Event Spotlight: Therapeutic Advancements, Innovations and Treatments in Musculoskeletal Health

On May 24, CHI hosted an insightful briefing in Washington, D.C. highlighting the importance of therapeutic advancements and innovations in musculoskeletal disease and injuries. The program was held on Capitol Hill, and was attended by congressional staff, patient advocates, industry representatives and members of the press, among others. The assembled panel of experts addressed a variety of issues in the area of musculoskeletal conditions, providing an excellent awareness-raising overview and highlighting some of the successful research, technologies, and treatments being offered by CHI members.

Todd Gillenwater, CHI’s senior vice president of public policy, opened the program by detailing the impact of musculoskeletal disease in the United States. In particular, he noted that in the U.S. alone, these conditions are a leading cause of disability, accounting for more than 130 million patient visits to healthcare providers each year. Further, he said the annual cost of treatment associated with musculoskeletal disease is estimated at a staggering $254 billion.

Then, CHI’s invited panel of experts took the podium in turn to present their own unique perspectives on musculoskeletal health. First to the podium was Dr. Said Ibrahim, professor of medicine and vice chair of the Department of Medicine at the University of Pennsylvania School of Medicine. His presentation focused on health disparity research in the area of joint replacement procedures, which has shown that minorities, African Americans in particular, are less likely than Caucasians to opt for elective joint replacement procedures. His findings, adjusted for key factors such as insurance coverage, indicated that the disparity was related to the fact that African Americans were less familiar with the procedures and more concerned about things like post-operative pain and recovery time. Ibrahim said he believes that this disparity is now well enough understood to be effectively addressed by a targeted educational campaign.

Dr. Deborah Kado, associate professor with the Departments of Orthopedic Surgery and Medicine at the Geffen School of Medicine at UCLA, presented research on hyperkyphosis — a musculoskeletal aging condition that creates humped necks or upper backs in men and women. The condition is now recognized as a geriatric syndrome, yet surprisingly little is known about its causes or potential means of prevention. Preliminary studies, including Kado’s own National Institutes of Health-funded projects, have demonstrated that the condition decreases lung function and quality of life, while increasing rates of falls, injury and mortality. Kado’s team has received renewed NIH funding to continue its work on hyperkyphosis through a 1,800-member cohort study of men over the age of 65.

Next to the podium was Laetitia Cousin, vice president of regulatory and clinical affairs and quality assurance with San Diego-based NuVasive. Cousin discussed NuVasive’s explosive growth led by their innovative, minimally disruptive spinal surgery devices and techniques. NuVasive’s next-generation surgical methods and tools make their procedure’s quality-adjusted life year (QALY) outcomes equal to or better than that of hip surgery, helping to erode spinal surgery’s poor 1990s-era reputation. Cousin closed by laying out two main obstacles to NuVasive’s willingness and ability to reinvest its recent profits in additional R&D and growth: U.S. Food and Drug Administration clearance/approval delays and the medical device excise tax. NuVasive recommended improved FDA transparency through guidance documents; improved FDA reviewer retention and expertise through training; improved FDA review process efficiency through earlier and more frequent collaboration with industry; and repeal of the device tax.

Last to present was Scott Simonet, Ph.D, vice president of research for Amgen. Simonet described the 15-year process to discover and develop Amgen’s denosumab, a drug that regulates bone density and helps the human body limit bone reabsorbtion. With precursor science first discovered in 1995, the product received FDA and European regulatory approval to treat osteoporosis in 2010, as well as FDA approval for cancer-related indications in the same year. While Simonet was sparing in his willingness to express complaints associated with denosumab’s approval process, he did make a point to show the length and complexity of the product’s discovery and development chain.

The presentations spurred a lively and candid follow-on discussion between the panelists and the audience. As the event closed, many expressed their thanks to CHI for organizing the session, with more than one attendee saying that that they had found it “very educational.”


CHI-Advancing California biomedical research and innovation

Executive Spotlight: Frank Ahmann, President and COO LoneStar Heart

Frank Ahmann

LoneStar Heart got its start in Southern California as CardioPolymers, with the goal of changing the way we treat heart failure and other cardiac abnormalities. Frank Ahmann, a veteran of the biotech and medical device industries, brought his expertise to LoneStar Heart following a management career in Europe and North America at Baxter International’s biotech and cardiovascular group, now Edwards LifeSciences. Among many products, he launched the first comprehensive system for the collection, processing, storage, and administration of hematopoietic stem cells. A German citizen who grew up in Mexico, Ahmann has strong ties to the European medical market and speaks English, Spanish and German. He holds a bachelor’s degree from the University of Texas at Austin and a master’s in business administration from Columbia University Graduate School of Business.

Q: Tell me something that makes LoneStar Heart unique.

A: We are not a typical venture capital-funded company. We have been funded privately by a very small group of wealthy individuals based in Texas. In the future, we expect to fund our growth through corporate partnerships and investments as well as the continued participation of our private investors.

Q: Talk about the technologies that originated at University of California San Francisco and led to the foundation of LoneStar Heart.

A: The original idea before LoneStar Heart was even formed was a company by the name of CardioPolymers Inc., based here in Southern California with technology from the University of California San Francisco (UCSF) and a gentleman by the name of Dr. Randall Lee, who was an electrophysiologist and professor there.

He was looking at a way to use an implantable hydrogel in combination with stem cells or growth factors. One of the shortcomings of stem cell therapies is that they don’t linger in the heart muscle very long or at all, and the effect of stem cell therapy and growth factor therapies is very, very limited and lasts for a very short time. So, nobody has really been able to show in significant clinical studies that stem cells in the heart regenerate tissue and improve long-term and permanently the condition of the failing heart.

The issue became “Can we make this better? Can we find a way for these stem cells to actually stay in the heart?” The one way to do that is to mix in these stem cells with the hydrogel.

Q: Have hydrogels been used in any other stem cell applications before?

A: Not in the heart at all. It is completely novel for the heart. As we were testing it, we found out that the hydrogel, without stem cells, had a very significant and positive effect on improving the mechanics of the heart, which led to the product that it is today: Algisyl. This product is essentially a gel that is derived from brown algae. It is extremely purified to remove all endotoxins and make it inert. It is liquid when you inject it and then it solidifies to the right degree when it is in the heart.

Normally, what you would expect is that the material will degrade after a few weeks. In our case, the material stayed put in preclinical models. After two years, the hydrogels were still there, in the same quantity and in the same position as they were in the beginning.

Suddenly, we found ourselves with a long-term, implantable device. It is a device because it has no pharmacologic or immunologic action.

Q: So how might this be useful in congestive heart failure?

A: A large majority of patients that have heart failure have a dilated, stretched out heart muscle that has a decreasing pumping efficiency and is incapable of delivering enough blood to the entire body. This is a vicious circle that continues to get worse with time and the implantable hydrogel actually stops or even reverses this negative trend. It accomplishes this by reducing the tension and the stress to the heart muscle purely through mechanical means.

Beyond this first step, to be able to achieve true regeneration of tissue and provide even greater efficacy, you will most likely have to combine a couple approaches. So, our idea has been all along to have the implantable hydrogel, which acts to mechanically improve the heart, combined with bioreactive small molecules or biologics that we have licensed from the University of Texas to provide the ability for tissue regeneration.

Q: What are you noticing in your initial studies?

A: Up to this point, we have treated a total of 11 patients — a majority of them are longer than one year out from when they received the implant. The safety, feasibility, and initial signals of efficacy look very positive. Therefore, we will soon begin a controlled randomized study in Europe to show efficacy delivering the product through surgical techniques. Later, an interventional catheter-based delivery will be added to the product mix.

We expect that in two years we will have enough data to receive approval to market in the European Union with the first version of the product.


CHI-Advancing California biomedical research and innovation

Event Spotlight: VC in the OC

Record-breaking attendance of more than 600 VCs and entrepreneurs convened for OCTANe’s Annual VC in the OC event, May 24, in Irvine, Calif. OCTANe CEO Matthew Jenusaitis kicked off with highlights from the OC Innovation Report, demonstrating that by quantitative and qualitative measures on the state of innovation, overall environment and investment, Orange County is an epicenter for medical technology and high tech in the U.S.

Next up, the “Alliance Strategies for Growth in the Life Sciences Industry” panel (sponsored by CHI member Deloitte) featured perspectives from Steve Pal (Allergan), Sharon Stevenson (Okapi Venture Capital), John Kehl (Edwards Lifesciences), Glenn Snyder and Jacques Mulder (Deloitte).

“Don’t overlook alliance opportunities with middle-size companies and consider the advantages of these compared to larger companies to open up the range of potential partners,” Stevenson advises.

“As a company, alliances are critical to Allergan to keep our growth rate of 12-15 percent per year," said Pal. "We are looking at technologies in all stages of development, whether early-stage or late-stage commercialization."

Kehl weighed in on Edwards Lifesciences investment in R&D: “Edwards will be flexible in structuring the deal, but the technology must be centrally relevant to our business. In the current environment, it is taking more and more to get product to market, so the R&D line is sacred and will grow through alliances.” Check out Deloitte’s study: "Critical Factors for Alliance Formation."

Mark Stevens, Partner at Sequoia Capital gave the lunch keynote. He described he and his wife Mary’s vision in creating the USC Stevens Institute for Innovation with a $200 million donation to develop a university-wide resource for USC students and faculty to transition beyond concepts into real-world implementation and address untapped opportunities. As far as new sources of start-up capital, Stevens recommends entrepreneurs access microfunds. Microfunds are typically run by high-wealth individuals with industry-specific experience who are very hands-on, investing smaller amounts and combining that with their bandwidth and connections to shepherd the company through early-stage development.

Don Milder, partner with Versant Ventures, provided his perspective on healthcare investing on the OC VC panel. He sees the U.S. Food and Drug Administration improving but still in need of reform.

"Never underestimate the power of one transforming a bureaucracy," he said. "That one individual who is making strides to improve FDA for all of us in med tech is Josh Makower."

CHI-Advancing California biomedical research and innovation

FDA Drug Lag: Challenges and Opportunities Working with FDA

CHI and Hogan Lovells convened a half-day program on the U.S. Food and Drug Administration (FDA) drug lag and the challenges and opportunities in working with the agency on new drug applications. Our guests heard from speakers including CHI’s CEO David Gollaher, Ph.D.; Rick Winningham, chief executive officer of Theravance Inc.; Marcea Lloyd, senior vice president, government and corporate affairs and general counsel at Amylin Pharmaceuticals; Beth Seidenberg, M.D., partner with Kleiner Perkins Caufield & Byers; Joseph T. Kennedy, vice president, general counsel and secretary for Transcept Pharmaceuticals, Shelley Chu, M.D., Ph.D. principal of Frazier Healthdcare; and Hogan Lovells partners Robert Church, Kevin Clayton, David Fox and Lynn Mehler.

Gollaher opened the proceedings in his keynote address, by providing highlights from CHI’s recent publication, Competitiveness and Regulation: The FDA and the Future of America’s Biomedical Industry. According to the report, which uses FDA’s own data to establish the relationship between regulation and the competitiveness of the industry, today’s FDA is not keeping pace with the innovation being produced here. The relationship between FDA and industry is strained by unexplained regulatory delays, a lack of clear standards for clinical data and an inconsistent and unpredictable pattern of communication, which has led to an increase in risk and a crisis in biomedical R&D funding. The resulting flight of product launches to EU countries should be cause for concern for everyone from policymakers to the patients who are most in need.

Subsequent speakers, including Lloyd and Winningham provided insights as executives from biomedical companies with products either currently in review at FDA or on the market, into the struggles these innovators are facing, with the capital markets in crisis and an uncertain regulatory process. Key takeaways from these people on the front lines included:

• This business is about patients. Period.
• Success depends upon taking, recognizing and managing risk.
• Surround yourself with smart advisors and even smarter employees.
• Precise communication is key – among all your trusted advisors and employees involved in the clinical trials, data analysis and regulatory approval of products, and regulators.
• It’s not just about strategy…perfect execution is key.
• Only the smart and persistent will survive in this climate.
• More companies will be forced to specialize and put all resources toward the most successful projects due to the higher barrier to entry.

Dr. Seidenberg, partner with Kleiner Perkins Caufield & Byers and Dr. Chu, principal with Frazier Healthcare, provided valuable insights from the venture capital perspective, explaining the consequences of increased risk, including money and people going overseas, not just to the EU, but to China. High tech and life sciences are both catalysts for growth overseas and Seidenberg noted that foreign executives are coming here to get educated and going back to their homelands to research, develop and commercialize medical technologies that have greater chance of being commercialized sooner overseas, rather than in the US. The regulatory and business environment in the US is “absolutely influencing our investing,” said Seidenberg, “we can’t sit back and let the US lose its competitive edge.”

When panelists, including Hogan Lovells experts from their global life sciences practice, Church, Clayton, Fox and Mehler, were asked what we can do to stem this tide of medical innovation leaving the U.S. in search of friendlier tax and regulatory environments, here were some of the insights shared:

• We need more dialogue between industry and regulators.
• We need clarification on the decision-making process, timelines and goals.
• We need more expert reviewers at FDA.
• We need to open the lens to assess risk and benefit in a systemic way.
• Without real, substantive change, the pain is going to go beyond investors and innovators – this is a crisis that is going to hurt everybody – most notably, the patients who need innovative, world-class therapies.

Stay tuned, as CHI and Hogan Lovells plan to release an Executive Summary on the proceedings from the meeting. For more information, please call CHI at (858) 551-6677.

CHI-Advancing California biomedical research and innovation

Executive Spotlight: Scott Johnson, President and Founder, Myelin Repair Foundation

A special executive spotlight from CHI and BayBiotech Review

Scott Johnson

Scott Johnson was only 20 years old when he was diagnosed with multiple sclerosis. In 2002, after waiting 26 years for a cure, Johnson took things into his own hands and leveraged his background as a business consultant and serial entrepreneur to create the Accelerated Research Collaboration model to reform the medical research and drug development system that has failed to produce desperately needed new patient treatments for millions living with chronic and debilitating diseases. In 2006, Johnson was named as one of Scientific American magazine's top 50 worldwide for business, science and policy leadership. In 2010, he received a Northern California Ernst & Young Entrepreneur of the Year Award. In 2011, Fast Company magazine named the Myelin Repair Foundation one of the top 10 biotech companies.

Q: What was the impetus of starting MRF?

A: In 1976, at the age of 20, I was diagnosed with multiple sclerosis. Unlike many who are diagnosed with MS, I was fortunate to be able to pursue an active business career, including leading three start-up companies. In 2001, I read a news brief in BusinessWeek that described work being done at Yale on myelin repair in MS. (Myelin is the insulating substance coating the nerves in the brain and spinal cord. It is also the substance that is damaged in MS. This damage is what causes the disease’s unpredictable symptoms). Up to that point, everything I had read about MS had focused on how to cure the disease or how to slow the immune reaction. So I picked up the phone, tracked the scientist down and started asking questions.

I learned two important lessons from my conversation with this scientist and others. First, scientists were starting to believe that regeneration or repair in the central nervous system was possible, and that it probably happens naturally in healthy people. Second, and perhaps the real lesson, was that it seemed that if you did things slightly differently throughout the entire continuum of medical research and drug discovery that the process of developing new medicines could be greatly accelerated. That was really the genesis of the Myelin Repair Foundation.

Q: What is the Accelerated Research Collaboration model and how is it different from traditional approaches to basic research and drug discovery?

A: The traditional model for medical research and drug discovery typically divides into several parts: basic biology, often conducted in an academic laboratory; pharmaceutical drug development; clinical trials; and FDA approval. For a variety of reasons, over the past several decades, these entities have grown farther and farther apart. The result has been a failure, essentially, to connect the vital dots that would lead to bringing a new medicine to market. That is why, in spite of a doubling of investment in research from 1995-2005, the number of new drug approvals has remained flat.

The Accelerated Research Collaboration model optimizes and integrates the contributions of all those who participate in the value chain of making new medicines. As a result, it provides a larger number of therapeutically relevant treatment targets in the pipeline, it translates discoveries made in animal models to the human system, it builds partnerships with pharmaceutical companies to develop and bring new treatments to market, and, ultimately, improves quality of life for millions living with diseases for which there are currently no effective treatment or cures.

Q: What are some of the exciting, new initiatives the MRF will be launching in the next 1-5 years?

A: The success of our discovery biology program has brought us many high-quality therapeutic targets and several new research tools that may be used more broadly in research for other neurological diseases.

At this time, we have two development paths before us: to validate the most promising novel myelin repair therapeutic targets through contract research organizations and to investigate the potential for repositioning of more than 40 targets that are in clinical development by various companies for other indications. We expect to pursue these paths in parallel and have developed a robust translational medicine platform to accomplish this.

We are also investing in the development of myelin repair biomarkers. Establishing one or more clearly measurable biomarkers will help us select the most promising of our targets for development.

Q: How are you measuring success in the near and long term?

A: Near-term success is already being measured by the number of targets identified in our funded laboratories as well as the number of new research tools that are enabling this research. In the longer term, of course, the only real measure of success will be one or more successful clinical trials for a myelin repair therapy. We are currently aiming for a myelin repair clinical trial for one of our targets in 2014.

Q: What is your fundraising strategy?

A: Though many think of us as a biotech company, we are in fact a non-profit organization supported by generous individuals, corporations and foundations with either an interest in finding a cure for MS or an interest in improving the outcomes of all medical research. In six and a half years, we have raised gifts and pledges totaling $43 million. We anticipate the next phase of our work will require as much as $80 million to complete.

Q: What is your partnership strategy?

A: There has been considerable interest from several companies in our both our portfolio of targets and our research tools. At this time, we are seeking partnerships with pharmaceutical companies who have an interest in myelin repair or who have a compound in clinical development for another disease indication that from our research appears to affect the same mechanisms for myelin repair. We are reaching gout to those companies now.




CHI-Advancing California biomedical research and innovation

Executive Spotlight: Tony Recupero, President and CEO Baxano

Baxano, based in San Jose, Calif., was founded in 2005 by Dr. Jeffery Bleich, who had the vision to create flexible tools to provide precision lumbar decompression from the “inside out.” Baxano’s mission is to develop innovative tools that restore spine function, preserve healthy tissue, and enable a better quality of life for the patients it serves.

Recupero brings over 20 years of experience in the medical device industry to Baxano. Prior to Baxano, Recupero led one of the largest and most effective direct sales forces in the spine market as vice president of sales for Kyphon Inc. Prior to Kyphon, Recupero was the national sales manager for Sulzer Spine-Tech Inc. He began his medical device career in sales and sales management with United States Surgical Corporation. Recupero is a graduate of The General Management Program at Harvard Business School and holds a bachelor’s degree in communications from State University of New York at Albany.

Q: Share with me a short history. What first brought you to Baxano?

A: I have been in spine technologies for the last 12 years and have gravitated to the introductions of revolutionary technologies. First, with Sulzer Spine-Tech and then with Kyphon, a local company that was acquired by Medtronic in 2007. I have always looked for technologies that represent advancements in care as opposed to “me-too” products.

I ran into Dr. Jeff Bleich, who is the founder of Baxano, a few years ago, in 2006. I saw the potential that the technology had – not only to provide patients with degenerative spinal stenosis a less invasive treatment but to potentially address a large subset of patients undergoing fusion today.

I have always been attracted to technologies that represent a leap forward and doing less invasive surgery with patients that help them recover faster. Ultimately, that is what attracted me to the company.

Q: How would you describe the focus of Baxano?

A: We are very focused on developing less-invasive, cost-effective technologies that can provide surgeons, patients and payors with options that will hopefully provide better patient care, while being cost-conscious because there is obviously a lot of stress on the healthcare system right now.

Q: Your product is aimed at patients with lumbar spinal stenosis. Talk about the product and what it is addressing in the marketplace?

A: There are 225,000 lumbar decompressions done in the U.S. every year. The procedure is typically done for patients that have lumbar spinal stenosis. That is the removal of some bone and some soft tissue that is creating pressure on nerve roots in and as they exit the spine.

There are also many spinal fusions done each year, and many of those fusions are done for spinal stenosis as well. Probably, at least another 250,000 fusions are done for a variety of reasons – a large subset is spinal stenosis.

What our device enables a surgeon to do is, instead of having to go from the outside in, they can go from the inside out so that it preserves tissue. We thread a wire through that space where the nerve lives, and it comes back out through the skin. We can then pull through thin, flexible devices that enable the surgeon to remove the tissue that’s pressing on the nerve without having to do as much unnecessary tissue removal.

Q: What sort of data are you gathering around your devices?

A: We have clinical trials that are enrolling right now that are single-arm trials that evaluate the use of the iO-Flex system and compare the outcomes to historical controls.

Basically, we are looking at standard spinal patient outcome measurement tools. There are four different measurement devices that are used to tell everything from patient pain to mobility. We also are studying the economics of it: the potential to save hospitals money by reducing operative time and length of stay, while improving long term outcomes.

The reality is that with devices these days, you just can’t simply add cost to a procedure; you have to demonstrate that your device either provides better patient care or that it somehow removes cost from the system.

We believe that we have potential to reduce operating time, but we are backing that up with clinical studies.

Q: When does that data come out?

A: We think we will finish enrolling the first of two studies in late 2011 and we will submit for publication the following year, so we have one year of data. So we would hope that we would have published data by 2012.

Q: How has the company been financed to date?

A: Last year, we closed a $30 million round of financing from some really top-tier investors, led by CMEA out of San Francisco. What was also validating for us is that one of the new investors is Kaiser Permanente Ventures. Kaiser, as a healthcare system, is typically very cost-focused, so for them to invest, it really made a statement that this is the technology with potential.

Q: Tell me about some of the company’s goals for the near future.

A: Our goal is to begin enrollment of a clinical trial that will demonstrate the utility of the device in lumbar spinal stenosis, as compared to some of the other techniques that are being done to treat the condition right now.

We also have goals set around numbers of surgeons that we want to train to use the devices.

We plan to expand our commercialization and we want to be able to, at the appropriate time, provide information to patients so that that they know there are alternative technologies and procedures that can help them.

Q: How well is Baxano positioned to fit within the parameters of healthcare reform?

A: We are really well positioned to address where healthcare is going. Payors are becoming more critical of technologies and procedures that do not have evidence of efficacy. Comparative effectiveness is the new direction in healthcare.

So, we think that this technology fits well with where healthcare is headed – less invasive, less cost.


This interview has been edited for length from its original version.


CHI-Advancing California biomedical research and innovation

Executive Spotlight: Brian Kennedy, CEO The Buck Institute

Brian Kennedy

Brian Kennedy joined the Buck Institute in July following a career in academia where he earned international recognition for his work in the basic biology of aging. He became only the second CEO in the institute’s history, coming from the University of Washington in Seattle where he served in the Department of Biochemistry. Kennedy earned his doctorate from the Massachusetts Institute of Technology, where he conducted research with famed biologist Leonard Guarente, Ph.D., whose pioneering studies led to the discovery that Sirtuins (SIR2) modulate aging.

Projections show that six out of 10 Baby Boomers will be living with one or more chronic conditions by 2030, and the Buck has dedicated its resources to extending healthspan, the healthy years of an individual’s life. The independent nonprofit organization, based in Novato, Calif., is the nation’s first freestanding U.S. institute devoted solely to basic research on aging and age-associated disease. Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating conditions such as Alzheimer’s and Parkinson’s disease, cancer and stroke.


Q: What do we know now about aging that we didn’t know, say, 10 or 20 years ago?

A: You can look at it from different ways. From a mechanistic perspective, we know a lot more potential things that are happening in our body that are driving the aging process. But we still don’t know the relevant contributions of different things like mitochondrial dysfunction — all those things happen with aging but we still don’t know how each of them contributes to the diseases of aging and mortality.

We have made a tremendous amount of progress in two areas. One is in the discovery of modulating agents. I think that it is clear now that aging is not intractable. You can actually slow aging — in all the model organisms now, from simple things like yeast and worms to mice and rats. The second area is dietary restriction. Last year it was shown that dietary restrictions extended the lifespan of primates.


Q: What are some of the biggest misunderstandings when it comes to aging and age-related research?

A: One of the biggest concerns is that the FDA doesn’t consider aging a disease. Now, why is that? I think the main reason is that 100 percent of the population gets it. So it is kind of a semantic argument, but it’s a problem because if you don’t consider something a disease, you cannot conduct a clinical trial.

There’s a very small amount of money that gets spent by the federal government on aging research. It is tiny in proportion to cancer. The NIH spends about $5 billion a year on cancer, about $3.5 billion on heart and lung disease, $2 billion on diabetes. They spend a little over $1 billion on aging but half of that is on Alzheimer’s, which is what I consider money well spent but is not what I would call a basic aging property. What we are saying is that we are spending a lot of money on the effects of aging, but aging is one of the causes. If you want to do something effective, you try to fix the primary problem, not the effects. But at the same time, the budget is shrinking on a federal level and we have to find ways to raise the money we need to do this research.


Q: The Buck mission is to increase the healthy years of life. So, in other words, you aren’t looking to necessarily extend life but to improve healthspan? Or, simply, take the edge off getting old?

A: It has long been known that cancer, neurodegeneration like Alzheimer’s disease, diabetes – these things increase dramatically in prevalence as we get older. And what we’re learning is that aging is actually a cause of these diseases – it is one of the causes. If you slow aging, you’re going to get benefits across a wide spectrum of disease.

What we want to emphasize is that extending healthspan is the most important thing, but extending lifespan might come along with that. But if you just tell people that you want to extend lifespan then they think about their 85-year-old grandmother who is sick and they think, “I don’t want to live longer than 85 when I am sick.” Now, the truth is that none of the models that we study do that. What they do is they extend healthspan — they make animals live longer until they start to get sick.


Q: Is it true that by studying aging, we might, for instance find the cure for cancer?

A: I think that what we’re going to find is effective, preventative measures to avoid the onset of cancer. And that’s probably true for cardiovascular disease, too. Things that slow aging are really preventing the onset of disease, and it is not yet clear in some of those cases that if you waited until after somebody got sick and then gave them the drug, whether that would be beneficial or not. That is something that is being studied but it is unknown at this point. The great study last year with rapamycin, a FDA-approved drug given to mice at 600 days of age (equivalent to a 65-year-old human), demonstrated how mice lived 15 percent longer, and lived healthier. So, I think that if you had a drug you could give to somebody at age 60, and have that kind of effect, there would be a lot of excitement around it.


Q: Talk about some of your most recent research. How does, for example, a compound intended for liver preservation become one looked at for Huntington’s disease?

A: People are starting to really understand that a lot of these different diseases have related components. Even though the mechanism of the disease is different, the events that make you prone to getting the disease in the first place may be more similar. Aging is one of those things. So the idea now is that if you have a drug, especially one that is clinically approved for one disease, thinking about it on a broader spectrum level is a useful thing to do.

From an academic perspective, we are looking at the most effective route to take the basic understanding that we have about aging and translate that to effective therapies for diseases. And using things that we already know are safe is one route to go down that path.

CHI-Advancing California biomedical research and innovation

Executive Spotlight: Bill Lis, CEO Portola Pharmaceuticals



Bill Lis, CEO Portola Pharmaceuticals

Bill Lis, CEO of CHI-member company Portola Pharmaceuticals has almost 20 years of experience in the biomedical industry. In 2007, he joined his old colleagues there after being at Scios Inc., a Johnson & Johnson company, for four years. He came in as chief business officer, was promoted to chief operating officer and then CEO. For Lis, it was a unique opportunity to join Portola as a senior executive and work again with a talented group of scientists whom he had had success with several years ago at COR Therapeutics. “We’re very passionate about thrombosis. It remains one of the most important areas for drug discovery and development because of the significant unmet medical need and our scientists have contributed several significant advances to the area over the past two decades,” said Lis in a recent interview with CHI.

“We’ve also begun to use our expertise and understanding of biological pathways and cell signaling in cardiovascular disease to expand our efforts into inflammatory diseases. What continues to emerge is the role of inflammation in cardiovascular disease and autoimmune disorders. So, I’m excited by the combined opportunities ahead of us.”

Q: What does the company look like today?

A: We now have roughly 86 employees. About 30 percent to 35 percent of them are people that have worked together for more than 15 years at COR Therapeutics and Millennium Pharmaceuticals. That is very unique in our industry and it’s what provides the foundation for the success we’ve had thus far. We also have a talented group of people who’ve joined Portola from other biotech companies and academia and they have enhanced our capabilities. What’s also unique about Portola is that we have fully integrated discovery research and development capabilities. We believe this gives us a competitive advantage and increases our R&D productivity.

Q: Who financed its early days?

A: Initially, we got funding from a very distinguished group of venture capitalists. We have, since then, added additional institutional investors or what you would call cross-over investors. These investors will, hopefully, help us expand and access a larger market for financing opportunities in the future.

Q: How did you get to the point where you are today, with roughly $1 billion in licensing deals with Merck and Novartis?

A: The value of Portola is really built around its people. These are people truly committed to the science of developing drugs that positively impact the lives of patients with very serious diseases and disorders.

As a team, we’ve executed on financing the company with private equity financing and on partnerships. But, as I said, we really got to where we are today based on the world-class R&D team that we have put into place. This is a unique team and we’ve built what we think is the appropriate amount of infrastructure and drug discovery and development capabilities. We really focus on the serious illnesses, the conditions that we think have the greatest medical needs, and then we’ve built compounds that we believe have pharmacologic properties that can significantly advance patient care over current standard-of-care agents.

Q: Talk about Portola’s lead development programs, elinogrel and betrixaban. What are these products addressing, from both a patient and a market standpoint?

A: As far as our lead products and their ability to address unmet needs — these are pretty straight forward. Elinogrel, a P2Y12 platelet receptor antagonist, and betrixaban, a direct acting oral Factor Xa inhibitor targeting the coagulation cascade, target a combined antiplatelet and anticoagulant market, for patients at risk for life-threatening blood clots. This market is projected to surpass $20 billion in the next several years. The products follow our R&D philosophy to discover compounds based on validated targets. Importantly, their pharmacologic properties are distinct from those of our competitors. Our goal now is to demonstrate in Phase 3 trials that these properties provide clear clinical advantages for patients. We hope to distinguish them broadly and for specific high-risk subpopulations.

Q: If you weren’t doing this, what would you be doing?

A: I have always had an interest in politics and world events. But I can’t think of any other industry that does more to improve human health and the quality of people’s lives worldwide.




CHI-Advancing California biomedical research and innovation

Executive Spotlight: Leland Wilson, CEO of Vivus

Leland Wilson

Wilson has been a director of Vivus since the company was formed in April 1991 and chief executive officer since November 1991. Prior to joining Vivus, Wilson was vice president of marketing and corporate development of Genelabs Technologies Inc. from 1989 to 1991. Wilson was group product director, later promoted to director of marketing, at LifeScan, a Johnson & Johnson company, from 1986 to 1989. From 1973 to 1986, Wilson served in several research, marketing and sales positions for Syntex Research and Syntex Laboratories Inc. He received his bachelor’s and master’s degrees from Pennsylvania State University and was a lieutenant in the United States Army.


Q: Vivus is among a small group of companies seeking FDA approval of the first prescription weight loss therapy in over a decade. Talk about what this means to your company and to those who await such a treatment.


A: We are fortunate in that we have two late-stage products in development. Clearly, though, the excitement in the stock market is around Qnexa because of the Phase 3 data that we have and because of the lack of effective products in this therapeutic category, which, I think, by everyone’s recognition is underserved.


Q: Can you share with us some highlights of the top-line results for Qnexa?


A: It is never-before-seen weight loss and that would include average weight loss in the neighborhood of up to 15 percent, in some cases held over a two-year period. We also noted the weight loss caused massive changes in risk of major cardiovascular events, which could help prevent early morbidity and mortality due to cardiovascular disease.


Q: Qnexa is also being tested for sleep apnea. Who, among those nighttime sufferers, might stand to benefit from this therapy?


A: It’s a devastating condition that affects breathing – you stop breathing during the night or your breathing is slowed or interfered with so that you don’t get enough oxygen. It’s an area of unmet medical need for patients.


We’ll be doing additional clinical trials in this area once we get approval for Qnexa.


Q: You, like others in the space, received a complete response letter (CRL) recently from the FDA. Any advice for companies working directly with the FDA under similar circumstances, waiting to advance important new therapies?


A: We got the CRL “lite” and fully expect, with minimal work on our part, to have an acceptable new drug application (NDA) submission. We have resubmitted our response to them, and we’ll be holding a meeting with them this month. We’ll resubmit formally, hopefully, soon thereafter. They wanted us to analyze our data in such a way as to give them assurance that this slight increase in heart rate (about 1.6 beats per minute) does not have any long-term sequela as far as long-term morbidity and concerns.


Also, topiramate carries with it a concern for teratogenic potential (birth defects). The issue there was two-fold. One, was to inform by a collection of information around the teratogenic potential of topiramate, and also Qnexa. It is largely a literature search on topiramate.


Q: Its sounds as if you are optimistic about your submission.


A: I am very optimistic.


Q: What else is on the docket for 2011?


A: We’re going to put in a NDA for our second product, avanafil, and we have also filed a European submission for Qnexa.


Avanafil is a PDE5 much in the lineage of Viagra, Cialis, etc. But it has some superior characteristics – more specific for the enzyme we’re tying to target (phosphodiesterase type 5).

We have excellent results in after 15 minutes of taking the oral pill, which is as much as 45 minutes to an hour and 45 minutes faster than the leading compounds in the market.

Q: Is the strategy still to seek a marketing partnership for Qnexa following FDA approval?


A: Yes, clearly Europe is an area where we need a partner. I think we’re going to be in a very good negotiating position to drive a good deal.


Q: Any remaining hurdles as Vivus prepares to launch its weight loss drug pending FDA approval?


A: The biggest area we have issues with is reimbursement. CMS does not cover medical treatments for obesity. The paradox in that is bariatric surgery is covered, but as a medical treatment it is not. On the private side, I would say obesity is largely not covered, however, some employers who are progressively minded do cover it. They pay the extra money to prove that overall it is a better outcome for their employees.


Certainly, in the last year, there’s been a huge rise in the awareness around obesity, specifically the contribution to the growth of diabetes as well as healthcare costs.


We’ve worked diligently on a pharmaeconomics model submitted for publication around cost of obesity and the savings that can be incurred on the public health side with the simple reduction of 5 percent or 10 percent weight loss.


We have brought our clinical data to private payers and to a number of folks in the public health area and they are very impressed with our data. While we may not have an entirely welcoming reimbursement environment the day of our launch, we’re quite confident that, say, a year after our launch it will be a very different picture. I think people will understand what obesity does and how much of a root cause it is of some of these other disease areas.


Q: What keeps you awake at night?


A: Our job here is to get a successful resubmission. The data all looks very, very good. We have to get an A+ on this report we’re filing and it’s a big one – a massive amount of work and data analysis. It is about pulling together and getting this done in a timely fashion.

CHI-Advancing California biomedical research and innovation

Executive Spotlight: Dr. Ed Holmes, President and CEO of the Sanford Consortium for Regenerative Medicine

Dr. Ed Holmes

The Sanford Consortium for Regenerative Medicine combines the intellectual resources of four of the world's leading biomedical research institutions (UC San Diego, the Salk Institute for Biological Studies, the Sanford-Burnham Institute for Medical Research and The Scripps Research Institute) to pursue collaborative research projects that advance the search for breakthrough cures. The Sanford Consortium unites San Diego's brightest researchers to work side by side to harness the regenerative power of stem cells to diagnose, treat and cure degenerative diseases and injuries. The Sanford Consortium integrates the collective knowledge of these foremost biomedical research institutions, with the support of surrounding industry and local community, to create a global resource for stem cell research.


Dr. Holmes is a distinguished professor of the University of California and vice chancellor/dean emeritus of Health Sciences at UC San Diego. He is also executive deputy chairman of the Biomedical Research Council and chairman of the National Medical Research Council, Singapore. Holmes has served on numerous advisory boards including the National Diabetes and Digestive and Kidney Diseases Advisory Council of the National Institutes of Health, the board of directors of Tularik and the scientific advisory board of GlaxoSmithKline, which he chairs. He is a member of the American Society for Clinical Investigation and the Association of American Physicians. He is also a fellow of the American Association for the Advancement of Science and a member of the Institute of Medicine of the National Academy of Sciences. He holds a medical degree from the University of Pennsylvania.


Q: Tell me about the origins of the Sanford Consortium.

A: We came into being after the bond issue (Prop. 71) was passed and the California Institute for Regenerative Medicine (CIRM) was formed. The San Diego community, including UCSD, Scripps, Salk and Burnham, decided to approach this by working together.


Q: The Sanford Consortium seems unique in that way. How did scientists in San Diego overcome the boundaries that can typically block them from coming together?

A: I think what’s interesting about this is it is really something that sort of happened on three levels. One, that the scientists actually wanted to work together. Also, the four institutional leaders (UCSD, Salk, Scripps and Burnham) saw an advantage to working together. And, then, we had community leaders in the form of Malin Burnham and John Moores and Irwin Jacobs in the beginning. And, now, Denny Sanford.

I think the four institutions and the scientists within them all working together is really what got us started. And that’s continued to be the foundation of what we do.


Q: Tell me about the building itself. What kind of progress has been made to date?

A: To get started, we need a place to house our folks. But it is important to recognize that, certainly, CIRM providing a $43 million major facilities grant was essential in this, but we would not have gotten there without the $30 million gift from Denny Sanford.

This is a beautiful location in every sense of the word—both views and the prime space. Chancellor Marye Anne Fox and UCSD helped us in that regard. This is one example of her vision—without her support we wouldn’t have gotten the loan we needed (public debt guaranteed by the UC Regents).

Denny gave us the $30 million and we’ll be using less than $20 million of that for construction of the building; the rest will be used to fund research. As for the rest, $43 million came from the CIRM grant and we sold $62 million worth of bonds, but it yielded $65 million worth of proceeds.

We are now on track for Sept. 22, 2011. We will be able to get in there July 1 and start installing equipment so that, by and large, we have a certificate of occupancy and, by the end of September, we’re ready to go.


Q: We’re at a dynamic time for stem cell research—especially with the first human trial on spinal cord injury. What excites you most about the research about to happen here?

A: We’ve begun to engage a wide group of scientists from all four institutions and you can see the genuine excitement. We’ve also begun to identify three theme areas to work in. Neurosciences, because that’s an important area for stem cell research. Also, in the area of cancer biology we’ve got a tremendous amount of strength, and in cardiovascular disease.

But what we’ve discovered is there’s so much more and we don’t want to exclude people, so we’ll probably concentrate on these three areas but embrace, though special projects, other things that would be important to bring into this.

We’re in the position to choose among the very best people, but, at the same time, we envision the consortium to be more than this building. It’s the science but it’s also all four institutions. Just because you’re not located in the building does not mean that you’re not a part of the Sanford Consortium. So, they’ve come up with some clever ways to engage people who might not be in the building long-term with special projects.

Q: Are there plans for engaging the local business community?

A: What we see as a tremendous opportunity as we build this out is, “How can we leverage what we have with partnerships in the private sector?”

One example is the basement in this building has a phenomenal capability for doing preclinical imaging studies that we think would be valuable to our investigators, but might also represent an opportunity to partner with the private sector. Some biotechs, particularly small biotechs, who cannot afford to buy some of the equipment that we will have. We would like to leverage both our science and our resources to work with this private sector and we’re just beginning our conversations.

We eventually want to do something with people. And it’s very hard to come up with things you do for people that don’t involve collaborations with the private sector. So, we have begun some very preliminary conversations right now with some of the biotech people in town. We’re also interested in talking to pharmaceutical and medical device leaders.


Q: A lot of this depends on the leveraging of federal funds and right now this is still up in the air, with stem cell research held up in the courts. What concerns do you have there?

A: Nobody can predict what’s going to happen in Washington and obviously it’s an up and down situation. But I would say the disquiet in Washington has been a boon for California. You find people who want to come anyway, but they want to come even more now. It’d be really nice if the federal government gets it sorted out—and I, personally, think they will. I’m optimistic the federal government will straighten itself out and begin to make investments.


Q: What kind of design plans does the building call for to get scientists working collaboratively?

A: For collaboration to work, first you need opportunity. And you need to run into people at the water cooler. We have rooms intended to reduce certain types of behavior and encourage collaboration. We have team rooms so six people can hook up computers at a time. It’s a smartboard, so they can write on the screen so it captures the image plus what they annotate on their screen.

We also learned that scientists go 10x horizontal before they go 1x vertical. Or, as we say, “The ability to collaborate is inversely proportional to the square of the distances.”

The building calls for wide open staircases and large open spaces that connect. It should allow people to more vertically circulate.


Q: Did you model this building after any other facilities in the country?

A: The exterior was designed to acknowledge that it has to fit contextually with the iconic structure that is the Salk. It started with the scientists back in 2007. They said, “This is what we think we need.” We had a lab planner work with them and come up with a program. And the architects then worked with the program to develop it.

This is a LEED gold building. We’re using chilled beams throughout.

We’re also taking advantage of the fact that we live in a great part of the world. We face the ocean here on top of the Torrey Pines Mesa, which allows for some fantastic views. We plan to build an open-air reception space and fully take advantage of the Southern California climate.

CHI-Advancing California biomedical research and innovation