Matthew Engel

One June 3rd, 2010 Nature Biotechnology hosted a ‘Meet the Author’ event at the Nature Publishing Group New York City headquarters. The invited speaker was Mark Kessel, Founder and Partner at Symphony Capital, LLC. Mr. Kessel is a world expert in innovative product development, mergers and acquisitions, and has spent the last several decades advising companies and financiers. His goal during this well attended and intimate event was to summarize the challenges facing the drug discovery endeavor and analyze previous and future scenarios in order to distill important lessons which can help the industry produce continued success. Before attending, each participant had each read an interview with Mr. Kessel and other business leaders from Bioentrepreneur entitled ‘Other ways of financing your company‘ which discussed trends in early-stage biotech investment. Currently, Mr. Kessel is composing an article for Nature Biotechnology regarding challenges in the pharmaceutical sector, and the business development initiatives designed to deal with them. This report will attempt to summarize the talk given by Mr. Kessel to a group of ~20 graduate students and young professionals, and the information he shared will be incorporated into his upcoming article.

Current Problems within the Pharmaceutical Industry

In the future, business development functions will hold the key to success for large pharma, which is composed of the top 15-20 largest pharmaceutical companies worldwide. The well worn traditional model, which has focused on short term successes, is limiting new breakthroughs in R&D. The traditional model for big pharma is as follows: identify new blockbuster compounds, conduct large phase III clinical trials, and mass market approved drugs to the developed world. However, Mr. Kessel asks if this model can really address the world’s current unmet need for new drugs and continued to describe hurdles facing the industry today and in the future. With pipelines becoming depleted, development costs increasing and a timeline of 10-15 years to market, the US pharma industry is encountering strong earning constraints. Unfortunately, Wall Street evaluates companies based primarily on their short term gains and punishes them for not meeting quarterly expectations. This is in contrast to investment in China which is following a controlled and purposeful ten year plan. From 2009-2014 there will be $130b lost in sales by big pharma due to products going off patent. Companies such as Pfizer are buying other companies (i.e. Wyeth), not to replenish their pipeline, but to increase their earnings in order to satisfy investors. In fact, parts of their R&D pipeline are actually being shut down. There has been an increase in direct-to-consumer advertising, which should be examined more carefully and may be promoting products inappropriately. There is growing pressure from generic manufacturers. The FDA has been under increasing scrutiny to look more closely at safety, and the regulatory environment is becoming tougher. For example, Mr. Kessel asked the audience a rhetorical question: do you think the FDA would approve an oncology compound that has been demonstrated to extend life for several weeks, but produces horrendous side effects? The FDA is under Congressional oversight, and there are concerns about how the industry is conducting itself. Another question: If the customer is currently paying $0.10/pill, would they pay $1.00/pill next year for a drug which provides marginal benefit? Mr. Kessel suspects that patients might not be willing to pay more for incremental benefits during these times of budgetary constraints. He wonders if consumers will even be able to buy the drugs they have been paying for in the past. In an effort to demonstrate the direction in which the healthcare industry is moving, Mr. Kessel shares the example of HUMANA. This is an example of an insurance provider and payer, which is currently collaborating with another company BG Medicines to discover and implement biomarkers for patients. One of the overarching problems with non-personalized medicine is that drugs will often benefit only a minority of patients afflicted with an illness. It would be ideal to target those who will respond to therapy and identify them with biomarkers, and avoid dosing patients who will be non-responders. Insurance companies are  willing to pay for the test, and patients who don’t carry the markers will not get the drugs, increasing efficiency while reducing side effects and costs.

Mr. Kessel foresees a convergence of the FDA and EMA (European Medicines Agency), with a greater focus on safety which will slow down the approval process. All drugs have a safety/toxicity trade off. In the US, we are looking for perfect safety. However, in some fields, we have deemed side effects acceptable, such as oncology. The future will show an increased focus on longevity. However, big pharma is not prepared to capture new innovation, due to their corporate structure and administrative weaknesses. Their strength lies in their ability to recognize and capture external breakthroughs. There is a need to bolster drug discovery. Cutting costs to maintain earnings is not the panacea. The use of outdated business models and flip-flopping strategies i.e. diversifying pipelines/focusing on core competencies is showing inefficient and non-optimal strategic business development.

The Role of Biotech and Generics

Biotech is viewed as a collective of small and nimble companies capable of performing high level R&D. What’s happening in biotech? There are major capital shortages. Programs are being cut and slowed down. Small companies without a year of cash reserves are being unduly punished by the market. There were 17 bankruptcies in the biotech sector last year, which is more than Mr. Kessel had seen in any year since he began practicing law several decades ago. VC’s have moved their interest to late stage compounds. Biotech is looking to big pharma for capital. The biotech industry is trying to distinguish themselves from large pharma - they don’t want to be “tainted” and need to retain their image and ability to charge as much as possible for their products.

China, Brazil, India, and Russia are viewed as rapidly growing global markets. Consumers in those nations will be frequently purchasing from primary generics producers - Pfizer, Teva, Sanofi. They are willing to pay more for name brand generics, which have increased perceived safety assurances. They are frequently opposed to generics produced in their home country. Most new compounds in development are coming out of the US. China will soon have a robust pipeline, as well. Their is a diminishing pack of Phase III compounds to pursue, creating a very small universe for pharma. There are many in-licensing deals occurring. The number of new compounds produced has been cut in half, while the budget spent on bringing them to market has doubled. Compounds which are in-licensed should be deployed. The need to maintain earnings is the most pressing issue for management. Pharma has the cash on hand, this is not the problem. However, that cash is only generating 2% interest sitting in the bank. For example, pharma is engaging in share buyback programs and purchasing outstanding shares with cash in order to control their per share income (less shares creates more revenue per share when revenue is held constant). Shareholders expect their investment to go towards innovation, instead of buying a financial instrument.

Approaches to Addressing Cutting Edge Science

Companies are assessing the cutting edge science being produced at academic institutions. VC is focusing less on early state companies. Pharma has set up their own VC wing. Sometimes they outsource their VC arm to third parties. They are investing in companies that have new platforms. Accelerator programs, such as Lilly’s Chorus have been developed as independent divisions to carry out drug development until Phase III, independent of corporate management. These divisions are sometimes spun out as new companies. There are new partnering deals occurring, drugs are becoming pre-partnered. Other companies are even experiencing foreign take overs.

How did Big Pharma Become the Partner of Choice?

The ultimate solution would be to combine the best of biotech with the best of pharma. Biotech has the entrepreneurial spirit, which can move fast and make quick decisions. Pharma has a global sales force in place, are experts with large clinical trials, regulatory affairs and has cash on hand. Pfizer has attempted a hybrid approach by creating a unique business development unit for each of its therapeutic areas, independent of each other. However, to change big pharma there needs to be a mandate from the top which awards risk taking. These companies are not taking on great compounds in order to avoid risk. Mr. Kessel suggests a change in compensation which allows leaders to shed their “risk avoidance” behavior. He mentions that “no one has ever been fired for not taking on a great compound”, but one can sure be fired for not getting their compound to pass FDA approval. Management consultants, such as McKinsey could be used to help change the corporate culture, though this often takes 5-10 years. There needs to be a creative approach to deal making which helps support innovation on the drug development side. The one size fits all approach needs to be dismissed, and the industry needs to consider new areas of opportunity. For example, the healthcare IT industry is developing databases on how patients respond to various compounds based on previous clinical trials. This could be used in the future to predict the human response to new drugs and streamline the regulatory pathway.

Final Comments

Biotech traditionally suffers from poor management, in that they don’t abandon their failing compounds early enough. Many opportunities still remain for large in-licensing deals (20-90 deals next year). Biosimilars will play an important role, though there will be less of them with more focus on generics. In the future, diversification will be key. Productivity will get worse and we will look to biotech for compounds. The Novartis Model will become more common, as big pharma purchases branded generics, consolidates, and acquires.

On Oct. 25, 2009 the Fundamentals of the Bioscience Program Alumni Organization launched its official alumni website: fobip.org/alumni. The Fundamentals of the Bioscience Industry Program is a semester long collaborative course covering information critical for students to prevail in the biotechnology, pharmaceutical, and business worlds. Graduate students are able to hear and watch seasoned professionals from both start-up and established companies describe their career paths and discuss their business models. The program has an excellent reputation for producing bright, motivated students who have been extremely successful in their careers.

The target audience for the alumni website is professionals working in the biotech and pharma industries. I wanted to create a resource that would feature useful articles from alumni and guest authors with experience relevant to program graduates. One of my goals was to put a spotlight on the alumni and draw attention to the high caliber of its course instructors, graduates, and applicants. We hope to feature articles covering the the financial industry, venture capital, intellectual property, technology transfer, recruiting, and academia in relation to biotechnology. We want to provide information that will be useful to the start-up entrepreneur, industry veteran, and job seeker. Without any advertising we have had already 1,000’s of page views and hundreds of unique visitors. I am hoping that the content we generate will be a useful resource and we are aiming to add interviews and new articles approximately every 2 weeks.

I dreamed up this concept in early Summer 2009 and discussed it with Kate Posnanski, Manager of Programs at the Center for Biotechnology. With the help of many program alumni such as Jenne Relucio and Banke Fagbemi, we were able to bring the project to fruition and launch the website this Fall. I decided to use my experience creating websites use Wordpress to generate the blog format with some additional features. We have an alumni page we are trying to build on every day featuring over a dozen of our graduates.

On the techie side, I used Wordpress as my publishing platform with the Red Evo News Blue theme from Red Evolution installed. This theme evens offers a modest support forum which was able to answer some of my questions about theme customizations about controlling the length of the except. The except is the text displayed on the homepage describing the content of an article in brief. Also, I took advantage of using custom fields for the first time. Before creating this site, custom fields were a complete mystery to me. I found this video tutorial EXTREMELY helpful, and now I use the custom field to display images on the homepage for each post. There are both thumbnail and featured image custom fields available, built into the Red Evo News Blue theme. This was also the first time I embedded a Google Calendar into a website. That part was extremely simple, and if you want to know how to do that check here.

In summary, I hope to continue building this special website, which I hold dear to my heart and hope it will bring alot of benefit to the Fundamentals Program and its graduates. Cheers!

By Mathew A. Engel

Day 1 Summary: Venture Capital Financing, Intellectual Property Management, and Emerging Business Models

The 2009 Life Science Summit took place from September 23 to 24, 2009 at the Hyatt Regency Hotel in Happauge, NY. There were hundreds of attendees representing the biotech industry and academia from all over the state. The industry attendees showed a diverse segmentation with strong representation from university technology transfer offices, law firms, venture capital firms, medicine, privately held biotech companies, mid and large-cap pharmaceutical companies. As a graduate student and alumni of the Fundamentals of the Bioscience Industry Program, I spent most of my time talking with accomplished professionals from successful companies who had experience commercializing technology, raising capital, or evaluating new ventures. Below I will summarize my findings from the most interesting sessions throughout the first day of the summit. Hopefully, in the near future I will publish a follow-up covering day 2.

What Does it Take to Build a Biotechnology Company in Today’s Environment

The opening plenary session was a great way to spark the crowd’s interest and attention. In the back of my mind, I am always thinking about starting a biotechnology company and therefore always eager to hear advice from seasoned industry veterans. These individuals, especially those who volunteer as panelists or speakers are often willing to share their knowledge and offer some deep insight to beginners. In this session the speakers focused on how to raise capital. Those who are evaluating your proposal will be thinking “where is the technology” and “where is the project”. It is suggested that you network and these connections will lead you to investors who can also guide you into small collaborations. Their role is to keep these smaller companies on track. Currently, most of the demand is for products in late stage clinical trials, in this space demand remains high. Pharma is limiting their investment to certain therapeutic areas. The days of massive deal for a new platform technology are behind us. The huge investment in genomics with no products to show for it was cited. Most deals come about because someone knew someone. It’s not just writing a business plan and patents (though that is still required!). Venture capital (VC) will only stay in for a very short time. Pharma will only jump in Phase II. VC largely invests in people they know. Mailing the best business plan in the world to VCs will get you nothing. You have to meet people some way that might invest. For example, some of the people on the panels today are Angel investors. Remember to “pick your partners”. The entrepreneur better be prepared to invest. Are there other options besides start-up? Many of the panelists, knowing what they do now, would not have chosen to start their own company. “Got to be ignorant to go do it”. Today, businesses are focusing on staying extremely lean - infrastructure is reduced. Reducing the amount of money necessary to operate. However, a company can only “be so lean” and achieve their business goals. VC is not going to be the “sugar baby” that’s going to take the company all the way through. There are drug discovery and medical chemistry labs on campus. The university should have a funding pool designated for small companies coming out of academia. One of the panelists spent time describing the experience of his friend who was trying to raise capital. His friend took no as just another opportunity to go back to him. However, it’s good to get someone with more experience and put together a team of people. “Build a culture and your company”. Medical devices is a great area to get into now. Diagnostics tools is a “neat area to be going into”. Get management in - VC looks at management team. Get help and advice from VC. Donald L. Drakeman, Venture Partner at Advent Ventures had previously ran a company and was now a VC. His motto is “management, management, management”. What makes great management? Management that will step aside.

Is the VC funding Model Broken?

Mary C. Tanner, Managing Director at Peter J. Solomon & Co. and Maggie Flanagan LeFlore, Managing Director at MedImmune Venture Inc. were two of the most outspoken panelists during this business workshop. The panel delivered an overview of the VC industry covering current trends in their investment strategies. VC’s are adaptable and clever. They are in the business of building private companies to be sold. Their goal is to reach a deal with your company, in which payments are made as milestones are met. LeFlore covered 18 deals in the last year. Private companies are easier to sell. Fewer and fewer big pharma are in the market for these investments. Their has been a fundamentals shift in exit strategy. Survival has followed those most adaptable to change. There are many exit strategies. How to get the VCs interest? Early stage risk is notorious, your goal should be to find little pockets of money to move things forward. Your faculty members better be well known (i.e. published in Nature, Science, Cell..). One of the panelists, E. Jonathan Soderstrom, Managing Director of the Office of Cooperative Research at Yale University had brought a compound to the attention of Lily. They asked for a proof of concept in humans! He did not even have that in animals. The message is that you cannot expect Lily or Genetech to fund your development costs when the product is highly experimental.

National Resource Defense Council Loses Legal Battle Against US Government

The National Resource Defense Council, local state environmental advocacy groups and Native American tribes have been protesting the construction of a new $12 billion pipeline which stands to stretch from Alberta, Canada to Wisconsin, US. On August 20th, the U.S. State Department approved permits for Enbridge Energy to begin construction. The pipeline will allow for 450,000 barrels of heavy crude to be pumped from tar sands in Canada, transported, ultimately to be refined in Wisconsin, as reported by the Associated Press. Tar sands, or oil sands, are extra heavy deposits of “unconventional crude oil” stored as bitumen deposits - a substance similar to tar, or asphalt. Bitumen contains lead, arsenic, selenium, mercury and many other toxic elements. Until recently bitumen recovery had not been considered profitable to extract due to the necessary mining process. Since this material is nearly solid, harvesting this material requires heating the tar until it is nearly boiling deep underneath the earth, and then separating out the sand and water. Some of the world’s largest tar sands reserves are in Canada, which produced 44% of its oil from this source in 2007.

Affect on US Oil Consumption

As of 2000, the US was consuming 19.6 million barrels of oil per day, one quarter of the world’s consumption at an annual rate of 7.2 billion barrels. This rate of consumption is increasing by 2% annually. It is estimated that Canada contains roughly 1.7 trillion barrels of tar sands oil, and at the aforementioned rate, is enough to last the US 237 years. However, it should be noted the cost of extracting the resource is very high - both financially and environmentally. This type of oil, referred to as unconventional oil requires surface mining or other in situ techniques that require massive amount of water and energy. Therefore, the economic benefit of mining this unconventional oil source was non-existent with the relatively cheap cost of fuel until 2005. The chart below illustrates the price of light crude oil on the NYMEX from 2001 through 2009.

Here we can see that crude oil peaked at over $140/barrel in early 2008. Economists may consider the correlation of these record high costs as a precursor to the current recession seen in the US right now. It is difficult to calculate if this was an example of correlation or causation - i.e. did the record high prices of oil spur on the recession? or did a recession cause the price of oil to collapse? This link provides historical charts tracing the price of crude oil back to 1983. The massive monetary and industrial investment in tar sands oil production and transportation infrastructure is a sign of an important trend to come in the near future - the probable increase in costs of crude oil. Since Q1 09 there is a clear rise in the cost per barrel, and this trend is likely to increase, barring unpredictable political events abroad. This commitment and investment in construction could only be worthwhile if the price of crude was expected to rebound with a dramatic increase in price. At $75/barrel, the intensive energy required for tar sands oil mining is not economically profitable. The NRDC case described above was dismissed by a federal judge on procedural grounds, claiming the NRDC lacked the proper authority to challenge the pipeline’s environmental impact permit.

Future of alternative energy at stake

With all the government pledges and political talk about alternative energy investment, technology development, and job creation, the presidential approval of this project to go forward was a massive disappointment. Economists and environmentalists alike agree that the current long-term strategy of investing in oil production is a major step in the wrong direction (see Thomas Friedman Hot, Flat and Crowded). Sierra Club Executive Director Carl Pope says ”This project will lock our nation into a dirty energy infrastructure for decades to come”. “Instead of increasing our reliance on oil and piping in pollution, the State Department should support clean, American energy and the jobs that come with it.” The decision by the federal government to allow this construction and old polluting technology infrastructure to go in place is a significant blow to the alternative energy industry. Instead of supporting the research, development, and commercialization of alternative energy technologies i.e. cleantech, the federal government is tacitly approving the influx of billions of barrels of oil, the carbon monoxide that is produced as a biproduct and released into the atmosphere, not to mention the destruction of the natural environment from which this tar sands oil came from. From an economic standpoint, this project will produce jobs in the short term, but threaten a nancesent industry from burgeoning in the long term which ahs the opportunity to transform our country and our world. This project will cost American jobs that could have been created in the high-technology industry which sustains long term financial growth, opposed to short term construction projects that do not add to any new industry.

Essentially, this is a major victory for big oil sanctioned by our own government which is acting as a mouth piece for the clean energy industry while doing literally nothing to practically support it. The rise of cleantech is not an if, but when. If it not now, it will be in the future when petroleum resources are no longer economically or politically viable or people realize that burning oil for fuel is not sustainable. And if America is not a leader in this innovation, surely China and India will step up to the plate.