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Sirtris drugs living better longer composition

N9-808-112 MARCH 18, 2008 TOBY STUART DAVID KIRON Sirtris Pharmaceuticals: Living Healthier, Much longer You can live to be a hundred if you stop all the things which make you want to live to be a hundred. Woody Allen One Weekend in March 2007, Dr . David Sinclair and Doctor Christoph Westphal co-founders of Sirtris Pharmaceuticals, a Cambridge, MA-based life sciences organization, navigated the company’s narrow hallways and filled offices into a conference room for their regular weekend strategy planning program.

When they reached the meeting room, Sinclair and Westphal reviewed their activities during the past week. Sinclair, who was an associate professor of pathology at Harvard Medical School and co-chair of Sirtris’s Technological Advisory Table, had had interviews with Charlie Increased, the Wsj, and Newsweek. Westphal, who was Sirtris’s CEO and vice chairman, experienced closed a $39 , 000, 000 round of financing, using the total quantity of invested capital in the company to $103 mil.

Sinclair and Westphal had been riding a wave of interest generated, simply, by their business promising research into age-related diseases, including diabetes, cancers, and Alzheimer’s. The company’s study into disease, however , only partly explained its physical appearance on the addresses of Clinical American, Lot of money, and the Wall Street Journal.

According for their suggestive headers ” “Can DNA Prevent Time: Unlocking the Secrets of Long life Genes (Scientific American), “Drink wine and live for a longer time: The exclusive story of the biotech startup searching for anti-aging miracle drugs (Fortune) and “Youthful Quest: Researchers seek out key to Antiaging in Caloric Cutback (Wall Street Journal) ” Sirtris was looking to develop prescription drugs that could handle diseases of aging, and so performing had the potential to extend the lifespan of human beings. The Sirtris team had, in fact , established the link between resveratrol, a compound found in reddish colored wine-producing vineyard, and sirtuins, a newly discovered family of enzymes with links to improved durability, metabolism and health in living things because diverse as yeast, rats and human beings. Sinclair and Westphal were building Sirtris around the progress sirtuin-activating prescription drugs for the diabetes market. The Sirtris team experienced developed its very own proprietary formulation of resveratrol, called SRT501, and was developing fresh chemical agencies (NCEs) that had been up to 1000x more potent promotors of sirtuins than resveratrol. Leonard Guarente and David Sinclair, “Can DNA Quit Time: Area code the Secrets of Durability Genes,  Scientific American, March 2006, David Stipp, “Researchers look for key to antiaging in calorie cutback,  Wall Street Journal, March 30, 2006. David Stipp, “Drink wine beverages and Live Longer: The exclusive history of the biotech startup looking for anti-aging magic drugs,  Fortune, March 12, 2007. See Appendix for photos of the addresses of the Wsj and Bundle of money. ____________________________________________________________ ____________________________________________________

Professor Toby Stuart and Senior Investigator David Kiron, Global Exploration Group, ready this case, with advice and contributions coming from Alexander Crisses (MBA 2008). HBS circumstances are produced solely since the basis for class discussion. Instances are not intended to serve as endorsements, sources of major data, or perhaps illustrations of effective or perhaps ineffective administration. Copyright 2008 President and Guys of Harvard College. To order copies or obtain permission to reproduce components, call 1-800-545-7685, write Harvard Business College Publishing, Boston, MA 02163, or head to http://www. bsp. harvard. edu. No component to this syndication may be produced, stored in a retrieval system, used in a spreadsheet, or perhaps transmitted in different form or perhaps by any kind of means”electronic, mechanised, photocopying, recording, or otherwise”without the agreement of Harvard Business University. 808-112 Sirtris Pharmaceuticals: Living Large, For a longer time In today’s approach session, which included Dr . Michelle Dipp, Sirtris’s senior representative of company development and Garen Bohlin, the company’s primary operating official, the team was discussing their upcoming move to new aboratory space within part of Cambridge, and three of the more pressing proper issues facing the organization. ¢ In-licensing. One concern was whether to in-license compounds coming from a biotech company to diversify Sirtris’s drug expansion platform beyond its thin focus on SIRT1, one of several sirtuin variants in the body of a human. Several users of the Sirtris executive staff were advocating a more well balanced risk profile as the company started to maximize investment in its drug advancement efforts. Relationship with Pharma.

As is almost always the case in biotech, the team was in discussions about a alliance with a few significant pharmaceutical businesses. They were looking at (a) what it would mean intended for the organization for being tied to a pharmaceutical organization at this stage of its advancement and (b) whether to postpone a deal breaker until Sirtris had even more clinical info. Was this kind of the right reason for the company’s background to do a deal? Nutraceuticals. Sinclair received a near-constant stream of e-mail and telephone calls from the community requesting Sirtris’s proprietary variation of resveratrol, SRT501.

For a while, he had contemplated selling SRT501 as a nutraceutical, an off-the-shelf health supplement that could not require FDA acceptance. This idea raised many questions regarding market opportunity, commercialization strategies, and the potential impact of any nutraceuticals providing on the Sirtris brand as well as the all-star group of scientists that had germane themselves with all the organization. ¢ ¢ Anti-Aging Science The quest for longevity has spurred the imagination of people in virtually every era in human history.

Historical Greeks imagined immortal gods, the 16th century The spanish language adventurer Ponce de Leon searched for the fountain of youth, and twenty-first-century experts test rodents for lifeextending biological compounds. Until the 1990s, the only proven means of increasing life-span in a animal was to reduce its calorie intake. In 1935, Cornell University researchers discovered that reducing calorie intake in rodents by 40% elevated their life-span by an average of 30-40%. Typical wisdom ecame that calorie reduction (CR) activates an evolutionary adaptive process that lowers metabolism to help family pets through times of foodstuff shortages or droughts. Many years passed prior to scientists could shed light on the biological device triggered by CR. When ever new information arrived in the 1980s and early nineties, it contradicted what had become the conventional wisdom. The new job indicated that instead of decreasing metabolism, caloric reduction is a biological stressor that triggers a defensive metabolic response.

Few researchers paid much attention to the shift because, as couple of serious scientists focused their very own academic occupations on antiaging studies. Extended life research started to gain traction as an academically reputable field of study inside the early 1990s, after ÜBER professor Leonard Guarente wonderful laboratory followed the molecular pathway of calorie decrease in yeast to sirtuins (silent information regulators), which are aminoacids (enzymes) which have been found in all cells. (See Exhibit one particular for schedule of scientific milestones in longevity study. ) In humans, you will discover seven types of sirtuins in different parts of skin cells and in different parts of the body. Sirtris Pharmaceuticals: Living Large, Much longer 808-112 Sirtris was focusing 90% of its RD on one sirtuin, called SIRT1 in individuals. For simplicity, any mention of the sirtuins, except if otherwise known, is to the family of sirtuins or SIRT1. David Sinclair In 93 while discovering Sydney, Down under, Guarente was taken to evening meal by several local yeast researchers, a bunch that included David Sinclair, then a young doctoral applicant at the School of New South Wales. During the dinner, Guarente mentioned that he had two students working on aging in yeast. I used to be incredibly thrilled by Lenny’s work,  said Sinclair. “I asked him so why the extended life field was so pre-occupied with looking for genes that ended lifestyle, rather than genes that could expand it. By the time we completed dinner, I told him I was likely to work with him at MIT.  Sinclair grew up in St . Ives, near Sydney Australia, the eldest son of parents who have both worked well in the medical diagnostics market. In secondary school, he was known as a talented course clown and risktaker, a new man who also aced technology classes yet could not resist setting off slight explosions in chemistry lab. Two years after their initially meeting, Sinclair made good on his assure and became a member of Guarente’s ÜBER lab being a postdoctoral other. Sinclair quickly established himself as a imaginative and successful researcher, publishing a 97 article in Cell with Guarente that described how the yeast equal of SIRT1 increased the longevity of yeast. When yeast cells divide (a sign of aging in yeast cells), they spin off extra clones of hereditary material named extrachromosomal rDNA circles (or ERCs). With each effective cell split, ERC copies accumulate in the nucleus.

The original cell, confronted with copying both equally its first genetic material and increasingly more00 ERCs, quickly runs away of energy and in the end dies. Nevertheless an extra replicate of the sirtuin gene was added to the cell nucleus, the formation of ERCs was repressed and the cell’s life was extended by 30 %. In 1999, Sinclair left Guarente’s lab for any tenure observe position in Harvard Medical School, but continued to collaborate with Guarente. 3 They identified that extra copies in the sirtuin gene extended lifespan of roundworms by as much as 50 percent. We were astonished not only by this commonality in organisms segregated by a vast evolutionary length but by fact that the adult earthworm body contains only nondividing cells,  wrote Guarente and Sinclair in their 06\ Scientific American article. four The search was about for sirtuin activating chemical substances, or STACs. This was a high-stakes search. “No substance or drug had ever before increased the experience of sirtruins said Doctor Dipp, passionately 2 David Stipp, “Drink wine and Live For a longer time,  Lot of money, February 12, 2007. several Dr . Sinclair obtained a BS with first-class respects at the College or university of New To the south Wales, Sydney, and received the

Earth Prize intended for his analysis. In 1995, he received a Ph level. D. in Molecular Inherited genes and was awarded the Thompson Award for best thesis work. He worked as being a postdoctoral investigator with Dr . Leonard Guarente at Meters. I. Capital t. being recruited to Harvard Medical College at the age of up to 29. Dr . Sinclair has received many additional prizes including a Sue Hay Whitney Postdoctoral Prize, and a unique Fellowship from the Leukemia World, a Ludwig Scholarship, a Harvard-Armenise Fellowship, an American Relationship for Maturing Research Fellowship, and is at present a New Scholar of the Ellison Medical Groundwork.

He won the Genzyme Outstanding Achievements in Biomedical Science Honor for 2004. http://medapps. med. harvard. edu/agingresearch/pages/faculty. htm, Accessed 1 . four. 07. some Leonard Guarente and David Sinclair, “Can DNA Prevent Time: Unlocking the Secrets of Durability Genes,  Scientific American, March 06\. 3 808-112 Sirtris Pharmaceuticals: Living Large, Longer known within the firm as “The General. “A compound that could activate sirtuins would raise the speed of cellular metabolism. It could have far reaching ramifications for man healthcare. In 2003, Sinclair discovered that resveratrol, a substance found in red wine, activated sirtuins in yeast cells, a discovery which indicated that in fact it might be possible to produce a medicine that could activate the sirtuin enzyme. A good way to activate the sirtuin chemical was to enhance the effects of resveratrol by giving this in extremely purified kind. Another was going to mimic the consequences of resveratrol applying an entirely new, more potent substance structure. Sirtris was going after both strategies through the SRT501 and new chemical substance entity medicine development jobs.

When Sinclair’s Nature article was printed September eleven, 2003, it had been hailed by many people scientists as a seminal conventional paper, but it also received criticism coming from members of the scientific community, including former colleagues coming from Guarente’s MIT laboratory. This article also attracted the attention of Dr . Christoph Westphal, who had recently been advertised to standard partner in Polaris Opportunity Partners, one of many larger Boston-area venture capital cash. Christoph Westphal In his four years at Polaris, Westphal had had several powerful investments and stints while founding CEO.

Between 2k and 2005, Westphal co-founded five firms and dished up as the original CEO at four of them. In every cases, Westphal recruited a CEO to change him and remained on the board because lead trader once this individual got the corporation off the beginning blocks. Two went community ” Alnylam and Momenta ” together a mixed market value of $1. some billion in early 2007. Philip Sharp, a Nobel Prize winning biologist and Sirtris advisor, described Westphal’s business and science acumen: Christophs mixture of skills is extremely rare. We havent found his comparable in 3 decades of working in biotech. a few In 2002, MIT’s Technology Review identified Westphal among the country’s leading 100 Youthful Innovators below 35. The son of two doctors, Westphal was obviously a former McKinsey consultant and physician, whom sped by using a MD/Ph. Deb. program in the Harvard Medical School in under six years. A polyglot (English, French, German, and Spanish) and accomplished music performer (cello), Westphal was referred to by several Sirtris table members because having “extraordinary energy and a popularity as a “rock star inside the biotechnology globe. He posseses an unusual mixture of abilitiesto be familiar with science and its commercial potential, and clarify it all evidently in an modest way that resonates with investors,  said Steve Freund, Taking care of Director and cofounder of Skyline Projects as well as a Sirtris director during the time of the case. Westphal had a exclusive approach to building biotech companies”his own setting of procedure. Westphal’s significant successes, Alnylam and Momenta, both went public just before many industry watchers thought them to be ready for an GOING PUBLIC.

In equally cases, Westphal teamed with world-renowned authorities (Alnylam with Paul Schimmel, a dominant scientist in the Scripps Company and biologist Philip Well-defined, Momenta with Robert Langer, an ÜBER Institute Teacher and among the world’s the majority of prolific scientist/entrepreneurs). Westphal explained the factors he appeared for as well as the approach this individual took in starting and building businesses: 5 David Stipp, “Drink wine and Live Longer,  Bundle of money, February 12, 2007. some Sirtris Pharmaceuticals: Living Huge, Longer 808-112 You need fantastic science. Second, you need a great story.

Third, you need wonderful venture capital support and lots of funds. I was a big believer in raising as much funds up front as it can be. Applying it and exploiting an expanding network among the list of biotech industry’s prominent players, Westphal got clearly produced a successful way of launching early on stage companies and then moving the CEO’s baton to another leader. In 2003, Westphal was looking for his next expense opportunity, when he encountered Sinclair’s paper in Nature. Westphal quickly realized that this was a novel and possibly watershed discovery if it could be extended to humans.

Westphal phoned Sinclair to discuss the prospects of commercializing his discovery. Launching Sirtris At the time, Sinclair was thinking of commercializing his be employed by many years. It happened in 1999, he practically joined his mentor, Guarente, in releasing Elixir Pharmaceutical drugs, a longevity-oriented biotech business. Several years after, as Sinclair finalized the 2003 Nature paper, he began exploring opportunities to form a company of his own. Sinclair described his initial meeting with Westphal, “He came in and refused to sign a nondisclosure arrangement. So , We told him I would not talk to him.

And he said, ‘David, if I walk out of this workplace, I’m not coming back. Thus i suggest you tell me just as much as you can. ‘ I ended up telling him more than I actually normally would have. It quickly became apparent that your dog is one of the best people I’d ever met. But it required months to comprehend that he’s also a wonderful guy. 6 After their initial getting together with, Westphal portrayed an interest in starting a company with Sinclair, but could hardly do so right up until he identified someone to change him since CEO of Acceleron, one of many companies he previously launched while at Polaris. In the mean time, Sinclair continuing discussions with other investors.

Westphal re-entered the picture six months after, expressing a readiness to get and move the enterprise together. Sinclair and Harvard (the owner of a lot of pieces of perceptive property that might be licensed by simply Sirtris) chosen to move forward with Westphal while the starting CEO. Following an painful decision method, Westphal decided to join Sirtris as its a lot of the time CEO. Unlike his different start-ups, his plan on this occasion was to stay with the company, which resulted in he would always be leaving behind the venture capital lifestyle and an increased six-figure wage.

Westphal explained his decision: Many people thought it was too risky to leave a prosperous VC job. I was going for a $500, 000 paycut and my wife and I got just acquired an expensive residence in Brookline close to Fenway Park. At that time, David got no info that demonstrated resveratrol stimulated sirtuins in mammals or perhaps could have an effect on mammalian glucose levels or insulin, although we all hoped everything would show true. My personal VC friends were telling me i was not being rational. Relatively they were right, yet I was anxious about Sirtris in such a way I had not yet been at my other companies. Scientific Advisory Board

Westphal set out to catch the attention of a world class Scientific Advisory Board (see Exhibit a couple of for particulars on the SAB). Virtually all early-stage biomedical corporations create planks of scientific advisors. Between 6 David Stipp, “Drink wine and Live Much longer,  Lot of money, February 12, 2007. five 808-112 Sirtris Pharmaceuticals: Living Large, For a longer time other tasks, SAB members advise the company on issues related to medical and experimental strategies, that they sometimes aid in securing usage of intellectual property produced by SAB members, and in addition they serve as sites that maintain your company abreast of developments in the broader technological community.

Sirtris’s goal was to collect the brightest scientists in the field of sirtuin research, including those who could generate IP for Sirtris and be the “eyes and ears in the company. Sinclair explained the organization of the Sirtris SAB: “Christoph said, ‘Give me a list of the top twelve people within your field. ‘ Within a week or two, i was having meeting calls with all of these people. In one case, a great academic would definitely start a competitor company, and Christoph travelled out to St . Louis and convinced him to join us instead. One observer referred to the Sirtris SAB and board of directors in the following terms (see Show 3 to get Sirtris Plank of Directors): Since combining forces with Sinclair, Westphal has prepared what is probably the most pedigree-rich scientific prediction board in biotech, which include MIT’s Razor-sharp, Robert Langer, one of medicine’s most productive inventors, as well of ÜBER, Harvard gene-cloning pioneer Jones Maniatis, and Thomas Salzmann, formerly exec vice president of Merck’s research arm. The group right now numbers 27, among them most of the world’s leading experts about sirtuins.

Westphal also put together an impressive set of directors”they include Alkermes’s Leaps, Aldrich, the Boston hedge fund manager and biotech veteran, and Paul Schimmel, a dominant scientist at the Scripps Research Institute in La Jolla, Calif., who have co-founded half-a-dozen biotech worries. Westphal’s right arm in Sirtris is definitely chief working officer Garen Bohlin, previously a senior executive by Genetics Commence, a biotech now owned or operated by Wyeth. 7 Growing Sirtris Throughout the spring and summer of 2004, Westphal and Sinclair went on a road show to community Boston-area investment capital groups.

In August, they obtained a $5 million seed (Series A) round of financing coming from Polaris Undertakings, Cardinal Companions, Skyline Endeavors and Techno Venture Administration (“TVM). Sinclair described their very own early attempts to raise capital: Christoph was very great at getting us in to consult with the majority of VCs in the Boston area more than a short period of your energy. Although a lot of persons said “no to us, Christoph arranged a small windowpane of time obtain and more than the usual few people began getting worried about staying left out. The short period of time built its very own momentum and helped travel interest in the corporation.

In November 2004, Westphal and Sinclair secured one other $13 million in a Series A-prime rounded. (See Show 4, which usually details five investment times, including buyers, dates and investment sums. See also Exhibit your five, which details pre-IPO funding at 3 comparable biotechnology firms. ) Regarding the initial two funding rounds, Westphal explained their very own ability to raise funds prior to firm had any mammalian data: We were very early on in terms of the science. We raised $18 , 000, 000 without any mammalian data, something which is almost uncommon in today’s world of biotechnology.

Part of our achievement was getting people bit by Sirtris irritate. We had a long-term eye-sight of where we’re able to go with the biology as well as the anti-aging message is extremely effective, especially when you are several David Stipp, “Live Permanently?,  Fortune, February your five, 2007. 6 Sirtris Pharmaceuticals: Living Huge, Longer 808-112 talking to lots of aging, overweight guys who are prime targets to get the medicines you want to develop. Sirtris got several decisions to make about how precisely to focus their drug development efforts.

Sinclair had made the theory that sirtuins played a task in diabetes, cancer, heart problems, neurodegenerative disorders and disorders related to mitochondrial disorders. Something was very clear: there would be simply no effort to claim anti-aging effects from any kind of drug the firm made, since the FDA did not recognize aging like a disease. The firm chosen to develop a medicine for diabetes, a large industry with outbreak numbers of type II diabetes in developed and developing countries, and an orphan drug8 for the mitochondrial disease MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like symptoms syndrome), a rare genetically inherited disorder. See Exhibit 6 for details on the global diabetes industry. ) Among 2004 and 2005, Sinclair began doing experiments that sought a connection between resveratrol and sirtuins in rats. “By early on 2005, David started receiving data in the lab that showed resveratrol was going to extend lifespan in a mammal,  Westphal explained, “At Sirtris, we had proof you could reduced glucose and insulin in mice. Out of the blue, we were getting real evidence that this actually could be a medicine, that this could actually be a very useful company. Sirtris began selecting its RD team, successfully staffing management positions with executives who had had lengthy stints in particular pharmaceutical and biotech companies ” including Millenium Pharmaceutical drugs, Alkermes, and GlaxoSmithKline ” identifying small molecules, producing drugs and advancing medications through clinical trials. With their mammalian data available, Sinclair and Westphal went back on the road looking for additional capital to financial Sirtris’s RD efforts. In March june 2006, Sirtris closed on a $27 million Series B-round of financing.

Within the next year, Sirtris made three significant advancements. (See Demonstrate 7 to get a timeline of Sirtris technological proofs of principle. ) First, the company created a ingredients for SRT501 that kept resveratrol in its effective form and increased it is absorption in to the bloodstream. The effect was that SRT501 could get 5 fold more resveratrol into the system than the finest other formulations currently available. Second, Sirtris started conducting trials in India, assessing SRT501 as a diabetes therapy.

The transition coming from an RD-only company to a clinical-stage company was, because Westphal remarked in a report, “an essential milestone in our plan to develop a rich canal of therapeutics to treat illnesses of maturing. Third, and possibly most significantly, Sinclair completed several experiments evaluating the effects of substantial doses of resveratrol on obese rats. In one try things out, middle-age rats fed substantial calorie weight loss plans with resveratrol were when compared to a control group given similar diet plans but devoid of resveratrol.

Amazingly, the mice fed resveratrol could run further, had been leaner, and, lived thirty percent longer compared to the high excess fat, no-resveratrol rats in the control group. (See Exhibit eight for a picture of mice on diet programs with minus the medication. ) Sirtris researchers were exhilarated by simply these results in part as the data suggested that sirtuins could be involved in taking care of or even delaying the onset of type-II diabetes. They were also excited since in the past experimental data on this rat style (Zucker-fa/fa) experienced tended to foreshadow an increased probability of success to get drugs in human tests. Orphan medicine status was a special designation by the FOOD AND DRUG ADMINISTRATION that approved drug makers a seven-year marketing monopoly along with tax savings for a great approved medication for diseases afflicting less than 200, 1000 people. The purpose of the orphan drug category was to offer an incentive to drug producers to focus a selection of their RD on smaller, fewer profitable marketplaces. Some of the even more well-known goals of orphan drugs contain cystic fibrosis and snake venom. several 808-112 Sirtris Pharmaceuticals: Living Large, Longer

In The spring 2006, Sirtris closed on a $22 million Series C round of financing, and obtained a $15 , 000, 000 line of opportunity debt via Hercules Technology Growth Capital. Throughout 06\, Sirtris continued to gain impetus as Sinclair’s research manufactured its approach into visible academic magazines, newspapers, and also other media. In June 06\, Sirtris announced that it had efficiently completed dosage eighty-five individual subjects within a Phase you safety and pharmacokinetic trial of SRT501. In March 2006, a paper about Sinclair’s work came out on the entrance page of the Wall Street Journal.

The next month, documents published in Cell and Nature demonstrated that resveratrol increased the endurance of mice two-fold and significantly expanded their lifespans. The 2006 Nature content also indicated that sirtuin service increased within the cell the quantity of functional mitochondria, the powerhouses that maintain a range of cellular activities including blood sugar metabolism. The discovery that sirtuin service increased the amount of functional mitochondria was, Sinclair suggested, “quite intriguing considering that the number of functional mitochondria was known to decrease with age.

Moreover, it was well-known in the scientific community that people with above average numbers of functional mitochondria, such as famed cyclist Puncture Armstrong, had above average strength levels. At the end of fall of 2006, Sinclair received an unsolicited email from Crimson Sox owner John Holly requesting a gathering. Westphal defined the meeting with Henry: This individual visits David and myself here at Sirtris. And hes a very shy, wonderful guy. After we all present him the company, he says, “How can one be helpful to you?  And I look at him, and I say, “I believe you could invest $50 million in the firm. And he says, “I dont think I can do 50 dollars million, yet I think I could do $20 million.  And I explained, “Can we close in two weeks?  John collaborated with Philip Lynch, the legendary past fund director of Fidelity’s Magellan Pay for, who did extensive research, and they stated, “OK.  Everyone wished in next. By March 2007, Westphal closed in another rounded of auto financing, raising 35 dollars. 9 million, from company executives, venture firms that had written for previous rounds, as well as John Henry and Peter Lynch.

Westphal described their fund-collecting success: We’ve always been capable to raise money, I think mainly because we had money. We were not desperate. They knew that they can couldn’t escape with planning to hammer us on the valuation, because whenever we don’t get the valuation we wish we simply won’t raise the money. Continuing to move forward Nutraceuticals Westphal and Sinclair had a long-running debate above the commercial chance represented by their proprietary formula of resveratrol (SRT501).

Sinclair had a good belief that there would be great public with regard to this formula long before the results with the clinical research on SRT501 were accomplished, and that Sirtris, one way or another, should start selling SRT501 to the community as a nutraceutical. Sinclair received an average of 30-50 emails a day from persons requesting here is how to obtain resveratrol. For a biotech company focused about drug development, a Sirtris foray in nutraceuticals would not be unmatched. For instance, Sigma-Tau Pharmaceuticals, a 50-year old Italy-based medicine company eight

Sirtris Drugs: Living Huge, Longer 808-112 specializing in rare diseases, had developed a nutraceuticals business around the FDA-approved medications for metabolic and renal conditions (carnitine deficiency) as well as cancer (antineoplastic therapy). Sigma-Tau had two nutraceutical divisions and marketed physician-recommended and clinically examined dietary supplements for patients with ulcerative colitis or irritable bowel syndrome. The opportunity in nutraceuticals could possibly be substantial. The global utraceuticals marketplace, which included sales of into the nutritional supplements, just like vitamin C and fish oil supplements, had believed annual product sales of $120 billion, and was developing at a compound total annual growth rate of seven percent. 9 For instance , the market pertaining to glucosamine chondroitin, a joint-health supplement most commonly taken by older people, exceeded $1 billion, and had been expanding in a double-digit rate. 10 The economics of the nutraceuticals marketplace were compelling. Total manufacturing costs for small molecule medications were commonly low, often in the array of 25 pennies per pill or significantly less.

Other costs would depend within the commercialization technique, of which there are numerous alternatives. Current sellers of products of resveratrol that were less bioavailable than SRT501 were charging prices in the vicinity of $1 per supplement. Westphal, yet , had doubts about if the timing was right for this kind of a endeavor, and if the firm should even marketplace a nutraceutical under its corporate company. There were a lot of issues: The nutraceuticals industry was unpredictable. It was, by and large, unregulated. Zero FDA authorization was necessary for selling products.

No proof was necessary to prove a product’s efficiency or even their composition. Sinclair had tested resveratrol supplements and found that some brands on the market acquired no lively resveratrol by any means. Other brands acquired only track amounts of energetic resveratrol, way too little to obtain any meaningful effects in humans. Even if Sirtris had a scientifically verified product, it had been not clear that science only would be enough to separate Sirtris’s supplying from the dozen or so resveratrol supplement companies. How will the company separate itself?

One final concern was your potential for client allegations about resveratrol’s protection. “The potential that somebody could characteristic a loss of life to SRT501 consumption may easily derail a nutraceuticals business,  said Sinclair. Another issue concerned Sirtris’s identity. Was your company a scientifically rigorous enterprise dedicated to developing FDA-approved medicines that physicians might prescribe to improve the health of individuals with aging-related disorders? Would the corporate brand suffer whether it started offering 501 like a nutraceutical, especially if it became, in part, a nutraceutical retailer like the makers of glucosamine?

On one hand, the Sirtris office walls were plastered with pictures of Sinclair and Westphal with Nobel award winning biologists and luminaries from the venture capital universe. On the other hand, there were the pictures of Sinclair and Westphal with celebrities, which include Barbara Walters and Mel Gibson. Abundant Aldrich, one of many company’s first investors and current plank member, described the issues in this way: “The Sirtris story can be described as balance. Is actually carefully made from the key science and Christoph and David’s public outreach.

It’s not clear if the nutraceutical way will taint that account or lengthen it.  Even if they were doing consider the nutraceuticals business, what was the company case for market entry? Just how much of a come back would warrant their participation in the market? And just how would industry entry be performed? Should the business set up an auxilliary brand or create a spin-off organization 9 http://biz. yahoo. com/bw/080220/20080220005585. html?. v=1. Accessed Feb 22, 08. 10 Richard Nagourney, “Study Sees Little Benefit in Chondroitin for Arthritis,  New York Instances, April 18, 2007. being unfaithful 808-112

Sirtris Pharmaceuticals: Living Large, Much longer devoted to SRT501? Would the subsidiary have the Sirtris term, e. g., Sirtris Well being, or will the part have another type of name, as Lexus is usually to Toyota? A few Sirtris management were favoring a wholly held nutraceutical subsidiary with a diverse name, help to make clear which the Sirtris manufacturer was dedicated to drugs based upon their NCE development system. “Our long-term investors similar to this option as they are in this firm for the NCEs. They’re not in it for the 501 data,  said Westphal. Yet another issue was price tag format.

Just how would a nutraceutical be sold: its very own retail stores, the web, supplement retailers, such as GNC? Would producing its own retail distribution remove from its medication development? Might partnering with a GNC dealer reduce control of the brand? Pharmaceutical Deal Throughout 2006, fresh evidence come about from laboratories around the world credit reporting Sinclair’s hypothesis of a connection between resveratrol, sirtuins and metabolic activity in mammals. Several pharmaceutical companies started talking with Westphal about a possible drug development partnership.

He awaited that the terms of a package could incorporate a significant straight up cash payment, an value purchase arrangement, non-milestone-based (i. e., guaranteed) RD support that would be likely to step up more than a four to five year period, and payments tied to clinical creation milestones. Sirtris would also receive royalties on product sales of any drugs caused by its SIRT activation software (See Display 9 for more details on the terms of a offer that might be likely and Display 10 for details of three deals among big pharma and other personal biotechnology businesses. As an alternative, they also believed that they may ink a deal with conditions similar to those in Demonstrate 9 however in which the pharmaceutic partner could take a 51% equity share in the business. As Westphal, Sinclair, and Dipp started again the dialogue they had been having at the begining of 2007 about the reasons pertaining to and against a deal, a single positive element that ongoing to come up is that having a medicine development deal was normally a condition of possessing a successful first public offering. Sirtris executives were hoping to take the firm public at some time in the not-too-distant future.

A successful IPO can deliver a few of the financial resources an organization needs to move drug development from the laboratory through trials. “The common biotech playbook says to get a partnership package done, in that case file for an IPO. Public investors are often reassured by the prior engagement of a pharmaceutic company,  said Westphal. Several panel members intent on gratifying the company’s capital needs acquired already been vocal their interest in exploring if the deal could be completed in attractive conditions.

Jeff Plage, a lifestyle sciences enterprise capitalist as well as the former director and chief operating official of Abbott Pharmaceuticals and a friend of Westphal’s, known that a common biotechnology firm would not become a strong IPO candidate until it finally had created some scientific data, effectively made points on two different exploration programs, founded intellectual security around its discovery of one or more fresh chemical agencies, and authorized at least one significant deal with a pharmaceutical organization. Another reason to contemplate an offer was that it may be a relatively inexpensive supply of additional capital.

Pharmaceutical lovers were typically willing to obtain an fairness stake in a premium to VC investors. As well, they may be willing to fund Sirtris’s RD programs. There were reasons to refrain from giving a deal. Westphal and Sinclair were building a company that they can hoped could have great as well as investment influence. Even though Westphal had been the founding CEO of several companies, this was the first business that he previously actively handled beyond the first 2 years. This was also Sinclair’s initially company. How would an offer affect the founders’ control over the company and its foreseeable future? 10 Sirtris Pharmaceuticals: Living Large, Longer 808-112

One more to consider deferring a deal breaker was Sirtris’s promising advancement new substance entities (NCEs). Resveratrol is a naturally occurring material and because it was already in the marketplace as a nutraceutical, intellectual property protection relevant to it would be restricted to “methods of use us patents, which could cover the application of resveratrol to take care of particular illnesses, such as diabetes, as well as ingredients work. Sirtris had just lately made advances in synthesizing new substances that could be as much as 1000 occasions more potent than resveratrol by activating SIRT1 and that would be entitled to NCE make up of matter patents.

Joining up with a huge pharmaceutical organization would need out-licensing these new compounds without knowing their very own full value. If Sirtris waited for new NCE data to arrive, it could be able to arrange a more rewarding deal than what might have been achievable in early 2007. Of course , in the event the NCE data came in and it did not produce the results Sirtris was anticipating, the pharma deal terms would be significantly worse, assuming that the pharmaceutical companies remained interested at that time. In-Licensing or perhaps Expanding the Scientific Foundation

From the very beginning of the business, Sirtris business owners had had an internal controversy over simply how much of the company’s resources to pay attention to SIRT1 vs . alternative sirtuin targets. The biotechnology sector was littered with companies and drug creation projects that had stalled in shifting from mouse button studies and toxicity screens to human being trials. A lot of board people were advocating that the organization diversify the product development platform. There were two main alternatives. One was going to investigate the six other human sirtuins.

The other was to in-license from one more biotechnology organization a compound that had a better regarded mechanism of operation. The study of sirtuins was still in its infancy, thus investigating the clinical likelihood of other sirtuins would demand a great deal of preliminary research, financing and time. (See Exhibit eleven for Sirtris financial data, 2004-2006. ) Even so, the clinical role of the other man sirtuins provided tantalizing business options. SIRT3, for instance, was found in mitochondria and was considered any drug concentrate on, but tiny was at present known regarding its functional role.

Developing a research program based on SIRT3 might enhance the company’s personal drug advancement efforts consist of mitochondrial disorders, including diabetes and MELAS. Several people of the SAB and the table of owners considered the in-licensing option to become an appealing option, although other folks disagreed. It will balance their particular investment in SIRT1, which was absorbing 90% of the firm’s RD expenses. Dr . Dipp explained that, after checking out more than one hundred or so potential substances to in-license, Sirtris got found a number of anti-diabetic substances that had better characterized effects than sirtuin-activating compounds. It would be what we call “me-too drugs. We understand how they work, and if we’re able to get them on the marketplace they would get at least a % of business. It’s something to have within your back bank.  If the firm introduced in 2005, Sinclair and Westphal debated whether to in-license a compound and decided against doing so. “I was the only person with the company,  said Sinclair, “who thought that all SIRT1 account activation was the right bet to make. I told Christoph, ‘dont stop this until you already know its incorrect. ‘ If perhaps Im wrong, find out sooner than later, and after that in-license some thing. Westphal presented another look at, “For the first 8-10 months on this company, I had been sitting there such as a venture person thinking that resveratrol will not be a fantastic drug. The a great tale, but very well have to generate other stuff to make the company around.  Though new trial and error data appeared to confirm that resveratrol activated SIRT1, and that SIRT1 activation could possibly be clinically essential, Sinclair, Westphal, Bohlin and Dipp extended to issue whether to concentrate the business time, funds, and other methods on that one target or perhaps divert more 11 808-112

Sirtris Drugs: Living Significant, Longer with the firm’s resources to added targets, which includes non-sirtuins. That they still did not have evidence that SIRT1 had the consequences in human beings that Sinclair believed they can one day see. Conclusion After discussing these kinds of three concerns for several several hours, Sinclair and Westphal chosen to summarize their particular views on the decisions that they needed to make. At an over-all level, they will remained convinced that sirtuin-activating drugs, if they could be successfully developed, could have a revolutionary impact on human disease.

However , they will recognized that Sirtris was still many years coming from completing advancement these medicines, much less production and advertising them. To reach that far away point might require effectively navigating technological and regulatory hurdles that had stymied the majority of additional biotechnology businesses at identical points in their history. Relating to a pharmaceutical drug industry affiliation report, just one in five compounds entering clinical trials attained FDA acceptance. 11 And, only 30% of accepted drugs recovered the average development cost of a brand new medicine. 2 Given all the unknowns about what could happen Sinclair and Westphal described a number of options for addressing the risks they faced: One approach would be to completely “hedge all their bets:  Sirtris can try to result in a pharmaceutical package, in-license a compound with better noted effects, and consider a nutraceuticals business around SRT501. One more approach will be to “swing intended for the fences (or, within a frequently used metaphor in the industry, “one shot at gold). This may continue the firm’s concentrate on a sirtuin-activating drug expansion platform.

In the event that successful, Sirtris could become, as one pharmaceutic executive advised, “the Yahoo of biotech.  Yet , an BÖRSEGANG (ÖSTERR.) would be not as likely in the interim, since marketplaces often prefer that biotech firms have a validating deal with a huge pharmaceutical company. A third way would be a “middle of the road path that incorporated several hedging, such as pursuing an in-licensing package, but also accepted a lot of risk, at the. g., deferring a potential pharmaceutical drug deal. Additionally, Sirtris could try to result in a pharmaceutical offer now, yet forego in-licensing and the nutraceuticals project. ******** The company seemed to have attained a critical point in its advancement. What way should Sinclair and Westphal take? And why? eleven PhRMA Pharmaceutic Profile Sector Report, 3 years ago. http://www. phrma. org/files/Profile%202007. pdf, Accessed Feb 28, 08. 12 PhRMA Pharmaceutical Profile Industry Record, 2007. http://www. phrma. org/files/Profile%202007. pdf, Seen February twenty eight, 2008. doze Sirtris Pharmaceuticals: Living Large, Longer 808-112 Exhibit you 1884: 1934 1986 Anti-Aging Science Fb timeline William Williams MD reviews that a going on a fast spider lives unusually very long, 204 days. Longevity in a fasting index, Science three or more: 4, January. 4, 1884] Clive McCay and Mary Crowell of Cornell University record delayed aging in mice on limited calorie weight loss plans. Roy Walford and Rich Weindruch present limited-calorie diet produces “youthful old rodents. Leonard Guarente of MIT mimics calorie restriction’s prolonged lifespan effects in fungus cells. David Sinclair of Harvard expands life of yeast skin cells with resveratrol. Marc Tatar of Brownish University and David Sinclair of Harvard report resveratrol extends your life of roundworms. Italian research workers are first to survey resveratrol prolongs the life-span of a vertebral animal (cold-water fish). David Sinclair and colleagues show resveratrol stretches life of warm-blood mammal (mice) and overcomes bad effects of a high-fat diet plan. JAMA. 06\ Apr a few, 295(13): 1539-48.

Lagouge, Meters. et approach., Resveratrol increases mitochondrial function and helps to protect against metabolic disease simply by activating SIRT1 and PGC-1alpha. Cell. 06\ Dec 12-15, 127(6): 1109-22. Civitarese, A. E. ou al., Caloric Restriction Boosts Muscle Mitochondrial Biogenesis in Healthy Humans. PLoS Scientif. 2007 Scar 6, 4(3). Adapted coming from http://www. longevinex. com/article. or net? story=Time%20Of%20Research%20Involving%20Calorie %20Restriction%20and%20Longevity, accessed Feb . 25, 08, and Sirtris documents. 2k: 2003 2005 2006: 2006 2006 06\ 2007 Supply: 13 808-112 Sirtris Drugs: Living Huge, Longer Exhibit 2

Sirtris Scientific Advisory Board BioPharma Expertise Tom Salzmann, Co-Chair SAB Ex – EVP Merck Julian Adams President and CSO, Infinity Peter Hutt Former FOOD AND DRUG ADMINISTRATION General Counsel Sirtuin Knowledge Biochemistry Ruben Denu, Wisconsin Anthony Sauve, Cornell Vern Schramm, AECOM David Sinclair, Co-Chair SAB, HMS Joshua Verdin, UCSF Mouse Genetics, Phenotypes James Alt, HMS, NAS, HHMI Johan Auwerx, ICB Structural Biology Cynthia Wolberger, JHU, HHMI Backlinks to Disease Ron Schute, Joslin, NAS Jeff Milbrandt, Washington College or university Jerrold Olefsky, UCSD Pere Pulgserver, HMS Eric Ravussin, Pennington Institute Li-Huei Tsai, MIT, HHMI

Bob Langer MIT, EM, NAE, IOM, Co-Founder Momenta, AIR Tom Maniatis Harvard, NAS, Co-Founder GI, Acceleron Phil Sharpened Co-Founder Biogen and Alnylam, NAS, Nobel Prize Allen Sybertz SVP Genzyme, Schering (Zetia) Eric Gordon Previous head of Medicinal Chemistry at BristolMyers, Founder of Vicuron Pharmaceutical drugs Chris Walsh Harvard, NAS, IOM, Genzyme, Vicuron Origin: Company. HHMI = Howard Hughes Medical Institute ICB = Mouse Clinical Commence in Strasburg, France EM = National Academy of Sciences NAE = National Academy of Engineers AECOM = Albert Einstein School of Medicine four Sirtris Pharmaceuticals: Living Significant, Longer 808-112 Exhibit several Sirtris Plank of Administrators (as of February 2007) Name Rich Aldrich (F) John Clarke Alan Blessure John Busenfreund Stephen Hoffman, Ph. Deb., M. Deb. Wilf Jaeger Stephen Kraus Richard Pops (F) Paul Schimmel, Ph. D. (F) David Sinclair, Ph. G. (F) Christoph Westphal, M. D., Ph. D. (F) Source: Firm. Background Founder, RA Capital. Managing General Partner, Primary Partners Momenta Managing Overseer, Skyline Projects Managing Representative, TVM Capital

Three Posture Partners Bessemer Venture Companions Chairman, Alkermes Professor, The Scripps Exploration Institute Associate Professor, Harvard Medical Institution CEO and Vice Seat, Sirtris Pharmaceutical drugs, Inc. F = President 15 808-112 Sirtris Drugs: Living Large, Longer Display 4 Sirtris Investors and Investment Models Round Date Investors Investment Pre-$ Value $2. eight M (A) Aug. 2005 Polaris Endeavor Partners, Capital Partners, Skyline Ventures and TVM $5 M A2 Oct. 2005 Polaris Opportunity Partners, Cardinal Partners, Skyline Ventures, TVM and The Wellcome Trust $13M $10. 9M B Scar 2005

3 Arch Associates, Cargill Projects, Novartis Bioventures Fund, Polaris Venture Associates, TVM, Cardinal Partners, Views Ventures, as well as the Wellcome Trust $27 M $32. 5M C Interest 2006 Bessemer Venture Partners, Genzyme Endeavors, QVT Pay for LP, Alexandria Real Estate Equities, Inc. Polaris Venture Companions, TVM Capital, Cardinal Companions, Skyline Projects, Three Arch Partners, The Wellcome Trust, Novartis Bioventures Fund, Cargill Ventures, Cycad Group, Search Ventures, and Red Abbey $22 M ($22 million in Series C-equity location, plus $15 million in venture debts financing coming from Hercules Technology Growth Capital) 95. 4M C1 Feb. 2007 John Henry Trust, Peter Lynch and several buyers from previous rounds $35. 9 million $184M Source: Company. of sixteen Sirtris Pharmaceuticals: Living Significant, Longer 808-112 Exhibit a few Pre-IPO Funding of Comparable Biotechnology Companies Company Anesiva (IPO 2004) Round/Date 2Q2001 Investors InterWest Partners, Suscripción Partners, T. P. Morgan Partners Investment $13 , 000, 000 2Q/2002 Bear Stearns Health Innoventures, Adhesión Partners, HBM BioVentures, J. P. Morgan Partners, InterWest Partners, MIC Capital, Cina Development Professional Bank (CDIB Ventures) Bristol Myers Squibb $50 million 4Q/2003 forty five million Cytokinetics (IPO 2004) 2Q/1998 Mayfield, Sevin Rosen Funds, Individual Investors $5. 3 mil 3Q/1999 Intercontinental BM Biomedicine Holdings, Vulcan Capital, Mayfield, Sevin Rosen Funds, NMT New Medical Technologies, Duke University, Person Investors Credit rating Suisse, Adhesión Partners, Lombard Odier Darier Hentsch, Mayfield, Sevin Rosen Funds, Vulcan Capital, NMT New Medical Technologies, Fight it out University, Person Investors GlaxoSmithKline $20 mil 4Q/2000 50 dollars million 2Q/2001 $14 million Momenta 2Q/2002 Cardinal Companions, Polaris Endeavor Partners $4. 4 million (IPO 2004) 2Q2003 1Q2004

Atlas Endeavor, MVM Limited, Polaris Endeavor Partners, Cardinal Partners Mithra Group, Polaris Venture Partners, Atlas Endeavor, MVM Limited, Cardinal Companions $19 mil $20 mil Source: Growthink Research. 17 808-112 Sirtris Pharmaceuticals: Living Large, Much longer Exhibit 6th Diabetes Market Data IncidenceofdiabetesintheU. S. Large numbers 15. 5 14. six 13. 6 2002 2004 2006 Worldwidemarketfordiabetes/metabolicdrugsbyclass($millions) june 2006 2010p Insulins Glitazones DPP? IVInhibitors Anti? Obesity GLP? 1Analogs Sulfonylureas ThyroidDrugs OtherOralAgents $0 $714 $75 $2, 875 $2, 118 $2, 039 $2, 099 $1, 573 $659 $493 $1, 718 $2, 026 $5, 214 six, 831 $16, 033 $9, 393 ¢ ¢ 90% of the total diabetic populace has Type 2 Diabetes Total direct and indirect costs associated with diabetes were more than $100 billion dollars in 2002 Source: Business. 18 Sirtris Pharmaceuticals: Living Large, Much longer 808-112 Demonstrate 7 Proof of Principle intended for SIRT1 Promotors Pre-clinical Beneficial Nature 2006 Nov 16: 444(7117): 337-42. Cell. 2006 Dec. 12-15, 127(6): 1109-22. Unpublished PLoS Medicine. 2007 Mar six: 4(3). JAMA. 2006 Apr 5, 295(13) 1539-48. Cellular. 2006 Dec 15, 127(6): 1109-22. Human being Physiological Individual Genetic Supply: Company. Demonstrate 8

Effects of High Doasage amounts of Resveratrol in Mice Two rats fed similar high-calorie diet in a Sirtris-sponsored study: The svelte 1 on the left received high dosages of resveratrol. Source: Business. 19 808-112 Sirtris Pharmaceutical drugs: Living Significant, Longer Exhibit 9 Potential Sirtris Pharma Deal Conditions ¢ Five year term. ¢ ¢ ¢ ¢ 19. 9% OR 51% equity share at a 50% high quality to most new share cost. a $20 million straight up for a unique option to become a member of Sirtris in developing and marketing chemical substances from its SIRT1 Activator System. 5 numerous years of guaranteed 3rd there’s r support amassing $100 million.

Payments to step up with time. $10 mil in season one. A mixture of royalties, perhaps manufacturing profits, and co-promotion fees that equate to about a 50/50 split of profits in the U. S i9000. This is an important point pertaining to Sirtris because the SIRT you activator program is a core program, plus the one that symbolizes 90% in addition of the firm’s value. The pharmaceutical firm will business lead marketing and region specific expansion ex-U. S., Sirtris to receive substantial, double digit royalties upon ex-U. S i9000. sales. Around $200 mil in milestones concurrent with risk lowering progress.

Approximately 15% upon successful completion of safety/PK of the SIRT one particular activator NCE in individuals, Roughly 25% based on declaration of sugar effects in phase 1b of NCE in man, Roughly 30% upon effective completion of a phase 2a efficacy study for a great NCE in man, and roughly 30% upon completion of phase 2b studies. ¢ ¢ a: Two diverse equity stakes were under discussion”19. 9% or 51% of Sirtris’s equity. All the other terms might remain similar in both scenarios. Supply: Company. twenty 808-112 -21- Exhibit 12 Comparison Negotiating between Comparable Biotechnology Start-ups and Large Pharmaceutical Companies

Company Anesiva is actually a late-stage biopharmaceutical company that seeks as the leader in the development and commercialization of novel beneficial treatments to get pain. The organization has several drug prospects in clinical development intended for multiple potential indications. GOING PUBLIC in 2004 (formerly referred to as Corgentech”this was your name in order to went public). Cytokinetics is a biopharmaceutical company dedicated to the discovery, advancement and commercialization of novel classes of smallmolecule therapeutics, particularly in the field of cytoskeletal pharmacology. IPO in April 2005

Deal Spouse Bristol-Myers Squibb Company Agreement Jointly develop and commercialize Corgentechs E2F Decoy (edifoligide sodium), a first-of-its-kind E2F Decoy treatment currently in Phase III development to get the prevention of vein graft inability following heart bypass graft (CABG) and peripheral artery (i. electronic., leg) bypass graft surgical procedure. Terms Bristol-Myers Squibb is likely to make an initial payment to Corgentech of $45 million comprising cash and an value investment in Corgentech, with all the potential for one more $205 million in clinical and regulatory milestone obligations.

BristolMyers Squibb and Corgentech will reveal development costs in the U. S. and Europe based on a pre-agreed percentage allowance. GSK provides committed money of approximately 50 dollars million over the minimum 5-year research term, including a $14 million in advance cash payment and a $14 million purchase of Cytokinetics preferred stock. In addition , GSK could make motorola milestone phone payments to Cytokinetics including $30-50 million per focus on for goods directed to each of over 10 mitotic kinesins which will be the subject of collaborative activities.

Sandoz has dedicated $600, 500 in an in advance cash repayment and has got the right to obtain $5-10 million in Momenta equity. RD payments believed to be $12 million and up to $50 million in contingent payments to go with development breakthrough. GlaxoSmithKline An extensive strategic cooperation to discover, develop and commercialize novel smallmolecule therapeutics aimed towards mitotic kinesins for applications in the remedying of cancer and other diseases. Momenta Pharmaceuticals begun based on private technology developed at MIT that enables high throughput, in depth characterization and engineering of sugars.

BÖRSEGANG (ÖSTERR.) in 06 2004 Sandoz/Novartis A strategic cha?non covering joint product development and commercialization in the area of complex pharmaceutical drug products. The collaboration can apply Momenta’s novel technical capabilities related to complex all kinds of sugar and the command of Sandoz in the common pharmaceuticals sector to follow the joint goal of commercializing items. Under the the agreement, Sandoz and Momenta will jointly manage product development and commercialization. Source: Recombinant Capital.

NOTICE: All bargains inked when biotech was still private. 808-112 Sirtris Drugs: Living Significant, Longer Demonstrate 11 Sirtris Financial info 2004-2006 (in thousands, besides share and per discuss amounts) Period from 03 28, 2005 (date of inception) through December 23, 2004 Period from Mar 25, 2004 (date of inception) through December 23, 2006 Season Ended Dec 31, 2006 2006 Statement of functions data: Revenue Operating expenses: Research and development Basic and management Total operating expenses Reduction from perations Interest cash flow Interest expenditure Net damage Net damage per share”basic and diluted Weighted common number of common shares utilized in net damage per share” basic and diluted Pro forma net loss every share”basic and diluted Shares used in processing pro forma net loss per share”basic and diluted Source: Firm. $ ” $ 68 $ ” 14, 242 4, 340 18, 582 $ 68 22, 494 8, 904 31, 398 (31, 330) 3, 635 (878 $(28, 573) 1, 190 699 1, 889 (1, 889) 45 ” $(1, 844) $ (0. 93) 7, 062 several, 865 twelve, 927 (10, 859) you, 143 ” $(9, 716) $ (3. 16) 18, 582) a couple of, 447 (878 $(17, 013) $ (3. 52) 1, 995, 468 3, 087, 716 some, 854, 646 $ (0. 20) eighty-five, 603, 228 22 Sirtris Pharmaceuticals: Living Large, Much longer 808-112 Appendix Fortune and Wall Street Journal Addresses Source: David Stipp, “Drink wine and Live Much longer: The unique story in the biotech start-up searching for anti-aging miracle prescription drugs,  Lot of money, February doze, 2007. twenty-three 808-112 Sirtris Pharmaceuticals: Living Large, Longer Source: David Stipp, “Researchers seek step to antiaging in calorie cutback,  Wsj, October 35, 2006. twenty four

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