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Pfizer Adds UCSF as First Partner in Academic Network

Pfizer has committed up to $85 million over five years to an expansive research agreement with the University of California, San Francisco, intended to speed the development of new biologic-based medications. More critically, the relationship with UCSF will be the first spoke in a network of academic collaborators, with Pfizer at the hub. Called the Center for Therapeutic Innovation, the goal is to bridge the gap between basic science and early clinical studies of potential drug candidates.

Anthony Coyle, former head of respiratory, inflammation, and autoimmune disease research at MedImmune, will lead the network. Coyle says CTI will eventually be comprised of seven or eight partners: three or four in the U.S., one or two in Europe, and the remainder in Asia or Australia. Expect to see two more U.S.-based partners, one in NY and the other in Boston, added to the network by the end of the year, he adds.

The creation of the CTI is Pfizer’s latest shake-up of the model for industry-academic collaborations. If you’ll recall, last spring, Pfizer caused a stir when it said it would give scientists from Washington University‘s School of Medicine access to data on 500 compounds that have gone through or are in some stage of clinical development. The hope is that fresh eyes with deep insights into the biology of disease and drug targets might lead to new uses for the compounds. See our recent cover story on the deal for much more detail on how that arrangement works.

Ultimately, Pfizer hopes that by breaking down some of the barriers that have hindered an open exchange between industry and academia—the right to publish, ownership of intellectual property, shared profits on products, to name a few—it will be able to get new drugs to market faster.

Coyle says the CTI will be solely focused on biologic-based drugs, mainly because he wants each center to be fairly autonomous and able to make decisions quickly. With the infrastructure required to develop small molecules, they would have had to rely on medicinal chemists “in distant locations,” and would run the risk of creating an “overburdened” project.

The first step in the UCSF collaboration will be a trip by Coyle and other Pfizer executives to the campus in December to explain the program. Because Pfizer believes the projects will only work if scientists are working side-by-side, the company will set up new labs that can accommodate up to 40 scientists close to the UCSF campus.

University scientists will have access not just to Pfizer’s drug development knowledge, but to its research tools—of particular note is that Pfizer is making its phage display libraries accessible to those working on joint projects. Pfizer, meanwhile, will have easier access to tissue samples and tools that can help it quickly understand which patient populations its drug candidates will be relevant in.

Proposals by UCSF scientists are reviewed by a steering committee comprised of four members from the university, and four members from Pfizer. And just like a biotech is funded, follow-up cash will be linked to the project achieving milestones.

“It’s almost like VC-based funding,” Coyle says. The deals are light on capital upfront, “and then projects are funded as they are successful. If there’s no success or a project didn’t meet the appropriate milestone, then there’s no additional funding.”

GSK Highlights Rare Diseases Approach

GlaxoSmithKline today outlined its strategy in rare diseases, while also unveiling its latest licensing deal in the area.

Created in February, the rare diseases unit will focus on four therapeutic areas–metabolism, central nervous system and muscle disorders, immunoinflammation, and rare malignancies and hematology—and will initially chase treatments for 200 diseases. “We believe that focusing on 200 diseases is a good compromise between the enormity of the task and what we can really address with the team we have in place,” Marc Dunoyer, head of GlaxoSmithKline’s rare diseases unit said on a call with reporters this morning.

Pursuing treatments for 200 diseases seems ambitious. After all, the rare diseases unit is comprised of just 30 people who work with scientists in GSK’s 38 discovery performance units as well as leverage outside opportunities.

But Dunoyer pointed out that roughly 3,000  rare diseases are rooted in genetics, which provides natural starting points for drug discovery campaigns. Further, the company appears to be looking for deals that bring technologies that can be applied across a range of diseases.

The company has already established a small network of partners with edgy drug discovery technology. Prior to the creation of the unit, GSK paid $25 million upfront for Prosensa’s PRO051, an RNA-based therapeutic now in Phase II trials for the treatment of Duchenne muscular dystrophy. GSK then bought the rights to a number of enzyme replacement therapies from JCR Pharmaceuticals. In March, GSK signed a broad pact worth up to $1.5 billion to use Isis Pharmaceuticals’ antisense technologies to develop therapies for rare diseases.

Today, GSK announced a partnership with Italian charity Fondazione Telethon and research organization Fondazione San Raffaele for the development of gene therapies based on the patient’s own bone marrow. In exchange for $14 million upfront and the promise of milestones, GSK gains access to a gene therapy that has completed Phase I/II trials in ADA severe combined immune deficiency, more commonly known as “bubble boy disease,” which affects just 350 children worldwide. The organizations will use the stem cell technology to develop treatments for a variety of other rare diseases based on single-gene mutations.

GSK isn’t the only drug company with a newfound interest in rare diseases. In December, Pfizer started a rare diseases unit, which recently set up an R&D group in Cambridge, Mass. Sanofi-Aventis has for months been trying to buy Genzyme in order to bolster its rare diseases portfolio. Novartis has also become interested in rare diseases as a foothold into larger markets.

Seattle Genetics & ImmunoGen on a Roll

The good news keeps coming for companies developing antibody-drug conjugates, which enable the targeted delivery of powerful chemo drugs. (click here for more info on how they work). On the clinical side, ImmunoGen and Roche have released a promising set of data for T-DM1, their drug linking trastuzumab with DM1, a derivative of the microtubule-disrupting agent maytansine, while Seattle Genetics and Millennium Pharmaceuticals offered the latest validation for SGN-35. Meanwhile, ImmunoGen sealed a deal with Novartis worth up to $240 million.
First to the clinical results: Although the trial was relatively small, ImmunoGen’s T-DM1 appeared to be as good at shrinking tumors as a combination of Herceptin and chemotherapy in patients with HER-2 positive, metastatic breast cancer. Importantly, patients in the T-DM1 arm experience significantly milder side effects than those taking the Herceptin/chemo combo. For example, 66.2% of patients in the chemo arm experienced complete hair loss, compared to 1.5% in the T-DM1 arm, and 57.4% of the Herceptin/chemo patients experienced neutropenia, or white blood cell count lowering, vs. 7.5% of the patients in the T-DM1 arm.
In a note to investors, RBC Capital Markets’ analyst Jason Cantor called the results “particularly groundbreaking” because no chemotherapy drug was added into the T-DM1 treatment arm. The trial “is significant validation of ImmunoGen’s technology and antibody-drug conjugation technology, in general.”
In August, ImmmunoGen and Roche had a setback when after FDA refused to accept their biologics license application for T-DM1 based on the Phase II data offered up in the filing. Roche had already started a Phase III study, and Cantor expects Roche to try again with FDA in mid-2012, putting a potential launch in the first half of 2013.
The positive data for T-DM1 comes on the heels of strong results for Seattle Genetics’ antibody-drug conjugate, SGN-35. Last month, the Seattle-based biotech said the drug was able to shrink tumors in 75% of people with Hodgkin’s lymphoma who had failed to see results with other treatments. Seattle Genetics expects to file a BLA for SGN-35 in the first half of 2011, with approval expected in the second half of the year.
Today, Seattle Genetics and Millennium said that SGN-35 shrank all or some tumors in 86% of patients with anaplastic large-cell lymphoma. Look for more data in both Hodgkin’s lymphoma and in ALCL in December during the American Society of Hematology annual meeting.
On the deal front, Novartis is coughing up $45 million upfront and up to $200 million in milestones to apply ImmunoGen’s antibody-drug conjugate technology (which it calls “TAP” for targeted antibody payload) to a select number of targets. ImmunoGen could also score research funding and additional support if it performs manufacturing for Novartis.

HCV News Extravaganza

Apparently everybody in the hepatitis C race was busy over the holiday weekend, as Tuesday brought a flood of news from the sector. There was good news, bad news, and an acquisition.

Last things first: the acquisition. Bristol-Myers Squibb announced it will fork over $885 million for Zymogenetics, its partner in the development of pegylated interferon-lambda, in Phase II trials to treat hepatitis C (HCV). If you’ll recall, last year BMS paid $85 million upfront and a $20 million licensing fee for access to the drug. Under that arrangement, the Seattle-based biotech would have scored up to $430 million in milestones if the therapy actually made it to patients. Given Zymogenetics product pipeline and its one marketed product, Recothrom, the $885 million price tag doesn’t sound so outlandish.

Interferon-lambda uses the same cell-signaling pathway as interferon-alfa, one of the two cornerstones of current HCV therapy. But as we wrote earlier this year, because interferon-lambda has fewer functions in the body than interferon-alfa, it is expected to be as effective with milder side effects.

Onto the bad news: Idenix Pharmaceuticals said FDA put a clinical hold on two of its hepatitis C drugs, IDX184 and IDX320, due to liver toxicities in a small trial testing the safety of giving both drugs to healthy people. The company’s stock took a beating on the news, with shares falling by 47% to close at $3.18 yesterday. The question now is which of the molecules is causing the elevated liver enzymes. Leerink Swann analyst Howard Liang commented on the issue in a note to investors this morning: “The lack of association between the liver toxicity signals and IDX184 exposure and more extensive safety data on IDX184 would suggest us to that IDX320 is more likely the culprit than IDX184, which is the more important asset in our view.”

And the good news (part 1): Vertex Pharmaceuticals released more positive Phase III data for telaprevir, its much-anticipated protease inhibitor for HCV. The drug candidate was tested in some of the toughest patients—those who didn’t respond to or had only a partial response to the standard of care (pegylated interferon and ribavirin) or whose disease relapsed after standard of care. Vertex said 65% of those HCV patients were “cured” when adding telaprevir to the treatment regimen, compared to 17% in the control arm, which was given just the standard of care. Take a look at the company’s press release for more details on each segment of patients, but the relapsers had the most success with treatment, with a smaller portion (31%) of the folks that didn’t respond at all to interferon and ribavirin seeing complete suppression of the virus. In other words: there’s still room for at least some of the many compounds in development to treat the infection.

In other potentially good news for a biotech developing HCV drugs, Leerink Swann’s Liang also noted that Roche appears poised to start a Phase III trial for RG7128, a polymerase inhibitor discovered by Pharmasset, by the end of the year. The earlier-than-expected start to the late-stage trial would put the compound in a strong position to be the first polymerase inhibitor approved for HCV.

Orexigen Partners With Takeda for Potential Obesity Drug Contrave

This morning Orexigen Therapeutics became the second of the three leaders in the obesity drug race to partner with a larger company. They’ve successfully courted Takeda, which now gets exclusive marketing rights to obesity drug Contrave in the U.S., Canada, and Mexico, if the drug gets regulatory approval. Orexigen’s shares soared on the news, first released in the pre-dawn hours this morning.

In the deal, Orexigen gets $50 million upfront from Takeda and could nab up to $1 billion more, depending on whether Contrave meets certain regulatory and sales milestones. Further details about the agreement are available on an Orexigen press release.

Contrave refresher: Contrave is a combination of two drugs already on the market: naltrexone, which is typically used to manage alcohol or opioid dependence, and the antidepressant bupropion. Orexigen’s developed a sustained-release formulation of those active ingredients. This is thought to alleviate the nausea that cropped up in clinical trials, but also could come in handy in terms of real-world prescriptions if the drug is approved. People might want to save money by taking the generic versions of Contrave’s two components but it isn’t clear how that would work for them.

In July we covered the first partnership deal in the obesity drug race, that of Eisai and Arena Pharmaceuticals, which is developing the obesity drug candidate lorcaserin. It’s worth stepping back to compare and contrast the deals. Continue reading →

Bayer to Eliminate Unsightly Chin Fat

As my husband and I recently looked through photos of our wedding, he kept repeating the same thing: “Yikes, check out my triple chin.” Click. “Another triple chin.” Click. “Hmm, maybe I need to work out.”

In reality, his perceived folds of flab were a result of unfortunate camera angles (I swear, dear. Your chin is splendid.). But if a day comes when he genuinely suffers from chin bulge, Bayer might have just the solution. Yesterday, the company agreed to fork over $43 million upfront and upwards of $300 million in milestone payments for Kythera Biopharmaceuticals’ ATX-101, an adipolytic agent “designed to reduce small volumes of facial fat.” Yes, that’s right, folks: it’s a chin fat drug.

Because I tend to cover pharmaceuticals that are more in the disease-modifying category rather than those in the aesthetics-modifying category, I was pretty shocked by the price tag. Then I took a look at Allergan’s sales forecast for its wrinkle smoother Botox—the company is predicting it will bring in about $1.3 billion this year. (Well, that’s before subtracting out the $600 million Allergan agreed to pay today to settle criminal and civil charges related to the marketing of Botox.)

In other words, the potential market for ATX-101 seems pretty vast. Indeed, I imagine my husband isn’t the only one to look at a photo (poorly angled or not) and cringe. ATX-101 is in Phase II studies, and seems to be administrated in a relatively painless injection.

All this made me wonder how one goes about getting rid of small fat deposits without, well, sucking them out. It looks like the folks at Kythera, which is conveniently based in Los Angeles, first thought the active component in the formulation of ATX-101 was phosphatidylcholine, a major component of biological membranes that sports a polar head and fatty acid tails. However, further studies showed that deoxycholate, a secondary bile acid put into the formulation to make the phosphatidylcholine micelles soluble, was actually the secret to getting rid of unsightly chin fat. Deoxycholate, a detergent, causes a shift in the osmotic balance of a cell–in other words, water rushes into the fat cell, causing it to burst.  The finding was curious, as deoxycholate appeared to be only affecting fat tissues when administered in vivo. Kythera eventually determined that deoxycholate isn’t necessarily selective for fat cells, but that tissues in the subcutaneous fat that are protein rich are resistant to its effects. Hence, when administered locally, it appears to be able to get rid of the fat without impacting other tissues. And there you have it, drug goes in, fatty chin goes out. Since later stage trials are pending, the chin-fat sensitive will have to stick to photoshop for now.

Are Lilly & Covance Trend Setters?

GSK said today that it had finalized plans to sell its Medicines Research R&D center in Verona, Italy, to contract research organization Aptuit. Normally a change of ownership causes fear in the hearts of employees, but in this case, all 500 workers in Verona will be transferred to GSK. They can do that because GSK is hiring Aptuit to perform R&D services at the site.

This kind of arrangement sounds awfully familiar. Readers may recall that in 2008, Eli Lilly sold its Greenfield, Ind., operations to drug development firm Covance. A good chunk of the Lilly staff came with the deal, as did a nice, fat, ten-year R&D contract worth some $1.6 billion. Covance is conducting toxicology testing and providing some other R&D functions for Lilly, and more recently signed a three-year pact to conduct analytical testing of Lilly’s bioproducts.

So why farm out what you previously owned? Lilly has said its Covance collaboration is about risk sharing and cost savings. The big pharma company thinks it can save tens of millions of dollars each year by putting the ball in Covance’s hands. Meanwhile, the goal is to reduce the amount of time it takes to choose a lead candidate and advance it through proof-of-concept studies in humans.

If rumors are true, Sanofi-Aventis will be the next to adopt this type of arrangement. Dow Jones reported this week that Sanofi would sell its Porcheville, France, and Alnwick, U.K., sites, along with 300 or so employees, to Covance. I’m going to go out on a limb and guess that the deal will also include an R&D contract.

In the press release, GSK’s R&D head Moncef Slaoui said the Aptuit deal “a modern option for drug discovery expertise to remain as part of the science research community in Italy.” Clealry, GSK had its hands tied by the Italian labor union, and couldn’t just shut down the site or compromise jobs in its sale. But I’m wondering how much money it will save by putting the work in other hands—well, the same hands under a new employer. How much of an impact can this strategy have?

Eisai Will Sell Arena’s Obesity Drug Lorcaserin, Pending FDA Approval

Arena Pharmaceuticals has landed a partner for marketing its weight loss drug, lorcaserin- Japan’s Eisai. This makes Arena the first of the three big contenders in the obesity drug race to nab a partner.

In the deal, announced in the wee hours of this morning, Arena gets $50 million upfront from Eisai, and stands to make more in milestone payments upon delivering the product for launch time, if lorcaserin gets approved by the FDA. Still more additional payments, which could total up to $1.16 billion, will be tiered based on how well lorcaserin sells. Eisai gets exclusive U.S. rights to market the drug. Arena’s stock jumped this morning on the news.

You can get the specifics on the deal from Arena’s press release.

OK. You know it’s news when the company provides snazzy photos with the press release.

Arena said last month it planned to go it alone with lorcaserin if it couldn’t find a partner. But at the time, Leerink Swann analyst Steve Y. Yoo said in a report to investors that “the best source of funding, in our view, would be an upfront payment by a partner for lorcaserin.”

Well, now Arena’s got that cash. What does it mean for the obesity drug race as a whole?
Around the interwebs a few folks are wondering whether the terms of the deal still signal some caution on the part of Eisai.

My two cents are that in the obesity area, safety may reassure potential partners more than efficacy does.

As we wrote back in 2009, lorcaserin disappointed investors as early Phase III trial results came to light, because the compound met some but not all of FDA’s numerical weight-loss benchmarks.

But lorcaserin’s safety profile is very good. Perhaps it’s because Arena had the most to prove. Lorcaserin targets the same serotonin receptor as fenfluramine, an ingredient in the infamous Fen-Phen obesity drug combo. Fenfluramine was associated with heart valve damage and a fatal lung disorder- it was pulled from the market in 1997.

But lorcaserin is different from fenfluramine- it is more selective for one specific subtype of serotonin receptor and avoids the one that’s found in the heart. Arena has had to pay special attention to safety throughout lorcaserin’s development and they haven’t run into heart valve trouble.

Given the history of failures in the weight-loss drug field (Fen-Phen, rimonabant, etc), and given that a weight loss drug will be taken by many people who are otherwise healthy and may not even be clinically obese, it could be that safety will turn out to be king.

RNAi Roundup #3

It’s time for another RNAi Roundup, this one featuring a few new faces and some oldies but goodies:

–Regulus Therapeutics, the microRNA company backed by Isis Pharmaceuticals and Alnylam, has signed a major partnership with Sanofi-Aventis. The French pharma firm will pay $25 million upfront, make a $10 million equity investment down the road, and provide three years of research support to gain access to Regulus’ fibrosis research program. The companies will collaborate on up to four microRNA targets, including Regulus’ most advanced efforts around microRNA-21. Regulus could score more than $750 million throughout the lifetime of the pact. The deal marks Sanofi’s second move in the RNAi space this year. In March, Sanofi signed up to use San Diego-based Traversa’s siRNA delivery technology.

–Santaris Pharma of Denmark and miRagen will jointly develop microRNA-targeted therapeutics for the treatment of cardiovascular disease. Boulder, Colo.-based miRagen will use Santaris’ locked nucleic acid drug platform to develop single-stranded LNA-based drug candidates. Santaris gets a minority stake in miRagen in exchange for use of its technology, and could see milestones and other payments as part of the pact.

–Cequent Pharmaceuticals has been granted patent protection in Europe for its TransKingdom RNAi technology, which uses non-pathogenic bacteria, such as modified E. coli, to deliver siRNA against certain genes. In April, Cequent was bought by Bothell, Wash.-based MDRNA in an all-stock deal worth $46 million. The purchase gives MDRNA two distinct siRNA delivery platforms.

–Mirna Therapeutics has won a $10.3 million “commercialization” award through the Cancer Prevention and Research Institute of Texas, a state-run investment program meant to spur innovation in cancer research. The money will be used to advance Austin, Tex.-based Mirna’s microRNA mimic discovery platform.

–Arrowhead Research, the parent corporation of Calando Pharmaceuticals, has raised $8.65 million in a direct stock offering. The money will be used to support Calando and Arrowhead’s other subsidiary, Unidym, a carbon nanotube technology firm. Calando recently showed in a Phase I study that its targeted nanoparticle technology could be used to deliver siRNA into cells.

–Alnylam came out with more data on the use of novel delivery lipids that carry siRNA into cell lines to improve the yield of biopharmaceutical manufacturing. Many biologics are produced by Chinese hamster ovary cells, but scientists have historically had few ways to control the output of those tiny drug factories. Alnylam’s goal is to turn off the activity of proteins that contribute to cell death, hopefully upping the yields of an otherwise expensive manufacturing process.

Forest licenses TransTech’s glucokinase activators

Interest in glucokinase activators, a class of diabetes compounds with a rocky past, appears to be reviving. Forest Laboratories agreed today to pay $50 million upfront and up to $1.1 billion in milestones for access to TransTech Pharma’s glucokinase activator program. The deal includes the rights to TTP399, which is poised to start Phase II trials, and several other compounds in pre-clinical and Phase I studies.

TransTech’s glucokinase activator (GKA) program was developed during a six-year research pact with Novo Nordisk. The Danish firm licensed the program back to TransTech in 2007, when it decided to divest its small molecule drug discovery programs.

So what makes glucokinase an interesting diabetes target? A few words on GKAs from our earlier coverage:

Glucokinase belongs to a family of enzymes called hexokinases, which catalyze the phosphorylation of glucose to glucose-6-phosphate, a critical first step in metabolizing sugar. Hexokinases are generally marked by their ubiquity—several serve housekeeping functions and are thus found in nearly every tissue in the body—and their tight bond to glucose.

But glucokinase is something of a black sheep among hexokinase kin. It is found in relatively fewer tissues, and its affinity for glucose is delicate. In the pancreas it is believed to “sense” just the right concentration of glucose in β cells to signal the release of insulin. And in the liver glucokinase initiates the first step of glucose metabolism, kicking into action after a meal and later sensing when the body is in a fasting state and needs to store glucose.

Back when we wrote about GKAs in 2008, several of the companies publicly working on this target talked up the dual roles of glucokinase in the liver and pancreas. While newer diabetes drugs like Merck’s Januvia and Amylin’s Byetta only affect the pancreas, GKAs were expected to have an effect on both organs, improving their control over blood glucose.

TransTech, however, is touting the fact that its GKA compounds are “liver selective.” The biggest safety concern with GKAs in development has been hypoglycemia, or low blood sugar. TransTech says that “by activating glucokinase selectively in the liver but not in the pancreas, it may increase glucose utilization and lower blood glucose levels without inducing excessive insulin secretion thus reducing the risk of hypoglycemia.”

Interest in glucokinase as a target has waxed and waned. Roche was actively pursuing GKAs not long ago, but a perusal of their public pipeline, which includes multiple diabetes programs,  shows no mention of the target. And a quick look at clinicaltrials.gov shows that Lilly suspended work on its program—licensed from OSI Pharmaceuticals for $25 million upfront in 2007–pending further toxicology testing.

Still, late last year, Amgen paid $60 million upfront for access to Array BioPharma’s portfolio of glucokinase activators. The deal included ARRY-403, now called AMG-151, in Phase I trials to treat type-2 diabetes.

We’ll have to wait for Phase II results to see if the target is worth the effort. Stay tuned!