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 Wonders About The Wolf

Huffing and puffing and blowing the NIH down?

The biggest financial news of the fortnight had to be the U.S. government’s failure to avoid the sequester budget cuts, and the odd collective yawn it produced. Even with the sword of Damocles poised above various agencies, markets kept climbing – including the Nasdaq and AMEX biotech indices (respectively up 3% and 2.5% this week, as of this writing). The stock shrug led some to accuse President Obama and his supporters of crying wolf.

Pre-sequester, one of the federal agency heads making dire predictions was NIH director Francis Collins, who said on a February 25 conference call that “somewhere in the neighborhood of 20,000 jobs will be lost.” Collins also pointed out the sequester will lead to delays and lost time in important drug development projects focused on cancer treatment, a universal influenza vaccine and Alzheimer’s disease.

(For "The Pink Sheet" DAILY's full sequester coverage, click here.) 

Now that the cuts are coming, we asked around to see if, in our little corner of the world, the wolf was still howling. In other words, how might the cuts trickle up into the biotech startup realm, with potentially fewer innovations to hone into new companies? Part of that trickle flows through the technology transfer offices of major non-profit research centers, so we started there. What do they think?

Scott Forrest, the tech transfer chief at the prolific Scripps Research Institute  of Technology in La Jolla, Calif. – which has helped spawn biotechs such as FoldRx Pharmaceuticals, now part of Pfizer, aTyr Pharma, CovX Research (also bought by Pfizer), Receptos and Ambrx -- told The In Vivo Blog he didn’t expect any near-term pain in the next, say, six months. "Beyond that, we’re practicing watchful waiting," said Forrest. "We just don’t know what to expect."

We wondered if there's a correlation between NIH budgets and biotech company formation. Bob Coughlin, the head of the biotech trade group in Massachusetts, the state that receives the most NIH funding, told us "the long-term effect will be seen four, five, ten years from now when we don’t have new therapies and ideas in our pipeline of future companies." 

But the National Venture Capital Association has never done a study on such correlation -- and its life science policy VP Kelly Slone told FOTF she isn't aware of one. So until we crunch those numbers ourselves, there’s no precedent to gauge potential fallout by that measure.

Todd Sherer, the president of the Association of University Technology Managers wouldn’t go as far as to predict the impact on company formation. But Sherer, who also runs tech transfer at Emory University in Atlanta, said funding does correlate to invention disclosures: "So if funding dollars go down, there will be some latency, perhaps two or three years, but expect to see a drop in the number of new invention disclosures that turn into licensable technology."

Sherer also said that the tech transfer bottleneck, already an impediment, will only get worse. "Through the global financial crisis, universities haven’t increased patent budgets or [added staff], despite the federal funding increases and the number of new inventions arriving. So we’ve had more inventions coming our way, but no increase in staff or budget to handle them, and with fewer outlets [among VCs or pharmas to license them]. We’re just now coming out of a perfect storm. I’m afraid we left important innovation along the roadside during the financial crisis, and we’re about to head that way again," said Sherer.

VCs like to say that the best technologies and product candidates will always rise to the top and attract money. But with the life-science venture population shrinking, and those remaining often in pursuit of later-stage investments that won’t take so long to mature, fewer VCs are even looking toward academia. As part of its annual A-List feature in January, START-UP asked dozens of life-science VCs to name the best sources of innovation. Only 15% said academia. Unscientific, true – but Sherer wasn't surprised by the sentiment. With universities dabbling more in translational science, and big drug companies forging ties left and right with academics, he said the odds of getting something licensed might be better when going "directly to Big Pharma and big biotechs and avoiding the start-up route. I haven’t seen data that that’s the case, but conceptually it seems possible." 

This all may be moot when the new federal budget is negotiated. But with wolves at the door and fiscal hawks flapping their wings -- and gums -- we aren't predicting anything. Howl as much as you want, but you'll never filibuster long enough to avoid...

Tesaro: Basking in the afterglow of its successful 2012 IPO, the publicly traded oncology developer sold 5.4 million common shares in a secondary offering at $18 per share that raised net proceeds of $91 million for the Boston-area company. Tesaro says the cash will go toward its development programs, rolapitant, niraparib and TSR-011, which were all in-licensed. The $18 price was $1.09 below the firm’s closing price February 22, the last business day before the offer was announced. Since the announcement Tesaro shares have risen to $24.36 a piece as of mid-day trading March 7. The firm, which debuted in late June at $14 a share, was one of several in the IPO class of 2012 to finish the year above its offer price. It’s a prime example of a recent biotech phenomenon that constrains the number of companies able to go public, but rewards those that manage to squeeze through the window. Tesaro executives and directors stand to benefit, as they owned nearly 70% of the company before the secondary offering. Their holding now stand at nearly 60%. Tesaro was formed by the former executive team of MGI Pharma, which was bought by Eisai in late 2007 for $3.3 billion. New Enterprise Associates, InterWest Partners and Kleiner Perkins Caufield & Byers were Tesaro’s three main venture backers, and all three still have Tesaro board seats. There were 13 biopharma and diagnostic IPOs on U.S. exchanges in 2012, and three venture-backed firms have debuted so far this year. (We’re not counting Pfizer’s animal-health spinoff Zoetis.) Citigroup and Morgan Stanley led Tesaro’s underwriters, who sold their full overallotment of 708,000 shares. -- Alex Lash

Ablynx: Belgium's publicly-traded Ablynx has raised €31.5 million ($41.2 million) in a private placement announced February 28, two weeks after announcing positive Phase II results for ALX-0061, a second rheumatoid arthritis-targeted product from the company’s Nanobody platform. The placement is the second largest financing in Europe’s therapeutic biotech sector this year, trailing only the $60.9 million raised by e-Therapeutics in February. Nanobodies are small-sized, single-domain antibody fragments that penetrate deep into target tissues. They also bind strongly to human serum albumin, which prolongs their circulation time in the body. The funds will support further development of ALX-0061, an IL6R inhibitor, and other Nanobodies. The funds give Ablynx greater flexibility over future development plans, allowing it to consider co-development or co-promotion – it has 25 programs in its pipeline, including five at the clinical development stage, and a roster of Big Pharma partners, including Boehringer Ingelheim, Merck Serono, Novartis and Merck & Co. It is also evaluating the attachment of therapeutic payloads to Nanobodies through recent agreements with Spirogen and Algeta. Euronext Brussels-listed Ablynx sold 4.4 million new shares at €7.20 per share, a 6.7% discount to the February 27 closing price. Pre-IPO shareholders and warrant holders also sold 1.9 million shares at the same price, bringing the total amount placed to €45 million. -- John Davis

Spring Bank Pharmaceuticals: Looking to create a new class of drug that potentially could be included in next-generation, all-oral antiviral regimens for chronic hepatitis C, Spring Bank announced a $10.5 million Series A financing on February 28. The funding, from Brock Securities and Gilford Securities, will help advance lead candidate SB 9200 into a Phase I safety and antiviral efficacy trial this quarter and further the Massachusetts biotech’s preclinical pipeline. SB 9200, derived from Spring Bank’s proprietary Small Molecule Nucleic Acid Hybrid technology platform, produces an antiviral effect by activating the host-immune response in HCV-infected cells, the company says. It targets two host cytosolic proteins, RIG-I and NOD2, to set off selective activation of immune response in the presence of viral infection. In preclinical study, the compound has shown synergistic activity with other HCV antivirals and demonstrated a clean safety profile. Spring Bank thinks ‘9200 will prove to pair well with other new direct-acting antivirals for HCV thanks to the potential for pan-genotypic activity and a high barrier to resistance. Previously, Spring Bank raised $600,000 in angel financing in 2009, got a $244,000 grant under the U.S. Qualifying Therapeutic Discovery Project in 2010 and received a $3.9 million grant in 2011 from NIH. The company’s preclinical pipeline includes programs for hepatitis B, respiratory syncytial virus, chronic obstructive pulmonary disease and broad-spectrum antibiotics. -- Joseph Haas

Daiichi Sankyo: The Japanese drug giant with a long history has jumped on a recent bandwagon by forming its own venture group, as our friends at PharmAsia News reported March 4. To date, Daiichi Sankyo has invested as a limited partner in other venture funds as a window into deal flow and to gain preferential co-investment rights. But it has now created its own direct-investment vehicle to be overseen by global R&D chief Glenn Gormley, who is based in New Jersey. It joins Merck Serono, Merck & Co., Shire and other pharma companies with relatively new venture groups. Daiichi Sankyo didn’t disclose how much cash the group will have to invest, but corporations are using even relatively small amounts to invest aggressively, as corporate venture becomes a larger part of the biotech funding landscape. Corporate groups are now frequent investors in early-stage companies, once a no-go zone. In 2012, for example, Novartis’s venture group was just as active in Series A investments as Third Rock Ventures, which is one of the few traditional VCs still gung-ho for company formation. -- Daniel Poppy and Alex Lash

All of the Rest: A Series E financing led by Invesco Perpetual brought Glide Pharma £14M… In a combination Series A/loan, Dezima Pharma raised €14.2M to fund development of a dyslipidemia candidate acquired from Mitsubishi Tanabe… Attempting to overcome mucosal barriers in treating disease, Kala Pharma closed on $11.5M in Series A financing… The Dundee Corp. provided $10.5M in additional funding to TauRx for its Alzheimer’s compound… Blaze Biosciences completed a $8.5M Series A to support work on high-res technology for tumor visualization… The venture arm of leading Korean aesthetic firm AmorePacific led a $7M Series B for Brickell Biotech… With proceeds going towards Alzheimer’s agent ladostigil, Avraham added $5.7M to its Series B, now totaling $8.7M… DecImmune raised $3.2M to help develop an antibody that reduces tissue damage due to heart attack… Botanical products company KannaLife raised $1.5M in Series A funds...using social media and nonprofit advocacy to solicit biomedical research materials, Sanguine Biosciences completed a seed round… Public Swedish autoimmune/cancer company Active Biotech raised SEK270M from Investor AB… Celsion’s zero coupon preferred stock offering grossed $15M… Opko Health led a $16.4M financing for RNA-targeting RXi Pharma...oncology-focused EntreMed privately raised $11M… To fund a clinical de-risking bioequivalence study of its lead Parkinson's candidate, Canadian biotech Cynapsus closed on $Cdn6M from a syndicate including an undisclosed strategic investor… In a follow-on offering, Immunomedics raised $14M… Diabetes-focused DiaMedica announced a public offering of units… Orphan drug company Hyperion is planning to sell 2.6M shares publicly…Merck Serono spun off (and seeded with €2.5M) its latest start-up Calypso Biotech to pursue inflammatory bowel diseases… OrbiMed Advisors is reportedly raising a second pain-Asia health care fund worth $500M. -- Amanda Micklus

Wolf yawn photo courtesy of Flickr user ArranET.