancreatic Cancer Program is pleased to announce new initiatives as well as steady progress in identification, development, and testing of candidate pancreatic cancer biomarkers. The pancreatic cancer team has joined forces with Dr. Hoda Anton-Culver, an expert epidemiologist and director of the Center for Cancer Genetics Research and Prevention at the University of California at Irvine, to augment our specimen collections for biomarker testing. Normal (disease-free) control (comparison) samples are essential to all of our biomarker studies. This is especially true for a disease like pancreatic cancer that has a low prevalence in the population. A biomarker for pancreatic cancer must have very high specificity (the ability to correctly identify people who do not have the disease) in order to avoid a high false positive rate when testing thousands of people. Thus all of our biomarker candidates must be rigorously tested against large numbers of age- and gender-matched controls to ensure that the specificity of the biomarker is high. Dr. Anton-Culver will work with the Canary team to collect these hundreds of required controls along with samples from patients with pancreatitis or pancreatic cancer.

Canary recently partnered with the Lustgarten Foundation to develop antibodies and assays for candidate pancreatic cancer biomarkers as part of the Lustgarten Pancreatic Cancer Biomarker Initiative. The Canary Early Detection Symposium provided an informal venue for all four groups involved in this project, including the Canary assay development team led by Dr. Brad Nelson, to meet and review progress. All of the groups’ antibody production efforts are under way, and the group is also working together to develop guidelines for the submission of antibody-generating hybridomas to the National Cancer Institute’s Early Detection Research Network.

The Canary Pancreatic Cancer Program is excited to welcome the development of a mo-lecular imaging project for pancreatic cancer that will complement our blood biomarker discovery and validation projects. As with other Canary science programs, the combined goal of the Pancreatic Cancer Program is to develop a blood test and an imaging test that together will detect pancreatic cancer early. For pancreatic cancer imaging, we will undertake a molecular ultrasound approach, a project led by Dr. Jürgen Willmann and Dr. Sanjiv Gambhir at Stanford University. Ultrasound is a promising screening tool for early cancer detection because it is highly sensitive and noninvasive, does not use ionizing irradiation, and is routinely available in most imaging departments. The Canary project will assess novel microbubbles targeted to a molecular marker of tumor blood vessel growth in early cancer, for detection of early-stage pancreatic cancer in animal models.





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The long-term goal of this work is to translate molecular ultrasound into a highly sensitive clinical imaging modality for pancreatic cancer screening using targeted microbubbles in patients.

Baseline ProgramThe importance of understanding biomarker performance in healthy patients and in the presence of potentially confounding benign conditions was a recurring theme at this year’s Early Detection Symposium. Canary Foundation continues to take steps to support this underfunded yet broadly important area of research. Dr. Pete Nelson, Canary’s prostate cancer team leader (and member of the baseline team), is initiating a pilot study to characterize normal levels and short-term (daily) variation in protein biomarker levels in the blood of apparently healthy men. This study will complement a study led by Dr. Martin McIntosh of Canary’s ovarian cancer team (and baseline team) characterizing normal levels and long-term variation (over months to years) in protein biomarker levels in the blood of apparently healthy women, using previously collected specimens. As described in the “Pancreatic Cancer Program” section, Canary is also supporting our pancreatic cancer team leader, Dr. Teri Brentnall, in building a specimen resource address-ing the need for blood from large numbers of controls including both apparently healthy individuals and patients with a variety of potentially confounding conditions. Together, these resources and data will provide an unprecedented picture of normal variation and a valuable means to filter candidate biomarkers. A recently published article in Wired magazine, “Why Medicine Should Care Less About ‘Sick,’ More About ‘Normal’,” highlights the dismal current state of knowledge of “normal” and features quotes from Canary science team member Dr. Pat Brown, who continues to help shape Canary’s efforts in this area.



Documents

Upcoming Events Message from the Founder...Vardy’s Jewelers is a family business in Cupertino, California, run by Vardy Shtein and his daughter, Fanya Hull, and son, Misha Shtein