{"componentChunkName":"component---src-templates-book-page-js","path":"/molecule/18/","result":{"data":{"mdx":{"id":"03092d61-2d1f-5f07-9bf4-56f28b890956","body":"function _extends() { _extends = Object.assign || function (target) { for (var i = 1; i < arguments.length; i++) { var source = arguments[i]; for (var key in source) { if (Object.prototype.hasOwnProperty.call(source, key)) { target[key] = source[key]; } } } return target; }; return _extends.apply(this, arguments); }\n\nfunction _objectWithoutProperties(source, excluded) { if (source == null) return {}; var target = _objectWithoutPropertiesLoose(source, excluded); var key, i; if (Object.getOwnPropertySymbols) { var sourceSymbolKeys = Object.getOwnPropertySymbols(source); for (i = 0; i < sourceSymbolKeys.length; i++) { key = sourceSymbolKeys[i]; if (excluded.indexOf(key) >= 0) continue; if (!Object.prototype.propertyIsEnumerable.call(source, key)) continue; target[key] = source[key]; } } return target; }\n\nfunction _objectWithoutPropertiesLoose(source, excluded) { if (source == null) return {}; var target = {}; var sourceKeys = Object.keys(source); var key, i; for (i = 0; i < sourceKeys.length; i++) { key = sourceKeys[i]; if (excluded.indexOf(key) >= 0) continue; target[key] = source[key]; } return target; }\n\n/* @jsxRuntime classic */\n\n/* @jsx mdx */\nvar _frontmatter = {\n  \"author\": \"Barry Werth\",\n  \"bookTitle\": \"The Billion-Dollar Molecule\",\n  \"isBook\": false,\n  \"numSections\": 25,\n  \"tags\": [\"a\"],\n  \"templateKey\": \"book-page\",\n  \"title\": \"Chapter Eighteen\"\n};\nvar layoutProps = {\n  _frontmatter: _frontmatter\n};\nvar MDXLayout = \"wrapper\";\nreturn function MDXContent(_ref) {\n  var components = _ref.components,\n      props = _objectWithoutProperties(_ref, [\"components\"]);\n\n  return mdx(MDXLayout, _extends({}, layoutProps, props, {\n    components: components,\n    mdxType: \"MDXLayout\"\n  }), mdx(ContentRef, {\n    id: 0,\n    mdxType: \"ContentRef\"\n  }, mdx(\"span\", {\n    className: \"stickup\"\n  }, \"I\"), \"n 1974, when Boger was in graduate school, his mother divorced his father after thirty-four years of a marriage that had grown, for her, irreparable. Despondent, Charlie Boger arrived on a Friday morning in October at the big brick Georgian Colonial where Joshua and his brothers had grown up, the house his mother liked to say \\u201Clived so good\\xA0.\\xA0.\\xA0. raised children so good.\\u201D He put a gun to his head and pulled the trigger.\"), mdx(ContentRef, {\n    id: 1,\n    mdxType: \"ContentRef\"\n  }, \"Joshua, at Harvard, was troubled but not shaken. He had not been close to his father for many years. The corollary of his deciding as a boy that he \\u201Ccontrolled the world\\u201D was an ability to wall off those things he didn\\u2019t or couldn\\u2019t influence. Such had been his relationship with his father. Equally headstrong, they had clashed since he was a child: Once, on a fishing trip to nearby Lake Norman, he threw back a fish and Charlie, furious, had knocked him out of the boat. Drenched, impotent with rage, Joshua refused to talk to him for the rest of the afternoon and for days afterward. By high school, with his parents\\u2019 marriage foundering, he had sealed his father out. When the call came that he had shot himself, Boger reacted cooly. \\u201COne of the consequences of deciding that you control your world is that you have to allow that everyone else does, too,\\u201D he says. \\u201CI\\u2019d have been much more grief-stricken if a drunk driver had killed him or if he\\u2019d spent months in a hospital bed.\\u201D\"), mdx(ContentRef, {\n    id: 2,\n    mdxType: \"ContentRef\"\n  }, \"Now, with the IPO, Boger\\u2019s mission funneled through that part \", mdx(\"a\", {\n    id: \"page_345\"\n  }), \"of himself that derived chiefly from his father: his ability to sell. Not that he was acting out a latent, one-sided struggle for autonomy. But he was enough of a student of psychology to know that men, especially, become who and what they are by vanquishing their fathers and father figures. At Merck, Boger had risen swiftly in part by renouncing his first sponsor, a tempestuous Egyptian Jew named Joe Rokash, who had brought him from West Point to Rahway. \\u201CLike all good sons, I ended up stabbing my father, stabbing Joe, in the back,\\u201D he says. Rokash had launched Boger\\u2019s ascent from bench scientist to scientific leader\\u2014a rise that was now about to culminate with his becoming CEO of a public company. His ability to sell a major deal on Wall Street, even more than his ambition to revolutionize the drug industry, required him to expunge his father\\u2019s failures as a businessman, to test how far he had come and where he would go.\"), mdx(ContentRef, {\n    id: 3,\n    mdxType: \"ContentRef\"\n  }, \"It was ironic. Boger\\u2019s chief ambitions had always been scientific; business was just an expediency, a necessity for enabling the science to occur. Success in business mattered to him only as a means to an end. Nor did he, like many in his position, glorify Wall Street as a proving ground. As head of Merck, Vagelos seemed to enjoy impressing investors. But long before his appearance at the Vista, twenty months earlier, Boger had concluded that Wall Street was hopelessly and irresponsibly capricious and thus beneath his talents intellectually, not to mention any discernible moral scope. More, though he was exceptional at it, he had little respect for the act of selling, particularly to an untutored audience. And yet Boger needed Wall Street infinitely more than it needed him. He would perform unhesitantly, single-mindedly, on its terms. He would do whatever it took to do an attention-getting deal.\"), mdx(ContentRef, {\n    id: 4,\n    mdxType: \"ContentRef\"\n  }, \"Initially, that meant recasting Vertex\\u2019s story to suit the rampant, overblown expectations of the stock market. As Aldrich put it, there was a lot of \\u201Cproduct\\u201D now \\u201Ccranking\\u201D to soak up the new money that was flooding into emerging biomedical companies. At the same time, the Regeneron debacle had made investors as skittish as cats. To Boger, naturally, this contradiction played all to Vertex\\u2019s strengths.\"), mdx(ContentRef, {\n    id: 5,\n    mdxType: \"ContentRef\"\n  }, \"Most of the companies going public were, strictly speaking, biotech companies: Like Amgen, their standard-bearer, they proposed \", mdx(\"a\", {\n    id: \"page_346\"\n  }), \"to make drugs by manipulating genes. But unlike Amgen and the first generation of gene-splicers, they weren\\u2019t simply talking about manufacturing proteins, which are notoriously hard to make, must be given as shots, break down quickly in the body, and are especially vulnerable to patent shakedowns. The new companies talked dazzlingly about \\u201Csuperdrugs\\u201D: \\u201Csmart\\u201D molecules that through more exquisite targeting or the application of advanced technologies or both would make conventional drugs\\u2014biotech and otherwise\\u2014obsolete. It was the difference between workstations and mainframes, pocket cellular phones and conventional desk models. There were stories about drugs that locked onto the sugar molecules that act like intercellular road signs, blocked them, and confounded inflammation: drugs that short-circuited DNA messages, thus defusing diseases like AIDS and cancer; genetically altered cells transplanted into organs to act as factories for churning out drugs against cancer and diabetes; turbocharged vaccines; kamikaze drugs that strapped antibodies, nature\\u2019s own disease fighters, to little micromolecular rockets and sent them speeding into errant cells.\"), mdx(ContentRef, {\n    id: 6,\n    mdxType: \"ContentRef\"\n  }, \"The major problem with these superdrugs, as Boger knew, was that no one had proven that they worked. There were major questions about the rationales behind them, about how to get them to their targets, about whether many of their targets were even active. Would the molecules survive in the body? What about side effects? No one knew because there were no data: The mechanisms were largely theoretical. Vertex, on the other hand, intended to make small molecules that inhibited known enzyme targets just as Merck and the other big drug companies had been doing for decades\\u2014\\u201Clittle pills in bottles with white cotton on top,\\u201D Boger liked to say. Such drugs were relatively easy to make and to patent and were known to work. The markets for them were established and huge. Boger knew he had to satisfy Wall Street\\u2019s hunger for superdrugs, but to the extent that he also could distance Vertex from the doubts about them, he knew he might also assuage Wall Street\\u2019s uneasiness and position the company as a surer bet.\"), mdx(ContentRef, {\n    id: 7,\n    mdxType: \"ContentRef\"\n  }, \"There were other structure-based design companies with claims equal to Vertex\\u2019s, most notably Agouron Pharmaceuticals, a seven-year-old La Jolla firm that was the first company dedicated exclusively \", mdx(\"a\", {\n    id: \"page_347\"\n  }), \"to using protein structures in drug design, but Boger scoffed at any comparison between them. In April, for instance, Agouron announced in \", mdx(\"i\", null, \"Science\"), \" that its crystallographers had solved the structure of a portion of the enzyme that enables the AIDS virus to hijack T cells. There had been a chorus of flattering press coverage, carefully orchestrated by the company, and its stock had soared on cue. A closer reading of the \", mdx(\"i\", null, \"Science\"), \" paper, however, revealed that the enzyme site, which the company identified as \\u201Cclearly an important clinical target,\\u201D in fact had \\u201Cno detectable activity.\\u201D \\u201CIt\\u2019s a dead target,\\u201D Boger sneered incredulously. \\u201CWhere\\u2019s the drug?\\u201D\"), mdx(ContentRef, {\n    id: 8,\n    mdxType: \"ContentRef\"\n  }, \"From a business standpoint, what differentiated Vertex\\u2019s story\\u2014and what Boger now intended to flog most assiduously\\u2014were three things: Vertex\\u2019s integrated approach, its first-among-equals attention to chemistry, and its lineage, which tracked impressively through the mainline of the pharmaceutical industry and Merck, then Wall Street\\u2019s favorite company. \\u201CSmart ex-Merck guys making drugs with computers,\\u201D Aldrich said, encapsulating. Agouron had exquisite crystallography, arguably the best in the world. But drug companies make their billions by selling molecules, not molecular structures. Unlike Vertex, Agouron seemed to commit itself fully to designing inhibitors only after a structure was solved, so that it would be unlikely, for instance, to produce a development like Vertex\\u2019s 367, a promising drug lead that preceded having the structure of FKBP-12 by several months. Like Schreiber, Boger intended to show that the future of biology led through the synthesis of new and better compounds, through chemistry, and for that Vertex\\u2019s bloodlines were impeccable. It had sprung from Merck. What else did investors need to know?\"), mdx(ContentRef, {\n    id: 9,\n    mdxType: \"ContentRef\"\n  }, \"Throughout May Boger worked on his slide show. In the past, he had tailored it for venture capitalists, drug company executives, and other scientists, who needed little explanation. But Boger was now about to face the most unsophisticated audience he had ever addressed: institutional investors, portfolio managers, syndicate players, floor traders\\u2014people who had little concept of what he was trying to do and who bought and sold stocks according to criteria he disdained. As always, he tried to imagine their thinking. He juxtaposed on one slide, for instance, cartoon drawings of a hypodermic \", mdx(\"a\", {\n    id: \"page_348\"\n  }), \"needle and a pill bottle. Next to the needle was the figure $5 billion, representing the total annual sales of all biotech drugs; next to the bottle, in much larger type, $160 billion, the total for small molecules. The slide deftly, if simplistically, combined several points. As Aldrich put it, \\u201CYou don\\u2019t see blockbuster drugs for acute situations. You see them for chronic cases, and that means ingestibles\\u2014pills. That\\u2019s where biotech falls down.\\u201D Boger was proud of the slide. Like a reference to \\u201Cpond scum\\u201D in his explanation of natural products screening, it confirmed Vertex\\u2019s place as a new paradigm in drug discovery, a Third Way, smarter and more rational than the big pharmaceutical companies, more lucrative and friendlier than biotechnology. It was something even the most uninitiated buyer could grasp.\"), mdx(ContentRef, {\n    id: 10,\n    mdxType: \"ContentRef\"\n  }, \"Boger had learned from his father when to be explicit and when to back off, letting, as with his discussion of potential markets, buyers\\u2019 reveries take over. But he also had to sell Vertex\\u2019s science, a more exacting exercise. Boger agonized over this reductive process. He went around and around with Holman and Kidder\\u2019s sales staff, who looked at him quizzically each time he used such fundamental nomenclature as \", mdx(\"i\", null, \"target, inhibitor\"), \", even \", mdx(\"i\", null, \"binding\"), \". After a morning with a Kidder delegation in which several of the salespeople urged him to use \", mdx(\"i\", null, \"stick to\"), \" instead of \", mdx(\"i\", null, \"bind\"), \" to describe the interfingering of molecules, Boger finally threw up his hands. \\u201CIt\\u2019s hard,\\u201D he complained. \\u201CI\\u2019ve never gone down to this level before. I may be able to get away with \", mdx(\"i\", null, \"safety\"), \", but \", mdx(\"i\", null, \"efficacy\"), \" I have to explain.\"), mdx(ContentRef, {\n    id: 11,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI\\u2019m thinking,\\u201D he sighed, \\u201Cthat this is all fine, but I better put it aside now and address the level of scientific education in America.\\u201D\"), mdx(ContentRef, {\n    id: 12,\n    mdxType: \"ContentRef\"\n  }, \"Ultimately Boger packaged Vertex\\u2019s story into fewer than thirty slides, 50 percent less than usual. Many of them were stunning new computer images modeled by Murcko, who for several days designed and photographed them instead of doing science and ambivalently thought them, if anything, too facile. One series of stick-and-ball diagrams showed FKBP-12 first alone, then with FK-506 suspended over the active site, then with FK-506 and an unidentified Vertex proprietary compound docking with the precision of two satellites. The progression made it seem as if the company had indeed put to practice Aldrich\\u2019s \\u201Cconnecting the dots\\u201D\\u2014inserting spacers between the atoms on FK-506 that were \", mdx(\"a\", {\n    id: \"page_349\"\n  }), \"essential to its activity\\u2014in order to make better drugs. Even more tantalizing was a luminous ribbon diagram of HIV protease with an inhibitor nestled Venuslike in its maw. How simple, one thought. Elegant, sensual even.\"), mdx(ContentRef, {\n    id: 13,\n    mdxType: \"ContentRef\"\n  }, \"Boger, an aficionado of slides and computer-generated molecular graphics alike, complimented Murcko profusely. \\u201CThese are great slides,\\u201D he said. \\u201CYou can build all kinds of purposes into these slides.\\u201D Aldrich, drifting in from his office next door, reprised the theme. Noting a slide stating that Vertex\\u2019s scientists had forty years combined experience in aspartyl proteases, Dave Livingston joked to him: \\u201CAnd on the business side, how many years combined experience do we have selling smoke?\\u201D Aldrich smiled, \\u201CIt\\u2019s the intensity of the commitment.\\u201D\"), mdx(ContentRef, {\n    id: 14,\n    mdxType: \"ContentRef\"\n  }, \"Science and business together had driven Boger through the previous period of publicizing Moore\\u2019s paper and handling \", mdx(\"i\", null, \"Nature\"), \", but now he was in complete, unmitigated sell mode, thinking only about money. The rush to file a red herring quickly before the SEC, so that Vertex could go public before the investment \\u201Cwindow\\u201D on Wall Street crashed shut, consumed all his effort and attention. Indeed, there were signs that he was already too late. By the third week in May, Regeneron was trading at $11.75, down from $22 just six weeks earlier. Isis, another glamour company with an intriguing story about blocking DNA, was said to be in trouble, and ImmuLogic, a Cambridge start-up specializing in peptide drugs, was forced to cut its initial offering price from a range of $14 to $16 down to $12. The business press had picked up on the jitters and was riding the story, particularly the \", mdx(\"i\", null, \"Journal\"), \", which began publishing daily predicitions of an impending shakeout. An amnesiac market, which since the first of the year had somehow forgotten that IPOs were extraordinarily risky, that almost all new public companies traded down from their initial prices, that even Amgen had gone to $3 and stayed there before reviving, suddenly was shocked to wake up with a stunning hangover. \\u201CThese people are just discovering compounds and they want a public market asking price,\\u201D a prominent fund manager complained indignantly. \\u201CWhy should I pay a public price for a venture company?\\u201D\"), mdx(ContentRef, {\n    id: 15,\n    mdxType: \"ContentRef\"\n  }, \"Boger, typically, was undaunted; as always, he was \\u201Cleaving things indeterminate\\u201D until the last moment when he would have to decide \", mdx(\"a\", {\n    id: \"page_350\"\n  }), \"whether or not to take the offering forward. Aldrich just as typically blamed the \", mdx(\"i\", null, \"Journal\"), \" series as much as the overheated market itself for the current spate of whiplash. Writing all day, from 7 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"A.M\"), \". often until midnight, faxing draft after draft to Kidder and to Warner and Stackpole, where legal secretaries were now typing documents for the SEC around the clock, consulting hourly with Boger and the board members, he proceeded as if Vertex was moving inexorably toward going public, though more and more he was sure they were too late. \\u201CWhen I saw Icos melting down and I heard from my friend at Merrill Lynch how bad ImmuLogic was doing, I laughed, \\u2018That\\u2019s it. It\\u2019s over,\\u2019\\xA0\\u201D he said. \\u201CBut you spend a day drafting. It draws you back in.\\u201D\"), mdx(ContentRef, {\n    id: 16,\n    mdxType: \"ContentRef\"\n  }, \"The red herring was finished on May 29, 1991, less than five weeks after Vertex decided to go public. It was an extraordinary document, not because it was different from the dozens of others new in registration with the SEC, but because it was like them\\u2014scant on substance (of which there was little to report), laden with risk factors.\"), mdx(ContentRef, {\n    id: 17,\n    mdxType: \"ContentRef\"\n  }, \"Especially this last. The company was obligated to note, for instance, that structure-based drug design had yet to yield an approved drug; that Vertex planned to hemorrhage money indefinitely; that it had \\u201Cno assurance\\u201D that it could find, develop, market, manufacture, or get approval for a drug much less profit from one; that many of its competitors had \\u201Csubstantially greater financial, technical, and human resources\\u201D; that it might not be able to survive without Boger, on whom it held a $2 million \\u201Ckey man\\u201D life insurance policy.\"), mdx(ContentRef, {\n    id: 18,\n    mdxType: \"ContentRef\"\n  }, \"Given so little certainty, such narrowed odds, it was perhaps a wonder that Vertex or any other biomedical start-up would be sanctioned to sell shares publicly. But that presumed an orderliness and public trust that went beyond Wall Street\\u2019s obligation or ken. Wall Street had only one cardinal rule, caveat emptor\\u2014buyer beware. By filing with the SEC, Vertex was fulfilling its debt to truth and the commonwealth. Whatever else, investors couldn\\u2019t say they hadn\\u2019t been warned.\"), mdx(ContentRef, {\n    id: 19,\n    mdxType: \"ContentRef\"\n  }, \"Boger had never denied or dismissed any of the risk factors. In the pharmaceutical industry, failure is the norm, even more so in small companies. Indeed, his rationale for starting Vertex was to shave incrementally, one by one, the risks inherent in drug discovery, \", mdx(\"a\", {\n    id: \"page_351\"\n  }), \"making the process more scientific, surer, more predictable. And yet now, with the risks openly acknowleged, Boger was free not to talk about them, to gloss them over, to sell Vertex\\u2019s story as if they\\u2019d already been brought under his steadfast control. He was as buoyant and all knowing as ever. Vertex may in fact have been a small, desperately unprofitable company with no products, unproven technology, and no guarantee of success, going up against a mountain of nightmarish uncertainties, but so was every other small company. Compared to them, Boger liked to say, Vertex was \\u201CAmgen.\\u201D Now that he would soon be talking to them directly, he was sure investors would have no choice but to agree.\"), mdx(ContentRef, {\n    id: 20,\n    mdxType: \"ContentRef\"\n  }, \"Rolling, Boger entered the registration period\\u2014four to six weeks during which the SEC would review Vertex\\u2019s filing while Kidder and the other underwriters premarketed the deal among the big fund managers who buy 60 to 80 percent of all IPOs\\u2014as fearless as if Vertex were reporting record profits. The company\\u2019s initial asking price, worked out after endless rounds of talks with Holman and Kidder\\u2019s sales force, was $13 to $15 per share\\u2014ambitious, but not overly so. Again Boger, starting far behind and deep in traffic, had pulled up even, only this time with Wall Street itself, and no one, not even he, could predict what Wall Street, in its infinite volatility, would do next.\"), mdx(ContentRef, {\n    id: 21,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 22,\n    mdxType: \"ContentRef\"\n  }, \"The scientists, understandably, saw another view.\"), mdx(ContentRef, {\n    id: 23,\n    mdxType: \"ContentRef\"\n  }, \"They saw unproven science, unmet expectations, uncertain goals\\u2014a story lunging out of touch with reality. They saw molecules that were still far from drugs, labs stretched to the limit, a Schreiber juggernaut. With immunophilins, they saw unanswered questions\\u2014How did FKBP-12 work? Was it the relevant target? How did it bind to FK-506? What accounted for the drug\\u2019s increasingly cyclosporinelike side effects?\\u2014that left them unsure how to go about designing new drugs or even whether better drugs could be designed. With HIV, they saw sorely overtaxed chemists struggling to get from out behind other companies\\u2019 patents, no protein for crystallography, and the brick wall of making a protease inhibitor to survive the gut. Perhaps worst of all they saw a growing lack of focus. It wasn\\u2019t that they hadn\\u2019t performed extraordinary \", mdx(\"a\", {\n    id: \"page_352\"\n  }), \"acts of individual science, but drugmaking needs careful leadership, and without Boger\\u2014who was cloistered with Aldrich or editing his slides or flying off to New York to meet with the Kidder sales force, or squeezing in a last-ditch trip to Japan in early June to try to sell the HIV project to \\u201Cour noodle buddies\\u201D\\u2014the project councils had begun to falter. Waiting for the emergence of self-actualized champions, Boger had deliberately not anointed lieutenants, leaving the scientists to chart through the myriad of scientific questions collectively. But the experiment was going badly, leaving the scientists frustrated, disappointed, resentful, spent, and, in a few cases, bereft.\"), mdx(ContentRef, {\n    id: 24,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CJoshua has to finish up talking to the money boys and get back and start stroking his people,\\u201D Jon Moore explained. \\u201CScientists need to be stroked. They need to be treated in a fatherly manner on a day-to-day basis.\\u201D\"), mdx(ContentRef, {\n    id: 25,\n    mdxType: \"ContentRef\"\n  }, \"Boger defended the paradox\\u2014going on the road to sell a scientific approach that required his leadership, which he was unable to provide because he was out selling it\\u2014as a necessary cost of doing business. He sounded like a father, like himself with his own kids or perhaps like Charlie Boger with him, explaining why he had to spend so much time away from home. Ultimately, he said, it would allow him to become more involved in the company\\u2019s science, not less, since a big bolus of money would release him from the constant pressure of selling projects and chasing deals. He envisioned a day soon when he didn\\u2019t have to go on every death march, when other companies would come to Vertex, when he would be more available to watch over things and make sure they worked as planned. The scientists, of course, didn\\u2019t believe him. Watching him go off to Warner and Stackpole or to meet with institutional investors, they imagined he had found a new enjoyment, a new challenge, a new mistress of sorts. They began to wonder whether Boger cared as much about science as about climaxing his own rise\\u2014\\u201Cbeing on the cover of \", mdx(\"i\", null, \"Business Week\"), \",\\u201D a few muttered.\"), mdx(ContentRef, {\n    id: 26,\n    mdxType: \"ContentRef\"\n  }, \"The pricing of Vertex\\u2019s stock had exacerbated their distrust. It was assumed, of course, that the IPO would make everyone connected with the company richer, perhaps spectacularly so, the cloning of millionaires being one of the most enduring\\u2014and appealing\\u2014clich\\xE9s about small companies that go public. But because \", mdx(\"a\", {\n    id: \"page_353\"\n  }), \"of the shaky market, Vertex and Kidder resorted to a mathematical sleight of hand in arriving at the price of individual shares. The maneuver, common among new publicly owned companies, is called a \", mdx(\"i\", null, \"compression\"), \" or \", mdx(\"i\", null, \"reverse split\"), \". It works by reducing the number of shares in order to buoy the stock price. When Vertex had first decided on a $13 to $15 range, the market was still supporting such optimistic prices. However, as the window drew down, other companies like ImmuLogic were forced to cut theirs. Rather than reduce its price, which not only would diminish Vertex\\u2019s cachet, but might be seen by investors as a sign of weakness, Boger and the board had opted for a 3 to 2 compression. The dollar value of each individual\\u2019s equity was unchanged\\u2014three shares at two dollars equals two shares at three\\u2014but many of the scientists still felt cheated.\"), mdx(ContentRef, {\n    id: 27,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CIt\\u2019s like, \\u2018What are you doing to me?\\u2019\\xA0\\u201D explains Holman. \\u201C\\xA0\\u2018I give you three, you give me two back? And then the stock price is lower than I thought it was going to be? It\\u2019s like I\\u2019ve lost twice here.\\u2019\\xA0\\u201D\"), mdx(ContentRef, {\n    id: 28,\n    mdxType: \"ContentRef\"\n  }, \"In the labs, the compression was rumored for days before it was announced. Boger, harried and thinking it a non-issue, eventually disclosed it in a perfunctory, hastily called meeting in the lunchroom in which he seemed both impatient and irritated at having to answer for it. Pockets of anger suddenly exploded. Dave Armistead, lead chemist on the immunophilins project, was particularly appalled. He and the other scientists had come to Vertex in large part because of the stock incentives, but now, he said, Boger was changing the game. It was tantamount to fraud. Sounding out other scientists about possible legal action against the company, he flexed for several days before calming down. \\u201CAs you can see, I\\u2019m not one of those people who\\u2019s enchanted with the idea,\\u201D he later fumed. \\u201CI\\u2019m not going to let it blow my year, but for a couple of days, I\\u2019ll moan.\\u201D\"), mdx(ContentRef, {\n    id: 29,\n    mdxType: \"ContentRef\"\n  }, \"Throughout June, the episode refused to diminish, burning like a corrosive through the unanimity that had peaked with Moore\\u2019s \", mdx(\"i\", null, \"Nature\"), \" paper. There was Boger\\u2019s handling of it, which many of the scientists saw as a reflection of his and the company\\u2019s new priorities. \\u201CIt\\u2019s Josh\\u2019s bullshit mode,\\u201D chemist Jeff Saunders complained. \\u201CHe\\u2019s not out to fuck anyone over, but at the same time he can be \", mdx(\"a\", {\n    id: \"page_354\"\n  }), \"condescending. When he flips into business mode, you know he\\u2019s doing something he doesn\\u2019t want to talk about.\\u201D There was the sense of collective impotence reflected by the fizzling of Armistead\\u2019s insurrection, which even his closest friend and rival Saunders, not unhappily, likened to \\u201Cbackground noise\\xA0.\\xA0.\\xA0. mouse nuts.\\u201D\"), mdx(ContentRef, {\n    id: 30,\n    mdxType: \"ContentRef\"\n  }, \"Worst, perhaps, was the sudden and inevitable jealousy among the scientists themselves. Not only did the compression suggest a shrunken pie, but SEC requirements now made public several of their exact portions. Thus, even as Boger\\u2019s 780,000 shares shrunk to 520,000, Navia\\u2019s 103,000 to 67,000, and Aldrich\\u2019s 87,500 to 59,000\\u2014holdings that, postcompression at $15 a share, would be worth $7.8 million, $1 million, and $900,000, respectively\\u2014resentment spiked. \\u201CIt was like having your pants taken down in public,\\u201D said Navia, who was doubly excoriated when Boger, needing to \\u201Cget another Merck name,\\u201D hurriedly made him an officer, so that Navia\\u2019s $92,000 salary was also disclosed. Altogether, the aroma was tart, sulfuric. Said Saunders, \\u201CClub V is becoming a lot more Squibblike in its science management relations. I\\u2019m impressed by how much greed is showing through here.\\u201D\"), mdx(ContentRef, {\n    id: 31,\n    mdxType: \"ContentRef\"\n  }, \"Scientifically, it was another frustrating period. Despite receiving a preprint of an article by Schreiber detailing how to grow so-called cocrystals, Vertex still hadn\\u2019t solved the structure of the FKBP-12/FK-506 complex on its own. Murcko particularly was distressed. \\u201CMerck has it. Abbott has it. Glaxo may have it,\\u201D he said. \\u201CWe don\\u2019t have it. We\\u2019re in a better position to understand the flexibility of the enzyme because we have the native structure as a starting point, but they\\u2019ve got a lot more computers and a lot more people. If the goal is to design drugs, they\\u2019re ahead.\\u201D\"), mdx(ContentRef, {\n    id: 32,\n    mdxType: \"ContentRef\"\n  }, \"Far from being the straightforward challenge of blocking FKBP-12 with a well-designed molecular monkey wrench that Boger had first envisioned and sold so successfully to the scientists and Chugai, the immunophilins project had become a scientific tarpit. The scientists had no idea what they were trying to accomplish. Were they trying to mimic Schreiber\\u2019s effector region? Hold open the swinging jaw of Yamashita\\u2019s flap? Both? Neither? What did the exposed handle of FK-506 do inside the cell? Were the drug\\u2019s side effects the result of binding to too many partners, or could they be trimmed away like so much fat and gristle? \\u201CThis is one hundred \", mdx(\"a\", {\n    id: \"page_355\"\n  }), \"times harder than anything I\\u2019ve ever worked on,\\u201D said Murcko, \\u201Cincluding HIV protease. It\\u2019s a nightmare of terror. A year from now all of us are going to be a lot more religious.\\u201D\"), mdx(ContentRef, {\n    id: 33,\n    mdxType: \"ContentRef\"\n  }, mdx(\"i\", null, \"Nature\"), \", with no reason to hurry now that Vertex\\u2019s X-ray structure was second behind Clardy and Schreiber\\u2019s (and perhaps retaliating for Boger\\u2019s indiscretion), took its time reviewing Yamashita\\u2019s paper. Navia, angered about having to \\u201Chang fire\\u201D in his imaginary war with Schreiber and stung by the reproach of the other scientists, fulminated. It took Yamashita, beyond caring, to stroke him and calm him down. \\u201CManuel,\\u201D Yamashita said, without a hint of irony, \\u201Cis a very great man.\\u201D\"), mdx(ContentRef, {\n    id: 34,\n    mdxType: \"ContentRef\"\n  }, \"Without the FKBP-12/FK-506 complex, Vertex\\u2019s two conflicting protein structures\\u2014Moore\\u2019s and Yamashita\\u2019s\\u2014offered little positive direction to the chemists, who were laboring unsuccessfully to make better compounds than 367. Both Moore and Yamashita assumed that the discrepancy, which was no longer relevant to publishing and unlikely to affect drug design, would be resolved imminently by having the structure of the complex. Thus they turned, in the absence of any clear direction and with the competition between them still unresolved, to other work. Boger was appalled. He was about to go around the world, trying to persuade wary investors that structure-based design at Vertex was already well underway, and its most marketable achievement was clouded with doubt.\"), mdx(ContentRef, {\n    id: 35,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CPeople have gotten lazy around here in the last few months,\\u201D he snapped after a project council meeting at the end of June. \\u201CWe\\u2019ve got two very different structures, and nobody seems concerned about it but me. These guys have short memories. Two months ago they pulled each other\\u2019s cookies out of the fire and now they\\u2019re not talking to each other. It\\u2019s bad science.\\u201D\"), mdx(ContentRef, {\n    id: 36,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 37,\n    mdxType: \"ContentRef\"\n  }, \"As he had with the Chugai deal, Boger again straddled the core dilemma of his world: To do science you need money, but to raise money competitively you need to project illusions that are the antithesis of science. You need to scramble hard.\"), mdx(ContentRef, {\n    id: 38,\n    mdxType: \"ContentRef\"\n  }, \"\\u201COur strategy going in,\\u201D says Holman, \\u201Cwas, Let\\u2019s pull out all the stops. This is a market that has us all nervous, so let\\u2019s at the end of \", mdx(\"a\", {\n    id: \"page_356\"\n  }), \"the day not look back and say, \\u2018Gosh, I wish we had done.\\xA0.\\xA0.\\xA0.\\u2019\\xA0\\u201D Kidder\\u2019s plan called for a \\u201Cfull-blown, massive marketing in the United States, Japan, and Europe,\\u201D a worldwide blitz that would start in Tokyo on June 27, 1991, gather speed through a five-day, five-city European whirlwind in early July, then peak with a two-pronged sprint across the United States\\u2014two teams each hitting two cities a day\\u2014climaxing in San Francisco and Seattle, Portland and Palo Alto, on July 12. By then investors would hopefully be in such a state that the deal would be oversubscribed two or even three to one, enabling Vertex to get its asking price or, as Regeneron had, a higher one. Still, Holman was taking no chances. Normally such road shows target only institutional investors, but he insisted on a second team consisting of Navia and Vertex\\u2019s new comptroller, Keith Ehrlich, to meet with retail buyers\\u2014individuals\\u2014who weren\\u2019t as \\u201Cprice sensitive\\u201D as the fund managers and might be induced to bid up Vertex\\u2019s stock.\"), mdx(ContentRef, {\n    id: 39,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CVertex is the kind of story where we were going to get the deal done regardless,\\u201D Holman says. \\u201CBut the market was overheating. It was the classic example: too many deals, deals being priced poorly, and everybody getting hurt by it. At the time we were finalizing the road show, Kidder alone had twenty-two deals in registration, with eight or nine of them on the road. The portfolio manager we would call, say, in Boston, would say, \\u2018Hey, I\\u2019ve got twelve invitations today for lunch.\\u2019 We had to do an enormous premarketing of our institutional people. We brought Josh to a hotel here and got people in from all over the country\\u2014insiders\\u2014to get them so excited that they would tell their client, \\u2018I know you\\u2019ve got twelve, but of the twelve this is the one you\\u2019ve got to come to.\\u2019\\xA0\\u201D\"), mdx(ContentRef, {\n    id: 40,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThe problem,\\u201D said Aldrich on the eve of the road show, \\u201Cis that a lot of investors have seen issue after issue go out and tank, so they say to themselves, \\u2018Why should I buy when I can wait a month and the stock\\u2019ll be half the price?\\u2019 It means we have to express total confidence in the offer. Even with my friends I\\u2019m saying \\u2018This is gonna go, there\\u2019s no question, so get some\\u2014if you can.\\u2019\\xA0\\u201D\"), mdx(ContentRef, {\n    id: 41,\n    mdxType: \"ContentRef\"\n  }, \"Stoking the atmosphere of a hot deal, Kidder\\u2019s plan was to present Vertex as the most tantalizing story in a season of stories\\u2014in Holman\\u2019s phrase, the cr\\xE8me de la cr\\xE8me. Boger, who always conceived of Vertex as being at the head of any class it was in, gladly \", mdx(\"a\", {\n    id: \"page_357\"\n  }), \"obliged. He walled off those aspects of the story that made it seem less than absolutely convincing, absolutely true. Reality would not, could not, intrude. Indeed, his final instruction to Nancy Stuart and the scientists as he left for Japan was not to let him know what was happening in the labs while he was gone. Ostensibly to preserve the accuracy of his presentation, the edict also allowed him a fig leaf of deniability in case of a setback. If there was bad news, he didn\\u2019t want to know it lest it detract from the picture he was perfecting, that he had to perfect, before the fact, of clear and orderly success. As if to reinforce this open-faced image\\u2014and perhaps another, of himself as the ex-Harvard/Merck wunderkind\\u2014Boger shaved his beard shortly before his departure.\"), mdx(ContentRef, {\n    id: 42,\n    mdxType: \"ContentRef\"\n  }, \"But reality did intrude. On June 24, the day before Boger and the others were scheduled to leave for Tokyo, a drug industry tip sheet, \", mdx(\"i\", null, \"F-D-C Reports\"), \", known commonly as the \\u201CPink Sheet,\\u201D published a story touting \\u201CVertex Pharmaceutical\\u2019s Orally Active HIV Protease Inhibitor.\\u201D Cribbed from the red herring with no independent follow-up, the article reported that Vertex had three small molecular compounds that blocked HIV protease in cells and that it planned to begin testing a drug in human patients by the end of 1992. In fact, the prospectus had said only that the company was \\u201Cseeking\\u201D to design an oral AIDS drug for asymptomatic\\u2014healthy\\u2014carriers of the virus. Vertex had no such miracle pill, nor did it claim to. Still, as Boger and the others took to the road, there existed now the impression that they would be selling an inside position in AIDS, an impression that didn\\u2019t displease Boger, who was seeking to position the company, but which worried several of the scientists.\"), mdx(ContentRef, {\n    id: 43,\n    mdxType: \"ContentRef\"\n  }, \"Deeply fatigued from a year of failing to do what the company now seemed to be saying he had already done, Tung especially was concerned. Like Boger, he thought science was like crossing a minefield, things constantly blowing up in your face. That was the thrill of it. By himself, Tung used to hop freight trains in California and Oregon when he was a student at Reed College, a school known for cultivating intellectually gifted but unconventional students. Drug discovery had that same atmosphere of risk, of being alone, on the edge. It was also messy, convoluted, unpredictable, inexact, and generally pursued under the most breakneck conditions. \", mdx(\"a\", {\n    id: \"page_358\"\n  }), \"Tung worried that by oversimplifying the process, Boger was creating the false impression that making drugs was like making pizzas. \\u201CI don\\u2019t think we\\u2019ve reached that point,\\u201D he moaned, \\u201Cbut I don\\u2019t know.\\u201D\"), mdx(ContentRef, {\n    id: 44,\n    mdxType: \"ContentRef\"\n  }, \"In fact, within days he and Livingston would learn that Vertex had made compounds that blocked HIV-infected T cells from reproducing and were \\u201Cbioavailable\\u201D: Fed orally to mice, they were getting to the bloodstream. The problem was, they were different compounds\\u2014\\u201Chorses and donkeys,\\u201D as Tung had put it. Livingston was torn. Boger could use such \\u201Cdata points\\u201D as ballast during his road show, but they were ambiguous. One obvious solution was to have the orally available compounds tested quickly in cells to see if they stopped the virus from spreading. But Vertex didn\\u2019t have its own cell assay, and Boger hadn\\u2019t authorized anyone else to contract for one. Standing in front of Boger\\u2019s office, Livingston, Murcko, and Tung puzzled over what to do. If they told Boger about the new data, they would contaminate his story. If they didn\\u2019t, they would be delaying vital experiments while maintaining the fiction perpetuated by the Pink Sheet.\"), mdx(ContentRef, {\n    id: 45,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CTell him we have to make a deal but don\\u2019t tell him why,\\u201D Tung suggested. \\u201CTell him he doesn\\u2019t want to know. Tell him that the people who are most informed believe it\\u2019s necessary and leave it at that.\\u201D\"), mdx(ContentRef, {\n    id: 46,\n    mdxType: \"ContentRef\"\n  }, \"Murcko shrugged. \\u201CHe\\u2019s a clever fellow. He\\u2019ll figure it out.\\u201D\"), mdx(ContentRef, {\n    id: 47,\n    mdxType: \"ContentRef\"\n  }, \"They decided to tell him nothing.\"), mdx(ContentRef, {\n    id: 48,\n    mdxType: \"ContentRef\"\n  }, \"As Holman had predicted, the road show was gathering momentum, playing to receptive out-of-town audiences. \\u201CIn Japan,\\u201D he says, \\u201Cwe had eighty-five people for lunch. It was the largest crowd I\\u2019d ever seen. In Europe, the crowds everywhere we went\\u2014with the exception with one or two cities\\u2014were enormous. People wanted to hear the story.\\u201D Speaking in London, Zurich, Geneva, Stockholm, and Paris on successive days, Boger had no indication whether the deal would sell\\u2014only 500,000 of the 3 million shares the company intended to offer would be available outside the United States, and it was too early for buyers to commit orders. Still, he returned to Boston on late Friday night, July 5, strongly encouraged.\"), mdx(ContentRef, {\n    id: 49,\n    mdxType: \"ContentRef\"\n  }, \"Boger brimmed with restless energy. He had traveled so frequently \", mdx(\"a\", {\n    id: \"page_359\"\n  }), \"in the past two years that he had trained himself, as a necessary efficiency of family life, to reorient himself quickly when he got home. Thus while Navia, Aldrich, and Ehrlich spent the weekend getting their clothes to the dry cleaners and trying to sleep off their jet lag before the next leg of the trip, Boger, a competitive if rusty athlete, shot baskets for two and a half hours Sunday in his driveway in ninety-five-degree heat, then drank a half gallon of water. Throughout the weekend, his youngest son, Sam, who\\u2019d seen little of him in recent months and at first hadn\\u2019t recognized him without his beard, said \\u201CBye-bye, Daddy,\\u201D whenever he left the room.\"), mdx(ContentRef, {\n    id: 50,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 51,\n    mdxType: \"ContentRef\"\n  }, \"Monday morning was Boston, as Vertex\\u2019s home city and a locus of big mutual funds, second in importance only to New York. The market was holding\\u2014barely. At 7:30 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"A.M\"), \"., a chauffeured limousine collected Boger and Aldrich at Vertex and swept them to an already broiling financial district for a day of meetings: 8:00, one-on-one with Fidelity Management and Research; 9:30, one-on-one with Massachusetts Financial Services; 11, one-on-one, State Street Research; noon, luncheon at the Meridian Hotel, where three weeks earlier Holman had shepherded another Kidder client, Cambridge Neuroscience, through a road show appearance attended by only some fifteen people. \\u201CPart of getting a happy client is making sure you control their expectations,\\u201D says Holman, who told Boger and Aldrich to expect a crowd of perhaps thirty while privately hoping for thirty-five.\"), mdx(ContentRef, {\n    id: 52,\n    mdxType: \"ContentRef\"\n  }, \"Fifty-five came. Inured by months of storytelling, most seemed impressed, if not entirely sold. \\u201CThis is either the greatest thing since sliced bread,\\u201D one institutional investor muttered on his way out, \\u201Cor a total scam.\\u201D\"), mdx(ContentRef, {\n    id: 53,\n    mdxType: \"ContentRef\"\n  }, \"Barred from attending, no Vertex scientists heard the remark. Had they, they might have despaired even more deeply for themselves and for the precarious validity of the science they were so desperately summoning in the labs.\"), mdx(ContentRef, {\n    id: 54,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 55,\n    mdxType: \"ContentRef\"\n  }, \"Modeled after the Palazzo della Cancelleria in Rome, the Villard Houses of the Helmsley Palace Hotel on Madison Avenue and 50th \", mdx(\"a\", {\n    id: \"page_360\"\n  }), \"Street in the heart of Manhattan are not simply an advertising shtick for Harry and Leona Helmsley, but a full-blown American Renaissance palace, just opposite the great granite apse of St. Patrick\\u2019s Cathedral. It swims in European opulence: vaulted gilt ceilings, lavish bas reliefs, towering marble fireplaces. Holman picked it for Vertex\\u2019s New York road show appearance over any number of other spaces nearer to Wall Street both for its grandeur and to emphasize Kidder\\u2019s faith in Vertex. \\u201CThe last time I used a room in New York that size for that many people was Genzyme in 1986,\\u201D he says. \\u201CThe book was oversubscribed. We had 3 million shares to sell and 30 million in orders.\\u201D\"), mdx(ContentRef, {\n    id: 56,\n    mdxType: \"ContentRef\"\n  }, \"How far Boger had come from the \\u201Cmeat market\\u201D at the Vista, twenty-one months earlier, few of the nearly eighty people who crowded to hear him now could suspect. Boger, who had trudged through more fruitless sales talks than he cared to remember, didn\\u2019t begrudge them their erratic interest. Still, he seemed slightly unnerved, as New York intends of even its most confident out-of-town guests.\"), mdx(ContentRef, {\n    id: 57,\n    mdxType: \"ContentRef\"\n  }, \"He began slowly, less assuredly than in Boston, though he quickly modulated himself. By now he had given this particular slide show perhaps a dozen times, and its rhythms were familiar. As the clanking of silverware on dishes subsided, he resorted to stock assertions\\u2014\\u201CWe have compounds moving toward clinical trials that have been designed by using this breakthrough approach,\\u201D he said\\u2014that both oriented his audience and let them know quickly where Vertex stood in areas that were central to them both.\"), mdx(ContentRef, {\n    id: 58,\n    mdxType: \"ContentRef\"\n  }, \"As elsewhere on the road show, Boger stayed within the lowest-common-denominator script he had devised with Kidder. Showing, for instance, Murcko\\u2019s FKBP-12/FK-506 slides, he lectured: \\u201CWe can see which parts of this drug actually touch the protein target. Only the atoms, or the bits, of this drug that actively touch the protein are necessary for its action.\\xA0.\\xA0.\\xA0. Think of it as building a scaffold, or as we often call it in the lab, \\u2018connecting the dots.\\u2019\\xA0\\u201D\"), mdx(ContentRef, {\n    id: 59,\n    mdxType: \"ContentRef\"\n  }, \"Explaining how the company selected drug targets, he said: \\u201CWe do not go into projects where the biology is uncertain. Vertex will never bring a compound into the clinic to test someone\\u2019s biological hypothesis. That\\u2019s too risky; we leave that to the NIH.\\xA0.\\xA0.\\xA0. We look \", mdx(\"a\", {\n    id: \"page_361\"\n  }), \"for the biology to be well understood. We look for the chemistry and the biophysics to be doable in a short period of time.\\u201D\"), mdx(ContentRef, {\n    id: 60,\n    mdxType: \"ContentRef\"\n  }, \"Flipping ahead, he continued: \\u201CThis information is used and has been used at Vertex to design much smaller compounds than FK-506 that bind to this protein in the body.\\xA0.\\xA0.\\xA0. These compounds are much simpler and much more specific than FK-506 for this binding site.\\xA0.\\xA0.\\xA0. We have shown these compounds have the expected biological activity in human cells.\\u201D\"), mdx(ContentRef, {\n    id: 61,\n    mdxType: \"ContentRef\"\n  }, \"Boger was assiduous about not simplifying his story so much that it was patently false or misleading. But it was equally clear that the dictates of selling necessitated a high sheen, the impression of a sure thing, perfect control. Parsing his speech, one could not help but question whether his story\\u2014of orderly, rational discovery\\u2014had anything to do with the harrowing fits and starts back in Cambridge.\"), mdx(ContentRef, {\n    id: 62,\n    mdxType: \"ContentRef\"\n  }, \"It was true, for instance, that Vertex had \\u201Ccompounds moving toward clinical trials.\\u201D But had they been \\u201Cdesigned\\u201D through a \\u201Cbreakthrough approach\\u201D\\u2014an approach that had only just solved, with enormous difficulty, the structure of its first protein and had yet to yield any vital information about how it stuck to FK-506 or anything else? And was it true that \\u201Conly the atoms, or bits, of [FK-506] that actively touch the protein are necessary for its action\\u201D? A compelling story, but in fact it was still unknown which bits of the molecule accounted for its activity; and given Schreiber\\u2019s increasingly viable assertion of a gafflike \\u201Ceffector\\u201D domain, it was less and less likely that it was only those atoms that bound to FKBP-12. Whatever Boger was describing, it was not the \\u201Cnightmare of terror\\u201D that now entangled Murcko and the others.\"), mdx(ContentRef, {\n    id: 63,\n    mdxType: \"ContentRef\"\n  }, \"There were other zealous assertions that probably would have exasperated the scientists had they heard them. Did Vertex really know the \\u201Cessential parts\\u201D of FK-506? Did anyone in the labs but Aldrich ever actually talk about \\u201Cconnecting the dots\\u201D? True, Vertex knew that if one gave an immunosuppressant to an organ recipient, it helped block rejection, but not whether FKBP-12, the object of all their structural efforts, was biologically relevant. It was still possible that the enzyme was a poor target or, worse, that the \\u201Csmaller and more specific compounds\\u201D designed at Vertex, while \", mdx(\"a\", {\n    id: \"page_362\"\n  }), \"active, would be useless as drugs. Was this biology that was \\u201Cwell understood\\u201D? How could Boger say Vertex had used structure-based drug design when it didn\\u2019t know what its target did or how it did it?\"), mdx(ContentRef, {\n    id: 64,\n    mdxType: \"ContentRef\"\n  }, \"It was a measure of Boger that even as he painted the gritty reality of science in its most simplified and positive light, he defended himself by saying that compared to most others in his situation he had been a paragon of restraint. It scarcely mattered. Wall Street had become so intoxicated with stories, so self-delusional, that any attempt at ethical salesmanship was like a reed in a flood. The investors would see what they wanted to see, hear what they wanted to hear.\"), mdx(ContentRef, {\n    id: 65,\n    mdxType: \"ContentRef\"\n  }, \"And what they heard seemed to enthrall them. If Vertex wasn\\u2019t at the point of designing drugs, Boger had clearly positioned the company to exploit those breakthroughs that would soon make it possible to do so. How soon was still a question, but Boger was a pioneer; he wouldn\\u2019t get trampled in the stampede. He knew the right moves, how to sell. Satisfied, the investors lobbed him a few easy questions, mingled determinedly, looked at their watches, and filtered outside and back downtown, there to add Vertex\\u2019s name\\u2014a name many of them had only first heard\\u2014to the roster of hot new companies, to ignite a buzz, to send it swirling into Wall Street\\u2019s raging cacaphony.\"), mdx(ContentRef, {\n    id: 66,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 67,\n    mdxType: \"ContentRef\"\n  }, \"Aldrich pressed the phone receiver morosely to his ear.\"), mdx(ContentRef, {\n    id: 68,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CSo you\\u2019re calling in your chits, right?\\u201D he muttered. His sunken eyes flashed gravely, beseechingly, as if he had a migraine, his voice a thin well of barely concealed abuse. \\u201CDoes Banker\\u2019s Trust have any chits?\\u201D\"), mdx(ContentRef, {\n    id: 69,\n    mdxType: \"ContentRef\"\n  }, \"There was a pause. \\u201CWhat did Alkermes trade for today?\\u201D\"), mdx(ContentRef, {\n    id: 70,\n    mdxType: \"ContentRef\"\n  }, \"Another pause. \\u201CSo did they trade up?\\u201D\"), mdx(ContentRef, {\n    id: 71,\n    mdxType: \"ContentRef\"\n  }, \"Aldrich rubbed his tired face. It was almost 8 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"P.M\"), \"., Thursday, June 13, the day after the road show. Aldrich was in his office, talking with Holman from New York, trying to establish with as much diplomacy as he could why the deal still hadn\\u2019t come together. He was querulous, incredulous, wrung out, like an absent son insistently trying to get a doctor to explain over the phone why the \", mdx(\"a\", {\n    id: \"page_363\"\n  }), \"treatment he\\u2019d advised for his father wasn\\u2019t working, why the old man had collapsed and now, suddenly and unexpectedly, teetered near death.\"), mdx(ContentRef, {\n    id: 72,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CIs the sales force still pushing this,\\u201D he asked, \\u201Cor are they looking at it as a dead duck?\\u201D\"), mdx(ContentRef, {\n    id: 73,\n    mdxType: \"ContentRef\"\n  }, \"He shook his head, dissatisfied with Holman\\u2019s reassurances. \\u201CHow many more do you think you need before you get the rest to pile on?\\u201D He stared blankly. \\u201CYeah, you don\\u2019t want to call too often. It\\u2019s a psychological thing. Once they smell weakness in it, forget it.\\u201D\"), mdx(ContentRef, {\n    id: 74,\n    mdxType: \"ContentRef\"\n  }, \"Hanging up, Aldrich was fuming. \\u201CEveryone did everything they had to except for the guy selling,\\u201D he said. \\u201CThe guy had us going out at $13 to $15, talked us into making a big drop, and still hasn\\u2019t delivered one order. That\\u2019s what really burns me.\\u201D\"), mdx(ContentRef, {\n    id: 75,\n    mdxType: \"ContentRef\"\n  }, \"It had been an unfathomable week. Buoyed, if exhausted, by the road show (\\u201CI wouldn\\u2019t wish it on a dog,\\u201D Navia moaned), they had returned expecting that Kidder would start racking up orders at once: A few institutions would take 100,000 shares apiece, Kidder\\u2019s salespeople would put out the word out that the deal was starting to gel, then a stampede. The illusion of scarcity: That was what they had all discussed. But Kidder had inexplicably failed to land a single account. Between them, Aldrich and Boger had gotten commitments for 400,000 shares, more than all three of their underwriters combined. The previous afternoon, desperate, they had agreed to drop the offering price from $13 to $15 to $9 to $11\\u2014a 30 percent discount\\u2014but still no takers. The scientists, predictably, were incensed. \\u201CThe ball,\\u201D Boger said wryly, \\u201Cmysteriously disappeared from the court.\\u201D\"), mdx(ContentRef, {\n    id: 76,\n    mdxType: \"ContentRef\"\n  }, \"To Holman, Vertex had been caught in a fatal cross-shear, a convergence of overwhelming events. \\u201CBy July, most institutions were looking at year-to-date increases in their portfolios of 25 to 30 percent,\\u201D he would recall. \\u201CThat\\u2019s a home run hit. What these guys were now interested in doing was preserving that for the rest of the year, because they\\u2019d get a nice year-end bonus for having a 30 percent return, and they were already there. What they didn\\u2019t want was to lose any money.\"), mdx(ContentRef, {\n    id: 77,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CEveryone moved to the sidelines. Six of the seven medical deals that were brought to market directly prior to Vertex were priced at \", mdx(\"a\", {\n    id: \"page_364\"\n  }), \"the bottom of or below their filing range, and all but one of the seven traded down within two weeks after the offering. So institutions were saying, \\u2018Market\\u2019s overheated. We\\u2019re getting burnt royally. I don\\u2019t care if you\\u2019ve got IBM, I don\\u2019t care if you\\u2019ve got Microsoft at the IPO, we ain\\u2019t buying.\\u2019 There was just this incredible fence-sitting going on.\"), mdx(ContentRef, {\n    id: 78,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CVertex,\\u201D he says, \\u201Cbecame the Company from Heaven, Deal from Hell. And it was the Deal from Hell not because of anything in our control. The only thing you can do in that situation is go back and tell them they have to lower their price.\\u201D\"), mdx(ContentRef, {\n    id: 79,\n    mdxType: \"ContentRef\"\n  }, \"Aldrich, in his anger, refused to believe that Kidder couldn\\u2019t simply muscle a few of its regular customers into buying Vertex stock, that like the remote, recalcitrant doctor on the phone, it couldn\\u2019t resort to heroic measures. But as one of a number of less than dominant companies in the field and with its recent history of regulatory and business difficulties, Kidder was wary of too hard a sell. \\u201CDrexel used to have the ability in the junk bond market to tell Vernon Savings, \\u2018You buy this goddamn bond, or I\\u2019m never trading with you again,\\u2019\\xA0\\u201D Holman says, \\u201Cand guess what happened to Drexel.\\xA0.\\xA0.\\xA0. Our style as a firm is not to work that way.\\u201D\"), mdx(ContentRef, {\n    id: 80,\n    mdxType: \"ContentRef\"\n  }, \"Boger, typically, wasn\\u2019t bitter about the sudden downdraft in Vertex\\u2019s fortunes; factoring everything, he still thought the company would go out at the upper end of its new range. But he was furious about the wanton cupidity it reflected. \\u201CI\\u2019m not depressed about Vertex,\\u201D he said after Aldrich told him about his conversation with Holman. \\u201CI\\u2019m depressed about the world.\"), mdx(ContentRef, {\n    id: 81,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI\\u2019ve had investors say to me, \\u2018I never buy a company that\\u2019s not in clinic for more than $100 million.\\u2019 They\\u2019re checklist people. It\\u2019s voodoo. I want to say to these guys, \\u2018Lighten up. All you\\u2019ve got to do is beat the S&P by one point and you\\u2019re a hero. Think a little longer term. If the stock goes down 20 percent after the IPO, big deal. It\\u2019s completely nuts to be spending your time trying to catch the last dollar.\\u2019\\xA0\\u201D\"), mdx(ContentRef, {\n    id: 82,\n    mdxType: \"ContentRef\"\n  }, \"One irony of going public was that Boger, who exalted control, was now powerless. The offering was entirely in the hands of Kidder and the other underwriters\\u2014in a larger sense, in the indifferent hands of the market itself. He and Aldrich waited throughout the next morning and early afternoon for Holman to call. When he \", mdx(\"a\", {\n    id: \"page_365\"\n  }), \"didn\\u2019t, they responded reflexively. Aldrich, the emergent dealmaker with only Chugai to his credit after a chain of bitter disappointments, ate his liver; Boger, the scientist, scrounged for data, checked and rechecked his hypotheses, groped for explanations. He checked the activity of seventeen biotech stocks every thirty minutes on his computer. The Dow was up thirty-two points overall by midafternoon, but there was little movement in the sector. It was frozen. Boger began to believe that that was Vertex\\u2019s problem. Institutions accustomed to trading biotech stocks didn\\u2019t know how to value a small company determined to take on huge markets against mammoth competitors. \\u201CWe\\u2019re too hard to pigeonhole,\\u201D he said brightly. \\u201CThe analysts who are telling these guys what to do are all biotech guys. You\\u2019d have to have been around since Syntex [prior to Amgen, the last full-fledged pharmaceutical company to emerge, in the late 1940s] to understand what we\\u2019re doing.\\u201D\"), mdx(ContentRef, {\n    id: 83,\n    mdxType: \"ContentRef\"\n  }, \"Once again, as during the darkest days of the Chugai deal, Boger and Aldrich resembled the faces of Janus. Aldrich\\u2014glowering, pessimistic, funereal\\u2014detected a \\u201Cblood in the water situation.\\u201D Every passing day that Vertex\\u2019s underwriters couldn\\u2019t close the deal told investors that the company was in trouble, making them wary and killing their incentive to buy. \\u201CWe may not be able to sell this deal at any price,\\u201D he fretted. He was still furious at the underwriters but also blamed himself and Boger for being \\u201Cnaive.\\u201D\"), mdx(ContentRef, {\n    id: 84,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThis is an acute demonstration of what happens when you go public, which is that what you feel about yourself is what others are willing to pay for you,\\u201D he said. \\u201CA couple of months ago we thought we were this great management team. Now we\\u2019re saying, \\u2018What the fuck are we doing?\\u2019 This is going to defuse a lot of hubris around here.\\u201D He was talking, it seemed, about Boger.\"), mdx(ContentRef, {\n    id: 85,\n    mdxType: \"ContentRef\"\n  }, \"Boger, conversely, was upbeat, philisophical. He, too, was self-critical but mostly for listening to Kidder in the first place, for relinquishing control on crucial decisions. \\u201CIt\\u2019s completely clear to me that if we\\u2019d set our range at $15 to $17, as we first wanted to, we\\u2019d have had to come down the same 30 percent. It\\u2019s a cat and mouse game with a single operant rule for the buyer: \\u2018Whatever the initial price is, I want it down 30 percent.\\u2019 Listening to Kidder and Cowen on that cost us $6 to $10 million. Now that we know that it\\u2019s an auction and has nothing to do with real value, we\\u2019ll take \", mdx(\"a\", {\n    id: \"page_366\"\n  }), \"our lumps and get down the road.\\u201D To Dave Livingston, one of the few scientists who dropped in repeatedly throughout the day to gauge how things were going, he predicted, \\u201CWe\\u2019ll go out in the middle of our reduced range, with orders for about 4.5 million shares.\\u201D That would give Vertex $30 to $35 million, far less than the $50 million Boger had told the scientists to expect.\"), mdx(ContentRef, {\n    id: 86,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThat\\u2019s the nightmare scenario,\\u201D Livingston said afterward, \\u201Cthat we raise only enough money to get us through the next couple of years and there\\u2019s not enough time to do what we\\u2019ve told the world we\\u2019re going to do. That could get very ugly.\\u201D\"), mdx(ContentRef, {\n    id: 87,\n    mdxType: \"ContentRef\"\n  }, \"\\u2022\\xA0\\xA0\\u2022\\xA0\\xA0\\u2022\"), mdx(ContentRef, {\n    id: 88,\n    mdxType: \"ContentRef\"\n  }, \"By the following Tuesday morning, July 22, Vertex\\u2019s new price range had \\u201Cjarred a couple of people,\\u201D said Holman, but still too few to assemble a deal. It was four trading days since Aldrich\\u2019s conversation with Holman\\u2014an eternity in such a volatile market\\u2014and Aldrich\\u2019s dark prophesy taunted them all. If they didn\\u2019t sell the offering soon, very soon, the market would simply turn against it, leave it for carrion. Vertex and the underwriters would be stigmatized: a putatively hot start-up that couldn\\u2019t make it out during one of the richest speculative bubbles in history. Canceling an IPO would make it much harder, perhaps fatally harder, to raise more money in the future. What corporate partner, what investors, would want to touch Vertex after it had been scorned by a market that had happily imbibed such dizzying stories as Regeneron? Aldrich imagined having to return defeated to the board, at whose pleasure he and Boger ran the company. If the board was forced to dig deeply to cover Vertex\\u2019s onerous burn rate, how likely, he wondered, would that pleasure be to continue? It wasn\\u2019t too late for the board to bring in bona fide management\\u2014senior people who, by implication, would have been able to take the company public where he and Boger hadn\\u2019t. Boger had no such worries\\u2014he was still confident that the deal would succeed and confident of his own indispensability\\u2014but he, too, was reluctant to arouse the board.\"), mdx(ContentRef, {\n    id: 89,\n    mdxType: \"ContentRef\"\n  }, \"At Kidder, the stakes were equally high, the mood as steep. Memories were fresh of its meltdown in the late 1980s. A failure by Holman, its top New York dealmaker, to pull together perhaps its \", mdx(\"a\", {\n    id: \"page_367\"\n  }), \"most prestigious offering in years would have dire implications. Holman\\u2019s banking staff decamped to the sales floor, doubling up on account calls that started before 7 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"A.M\"), \". and finished after midnight. They patched in Boger at home. Chortled Boger, \\u201CI don\\u2019t think Kidder can afford to have this one go down.\\u201D\"), mdx(ContentRef, {\n    id: 90,\n    mdxType: \"ContentRef\"\n  }, \"With a \\u201Cbook\\u201D of 3 million shares, Vertex needed commitments of something more than that before it could set a final price and ask the SEC and NASDAQ, the over-the-counter stock market, to approve trading. As the number of commitments crept up Tuesday night and early Wednesday, Kidder thought it might be able to sell a smaller offering, but not all 3 million shares. Holman quietly began \\u201Cputting pressure on the system.\\u201D \\u201CMany people in the firm, many senior people,\\u201D he says, \\u201Cnow bought stock to get the deal done. You don\\u2019t like to go to your partners and say, \\u2018We need you to put up some of your cash in your personal account.\\u2019 But a number of people did that. We were looking for any order we could get.\\u201D\"), mdx(ContentRef, {\n    id: 91,\n    mdxType: \"ContentRef\"\n  }, \"Finally, at 3 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"P.M\"), \". Kidder\\u2019s top managers met internally to price the deal. They calculated that at $9 a share, the bottom of Vertex\\u2019s range, they had scraped together enough subscriptions to sell 2.75 million shares. The meeting was tense, urgent: They were running out of time. Another day and the deal would likely unravel. Holman phoned the other underwriters, who wanted an even smaller offering. Subscriptions had reached barely 3.25 million shares. Without an \\u201Caftermarket\\u201D\\u2014enough interested buyers so that those who bought at the IPO would have someone left to sell to\\u2014Vertex\\u2019s stock was headed inevitably down. At 4:15 Holman called Boger, who all along had accepted Kidder\\u2019s recommendations. Now, Boger told him he was willing to yield on price but not an iota on the size of the deal.\"), mdx(ContentRef, {\n    id: 92,\n    mdxType: \"ContentRef\"\n  }, \"\\u201COur line in the sand,\\u201D Boger recalls, \\u201Cwas, we do 3 million shares or we do nothing.\"), mdx(ContentRef, {\n    id: 93,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CI could hear Al\\u2019s voice breaking as he saw his next three bonuses crumbling to sand.\\u201D\"), mdx(ContentRef, {\n    id: 94,\n    mdxType: \"ContentRef\"\n  }, \"It may be, as Aldrich believed, that Boger\\u2019s resolve was pragmatic: During the pricing meeting, Kidder\\u2019s lawyers had warned that if they cut the size of the deal, the SEC might require the underwriters to recirculate it. \\u201CThe deal was too fragile,\\u201D Aldrich said. \\u201CRecirculation would have killed it.\\u201D But Boger was determined for \", mdx(\"a\", {\n    id: \"page_368\"\n  }), \"other reasons. Having come to regard the underwriters, who he thought had done a fine job up to and including the road show, as ineffective, he resolved to salvage the final marketing of the deal himself. \\u201CWe got no good predictive advice about this deal from any of them,\\u201D he said. \\u201CWhen I realized they didn\\u2019t know any more than I did, I decided to take over.\\u201D Oddly, he justified his hard line with a perverse populism. \\u201CI think its important to have those shares out there. There are worse things than making a lot of stupid investors rich, but if I\\u2019m going to do it, I\\u2019m going to make a lot of them rich. If we only sold 2 million shares, that wouldn\\u2019t be enough investors. I want to make a lot of people happy.\\u201D\"), mdx(ContentRef, {\n    id: 95,\n    mdxType: \"ContentRef\"\n  }, \"Boger had not wanted to try the board\\u2019s faith in him, but by now he had no choice: He needed to sell another 250,000 shares, fast. Even if its members agreed, Vertex still would have only a hair-thin margin, a so-called gross book of 3.25 million shares on a 3-million share offering. \\u201CWe couldn\\u2019t afford to drop out Aunt Ruth,\\u201D he joked about the precarious ratio. At 5 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"P.M\"), \". and for the next three and a half hours, he became a whirlwind, phoning board members nonstop. He got Schmidt in New York, Kinsella in his car. Frank Bonsai, a board member from Maryland, was vacationing in Wyoming, miles from the nearest phone. Insistently, Boger scared up a driver with a jeep and a portable phone to track him down. Nothing throughout the IPO had been so distasteful or so fraught. The last time the original investors had bought Vertex stock, a year earlier, it had cost them $2.50 a share; now Boger was asking them to reach down and buy blocks of up to 80,000 shares at $9. Remarkably, they all agreed. \\u201CThey were troopers,\\u201D Boger said, \\u201Cbut I had to spend capital I didn\\u2019t want to spend. Benno had to put up $720,000. It was a crime.\\u201D\"), mdx(ContentRef, {\n    id: 96,\n    mdxType: \"ContentRef\"\n  }, \"Holman, a bachelor, was hosting a dinner party that night at his apartment for twenty-five Kidder interns, but he stayed in his office till nine, awaiting Boger\\u2019s call. Satisfied now that they could sell all 3 million shares, he and Boger agreed to price the deal at $9. It had been an interminable scrape: from the $18 to $20 that Boger and Schmidt first imagined they could get after the Regeneron offering to the $15 to $17 Boger proposed at the outset of the IPO in early May to the shrunken $13 to $15 of the postcompression period to last week\\u2019s discount of $9 to $11 and, finally, to the bottom \", mdx(\"a\", {\n    id: \"page_369\"\n  }), \"of that range. Other companies had gone lower, to $7 in some cases. Taken together, the compression and the plummeting price had devalued by two-thirds the instant riches that the scientists first envisioned when Boger began selling them on the idea of going public less than three months earlier. Still, it was $27 million for a two-and-a-half-year-old company with no products, no profits, and no assurances\\u2014other than Boger\\u2019s overwhelming confidence\\u2014that it would ever have either. By absorbing the last measure of risk themselves, Kidder and Vertex had assembled a deal that they\\u2014and Wall Street\\u2014could live with.\"), mdx(ContentRef, {\n    id: 97,\n    mdxType: \"ContentRef\"\n  }, \"Holman, exhausted, caught up with the party at his house after 9. \\u201CMy job was basically over,\\u201D he said. Boger, attending to the piles of paper on his desk, got home shortly before 12.\"), mdx(ContentRef, {\n    id: 98,\n    mdxType: \"ContentRef\"\n  }, \"But the deal was not easily retired. Throughout the night and deep into the next afternoon, a succession of endlessly unnerving legal and regulatory snarls held up final SEC and NASDAQ approval. Boger and Holman spoke by phone four more times between midnight and 3:30 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"A.M\"), \"., then increasingly, alarmingly, throughout the day on Wednesday. Aldrich was grim, beside himself, fearing that the deal wouldn\\u2019t be closed that afternoon and that skittish investors, again smelling blood, would back away. Finally, at 3:59 \", mdx(\"span\", {\n    className: \"smallcaps\"\n  }, \"P.M\"), \"., an hour before closing and after the company had threatened to take the deal to the rival American Stock Exchange, NASDAQ approved the sale of Vertex stock. It finished the day unchanged.\"), mdx(ContentRef, {\n    id: 99,\n    mdxType: \"ContentRef\"\n  }, \"It was over. From a dead stop, Boger had taken Vertex in less than three months from a cash-poor, closely held start-up to a public corporation with $30 million in the bank, he and Aldrich selling more than 600,000 shares, a fifth of the offering, themselves. He had turned himself inside out to do it, from a scientist cum entrepreneur to a public showman and administrator who also was in charge of the company\\u2019s science. Now, it was that science, struggling and unfocused, that needed his attention most. Boger turned to it full-faced. Whether it would receive him back as unambivalently was another matter.\"), mdx(ContentRef, {\n    id: 100,\n    mdxType: \"ContentRef\"\n  }, \"\\u201CThe problem with the IPO was that it raised people\\u2019s expectations,\\u201D Dave Armistead said. \\u201CPeople thought we were going to go out at $15 to $20\\u2014precompression\\u2014and started figuring in their \", mdx(\"a\", {\n    id: \"page_370\"\n  }), \"own minds what it would take to become a millionaire. Then the compression came and knocked them down a third, then the final price discounted them by a third again.\\xA0.\\xA0.\\xA0. Then there was the prospectus, which showed who\\u2019d gotten how many shares. Chemistry had a pretty good year last year. Crystallography did nothing. But crystallography as a group got more bonus shares than chemistry, even though there are more chemists. It\\u2019s like Merck. People began to see that it wasn\\u2019t just performance that determined compensation. That\\u2019s dangerous.\\u201D\"), mdx(ContentRef, {\n    id: 101,\n    mdxType: \"ContentRef\"\n  }, \"Among the scientists, Boger\\u2019s absence had been interpreted as neglect, his selling as betrayal. As he returned to the day-to-day operation of the labs, he knew he had to allay the damage of his being away, but how much and with what intensity he didn\\u2019t know and resented having to consider. Having done his part, he found himself more and more intolerant when the scientists didn\\u2019t do theirs. It was not, he acknowledged, a healthy attitude: a leader impatient with those he\\u2019s leading. Boger had drawn his ideas on leadership from Hannah Arendt, who said that power devolved directly from the confidence of the governed. But the IPO had exposed a rift between the dictates of his position and theirs. Now, for the first time, the scientists, the original buyers of his story, had come to distrust him, some acutely. Boger knew the feeling. He had had it often himself about others above him.\"));\n}\n;\nMDXContent.isMDXComponent = true;","fields":{"slug":"/molecule/18/"},"frontmatter":{"isBook":false,"title":"Chapter Eighteen","bookTitle":"The Billion-Dollar Molecule","numSections":25,"tags":["a"],"author":"Barry Werth"}}},"pageContext":{"id":"03092d61-2d1f-5f07-9bf4-56f28b890956"}},"staticQueryHashes":["4080856488"]}