Deals of the Week Has Playoff Fever and Poison Ivy

Deals of the Week! doesn't usually get up on our soapbox and complain unless it's to gripe about undisclosed deal terms, vaguely worded press releases, or an unwillingness to make CVRs tradeable.

But c'mon, pharma, it's time to develop some new products against poison ivy.

This week we saw loads of deals -- alliances, options, out-licensing, deals, deals, and tweaked deals and no-deals. But were any of them around poison ivy treatments? No. A quick search of clinicaltrials.gov for 'poison ivy' or the dreaded 'urushiol' turn up zilch. Our own databases reveal very little poison ivy dealmaking in the past twenty years. Did Project Bioshield or any of its ilk fund research into this scourge? Nope. This makes no sense. If this blogger's back yard is anything to go by, the market will be huge.

Now please excuse us while we scratch the hell out of our legs and go invest another $50 in bandages and feeble lotion at CVS. Oh, and go Phillies!

You're gonna need an ocean of ...

Fate Therapeutics/Becton Dickinson: Fate Therapeutics of San Diego will bring its induced pluripotent stem (iPS) cells to market thanks to a commercial deal it signed with biomedical equipment provider Becton, Dickinson, the firms said Oct. 14. No financial terms were disclosed, but BD will pay Fate an upfront fee, research funding, commercial milestones and royalties on the products BD sells. Fate is one of a handful of biotechs reprogramming adult cells into iPS cells -- an alternative to stem cells derived from human embryos -- with the goal of using iPS cells as lab tools for drug discovery. BD will be responsible for commercial-scale cell production and marketing. In an interview with the IN VIVO Blog, Fate CEO Paul Grayson declined to say specifically when the cells would reach the market. The partners will only sell what Grayson called "plain vanilla" iPS cells, not yet differentiated into various cell types. Fate is working on differentiated cells but for now keeping them for internal use. With the BD deal, Fate becomes the second firm to sell iPS cells. Cellular Dynamics, spun out of the pioneering Wisconsin lab of James Thompson, has been selling iPS-derived cardiomyoctes for nearly a year. -- Soon to be Disappointed SF Giants Fan Alex Lash

Exelixis/BMS: In a turbulent year during which it changed CEOs and laid off staff, Exelixis’ low point might’ve come in June, when key partner Bristol-Myers Squibb Co. walked away from the companies’ agreement to co-develop Phase III cancer-fighting drug XL184. Yet the two are already working together on new programs in diabetes and inflammation: In a series of deals announced October 11, BMS said it would pay $60 million upfront for exclusive development and commercialization rights to a preclinical Exelixis diabetes program that includes the TGR5 agonist XL475, as well as the right to collaborate on a discovery-stage inflammatory disease program centering on RAR-related orphan receptor antagonists. Milestone payments could add $505 million to the deal, plus Exelixis would garner royalties if the programs produce marketable drugs. Simultaneously, BMS and Exelixis said they would unwind some existing oncology agreements; Exelixis opted out of a co-development arrangement on Phase Ib cancer drug XL139 in exchange for a milestone payment, while BMS waived its final option on a 2006 deal covering three targets. The deals bring much-needed cash to the notoriously spendy Exelixis, which despite some recent cost-cutting is now shouldering the high cost of moving XL184 forward by itself.--Paul Bonanos

Merck/Lundbeck: With a large number of atypical antipsychotics competing for attention, any new entrant will have an uphill battle to gain traction, and so Merck has called in the cavalry. The Big Pharma has licensed to CNS-specialist H. Lundbeck exclusive commercialization rights to its recently approved Sycrest (asenapine) for all markets outside of the US, China and Japan. The Danish company paid an undisclosed upfront fee for the rights, and will also make product supply payments to the US company. Asenapine was launched in the US as Saphris by Merck last year, for schizophrenia and for mania associated with bipolar disorder, but has so far disappointed. Making matters trickier in the EU, the schizophrenia indication was turned down in there because regulators were not convinced of the agent's clinical effectiveness. -- John Davis

Lundbeck/Genmab: When you have a product that accounts for around half of your revenue, and that product is nearing patent expiry, you know you have your work cut out for you. Lundbeck, whose antidepressant Cipralex/Lexapro (escitalopram) accounted for 56% of its revenues in the first half, announced last month that it wanted to work with more external partners, and would cull some of its own researchers, as part of a new R&D strategy. The first fruits of this new policy were seen this week, in the Merck deal noted above and in a tie-up with fellow Danish firm Genmab, which will create novel human antibodies to CNS targets identified by Lundbeck. Genmab will receive an upfront payment of €7.5 million and, if the collaboration is successful, it could receive €38 million in milestones, and single-digit royalties as well. Genmab has an option to pursue non-CNS leads that it identifies during the course of the work, and in that case would pay milestones and royalties to Lundbeck. Genmab has been through a torrid time in the past few months, and wants to use its antibody research capabilities as a “profit center, not just a cost center,” according to newly appointed CEO Prof. van de Winkel. -- JD

Pfizer/King: In its first “bolt-on” acquisition since the mega-merger with Wyeth last year, Pfizer has reached an agreement to purchase King Pharmaceuticals for $3.6 billion. The deal, announced Oct. 12, is subject to a tender offer under which Pfizer would buy up outstanding stock in King for $14.25 a share – a 40% premium over the specialty pharma’s closing price on Oct. 11 – but both companies’ boards have agreed to the sale, with closing anticipated in fourth-quarter 2010 or the first quarter of next year. In recent months, Pfizer has outlined a strategy for bolstering its finances prior to the U.S. patent expiration of Lipitor late next year under which it would look for transactions valued at between a few billion to several billion dollars that complement the company's core businesses and add incremental revenues. King will bring to Pfizer a narrow portfolio of highly specialized pain therapies and a well-trained specialty sales force, as well as Remoxy, a tamper-resistant formulation of oxycodone under review at FDA. Pfizer believes King offers commercial synergies: some of King's drugs can be dropped into the Big Pharma's primary care sales force bags, an area where Pfizer is strong and King is not. Pfizer's two key marketed pain products, Lyrica and Celebrex, in turn, can benefit from the support of King's specialized sales force; currently Pfizer's detailing emphasis for them is on primary care doctors. –Joseph Haas and Wendy Diller

UCB/Synosia: An accomplished in-licensor of pharma's unwanted assets, Synosia Therapeutics has finally found itself on the other side of a deal: On Oct. 12 the biotech said it out-licensed its two lead Parkinson's disease candidates, SYN-115 and SYN-118, to Belgian CNS specialist UCB, which will conduct Phase III clinical trials and commercialize them. The companies will also set up a broader alliance, under which compounds from either group will be evaluated by Synosia through to the end of Phase II, at which point UCB will conduct further development and commercialization. In return for rights to the two Parkinson's disease products, UCB will make an undisclosed upfront payment and pay regulatory and commercial milestones, which could give rise to an additional $725 million in funding for Synosia. UCB has also led a $30 million series C funding in Synosia with an equity investment of $20 million. The other $10 million came from existing investors, which include Versant Ventures, 5AM Ventures, Novo A/S, Aravis Venture, Investor Growth Capital and Swiss Helvetia Fund. The deal goes some way toward validating Synosia's in-licensing strategy: '115 and '118 came from Roche and Syngenta, respectively. -- JD

Novartis/Immunogen: Last week we at IVB rhetorically asked one another: where are all the deals in antibody-drug conjugation technology, an exiting area seemingly bereft of deals lately. Well well. Just like that, antibody-drug conjugate developer ImmunoGen licensed its platform technology to Novartis for $45 million upfront to create enhanced cancer-fighting antibodies against unspecified targets of Novartis's choosing. ImmunoGen would get up to $200.5 million in milestones for each target that leads to a conjugate, plus royalties on sales if the drugs reach the market. Announcing the deal Oct. 11, the companies declined to say how many targets Novartis has rights for, but ImmunoGen retains ownership of the cytotoxic small molecules and chemical linkers plus other know-how that it contributes to each therapeutic. The Novartis deal comes just as ImmunoGen and Roche released promising interim Phase II data for T-DM1 in first-line treatment of HER2-positive metastatic breast cancer. That compound, a combination of ImmunoGen's small molecule maytansinoid DM1 and Roche/Genentech antibody Herceptin (trastuzumab), is currently industry's most advanced ADC candidate. --S.t.b.D.S.F.G.F.A.L.

Mingsight/Pfizer: Big pharmas are in the throes of revamping their R&D pipelines and that means deprioritizing certain assets. But does that mean outlicensing? Maaaybe. An analysis in the soon-to-be-published October IN VIVO shows that outlicensing volume has declined dramatically since 2007, when a total of 54 programs from big pharma, big biotech, and specialty players were offloaded to new partners. This year through August 31, there have been only 10 such deals. But for the VCs and biotech execs looking to jump-start a newco with already validated molecules, this week’s alliance between Pfizer and MingSight proves that outlicensing in the biopharma wilderness, truly a rare bird, does still exist. MingSight, a still stealthy biotech with bases of operation in both China and San Diego, has acquired exclusive worldwide rights to two preclinical compounds from Pfizer that are being developed as treatments for diabetic retinopathy, and potentially uveitis and dry eye. Under the terms of the agreement (which really weren’t disclosed in any substantive way), MingSight has agreed to pay Pfizer an upfront fee, paid in the form of cash and a convertible note, as well as development and sales related milestone payments, and royalties on future sales. MingSight’s dual citizenship is noteworthy; this kind of hybrid approach, with its emphasis on keeping R&D burn low by moving the work to the still lower-cost China, is becoming an increasingly attractive model in the start-up arena, where the mantra of the day is capital efficiency. In-licensing has been the model du jour for founding ophthalmology companies for much of the past decade, as companies look to repurpose drugs that have already been vetted in preclinical or clinical studies in non-ophthalmic indications for use in the eye.—Ellen Foster Licking

Ablynx/Merck-Serono: Ablynx has proven to be the master of Merck-Serono's domain (antibodies) as the two companies are doubling down on their collaboration in the space. On Monday Ablynx announced it would receive €10 million up-front to develop its proprietary Nanobody domain antibodies against a M-S nominated inflammatory disease target. Ablynx will hand off the package to M-S at the IND stage, handling all discovery and preclinical activities (and covering costs, excluding manufacturing costs) on its own. When (if?) Merck-Serono takes over Ablynx will receive a €15 million milestone and can opt-in to a 50/50 co-development deal on the project -- if not, Merck gets worldwide rights and Ablynx will receive milestones and royalties down the road. The companies have been working together since September 2008, on two targets in oncology and immunology. -- CM

image by flickr user cygnus921 used under a creative commons license

Deals of the Week: Holiday Shopping

Having trouble this holiday season deciding what to get for the Big Biotech CEO in Your Life Who Has Everything? Join the bidding for Facet Biotech! The reserve may be quite high--higher than $17.50 per share, anyway--and it's not technically an auction (because Facet isn't necessarily going to sell, which would be sure to garner it some negative feedback on eBay). But is money really a problem when it comes to that special someone?

And don't worry about losing any of Facet's drug candidates if you're the winning bidder. "The Pink Sheet" DAILY noted this morning that while Facet's top compounds are tied up in partnerships, including Biogen Idec's co-ownership of its most advanced drug, daclizumab for rheumatoid arthritis, none of the agreements will be affected by a change-of-control.

"In each of our three collaborations, the non-acquired entity would not have a right to terminate the collaboration," Facet CEO Faheem Hasnain told "The Pink Sheet" DAILY. "In fact, the acquiring entity would step right into Facet's shoes."

Whatever you do, though, just don't materially undervalue those shoes while overstating their liabilities. That approach has gotten Biogen Idec nowhere. Respect the shoes!

Meanwhile the rest of you biopharma dealmakers have had a busy week (makin' AND breakin' deals), so we oughta get to it. The following companies won't be trawling the malls on Christmas Eve, they're ...



GSK/Intercell: Not even Santa Claus himself could earn this much for delivery. This morning Austrian vaccines company Intercell said it licensed to GSK its patch vaccine delivery technology in a deal worth €33.6 million ($49.4 million) in up front cash. GSK also agreed to purchase up to €84 million worth of Intercell shares in a "staggered shareholding purchase option" that could reach a 5% holding in the biotech (€28 million u/f for 0.9mm shares at an 18% premium, other investments milestone-based). The development and commercialization deal will include Intercell's Phase III travelers' diarrhea vaccine, a Phase II pandemic flu vaccine, and future patch vaccines. Intercell will be eligible for a slew of milestone payments and profit sharing on the projects already in development, as well as milestones and royalties for future products that include its patch technology. GSK is now Intercell's second strategic investor--Novartis owns about 16% of the company through a 2006 deal for a Japanese encephalitis vaccine and a monster 2007 deal for the biotech's vaccines for bacterial infections. Intercell has a variety of other partners, including Merck, Sanofi-Pasteur, and Kyowa Hakko Kirin. For more on Intercell and the market for adult vaccines, check out this recent IN VIVO feature.--CM

Novo Nordisk/ZymoGenetics: This is Novo/Zymo IL-21, the Sequel. In a second deal around the IL-21 cytokine, these two companies' long, entwined history continued this week when Novo Nordisk licensed from ZymoGenetics a preclinical anti-IL21 antibody for auto-immune and inflammatory diseases. The terms look good for Zymo: $24 million up-front, reflecting the value of IP around the target that was included in the deal. As Novo EVP and CSO Mads Krogsgaard Thomsen told "The Pink Sheet" DAILY: "we're buying all IP surrounding [the blocking of] IL-21 as a concept, and its utility in different disease areas." That move should provide the Danish firm with "a good degree of exclusivity on this target," he says. "We now have global patent rights to block cytokine IL-21; no one else can do that." (Competitors could block the IL-21 receptor, however, just not the molecule itself.) ZymoGenetics is eligible to receive $157.5 million in potential milestones, up to and including the antibody's regulatory approval in major global markets, and royalties on net sales. ZymoGenetics may opt to co-promote the biologic in the U.S., for a $10 million fee and a 15% contribution to Phase III trial costs. In this scenario, US royalty payments would increase from single to double digits. Novo is familiar with ZymoGenetics efforts in the IL-21 space; until last year when it retrenched into diabetes and opted out of the alliance, it was the biotech's partner on its recombinant IL-21 cancer project. Novo is confident that blocking the cytokine has broad applicability in immune disorders. Hence why it's snapping up that IL-21 IP. --CM/Melanie Senior

Celgene/Gloucester Pharmaceuticals: In a move that adds to its hematological cancer franchise, Celgene purchased privately held Gloucester Pharmaceuticals and its recently approved Istodax (romedepsin) for $340 million in upfront payments, plus potential milestones that could total another $300 million. The deal secures a nice exit for Gloucester’s five venture capital investors – Novo A/S, Apple Tree Partners, ProQuest Investments, Prospect Venture Partners and Rho Ventures – who backed the biotech with a $29 million Series D round in August. Over Gloucester’s six years of operations, the investors kicked in a total of roughly $100 million. Celgene predicts the Gloucester purchase will be accretive to earnings by 2011, in part because it would not need to add to its marketing and sales infrastructure since it already sells hematological cancer drugs Revlimid, Thalomid and Vidaza.--Joseph Haas

BMS/Tranzyme: In its first alliance with a Big Pharma company, Tranzyme Pharma will receive $10 million upfront plus two years of research funding from Bristol-Myers Squibb in a collaboration to discover potential new macrocyclic compounds, which have potential in a wide range of therapeutic areas, including oncology and metabolic disease. Announced Dec. 7, the deal is not Bristol’s first foray into the macrocyclic space – in April, it paid $5 million upfront plus $7.5 million in research and development funding to Ensemble Discovery to develop macrocyclic compounds called Ensemblins against eight undisclosed targets. It’s likely Bristol is trying to get ahead of the curve on what Tranzyme calls an underdiscovered area – no other Big Pharma companies are doing deals in the space and Tranzyme has thus far not partnered any of its clinical or preclinical assets. The new deal centers on Tranzyme’s MATCH (Macrocyclic Template Chemistry) drug-discovery platform. The biotech will perform early lead discovery against a range of undisclosed targets specified by Bristol, which will then be responsible for lead-optimization, preclinical and clinical development, and commercialization. Tranzyme will receive two years of research funding ranging between $3 million and $6 million and could earn regulatory milestones up to $80 million for each target program, as well as sales milestones and royalties.--JH

Mylan/Pfizer: Details are scant on the authorized generic agreement around the Wyeth antidepressant Effexor XR. But Mylan said early this week it had reached an agreement with Pfizer to sell the long-acting capsule formulation as early as June 1, 2011. Doses equivalent to Mylan's planned generic venlafaxine capsules racked up $2.9 billion in sales in the year to September 30, the company said in its release. Legislation that would curtail or even ban brand/generic settlements is winding its way through Congress these days (it may even catch a ride on the behemoth of health care reform) and we know where the FTC stands on these deals.--CM


Lilly/Isis: Lilly and Isis called it quits this week on their 5-year collaboration on LY2275796, a second-gen antisense compound targeting eukaryotic initiation factor-4E that recently completed Phase I trials in oncology. Isis is paying an undisclosed amount to take back the product, arguing that ‘5796 got lost in the shuffle after the big drugmaker’s 2008 ImClone acquisition. Is this spin control or honest truth? Data related to ‘5796 are sparse, with Isis failing to provide an update at its recent R&D day, leading Joseph Schwartz, an analyst at Leerink, to write in an investor note: “it’s logical to conclude that lack of anticancer activity and/or toxicity may be the reason why LLY [Lilly] is not pursuing it.” As Isis CEO Stanley Crooke points out in “The Pink Sheet” DAILY, Lilly has right of first negotiation to opt back in to the molecule’s development when—or if—it enters Phase III studies. (The two companies are also still partners on a Phase II antisense prostate cancer drug.) So, maybe for Lilly this is about curbing risk: with critical drugs coming off patent near-term (including Zyprexa and Cymbalta), Lilly needs late-stage assets to bolster its flagging pipeline, not early stage, highly risky products that are going to be a drain on resources. Better to let Isis carry the risk—and cost—but keep a just-in-case door open. The central question for many investors becomes will another partner, Genzyme, reach the same conclusion? Recall Genzyme and Isis announced a lucrative tie-up in January ‘08 on the CV medicine mipomersen, with Isis garnering $175 million in upfront cash and another $150 million in equity. Six months later, the two revised the deal terms, with Isis having to pony up more development money after data from a competing trial highlighted the regulatory risks associated with cardiovascular studies. Mipomersen is much further along than the Lilly cancer drug, and recently scored good data at the American Heart Association meeting, giving partner Genzyme some positive news to tout after a string of manufacturing and regulatory gaffes. But the Phase III medicine has also been the subject of questions, especially related to adverse liver side-effects and high clinical trial drop-out rate.--Ellen Foster Licking

GSK/Cytokinetics: Cytokinetics continues to phase out its oncology R&D and on Thursday announced it had scrapped a third and final cancer program with GSK (GSK decided not to opt into two others late last year). GSK will complete an ongoing Phase I trial of the compound, GSK-923295, in advanced, refractory solid-tumor patients. Then rights will revert to Cytokinetics, which says it is de-emphasizing its oncology work in favor of its core muscle-related R&D (which includes the Amgen-partnered cardiac contractility program discussed here). The three GSK-partnered programs were the company's entire clinical oncology portfolio.--CM

Genentech A Wholly Owned Member of the Roche Group/Seattle Genetics: As the Roche Pipeline Purge rolls on, the latest casualty is SeaGen. Genentech paid $60 million up-front for access to SGN-40 (dacetuzumab) in 2007 and at least $8 million more in milestones since then. But this morning the companies said that Roche was giving back rights to the anti-CD40 antibody in development for non-Hodgkin's lymphoma and multiple myeloma. The end of the SeaGen alliance follows Roche's decision this past week to drop partnerships with Actelion and GenMab. But you can't just blame Roche's re-org. Earlier this year a trial of SGN-40 in diffuse large B-cell lymphoma was halted when an interim analysis suggested the trial would not reach its goals. In any case, hold onto your hats, Genentech partners! --CM

The Horse Race at Bristol

We admit to being impressed with the smaller-is-better strategy from Bristol-Myers Squibb under CEO Jim Cornelius.

He didn’t really have much choice, of course. The company’s got nearly $8 billion in revenue at risk by 2012 from the patent expirations of Plavix and Abilify. And Bristol doesn’t have the pockets Pfizer does to go buy itself a couple of years of earnings respite (see our analysis of Wy-Pfi here).

Instead, Bristol is going to take its lumps – and then re-set the growth clock from a smaller base with the products that will then be maturing from its “string of pearls” deals. And those products will have made Bristol a very different company – a specialist biopharma.

So granted Bristol is still independent when that time comes, who should run it? In creating a four-man executive committee, including himself, Jim Cornelius looks to have fired the starting gun in a three man race, with president and COO Lamberto Andreotti in pole position. Andreotti is a marketing guy – with as much or more experience in the kind of products Bristol is getting away from as in the products Bristol is going towards. He’s never run a biotech company, certainly. But since the directors appoint the CEO, a betting man would wager they’ll go with one of their own -- and Andreotti's just been appointed to the board. That's what the directors did last time, after all, appointing Cornelius to what was then supposed to be an interim role.

Then there’s Jean-Marc Huet. Smart young guy – and if not entirely the architect of Bristol’s spin-off strategy, then certainly its field commander (he arrived in ’08, after the sale of the imaging business and when the Convatec deal was well underway). And he was a pretty successful officer, too: the Mead-Johnson IPO managed to raise $720 million in what seems like the only IPO in forever. He gets pretty good marks from investors – Bristol’s stock has done better than most Big Pharmas since Huet’s arrival. And Cornelius was a CFO as well (a dim memory tells us he was the youngest CFO in Lilly’s history). But Huet doesn’t have much experience in health care (his background is more in the consumer world) – and right now, Big Pharma’s front-and-center example of a non-health care exec running a pharma, Jeff Kindler, hasn’t been winning too many admirers.

Elliott Sigal, the last member of the triumvirate: a biotech guy (was CEO of Mercator Genetics) and quite definitely the architect of the company’s scientific externalization strategy and its focus on high-medical-value, focused-market drugs. Along with an impressive string of deals, Sigal’s presided over an extraordinarily productive time for Bristol’s R&D – nine NMEs approved in five years, by our count (and yes, we know – can’t give him all the credit for that good fortune; have to acknowledge his predecessors, including the late James Palmer). So could Sigal get the top job? Maybe. But since Merck’s Roy Vagelos, Big Pharma’s been too chicken to appoint an R&D guy to run the business.

So the smart money’s on Andreotti. But Cornelius – as anyone who knows him can tell you – is a pretty close-to-the-vest guy. And he’ll undoubtedly have the biggest say in who gets to be his successor.

Image from Flickr user BiggerPictureImages.com and used under a creative commons license.

While You Were Saying Goodbye to Summer

going, going, gone.

Outta here like a Ryan Howard shot to deep right field, vanished like Keyser Soze, Summer 2008 is now just a memory. Hey, at least football season has begun, right? Below, our roundup of what you might have missed while enjoying that last BBQ of the season.

• European Society of Cardiology: News came thick and fast out of this annual meeting in Munich. The results of a potentially important study of stents vs scalpels in treating clogged arteries are in, and surgery has come out on top. Lilly and Daiichi's prasugrel got a boost in diabetics prior to its 26th September FDA deadline. An analysis of the previously released Triton-Timi 38 trial showed that prasugrel was more effective than standard-of-care clopidogrel (Plavix) in that patient population, reports Reuters. Pronova/GSK's Omacor (fish oil) met both primary endpoints in a Phase III outcomes study in patients with heart failure, who were 9% less likely to die than patients given placebo. AZ's Crestor didn't fare as well in a similar population. Finally, Bayer said it would speed up development of rivaroxaban--putting a little extra pressure on Pfizer/BMS, whose rival candidate apixaban hit a snag last week, as we wrote about here. For more news out of the meeting, click here.
• Shionogi & Co. is the latest in a pretty long line of Japanese pharmaceutical companies buying up cheaper American firms to help expand into western markets. Shionogi bought Sciele Pharma for $1.1 billion ($31/share, a 61% premium to the stock's previous close) plus the assumption of $325 million in debt, the companies announced on Monday. Atlanta-based Sciele had revenues of more than $382 million in 2007, and specializes in women's health, cardiovascular disease, diabetes, and pediatrics. For more on Japanese Pharma appetites, see here, and look for a feature on these trends in an autumn issue of IN VIVO.
  
• Oncology expert Prof. Karol Sikora of CancerPartnersUK diagnoses the ills of the country's NHS and writes this prescription in The Sunday Times: "Radical structural change to the NHS is vital. Competition and choice drive up quality and access, so leading to greater value, just as we’ve seen in other consumer areas such as mobile phones, budget airlines and the high street. Sensible incentives linked to performance and outcomes are essential. Drastic reform, not more money, is now needed."
• Novacea, which begun a strategic review in May after Schering-Plough canceled an alliance around its entered an agreement to merge with Trancept Pharmaceuticals (nee TransOral Pharmaceuticals, click here for our admittedly old 2003 profile of the firm). The latter company, a privately-held specialty pharma that specializes in tweaking the pharmacokinetics of CNS compounds, has raised more than $70 million in venture funding but--surprise, surprise--has been unable in this climate to tap the public markets. If investors buy into this reverse merger, TransCept backers will hold 60% of the combined company, which, the companies say, will have enough cash to pursue FDA approval for and launch its Intermezzo lozenge formulation of the insomnia drug zolpidem (the now-generic Ambien).
• Lipitor ads are back after six months off the air, but you mean nasty bloggers won't have Dr Jarvik to kick around any more! According to the WSJ, Jarvik's out and heart attack survivor John Erlendson is in. What are the odds that he's a rower?
• In the latest installment of its A1 "The Evidence Gap" series, The New York Times asks why more than three million people still take Vytorin/Zetia every day, and notes that some prominent cardiologists are now calling for it to be taken off the market.
  
• The Guardian adds up the challenges facing Big Pharma and, well, that's pretty much it. Would have been nice to see some answers in there too.
  
• Speaking of The Guardian, Ben Goldacre's Bad Science (the book) is on shelves now (at least in the UK). Go on, buy one. And if you haven't already, click the link to his web site in our blogroll to the right to get a preview.
  

Apixaban: Bad News Highlights Good Strategy

The delay announced yesterday to Pfizer and BMS's apixaban blood clot prevention therapy is certainly a setback for the two pharmas, though they presented the news--and the market reacted--relatively smoothly.

Apixaban--pitted here in a head-to-head against current standard Lovenox, from Sanofi-Aventis, for the prevention of venous thromboembolism in knee replacement surgery patients--just barely failed to show non-inferiority, thanks to a much better than expected result for Sanofi's drug (see the companies' release for the statistical details). This was the first of eight Phase III trials planned for the compound, and ongoing studies aren't affected by yesterdays news, BMS apixaban program head Jack Lawrence told Reuters.

But still, the failure will add at least several months or more to the drug's development program and with rivaroxaban from Bayer/J&J already a half-step ahead, every little bit helps. An NDA for the compound, an oral Factor Xa inhibitor, won't be filed in 2009 as planned.

All of which validates Bristol's decision to go halvesies on the apixaban program with Pfizer in the first place, in a deal we've been fans of since it was announced back in April 2007.

To reacquaint you with the terms: in exchange for $250 million upfront cash and up to $750 million in development and regulatory milestones Pfizer gets an equal share of profits and foots an equal share of commercialization expenses, and Pfizer will fund 60% of any development costs from January 1, 2007 onward. (BMS's similarly risk-sharing and lucrative pact with AZ in the diabetes space provoked our admiration only a few months earlier.)

So with each setback, Bristol's strategy--sharing risk on important projects and increasingly biotech-like--seems cannier. That said, it's fair to ask just how many snafus Bristol's reputation can take before those nine-figure upfront payments dry up: after all, its other big risk-hedging adventure was on the now-dead muraglitazar PPAR deal with Merck & Co. back in 2004, which brought in $100 million upfront and at least $55 million in milestones before stumbling at FDA.

And it's not only Bristol among Big Pharma that's spreading the risk--and possibly the massive reward--on late stage development projects. We'll have more to say in the next IN VIVO about Eli Lilly's $300 million financing deal with TPG-Axon and Quintiles' NovaQuest on its two lead (Phase III) Alzheimer's disease treatments.

And who can forget our multiple pleas for your input on Amgen's potential future deal for denosumab? Certainly the project is now less risky/more expensive since Phase III results in its post-menopausal osteoporosis study were positive, but as Amgen's most important pipeline product in years perhaps (some day) the biggest sign that at least a few Big Pharma (and Big Biotech) now think differently about clinical and commercial risk.

DotW: Dog Days

As the dog days of summer come to an end, it's time for last-minute barbeques and beach trips before the frenetic fall calendar of investor and scientific meetings commences. It's been a week filled with news--though not necessarily of the biobucks variety.

Lilly and partner Daiichi Sankyo published positive Phase III data for their anti-platelet drug prasugrel in the European Heart Journal, while shares of Amylin took a bath thanks to concerns that the drugs may cause pancreatitis. Meantime, a group of Harvard researchers published a study in the New England Journal of Medicine this week questioning the cost-effectiveness of HPV vaccines such as Merck's Gardasil and GSK's Cervarix.

The Food and Drug Administration must have finally used up all its "approvable letter" stationery. Johnson & Johnson's Doribax, an IV-antibiotic already approved for intra-abdominal infections, has the dubious honor of receiving the agency's first "complete response" letter regarding its use to treat hospital-acquired pneumonia. J&J, which declined to make the letter available to journalists at The Pink Sheet Daily, is currently "reviewing the agency's letter and will work to resolve any outstanding questions," the pharma said in a statement.

But dog gonnit. We aren't just waiting with baited breath for J&J to respond to regulators. We continue to watch the Roche/Genentech chess match. Roughly one week after it rejected Roche's initial buy-out offer, Genentech announced a $371 million retention plan that covers "substantially all employees," including executive officers in lieu of the biotech's planned 2008 stock option grants. Whether the proposed payola is enough to convince senior execs to remain at the company is a subject of heated debate, as regular readers of both CafePharma and Derek Lowe's In the Pipeline already know.

As we enjoy the last hazy days of summer, here's a look at the week's deals....

BMS/PDL: PDL BioPharma is a biotech that has been dogged by troubles, but the company announced a bit of good news this week: the company partnered its Phase I antibody for multiple myeloma, elotuzumab (formerly known by the tongue-tripping moniker HuLuc63), to BMS in a deal worth a modest $30 million up-front and up to $480 million in additional development and regulatory milestones. The deal also gives BMS an option to expand the collaboration to include PDL241, another antibody still in preclinical trials. The deal is back-end loaded, requiring PDL to complete on-going Phase I studies and provide support for Phase II trials, but does allow for profit-sharing on elotuzumab sales in the US. (Outside the US, PDL will receive undisclosed sales royalties.) Still investors are likely to view the news as positive given the risky nature of elotuzumab, a first-in-class therapeutic that binds to a cell-surface protein called CS-1 that's found selectively on myeloma cells. And the announcement deflects concerns about recent or impending staff departures: Pat Gage, PDL's CEO left in late May and the company's CSO, Donald Richard Murray, will resign at the end of this month. For BMS, the deal shows the New York-based pharma is conducting business as usual despite the drama associated with its proposed takeover of ImClone. Moreover, it deepens the company's footprint in oncology, especially the multiple myeloma space, building on the pharma's May acquisition of Kosan, which has the Hsp90 inhibitor tanespimycin in Phase III trials.


TEVA/Cel-Sci: Cel-Sci announced Tuesday that it gave Teva the OK to market and distribute it's head and neck cancer drug Multikine in Israel and Turkey. Precise financial details weren't disclosed but once the drug has been approved, Cel-Sci will make the product, while the Israel giant will be responsible for sales. Teva will also participate in the global Phase III clinical trial and fund a portion of the studies. The stock bounced on the news but sharply retreated on a day generally associated with market turmoil. The steep drop prompted Geert Kersten, Cel-Sci's CEO to issue a letter to shareholders, saying:

You asked, "How is it possible that the stock can be down after such a good announcement?" As the company's largest shareholder...I am as puzzled andas disappointed as you.

We've noted before that licensing deals don't always give company stock prices a much needed bump. But in this case, Kersten and others believe something nefarious may be afoot as short sellers "painted the tape," illegally dumping large volumes of the stock just before the close of business August 19 in order to make the stock look weak and unattractive. Kersten implores his shareholders to contact their congressional representatives to convince regulators to delve into the trading records of the last several weeks to resolve the issue. Meantime The IN VIVO Blog will continue to follow the situation and update you with any further news.

Lilly/Monsanto: Lilly continues to pursue a diversified business strategy, announcing late Wednesday that it would pay $300 million for rights to Monsanto's synthetic milk-producing hormone, Posilac, which is better known as recombinant bovine somatotropin (rBST). In addition to global sales rights, Lilly also obtains the Georgia-based manufacturing plant as part of the deal. The announcement comes at at time of growing consumer opposition to the use of hormones, particularly in dairy and meat products. Still, for many pharmaceutical companies, the looming threats of patent expiries and increased regulatory scrutiny make diversified business models built on generics or consumer products-a la Novartis's stake in Alcon and Daiichi's purchase of a controlling interest in Ranbaxy--more attractive. And Lilly has showed in other ways its interest in mitigating risk. Earlier this summer, it partnered its Phase III Alzheimer's drug with private-equity play TPG-Axon and Quintile's NovaQuest unit and off-loaded its R&D risk by teaming up with Covance. For its own part, Monsanto's decision to sell-off Posilac is in keeping with a stated mission to divest of smaller animal units in order to concentrate efforts on popular crop-agriculture product lines, including the herbicide Roundup.

King/Alpharma: Latebreaker! King Pharmaceuticals takes top dog in biobucks this week with its $1.4 billion unsolicited bid to acquire Alpharma. The Tennessee-based specialty pharma is behaving more like a dog with a bone, threatening to turn hostile if Alpharma's board refuses to accept the bid, which it apparently presented to the company in early August. Alpharma execs weren't available for comment--of course--but Reuters reports that the company appears to have rejected the bid. King's offer of $33 a share represents a 37% premium over the $24.04 closing price of Alpharma's stock on August 21. Not too surprisingly, Alpharma shares surged 41% premarket to $34, while King fell 1% to $11.12. By disclosing the rejected bid, King appears to be putting pressure on Alpharma in hopes of completing a friendly deal. That King is willing to go to extreme measures shows its desperation. Earlier this month, King reported that its second-quarter net income tumbled 34% as sales of its blood-pressure drug Altace stalled thanks to competition from generics. After losing a patent case last year, King has sought to refocus its portfolio with an emphasis on pain therapeutics. With its extended release morphine product Kadian and the NSAID containing Flector patch, Alpharma would give King several branded products in this arena.

(Photo courtesy of Flickr user NinJA999 courtesy of a creative commons license.)

While You Were at the Beer Festival II

For those of you expecting an Olympic theme to the weekend roundup, well, there's always next week. Because this weekend we enjoyed our annual pilgrimage to the Great British Beer Festival in London. A quick review was in the works until a quick look at last year's beer festival post revealed we were about to say pretty much the same exact thing.

Suffice to say that Sharps, Caledonian, and Hook Norton were bringing their A-game as usual (wish we could say the same about our photographer). Another stalwart putting in a good showing was Cairngorm; its Trade Winds was particularly nice though we're still leaning toward old favorite Sharps' Atlantic IPA as our beer of the fest. A nice surprise for us was a lemongrass beer from Hop Back, Spring Zing.

There was little industry news with zing over the weekend, so we've put on the beer goggles so you don't have to:

• Pfizer has reached another settlement over a generic Lipitor, Reuters reports, though there are no details available regarding the Big Pharma's deal with Apotex.
  
• IMC11F8 is the catchy name given to Imclone's next-generation, fully human antibody viewed by many as a son-of-Erbitux. The candidate, not yet in pivotal trials, is at the core of the ongoing BMS/Imclone negotiation, points out today's Wall Street Journal. Bristol claims rights to the follow-up under the companies original 2001 alliance. Imclone disputes that entitlement, though hasn't always done so, says the Journal.


• Via the SF Chronicle, one doctor's crusade to, uh, get a cool epocrates application on his iPhone so he didn't have to carry around an extra gadget.

While You Were Dominating the Competition

If you were too busy playing in the Wimbledon semis and finals this weekend (or maybe just watching) to keep up with the news, IN VIVO Blog is here to help.

• Inhibition! Some news out of the International Society on Thrombosis and Haemostasis in Geneva this weekend. First up, Bayer's rivaroxaban was significantly more effective than Sanofi-aventis' Lovenox in preventing blood clots after knee surgery, Reuters reports. Rivaroxaban, a Factor Xa inhibitor, is being developed with Johnson & Johnson. Another Factor Xa inibhitor, Pfizer and BMS' apixiban (which is approximately a year behind rivaroxaban in development), also posted solid results, in a mid-stage trial. Reuters has the story.
  
• Indecision! UK's National Institute for Clinical Excellence (NICE) has changed its mind, and now considers Eli Lilly's Alimta cost-effective in treating mesothelioma in certain patients.


• Interference!! Roche and Alnylam announced this morning a broad alliance in RNAi therapeutics, worth up to $1 billion. Alnylam gets $331 million up-front in cash and equity payments. We hope you're not all RNAi'd out cause there'll be more on this later ...

A June Wedding for Bristol/Sanofi?

Something tells me that talk of a potential acquisition of Bristol-Myers Squibb by Sanofi Aventis will heat up again in exactly one month.

The on again/off again speculation about a merger of the Plavix partners is decidedly off at the moment. And yes, yes, I know that my fellow IN VIVO bloggers think that Bristol's deals with AstraZeneca and Pfizer will make a Sanofi bid economically dumb. But two events coming up in mid-June could spur some desperate action.

For Richer, For Poorer

On June 15, BMS expects to be officially released from the terms of a deferred prosecution agreement it signed two years ago. The DPA has been the sword of Damocles hanging over Bristol, making it essentially untouchable for would-be-suitors—especially once Bristol ran into further trouble with its spectacularly misguided attempt to settle patent litigation over Plavix.

Bristol has now agreed to settle charges arising from that debacle—and says it has been assured that the deferred prosecution agreement will be released on schedule as long as it stays out of trouble between now and June 15. (That seems easy enough, but given Bristol’s history, its probably best not to count the chickens just yet…)

And, since “interim” CEO Jim Cornelius pulled off a Dick Cheney style CEO search—ending with himself as the new CEO—there is no reason to assume that Bristol is committed to independence for the long run.

But the real impetus for renewed speculation will probably come two days before June 15, when Sanofi Aventis’ much touted obesity therapy rimonabant goes up before an FDA advisory committee.

Sanofi insists the meeting is a good news event for the troubled application. Maybe. But given the company’s misreadings of FDA so far, Sanofi’s optimism probably shouldn’t inspire too much confidence. I think Kate Rawson has it right in the May issue of The RPM Report: Sanofi will be lucky if the drug gets even a strong minority support from the committee.

This does not seem to be a good time to take a big drug before an FDA advisory panel. Especially one with a safety signal. Perhaps most especially one with a safety signal (in this case depression) that dovetails with a major focus of congressional scrutiny. Did you see what happened to Arcoxia?

If rimonabant suffers a similar setback before the committee, Sanofi will be under even more pressure to make another move. So expect the merger speculation to heat up just before summer arrives.