Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News
As M&A Rebounds, So Do Buyout Prospects for Biopharmas
After a relatively quiet 2017, biopharma merger-and-acquisition (M&A) activity has surged during the first two months of 2018, judging by the parade of multi-billion-dollar deals already announced this year.
Two of those deals were struck by Celgene, which has disclosed plans to acquire Juno Therapeutics for $9 billion and Impact Biomedicines for $7 billion. Sanofi is buying two rare-blood-disorder-drug developers—Bioverativ for approximately $11.6 billion and Ablynx for $4.8 billion. Roche joined the parade by agreeing to snap up Flatiron Health for $1.9 billion, while Takeda Pharmaceutical got the year in biopharma M&A off to a flying start with its up-to-€520 million ($641 million) purchase of TiGenix.
Measured in dollars, this year is closer to last year than the headlines would indicate. The 2018 deals added up to a combined $34.94 billion—just under the $35.2 billion value of M&A deals for January–February 2017. The period saw Johnson & Johnson’s $30 billion acquisition of Actelion, announced in January 2017 and completed in June, as well as Takeda’s $5.2 billion purchase of Ariad Pharmaceuticals. In between those amounts was the $11.9 billion purchase of Kite Pharma by Gilead Sciences, announced in August and completed in October.
Bloomberg recorded $95.379 billion in 2017 biopharma deals. Biopharma accounted for about half of the more than $200 billion in “life sciences” M&A recorded by EY last year, though its definition of life sciences includes medical technology.
More M&A means a greater likelihood of biotech and pharma takeover targets being acquired. And once again, GEN is highlighting 10 biopharmas that have generated the most buzz about being bought out in recent months, based on notes to investors and comments in news outlets. Only one of the 10 companies on our 2017 list has found a would-be buyer (Juno), while Kite made GEN’s 2016 Takeover Targets list. The 2015 list featured Juno, Ariad, and a third company that eventually was acquired, Medivation (by Pfizer, for $14 billion).
This year’s list combines six new names with four companies spotlighted last year. For each company mentioned, this list explains where talk of acquisitions has surfaced, and why.
Small- to medium-capitalization biopharmas continue to dominate Wall Street speculation about top buyout prospects by showing promise for reasons ranging from approvals for new products and rising sales to successful clinical programs in indications that are expected to generate billions in new revenues.
AveXis generated positive vibes about its ability to attract a buyer this year thanks to positive clinical results. In November 2017, AveXis published Phase I data for its lead product in The New England Journal of Medicine, showing that all type 1 spinal muscular atrophy (SMA) infant patients who received a one-time intravenous dose of gene therapy AVXS-101 via an adeno-associated virus serotype 9 (AAV9) vector were alive and event-free at 20 months of age.
Martin Auster of Credit Suisse sees AVXS-101, now in a pivotal study, emerging as a foundational therapy for type 1 SMA, and eventually other SMA types. Martin Auster at Credit Suisse also thinks AveXis can launch AVXS-101 in 2019 as planned, based on recent FDA approvals of a gene therapy (Spark Therapeutics’ Luxturna™) and two cell therapies (Novartis’ Kymriah™ and Gilead Science/Kite’s Yescarta™).
“The current M&A environment could also make AVXS [AveXis] an interesting target given proximity to revenues and pipeline,” Citi analyst Mohit Bansal observed January 26.
That pipeline includes development of AVXS-101 for type 2 SMA (now in Phase I) and of an undisclosed preclinical AAV9-based gene therapy for Rett’s syndrome, announced January 16. “While the most important catalyst this year is the company filing for SMA type 1 approval in 2H’18, we think once that happens, the pipeline data catalysts (SMA Type 2 & Rett’s) would be in [a] 12-month window,” Bansal said. Should AveXis find itself a takeover target, he added, its stock price could zoom to between $185 and $250 a share—well above its February 16 closing price of $116.55 per share.
Arpita Dutt of Zack’s Investment Research included AveXis among six biotechs she said in January “are often considered acquisition targets” (the other five were bluebird bio, BioMarin Pharmaceutical, Puma Biotechnology, Incyte, and Exelixis).
Biogen has been talked about on both sides of the proverbial M&A fence in recent weeks, as both a potential takeover target and a buyer.
Keith Speights of The Motley Fool included the company among “Top Three Takeover Targets for Pfizer” in January. He reasoned Pfizer would be attracted to Biogen’s multiple sclerosis franchise of three marketed treatments, the SMA drug Spinraza® (nusinersen), and a rich pipeline that includes Phase III Alzheimer’s disease candidate aducanumab. That pipeline was cited in December 2017 by The Motley Fool’s George Budwell, who listed Biogen among five biotechs “all likely to get taken out in 2018.” A Pfizer takeover of Biogen seems moot, given the pharma giant’s exit in January from neuroscience, and elimination of 300 neuroscience jobs.
Strong fourth quarter 2017 results, plus its up-to-$217 million acquisition of ALS candidate KPT-350 from Karyopharm Therapeutics in January, led to talk that Biogen’s M&A activity would be as a buyer. So too did a 15% spike in Acorda Therapeutics shares on January 19, following rumors it would be bought by Biogen. “Biogen most definitely needs to do another deal, optimally a large one,” Geoffrey Porges of Leerink Partners, told CNBC. As Forbes reported, Alethia Young of Credit Suisse suggested future deals should add to Biogen’s top line and broaden its mix of treatments: “We think investors are looking for deals that could help with near-term growth and pipeline diversification away from Alzheimer’s.”
Speaking of Alzheimer’s, Biogen’s mid-study changes to its Phase III program for aducanumab, such as increasing the sample size, jolted investors enough to trigger a February 14 selloff that sent shares down 9%. Jefferies analyst Michael Yee said Biogen “needs to go out and buy de-risked neuro/orphan companies to ‘change the narrative’ to being a binary Alzheimer's company to one with products even if Alzheimer's doesn't work.”
So persistent is the narrative that BioMarin Pharmaceutical is a takeover target that the rare disease drug developer has appeared on every such list compiled by GEN—from the first such list in 2013, when Roche was said to have cast its eyes on the company, through last year's list.
Todd Hagopian, whose Hagopian Institute BioMed Extreme Value (HIBEV) biotech fund at Marketocracy last year returned 38%, declared BioMarin “My favorite rare disease company right now,” based on its six marketed treatments and five pipeline candidates.
BioMarin has projected finishing 2017 with revenue of between $1.29 billion and $1.32 billion, up 15.5% to 18% over 2017 (actual results were released after deadline on February 22). Top drivers of growth include Kuvan® (sapropterin dihydrochloride), the first and only FDA-approved phenylketonuria (PKU) treatment, which generated $300.1 million in the first nine months of 2017, up 16.4% year-over-year; and Vimizim® (elosulfase alfa), whose revenues grew to $299.3 million in Q1–Q3 2017, up 15% from a year earlier.
“While they will be expensive, this will be a lower-risk acquisition because you absorb over $1 billion in revenue immediately, and then can use the growth forecast to help raise the overall growth rate of the acquiring company,” Hagopian told Marketocracy founder and CEO Ken Kam in Forbes on January 24.
Despite rising revenue, BioMarin has projected a net loss for 2017 of $110 million to $130 million, which has kept its share price at between $80 and $100 since 2016, a key reason for the persistent takeover talk.
“A strong product pipeline and an existing portfolio of proven drugs makes it worthy of consideration as a buyout candidate,” according to Jeff Reeves of MarketWatch. “At $14 billion, it is hardly the cheapest biotech out there, but Big Pharma execs know they will get something substantive in this firm.”
bluebird bio has been labeled a takeover target by no fewer than eight analysts and/or news outlets since December. A key reason is strong Phase I trial results generated in December by the company’s anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy bb2121, being co-developed with Celgene.
In 21 patients with late-stage relapsed/refractory multiple myeloma (r/r MM), bb2121 yielded an objective response in 17 of 18 patients in active dose cohorts (94%), with complete response in 10 of 18 patients (though 3 of the 10 were unconfirmed). “This kind of success is simply too impressive to overlook,” Jeff Reeves extolled in MarketWatch on January 28.
In The Motley Fool, Todd Campbell of Gundalow Advisors and E.B. Capital Markets predicted that: “If bb2121 wins approval, then it has a very good shot at becoming a blockbuster.” Should bb2121 win FDA approval as expected in 2019, bluebird would split U.S. profits with Celgene while collecting milestone payments and royalties on ex-U.S. sales: “An acquirer could find that co-commercialization opportunity in the U.S. very attractive.”
Also attractive, Campbell added, were two late-stage pipeline candidates: LentiGlobin®, a treatment for transfusion-dependent β-thalassemia (β-thalassemia major) and severe sickle cell disease, and the cerebral adrenoleukodystrophy treatment Lenti-D™. Over the coming year, bluebird is expected to file for approvals for both. “It's anyone's guess who might step up to buy it, but I could argue the deal makes sense for any company that currently markets multiple myeloma drugs, including Celgene, J&J, Merck & Co., Amgen, and Bristol-Myers Squibb.”
In a January 22 note to investors, Maxim Group analysts Jason McCarthy and Jason Kolbert said bluebird’s attractiveness as a takeover candidate was enhanced by the $11.9 billion acquisition of Kite Pharma by Gilead Sciences, completed in October 2017, followed January 22 by Celgene announcing its planned $9 billion purchase of Juno Therapeutics: “Cell therapy is integrating into the oncology treatment paradigm and both Kite and Juno are now off the table, which in our view could leave bluebird as the next takeover target.”
When JP Morgan surveyed analysts for its “Buyside Survey” in December, Clovis Oncology topped the list with 31 responses (10% of respondents) citing the company among “your top M&A candidates in the sector.”
Clovis markets Rubraca® (rucaparib), a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer in patients treated with two or more chemotherapies. Rubraca launched in Q3 2017 with $16.8 million in net sales (full 2017 results are to be released February 26).
Those numbers are expected to rise in 2018, since Rubraca is expected to launch in Europe and win approval for at least one additional indication—maintenance treatment in women with platinum-sensitive recurrent ovarian cancer, for which Clovis has been granted priority review by the FDA. The agency has set a Prescription Drug User Fee Act (PDUFA) target decision date of April 6. Clovis has already announce positive data in the indication from the Phase III ARIEL3.
Rubraca is in four other Phase III trials: ARIEL4 in ovarian cancer (treatment); combination studies with Bristol-Myers Squibb’s Opdivo® (nivolumab) in ovarian cancer (maintenance) and triple-negative breast cancer; and TRITON3 in prostate cancer.
“Look for an expanded label on their signature drug to reignite buyout interest by the end of the first quarter,” predicted Todd Hagopian, who oversees the Hagopian Institute BioMed Extreme Value (HIBEV) biotech fund at Marketocracy, in Forbes on January 24. He also cited Clovis’ stock price, which closed February 16 at $54.15 a share, and traded as high as $100 in September, after the company was a rumored takeover target of Eli Lilly.
GlobalData Healthcare cited the oncology focus of Clovis (as well as bluebird bio and Puma Biotechnology) as a driver of takeover talk, along with the fact many biopharma giants are now flush with cash after the overhaul of U.S. tax laws enacted in December by President Donald Trump: “This excess liquidity can allow large pharma companies to take more risks, especially in oncology, where acquisitions are particularly attractive.”
A growing investor appetite for oncology-focused biopharmas has kept Incyte on numerous takeover-target lists. Mizuho’s investor survey listed the company among the top-four that investors believe are most likely to be acquired. One important reason why is rising sales of Incyte’s marketed drug Jakafi® (ruxolitinib), approved for myelofibrosis and polycythemia vera (PV) with more indications expected.
Jakafi grew into a blockbuster in 2017 with revenues of $1.13 billion, up 33% from 2016. The company has projected 2018 Jakafi revenues of $1.35 billion to $1.4 billion. The company expects to report data later this year from the pivotal REACH1 trial of Jakafi in steroid-refractory acute graft-versus-host disease (GVHD). A successful REACH1 will lead to a supplemental NDA for the new indication, Incyte said February 15.
Another asset of interest to investors is Iclusig (ponatinib), for which Incyte has an exclusive license signed in 2016 with Ariad Pharmaceuticals (since acquired by Takeda Pharmaceutical) to develop and commercialize Iclusig in Europe and other ex-U.S. countries. Incyte’s share of Iclusig revenues more than doubled in 2017, from $29.6 million to $66.9 million.
“The primary reason why Incyte is ripe for buyout is its two products on the market, Jakafi and Iclusig,” Zacks Equity Research stated December 11. “Incyte’s strong oncology portfolio makes it a lucrative target for companies like Gilead, Amgen, and Bristol-Myers Squibb.”
Incyte also enjoys a deep cancer pipeline, with data expected in the first half of 2018 from the Phase III ECHO-301 trial assessing epacadostat with Merck & Co.’s Keytruda® (pembrolilzumab) in melanoma.
Not all of Incyte’s sailing has been smooth. In April 2017, the FDA issued a Complete Response Letter declining to approve the rheumatoid arthritis candidate Incyte co-developed with Eli Lilly, Olumiant (baricitinib), pending additional clinical data. But in December, after talks with the agency, Lilly re-filed the U.S. application for Olumiant, which is approved in Europe.
Puma Biotechnology won FDA approval in July for its kinase inhibitor Nerlynx (neratinib) in early stage HER2-positive breast cancer following adjuvant Herceptin® (trastuzumab)-based therapy. Puma achieved market authorization in an indication targeted by the company that markets Herceptin. Genentech, a member of the Roche Group, has been developing a combination treatment consisting of Herceptin, another Genentech/Roche treatment Perjeta (pertuzumab), and chemotherapy.
In June, Genentech presented data at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago showing that its combination significantly reduced the risk of breast cancer recurrence or death (measured by invasive disease-free survival or iDFS) by 19% in people with HER2-positive early stage breast cancer compared to Herceptin and chemotherapy alone. That result was statistically significant, but smaller than expected—fueling speculation about whether the benefit was enough to wean doctors off prescribing Herceptin alone, or dissuade them from Puma’s Nerlynx.
Puma shares more than quadrupled during 2017, to a year’s high of $132.45 on November 8, before falling by nearly half since then, to $67.05 on February 16. Much of the decline has come since Puma’s January 23 acknowledgement that it was unlikely to gain European approval of Nerlynx this month. Yet shares remain more than double the $29 closing share price of May 8, days before an FDA advisory panel recommended U.S. approval of the drug.
“After the recent price drop, company shares look quite attractive,” John Engle, President of Almington Capital-Merchant Banker, commented at Seeking Alpha. “The mounting possibility of a buyout further colors the picture in Puma’s favor.”
Citigroup reiterated its buy rating on January 24, though it lowered its share price target from $164 to $146. And the company ranked second on JP Morgan’s “Buyside Survey” in December, with 29 responses (10% of respondents) citing the company among “your top M&A candidates in the sector.”
The prospect of a blockbuster drug for major depressive disorder (MDD) has further catapulted Sage Therapeutics to takeover-target status recently, following two positive announcements of clinical data since November.
Both centered on SAGE-217, a next-generation neurosteroid under development for MDD and sleep disorders. On December 7, the company trumpeted Phase II results showing that SAGE-217 achieved a statistically significant mean reduction in Hamilton Rating Scale for Depression (HAM-D) total score from baseline to Day 15 of 17.6 points, compared to 10.7 for placebo. Investors responded that day by sending the stock price surging 70%, to $156.27 from $91.90 a day earlier. Share prices have risen since then, closing February 20 at $163.18.
“Sage Therapeutics is almost certainly on the radar of most big pharmas at this point. The anti-depression drug market, after all, is worth tens of billions in annual sales,” George Budwell at The Motley Fool wrote on December 13. “In short, SAGE-217 may have what it takes to be a franchise-level anti-depression drug, which is a highly sought-after commodity in the pharmaceutical industry.”
Budwell predicted that SAGE-217 “appears more than capable of producing approvable results in a forthcoming late-stage trial.”
Sage followed up January 31 with Phase I/II results showing SAGE-217 significantly improved median sleep efficiency to 85% for the 30 mg dose, and 88% for the 45 mg dose, compared with 73% for placebo.
Another pipeline prospect for Sage is brexanolone. On November 9, Sage disclosed results from Phase III studies of in severe and moderate postpartum depression, showing statistically significant reductions in HAM-D total score compared with placebo at 60 hours.
TheStreet.com in September reported on a note to investors from BMO Capital Markets analyst M. Ian Somaiya, who predicted the company’s pipeline would attract a buyer in Alexion Pharmaeuticals after its disclosing plans to eliminate 20% of its workforce and move its headquarters to Boston.
Spark Therapeutics’ distinction of winning the first U.S. approval for a gene therapy for a genetic disease has revived speculation that the company is a buyout target. Following a unanimous advisory panel recommendation, the FDA on December 19 approved Luxturna™ (voretigene neparvovec-rzyl) as a one-time gene therapy for patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy.
However, Spark’s share price has yet to recover from the 54% tumble it took December 11, when investors responded to strong clinical data released the same day for another hemophilia A gene-therapy candidate by Spark rival BioMarin Pharmaceutical.
Spark reported a 100% reduction in annualized bleeding rate (ABR) and 98% reduction in annualized infusion rate (AIR) in the first four patients following at least 12 weeks post-infusion with SPK-8011 in a Phase I/II study. However, BioMarin showed Factor VIII activity levels in or near to the normal range (median and mean values of 49%) among three patients with the longest follow-up after dosing with Valoctocogene Roxaparvovec—compared to much more variable Factor VIII levels shown by SPK-8011.
While Spark shares fell to $47.72, BioMarin shares began climbing that day, from $81.99 to $88.11, then soaring to $92.63 on February 1 before dipping back. “Investors could be over-reacting to the Spark Therapeutics hemophilia A data,” wrote Todd Campbell of Gundalow Advisors and E.B. Capital Markets in The Motley Fool.
Analyst Martin Auster at Credit Suisse, according to 24/7 WallSt, expects better clinical news on SPK-8011 later this year, with that and other hemophilia-treatment programs adding to a solid base for growth from Luxturna and its gene-therapy development, manufacturing, and regulatory expertise. Among hemophilia programs is the Pfizer-partnered SPK-9001, which in December showed a 97% reduction in ABR and 99% reduction in AIR among all 11 participants in an ongoing Phase I/II trial.
Tesaro is one of three companies with approved poly (ADP-ribose) polymerase (PARP) inhibitor treatments on the market, accounting for its interest among market-watchers scouring for biopharma buyout candidates.
Tesaro’s once-daily, oral PARP inhibitor Zejula™ (niraparib) won FDA approval in March as a maintenance treatment for women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrated a partial or complete response to platinum-based therapy. In November, Tesaro won European Commission approval for Zejula in recurrent ovarian cancer.
Zejula recorded $65.321 million in revenues during the first three quarters of 2017 (fourth quarter results come out February 27), and the treatment is expected to generate much more next year. “Use in the post-treatment maintenance setting is increasing, and studies could expand its use into early line ovarian cancer and non-small-cell lung cancer treatment. Those markets are worth about $8 billion,” Todd Campbell of Gundalow Advisors and E.B. Capital Markets wrote in The Motley Fool.
Another attraction of Tesaro for would-be buyers is its stock price, which has fallen by two-thirds over the past year—from $190.27 on February 21, 2017, to $62.01 on February 21 of this year. Investors have questioned Tesaro’s ability to compete as additional PARP inhibitors emerge, though Seamus Fernandez of Leerink upgraded the company’s rating to Outperform in November, reasoning Zeljula remained in a favorable position. But in January, Piper Jaffray analyst Christopher Raymond cut his price target on Tesaro to $80 a share from $117, after dialing back his fourth-quarter sales forecast for Zejula to $48 million from $53 million.