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% THE DOW JONES BUSINESS AND FINANCIAL WEEKLY www.barrons.com MAY 2, 2016 An Interview With Sam Isaly Founder and CEO, OrbiMed Advisors A Healthy Prognosis For Some Stocks: Drugs and Robots By Johanna Bennett Sam Isaly has been busy. The founder of OrbiMed Advisors, the world’s largest independent health-care investor, manages a $15 billion global portfolio of biotechnology and health-care stocks, as well as some private-equity and venture-stage companies. He and his colleagues — many of whom have Ph.Ds or M.Ds, or are former CEOs — look for companies with breakthrough therapies, undervalued pipelines, or other catalysts the rest of the market doesn’t see yet. And today, he says, the market is missing a lot. Isaly’s record is stellar. Though most of his assets are in institutional accounts, he also manages the $1.5 billion, 46-stock Eaton Vance Worldwide Health Sciences fund (ticker: ETHSX). Its performance earned him a spot in a recent feature (“The Market Beaters,” Jan. 9) for outperforming the broad market over every major time period going back 25 years. (Isaly launched both his firm and the Eaton Vance fund in 1989.) This past year, however, has been tough. The fund is down 8%, further than the benchmark MSCI World Healthcare’s 6.6% fall, though still ahead of two-thirds of the other health-care funds tracked by Morningstar. Barron’s sat down with Isaly in his midtown Manhattan offices to talk about last summer’s biotech bust, health care’s mergers-and-acquisitions landscape, and the scientific developments that he’s most excited about. (Hint: It involves robots!) Barron’s: What’s special about health-care investing? Isaly: Health care is the epitome of change. That change isn’t just new drugs and medical technology, but also how health care is delivered to patients. I can’t think of anything more boring than steel, or retailers, or all manner of other pedestrian businesses. Health-care stocks have certainly been the epitome of change recently. They fell 12% '! # #' $ # !&&" $# # & #& $# # "! ' # !"" #$#% $ # # "%( " ' from July through February, with some biotechs falling more than 40%. This year, the sector has rebounded 11%. What’s going on? Before the selloff, health-care stocks enjoyed a five-year boom, but stock prices, mostly drugmakers, overshot to the upside. It was natural for a correction to occur, but it fed on itself, fueled in part by a soft broader market and investor panic. So then stock prices overcorrected to the downside. Not often have I seen a selloff this severe. Was the selloff warranted? No, given the pace of scientific innovation, which is just as exciting today as it was eight months ago. There are exciting developments that haven’t been properly reflected in many stock prices over the past 10 months. Like what? Look at the cancer drug Opdivo from Bristol-Myers Squibb [BMY]. It’s referred to as an immuno-oncology therapy because it harnesses the body’s immune system to fight cancer cells. The drug has had enormous success since it was approved by the FDA in late 2014. We expect global sales to reach nearly $5 billion this year. Ono Pharmaceutical [OPHLY], the Japanese drugmaker that discovered Opdivo and partnered with Bristol, has more than doubled in value in the past year; its portion of Opdivo sales will be about $1 billion. Bristol’s portion is $4 billion, yet its stock is up just 12%. Among the big biotech names, Vertex Pharmaceuticals [VRTX] has a new cystic-fibrosis drug that could be huge, and the company has just started to turn a profit. The share price, however, got crushed last summer and is down 33% in 2016. Are health-care stocks still cheap? They are cheap across the board — especially biotech, which is trading at the same price/earnings ratio as the broader index, which is unusual. Volatility throughout the sector will continue as new technology disrupts markets and stock prices, but the outlook for the sector is underpinned by continued M&A activity. Today, biopharmaceutical firm AbbVie [ABBV] announced a $5.8 billion deal to acquire Stemcentrx, a biotech start-up, and Abbott Laboratories [ABT] unveiled a $25 billion deal for St. Jude Medical [STJ]. Strategic buyers take advantage of stockprice distress. So you’re optimistic. Optimistic isn’t a strong enough word to describe my outlook for the long haul. In (over p lease) The Publisher ’ s Sale Of This Reprint Does Not Constitute Or Imply Any Endorsement Or Sponsorship Of Any Product, Service, Company Or Organization. Custom Reprints 800.843.0008 www.djreprints.com DO NOT EDIT OR ALTER REPRINT/REPRODUCTIONS NOT PERMITTED the short term, my uncertainty stems from the ferociousness of the selloff. Which other drugmakers do you like? We are also enthusiastic for Eli Lilly [LLY]. It is a relatively new position in the fund, based on solanezumab, the company’s experimental drug for Alzheimer’s disease. Several big drugmakers have tried and failed to develop drugs that slow the progress of Alzheimer’s. So why Lilly? Solanezumab subscribes to a leading theory in Alzheimer’s research that the accumulation of beta amyloid in the brain contributes to the disease by gradually building up into plaque. That has yet to be definitively proved. But with Lilly coming off a severe patent cliff, current earnings forecasts are trough estimates. If you consider the probability of clinical success and Lilly’s valuation, it is worth the risk. Which innovations are capturing your attention? We’re looking at gene therapy, which is technology that attempts to repair a genetic imperfection or defect that causes disease. There are some promising therapies being tested, including a sickle-cell anemia drug from bluebird bio [BLUE] and a hemophilia treatment from BioMarin Pharmaceutical [BMRN]. There are also a handful of public companies working on technology known as Crispr, which involves cutting away bad genetic material and inserting good material. Yet there are no gene-therapy treatments available right now. So how do you invest? It’s an exciting science that is coming closer to reality. Right now, therapies for single-gene disorders, such as hemophilia and sickle-cell anemia, show more promise than those for multiple-gene disorders, such as diabetes. We have dabbled with bluebird bio because it is a leader in the field, but we aren’t big participants. Ultimately, gene therapy will be extremely remunerative. What else are you excited about? Gene sequencing — the technology that maps the human genome and cancer DNA — is widely used in research labs. The equipment developed by Illumina [ILMN] has made it possible to sequence a single person’s genome for less than $1,000. So now the technology is moving out of the lab and into the clinic, where it can help identify predispositions to certain diseases, and develop better diagnostic tests. Illumina cut its 2016 sales forecast two weeks ago, and the stock fell 25% in a day. It hasn’t recovered. That was a disappointment, but the outlook remains strong. Illumina isn’t cheap based on valuation, but the expansion of gene sequencing into the doctor’s office implies huge additional demand for equipment and reagents [a substance required for chemical analysis], both of which are made by Illumina. Profit could double in the next five years. What’s new in medical equipment? Intuitive Surgical [ISRG] makes and sells surgical robots — the surgeon uses a joystick to maneuver robotic arms to perform prostate and hernia operations, and hysterectomies. The procedures are far less invasive than traditional surgeries, and require less recovery time. It is still unclear if it is dramatically more cost-effective for hospitals to use the robots. The machines cost in the seven figures, while a scalpel can cost less than $20. But recent quarterly results showed that the company has placed more machines in hospitals, and the number of surgeries performed using the robots increased 17%. Like Illumina, Intuitive Surgical is a razor/ razor-blade business model, generating revenue from the sale of both the machines and the consumables used in each procedure. Is the Affordable Care Act still a profit driver for health care? The expansion of health benefits to millions of uninsured Americans has provided a boon to insurers, hospitals, drugmakers, and pharmacies. Most of that expansion came in 2014 and 2015; in 2016, it has started to slow down. And if the Republicans win the White House and control Congress, the ACA could be repealed and replaced. I don’t expect the Republicans to repeal the legislation without putting something in its place. That said, we do like the hospital chain HCA Holdings [HCA]. The cost of uncompensated patient care is rapidly falling as hospitals treat fewer uninsured patients, which is good for profit. Also, utilization, measured by admissions and length of stay, is rising at a pace in the low-single digits. The push to control rising drug costs has opened the door to so-called biosimilars, which are lower-price copies of branded biotechnology drugs, made by combining live cells. The pharmaceutical industry was devastated by the tidal wave of generic drugs in the early part of the decade. Do biotech companies face the same threat? It isn’t likely to be as catastrophic. Companies that develop and make biosimilars face some real issues, namely high capital costs. Biosimilars are harder and more expensive to manufacture than generic pharmaceuticals — a manufacturing plant and equipment costs perhaps $100 million — and the clinical trials can be more complicated. Our biosimilar play is South Korea’s Celltrion [068270.Korea], one of a few pure-play biosimilar companies. The stock has had a good run, and we continue to own it because the company has a series of products that could soon reach the market. Turing Pharmaceuticals bought a decades-old antibiotic and raised its price from $13.50 to $750 per pill, and Valeant raised cardiac-care drug prices as much as 525%. Is the political outrage justified? Is it real or rhetoric? The real power to control drug pricing sits with the health insurers and pharmacy benefit managers. We don’t need a central command. We are already seeing the effect that pressure — most notably from benefit manager Express Scripts [ESRX] — is having on drug prices. While the so-called list price for prescription medications rose 12% last year, what insurers and employers actually paid rose just 2.8%. We have to ask. Which presidential candidate would health-care investors fare best with: Hillary Clinton or Donald Trump? Changes from Clinton would be more traditional, probably more negotiable, and thus less of a threat. As for Trump, we don’t know where he might come down. He has mentioned the possibility of negotiating Medicare drug prices, which for the moment isn’t allowed under current law. Trump isn’t well known for his health-care position, and could well become troublesome for investors. Thanks, Sam. n Legal and Compliance Disclosures Performance information referenced herein has not been audited or verified by any independent party and should not be considered representative of the performance that may be achieved by any particular investment or the returns that may be received by a particular investor in any investment fund or account managed and/or sponsored by OrbiMed Advisors LLC or its affiliates (together, “OrbiMed Funds”). Past performance is no guarantee of future results. Particular investments referenced herein may not be representative of current or future portfolio investments of OrbiMed Funds. In addition, references to potential numbers or sizes of investments or other portfolio metrics are illustrative only, and an OrbiMed Fund’s actual portfolio may differ. OrbiMed Advisors LLC (“OrbiMed”), together with its affiliates, is the largest global healthcare-dedicated investment firm based on net assets under management as determined from publicly available information as of March 31, 2016. Commentary contained herein represents the thoughts and opinions of the specified commentator as of the date of this article and is subject to change based on market and other conditions. The opinions expressed are not necessarily those of OrbiMed or its affiliates. These opinions are not intended to be a forecast of future events, a guarantee of future results, or investment advice, and OrbiMed does not warrant or guarantee the accuracy or completeness of the information presented herein. The information provided is not to be construed as a recommendation or an offer to buy, or sell or the solicitation of an offer to purchase, any security or interests in any investment fund. This document is provided for informational purposes only. OrbiMed is an investment adviser registered with the U.S. Securities and Exchange Commission (the “SEC”) that specializes in the investment of clients’ assets in healthcare companies across a number of products and strategies. This document contains information which may not be applicable to other OrbiMed Funds. The information contained in this article is not intended to supplement or replace disclosures made in Part 2 of OrbiMed’s Form ADV or in the prospectus or other offering document of any OrbiMed Fund. SEC registration does not imply a certain level of skill or training. Article reprinted with permission.