Well, that flew by. Unlike the little elf in the video above (and if you don't know Nick Lowe, 'tis the season to make your acquaintance), no one in biotech has had time to wait around this year, it seems. The calendar has been marked by several trends that we and our colleagues have followed closely, but none as important as the rush to jump through the IPO window.
It’s fitting, then, that we kick off our final 2013 column with a chat about initial public offerings. TetraLogic went through some contortions to go public this fortnight (see blurb below), but it was more a stumble than a sprint for what was likely the sector's final IPO of the year. Activity hit its peak this spring and summer, then fell off sharply in the fall as the federal government bumbled its way into a shutdown and a botched launch of the “Obamacare” insurance exchanges. We’re not implying causality, mind you, although the shutdown did absolutely nothing positive for the economy. More likely, the sheer volume of IPOs (38 through October 31) skimmed the cream off the pot.
Can the pipeline reload for 2014? Public investors will return after the ball drops looking for late-stage, near-commercial (or near-approval) companies, of course, but we saw in 2013 a certain appetite for higher risk bets like bluebird bio and OncoMed Pharmaceuticals, whose paths to the public markets we chronicled recently in Start-Up.
And the prospect pool for biotech should be stronger than it’s been for several years. This is a bit counter-intuitive, so bear with us. The MoneyTree report, a collaboration between PricewaterhouseCoopers and the National Venture Capital Association, said recently that through September 30, the 541 publicized biotech and device venture deals comprised the lowest nine-month total since 2005. And only 104 life science companies raised first-time venture capital, the worst showing since 1996.
So what’s all this about a strong pool of prospects? By our near-final count, life science Series A fundings have already topped 2012’s count, both in deal flow and dollars committed. Note the difference: MoneyTree counts first-time venture raises; we count Series A’s, but not seed rounds, because we feel it’s a better gauge of companies with real promise. (See Bruce Booth’s description this week of Atlas Venture’s seed-funding program for a glimpse of the fragility of seed-stage biomedical companies.)
Landing Series A cash is obviously no guarantee of permanence, but the gatekeepers are ever more vigilant. For cutting-edge science, groups like Atlas, Flagship Ventures and Third Rock Ventures spend a year or more hammering on an idea, forcing it through iterations, proving its worth, before committing serious dollars. And if the ideas aren’t truly novel, there are other de-risking strategies; many Series As these days are for programs spun out of other companies, run by trusted management teams, or both.
In other words, there’s still plenty of risk in a Series A investment, but perhaps not as much as you’d think. And by our count, Series As particularly on the biopharma side are doing well. OK, maybe the $120 million A round for Juno Therapeutics has skewed the dollar figures just a wee bit, but the deal flow is still on track for well more than 100 financings in 2013, on top of the 100 or so in 2012. We’ll have the final count and a deeper dive into the Series A class of 2013 in the upcoming Start-Up, right around the time the JP Morgan conference is in full swing.
What do you think? Do the 200-plus companies that have had their Series A stockings stuffed in the past couple years represent a healthy pipeline? Since the Great Recession faded, the investors who've had cash to make bets with have insisted there's been no better time. In 2014, we should start to see if they're right.
Meanwhile, there's no better time for you to spend a few days unplugged from your screens, relaxing with friends and family. May your holidays be safe and warm, and here's your first present: A delicious, sustainable, locally sourced, gift-wrapped edition of...
Atara Biotherapeutics: With news of Atara’s new $38.5 million Series B round also comes news of its $20 million Series A, quietly completed in March. The Brisbane, Calif.-based company was established in fall 2012 via a partnership between Amgen and venture stalwart Kleiner Perkins Caufield & Byers, and endowed with a portfolio of six former Amgen assets, all in the transforming growth factor (TGF)-beta family of compounds. First-time backers in the new round included Amgen Ventures, Celgene Corp., and crossover fund EcoR1; they joined Series A investors Alexandria Venture Investments, DAG Ventures and Domain Associates, as well as KPCB. The Series B remains open, and Atara CEO Isaac Ciechanover told “The Pink Sheet” DAILY it hopes to bring in a final investor within 90 days. The corporate venture units’ investments were “purely financial,” he said; Amgen itself holds equity but did not invest cash during the Series A. Atara is an umbrella company that operates three “sister company” subsidiaries named for Christopher Columbus’s three ships used in 1492. Its most advanced drug, PINTA745, is a myostatin inhibitor already in Phase II for a muscle-wasting disorder found in end-stage renal disease patients; it’s housed in Pinta Biotherapeutics. The company also hopes to submit an IND for activin inhibitor STM434, one of Santa Maria Biotherapeutics’ three compounds, and begin trials in ovarian cancer during 2014; farther along will be Nina Biotherapeutics’ antibody NINA842 for cancer cachexia, which Ciechanover said is about 18 months from the clinic. – Paul Bonanos
Crescendo Biologics: The UK firm has raised £17.5 million ($28 million) in a Series A financing to pursue development of its variable heavy-chain antibody fragments as therapeutics. The round was led by new investor Imperial Innovations Group, and included for the first time Astellas Venture Management. Sofinnova Partners (the European group) also participated in the round after providing seed funding to Crescendo, which was formed in 2009. The funds are expected not only to support development of the platform technology but also proof-of-concept clinical studies of its antibody fragments, applied topically in psoriasis. The firm will also pursue studies in oncology. Crescendo makes its fragments by first eliminating antibody production involving genes located in three chromosomal regions in mice, and then adding DNA-containing genes for the human antibody heavy chain. Marianne Brüggemann and colleagues at the Babraham Institute in Cambridge, UK, pioneers of the first wave of transgenic technology exploited by Medarex and Regeneron Pharmaceuticals, were involved in this work, Crescendo CEO Mike Romanos told “The Pink Sheet” DAILY. Psoriasis has been selected as the first target for Crescendo’s fragments as they can be formulated into creams and penetrate into the relevant region of the skin following topical application, Romanos said. Although systemic monoclonal antibodies have had a tremendous impact on severe psoriasis, milder cases are poorly served with current therapies, and a non-immunosuppressive treatment should be useful, Romanos said. The first fragment should enter clinical trials at the end of 2015 in psoriasis, and if successful, the work could be expanded to include atopic dermatitis and other inflammatory dermatological disorders. – John Davis
Acucela: The Seattle biotech filed on December 17 to raise up to $125 million in an IPO on the Tokyo Stock Exchange’s Mother’s Market. The company has a partnership with Otsuka under a 2008 deal for lead compound, emixustat, which is in Phase IIb/III testing to treat dry age-related macular degeneration (AMD). Acucela started the trial in the first quarter of 2013 and expects that if 12-month study results warrant, it will submit to FDA and EMA for approval. There is no FDA-approved treatment for dry AMD. If you’re not familiar, biotech offerings on the Mother’s Market are for the most part relatively small, and like the London Stock Exchange’s AIM market, often raise tiny subsequent offerings. They typically suffer from chronic low liquidity and languish with little investor attention as small caps. Retail investors, and their whims, are a big factor on the Mother’s Market, which specializes in high growth and emerging stocks. That combination makes it very volatile. This year, some biotechs have proven hugely popular. For example, peptide therapeutic company Peptidream, which isn’t in the clinic yet but has several discovery partnerships, conducted a $68 million IPO on the Mother’s Market in June and is now worth about $1.6 billion. Acucela founder, President and CEO Ryo Kubota is a Japanese ophthalmologist who has trained, practiced and taught in both the US and Japan. In addition to its Seattle headquarters, the biotech also has a Tokyo office. – Stacy Lawrence
TetraLogic: The Phase II cancer company closed on December 12 with what was likely the final IPO of the year, but that was only after it had slashed its price in half to $7 per share from a range of $13 to $15. Even with the discount, its shares have remained flat in early trading. That’s with existing investors Amgen and Pfizer as well as company executives agreeing to purchase most of the shares offered at IPO. Not just some, but most: That’s a first in our IPO experience. Was this a venture round or an IPO? Insiders bought a whopping 4.6 million shares of 7.2 million sold. (TetraLogic hasn’t yet fared as well as another recent discount IPO: Relypsa, which priced in November and is now up 137%.) Overall the biotech IPO class of 2013 is holding its own. The 44 IPOs this year are up 41% as a group with more winners than losers. Only about one-quarter of them have lost ground or are flat from their IPO prices. That’s better than coin-toss odds – and that’s saying something in biotech. TetraLogic hopes to gain some traction with its small molecule mimics of Second Mitochondrial Activator of Caspases technology (SMAC-mimetics). Its lead program is birinapant, which is in Phase I and Phase II testing in hematological malignancies and multiple solid tumors. The biotech plans to start a randomized Phase II trial for birinapant and azacitidine versus azacitidine alone to treat myelodysplastic syndromes in the first half of 2014. – S.L.
Best of the Rest (Highlights of Other Activity This Fortnight): In the second Xention spin-off following Provesica three years ago, Ario Pharma completed a $3M Series A round to pursue TRPV1 antagonists in chronic cough…in its second secondary offering in the last few months, Xoma netted $54M to pay for development of Phase III gevokizumab for non-infectious uveitis and its preclinical XMet program of insulin activators and sensitizers…days before announcing its acquisitions of CNS spec pharma NuPathe, Endo raised $700M in a 5.75% convertible notes sale…and Versant Ventures pledged investments in Canadian life sciences start-ups. – Amanda Micklus