NICE's Future is Assured, Says Departing Chairman Rawlins

"The future of the National Institute for Health and Clinical Excellence is assured," said its long-serving chairman, Professor Sir Michael Rawlins, speaking at the start of the institute's annual meeting on Tuesday 10 May in Birmingham, U.K.

Addressing a packed auditorium in the U.K.'s second-largest city, Rawlins pointed to the way the proposed Health and Social Care Bill will give NICE a new name – the National Institute for Health and Care Excellence – and will remove it from political interference by establishing it as a new non-departmental body.

The existing roles and responsibilities of NICE are however expected to remain unchanged, but the new NICE will take on additional responsibilities for generating advice about social care.

This year, NICE still expects to publish 39 technology appraisals (including drug appraisals), 21 clinical guidelines, 5 public health guidelines and 30 quality standards.

Rawlins accepted that treatment guidelines for specific disease conditions are now addressed by several appraisals, which is why the institute has just launched "NICE Pathways", its online resource that brings together all the relevant appraisals for each specific condition, producing a path of care.

Rawlins was not so forthcoming on one issue of particular interest to the pharmaceutical industry, however: value-based pricing. He claimed that NICE would play a critical role in developing such pricing for medicines in the U.K., but said the details of how this would work in practice have yet to be decided.

No surprise there, perhaps: after all, the British pharmaceutical industry appeared to be similarly in the dark about VBP at a March press conference. And although industry hasn't voiced strong opposition to VBP in principle (it would rather play a role in designing it), it does worry that VBP is incompatible with the wider set of proposed reforms in the U.K, which may lead to health care being commissioned by consortia of general practitioners. The worry: the likely volume of prescribing of a particular medicine, a vital component of deciding a price, cannot be estimated if each of the 400 or so consortia have different prescribing formularies.

But with the success of this wider set of health care reforms (known as the Health and Social Care Bill) looking increasingly uncertain, this particular worry may go away. The Bill's progress has been halted while politicians take stock of its implications, following concerns that it was being rushed into law without proper debate.

With the future shape of health care management in the U.K. in the balance, there's everything to play for for those (including NICE) involved in managing health care in the U.K. But Rawlins himself, while expressing his confidence in the agency's future role, is calling time: he will not put himself forward as a candidate for chairman of the new NICE next year, he told the audience in Birmingham. That makes this his last year, after leading the agency since its inception 12 years ago.

--by John Davis

Deals of the Week Cares Enough To Send The Very Best

Even if it's just a Hallmark holiday, Mother's Day is still special to Deals of the Week. We'll be spending some time this weekend contemplating the sacrifices our moms made for us, and honoring them for what they gave us.

But like Anna Jarvis, one of the holiday's founders, we're not so crazy about the way Mother's Day has become commercialized over the years. Just a few years after hatching a plan to memorialize her mother with a special day everyone could share, she became a vocal opponent of the holiday's industry, despising saccharine cards and similar trite gestures so much that she was once arrested for disturbing the peace while protesting a celebration. A lot can happen between the time an idea is conceived and the moment it turns into a billion-dollar juggernaut. A well-intentioned plan can go sour when big money's at stake -- a notion with which readers of this column are likely all too familiar.

Indeed, this week's "no-deals" show how four companies took interest in others' ideas, only to walk away as their projects marched toward commercialization. Meanwhile, one company that faced a hostile bidder has plenty of reasons to thank its new parent -- a relationship we'll explore in...

Teva/Cephalon: Teva's gentler, kinder – and more lucrative -- offer to buy Cephalon for $6.8 billion in cash may be viewed as the rescue of a biotech flagbearer from the hands of Valeant, a scruffy, R&D-hating, efficiency loving hostile bidder. Teva plans to use Cephalon to build out its specialty pharma branded business, now at $4.6 billion in annual sales, to $9 billion by 2015. To do so, it'll capitalize on Cephalon's R&D capabilities, pipeline, and currently marketed products. That's in stark contrast to Valeant, which had planned to discontinue Cephalon's pipeline programs. But Teva's and Valeant's approaches may not have been as far apart as executives' speeches would have listeners think. Valeant, which offered $5.7 billion for Cephalon, would almost certainly have come up in price. And Teva, like Valeant, is placing a heavy emphasis on cost synergies and cash flow from marketed products to make this deal work financially. Teva expects to attain about $500 million in cost savings a year by year three after the deal closes, executives said. The difference, perhaps, is where and how those cuts would be made. Valeant was ready to go in and axe much of Cephalon; Teva will more likely bundle the best from its own assets and the acquiree's before deciding what to jettison. Teva is currently engaged in patent spats concerning multiple sclerosis therapy Copaxone (glatiramer), while its robust generics business will confront headwinds as the number of large innovative drugs expected to go off patent falls off post 2012. Many of Cephalon's late-stage pipeline assets could start to contribute to the company's revenues by that time. - Wendy Diller

Allergan/Molecular Partners: Coinciding with the announcement of Phase I/II trial results for its VEGF-antagonist drug candidate at the Association for Research in Vision and Ophthalmology conference, Molecular Partners AG reached an agreement with Allergan Inc. to out-license the molecule for a $45 million upfront payment. Privately held Molecular Partners will be eligible to receive up to $375 million in development, regulatory and sales milestones under the deal announced May 4, and could earn tiered, double-digit royalties on sales of MP0112, a designed ankyrin repeat protein (DARPin) about to enter Phase IIb development. The two companies will collaborate during Phase IIb, after which Allergan will be responsible for all development and commercialization activities. With ‘0112 investigated in both wet age-related macular degeneration and diabetic macular edema, the partners hope to position the molecule as a best-in-class treatment for neovascular eye disease, with a dosing frequency advantage over current wet AMD standards Lucentis (ranibizumab) and Avastin (bevacizumab). Molecular Partners uses its designed repeat protein technology platform to develop small target-binding proteins that perform significant functions in cell signaling and kinase inhibition. Combining some of the benefits of antibodies and small molecules, the Swiss biotech says DARPins offer lower molecular weight and better affinity, stability and selectivity compared to traditional antibodies. –Joseph Haas

Onyx/S*Bio: What was once considered among the biggest deals between a U.S. company and an Asian biotech has come undone. Onyx Pharmaceuticals walked away from its option agreement with Singapore’s S*Bio, covering two janus kinase inhibitors. The tie-up, originally announced in January 2009 and broadened in 2010, cost Onyx $25 million upfront plus an additional $20 million when it was expanded; milestone payments could have made the original deal worth $550 million in total. Onyx had negotiated an option to license, develop and commercialize two drugs, SB1518 and SB1578, in the U.S., Europe and Canada; the former drug was in Phase II for myelofibrosis and had been studied for lymphoma. Onyx’s decision came as the company announced redoubled focus on its potential blockbuster proteasome inhibitor carfilzomib, obtained when it acquired Proteolix in 2009. S*Bio said it will seek a new partner urgently, with a goal of beginning a pivotal Phase III trial on SB1518 later this year. - P.B.

AstraZeneca/Targacept: AstraZeneca opted not to license Targacept’s selective alpha 7 neuronal nicotinic receptor modulator, TC-5619, a schizophrenia treatment. TC-5619 is considered by Targacept to be one of its most promising assets; it recently announced positive results in a mid-stage study in schizophrenia patients. Yet, the compound failed a Phase II proof-of-concept study in attention-deficit/hyperactivity disorder. The biotech has vowed to move forward with '5619 on its own; saying it has the cash to fund further trials by itself. This is not the first time the British pharma has decided not to work with the Winston-Salem, NC-based biotech. Two years ago Targacept announced that another NNR compound, AZD3480, was not going to be pursued in Alzheimer's disease or schizophrenia after two poor mid-stage (Phase IIb) results. In October, AstraZeneca dropped Targacept’s ADHD drug, AZD1446, when it failed to perform better than a placebo in a Phase II trial. Yet Targacept’s future relies largely on the success of AZD5214, a major depressive disorder treatment that is partnered with AstraZeneca and is currently in Phase III trials. -Lisa LaMotta

Pfizer/Rigel: Six years ago, Pfizer licensed a portfolio of preclinical spleen tyrosine kinase inhibitors from South San Francisco-based Rigel. Although the companies identified a promising lead candidate, R343 for allergic asthma, Pfizer has returned all rights to the drug program to Rigel, giving the company full control of the drug as it heads for Phase II trials. Pfizer had paid $10 million upfront and acquired $5 million of Rigel stock at a premium price when the agreement was announced in 2005, although analysts said milestone payments could have added $200 million to the deal's value. With the partnership unraveled, Rigel now says R343 is its most advanced clinical asset; the company did not say whether it would seek a new partner, but claimed it will design a Phase II trial later this year. Rigel said the decision came out of Pfizer's desire to exit the allergy and respiratory area completely. - P.B.

Sanofi-Aventis/Metabolex: Well-funded, privately-held Metabolex seemed to have scored a coup last June when Sanofi licensed its oral GPR119 receptor agonist, MBX-2982, for type 2 diabetes. But that deal, too, has come apart: In a regulatory filing, Sanofi said it would walk away from the agreement, reportedly after seeing the data from a Phase IIa trial. Full terms of the agreement were never released, but Metabolex will keep the upfront payment from a deal valued that could have been worth up to $375 million including milestones. The licensing was part of Sanofi's push to diversify beyond Lantus, the primary drug in its diabetes franchise. Metabolex, backed by a long list of investors including Alta Partners, Novo Ventures, Venrock Partners and Versant Ventures, hasn't yet said whether it will seek a new partner. - P.B.

At Allicense, VCs Avoid The Creep

If Tuesday’s discussions at Deloitte Recap’s Allicense conference focused on how VCs are putting their money into new biotech companies, Wednesday’s sessions dealt largely with the challenges they face in getting their money out – and what they’re doing about it. Privately-held start-ups are continually struggling with structured buy-out deals that delay full liquidity. Those few companies that can go public must debate internally whether to partner their assets beforehand, a variable that may not be as validating as once thought. And some have even looked for liquidity through creative asset-based financing arrangements that provide returns without an M&A deal or a public listing.

As Cooley LLP life sciences partner Barbara Kosacz pointed out during an afternoon panel, the weighting of earn-out deals has shifted heavily toward milestone-based biobucks, a trend she doesn’t see turning around anytime soon. “It used to be the icing, not the cake,” she said, postulating that a $500 million upfront deal with a $100 million earn-out is largely a thing of the past. Now, she says, “we have creep” – a series of incremental shifts that have devalued upfronts and placed more weight on contingencies that may never materialize.

In tandem with the shift have come more complicating factors, as various panelists noted: retention of original management, earn-outs booked as liabilities, and diligence clauses that can lead to potential conflicts over whether the buyer did its best with its acquired assets. Former Calistoga Pharmaceuticals chief business officer Cliff Stocks, whose company sold to Gilead for an impressive $375 million upfront in February, even suggested that sales royalties could increasingly come into play as an earn-out component, with shell companies being set up to collect royalties and redistribute them to selling stakeholders. It'd be yet another way M&A deals will continue to take cues from licensing arrangements, as they have for some time.

Though the IPO market has been difficult for years, another afternoon session zeroed in on the companies that can get reach the public markets – and whether their partnerships have been a boon or a liability. Moderator Michael Brinkman explained that where partnerships were once seen as validation, more current prevailing wisdom is that a good asset is worth holding onto completely. Indeed, just two IPOs since the beginning of 2010 had significant partnerships – Ironwood's multiple geographic carve-outs for linaclotide and Zealand with Sanofi – with the remainder going solo. While the few companies with partnerships commanded slightly higher valuations, and most panelists agreed that a pharma partner’s diligence goes deeper than any retail investor's would, Anacor CEO David Perry pointed out that partnering can add risk too, in the event that the licenser changes its priorities.

As far as creative asset-based financings go, we’re no stranger to mouse antibody platform developer Ablexis’ one-of-a-kind Series A deal that looped in five pharma partners to provide its VC investors with eventual liquidity, obviating the need for an IPO or M&A deal to provide returns. That agreement, which featured an LLC structure to avoid double taxation of proceeds passed back to investors, took our Roger award for Exit/Financing Deal of the Year in 2010, and was discussed at length in a morning panel. Pfizer Venture Capital’s Barbara Dalton, who backed Ablexis alongside Third Rock Ventures in the $12 million round, affirmed that such arrangements aren’t for every company, and are best suited for “variations on a theme”-- companies that add value to known science. Does Pfizer still view it as a good deal? “I’m looking forward to more transactions like this one,” she said.

Deals Of The Week: CATT Fight

Well, the cat (er catt) is out of the bag – and, n,o we aren’t talking about Kate Middleton’s decision to wear a long-sleeved ivory confection with flower appliqué details when she tied the Windsor knot.

While fashionistas, pundits, and the British nation had their eyes trained on Westminister Abbey, the biopharma industry was focused on the release of data comparing the utility of the high priced Lucentis versus the much cheaper Avastin to treat wet age-related macular degeneration. And as everyone now knows, the data from the 1200-patients trial sponsored by NIH suggest that in this particular setting, there seems to be little reason—based on overall outcomes—to spend thousands of dollars on Lucentis when Avastin works just as well for a fraction of a cost.

Dr. Phillip Rosenfeld, an ophthalmologist at the University of Miami Miller School of Medicine, was particularly blunt in his assessment in a NEJM editorial that accompanied the data’s publication: "Healthcare providers and payers worldwide will now have to justify the cost of using ranibizumab [Lucentis]," he said.

That’s not to say Genentech and Novartis aren’t channeling their inner Churchill (or perhaps, more appropriately, their inner John Paul Jones). Already the companies are highlighting potential unanswered safety questions, including discrepancies in dosing and a slight increase in the incidence of non-specific serious adverse events, mostly hospitalizations. Expect the drug companies to play up whether the controlled conditions of the NIH trial can adequately be replicated in a real world setting too.

Given we are talking about people’s sight, those questions may provide a persuasive argument for docs and patients wary of not using the formulation that has FDA’s stamp of approval. Provided payers play along, of course.

And that's why Medicare’s decision is so critical. Avastin vs. Lucentis has become the poster child for the comparative effectiveness debate; thus, you can bet industry will be watching closely to see whether or not CMS initiates a coverage review that would limit Lucentis’ use. Such a decision would certainly give private payers more license to limit the medicine as a first-line treatment option.

The ripples of CATT will almost certainly be felt outside the walls of Novartis and Roche/Genentech as well. Ophthalmology – particular treating diseases that blind—has become an area of interest for big pharma because of the unmet medical need for new therapies. Because back of the eye diseases are treated by a highly trained and technically savvy group of specialists, the sector has long been a favorite of the venture community as well.

What does this mean for new AMD drugs coming down the pike like the complement inhibitors developed by Optherion or the anti-PDGF inhibitor developed by Opthotech? Given such medicines work by a different mechanism of action than the anti-VEGF inihibitors Lucentis and Avastin, their value proposition is still a little bit easier to explain. But whether potential partners will bite without superiority data is another question.

Certainly the CATT data seem to make life much tougher for Bayer and Regeneron, who now face some thorny questions about their VEGF Trap-Eye medicine, aflibercept. Phase III data released last fall showed the drug to be non-inferior to Lucentis, with fewer doses required. But with data from CATT suggesting drugs like Lucentis and Avastin can be given at less frequent intervals, a dosing advantage alone seems unlikely to be enough to ensure Regeneron and Bayer coverage and commercial uptake of their medicine – especially when data showing a much cheaper alternative can do the job.

Whether you think the CATT results are the cat’s meow or worth nothing more than a cat call, it’s time for another edition of deals of the week…

Johnson & Johnson/Synthes: The deal garnering the lion’s share of the PR this week is Johnson & Johnson’s $21.3 billion tie-up of orthopedic trauma device maker Synthes, announced April 27. Under the terms of the deal, J&J will pay $181.75 per share for Synthes in cash and stock, an 8.5% premium over Synthes’ stock price close on April 26 and a 21.7% premium over its close on April 14, when rumors about a possible tie-up first surfaced. It’s the largest deal in J&J’s history, coming half a decade after the diversified giant passed on upping its $25 billion bid for Guidant. Strategically the Synthes buy-out makes a lot of sense: it gives J&J the pole position in orthopedics boosting sector revenues from around $5.6 billion to more than $9 billion, and deepens its expertise in trauma fixation devices, an arena less prone to payer oversight and the vagaries of a slowing economy. (Fixing the damage arising from a major accident ain’t exactly elective.) At the time of the Guidant bidding war, analysts noted J&J’s interest in that company and the size of the deal said a lot about the health care company’s view on the relative merits of investing in med-tech versus pharma. Given the Synthes acquisition, the question of J&J’s dedication to Rx is sure to resurface, though the early approval of Zytiga may help the balance.

One interesting wrinkle is whether this big orthopedic deal could presage additional dealmaking in CV, since within J&J there’s historically been a school of thought linking opportunities in these two markets. As rumors about the possible J&J/Synthes tie-up coalesced, speculation ran the gamut. Thanks to the precipitous drop in market share of its drug-eluting stent biz, some predicted J&J would exit CV altogether, selling off its Cordis business; others said 'no,way,' opining this will spur J&J to re-up in CV, perhaps via acquiring percutaneous valve-leader Edwards Life Sciences.

Because J&J is paying for Synthes mostly in stock -- just 35% of the payment is cash -- the health care firm has plenty of ammunition for additional deal making. Given J&J's hefty balance sheet, its use of stock to ink the deal took some by surprise since it creates additional unwelcome earnings pressure. Even though the deal bolsters the struggling DePuy subsidiary, which like the consumer division, has seen major setbacks due to recalls, some claim J&J is simply putting a Band Aid (pun definitely intended) on its problems. Critics argue the company’s manufacturing problems are significant and that integrating Synthes will detract from the hard work required to fix a broken system. —The EBI Device team

Kadmon/Nano Terra: Sam Waksal’s Kadmon is at it again. After its deal-making bonanza last fall – recall the firm acquired Three Rivers and set up a strategic partnership with Valeant—Kadmon is teaming up with privately-held Nano Terra, a nanotech accelerator developing technologies with applications from biopharma to more industrial settings. Terms of the tie up weren’t disclosed but they do provide Kadmon with an exclusive license to three novel, clinical stage assets and access to Nano Terra’s proprietary Pharcomer Technology drug discovery platform. (FYI, the product candidates and the Pharcomer technology were originally developed by another private biotech, Surface Logix, and only recently acquired by Nano Terra, though no formal announcement about that deal appears to have been made.) Perhaps the most interesting asset for Kadmon is Slx-2119, a selective Rho-associated coiled-coiled kinase 2 (ROCK2) inhibitor that impacts cell shape and cell migration and may play a role in diseases as diverse as diabetes, cancer, and spinal cord injury. As part of the recent alliance, the assets and technology will be transferred to a new joint venture owned by Kadmon and Nano Terra called NT Life Sciences.—EFL

Sequella/Maxwell Biotech Venture Fund: Anti-infectives developer Sequella of Bethesda, Md., signed an unusual deal that gives Maxwell, a venture fund that specializes in Russian investments, rights to tuberculosis treatment SQ109 in Russia and the Commonwealth of Independent States, which includes Armenia, Kazakhstan, and Ukraine. Maxwell is taking an undisclosed equity stake in Sequella, but the parties do not consider the transaction a round of funding. Sequella could receive up to $50 million from Maxwell, the first tranche being an upfront payment and near-term milestones that the companies declined to disclose. Run by former Pfizer discovery executive and incubator chief Alex Polinsky, Maxwell has responsibility for development and approval of SQ109 in its licensed areas. Sequella has completed three Phase 1 studies of SQ109 in the U.S. and is currently running Phase 2 efficacy studies in TB patients in Africa. It is also testing the compound as a treatment for Helicobacter pylori infections and fungal infections. Sequella officials told the IN VIVO Blog that the company has not raised traditional rounds of venture capital, instead leaning on individual investors and hedge funds to supplement government grants. -- Alex Lash

Eli Lilly/Medtronic: While drug companies routinely team up with device makers to find better ways to deliver drugs, the April 26 deal between Eli Lilly and Medtronic, to research and develop a new treatment for Parkinson's disease is notable for two reasons. For starters, the collaboration involves two very early stage technologies. But the alliance also facilitates Lilly's move into a new area of CNS that heretofore hasn’t been a primary focus. If all goes according to plan, the alliance will result in a combination of Lilly's modified form of glial cell-derived neurotrophic factor (GDNF) and Medtronic's implantable drug infusion system. Because the large protein growth factor can't get past the blood brain barrier, and, on its own, isn't targeted, the Medtronic device would deliver it directly to the dopamine-producing neurons that degenerate as Parkinson’s disease advances. The companies aren't disclosing much about the terms of their alliance, except to note that it is a 50-50 split in both costs and revenues and spans clinical development, regulatory and ultimately commercial stages. The aim is to produce a combination product that can be submitted jointly for regulatory approval. The partners don't have a fixed time line for getting their therapy through development, but expect to move it into the clinical within five years, said Ros Smith, a senior research director of regenerative biology at Lilly.While the modified GDNF is most advanced, Lilly also has several compounds in pre-clinical development for Parkinson's disease. Medtronic, for its part, doesn't currently sell a device that delivers drugs directly to the brain, although it markets a deep brain neurostimulation technology for treating Parkinson's disease and sells implantable pumps and catheters for delivery to the spinal cord.--Wendy Diller

Image courtesy of flickrer privatenobby used with permission through a creative commons license.

Financings of the Fortnight Covets Thy Neighbor's Bubble

The B-word is back, and it rhymes with "trouble." With 21 US IPOs in April alone, no wonder the barbarians are lined up at the gates, clamoring to get a piece.

There have been 31 initial filings this month, the most active month since 40 companies filed in August 2007, according to IPO watchers Renaissance Capital. Exciting, no? So how many of these newly minted or wannabe public companies are in our little corner of the world? Two IPOs, Tranzyme and Sagent Pharmaceuticals, and no new filings.

Let that sink in for a moment. It's Bubble 2.0, or 3.0, or 6.0, with little old ladies in Pasadena trying to grab a piece of Facebook on private secondary markets, and not a single biotech firm filed papers this month.

Now, there might be some moral high ground in keeping one's distance from ye olde irrational exuberance. A bubble is generally a bad thing, leading to Pets.com and far too much exposure of Angelo Mozilo's tanning-bed face. No wonder the other side is protesting too much. See how hard this tech VC argues that the current mania is anything but a bubble?

But to those on the bio side of the fence, the lush green grass of Mark Zuckerberg's backyard looks awfully tempting. At BayBio last week, when talk on a mid-stage funding panel got around to building strong biotech companies, Pfizer business-development executive Jim McLoughlin cautioned other panelists to think long-term and not create a bubble. (As if they could.) Versant Ventures managing director Camille Samuels jumped in: "Hey, I'll take a bubble!"

She said it with a laugh, but consider the VC's alternative these days: Waiting for guys like McLoughlin (and the committees behind them) to decide they like your portfolio firm's Phase II asset enough to offer a modest up-front payment and earn-outs or milestones.

European investment firm LSP Life Science Partners isn't waiting around for the private equity exit ramp to materialize. Not only is it launching a public-equity fund, it has floated the fund, dubbed LSP Life Sciences Fund, on Euronext Amsterdam.

The firm claims a 150% return on public investments, which it began making in 2008 on behalf of Dutch pension fund administrator APG Investments. Its new dedicated fund, for which it raised £30 to £35 million privately, follows in the footsteps of life-science VCs like Abingworth, MPM Capital, and OrbiMed Advisors who have begun straddling the fence in recent years. On the private side, LSP's fifty or so holdings have included Jerini, KuDOS, U3 Pharma and Movetis. The first three sold privately, while Movetis listed in late 2009 before Shire gobbled it up a few months later. Our "Pink Sheet" colleagues will have more on LSP soon, so we don't want to, ahem, burst their bubble. Instead, let's pop the cork on another bottle of...

Synta Pharmaceuticals: On April 15, cancer and inflammation drug discovery company Synta Pharmaceuticals raised $35.2 million in a registered direct offering, the second-highest grossing PIPE this year behind Arena Pharmaceuticals. Synta sold 7.2 million shares at $4.89, a 6% discount to the ten-day average. Company insiders bought about 22% with institutional investors scooping up the rest. After several ups and downs in its ten-year history, Synta is The Little Discovery Engine That Could, dusting itself off after each disappointment. And there have been several. The Shionogi BioResearch spin-off raised more than $200 million in venture financing before a failed IPO attempt in 2005. Less than two years later, and after another $40 million cash infusion, the company finally went public, selling shares at $10 a pop. Soon thereafter it secured its first Big Pharma partner when GSK acquired US co-promote rights to the biotech’s elesclomol, an apoptosis-inducing candidate that disrupts cancer cell energy metabolism. But Synta got a shock in March 2009 when Phase III trials in metastatic melanoma showed more deaths in the elescomol arm than with the standard-of-care arm, and the trial was shut down. GSK returned rights, but not before forking over $130 million. After the elesclomol failure, Synta has pinned its hopes on its lead compound the Hsp90 inhibitor ganetespib, which is unpartnered.* For the April 15 RD offering, Synta issued no warrants and did not use an underwriter. -- Amanda Micklus

Silence Therapeutics: The shingle Silence hung out to advertise a placement of 275 million shares, with hopes of grossing up to £5.5 million, is a sign of the times for the RNA interference crowd. Silence is the latest RNAi firm to find itself in financial or strategic difficulties, and if shareholders don't approve the new stock sale, announced April 25, the company says it will run out of cash by the end of the third quarter. Whether or not that transpires, Silence says it is shutting down its California office, a legacy from its December 2009 merger with Intradigm, and looking to replace CEO Phil Haworth. When Silence and Intradigm tied the knot, the firms hoped their combination would speed the development of delivery systems, a major obstacle in turning fragile short interfering RNAs into viable therapeutics that reach their intended targets. Investors such as Alta Partners and Frazier Healthcare also backed the merged entity with a £15 million financing priced at 23 pence a share. If that sounds bad, please note that the new placement is priced at 2 pence a share. No, that's not a typo. Momentum in RNAi has been on the wane for the past two years, then came big red flags last fall when two major partners of Alnylam Pharmaceuticals delivered bad news. First Novartis, a 13% owner of the biotech, passed on an expensive option to expand its collaboration, then Roche said it was dropping all RNAi-related work. More dark skies earlier this year came when delivery firm Tekmira Pharmaceuticals brought a lawsuit against Alnylam; and RXi, undergoing a management overhaul, bought a struggling company for its late-stage breast-cancer treatment and shifted its focus away from RNAi. To top it all off, Merck & Co.'s $1.1 billion purchase in 2006 of Sirna Therapeutics, once Alnylam's rival, has yielded nothing that Merck is willing to discuss publicly. Meanwhile, Silence is offering shareholders a chance to buy up to £1 million in shares before the placement. Those who participate in full will only be diluted 45% by the placement; otherwise dilution will be about 54%, the company said in its notice to shareholders. -- Alex Lash

Bluebird Bio: When a VC at last week's Bay Bio meeting was asked about the next big thing, he pointedly said it wouldn't be RNAi, which was reminiscent of gene therapy. (He didn't mean it as a compliment.) Bluebird Bio begs to differ, having just raised a $30 million C round from new investor ARCH Venture Partners and others to pursue its gene therapy technology, called LentiPak, to treat rare diseases such as childhood cerebral adrenoleukodystrophy (CCALD) and beta-thalassemia/sickle-cell anemia. Formerly known as Genetix Pharmaceuticals, Bluebird aims to get lead program Lenti-D into a registrational Phase II/III trial for CCALD later this year. The firm says its technology, using lentiviruses instead of retroviruses as the viral vector, should provide better safety than the now-infamous gene trials of the previous decades. The LentiPak technology works this way: A patient's hematopoetic stem cells are extracted, exposed to a viral vector, then re-inserted into the patient, reconstituting his or her bone marrow. In addition to ARCH, the Series C is backed by returning investors Third Rock Ventures, TVM Capital, Forbion Capital Partners and Easton Capital Investment Group. Genzyme Ventures, which co-led last year's Series B, is not involved because of the ongoing merger with Sanofi-Aventis, Bluebird CEO Pat Leschly told "The Pink Sheet" DAILY. -- Joe Haas and A.L.

Circassia Holdings: Yes, Virginia, there are refreshing wellsprings of early-stage capital out there, and Circassia is fortunate to be in deep with one of them. The UK allergy vaccine developer said April 19 it has raised £60 million ($98 million), the second largest European venture round this year and one of the largest ever. It was led with a £15 million tranched commitment from Imperial Innovations Group, the tech transfer and investment arm of Imperial College, London, where Circassia's T-cell vaccine platform ToleroMune was developed. Imperial Innovations has exclusive rights to IP coming from the college, as well as access to technology from three other top UK schools. It recently said it has commitments from shareholders to contribute another £140 million ($220 million), nearly three times what the group has invested in start-ups. It's also one of the rare investment funds to go public itself, having raised £26 million in a 2006 listing on the AIM exchange. (Perhaps an inspiration for LSP?) Imperial has been a backer of Circassia since its founding in 2006, and the majority of the funds raised in this round will go towards financing phase III development programs for Circassia's cat and ragweed allergy therapies. Circassia also aims to use the funds to complete phase II testing of the company's house dust mite and grass allergy T-cell vaccines, and will advance the development programs for three additional allergy therapies and its psoriasis treatment, PAP-1, a selective Kv1.3 inhibitor, recently acquired from Airmid Inc. -- Faraz Kermani

Photo courtesy of flickrer Beige Alert under a Creative Commons license.

Melanie Senior contributed to this week's introduction.

*Due to an editing error a previous version of this column stated incorrectly that Synta's ganetespib compound was partnered. We regret the error.

Preparing for the CATT Study: Will Makena Controversy Have an Impact?

The first public presentation of data from the National Eye Institute’s head-to-head study of Lucentis vs. Avastin in macular degeneration will take place this weekend. The Comparison of Age-Related Macular Degeneration Treatments Trial (CATT) is sure to go down as an early landmark in the era of comparative effectiveness research—though exactly how it will be remembered is less clear.

We have written extensively about the unusual situation Genentech faces with the CATT trial—basically a government run study designed to prove that one Genentech product (Avastin) is just as good as another (Lucentis) at a vastly lower cost. The study was initiated and designed completely without Genentech’s help, prompted by outrage among providers who had been using Avastin off-label for AMD who experienced sticker shock when Lucentis was launched at a price of about $1,500 per dose, compared to $50 for the unapproved, microdose of Avastin.

It took a very long time to get the study off the ground, thanks in part to a series of administrative hurdles posed by the unusual circumstance of conducting a study in the Medicare population without the support of a willing sponsor. The planning for the trial began in 2005, but it didn’t really get going until 2008.

Now, at least, it is wrapping up—and in a juicy irony the study results will be reported right on the heels of a completely different controversy over an attempt by a sponsor to sell a product at $1,500 a dose to providers comfortably using an unapproved alternative that costs about $50 a dose. That, after all, describes the situation with KV Pharmaceuticals’ pre-term labor drug Makena.

The situations aren’t perfect parallels of course. KV launched Makena earlier this year, becoming the latest sponsor to pursue a strategy of obtaining FDA approval for a widely used unapproved medicine, in this case, the pharmacy-compounded ingredient 17P. Makena received an Orphan Drug designation, the only exclusivity KV can count on since the active ingredient is long off-patent. The application itself was an abbreviated one, referencing clinical studies conducted by the National Institutes of Health demonstrating a benefit in delaying pre-term labor in high risk women. (Though the NIH study wasn’t enough for a full approval; Makena received an accelerated approval with the sponsor committing to demonstrating a clinical benefit in the health of newborns.)

Lucentis feels very different. The active ingredient is a modified version of the monoclonal antibody known as Avastin, optimized (Genentech says) for use in the eye. Avastin itself is high science, the quintessential biotech breakthrough, an angiogensis inhibitor whose benefits were demonstrated at high cost and high risk by Genentech.

But the controversy around the two therapies is essentially the same: providers reacted to a de facto 3,000% price increase by complaining to anyone who would listen. Congress took note and pushed federal agencies to respond.

The nature of those responses has been very different. For ophthalmologists, use of Avastin is now common practice, especially for uninsured patients or in any circumstance where securing reimbursement for Lucentis may be in doubt. And the CATT study is supposed to help preserve the status quo by demonstrating non-inferiority between the two treatments.

For Makena, the key response came from FDA, which announced March 30 that it would not clamp down on compounders who continue to make 17P. (You can read more in “The Pink Sheet,” here.)

That simple action, coupled with CMS’ same day “reminder” to state Medicaid directors that they can continue to pay for compounded 17P if they choose, dramatically changes the commercial picture for KV, and the company reacted by slashing its price. The rest of the story has yet to be written, but we suspect KV will ultimately drive compounders out of the market and that will be that.

But the considerable attention generated by Makena should mean that the CATT study will garner even more interest than it already commands.

The question is, exactly what will that interest lead to?

That is where another connection to Makena comes into play: the question of how safe it is to use unapproved alternatives to an FDA approved therapy. Roche/Genentech has stressed that issue as a key concern with off-label use of Avastin all along, and the company sponsored a review of Medicare claims data that suggests there are indeed more adverse outcomes associated with that use than with Lucentis.

And recent comments by Center for Drug Evaluation & Research Director Janet Woodcock about the Makena controversy may shed light on how FDA views the issue.

Woodcock spoke at the Food & Drug Law Institute annual meeting in early April, less than a week after FDA issued the public statement on compounding and Makena.

It was therefore inevitable that she would be asked about the issue. Inevitable, and also a bit unfair. The controversy over Makena is clearly a political issue, with Ohio Democratic Senator Sherrod Brown spearheading an all out campaign for federal agencies to do something to address what he (and plenty of provider groups) felt was an outrageously high price for the drug. So FDA’s announcement that it would not clamp down on compounding of Makena clearly began at a level much higher than the CDER director.

Moreover, any drug regulator is bound to feel strongly that an FDA-approved product is safer than a pharmacy compounded product. Woodcock, who has devoted considerable energy to upgrading quality control in (regulated) pharmaceutical manufacturing, probably has stronger feelings on that score than most.

But it is Woodcock’s job to defend agency policy, and defend it she did.

She began by stressing the importance of placing the issue in the context of conflicting societal pressures. In the case of Makena, Woodcock suggested, the agency’s decision aimed to find that balance. In its March 30 public statement, FDA stressed the “unique” circumstances surrounding Makena, underscored the importance of assuring sterility in the injectable product, and noted that FDA may revisit its enforcement discretion at any time.

“We want a lot of things as Americans,” Woodcock noted. “We want orphan incentives. We definitely want people to study drugs in pregnant women, which they don’t do. We want affordable drugs. We want high quality parentals that are not contaminated with bacteria and killing people.”

“Sometimes all these wants conflict with each other. The question is, with all these different societal desires, how do we define a balance amongst them?”

Moderator Daniel Kracov (Arnold & Porter) suggested that the issue is whether it is appropriate for FDA to “play that role” of arbitrating among those competing desires.

Woodcock responded by stressing the limits on FDA’s ability to regulate compounding—not just questions about the scope of its authority, but practical limitations on its resources.

“In general, our enforcement policy on compounding has been that we are taking a risk-based approach and we are going after compounders that are having contaminated drugs.” She cited a recent outbreak of septic meningitis associated with total parenteral nutrition compounded by a pharmacy in Alabama. (Coincidentally, FDA issued a safety alert tied to that outbreak on March 30, the same day it announced its Makena policy.)

In addition to focusing on cases of contamination, “we will also go after serious health fraud,” like if a pharmacy is offering some substance as a replacement for insulin. “We have the risk-based approach down from that, but those are the primary objectives right now in compounding, because we have many many tasks that we have to enforce against.”

Panelist Nancy Buc (who recently retired as a partner at Buc & Beardsley) pressed Woodcock, noting that her own priority lists highlights injectable products as a priority. “One of the things that Makena brings us is GMPs and presumably sterility. Are you going to inspect the people who are compounding more than one dose for sterility?”

“I would ask you are we going to inspect people who are compounding drugs that are injected directly into the epidural space, or into the cerebral spinal fluid,” Woodcock responded.

“There are many concerns here. There are many, many compounded drugs that are intravenous. That poses a higher risk than the intramuscular injection” that is used for Makena and 17P compounds. “If you start talking about risk, I think there is a hierarchy. The greatest concern to me would be drugs injected into the eye, or into the central nervous system. Next would be drugs that are injected intravenously…then would be drugs that are injected intramuscularly.”

That’s right: drugs injected into the eye are the highest risk in the CDER directors view.

Was the CATT study already on her mind? Not really. “I wasn't thinking of Avastin in particular,” Woodcock told us when we contacted her about her remarks.

In fact, “I believe the division of Avastin vials is considered repackaging not compounding.”

“However,” Woodcock stressed, “I believe injection in or near the CNS is one of the highest risk situations for sterility problems.”

When weighing the impact of the CATT study findings, it seems safe to say that whatever impact they have, it won’t result in FDA issuing a statement saying it has no problems with widespread off-label use of Avastin.

Navigating The FDA Advisory Committee Road To Success … Or Not

On the eve of FDA’s Antiviral Drugs Advisory Committee reviews of the first protease inhibitors for hepatitis C, the drugs’ sponsors – Merck (boceprevir) and Vertex Pharmaceuticals (telaprevir) – are no doubt scrambling to make sure everything is in order.

Presumably, the companies have already locked down their slide decks, put the finishing touches on their presentations, researched the backgrounds of the committee’s standing members and shipped their AdComm teams off to hotels near FDA’s White Oak headquarters, where the meetings will take place.

Boceprevir and telaprevir are viewed as therapeutic breakthroughs in the treatment of HCV, both having shown improved cure rates when added to the current standard of care. However, the drugs have complicated and differing dosing regimens, which are likely to be an area of AdComm discussion.

Merck, which will present its case on April 27, is an old hand at the AdComm process, having most recently gone before a panel in December when it unsuccessfully sought to add prostate cancer risk reduction language to the label of its BPH drug Proscar. Vertex, on the other hand, is making its maiden voyage on the USS AdComm. The company will present its case on April 28 and should benefit from hearing panelists’ questions and concerns in their review of boceprevir the day before.

No matter how well prepared the sponsors think they might be, the AdComm road is littered with landmines. That, in a nutshell, was the message conveyed by AdComm meeting veterans at the Center for Business Intelligence’s Second Annual Forum on Effective Preparation for FDA Advisory Committees in Washington, D.C. last month.

At the two-day conference, battle-hardened veterans of the AdComm process – including pharma employees and consultants who make their living preparing drug companies for meetings – shared experiences from the trenches and offered some best practices to consider when tackling what has become a significant hurdle in drug development.

Some suggestions fall in the common sense category. It's imperative not only to have good communications with FDA leading up to an AdComm, but also to begin the meeting planning process early. Practicing presentations and Q&A is not surprisingly also considered good AdComm hygiene. But the CBI speakers voiced some additional pearls of wisdom that sponsors appearing before FDA committees might want to keep in mind, starting with…

Know Your AdComm
Pete Taft, founder and CEO of PharmApprove, a company that provides AdComm meeting preparation services, said sponsors should be ready to deal with four general types of personalities on FDA panels:

the expert – someone who knows a lot about your field and possibly your product, and is going to be well prepared for the meeting;

the judge – an individual who is swift to make judgments about your product or argument;

the thoughtful one – a quiet panel member; and,

the naysayer – the “Simon Cowell of AdComs” who you can either fight or forget about securing their vote.

PharmApprove has interviewed former AdComm members to find out how they prepare and what they expect from sponsors. At the top of their list is this nugget of wisdom...

Keep It Simple, And Don’t Be Irritating
The importance of clarity and simplicity in a sponsor’s presentation was echoed by FDA Director of Advisory Committee Oversight Michael Ortwerth, the lone agency presenter at the CBI conference. “That’s a really important thing, that the message is clear … and slides are very well put together,” Ortwerth said. “When you have slides that are so busy and so ladened and heavy, then you can’t focus on what the actual issue is.”

If AdComm members don’t like busy slides, they’re also not thrilled with sponsors or presenters who come off as cocky or overconfident. “I’ve always had this intuitive sense that if we press the committee or cause them to feel irritated, that some of that emotion will be transferred to their rational thinking,” said Taft, whose suspicion has now been confirmed. He noted the comments of a former AdComm chairman, who said: “You don’t want to make me angry about you, because then I transfer that from you onto the data and onto the drug.”

AdComm prep needs to be heavy on practice, planning and contingency planning, the speakers said. In the course of advance planning, it’s important that sponsors …

Don’t Let Belly Dancers Get In The Way
Don Cilla, vice president and product development team lead at AstraZeneca’s MedImmune division, led the company’s AdComm team for the June 2010 review of motavizumab for prophylaxis of respiratory syncytial virus. He recommends conducting AdComm team practice sessions and holding pre-meeting preparations in the same hotel ballroom that FDA will use for the meeting (when they’re not being held at White Oak). At the time of the motavizumab meeting “there was a convention of belly dancers that had that room booked for the three days leading up to it, so we couldn’t get in there to practice.”

If the company's AdComm team is all staying, and eating, together as a group for two or three days before a meeting, they should …

Avoid Eating The Mayonnaise
One of the speakers at the CBI conference recounted how a consultant, upon seeing open mayonnaise sitting at a buffet, banned all condiments at future meals so as to avoid the risk that team members would come down with a debilitating case of food poisoning on the day of the big meeting. “We had backups for everybody,” Cilla said of his team for the motavizumab meeting. “We didn’t know if they were going to get the bad mayonnaise or the Mexican food the night before or if they just couldn’t get there.”

While sponsors should plan for anything and everything to go wrong logistically, there are some factors they may have no control over. This includes the possibility that committee members will be suffering from …

An Avandia Hangover
Back-to-back scrutiny of different drugs on consecutive days can have a detrimental effect on those coming at the end of a multi-day meeting, suggested Alexander Fleming, president and CEO of the consulting firm Kinexum.

Case in point is Vivus’ obesity drug Qnexa. At a July 15 meeting, FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted 10-6 against approval due to safety concerns. The negative vote took some FDA officials by surprise, but Fleming believes timing was a crucial factor. The Qnexa review marked the third consecutive day of work for the committee, its two previous days having been spent on an extensive and intensive review of the cardiovascular safety of GlaxoSmithKline’s diabetes drug Avandia.

“If nothing else, the advisors had to be exhausted” by the time they got to Qnexa, Fleming said. Calling the AdComm timing “pure bad luck” for Vivus, Fleming said the company knew “this was going to be a real disadvantage to them ... and only in retrospect do you see how it really had a major effect.”

Sponsors also may have no control over an AdComm’s walk down the path of …

Comparative Effectiveness And Cost
Disease background presentations by the sponsor are a hallmark of any product-specific AdComm. A good presentation will include a comparison of products that are on the market, including mechanism of action and limitations, said Mary Rofael, COO of scientific and regulatory communications at ProEd Communications, a firm that provides AdCom prep services.

“Many of you will say we’re here at an advisory committee, the committee should focus on evaluating the benefit/risk of a particular product,” Rofael said. “In this day and age you can’t stop people from thinking about comparing it to what they’re using currently or what’s on the market. It’s just a discussion that’s going to take place. Whether or not you engage in it, that’s a different story, but it’s important to anticipate it because these kinds of questions are being asked more and more today.

“It’s almost like the question of cost,” Rofael continued, venturing down a road that almost no sponsor wants to travel during an AdComm. “The advisory committee room is the only room where cost is not discussed … but eventually I think it’s going to make its way in. People are starting to ask about the cost of products and what the burden of cost is on the health care system.”

Aside from the detour down the cost path, what’s a sponsor to do when an AdComm’s discussion of the data starts …

Spiraling Out Of Control?
If the panel’s conversation has gone awry at some point after the sponsor’s presentation, the best a company can hope for is that the meeting agenda includes an upcoming break, said PharmApprove principal Martha Arnold. “If there’s a situation where things just are spiraling out of control, and … you think perhaps the committee is dealing with information that is just plain wrong, that there’s been a misinterpretation either of your data or FDA’s data, if there’s a break you have an opportunity to at least approach the chair” and express concern, she said.

If there are no further scheduled breaks, the sponsor could pass a note to the panel’s industry representative “or tap them on the shoulder and say, ‘Hey, can you help us out here,’” said Bruce Burlington of DB Burlington Consulting, who often serves as the industry rep on AdComms. “Alternatively, if it’s really outrageous, just stand up and say, ‘Mr. Chairman, I request your permission to insert a correction in the discussion at this point.’”
It may be more problematic, however, for sponsors to insert themselves into the process of …

Question-Morphing
Anyone who has sat through at least a handful of AdComms can confirm that panelist confusion over the wording of FDA’s questions is a fact of life, often leading to discussions as to whether and how the questions should be re-written on the fly. While these question-writing “audibles” can be disconcerting for sponsors, so can the initial questions themselves.

CBI conference attendees cited tremendous variability among review divisions in the types of questions posed at AdComs, ranging from straightforward questions on risk/benefit to queries that run multiple pages and “in essence make the FDA case in the form of a question,” one conference attendee said.

FDA’s Ortwerth acknowledged room for improvement in how review divisions ask questions. “It is important that there be consistency in the way we try to communicate. … There needs to be the right way to communicate something and a clear way to communicate something and not to drive the direction of the answer.”

Even if sponsors are able to navigate all the trouble spots outlined above, they need to keep in mind that they can …

Spend Big Money, But Still Lose Big
Preparing for an AdComm involves shelling out big bucks, all of which can be for naught if a drug is decimated when it comes to the panel’s vote. MedImmune’s Cilla said his company spent approximately $900,000 on AdCom preparations for motavazimub, which included the cost of consultants, meeting space and four mock panel meetings at approximately $60,000 each. The investment resulted in a 14-3 AdComm vote against approval, which was followed by an FDA “complete response” letter and the company’s decision to withdraw the BLA.

Sanofi-Aventis Associate Vice President of Global Regulatory Affairs Kevin Malobisky said his company spent about $1.3 million preparing for one meeting that resulted in a 14-0 vote against approval – an apparent reference to the unsuccessful June 2007 AdComm for the obesity drug Zimulti (rimonabant).

Were IN VIVO Blog writing an AdComms for Dummies manual, we might put it this way: it's expensive and a lot of work to prep for an AdComm, but you have to do it. Even so, there's no money-back guarantee.

Maybe we should start consulting--at least we've got a sense of humor.

-- By Sue Sutter (s.sutter@elsevier.com)

Deals Of The Week: Managing Expectations

Amgen issued its first dividend ever this week, a move that may officially settle the debate over the Thousand Oaks, Calif. firm's status as biotech or pharma.

Either way, it’s ironic that as it finally gave back cash to its investors, Amgen’s share price dropped roughly 4% to close April 21 at $53.69.

Maybe investors didn’t like the idea that Amgen has officially "pharma-fied" itself. More likely, the reaction stems from unmet expectations.

Amgen has a lot of cash in its coffers, about $17 billion, and even with plans to return much of it to shareholders over the next five years, the initial pay out was smaller than hoped for and well below the threshold set by bigger drug makers. (Proof, yet again, that if you want to act like the big boys you have to play by their rules.)

Still, Amgen deserves some credit for trying to assuage investors and still maintain financial discipline. Amgen’s Prolia/Xgeva franchise has launched with mixed success, with osteoporosis sales lagging as oncology sales are off to a stronger-than-expected start. For the drug maker to meet the ambitious goals outlined by CFO Jonathan Peacock in his business day review (see here for more), the company has no choice but to continue to invest in denosumab’s commercialization--especially in the primary care setting. And it's going to take cash to deploy sales reps to educate physicians, patients and payers about the benefits of Prolia over Zometa and generic alternatives.

And with the Epogen franchise on the wane, Amgen also needs to show investors it can move beyond an all-denosumab-all-the-time strategy. Thus, it can’t afford not to invest in its pipeline, which in turn means maintaining a high R&D burn. (Not a popular sentiment in any corner of our industry these days, but especially in the eyes of Valeant’s CEO Michael Pearson.)

In doing the right thing with its new dividend, however, Amgen got slapped on the hand anyway, a useful reminder that success in this business is as much about managing investors’ expectations, when it can take years to deliver positive results. Here at IN VIVO Blog, we have no problem under-promising and over-delivering. (That’s one benefit of being a free publication.) In honor of Earth Day, chocolate rabbits, and egg rolls (not the brown and crispy but the hard boiled variety) we bring you another edition of...

Sanofi-Aventis/Stanford University: At the JP Morgan confab this winter, Sanofi CEO Chris Viehbacher promised his company would do R&D better. If this week’s tie-up between the French pharma and Stanford University’s interdisciplinary Bio-X Center doesn’t convince you that one crucial leg of Sanofi’s R&D plan is partnerships with academia, well, you haven’t been paying attention. In March, the company inked deals with Columbia University (diabetes) and the French Vision Institute (ophthalmology, bien sur), having already allied itself with institutions such as Cal Tech, Harvard, and MIT. The Stanford collaboration hews closely to the other research partnerships in its structure and ambitions, not to mention in the lack of disclosed financials. As we explained in this IN VIVO feature, Sanofi’s view of academia-industry partnerships puts heavy emphasis on aligning with the top minds in a particular field and building mutual trust via joint-steering committees. Under the terms of this most recent collaboration, a funding committee staffed by Stanford and Sanofi researchers will fund up to five programs annually. Sanofi will also host an annual research forum to bring together Sanofi and BIO-x researchers to discuss science, and may even host post-docs at the company. (Stanford also has the option to invite Sanofi scientists to be visiting scholars.) As we note in this 2009 Start-Up feature, such moves are becoming more and more common, as industry players hope to develop stronger relationships with bright scientists in their efforts to amp up the innovation in their pipelines. --EFL

Ariad Pharmaceuticals/ReGenX: Ariad has struck three new licensing deals for its Argent cell-signaling regulation technology to help further fund its internal oncology programs ponatinib, ridaforolimus and AP26113. Through the three agreements, Ariad will receive undisclosed upfront fees, as well as potential milestone and royalty payments. Privately-held, Washington, DC-based ReGenX Biosciences will use Argent as a complimentary tool to its internally developed NAV gene delivery technology, giving the smaller biotech access to technology that increases its ability to control the genetic payload being delivered. The start-up, which was founded in 2009, has proprietary technology that uses recombinant adeno-associated viral vectors to deliver genes to cells. Ariad's alliance with ReGenX also includes an equity stake, so should any of these discoveries bear out, Ariad stands to gain outside the clinical milestone payments and royalties that are standard licensing fare. Bellicum Pharmaceuticals of Houston, TX, meanwhile, is licensing Ariad's technology for its experimental cancer vaccine and cell therapies. Bellicum has used the Argent technology in Phase I/II trials of the BPX-101 DeCIDe immunotherapy and CaspaCIDe DLI. The third agreement was struck with Clontech Laboratories, a Mountain View, CA-based research reagents provider. Clontech has licensed the technology to provide it to researchers worldwide. -- Lisa LaMotta

Baxter/Prism Pharmaceuticals: Specialty pharma Baxter International entered an agreement to buy privately-held Prism Pharmaceuticals April 18, in a deal slated to include a $170 million upfront payment and up to $168 million in potential future milestones tagged to sales of Prism’s FDA-approved anti-arrhythmic drug Nexterone (amiodarone HCl). The two companies expect the transaction to close during this quarter. Prism first obtained FDA approval of Nexterone in December 2008, but waited to commercialize the drug until after gaining approval for a more convenient, intravenous pre-mixed bag formulation. That formulation was approved in November 2010. Baxter said that formulation should offer numerous conveniences to clinicians in the acute care setting. The ready-to-use product requires no admixing, which helps eliminate potential medication errors associated with compounding, and it can be stored for two years at room temperature. Having been selected as contract manufacturer for the premixed IV bags by Prism, Baxter likely brought considerable knowledge of Nexterone to the transaction. Morgan Stanley analyst David Lewis, in an April 18 note, was bullish on the deal, saying it would bolster momentum and is consistent with Baxter’s stated M&A strategy. “Prism is likely a low-risk deal that will leverage Baxter’s strong sales channel in IV injectables,’ he wrote. “We expect to see more deals in the several hundred million dollar range in coming quarters.” -- Joseph Haas

SciClone/NovaMed: On April 18, SciClone Pharmaceuticals announced it was taking out privately-held NovaMed Pharmaceuticals, a Shanghai-based specialty pharma backed by US venture groups. The deal is worth $62 million upfront, with $24.7 million coming in the form of cash, and another $37.1 million in SciClone stock. For NovaMed’s backers, which include Atlas Venture and Fidelity Asia Ventures, the upfront cash alone appears to provide an exit, though barely. Since its founding, NovaMed has raised $18.8 million via two financings, meaning the cash portion of the deal provides a step up of 1.3. (The SciClone stock is a nice sweetener, but it doesn’t provide the liquidity most VCs really want.) The deal also includes earn-outs worth up to $43 million tied to revenue and earnings targets for legacy NovaMed products. If all the milestones are met, we calculate the step up for Atlas and Fidelity increases to a healthy 5.6. The deal significantly broadens SciClone’s commercial footprint in China, increasing its current number of sales reps more than three-fold to 680. NovaMed’s CEO, Mark Lotter, will stay on to manage the commercial team, and SciClone says the group will be structured as an independent entity. In contrast to big pharmas (see below), biotechs have been slower to commercialize their products in China, but the country has been of strategic interest to SciClone for some time. The firm has been selling its flagship immunomodulator Zadaxin in China since 1996 and has two oncology products, DC Bead and Ondansetron RapidFilm, winding through China's regulatory process. -- Josh Berlin and EFL

Pfizer/Shanghai Pharmaceutical Holdings: On April 21, Pfizer and China's second-largest distributor Shanghai Pharmaceutical Holdings announced a memorandum of understanding to explore business opportunities in China, including the potential to jointly register, commercialize and distribute an undisclosed branded Pfizer product. But near-term the value of the memorandum is undoubtedly increased sales potential of Pfizer’s Prevnar 7 vaccine, which is the drug maker’s biggest revenue generator after Lipitor. For Big Pharmas looking to commercialize products in China, distribution alliances with in-country players are one way to rapidly gain market share, even as they add their own “boots on the ground” capabilities. Indeed, such strategies makes sense given China’s highly fragmented health care market and the difficulty penetrating its rural markets. Pfizer and SPH have a long working history already, with the Chinese pharma acting as the multi-national’s largest distributor in this region. Apart from joint commercialization of Pfizer's innovative products, Pfizer and SPH are also exploring a range of future potential collaborations in R&D, manufacturing and other potential areas. -- Dai Jailing

(Image courtesy of flickrer iaintait used with permission through a creative commons license.)