Deals Of The Week: New Academia/Industry Partnership Template In Eisai/JHU Collaboration?

As founder and president of a coalition working to enhance academic drug-discovery and collaborations between academia and industry, Barbara Slusher has a good idea of the advantages and pitfalls of such arrangements. She points to ongoing work between Japan’s Eisai and Johns Hopkins University, where she serves as director of neurotranslational drug discovery at the medical school’s Brain Science Institute, as a potentially more mutually rewarding template for academic/industry tie-ups.

In October 2011, Eisai signed a five-year drug-discovery alliance with JHU, initially slated to focus on central nervous system targets. Slusher, who heads up the Academic Drug Discovery Consortium (ADDC) in addition to her responsibilities at JHU, said the partners are about 18 months into a partnership currently focused on two targets, one undisclosed. The other is aimed at identifying drug-like molecules that inhibit xCT, a glutamate cysteine exchanger that Eisai believes could offer potential in combating inflammatory disease.

Barbara Slusher, JHU Brain Science Institute
and Academic Drug Discovery Consortium

Under this alliance, written to last the greater of five years or to the completion or termination of all related projects, the Brain Science Institute reviews target research throughout JHU’s roster of researchers and presents potentially novel and interesting targets for Eisai’s review. Eisai then selects the targets of greatest interest for the high-throughput screening collaboration.

The compound libraries generally available to academic researchers are not as large, diverse or drug-like as those found within a biopharmaceutical company’s library, developed through years of wide-ranging R&D work, Slusher said. Slusher came to JHU in 2010 after working in drug discovery at five biopharma companies, including Eisai, and set a goal of establishing collaborations offering greater potential for academic discovery work.

“One of the things that my team did when we first came to Hopkins was try to establish a relationship with a pharma company such that if any targets we identified were of interest to the company, we would develop a high-throughput screening assay, share that with the company, and they would screen using our assay and compound library,” she said.

“At the point that they find hits, they then transfer those back to my team here and we do all the drug discovery and chemistry to identify a compound to get to the clinic,” Slusher added. “At that point, Eisai has first rights to license that compound.”

“The exciting thing about this collaboration is that it is truly a win/win,” she continued. “From my perspective, academia is excellent at identifying new targets of therapeutic interest, but our screening ability is limited due to the size and quality of the compound libraries available. Our collaboration with Eisai gives us access to a real pharma library. From the Eisai side, the collaboration provides access to new targets and novel therapeutic approaches.”

Lynn Kramer, Eisai’s chief clinical officer and president of its Neuroscience and General Medicine Product Creation Unit (PCU), concurs, saying the JHU tie-up and a similar partnership with University College London, offer Eisai “a novel target identification program that incorporates early drug development.”

“For us, it expands the novelty of our programs and it’s designed to utilize the best skills from each of the two partners to facilitate drug development and pass the compounds back and forth between our strengths and their strengths,” he said. The Brain Science Institute is a little unique from an academic perspective in that it has a number of people who have a lot of drug-development experience in pharmacokinetics, medicinal chemistry, toxicology and animal models,” skills that increasingly are available in top academic medical centers as they try to move up the research value chain.

Lynn Kramer, Eisai

Slusher’s team sorts through the most-promising research from a consolidated team of about 550 researchers to find target prospects for Eisai. His company therefore has access to the most concentrated group of neuroscience researchers outside of Boston, but with a single point of contact and first rights to option programs, Kramer said. JHU advances the programs selected by Eisai as far as the IND-ready stage, with pre-arranged terms for licensing fees, milestones and royalties on those assets it takes in-house.

“Eisai has the ability at multiple stages to come in and acquire the project,” Slusher said. “Depending upon when they in-license, the value derived by the university varies. If Eisai in-licenses the drugs early in the process, Johns Hopkins derives less value than if they in-license late in the process. It’s correlative to the amount of effort we’ve put in.”

About 18 months into the collaboration, JHU has developed assays for the two targets, Eisai has conducted high-throughput screening and is now sending first hits back the university for the next stages of work. “We probably have a year or two of chemistry and drug discovery to do before leads will be identified as options for the company,” Slusher noted. “This whole process probably likely will take three to five years.”

Kramer would not specify Eisai’s internal goals for producing a first clinical candidate from the partnership, other than to say “our goal is in the not-too-distant future – by that I don’t mean in a year. This takes a while.”

In general, Kramer thinks further collaboration with academia will be beneficial for his company. ADDC, founded in 2012, intends to serve as a clearinghouse for both academia and industry on research taking place within U.S. and international drug research programs. It doesn’t do tech-transfer work itself, but aims to make it easier for academics and biopharmaceutical companies to work together.

“You see from our two associations that they’re very flexible,” Kramer said. “We have gotten away from a lot of the intellectual property issues that used to plague the industry, because we’re really interested in molecule IP, not target IP, which used to lead to years of back and forth and impaired academic development. By getting over that hurdle, I view the academic groups as our ‘bread-and-butter’ for novel targets. It’s very hard in the industry to develop a novel, previously unidentified target – it’s too expensive and takes too long.”

It wasn’t just the academic world that biopharma companies were dealing with this past week, though. Read on for …

Teva/NuPathe: Teva expects to launch the migraine patch Zecuity (sumatriptan iontrophoretic transdermal system) in the first half of 2014 after acquiring the developer, NuPathe. The two announced the acquisition plans Jan. 21, with Teva’s $3.65 per share offer, approximately $144 million upfront, trumping rival bidder Endo’s proposal of $3.15 per share. Teva, which needs near-term revenue generators, gains a new product to add to its specialty central nervous system portfolio. FDA already approved the drug in January 2013, but NuPathe held out on commercializing it in order to find a partner. The drug is the only patch approved for migraine. The Israeli pharma’s offer represents a significant 58% premium over the $2.30 NuPathe shares closed at on Dec. 13, the last business day before Endo announced its intentions to buy the company. But it doesn’t offer much financial reward for longer-term investors. NuPathe’s stock opened at $3.80 about a year ago, on Jan. 18, the day after Zecuity was approved by FDA. NuPathe investors could receive additional payments, however, of up to $3.15 per share based on the future sales performance of Zecuity. Investors will receive $2.15 per share if net sales of the product are at least $100 million in any four consecutive calendar quarters on or prior to the ninth anniversary launch date. Another $1.00 per share in cash is payable if sales are at least $300 million in any four calendar quarters over the same time period. - Jessica Merrill

Par Pharmaceuticals/JHP Pharmaceuticals: Par Pharmaceutical is looking to expand the types of generic drugs it can offer beyond the solid, oral-dose pills it has been producing for years. The Woodcliff Lakes, N.J.-based company announced Jan. 21 that is has entered into an agreement to acquire privately held JHP Pharmaceuticals for $490 million in cash, a 2.5x return on investment for JHP’s main investor, private equity firm Warburg Pincus. Par has arranged for $505 million in debt financing to cover the deal and related costs. JHP and all of its assets, including a sterile manufacturing facility in Rochester, MI, will become a wholly owned subsidiary once the deal closes later this quarter. JHP was launched in 2007 when it acquired biologics contract manufacturing assets acquired from King Pharmaceuticals (now part of Pfizer) for $92 million. JHP performs contract manufacturing services worldwide for pharma and biotech customers, producing sterile injectables that require liquid, lyophilized and suspension formulations. The King deal also included branded hospital and acute-care drugs that JHP distributes. The main appeal of JHP to Par is the 14 specialty injectables that it already has on the market, as well as 30 additional candidates it has in its pipeline. Par is looking to expand into high-barrier-to-entry injectable generics as some of the major players in that space falter due to manufacturing problems. - Lisa LaMotta

Biocon/Advaxis: India’s Biocon and New Jersey biotech Advaxis announced an exclusive licensing pact Jan. 22 for co-development and commercialization of ADXS-HPV, a novel cancer immunotherapy for treatment of human papillomavirus (HPV)-associated cervical cancer in women. The deal covers India and key Asian emerging markets and gives Biocon access to Advaxis’ innovative and proprietary technology for the development of other novel therapeutics. Advaxis recently completed Phase II clinical trials in patients with recurrent cervical cancer in India, and the immunotherapy also is being evaluated in three clinical trials for HPV-associated cancer like recurrent advanced cervical cancer, head and neck cancer, and anal cancer. A spokesperson for Advaxis said the company will receive double-digit royalties on all sales of its immunotherapy product. The biotech will have exclusive rights to supply ADXS-HPV to Biocon, and Biocon will be required to purchase its requirements of ADXS-HPV exclusively from Advaxis at the specified contract price, which may be adjusted periodically. In addition, Advaxis will be entitled to a “six-figure” milestone payment if net sales of ADXS-HPV for the contract year following the initiation of clinical trials in India exceed certain specified thresholds. - Vikas Dandekar

McKesson/Celesio: In a “No Deal” that has turned into a deal, 10 days after saying its proposed acquisition of German drug wholesaler Celesio had fallen through, U.S. drug wholesaler McKesson has reached agreements that will allow it to complete the purchase after all. McKesson launched its bid to greatly expand its global reach through Celesio in October 2013. However, on Jan. 13 it announced that the deal could not be completed due to its failure to acquire 75% of outstanding Celesio shares through a tender offer. Then, in a Jan. 23 release, McKesson said it had reached an agreement with Franz Haniel & Cie. GmbH to acquire its entire holding of Celesio shares at €23.50 per share and another agreement with an affiliate of Elliott Management to acquire Celesio convertible bonds, which will be enough to give McKesson more than 75% ownership of Celesio on a fully diluted basis. The transactions are expected to close within 10 business days. McKesson plans to launch a voluntary tender offer to purchase shares from the remaining minority shareholders shortly after the close of the other transactions. The company said it will consolidate the financial results of Celesio during its fiscal fourth quarter ending March 31, and McKesson’s earnings will reflect its proportionate share of Celesio’s earnings. It expects to realize annual synergies of between $275 million to $325 million four years after the close of the deal. - Scott Steinke



Photo credits: Johns Hopkins University, Eisai Co. Ltd.

Financings Of The Fortnight Does Bollywood On A Budget

With IPOs still the twitter, er, talk of the town, the relative lack thereof the past couple weeks in our little corner of the world was noticeable. So forgive us if we were distracted from our IPO perusings by a particular firm that emerged from the roadshow scrum: top Indian film producer Eros International. Your FOTF correspondent has a soft spot for Indian cinema, having visited a couple local movie houses for the full Bollywood experience on a monthlong trip to India in late 2004. (We’ve ever since lobbied for chaat vendors to roam the aisles, sport stadium style, in American movie theaters.)

Eros went public this week, but only after taking a small haircut, so we figure a more budget-conscious approach to Bollywood spectacle is a better way to go.

FOTF is all about self-improvement, if you hadn’t noticed. We always make the healthy lifestyle choices: organic sustainable olives in the martini, strengthening those abs and buns to a bhangra beat, and regular salon visits.

Haircuts have been in the news for biotech, too, after a summer of letting it all hang out. Considered the highest profile of the current road-show warriors, Relypsa finally priced late last night after a couple of downgrades – or, if you prefer, a haircut a la Sweeney Todd. (For more, see our roundup below.) Antibody firm Xencor has amended terms, too, looking to raise $75 million by doubling its shares offered to 10.7 million and cutting its proposed price range in half. (As of this writing it hasn’t yet priced. 

Others have flat-out tabled their IPO efforts: Both gene therapy firm Celladon and diagnostic firm CardioDx postponed due to market conditions. That makes three four withdrawals or postponements in the past month. [UPDATE - On November 15 Xencor postponed its IPO.]

Companies that have made it out this year are also feeling a pinch. At the end of October, the biotech IPO class of 2013 was the best performing industry sector, up 47% as a group. (High tech, by comparison, was up 41%.) The past two weeks, however, those post-IPO biotech gains have slipped to 27% and now trail several other sectors. Still not too shabby. Who wouldn’t want a portfolio of stocks that are up 27% for the year? But the biotech slump, which actually started at the end of summer, is unmistakable.

Is it just a blip, a bump, or is it a big yellow flag? If we knew the answer, we wouldn’t be journalists, we’d be day traders working from home in our sweatpants, leaving after the final market bell at 1pm (FOTF is a West Coast shop all the way, dude) to do our Bollywood workout.

But here’s something to chew on. All those biotechs that went public this spring and summer? From right about now through December or so, their lock-ups are about to end. And a whole bunch of VCs who feel the hot breath of limited partners on their necks (yuck) will be looking to cash out. It won’t happen all at once, of course. Many venture investors can afford to cool their heels, as our colleague Stacy Lawrence reported in June.

But many can’t. And what might that do to stock prices? In an upcoming feature in Start-Up, Stacy dives into three recent biotech IPOs as well as the recent market dynamics. Two biotechs from the class of 2012 IPOs, Intercept Pharmaceuticals and Chimerix, recently saw their VCs sell directly into the public market, with mixed effects on the company’s shares. Will other VCs looking to sell to the public be staring down the barrel of a buyer’s market in the coming months? OrbiMed Advisors’ co-head of global equity Jonathan Silverstein doesn’t think so. “We’ve been approached on a number of IPOs by public investors who say they only have a 2% position and they want 5%. We are not necessarily interested in selling, but it’s nice to hear now.” OrbiMed's LPs don't seem too worried. That Silverstein quote comes from a recent story in “The Pink Sheet” DAILY about the firm’s new $735 million venture fund.

In the next START-UP, we break down the recent IPOs and acquisitions in OrbiMed’s portfolio to see what helped them sell that new fund. Until then, break it down old school style. Time for the Electric Slide.

At least it’s better than doing the Biotech Slump. If you prefer the Harlem Shake, well, there’s not much we can do for you. Get it out of your system, then crunk on over to the latest edition of…

Relypsa: The polymeric therapeutic specialists priced their initial public offering late Thursday, November 14, selling 6.85 million shares at $11 each for net proceeds of $67.4 million. It’s quite a comedown from the firm’s initial plans, which aimed for a top goal of $138 million back in October. The ambitious target was driven in large part by the amount of cash venture backers have sunk into the company:  more than $180 million over three financing rounds, according to Strategic Transactions. The firm spun out of Amgen in 2007 after that company bought Relypsa’s predecessor Ilypsa for its phosphate binder to treat hyperphosphatemia. That drug stalled soon after, but Relypsa carried on with former Ilypsa employees. 5AM Ventures and New Leaf Venture Partners led the $33 million Series A and were joined by the Sprout Group, Delphi Ventures, CMEA Ventures, and Mediphase Venture Partners. OrbiMed Advisors, which came in to lead the massive $70 million Series B round, is the largest shareholder going into the IPO, with a 44% stake. 5AM is next with 22%. Existing investors – including a limited partner of the venture investors – have said they could buy as much as $20 million worth of the IPO shares, according to the company’s final registration statement. Underwriters led by Morgan Stanley, BofA Merrill Lynch and Cowen have the option to sell 1.03 million additional shares. – A.L.

Synta Pharmaceuticals: The small molecule oncology developer raised $52 million in a sale of 14 million shares of common stock at $3.75 each as it moves toward a pivotal trial for its lead program, ganetespib in non-small cell lung cancer. It’s the second time around for the Massachusetts firm, whose first lead drug, elescomol, failed in Phase III trials for stage IV metastatic melanoma. The company learned in 2009 that more people died on an elesclomol/chemotherapy combination than on chemo alone. It went into restructuring mode and emerged with ganetespib, a heat shock protein 90 (hsp90) inhibitor. Its most advanced hsp90 competitor, retaspimycin from Infinity Pharmaceuticals, has been terminated, which leaves ganetespib breathing room but also raises questions whether the entire class is compromised. Synta told analysts earlier this month about adjustments to its Phase III trial, dubbed GALAXY-2, that will shift the patient enrollment away from Eastern Europe and boost the study population. The disclosures didn’t stop the slide in Synta’s share price, which has fallen nearly 50% since late October. The firm is also working on a small molecule drug conjugation platform to link an hsp90 inhibitor to a toxic payload. Underwriters led by Jefferies have the option to buy up to 2.1 million more shares. – A.L.

ArGEN-X: The Belgian antibody company has raised 5 million Euros ($6.8 million) to extend its Series B round to $44 million. The new infusion of cash comes from Flemish regional investment firm PMV. The cash will go toward ArGEN-X’s preclinical compound ARGX-113, being developed to treat autoimmune disease. The compound is an antibody fragment that aims to clear autoantibodies – the antibodies produced by a patient’s own immune system that go haywire and cause autoimmune disorders. The company’s technology used to create ARGX-113 is dubbed “ABDEG,” or antibodies that enhance IgG degradation. The firm also has two antibodies in the clinic, an anti-CD70 agent and an anti-cMET agent, both in Phase Ib. Both were discovered using a different platform, SIMPLE, based on the immune system of llamas.  The first tranche of ArGEN-X’s B round was co-led by OrbiMed Advisors and Seventure Partners and included existing investors Forbion Capital Partners, Credit Agricole Private Equity, LSP, BioGeneration Ventures, the Erasmus Biomedical Fund, Thuja Capital and VIB. Its Series A round brought in $19 million over two tranches. – A.L. 

Karyopharm Therapeutics: In the fortnight’s only other IPO, Karyopharm netted $101 million by selling 6.8 million shares at $16 a piece. Despite all the talk of haircuts and postponements elsewhere, the offer priced at the top end of its proposed range. The IPO cash matches what Karyopharm raised in two private rounds from institutional investors (Delphi Ventures) and wealthy individuals. Before IPO, Karyopharm was 46% 61% owned by Chione and Plio, two investment vehicles that share the same address on the island of Cyprus and are linked to Slava Smolokowski, a Polish energy baron who has also put his considerable fortune into Broadway. (His big hit was as a producer was Fela!, a hugely acclaimed Broadway show about the legendary Nigerian musician and political activist. According to Playbill, Smolokowski was educated as a musician and played in a rock band for some time.) The firm says it has discovered and developed small molecules to inhibit the nuclear export protein XPO1, which cancer cells amplify to promote the transmission of tumor suppression proteins from the nucleus to the cytoplasm. Getting those suppression proteins out of the nucleus gives a tumor cell a better chance to survive. By inhibiting XO1, Karyopharm believes it can trap the suppression proteins in the nucleus and let them do their job – trigger apoptosis. Karyopharm’s technology was brought out of Epix Pharmaceuticals, which was liquidated in the late ‘00s. Epix CEO Michael Kauffman and SVP of drug development Sharon Shacham are behind Karyopharm, and they licensed key IP from Epix. The company says half the IPO proceeds will help pay for Phase II/III trials for selinexor, its lead candidate, which Karyopharm says in its filing documents has already administered to more than 170 patients in three Phase I trials for various malignancies. Phase II/III could start in two cancer indications in the first half of 2014. – A.L.

Best of the Rest (Highlights of Other Financing Activity This Fortnight): Liquidia Technologies spun out ophthalmic-focused start-up Envisia Therapeutics, which received $25M in Series A financing and will use Liquidia’s PRINT technology to develop a new glaucoma treatment…less than a year after reverse merging to go public, Ocera Therapeutics completed a $28M PIPE to fund studies of its oral and IV hepatic encephalopathy candidate OCR002…to fund commercialization of Esbriet in Europe and various other development and regulatory activities surrounding the IPF drug, InterMune raised $84M in a FOPO…After reporting growth in the Q3 2013 net product sales for its sold marketed myelofibrosis product Jakafi, Incyte sold two $350M series of convertible senior notes…TVM Capital officially announced (as Start-Up reported in September) that it is no longer investing in IT,  but instead focusing on life sciences and health care. -- Amanda Micklus

Deals Of The Week Wonders Whether Heated Competition To Buy Ache Laboratorios Will Muddy The Brazilian Waters

Could a bidding war for Brazil’s privately held Ache Laboratorios do for Latin America what Abbott Laboratories’ gargantuan purchase of part of India’s Piramal Healthcare did for biopharma M&A in India?

Call it the “Piramal effect,” if you will. Abbott reset expectations among India’s domestic pharma world with its $3.72 billion purchase in 2010 of Piramal’s branded generics business. Brazil hasn’t yet seen the kind of blockbuster deal that would raise prices across the board; the highest value deal in that market to date is Sanofi’s $662 million buyout of Brazilian generics firm Medley Pharmaceuticals in 2009.

Sanofi got in early – staking its claim before big pharma’s buying spree in emerging markets generated significant deal inflation – but the deal hardly lifted the value of Brazilian companies across the board. That transaction was followed by smaller deals, such as Takeda’s $251.5 million (BRL 500 million) buyout of Brazilian branded generics specialist Multilab Indústria e Comércio de Produtos Farma about one year ago, which also included potential for up to BRL 40 million in earn-outs.

But, now comes word that could blow all previous Brazilian deals out of the water – Abbott and two of its big pharma competitors, Pfizer and Novartis, are preparing a second round of bids to buy Ache, Brazil’s leader in the sale of prescription drugs. The rumored price tag for Ache, fourth overall domestically in drug sales when over-the-counter products are included, ranges between $4 billion and $5 billion, a matter complicated by talk that at least one of three ownership families does not wish to sell. Ache’s public stance is that it is not up for acquisition.

Ache reported net earnings of $270 million for the 12 months ending Sept. 30, 2012. Nonetheless, a source familiar with the company told Deals of the Week that Ache remains an appealing investment for big pharma due to higher gross margins than its domestic competition, high top-line growth and strong relationships with distributors. In an emerging-markets competition where it is difficult to acquire worthy assets without overpaying, the three pharmas are facing a reality that a price tag above $5 billion – about 20 times EBITDA (earnings before interest, taxes, depreciation and amortization) – may be required just to get a foot in the door.

One pharma executive who asked not to be named told DOTW that his company is so discouraged by prices for assets in the primary emerging markets that it already is looking to next-generation possibilities such as Nigeria and Colombia.

As an article in The Atlantic notes, for overall business climate, Brazil recently has been viewed as the shining jewel of the so-called BRICS nations (Brazil, Russia, India, China, South Africa), with an average real gross domestic product growth rate of 4% between 2004 and 2010, including an eye-opening 7.5% in 2010. Add in low unemployment and a fairly industry-friendly regulatory environment, and Brazil perhaps was positioned to join China as the top emerging market for biopharma.

An early 2013 Business Monitor International report states that total pharmaceutical expenditure in Brazil in 2011 was more than $28.7 billion, and that total was expected to grow by 7.6% in local currency terms in 2012 (while declining in U.S. dollar spending due to exchange-rate fluctuations.) However, the biopharma opportunity in Brazil is being diminished by drug rebates, which are increasing both in total numbers and in size.

Meanwhile, GDP declined 0.9% in Brazil last year, combining with a 6% inflation rate to tarnish the South American giant’s emergence. Outside investment hoping to tap Brazil’s huge population, highlighted by a rising consumer class, faces what is known as “the Brazil cost” – a combination of high tariffs, poor infrastructure and red tape that increase the cost of doing business, the Atlantic reported.

But industry interest in tapping the Brazilian market cannot be denied. A review of Elsevier Business Intelligence’s Strategic Transactions database reveals six major equity investments in Brazilian biopharma holdings this decade. Beside last May’s Takeda/Multilab transaction, these include:

• Valeant Pharmaceuticals paying $28 million in May 2010 for Instituto Terapeutico Delta, a private branded generics and OTC company focused largely on dermatology;
• Pfizer anteing $240 million plus performance-based earn-outs to acquire 40% of generics firm Laboratorio Teuto Brasileiro in October 2010;
• Amgen ponying up $215 million in cash for Bergamo, a hospital-focused company with an emphasis on oncology, in April 2011;
• Merck investing an undisclosed amount in February 2012 to create and own a 51% stake in a Brazilian joint venture with Supera Farma Laboratorios, Cristalia Produtos Quimicos Farmaceuticos and Eurofarma Laboratorios; and
• UCB Group paying an undisclosed sum with potential for performance-based earn-outs to acquire 51% of specialty pharma Meizler Biopharma. The May 2012 deal included an option for UCB to buy out the remainder of the company.

While we await the outcome of the multi-company pursuit of Ache – GlaxoSmithKline reportedly dropped out of the bidding a while back – other biopharma deal-making was completed in the past week as we tally up …

AstraZeneca/AlphaCore: Following through on CEO Pascal Soriot’s promise to rebuild the company’s cardiovascular pipeline, AstraZeneca announced its third cardiovascular deal in two weeks. In the latest tie up, announced April 3, AstraZeneca’s biologics unit MedImmune acquired private biotech AlphaCore Pharma for an undisclosed sum. The big pharma gains ACP-501, a recombinant human lecithin-cholesterol acyltransferase (LCAT) enzyme that is believed to play a major role in removing cholesterol from the body and also may increase levels of high-density lipoprotein (HDL) cholesterol, better known as “good cholesterol.” A Phase I trial testing the drug met its primary safety and tolerability endpoint and also showed that ACP-501 raised HDL cholesterol in patients taking it. The cholesterol space is a high-risk, high-reward area of drug development, given the growing regulatory and commercial hurdles. But Soriot vowed AstraZeneca would embrace risk as a key to unlocking success in the drug-development process during an overview March 21 in which he unveiled his turnaround plan for the company. Cardiovascular disease is one of three core therapeutic areas the company has committed to. In March, the company signed two deals in the field: an option agreement with messenger RNA developer Moderna Therapeutics for up to 40 programs in exchange for $240 million upfront and a research partnership with Sweden’s Karolinska Institute. - Jessica Merrill

Bind Therapeutics/Pfizer: Nanotech company Bind Therapeutics has inked its second deal with a major player this year, signing a collaboration with Pfizer on April 3. Pfizer will pay Bind to combine its Accurins technology with small molecules provided by the big pharma. Pfizer will pay $50 million in upfront and near-term development expenses per molecule and Bind is eligible for $160 million in regulatory and commercial milestones for each product that reaches the market. Bind did not retain any commercialization rights, but will receive tiered royalties on worldwide sales. The company would not reveal the number or kinds of molecules covered by the deal or the therapeutic area of focus, but did say the agreement covers more than one molecule. The Accurins technology has been explored in the areas of oncology, inflammatory diseases like arthritis and cardiovascular indications. In January, Bind announced a similarly sized agreement with Amgen to develop and commercialize kinase inhibitor nanomedicines to treat solid tumors. - Lisa LaMotta

Ra Pharma/Merck: Less than a year after exiting stealth mode, Ra Pharmaceuticals has landed its first partnership, aligning with Merck to help the pharma discover and develop drugs for difficult-to-hit protein targets. Under the agreement announced April 1, Ra will use its proprietary Extreme Diversity platform to find and develop cyclomimetic candidates that can address intracellular protein-protein reactions in multiple undisclosed therapeutic areas. Ra will receive an undisclosed upfront payment and research funding; discovery, development, regulatory and commercialization milestones could bring its full remuneration to $200 million. While the deal stemmed from early conversations between Ra executives and Reid Leonard, head of Merck Research Ventures Fund, it does not include an equity component for the pharma, Ra President and CEO Doug Treco said. It also includes no risk-sharing, such as a co-promotion option down the road. Ra is developing what it terms a new class of drugs, peptide-like molecules offering the diversity and specificity of antibodies along with the attributes of small molecules, such as oral bioavailability. Cyclomimetics, the cyclic polymer drug candidates produced with Ra’s technology, are characterized by their cyclic structure and backbone as well as side-chain modifications that can provide beneficial properties not offered by natural peptides, the company says. It claims that Ra’s platform produces molecules that are highly specific and stable, offering improved cell permeability and potential for increased bioavailability as well as longer half-lives. - Joseph Haas

Astellas/Ambrx: In its latest tie-up with a major pharmaceutical player, Ambrx announced April 5 that it will collaborate with Japanese pharma Astellas Pharma on a series of antibody-drug conjugates (ADCs) in the oncology setting. Astellas will pay the biotech $15 million upfront, as well as $285 million in potential development, regulatory and sales-based milestones to discover and develop an undisclosed number of molecules that use its site-specific ADC technology. Last June, Ambrx inked a deal with almost identical financials with Merck. While details of the targets the companies intended to focus on were not disclosed, it was revealed that they would focus on areas “beyond oncology.” Ambrx also has tie-ups with Eli Lilly and Bristol-Myers Squibb. Previously it had arrangements with Wyeth, Roche and Merck Serono. ADC technology, which allows drugs to be targeted to a specific site carrying a therapeutic payload, have become a hot space since Seattle Genetics got approval of its ADC lymphoma drug Adcetris (brentuximab vedotin) in August 2011. - L.L.

Agios/Foundation Medicine: Agios Pharmaceuticals and Foundation Medicine signed a pact April 4 to use the latter’s clinical assay, FoundationOne, to create diagnostics which could identify ideal patients for Agios’ compounds aimed at cancer metabolism. No financial terms were disclosed. The diagnostic-discovery collaboration will focus on Agios candidates intended to inhibit tumors that carry mutations in the IDH1 and IDH2 metabolic enzymes. The work will seek to identify tumor genomic alterations that would be most likely to respond to Agios’ candidates, and to potentially develop and commercialize companion diagnostics for Agios compounds. Foundation, which developed the FoundationOne genome analysis profiling system for personalized cancer treatment decision-making, raised a $42.5 million Series B financing in 2012 with a syndicate of venture capital and corporate venture outfits. The round was topped off with an additional $13.5 million this past January from individual investors including Bill Gates, Yuri Millner and new board member Evan Jones. Agios, partnered since 2010 with Celgene on cancer metabolism R&D efforts, raised a $78 million Series C round in 2011 and announced plans to branch out therapeutically into rare genetic disorders. - J.A.H.

Novartis/ImmunoGen: ImmunoGen on April 4 updated the status of its 2010 licensing agreement with Novartis to apply the biotech’s Targeted Antibody Payload (TAP) technology platform to create cancer-fighting antibodies for undisclosed targets chosen by the multinational pharma. Under an amendment to the agreement, Novartis has exclusively licensed one compound against a still-undisclosed target, while taking a non-exclusive license to a second compound which can be converted later to an exclusive license. ImmunoGen will receive $4.5 million upfront under the amendment and could earn between $200 million and $238 million in milestones pegged to the two compounds, plus potential sales royalties. Of the upfront money, $1 million is an option exercise fee, while the remaining $3.5 million, which could be credited against future milestone payments, will be paid if Novartis terminates development of one or both compounds. In a same-day note, Cowen & Company analyst Simos Simeonidis called the developments “an incremental positive for ImmunoGen” that helps to validate the TAP platform. In October 2010, Novartis paid $45 million upfront for the license, intended to help it create antibody-drug conjugate (ADC) therapeutics for cancer. The deal offered the potential for up to $200.5 million in milestones for each target leading to development of an ADC, as well as sales royalties on any products reaching market. - J.A.H.

ArQule/Daiichi Sankyo: In our “No-Deal” of the week, collaborators ArQule and Daiichi Sankyo have decided to terminate an early-stage collaboration around Phase I oncology compound ARQ-092. The news comes just months after a Phase III setback of the companies’ later-stage oncology compound tivantinib, which the two companies will continue developing together. Daiichi opted to license ARQ-092 in November 2011 and paid $10 million upfront at the time, as well as Phase I development expenses. ArQule stood to gain $255 million in milestone payments and the deal included development of multiple compounds; the program now has been returned to the Woburn, Mass.-based company. Meanwhile, tivantinib failed to show overall survival in a late-stage trial in non-small cell lung cancer. The drug’s development focus now has been shifted to liver cancer. The partners signed their initial agreement for tivantinib (known then as ARQ-197) in November 2008. Daiichi agreed to pay $60 million upfront, as well as $560 million in milestones to license the c-Met receptor tyrosine kinase inhibitor. - L.L.

Photo Credit: Muddy Amazonia

Deals Of The Week Jump Starts The Summer Reading List

High on the New York Times List of Bestsellers (in the hardcover advice & miscellaneous category) this spring has been the book “Reverse Innovation: Create Far From Home, Win Everywhere.”

It’s by two well-known Dartmouth business school professors, Vijay Govindarajan and Chris Trimble, and tracks how innovation originating in emerging markets is finding its way into the broader global business world. Since the topic’s increasingly relevant to pharma – although the book isn’t specific to healthcare -- and since the book arrived on my desk this morning, I’m giving it priority status for my Memorial Day weekend reading. Besides, it ties in nicely with one of the themes on my mind since attending the US-India Chamber Of Commerce Healthcare Summit on May 11 in Cambridge, MA.

That meeting was focused on biopharma, and started with a talk by Elias Zerhouni, president of Sanofi's Global R&D, on innovation and India. Billed as the keynote, he had to cancel plans to attend at the last minute and instead participated from Paris, via a near-lifelike videocast.  “I was struck several years ago by the extraordinary ability of the healthcare system in India to adopt new technologies to provide high quality care at low cost…so I know there is the fundamental power and energy to create in India,” he started off.

Sanofi, of course, bought India’s Shantha Biotechnics vaccines business, where it is working to produce vaccines at low cost for the global market.  The company also has a partnership with Glenmark on developing a monoclonal antibody for inflammatory diseases. “It is possible to see that India has capability of addressing very fundamental obstacles that exist in R&D,” Zerhouni said. "…No one, no country, no organization, has all the needs to master the complexity of biology and to have access patient population and patient samples that would give us profound insights into disease. The role of India is to innovate, not just the delivery of health care, which it has been excellent at doing, not just be less costly, what makes the difference is creativity.”

Zerhouni wasn’t specific but others at the one-day conference gave examples. The Boston Consulting Group has studied India’s capacity for innovation in healthcare, which BCG partner Bart Janssens, who is based in Mumbai, called India’s “magic beans.” According to BCG, these are information technology and computational research, which could help direct pharma’s growing appetite for big datasets (biology is becoming an information science, one speaker noted). Also on the list: nanotechnology and, to no one’s surprise, process efficiencies, a hot topic, particularly in the area of translational research .

And much of the discussion centered around innovative approaches to clinical trials, where India and U.S. academic institutions and MNCs are working aggressively on projects that are sure to change the nature of the way clinical trials are done globally -- but may not be moving fast enough, as colleague Josh Berlin points out in his excellent take on the summit. 

In health care, much of the reverse innovation activity has been on the device side, which Govindarajan and Trimble, along with GE CEO Jeff Immelt, wrote about in the Harvard Business Review in October 2009. That article received a lot of attention and gave some circles in pharma food for thought, although pharma seems to be a step behind.

Nevertheless, as I grab the book and run out the door, with more say on this post-holiday, it seems worth pointing out a mainstay of pharma's efforts to capture innovation, namely through deal making. And this week's activities boil down to....

 

 

IMI/GSK/AZ/Sanofi/Basilea/Janssen Pharmaceuticals: In an effort to address concerns about the increasing resistance of bacteria to the currently available antibiotics, a European initiative launched in November announced May 24 that it is forming a public-private collaboration coined NewDrugs4BadBugs to fund the development of new antibiotics. The Innovative Medicines Initiative, part of the EuropeanCommission’s Action Plan against the Rising Threat From Antimicrobial Resistance, is providing €119 million ($149.6 million) in funding. Private companies – GlaxoSmithKline, Sanofi, AstraZeneca, Janssen, and Basilea – will contribute a combined €114.7 million ($144.1 million). Perhaps more important, however, is the companies’ commitment to share data.  The group is forming a committee, which will build a website that can facilitate the sharing of this information, including specifics on failed targets and clinical trial data. The focus of the overall program will be to develop better networks of researchers, create more fluid trial designs, and provide incentives for companies to participate. The collaboration in the EU happens to parallel proposed legislation in the U.S. that is meant to increase the exclusivity period for antibiotics developed to combat certain types of multi-drug resistant bacteria. Both the U.S. and EU are trying to increase the number of antibiotics under development as more and more people continue to die from infections that were not previously fatal. --Lisa LaMotta

Labcorp/XDx:  With Labcorp., molecular diagnostics developer XDx has found a partner to enable it to resume development of a diagnostic to predict when lupus flares may occur. Lupus has always been in XDx’s sights.  But its early discovery efforts were not sufficient to winnow down potential candidate markers to a set ripe for clinical validation. It also had tabled a clinical study in 2010, SAGE, 600 patients short of its original goal of 1000, because it had to direct resources toward its lead product, the heart transplant diagnostic, AlloMap. 

However, through SAGE, XDx obtained an exotic lupus-oriented set of samples: blood and information on clinical parameters collected monthly from patients. “We knew a certain percentage of these patients would have a significant flare event,” says COO Mitchell Nelles. By drawing blood monthly, the company would have samples before and after flare events, allowing XDx to look for biomarker signatures which could then be used to predict those flares. Now, Labcorp has shown interest in this diagnostics discovery approach. In a deal announced May 23, the companies are collaborating to develop a test to predict lupus flares, to which Labcorp will have full US commercial rights.

A flare predictor test could potentially tell a physician when to intervene with a drug.  Even more important, if it were to have a high negative predictive value, the test could tell a physician when to reduce the use of steroids and minimize side effects or generally adjust downward the level of medication.  The aim would be “not just preventing the flare, it’s not having to give more medicine than a patient needs,” Nelles says.  “We’ve seen that in the transplant field and also autoimmunity. The opportunities to reduce medication to the lowest level possible can have a profound clinical impact.” The test would likely contain a combination of gene expression and protein biomarkers. XDx retains the right to work with other potential pharma/biotech partners to develop a companion diagnostic to predict drug response and otherwise manage therapy.  It had previously worked with Bristol-Myers as part of BMS’s clinical plan to develop its arthritis drug Orencia in lupus, an effort which ultimately failed due to the drug's lack of efficacy in Phase III. – Mark Ratner

GSK/Auxilium: GlaxoSmithKline and Auxilium Pharmaceuticals announced May 21 that they have teamed up on the marketing of the Malvern, Pa-based biotech’s testosterone gel, Testim. The co-promotion agreement is set to begin early in the third quarter and is slated to last until September 2015. That's when generics start to infiltrate the $1.4 billion testosterone gel market, which is currently all branded. In the meantime, this promotion will help Auxilium maximize its product before competition arrives. The British pharma will be responsible for increasing awareness of U.S. physicians, while Auxilium will still manufacture the product. GSK will receive revenues on the drug if it exceeds an undisclosed baseline sales figure. Testim, which is meant to treat conditions related to low testosterone levels, generated sales of $208 million in 2011 and accounted for about 80% of Auxilium’s revenues. Just a day after announcing the deal, Auxilium filed suit against Watson Pharmaceuticals in the U.S. District Court of N.J. claiming the generic drug maker’s plan to launch a generic of Testim is in violation of several patents. Other testosterone gel manufacturers like Par Pharmaceuticals and Abbott have reached agreements with Watson to keep a low-cost generic off the market until at least August 2015 – it appears Auxilium is trying to get the most out of its branded product before the competition arrives. --LL

DaVita Inc./HealthCare Partners:  DaVita, which manages more than 1,800 dialysis centers across the U.S serving 145,000 patients, is buying one of California’s largest independent physician associations, HealthCare Partners, for $4.4 billion. HCP generated $2.4 billion in revenues in 2011 from services its 700 physicians provide to 667,000 people in Southern California, Central Florida and Nevada. The deal is valued at about 8.4x HCP’s 2011 EBITDA. That’s big news in the provider services and dialysis worlds, but what does it mean for pharma?

Once integrated into DaVita, HCP will operate as a separate subsidiary and its current management will continue to run daily operations. DaVita isn’t likely to get much of a bump in its presence in the dialysis market. Rather, it sees the addition of HCP as a way to build on an integrated care approach, based on HCP’s ongoing efforts to work closely with payers and consumers. While the companies were not specific about how HCP interacts with the groups it services, they noted in the analysts’ call that in certain disease categories — chronic obstructive pulmonary disease, for example — more integrated care with physicians and patients working closely together resulted in shorter hospital stays and no increase in hospital readmissions. In addition, HCP collects claims and administrative data, which, combined with clinical data, allows it to develop clinical programs geared to specific patient populations. 

This strategy, while not directly impacting pharma in the near-term, reflects a move on the part of providers and payers to seek what is increasingly known as “a continuum of care” for patients.  Pharmaceutical companies have generally taken a wait-and-see approach to such efforts, before responding with new product portfolios and commercial models that address the shifting needs of their constituents. But the trend is on their minds and some, particularly those involved in diabetes, such as Sanofi, are forging ahead with continuum of care strategies; Endo Health Solutions, which recently changed its name from Endo Pharmaceuticals to better reflect the diversity and focus of its pipeline, is taking a continuum of care approach to the urology and oncology sub-segments.—LL

 

Takeda/Multilab Industria: Japanese firm Takeda Pharmaceutical claims a leading position in Brazil’s pharmaceutical space with the May 25 purchase of Multilab Industria e Comercio de Produtos Farmaceuticos, which manufactures branded generics and OTCs. The transaction, worth an upfront payment of BRL 500 million ($245.5 million), plus up to BRL 40 million, makes Osaka-based Takeda one of Brazil’s top 10 pharma players and brings it the country’s top-selling OTC cold and flu remedy, Multigrip. Takeda expects to close the deal by September.

Through its 2011 acquisition of Swiss firm Nycomed, Takeda has an OTC presence in Brazil, including the analgesic brand Neosaldina, and Rio Grande do Sul-based Multilab is expected to complement that business via its established distribution network, especially in emerging parts of Brazil. Takeda recently projected sales in Latin America, including Brazil, will reach JPY 52 billion  ($651.9 million) in 2012, and the firm does not plan to revise this year’s earnings guidance following the deal. Multilab generated revenue of about $68.8 million in 2011.--Dan Schiff

Valeant/Swiss Herbal Remedies Ltd.: Aggressive pharma acquirer Valeant Pharmaceuticals purchases assets from Canadian natural health product firm Swiss Herbal Remedies, the latest consumer health pickup for Montreal-based Valeant. In a May 24 release, Valeant said Swiss Herbal is well-known in Canada and will complement the Cold-FX NHP brand Valeant acquired along with Afexa Life Sciences in 2011. Valeant paid less than 1x sales for the assets from Richmond Hill, Ontario-based Swiss Herbal; the assets generated 2011 net revenue of CA $28 million (U.S. $27.4 million).—DS

Suneva/Spear:  Fallout from Valeant's hectic deal-making pace continued May 24 as the anti-wrinkle product Refissa (tretinoin 0.5%) moved to a new home for the second time in less than a year. In December 2011, following Valeant’s buyouts of Sanofi’s Dermik Laboratories and Janssen’s Ortho Dermatologics, the Federal Trade Commission required the specialty pharma todivest three dermatology products from its portfolio – Refissa, acne medication BenzaClin and topical flurorouracil cream 5FU. Valeant sold Refissa, indicated for fine facial lines, hyperpigmentation and tactile roughness, to Spear Pharmaceuticals, and the other two products to Mylan Pharmaceuticals. For undisclosed financial terms, Spear has sold worldwide rights to Refissa and a generic version developed and launched by Spear to privately held Suneva. Suneva CEO Nick Teti said his firm is entering the prescription topical aesthetic space, which he called a potential $100 million market opportunity. The addition will enable its marketing force to offer aesthetic physicians “a comprehensive anti-aging solution,” also include Suneva’s proprietary ReGenica skincare products and its injectable filler Artefill. Suneva called the deal transformational and said Refissa will be a key driver of sales growth over the next five years.—Joseph Haas

image from flickr user mySAPL used under creative commons

DotW: Wishful Thinking

The biotech M&A storm is coming. Really. So sayeth the good attorneys at the UK patent firm Marks & Clerk, based on survey data of 381 pharmaceutical execs who predict industry consolidation as various players attempt to hurdle the looming patent cliff.

Added to IN VIVO Blog’s To-Do List: Call Marks & Clerk to determine where to purchase the rose-colored glasses apparently so in fashion.

We admire the glass-half-full sentimentality. It’s cheaper than Prozac or Paxil (though purchasing either would help sales at certain pharmas). We’re just a bit skeptical that the patent cliff will translate into a big-pharma buying spree of innovative biotechs. Here's why: For starters, the big acquisitions of 2010 have mainly been about diversification, marketed products, generics, emerging markets or some combination thereof. Innovative pipeline material? Not so much. Big pharmas want revenue.

According to Elsevier’s Strategic Transactions database, the top deals of 2010 have been Merck’s acquisition of Millipore, Teva’s purchase of ratiopharma, Astellas’ flight into oncology with OSI, and Charles River’s take-out of WuXi. Of these, only the Astellas/OSI transaction fits the patent-cliff theory, in which a drug maker pays top dollar for a biotech to replace revenues lost to looming--or current--generic competition. And companies like OSI, with money-making products far from patent expiry, remain a relative rarity, which as we’ve pointed out in our reporting, is one reason that biotech’s price tag climbed as high as it did.

We’ve said it before. On the private side, companies can’t rely on the stalking horse of IPOs to force pharmas into acquisitions; M&A--when it happens-- will likely to be in the guise of earn-out heavy deals, with eye-popping returns (think >5X when all the milestones are factored in) for the future. (Want data? See here and here.)

Other forces are lined up to stifle the oft-predicted M&A storm. On the public side, many smaller biotechs are still struggling to attract investor love. (Will ASCO help?) For European companies, the debt crisis isn't going to help. With biotechs’ stock prices trending down, there’s simply not much pressure for Big Pharm to get involved in pricy bidding wars. Moreover, big pharma buyers are burdened with infrastructure and more early stage programs than they can afford to develop, suggesting that when they do bring programs in it will be via alliances not acquisitions.

Does IN VIVO Blog think there will be some M&A? Absolutely--and if there isn't, this column will get awfully lonely. But are we talking Perfect Storm? Boom Times? That smacks of wishful thinking. Any doubt? Take a look at this week’s round-up of deals, which emphasize R&D on the cheap, EMs, and branded generics.

Astellas/OSI: Japanese drug maker Astellas' pursuit of OSI Pharmaceuticals was rewarded on May 17, 2010 with a $4 billion merger agreement supported by both companies' boards. At $57.50 per share, the deal cost $500 million more than the original hostile bid that Astellas launched in late February, and it will consume roughly half of the drugmaker's available cash. It seems no other white-knight bid emerged to counter Astellas' hostile offer, which turned semi-friendly at the end of March. Astellas, meanwhile, had made OSI the linchpin of its strategy to become a global oncology player. To walk away empty-handed would have raised serious questions about Astellas management, especially in the wake of its previous hostile bid, an unsuccessful run at CV Therapeutics. The newly sweetened price is a 55% premium to OSI's stock price on February 26, 2010, the day before the Japanese firm publicly disclosed its $52-a-share hostile offer for the biotech. The price is also 50 cents more than the informal offer in the $55-to-$57 range that Astellas originally suggested in 2009, according to SEC filings. With its ability to do further big deals limited for now, Astellas must extract full value from both Tarceva and OSI's earlier stage molecules. The key will be retaining and integrating OSI's management team into Astellas' U.S. operations.—Ellen Foster Licking

Abbott/Piramal: Rumors have been circulating for weeks that Piramal, one of India's leading biopharma players, was up for sale. There was quite a bit of truth to the rumor mill, except the buyer wasn't one of the usual suspects: GlaxoSmithKline, Sanofi-Aventis, or Pfizer. The ultimate winner was Abbott, which also made waves with last week's collaboration with Zydus Cadila and the creation of its established product unit. Abbott says the deal gives it the numero uno position (in Hindi, that's nambara ēka) with 7% market share in the Indian pharmaceutical market. It doesn't come cheap. Abbott will pay a total of $3.7 billion for Piramal, but not all is upfront cash. Piramal gets an initial payment of $2.12 billion and then $400 million annually for the next four years starting in 2011. (A hedge, perhaps, to mitigate the snafus Daiichi Sankyo has encountered with Ranbaxy?) Structured this way, Abbott says the all-cash transaction will not impact its ongoing earnings per share guidance. The strategy behind Abbott's deal is obvious and one familiar to IN VIVO Blog readers. Indeed, it can be summed up in three catch phrases: diversification, branded generics, and emerging markets. --EFL

Pfizer/Washington University: The R&D belt continues to tighten, and nervous companies ask more loudly how best to cheaply and efficiently identify innovative medicines? What about academia? What about new uses for existing medicines? Why not combine the two? This week Pfizer announced a five-year collaboration worth $22.5 million with Washington University in St. Louis in what is essentially a re-profiling experiment of 500 compounds originated at Pfizer. Don Frail, the chief scientific officer of Pfizer’s Indications Discovery Unit and the brains behind the deal, said the partnership could result in the university participating in clinical trials and holding downstream financial rights to drug candidates. Pfizer, meanwhile, can tap the thinking of a different group of researchers, and it won't spend an additional dime (beyond the $22.5 million) developing idle programs. Indeed, just one moderately successful product from the tie-up could cover Pfizer’s investment many times over. Wash U researchers will submit proposals for studies of compounds to a joint advisory committee. Pfizer researchers will work with Wash U scientists, with the university owning rights to its discoveries and the ability to negotiate terms for their development and commercialization.--Joseph Haas and EFL

Quintiles/Kaiser Permanente: It's not the kind of deal we normally cover, but we were intrigued by a collaboration between a major CRO and a leading insurer/health provider. With a dearth of details in the press release, IN VIVO Blog is still intrigued. We thought perhaps this deal augured a future wave of partnerships, in which pharmaceutical companies—or their CROs—ally with groups to develop outcomes-based data to support the commercial prospects of drugs under development. While this may be one of the longer term outcomes of the project, for now the emphasis is on enhancing the quality and productivity of clinical research. As such, Kaiser’s Southern California Permanente Medical Group becomes Quintiles’ fourth global prime clinical research site, joining the University of Pretoria in South Africa, Queen’s Mary College in the UK, and Washington D.C.'s Washington Hospital. Adam Chasse, Quintiles’ head of global prime sites, says the interests of both groups are mutually aligned since SCPMG wants to expand its clinical research efforts while the CRO hopes to tap the physician expertise within Kaiser--as well as its diverse patient base.--JH and EFL

Sanofi/Nepentes: Once again Sanofi-Aventis is expanding its consumer products business with a $130 million offer for the Polish drug, dietary supplement, and cosmetics firm, Nepentes Group. Sanofi announced May 19 it would pay approximately $8-a-share to Nepentes’ main shareholders and $8.60-a-share to minority shareholders in order to establish a presence in Europe’s fifth leading consumer health care product market. According to “The Tan Sheet," Sanofi believes it can boost Nepentes’ growth by extending distribution of its products, which include Selsun Blue, Melisana Klosterfrau supplements, and the Marimer line of nasal sprays, to additional markets. The Nepentes transaction marks the seventh consumer deal for Sanofi since CEO Chris Viehbacher outlined plans in February 2009 to double the drug maker’s OTC offerings in five years, primarily through bolt-on acquisitions. The most costly so far is Sanofi’s acquisition of Chattem for $1.9 billion. It’s all part of Sanofi’s larger strategy to diversify into arenas less risky than branded pharmaceuticals while simultaneously tapping those necessary "pharmemerging" markets.--Malcolm Spicer

Image courtesy of flickrer furiousgeorge81.

Abbott Charges Into India

Rumors have been circulating for weeks that Piramal, one of India's leading biopharma players, was up for sale. And just as staunchly, management tried to quell the gossip (as recently as yesterday--if you are keeping track.)

Turns out there was quite a bit of truth to the rumorville. Only the buyer wasn't one of the usual suspects. Both GlaxoSmithKline and Sanofi-Aventis' names have been twinned with Piramal in part because of their aggressive moves into both emerging markets and branded generics.

The ultimate winner of Piramal? Abbott, which has been making its own waves in recent weeks through last week's collaboration with Zydus Cadila and the creation of its established product unit.

Abbott claims the deal gives it the numero uno position (in Hindi, that's नंबर एक or nambara ēka) with 7% market share in the Indian pharmaceutical market, but those bragging rights are costing it a pretty penny. Abbott will pay a total of $3.7 billion dollars for Piramal. Interestingly, not all of it is upfront cash--Piramal gets an upfront payment of $2.12 billion and then $400 million annually for the next four years starting in 2011. (A hedge perhaps to mitigate the snafus Daiichi Sankyo has encountered with Ranbaxy?)

Structured this way, Abbott says the transaction, which is still subject to Piramal shareholder approval, will not impact its ongoing earnings per share guidance in 2010. The diversified health care company plans to fund the deal with cash on the balance sheet.

The strategy behind Abbott's deal is obvious and one familiar to IN VIVO Blog readers. Indeed, it can be summed up in three catch phrases: diversification, branded generics, emerging markets. Abbott's CEO and chairman Miles White decided to elaborate however, stating in the press release announcing the news:

This strategic action will advance Abbott into the leading market position in India, one of the world's most attractive and rapidly growing markets. Our strong position in branded generics and growing presence in emerging markets is part of our ongoing diversified pharmaceutical strategy, complementing our market-leading proprietary pharmaceutical offerings and pipeline in developed markets. (Highlights courtesy of IN VIVO Blog.)

We'll have more on the deal later in "The Pink Sheet" DAILY and PharmAsia News. But for now we'll go out on a limb and say that one of the immediate impacts of the deal has got to be the increased liklihood of getting an authentic curry in Abbott Park, Illinois.

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

DotW: You Can Get Anything You Want At IN VIVO Blog

This post is called Deals of the Week, and it's about deals, and the week, but Deals of the Week is not the name of the blog, that's just the name of the post. And that's why I called the post Deals of the Week.

You can get anything you want at IN VIVO Blog.
You can get anything you want at IN VIVO Blog.
Log right in, it's a click away.
Just a finger tap. You don't have to pay.
You can get anything you want at IN VIVO Blog.

Now it all started two Thanksgivings ago, two years ago on Thanksgiving, when Chris Morrison and I started writin' a blog about deals, but not every day, just once a week. And writin' about deals once a week, you know it's a lot of work. (Hint. Hint.) And there's a lot of garbage you gotta sift through, but we decided it would be a friendly gesture on behalf of readers.

So we trolled around the Internet with our shovels and rakes and other implements of destruction (aka Elsevier Business Intelligence's Strategic Transactions database) looking for deals to analyze. But then a big bad editor (also known as Officer Roger) said why are you doin' that? We are closed on Thanksgiving.

And we had never heard of a blog closed on Thanksgiving before (we don't get out much) so with tears in our eyes we drove off into the sunset looking for another place to dump our garbage -- I mean our deals.

We didn't find one. So we wrote our post anyway, went back and had a Thanksgiving Day that couldn't be beat, went to sleep, and didn't get up until the next morning when we got a call from Officer Roger...

And it's been a recurring feature here at IVB ever since. (Fortunately, not another case of American blind justice since we always arrive at the truth of the matter and it doesn't even require 27 eight-by-ten color glossy pictures with circles and arrows and a paragraph on the back of each one.)

In honor of the day, we hope you consider joining the IN VIVO Blog Movement. All you've got to do is walk into the office wherever you are, just walk in and say ,"You can get anything you want at IN VIVO Blog." And walk out.

You know if one person, just one person does it, they might think he's really sick and they won't take him... And can you, can you imagine fifty people a day, I said fifty people a day (okay, we'd really like 1000) walking in, quoting a line from IN VIVO Blog and walking out?

And friends, they might think its a movement. And that's what it is, the IN VIVO Blog Movement.

Remember Deals of the Week? (This is a post about Deals of the Week.) Without further ado, we bring you this week's installment inspired by Arlo Guthrie. Feel free to sing along in four-part harmony. With feeling. 'Cuz you can get anything you want at the IN VIVO Blog. (Excepting Roger.)

Clovis Oncology/Clavis Pharma: What's a letter of the alphabet between friends? Pat Mahaffy and his former Pharmionites at Clovis have started to spend the huge $145 million A round they announced in May. Their first deal is for intravenous CP-4126, what they hope to be an improved version of Eli Lilly's Gemzar, under development at Norwegian firm Clavis.

Clovis is paying $15 million upfront and up to $365 million in milestones to take over clinical trials in pancreatic cancer and other indications and develop a companion diagnostic. Clovis gets rights in the Americas and Europe and will double enrollment to 250 patients in a recently launched Phase 2 for newly-diagnosed advanced pancreatic cancer. Clavis's proprietary platform adds a lipid vector to existing drugs that, if early data bears out, will boost efficacy without adding safety concerns.

For CP-4126, the proposition is to boost uptake of gemcitabine in patients who fare poorly on the parent drug because they have low levels of a nucleoside transporter protein known as hENT1 required for entry into tumor cells. The lipid vector allows gemcitabine to bypass hENT1 and find another way into the cell, Clavis officials say. No doubt careful attention will be paid to the low-hENT1 population in Phase II studies. Pay careful attention, too, to Clovis, to see how far $145 million can take a specialty-focused cancer startup these days. Let's see, $15 million upfront, plus clinical trial costs (including the diagnostic development), plus milestones to Clavis, plus operations in three locations (Boulder, Colo., San Francisco, London), plus other deals the firm no doubt wants to do...it adds up fast. With its mid-recession A round, Clovis showed it could buck economic trends. Will we see a B round soon? As Clavis CEO Geir Christian Melen told "The Pink Sheet" DAILY this week, Clovis's Mahaffy has "strong shareholders with deep pockets." -- Alex Lash

Novartis/Incyte: To whet your appetite for the multi-layered yumminess of turducken, official Thanksgiving Beast of the IN VIVO Blog, check out the deal Incyte announced this week.
It's not just two drugs wrapped into one deal, it's two kinds of upfront cash! Novartis is paying a $150 million signing fee plus an immediate $60 million milestone for rights to two compounds, an oral JAK1/JAK2 inhibitor in Phase III for myelofibrosis, and an oral cMET inhibitor about to enter Phase 1 for multiple cancers. The $60 million is a reward for INCB18424, the JAK inhibitor, having started Phase 3 in July of this year. Novartis gets ex-U.S. marketing rights to the compound in all hematology-oncology indications and will pay tiered, double-digit royalties. Incyte keeps rights in the States as well as rights in the psoriasis indication. For the cMET inhibitor, INCB28060, Novartis takes over worldwide development after Phase 1 and also has worldwide commercial rights with royalties back to Incyte. Incyte also keeps a co-development and co-promotion option on the compound. Total biobucks for the deal could top $1 billion, though with the cMET inhibitor so early in development, chances of Novartis paying every last dollar are roughly the same as seeing a turducken in the wild. -- Alex Lash

Jubilant/University of Alabama/Southern Research Institute: These days drug makers are looking to trim their overly fat infrastructure even as they bulk up on much needed pipeline products. How best to do this while maintaining a lean budget? One increasingly popular approach is to leverage the lower cost innovation available in India and China. (FIPNets!) Another is to take advantage of the knowledge within the world's ivory towers--in other words, deals with academia. In an interesting twist on the virtual R&D model, Jubilant Organosys, one of the go-to India companies for major pharma players, is seeking out innovation by forging ties with the University of Alabama and Southern Research Institute to develop new meds in the oncology, metabolic disease, and infectious disease space. The press release calls it "a unique US-India arbitraged and leveraged partnership." So based on the trickle down economics theory of deal affordability, transactions with emerging-market players provide pharmas more generous terms than with US or European biotechs, but partnerships with academia are an even better bargain. (What about deals with Indian or Chinese universities?) This is the second academic partnership Jubilant has signed this month--it inked an agreement with Duke University on Nov.10 to translate Duke discoveries into new medicines. Specific financial details of the most recent tie-up with UAB/SRI weren't disclosed. But the three groups are definitely working together to identify and develop the most promising targets discovered at their various organizations with the goal of shepherding programs through Phase II before out-licensing to other drug makers. Should a partnership materialize, revenues stemming from these alliances--presumably milestones and royalty streams--will be distributed to the three investment participants in some fashion. -- Ellen Licking

Cephalon/Ception: Okay, it's not really a "no deal"; the Cephalon/Ception transaction is more accurately described as a "no deal yet." That's because Cephalon is extending (we'd say postponing) its option-to-acquire Ception Therapeutics after a Phase II/III study of the smaller co's lead compound, reslizumab, yielded disappointing results in treating the rare autoinflammatory disease eosinophilic esophagitis (EE). Recall that way back in January, Cephalon acquired the rights to buy Ception for $250 million on top of a healthy $100 million upfront pending a positive outcome in the EE trial. It's possible the deal may still come to fruition -- reslizumab isn't leftover turkey, yet -- but now Ception has to prove the drug has the goods (i.e. Phase II data) in a different indication, eosinophilic asthma, before Cephalon ponies up the money. Results from these asthma studies are expected to be revealed sometime in the first quarter of 2010.

There's no question reslizumab, an anti-interleukin 5 monoclonal antibody, is an important asset to Cephalon. It's one of the company’s only near-term pipeline opportunities given the pending genericization of Provigil. Indeed, Cephalon execs highlighted reslizumab and its expected mid-2010 BLA filing as a near-term growth driver during a recent R&D day. It's also clear Cephalon is hitching its wagon to therapeutics that treat inflammation. In addition to the Ception transaction, in the past year the company has inked three deals in the space, with ImmuPharma, Arana, and most recently BioAssets. -- Jessica Merrill and Ellen Licking