It’s been another IPO-intensive couple of weeks here at FOTF HQ. We keep looking for other things to write about, but sometimes the fastest shave on deadline is with Occam’s razor. Or something like that. We didn't exactly ace our philosophy classes in college.
You don’t have to be the sharpest tool in the shed to notice how life-science IPOs have re-inserted themselves into the daily chatter this year, and there’s one upcoming issue that makes for fascinating conversation: bluebird bio, a big-idea company (gene therapy for rare diseases) that apparently strives to avoid capital letters. The firm later this year expects to enter a Phase II/III study with its lead program Lenti-D to treat young boys with the rare hereditary disorder childhood cerebral adrenoleukodystrophy, or CCALD. Also this year, bluebird should launch a Phase I/II trial for another gene transfer product, LentiGlobin, to treat ß-thalassemia major and sickle cell disease.
A bell-ringing IPO would be notable for at least three reasons. First, if someone told you five years ago that public investors would one day line up to buy shares in a gene therapy company, you probably would have had that person tested for the stark-raving-mad gene. But this decade the field has enjoyed quite a turn-around, as our Start-Up colleagues explained last summer. A large step in that journey came a couple of months later, when the European Union approved uniQure's Glybera despite a spotty track record.
Perhaps true optimists would say they never doubted that gene therapy, like so many biomedical technologies, would take more than two decades to find its way into commercial products. But a lot of other biomedical technologies aren't effectively shut down for years because of daunting safety concerns. Glybera’s approval was one kind of validation of gene therapy; a bluebird IPO would be another.
In a sense, though, public investor validation happened nearly a year ago, before the Glybera approval, when bluebird raised its $60 million Series D. The round included its previous VC backers, but new to the company’s cap table were hedge funds, so-called “crossovers” that have made their presence felt in biotech the past few years. The idea is that public investors with biotech savvy want a foothold in an elite circle of privately held firms so they’re in position to benefit from a boffo takeout offer or from an inside seat at IPO. Once in, as with bluebird’s D round, liquidity is probably no more than a couple years away. The crossovers bring much-needed cash to a mezzanine round, but they also bring a certain amount of impatience.
So when bluebird said Deerfield Capital, RA Capital Management, Ramius Capital Group and two undisclosed public funds pitched into last year Series D, it was pretty clear where the firm’s sights were set. Those undisclosed public funds are likely affiliated with Fidelity and The Capital Group, both of which are listed in bluebird’s S-1 as having invested for the first time in the Series D, and which own about 12% and 9% pre-IPO respectively. We don’t know yet how much bluebird is aiming for, but the firm has raised north of $100 million since a 2004 recapitalization. (It was known as Genetix Pharmaceuticals until 2010.)
Raj Shah, partner at RA Capital Management, one of bluebird's "crossovers," told FOTF that his firm had been waiting for a gene therapy company to produce good animal data. When bluebird showed its two lead programs were “unequivocally active” in humans, RA jumped in and is prepared to increase its position at the IPO. “We want exposure to the best technologies in this space,” said Shah. The EU approval of Glybera was encouraging, said Shah, but “FDA's recent IND acceptances of bluebird’s programs are also quite validating for the gene therapy space.”
It’s not the same as approval, of course – no gene therapy product has made it to market in the US – but it’s a significant point and speaks to the company’s approach of using a method that has elements familiar to regulators. The company extracts the patient’s own hematopoetic stem cells, makes the genetic modification ex-vivo, and transfuses the modified cells back into the patient.
The third reason to take note of bluebird is its largest owner, Third Rock Ventures, which appears in this column as often as a Kardashian on the New York Post’s Page Six. Third Rock owns 28.1% of bluebird, double the stake of the next largest owner, TVM Capital (with 14.3%, and ARCH Venture Partners is next with 10.6%). The Boston firm has had no problem raising funds – and funds, and funds, and more funds – with two exits, and two other portfolio companies in option-to-acquire agreements with larger partners.
But bluebird as far as we can tell would be its first IPO, and cofounder Mark Levin told our "Pink Sheet" DAILY colleagues that there should be more in the coming year. (The story on Levin’s talk this week at the Harvard Club in New York is coming soon. The dressed-down Levin had to don a tie to speak at the stuffy club, which made for good comedy at the start of his talk: "How many people here had to borrow a tie to get in?" he asked the crowd. "I actually heard someone had to get a pair of pants.")
Fully clothed or not, every venture firm wants its portfolio companies to be public and liquid, of course, but if TRV notches multiple issues in the next several months, it could be a big validation not only of its company formation process but also its ability to shepherd those firms quickly to important milestones -- important enough for the still-small coterie of public biotech specialists to buy in. That is, if the companies going public are the ones in TRV’s portfolio that have grown from true early-stage seedlings into viable businesses.
We’re getting a bit ahead of ourselves. Yes, biopharma firms are going public, but on the whole, they’re still not big-science risk takers. A couple pain-med companies here, a PE-backed CRO there (see our Quintiles blurb below), and the next out the door is probably going to be a firm with $300 million-plus in venture backing that’s hoping public investors buy its rationale for yet another blood thinner on the market. (See our Portola Pharmaceuticals blurb below.)
Meanwhile, venture firms continue to cozy up to Big Pharma to help raise new funds or to help defray the risk of their early-stage efforts, as Avalon did with GlaxoSmithKline, in a deal that got our DOTW brethren thinking deep thoughts a couple weeks ago.
Now Atlas Venture is the latest to pull in big drug companies as limited partners. The venerable firm said this week it has Amgen and Novartis on board, although neither is accorded special rights to either invest in or acquire the companies that Atlas starts up. However, Atlas pledges to “explore areas of mutual interest” with its Pharma LPs, and Amgen and Novartis are free to invest directly in the Atlas companies from their own venture funds, both of which are extremely active. The key, Atlas partner Jean-Francois Formela told our PSD colleagues, is not to do anything that would lead the firm or its LPs to “unnatural behavior,” which we have to nominate for quote of the year. Because, when you think about it, what exactly is natural behavior for a VC and its investors? (We know a few entrepreneurs who would love to answer that in a manner unsuitable for family viewing.)
It all brings us back to philosophy: the Platonic ideal of venture capital, and all that. Are your investments the true essence of your existence, or just shadows on the wall of your portfolio? A famous philosopher once said, "I know kung-fu." But, grasshopper, if you have traveled this far, it is infinitely better to know…
Quintiles Transnational: The massive contract research organization’s return to the public markets, timed perfectly, was by no means a typical biopharmaceutical IPO. The May 8 issue raised a staggering $1.1 billion and pushed the company's market value to $6 billion as Wall Street’s interest in biopharma continues to rise. As you might guess from the dollar totals and the fact that Quintiles went private a decade ago, this was a private equity deal, not a venture capital exit. Quintiles founder and Executive Chairman Dennis Gillings, Bain Capital and TPG Capital each made more than $150 million in the IPO, and each continues to hold about 20% of the company, assuming the percentage of shares to be sold was the same in the final sale as reported in the S-1. Bain became the lead Quintiles investor in 2008, when several new private equity investors came in. The investors weren’t waiting for an IPO to get paid; they've already cashed out about $1.5 billion in dividends in the last five years. In addition, Gillings and investors split a one-time $25 million payment upon the IPO. Quintiles will use most of the proceeds to make that investor payment and pay down more than $350 million in debt. The IPO priced at the top of its range at $40, and – in another sign this was no ordinary biopharma IPO – the number of shares sold by insiders ballooned at the last minute by more than 5 million. For most VC-backed biotechs, insiders have to buy shares to get an IPO done. – Stacy Lawrence
Portola Pharmaceuticals: The next biotech IPO likely to price is for hematology firm Portola, which is currently on the road to talk up an IPO slated for the week of May 20. Portola had $125 million in cash on March 31, and wants to raise $100 million through the sale of 6.9 million shares at $13-$16 each, not a massive sum considering the firm has raised at least $306 million in venture financing. Pre-IPO, the firm’s largest shareholders are an arm of the Singapore government’s investment company, MPM Capital, Prospect Venture Partners, and several other venture firms hold more than 5 percent. At the proposed mid-point, Portola would be valued at $469 million. Portola’s lead compound is the oral anticoagulant betrixaban, a once-daily Factor Xa inhibitor that ex-partner Merck handed back to Portola in 2011. Portola hopes to carve out a market in the crowded field for the drug after hospitalization. There are other differences that Portola hopes will catch the fancy of public investors. Betrixaban is in Phase III for the prevention of venous thromboembolism (VTE) in acute medically ill patients; there isn’t another novel oral anticoagulant in the clinic or approved for this indication, according to the company. On the road show, Portola CEO William Lis pegged the betrixaban market at $3 billion to $4 billion, based on the current price of orals of about $8 daily, and assuming 35 days of usage post-hospitalization. Lis expects to market betrixaban to hospitals, so he estimates a sales force of about 100 will be sufficient. The firm’s next candidate is PRT4445, a Phase II antidote for Factor Xa inhibitors. – S.L.
Isis Pharmaceuticals: The publicly traded antisense developer said May 8 it priced a secondary offering of 9 million shares of common stock at $19 per share. Isis gathered $162.5 million in net proceeds from the sale, a sizeable amount to help the firm push through its deep pipeline, with nine compounds expected to produce Phase III or significant Phase II data by early 2014. The offering cashes in on momentum the firm has seized in the past several months – not least of which was the Kynamro (mipomersen) approval in late January for the treatment of the very rare homozygous familial hypercholesterolemia. Meanwhile, Isis’s dealflow continues unabated, as our DOTW brothers and sisters note in this post. The firm has raised more through partnerships, about $2 billion, than it has from equity sales; at the end of 2012, the firm had the potential to earn up to $5.1 billion in future milestones. It’s also worth noting that Isis owned nearly 21% of Regulus Therapeutics, which it and Alnylam Pharmaceuticals established jointly in 2007, when Regulus went public in October 2012. As of the end of February, the most recent disclosure, the stake had dipped just below 20%. Regulus debuted at $4 a share and has risen 82% to $7.29 as of May 15. Underwriters led by Goldman Sachs and JP Morgan have the option to sell an additional 1.35 million shares.-- Alex Lash
Lumena Pharmaceuticals: It’s a new company wrapped around a very old product. Lumena announced a $23 million Series A round to redirect toward orphan indications a compound that was tested more than a decade ago in more than 1,400 patients. The tests were run by Searle and then Pharmacia, where Lumena’s current VP of research worked on the program to fight high cholesterol. (Subsequent acquirer Pfizer shelved the program.) Lumena is aiming to treat cholestatic liver disease, which is characterized by retention of bile acids in the liver, resulting in painful symptoms related to an intractable itch. Sufferers of various forms, including Primary Biliary Cirrhosis, the pediatric Alagille Syndrome and Progressive Familial Intrahepatic Cholestasis, often have difficulty sleeping, and have been known to scratch their skin until they bleed and scar. Lumera will use the Series A proceeds to run Phase III trials in each of the orphan indications. The firm has been in stealth mode since 2011 with Pappas Ventures partner Mike Grey serving as CEO. Pappas led the round and recruited Alta Partners and RiverVest Venture Partners to join. Like many venture firms seeking to avoid high-risk, high-cost projects, Pappas was interested especially in pharma opportunities with defrayed risk and short clinical development paths. Grey said the prior clinical work and orphan indications requiring smaller trials made LUM001 appealing. The compound inhibits apical sodium-dependent bile acid transporter (ASBT). That protein is critical in the process of reabsorption of bile acids from the small intestine, specifically the lumen, where the body absorbs nutrients from digested food. – Paul Bonanos
All The Rest: The fortnight’s largest venture round was GPCR therapeutics developer Trevena’s $60mm Series C round to which Forest Labs committed $30mm and also optioned the company’s Phase IIb-ready TRV027 for acute decompensated heart failure… In a Series E round, oncology-focused Tokai Pharmaceuticals took in $35.5mm…Kite Pharma’s Series A preferred stock financing – including the conversion of $15mm in outstanding promissory notes – garnered the cancer immunotherapeutics developer $35mm…Belgian biotech Cardio3 Biosciences raised €19mm ($25mm) in venture funding: €7mm in new equity committed by existing investors and €12mm from the conversion of existing convertible loans…Virtual company Tacurion Pharma (formed by Drais Pharmaceuticals) raised $15mm in an A round from backers including Astellas, which also out-licensed its nocturia candidate to the start-up…In a round led by Mérieux Développement, which was joined by return backer Shire, NeuroPhage Pharmaceuticals scored $6.4mm…Callidus Biopharma closed a $4.6mm Series A financing to speed up preclinical studies of candidates in Pompe and Gaucher diseases…In a registered direct offering, Dyax will issue 8.9mm common shares priced at $2.30 and 41k Series 1 preferred shares (priced at $230 and convertible into 100 shares) for proceeds of $30mm…A stock purchase agreement with Lincoln Park Capital Fund grants Zalicus the right to sell up to $25mm worth of its common stock to support clinical trials of lead pain candidates Z160 (Phase II) and Z944 (Phase I)…Through an RDO of 3.9mm shares at $4.14, Omeros brought in $16.1mm…A follow-on public offering of 63.3mm shares at RMB12.25 ($1.99) each, resulted in proceeds of $126mm for Chinese CRO Zhejiang Huahai Pharmaceuticals…Acadia Pharma netted $94mm through its FOPO of 8mm shares priced at $12.50…Rockwell Medical brought in net proceeds of $33.1mm in its FOPO, selling 11.5mm shares at $3.05…Cyclacel Pharmaceuticals expects to see $20mm in proceeds from a public offering of 6.7mm shares at $3…In a FOPO of 9.5mm shares at $1.50, Discovery Laboratories netted $13.4mm…Initial public offerings that priced: Receptos netted $68.3mm through the sale of 5.2mm shares at $14, the low-end of its $14-16 range; Ambit Biosciences, first planning to sell 4.6mm shares at a $13-15 range, priced 8.1mm shares at $8, still bringing in $65mm; and after trying since 2007, Insys Therapeutics finally completed a $34.2mm IPO by selling 4.6mm shares (including overallotment) at $8, way below its $16-18 range, which was later cut to $8-$10…Alocobra upped the number of IPO shares it plans to sell to 2.275mm at a $10-12 range; increased from the 1.4 mm shares in its March S-1 filing…Kamada, which filed for its IPO in April, announced it would sell 5.6mm ordinary shares…Biotechs that filed for IPOs: OTC cellular therapeutic vaccines developer Heat Biologics and Esperion Therapeutics; the latter cardio-focused company went public in 2000, but was acquired in 2003 by Pfizer, which spun it off to investors five years later…Vivus plans to offer $200mm worth of 7-year, convertible senior unsecured notes…Alimera Sciences (ophthalmic pharmaceuticals) has secured a $20mm debt facility – $5mm in a principal term loan, plus up to $15mm more as a working capital line of credit – through Silicon Valley Bank…Theravance is splitting into two separate public entities, one to focus on its 2004 GlaxoSmithKline deal, the other to perform R&D; and in a separate arrangement, Elan will make a $1bn cash payment to Theravance in exchange for a 21% stake (held by GSK under the 2004 deal) in royalties related to a portfolio of four Theravance respiratory drug programs…In fund news: Merck KGAA pledged to increase its investment in its corporate venture capital fund MS Ventures, raising its funding level to €100mm ($129mm) from up from its initial €40mm at the fund's inception in March 2009. -- Maureen Riordan
Photo courtesy of IngytheWingy, who seems to have a thing for public transportation.
Thanks to Mike Goodman for his contributions this week.
