The Cure

by Geeta Anand

  “The bovine version is only for lab work,” Canfield said between his teeth. His tone was turning defensive as the questions kept coming. He said he was working on making a different, human version of the PTase enzyme for use in the drug trials.

  “What about uncovering enzyme?” asked Roth, naming the second processing enzyme Canfield needed to make his Pompe enzyme.

  “Making it in T-293, taken from human kidney cells.”

  “Oh no—the FDA would never allow that, either,” Hurley said. Her big eyes seemed to grow wider with each of Canfield’s answers. Kidney cells weren’t considered sterile enough to be used as a factory for growing enzymes or any other protein for human therapeutic uses.

  “Well, we’re planning to change the cell line,” Canfield said defensively. He was breathing heavily now as he paced in front of the whiteboard.

  “Are you going to make all three enzymes under GMP?” Roth asked. GMP stood for good manufacturing practices, and was shorthand for the stringent and necessary FDA guidelines for producing any medicine that would be injected into a human.

  “We haven’t entirely thought through that yet,” Canfield said, putting the cap on his marker and slamming it on the whiteboard ledge in frustration. Canfield was a high-ranking scientist at the University of Oklahoma, and he was not accustomed to being questioned so aggressively and superciliously.

  “And when do you believe you’re going to go into clinical trial?” Roth asked.

  By now, Canfield was answering in only one or two words. “One year,” he said. He stuffed his hands in his pockets and looked down.

  “Can you write out the manufacturing process, please?” Hurley asked.

  For the next fifteen minutes, with the eyes of the Neose team trained on his back, Canfield stood at the whiteboard writing equation after equation. When he finally turned around, his choppy handwriting in black ink stretched the length of the conference room wall. First, he would make the missing Pompe enzyme in a process similar to Chen’s. Then, to attach the right carbohydrates and phosphates to the enzyme, he would use the two processing enzymes—PTase and uncovering enzyme—neither of which anyone was known to have characterized, let alone made in a lab. He described six different purification steps along the way.

  “Oh no, you can’t do this in one year,” Hurley said after a few minutes of intently studying the equations.

  “We can,” Canfield retorted, only to be interrupted in midsentence by Roth, who had risen to his feet, red-faced.

  “This is bullshit. Are you serious?” he shouted, turning and stomping out of the room. A minute later, Hurley and the other Neose officials followed in quick but measured order.

  Canfield dropped heavily into his seat between John and Doug, his arms crossed tightly, stroking his beard and looking like the most wronged man in the world.

  “This is awful,” he mumbled.

  John sat silently. It was one of those rare instances in his life when he couldn’t think of anything to say or do to make things better.

  Luckily, Doug had mastered the art of calming Canfield. He pushed his chair back, crossed his hands behind his head, and said softly, drawing out each word, “Well, Bill, now, this is just business. They’ll be back to the table. They’re just posturing. Give it a little time. It’ll all come together and everything will be okay.”

  “We’ve been negotiating with them for months and months. What do they want?” Canfield fumed. “Why are they asking all of these questions? Of course we don’t have all the answers—that’s why we want to partner with them.”

  A few doors down, Hurley and the other Neose officers found Roth swearing in his office. “Canfield thinks just because he says it’s going to happen, we should believe it will happen—in one year! You have a scientist pooh-poohing the complexity and a CEO who wants more than life itself to get it for his kids. Not a good combination.

  “If you’re going to make a soufflé for the first time, you can’t set out at six to make it for dinner at seven. It’s not going to happen, even if you’ve got the right recipe,” he finished.

  “I don’t know a single company that has taken a drug from a test tube into a human trial in a year,” Hurley said, agreeing with Roth. “It will take them a minimum of five years to fine-tune the lab work, set up manufacturing, and test in animals. These guys don’t know what they’re doing.”

  “I don’t know if we should do anything with a hotheaded guy like Bill Canfield,” Roth said.

  Roth didn’t return to talk with Canfield and his team that day. Instead, Sherrill Neff, the tall, eloquent, white-haired chief operating officer who had sat silently through the presentation, returned to smooth things over. In an apologetic voice, he said he knew the meeting had been tough. Unfortunately, Roth and the others had other meetings to attend that day and couldn’t return. But he promised he would be back in touch with Canfield as soon as the team had a chance to reflect on what they’d heard that day. Neff had a kind, thoughtful, almost fatherly way about him that made John like and trust him immediately.

  Canfield and Doug flew back to Oklahoma, and John drove the two hours home, feeling like a fool. He’d signed on with Canfield’s company without asking enough questions. First, he hadn’t known how little money Canfield had in the bank. Next, he hadn’t realized the uncertainty of Canfield’s commitments from investors. And, finally, as today’s meeting had revealed, he had nowhere near understood the complexity of Canfield’s development process for the Pompe enzyme. John wasn’t a scientist, but he had a sinking feeling the Neose team and the Oklahoma venture investors might be right. Canfield was an excellent academic scientist, but did he have any idea how to turn his breakthrough findings into a medicine? And even if he did have a clue, how plausible was the goal of beginning clinical trials in one year?

  When John had made the decision to leave Bristol-Myers, he’d faced this uncertainty on a seemingly smaller scale. His mentor at Bristol-Myers, Brian Markison, had encouraged him to join Canfield. “If it works,” Brian had said, “you save your kids, you help a whole lot of people, and you make more money than you ever need. If it doesn’t, you come right back here.”6 Should he cut his losses and go back to Bristol-Myers now? He couldn’t think of how a first week in a new job could have gone worse.

  John pulled up to his house to find Aileen and the kids outside. Megan, now three and a half, and Patrick, now two, sat on his blue Naval Academy blanket in the front yard, their ventilators swishing evenly. Aileen sat between them, while John Jr. rode a tricycle in the street.

  “Daddy,” Megan shouted, arms outstretched. He ran over to lift her up in the air. Patrick squeaked and waved both arms.

  “Why aren’t you sitting in your usual spot?” he asked Megan, pointing to the top of the brick steps, where she usually presided over the entranceway.

  “I fell down,” Megan said, using a combination of speech and sign language.

  “Oh yeah—we had a little accident, John. She fell off the stoop,” Aileen said, in a singsong voice, deliberately casual because the kids were listening. “Luckily, I caught Megan, but it was a little lesson for us all, wasn’t it, honey?” She gave Megan a kiss as she lifted her out of her father’s arms so he could greet Patrick.

  “Hey there, how’s my redheaded stepchild?” he asked, picking up Patrick. John’s doting on Megan had become a family joke. Aileen had to remind him repeatedly not to forget his youngest.

  “What’s wrong with his thumb?” John asked, noticing a big blister on Patrick’s finger.

  “I’d been wondering that for a few days and I just figured it out,” Aileen said. “He’s so smart that he’s figured out a way of moving his head without using his neck muscles. I guess they’d gotten so weak he couldn’t turn his head anymore. So he’s been biting down on his thumb and using his arm to pull his head around.”

  John kissed Patrick’s thumb, hiding his face in the boy’s hand for a minute as he absorbed the blow Aileen had so casually delivered. The children we
re growing weaker, just as the doctors had predicted. Megan couldn’t sit up on the top step anymore. And Patrick couldn’t turn his head without using his arm as a lever.

  “Daddy,” he heard little John calling from the street. He lifted his face and turned around to see his eldest child pulling open the passenger side door of the family van. A cloud of balloons in every color rose into the air. Aileen shrieked and ran down the street, leaping into the air in her short floral-print dress, grabbing at the balloon strings.

  With a start, John realized it was his own birthday. He was thirty-three years old.

  Aileen, clutching the strings of the two balloons she had saved, was walking toward him. “Good Lord. I bought thirty-three balloons and now we only have these,” she said in a fit of giggles, grabbing John Jr. and swinging his chubby hand.

  “Happy birthday, John,” she sighed, kissing him. “Let’s go inside and have cake.”

  “Sure,” he said.

  “You don’t look right. How are you?” she asked.

  “Oh great—just great,” he said wearily, shaking his head and rolling his eyes at Aileen, signaling it wasn’t a good day, but he’d tell her about it later. He picked up Megan and her ventilator. Aileen let go of John Jr.’s arm and gathered Patrick and his ventilator, and together they took the children inside.

  Within a few minutes Aileen and the children were sitting around the small kitchen table wearing pointy party hats, singing “Happy Birthday.” John blew out his thirty-three candles with gusto, grinning as his children cheered.

  There was no way he could quit Canfield’s company, he thought as he cut the chocolate cake. The children were getting weaker by the day, and he had no other plan for saving them.

  That night, as he and Aileen ate dinner, he tossed out an idea he hoped she would go along with for getting Canfield’s company some quick cash. “The company needs money right now, Aileen,” he said. “I’d like to step up to the plate and help out. The only money we have is in this house, but the good news is that it has already appreciated. I bet I can get a hundred grand out of it if we take out a second mortgage.”

  “You just started and this company is already out of money,” Aileen repeated, blinking her surprise. “What’s going on, John?”

  “Some of the investors are taking a little longer to line up than we’d expected,” John said, keeping his tone casual. “It’s just a cash flow problem. Canfield’s getting some money and I want to be able to show I can help, too.”

  “If you’re asking if I think it’s okay to mortgage the house, you have my permission. Do what you need to do, John,” she said, as she had so often before.

  In the fifteen months since he had stormed out, Aileen, too, had become more forgiving and supportive. She didn’t question John’s decisions on business or family finances, even if it wasn’t clear to her that he was right.

  She didn’t ask for details on the company’s problems and he didn’t offer her any.

  John arrived in Oklahoma the next week with a check for $100,000, having taken out the second mortgage on his house.7 Luckily, Canfield was having a better week. He had been calling down a list of local doctors and dentists, and he had managed to raise another $200,000, mostly in increments of $5,000 and $10,000.

  Then John asked Canfield’s permission to phone Neose and talk to Sherrill Neff, Neose’s chief operating officer. “Let me work something out, business person to business person,” John told Canfield, trying to sound more confident than he felt.

  Over the next few weeks, John essentially gave Neose a deal so good—and, honestly, so one-sided in Neose’s favor—that the company finally couldn’t say no. To convince Neose to put in $562,000, John gave the company the option of becoming a partner and owning half of the revenue of the Pompe medicine—with no deadline attached. Partnership requires periodic infusions of cash at key milestones, and by deferring a decision on a long-term association, Neose hadn’t committed to any future business dealings. It was a bottom-of-the-line bargain, and a much-needed lifeline for Canfield and John’s company.8

  With the start-up funds in place and their “partner” Neose giving their company some gravitas, John and Canfield set out to raise serious venture capital. John turned immediately to the only old boy’s network that he knew. He called Josh Phillips, a buddy from the Friday afternoon pizza parties at Harvard Business School where he used to give out his infamous Kiss-Ass awards.

  Only a few weeks earlier, Josh had sent out a blast e-mail saying he’d become a partner in a small Boston area venture firm, Catalyst Health & Technology Partners. Now John e-mailed Josh back, describing his new company and asking if Catalyst might be interested in investing. Josh, who had always admired John’s sense of humor and charisma, invited him to make a presentation to his firm.9

  John used part of the Neose investment funds to hire a consulting firm to help him write a business plan and draft a snazzy, thirty-slide PowerPoint presentation. The consultant, Skip Irving from Health Advances in Boston, led a brainstorming session to help John and Canfield christen the company with a new name. Canfield had called it Targeted Therapies Inc., which was serviceable but dull. The new name chosen was Novazyme, a play on the words new and enzyme.

  Several weeks later, in Catalyst’s Newton, Massachusetts offices, John debuted the business plan. His new key selling point was that Canfield’s scientific approach could be used not only to make the deficient Pompe enzyme, but also enzymes missing or deficient in patients with the other forty-eight lysosomal storage diseases. Even though these diseases were extremely rare, a treatment for just one of them could be priced so high it could yield a fortune. He put up a slide showing Genzyme’s projected annual revenue that year from its Gaucher disease treatment—$540 million.

  “Imagine the economic potential of a new, improved technology to make a whole line of drugs like Genzyme’s,” he said. “The market potential isn’t just millions or hundreds of millions—it’s billions.” He clicked to a slide that put the market potential at $6 billion.10

  John acknowledged that a much larger competitor, Genzyme, was developing two enzymes for Pompe disease that were further along in development—Chen’s and Pharming’s—but he called them “vastly inferior” to Canfield’s. Then he presented an outline for developing Canfield’s science into a medicine. He had modified Canfield’s original time frame, but only slightly. “Novazyme can begin clinical trials for Pompe disease in twelve to eighteen months,” he declared confidently.

  As he wrapped up his presentation, John searched the faces of the businessmen at the table for clues as to how his pitch had been received. It was hard to read the polite, smiling faces of the group, but John got the signal he wanted from Josh, who turned a little and flashed a thumbs-up that only he could see.

  After John left, Josh turned to his senior partner, David Hendren, and said intently, “This company can threaten Genzyme’s cash flow.” He had recognized something that John, focused on getting clinical trials started for his own kids, had not fully absorbed: Canfield’s science represented such a threat to Genzyme’s core business that there was a good chance the bigger company would feel compelled to buy the smaller one.

  “If it works, there’s a big exit potential,” Josh said, using venture capital investors’ lingo for the opportunity to make a quick sale at a big profit. They agreed that Josh should rush to Oklahoma the next week to check out Novazyme and negotiate a deal before the little company was discovered by other, bigger venture firms.

  Negotiations on the terms of a deal flowed easily. Catalyst agreed to put in $1.5 million and commit to raising another $1.5 million in return for owning about 7 percent of the company. The HBS network had lived up to its reputation.11

  With the commitment for $3 million, John and Canfield were ready to take a break from fund-raising. They thought they had enough money to get them through at least six months, possibly a year. But Roth of Neose had set up a few other meetings with venture capital firms, and though th
ey seemed like long shots, the two men thought it better not to cancel for fear of hurting their already tenuous relationship with the Neose chief executive.

  To the astonishment of both John and Canfield, both venture funds not only wanted to invest, but gave them more money than they asked for. Perseus Soros, a new biotech fund sponsored by billionaire George Soros and run by Dennis Purcell, one of the world’s most successful biotechnology investment bankers, initially offered $1.5 million. But a week later, when HealthCare Ventures, one of the oldest and most successful biotechnology venture funds, insisted on investing $3 million, Perseus Soros raised its stake to match the $3 million. Catalyst, trying to keep up, increased its investment to $2 million. By the time the A Round was finalized, Novazyme had more than $8 million in the bank.12

  Standing side by side in their dark business suits at the windows on the thirty-second floor of Perseus Soros’s Manhattan office overlooking Central Park, John put an arm around Canfield.

  “Doc,” he said, grinning, “we’ve sure come a long way.”

  14

  Failure Is Not an Option

  Summer–Fall 2000

  Oklahoma City, Oklahoma

  With Novazyme’s finances secure, John set about trying to build the kind of company he’d dreamed of discovering when he was just a dad trying to fund research to save his kids. Almost all drug companies proclaimed themselves “patient friendly,” but most employees had never met anyone their medicines were designed to treat. Companies were caught up in the pedagogy of science and drug development that held objectivity almost above all else. Patients were statistics in clinical trials, human subjects whose success was viewed in terms of means, medians, and “p values”—the calculation of the statistical significance of the data, often measured in terms of their survival or death. These were calculations intentionally devoid of emotion. Embraced in theory, researchers at most companies tried to keep patients at bay, fearing for the emotional bias they might bring to the rigors of scientific research and drug development.