NEW YORK (Reuters) - Canada's Valeant Pharmaceuticals International is nearing a deal to acquire eye care company Bausch & Lomb Holdings Inc from Warburg Pincus LLC for about $9 billion, a person familiar with the matter said on Friday.

Valeant shares reached their highest level since 2001 on the news and were up 10 percent at C$84.33 in Friday afternoon trading in Toronto.

The move comes after Valeant made an attempt last month to acquire generic drugmaker Actavis Inc in an all-stock deal that would have topped $13 billion, people familiar with the matter previously told Reuters. The talks broke down and Actavis ended up with a deal to buy pharmaceutical company Warner Chilcott Plc.

The person that spoke on Friday requested anonymity because the matter is not public. Valeant could not be immediately reached for comment. Bausch & Lomb and Warburg Pincus declined to comment.

The Wall Street Journal, which earlier reported on the talks, said a deal might come as soon as next week.

Valeant has been on the acquisition trail since its 2010 takeover by Biovail Corp, which assumed the Valeant name. It has been pursuing deals with strong cash flow in high-growth areas where big pharmaceutical companies have little presence, its Chief Executive Michael Pearson said earlier this month.

Bausch & Lomb filed with U.S. regulators for an initial public offering in March. A source had told Reuters that its private equity owner Warburg Pincus had been exploring an outright sale of the company at the same time.

(Reporting by Greg Roumeliotis in New York; Editing by Lisa Von Ahn and Phil Berlowitz)

A Florida company trying to make the practice of pill splitting safer and easier has raised at least $1 million in its latest round of funding.

According to a Form D filing, Accu-Break Pharmaceuticals Inc. could continue raising up to $1.5 million in equity, debt and other securities. The company’s vice president of business didn’t reply to an email request for comment, but it was noted in the filing that proceeds would be used for general expenses and R&D.

Accu-Break is the developer of technologies that enable oral drug tablets to be subdivided into smaller doses.  Its proprietary technologies involve use of a drug-free break layer inside of tablets.

The company seeks licensing agreements with pharmaceutical companies. Last year, it signed a licensing deal with New Delhi’s Alembic Pharmaceuticals Ltd , which said it would launch five generic drugs over two to three years using the technology.

The FDA generally advises against pill splitting unless it’s specified in a drug’s labeling, because it may result in inaccurate or inconsistent doses. But it’s commonly done in an effort to save money or make them easier to swallow.

[Pill bottle courtesy of flickr user prudencebrown21]

COPENHAGEN, May 24 (Reuters) - Danish drug maker Novo Nordisk said it could launch obesity treatment liraglutide in the United States by the end of next year and rejected some analysts' doubts over the medicine's commercial potential.

The world's biggest insulin producer is hoping the treatment for severe obesity will help to at least partly offset the delay to its next generation insulin treatment Tresiba after U.S. regulators asked for more tests.

Novo said on Thursday a final stage clinical trial showed patients treated with 3 mg of liraglutide - which is already on sale as a treatment for type-2 diabetes under the brand name Victoza - had an average 8 percent weight loss.

But some analysts on Friday questioned whether the results were strong enough to secure the drug's success.

"The modest efficacy supports our hypothesis that the drug is unlikely to be a significant commercial success," Deutsche Bank analysts said, adding they were also concerned by the high price of the injectable drug.

Liraglutide is expected to cost around $25 per day as a treatment for obesity and could be a lifelong treatment. That compares with about $5 per day for rival Belviq, made by Arena Pharmaceuticals, and Qsymia from Vivus.

Novo Chief Scientific Officer Mads Thomsen told Reuters the higher price was justified because liraglutide was a better product than competitors.

He said the treatment was likely to be launched in the United States - the world's biggest drugs market - at the end of next year or the start of 2015.

Analysts who believe the drug will be a success estimate it could achieve peak annual sales of around $4 billion.

Sydbank's Soren Hansen said the key issue was whether liraglutide would qualify for reimbursement, which is when authorities help patients to pay for the cost of a drug.

"The study shows some good effects ... but whether that is enough to justify reimbursements, I am not sure," he said.

At 1000 GMT, Novo Nordisk shares were up 0.8 percent at 976.5 Danish crowns, compared with a 0.1 percent rise in the STOXX Europe 600 healthcare index.

Aveo's shares were down about 13 percent in extended trade, after closing at $2.70 on the Nasdaq.

Astellas does not intend to fund any future studies of the drug, tivozanib, in renal cell cancer, Aveo said in a regulatory filing on Thursday. (http://r.reuters.com/caz38t)

Earlier this month, an advisory panel to the U.S. Food and Drug Administration decided in a 13-1 vote that an additional trial would be needed before tivozanib could be approved for renal cell cancer.

Staff reviewers for the FDA had previously noted that kidney cancer patients on tivozanib did not survive longer when compared with patients on Bayer AG and Onyx Pharmaceuticals' drug, Nexavar.

Following the advisory panel vote, Aveo and Astellas had said they would work with the FDA to address the issues raised by the panel.

Aveo said in Thursday that it was evaluating the effect of the Astellas decision on tivozanib's clinical and regulatory path going forward.

(Reporting by Pallavi Ail in Bangalore; Edoting by Anthony Kurian)

Who will win this year’s MassChallenge? The Boston accelerator is set to get its fourth session underway with the announcement of the 128 new startups that will participate. A quarter of them are life science or health IT companies, and some of them sound particularly promising.

Benevolent Technology for Health, for example, is focused on making an affordable, self-adjustable prosthetic device for the developing world. DS Labs Inc. is developing a discreetly worn breast pump. Sensulin LLC could have a glucose-responsive insulin for type 1/type 2 diabetes patients. And Vecoy Nanomedicines won the pitch contest at FutureMed with its nano-scale “virus traps” to kill infections.

The selected entrepreneurs will get four months of mentorship and office space at MassChallenge’s offices. At the end, they will pitch for $1 million in cash prizes. MassChallenge says it received 1,200 applicants from 40 countries and 30 states. Notably, a handful of the life science companies are from Israel.

Here’s the rest of the list:

• B.B.R. Medical Innovations Inc. (inline IV fluid sterilizer)
• Calista Therapeutics (cystic fibrosis drug)
• CONTINUUS Pharmaceuticals (continuous manufacturing for pharmaceuticals)
• Elegant Therapeutics
• Gentoo (compression vest for infusion pump equipment)
• Gweepi Medical (sensor-embedded adult diaper)
• HackCriticalCare
• Hemova Medical (access port for dialysis)
• Home Analytics
• INRFOOD (“personalized food GPS”)
• Integrative Enzymatics (drugs for metabolic disorders)
• iQuartic Inc. (EHR data mining)
• Keraderm (non-surgical wound healing)
• Little Sparrows Technologies (low-cost phototherapy for jaundice)
• MedAlert (data analysis to prevent prescription errors)
• MobiStine (mobile apps for new parents)
• Mofin Technologies (mobile tools for coordinating care)
• MouseHouse
• MyZooPets
• Neural Analytics (tool to measure intracranial pressure non-invasively)
• Noliva Therapeutics LLC (cancer drugs that block protein-protein interactions)
• QMedic (wearable sensor to monitor seniors)
• Quad Technologies LLC (dissolvable hydrogel for biologics purification and cell separation)
• Thompson SCI
• Veraquel Technologies Inc. (peptide purification)
• Verbal Applications (communication software for patients with speech limitations)
• Volvox Biologic Inc. (glycan detection tool for biologic drug development)
• WaveGuide (hand-held diagnostic tool for tuberculosis)

CHICAGO (Reuters) - U.S. scientists say a dramatic result last year suggesting that a cancer drug already approved by U.S. regulators could quickly clear out Alzheimer's plaques in mice was too good to be true.

The study, published last year in the journal Science, showed the skin cancer drug bexarotene cut the amount of an Alzheimer's-linked protein called beta amyloid by half in three days. It also reversed Alzheimer's symptoms, restoring a sense of smell in treated mice and allowing them to resume nest building activities.

The news sent patients clamoring for the drug, and some doctors began prescribing it, even though it had not been tested in people with Alzheimer's. But researchers at several U.S. centers reported in the same journal on Thursday that they were unable to reproduce the most dramatic aspects of the findings in their own labs.

Gary Landreth and colleagues at Case Western Reserve University in Cleveland, the scientists behind the original research, say the drug still has merit, noting that the latest studies confirmed other aspects of the research showing the drug cleared out soluble forms of beta amyloid from the brain.

Scientists say the controversy is a stark reminder of the need for studies to be replicated by other labs, and it underscores the desperation of Alzheimer's sufferers to find effective treatments for the fatal, brain-wasting disease that affects 5 million Americans and 38 million people worldwide.

'VERY DRAMATIC'

"I was a fan of the original study," said Dr. Samuel Gandy, associate director of the Mount Sinai Alzheimer's Disease Research Center in New York, who was not involved in any of the studies.

"It was very dramatic. It cut plaque loads by three-quarters over less than a week. No one had ever seen anything like it before."

Gandy has had several patients asking for the treatment. Although U.S. doctors are free to prescribe any treatment approved by the FDA, Gandy said the drug has substantial liver toxicity and requires very careful monitoring.

"I have universally declined and advised others to decline."

There is no cure or effective treatment for Alzheimer's disease, a progressive form of dementia steadily destroys brain cells, and several large companies have failed in late-stage clinical trials, with the most recent being Baxter International's drug Gammagard earlier this month.

Sangram Sisodia, a professor of neuroscience at the University of Chicago, said he and his colleagues were curious about the initial report in 2012.

"It was hot stuff. It was the new miracle drug for Alzheimer's. Even Doctor Oz proclaimed such," said Sisodia, referring to a popular FOX TV show hosted by Dr. Mehmet Oz.

"People were clamoring for this drug after he went on TV and was pushing it."

Sisodia said he and fellow Alzheimer's colleagues, who included Dr. Rudolph Tanzi of Massachusetts General Hospital in Boston and Dr. David Holtzman of Washington University School of Medicine, wanted to see if the stunning results could be replicated in their own labs, a standard part of the scientific process.

Researchers failed to see any effects on Alzheimer's plaques in three strains of mice that were treated with bexarotene.

"There is absolutely no reduction in amyloid levels in the brains of mice treated with this compound," said Sisodia of his group's efforts, which were published as a technical comment in the journal Science. Teams at the University of Florida and researchers at the University of Leuven in Belgium published similar findings in the same journal.

TEMPEST IN TEAPOT

Landreth, who has formed a company to study the compound, says the teams are all focusing on the dramatic changes in solid forms of beta amyloid reported in the study, which, despite the press it got, was not the study's main finding.

"We concluded that plaques didn't matter and said so explicitly. As we look at the comments we just don't get it," he said. Landreth can't fully explain why the teams were unable to confirm the findings on plaque.

Even so, he said the latest studies do confirm some of his main findings which suggest the treatment significantly reduces the amount of soluble forms of beta amyloid that float in interstitial fluid that bathes brain cells.

Some studies have suggested that this soluble form of beta amyloid is the more toxic form of the protein, and removing it could offer significant benefits to patients.

A fourth study by a team at the University of Pittsburgh appears to back up his assertion.

The team was able to verify that the drug bexarotene significantly improves cognitive deficits in mice with gene mutations linked to human Alzheimer's. And it confirmed that the compound decreased small bits of toxic beta amyloid in the fluid that surrounds brain cells. But it, too, failed to show a reduction in amyloid plaques.

"We believe these findings make a solid case for continued exploration of bexarotene as a therapeutic treatment for Alzheimer's disease," Dr. Rada Koldamova, who led the study, also published in Science, said in a statement.

Landreth says the current "scientific tempest in a teapot" does not deter his plans to study bexarotene in people.

His company, called ReXceptor Inc., plans to start early stage trials in a group of six healthy adults within the next few months. The team hopes to prove the drug works by flushing soluble bits of the toxic protein out of the brain.

"We should have an outcome by Christmas," Landreth said.

(Reporting by Julie Steenhuysen; Editing by Leslie Gevirtz)

COPENHAGEN (Reuters) - Denmark's Novo Nordisk, the world's biggest insulin producer, said Phase III study results had shown people treated with its liraglutide drug had an 8 percent weight loss.

"These data, together with previously reported Phase III trials, consistently demonstrate clinically significant weight loss and improvements in obesity-related risk factors in people with obesity," chief science officer Mads Krogsgaard Thomsen said in the statement.

Just how big the product could be is fiercely debated by analysts. Novo recently declined to reveal Novo's in-house forecasts but said the new product would cost around $20 a day, or more than $7,000 a year, so it would take fewer than 150,000 patients to make it a $1 billion-a-year product.

The injected drug, already on the market as a treatment for type-2 diabetes under the brand name Victoza, is in final-stage clinical testing.

The company is hoping the drug will offer a new driver to its business, after a refusal by the U.S. Food and Drug Administration to approve diabetes drug Tresiba, demanding a major new study on cardiovascular risks.

In March, Novo reported that overweight and obese diabetes patients given high doses of liraglutide achieved 6 percent weight loss in a clinical trial, causing its shares to drop over 4 percent.

It said in a statement on Thursday that from a mean baseline weight of 106 kilograms, the average weight loss for people treated with liraglutide 3 mg was 8.0 percent compared with 2.6 percent for people treated with a placebo.

Novo Nordisk expects to complete the remaining Phase IIIa trial in the third quarter of this year, and to file the drug for regulatory review as a treatment for obesity in the United States and the EU around the turn of the year.

(Reporting by Mette Fraende; Editing by David Holmes)

It’s been 17 years in the making, but Acumen Pharmaceuticals hasn’t given up hope for its approach to a disease-modifying drug for Alzheimer’s disease. After restructuring to become a virtual biotech and raising a $20 million Series A, Acumen is marching forward with preclinical development of an antibody that binds and captures soluble oligomers of the amyloid beta peptide in the brain.

The company’s story dates back to 1996, when it was formed to protect patent filings of discoveries made by William Klein and Grant Krafft at Northwestern University and Caleb Finch at the University of Southern California.

At that time, it was common belief that Alzheimer’s was caused by a buildup of beta-amyloid plaques in the brain, said CEO Bill Goure. The team’s research, though, had led them to believe something else.

They found that soluble oligomers they called amyloid beta-derived diffusible ligands, or ADDLs, were toxic to neurons and proposed that ADDLs were important to the cause of Alzheimer’s disease. That was controversial at the time, Goure said, but as science evolved over the next decade, soluble oligomers became a key part of the Alzheimer’s conversation.

As a result of that paradigm shift in the science community, Acumen landed a drug development deal with Merck & Co. in 2004, Goure said. With the money from the deal, the company established an R&D center in California to advance other activities associated with those soluble oligomers.

But that was short lived; in 2008, the company pivoted and converted itself to a virtual company, shutting down that facility. Goure, then the chief operating officer, became CEO, leading the company through a financial restructuring under which it eliminated its debt and began the process of reacquiring its drug candidate from Merck, which was at the time merging with Schering-Plough.

“We were concerned that Merck wasn’t advancing our program as fast as we thought they should have,” Goure said.

Acumen reacquired all of its rights to ACU-193 in 2011, and in the meantime licensed rights for another small molecule that blocked the formation of soluble oligomers to Merz Pharmaceuticals GmbH in early 2010.

The next and most recent milestone in its restructuring was the close of a $20 million Series A round last month. With funding from BVF Partners, NeuroVentures Fund, Praxis Technologies, Glynn Ventures and other investors, Acumen plans to continue in-vivo efficacy studies in transgenic animal models and begin IND-enabling safety studies in the fourth quarter of the year.

Goure said he hasn’t been discouraged by the disappointing Phase 3 study results of two other antibodies for Alzheimer’s reported last year. “When we look at all the other AB immunotherapies being developed today, all of those other antibodies do not have selective binding to soluble oligomers — they target plaque or monomers,” he said. In other words, they are based on outdated assumptions about Alzheimer’s.

But if the soluble oligomer hypothesis is now widely accepted, are other drug companies getting on board? According to Acumen, although the toxicity of soluble AB oligomers has been well studied, there is limited data showing the effects of molecules interfering with their actions. Goure said Abbott Pharmaceuticals had a fairly robust program going, but appears to have shut it down. Cognition Therapeutics is taking a different approach, identifying a small molecule that’s designed to prevent the binding of toxic oligomers to receptors on the surface of neurons.

As Acumen marches forward with just two formal employees and a host of service provider partners, Goure said he has complete faith in the company’s new model.

“If you look today at skills necessary to develop a therapeutic, very few small companies can acquire those skills, and those that do can’t do it in a cost effective manner,” he said. “Those skills shift as you go from pre-clinical to IND to clinical studies. Small companies either find themselves hiring and firing to adapt their expertise, or trying to adapt their workforce to areas they don’t have skills for. It makes more sense to buy the skills and expertise you need when you need them.”

It said products launched since 2009 are due to account for nearly half of its pharmaceuticals sales by 2017. It also said that it plans to continue developing its pipeline of new development stage drugs in Japan and China.

CHICAGO (Reuters) - Kathrin Jansen is a microbiologist with at least two breakthrough vaccines to her name: she brought the cervical cancer vaccine Gardasil to market for Merck and helped develop the $4 billion a year pneumonia and meningitis vaccine Prevnar 13 for Pfizer.

Jansen's next vaccine success could come by taming the superbug MRSA, a drug-resistant bacterium that she has seen ravage a healthy man up close and personally.

Methicillin-resistant Staphylococcus aureus infects an estimated 53 million people globally and costs more than $20 billion a year to treat. In the United States alone, MRSA kills 20,000 Americans each year, exceeding annual deaths from AIDS.

Jansen watched the infection unfold two years ago when visiting her stepfather, who was in the hospital for a hip replacement. The man in the bed next door died soon after MRSA attacked the vascular graft in his leg.

"He went in healthy and died very quickly," recalls Jansen, senior vice president of vaccine research and early development at Pfizer Inc, the world's largest drug maker. She says the experience steeled her resolve to develop an effective vaccine that could prevent such deaths.

But Staphylococcus aureus has proven a tenacious adversary. In the past decade, vaccine candidates by Nabi Biopharmaceuticals and Merck & Co Inc failed in costly, late-stage clinical trials. Now, led by Jansen, Pfizer is taking a shot. Competitors, including vaccine giants GlaxoSmithKline, Novartis and Sanofi, are, too.

And while the race could lead to a viable vaccine, potentially worth billions in sales, critics say companies may be risking costly failure with so much work on a bacterium that is still barely understood.

'BAG OF TROUBLE'

Staph has been living in and on its human hosts for centuries. At any given time, 25 to 35 percent of individuals will test positive for staph, often with no symptoms. But the bacterium can cause a range of diseases from boils and impetigo to raging blood infections and deadly bacterial pneumonia.

The discovery of penicillin in 1928 gave doctors a way to defeat staph infections, but overuse and misuse gave rise to drug-resistant staph. Methicillin was developed to overcome drug-resistance, but by the 1960s, staph evolved new defenses to overcome this more powerful version of penicillin.

Thus began the decades-long battle against methicillin-resistant staph, now the most common cause of hospital-acquired infections that is increasingly spreading into army barracks, prisons and daycare centers.

Dr. Bill Gruber, a Pfizer senior vice president who led clinical trials for Prevnar 13 and is running the company's Staph aureus trials, thinks of the bacterium as "a little bag of trouble."

"Basically, it has a number of different toxins and defenses to try to defeat you."

That may explain why vaccines from Nabi and Merck failed. Both tried to defeat this bug by attacking on just one front.

The vaccine by Nabi, now Biota Pharmaceuticals, focused only on the sugar capsule the bacteria make to hide from the immune system, while Merck's focused on a single protein that helps staph gets its nutrition. Neither lived up to expectations.

"We've learned that just focusing on one target of Staph aureus might not be sufficient," said Dr. Buddy Creech, an infectious diseases expert at Vanderbilt University.

IT TAKES STAMINA

Jansen has been working on a Staph aureus vaccine for the past decade, first at Merck, then at Wyeth, and now at Pfizer.

The East German-born scientist - who fled to the West in 1960 and earned her PhD in biology at Philipps University in Marburg - says it takes stamina to develop a successful vaccine, a process that can take 15 years or more. With the cervical cancer vaccine Gardasil, which had 2012 sales of $1.6 billion, it took 14 years from lab bench to government approval. "That's actually a fast development program," she said.

With Staph aureus, it took eight years from the first experiments to human safety trials. Now, it could take another seven to 10 years to wind up clinical trials, putting the team about midway through the process.

Pfizer's initial vaccine targeted three mechanisms key to staph's survival and ability to cause disease. Two of those focused on sugar capsules. The third attacks a mechanism called "clumping factor," which allows bacteria to stick to proteins when they enter the body.

But Jansen's team wanted one more point of attack. They added a fourth antigen, a protein that allows the bacterium to steal manganese - a key nutrient - from host cells.

The result is a four-antigen vaccine that generates antibody responses at distinct points of the life cycle of the bug. The company is testing this in Phase 1/Phase 2 trials in healthy adults in the United States.

If Pfizer gets the results they hope for, likely later this year, the company expects to meet with regulators to iron out a plan for larger trials involving thousands of individuals.

Initially, the vaccine would be aimed at preventing infections in millions of people globally who need elective procedures such as a hip replacement. Ultimately, it could be used to protect people at risk in the broader community.

RIVAL VACCINES

Pfizer is furthest along, but the large, untapped market, estimated to be worth $3 billion to $4 billion a year, has drawn interest from several companies.

GlaxoSmithKline has been quiet about its approach. The drugmaker had been partnering with Nabi's failed StaphVax candidate, and in 2009 bought another Nabi candidate called PentaStaph for $46 million.

Company researchers declined to discuss their program, but Glaxo spokeswoman Melinda Stubbee confirmed the company has a four-component vaccine in Phase 1 development. "We are still evaluating the data and haven't yet announced plans to present the data or to pursue further development," she said.

NovaDigm Therapeutics, a private company based in Grand Forks, North Dakota, is developing a single-antigen vaccine that targets both staph and yeast infections caused by the fungus Candida.

Other rivals with early-stage programs include Novartis, which has a vaccine in Phase 1 trials, and Sanofi, which is partnering with privately held biotech Syntiron.

Although academic researchers applaud these efforts, they say companies may be rushing into trials too soon, especially when so much is unknown about how staph interacts with people.

"Our development of Staphylococcal vaccines has predated an adequate understanding of the human response to infection," Creech said.

For instance, it is still not clear whether a Staph aureus vaccine that protects against skin infections will also protect individuals from bloodstream infections. It may be that instead of preventing infection, some vaccines will merely blunt infection.

Dr. Robert Daum, who leads the MRSA Research Center at the University of Chicago Medical Center, doubts any of the current candidates will make it into widespread use. "I am convinced we need a vaccine. I'm just not sure anyone knows how to make one yet."

Jansen, who knows Daum, said she understands his skepticism. "I'm a microbiologist. I know bacteria pretty well. They are very potent adversaries."

She says there's a reason the company was not the first out of the gate. "We wanted to make sure that we looked under all the rocks and found what we needed to find."

Tests in animals and people suggest the vaccine induces production of antibodies that defeat staph's defenses and kill the bacteria. "To our knowledge, we are the only ones who have demonstrated very, very robust killing responses."

That was enough for Jansen. "We essentially said, 'That's it. We put it together as best as we know how. Now is the time to test it.'"

(Editing by David Greising, Mary Milliken and Tim Dobbyn)

It’s time to do an update on the treatment of atrial fibrillation. It’s been a while, and there are worthy things to report from the real world.

Stroke prevention in AF:

Always start with basics: The most important aspect of treating atrial fibrillation is preventing stroke. Although there are some innovative devices and procedures in development, the only proven way to prevent stroke in patients with AF is to use drugs that block coagulation—anticoagulants. (I used to call them blood-thinners, but that’s not accurate; the blood is the same viscosity on or off an anticoagulant.)

In recent years, three novel oral anticoagulants (dabigatran (Pradaxa), rivaroxaban (Xarelto) and apixaban (Eliquis)) have been approved as alternatives to warfarin for patients with AF. The evidence base in support of these new agents is robust. More than 50,000 patients across the world have been enrolled in studies comparing novel anticoagulants head-to-head with warfarin. The results were clear: the new agents were either equivalent or superior in both efficacy (stroke prevention) and safety (bleeding). There was also a consistent trend towards lower mortality with the novel drugs. Other advantages of the new agents include convenience (no INR testing), lack of dietary or drug-drug interaction and rapid anticoagulation after an oral dose (rather than days for warfarin).

But there are headwinds as well. The new drugs are costly, for some, unaffordable. The drugs may be more convenient for patients, but it’s a different story for office staff toiling in the bloated US healthcare system. I know a medical assistant who spends almost every day, all day, just doing pre-authorizations for novel anticoagulants. Five to ten minutes per patient turns into a full-time job with benefits, just for sending information—in triplicate—to insurance companies. Imagine that.

Dabigatran (Pradaxa):

Being first to the marketplace cut both ways. On the one hand, Boerhinger Ingelheim got a head start in a market that had waited nearly 50 years for a warfarin alternative. To say people were excited to have something better than a rodenticide would be a severe understatement. Once approved, dabigatran use soared.

Irrational exuberance usually ends the same way. It turns out there was a steep learning curve with dabigatran. Investigations of early bleeding reports exposed errors in prescribing and clinical judgment. To be fair though, most of the adverse events were simply bleeds that occur when one blocks coagulation, which is the tradeoff when trying to prevent stroke. This notion was born out in subsequent reports of dabigatran-related bleeding events, which failed to reveal a signal of harm. Logic aside, it did not take many adverse event reports to spark the “Bad Drug” ads in mainstream media.

Dabigatran has two other pesky issues: First, in at least 10% (probably closer to 20%), patients experience stomach and esophageal discomfort with the acidic capsule. These are real problems that I have seen range from minor nuisances up to esophageal ulcerations. This is a big issue because patients often feel bad with their AF; it’s not good when their new drugs make them feel worse. Plus, there’s a lot of education to cover with AF; getting bogged down in dealing with stomach pain from an anticoagulant distracts and creates extra work. Finally and not to be dismissed easily: dabigatran must be taken two times per day—a tough ask for many.

Rivaroxaban (Xarelto):

These problems paved the way for rivaroxaban (Xarelto). The once-daily drug is well tolerated and does not often cause stomach pain. The convenience of once-daily dosing is huge. Studies show adherence is better with medicine taken one time per day.

Yet rivaroxaban started slowly. Clinicians were worried the drug wasn’t as effective as dabigatran or warfarin. The Rocket-AF trial showed rivaroxaban to be non-inferior to warfarin, while dabigatran and apixaban could boast superiority from their trials. In fact, debate over Rocket-AF was heated, and the drug had a tough FDA hearing. Then, once approved, it entered a landscape marred by bad-drug ads. Insurance companies make (emphasis on present tense) it tough too; they aren’t paying for a new drug without adding hurdles. (Five to ten minutes of extra paperwork per patient adds up to…)

I was tentative about rivaroxaban for a different reason. As a proceduralist, I was worried that the new anticoagulant had not been tested in AF patients destined for procedures. Unlike dabigatran, which has a solid evidence base as an effective peri-procedural anticoagulant, there was simply no data with rivaroxaban. Could I use it before cardioversion or AF ablation? Would a once-daily non-inferior anticoagulant stand up to the rigors of left atrial ablation? Was it worth switching a patient doing well on rivaroxaban to warfarin before their procedure?

I am happy to report some early information on peri-procedural use of rivaroxaban.

There were 5 studies presented at the Heart Rhythm Society sessions earlier this month. The data were encouraging. For those interested in the medical details, I summed up the abstracts in a short post over at Trials and Fibrillation on theHeart.org.

The presented data mirror my experience. Over the past year, I have yet to see a major adverse event with rivaroxaban, and this experience includes cardioversion and AF ablation. I asked around and my colleagues echo the same sentiment. Although early, and I could be wrong, I don’t think this is fluky. Consider that in the Einstein-PE trial, rivaroxaban, albeit at a higher dose, proved to be an effective strategy to treat pulmonary embolus (blood clot in the lung.) This is significant because PE is a disease that requires potent anticoagulation. That rivaroxaban worked so well speaks to its anticoagulant effects.

Apixaban (Eliquis):

I have not used the newly approved drug enough to render an opinion. Its clinical trial boasts the most impressive data against warfarin, and apixaban is the only one of the new agents that can claim a mortality reduction. As a twice-daily drug, adherence will be an issue. I’ll give you an update when I know more.

Conclusions:

Drugs that block normal coagulation increase the risk of bleeding. That’s how they prevent strokes. It’s a trade-off. The cost of preventing stroke is an increased risk of bleeding. In patients with AF and risk factors for stroke (high blood pressure, diabetes, prior stroke, weak heart muscle, vascular disease, female gender and age > 65), multiple trials have shown a net clinical benefit in favor of anticoagulation. But we must be mindful of two important issues: the risk of stroke in AF is not binary (yes or no); rather it varies depending on associated diseases. (See CHADS-VASC score.) Patients at higher risk of stroke enjoy more risk reduction from anticoagulants than lower risk patients.

Second, and most important, the decision to take an anticoagulant should be a shared one between patient and doctor. The risk of stroke on and off anticoagulants should be presented. Bleeding risk should be considered as well. I never tell my patients they need to take an anticoagulant. I simply try to replace fear and ignorance with the best evidence. Then I am comfortable with what they choose, for it is always their choice.

And to ward off commentary that I am promoting dangerous anticoagulants, let me leave you with the obvious:

It is better not to get AF. If you prevent the disease, then you don’t have to face tough decisions about drugs and procedures. Good movement, good food, good sleep and good attitudes will make it more likely that you will see me on a bike ride than in the clinic.

JMM

NEW YORK (Reuters Health) - In a new study, people with high blood pressure who could communicate with their pharmacists online had better blood pressure control a year after that service ended.

Previously researchers had found that patients randomly assigned to the web-based pharmacy care did better than those who used a patient website but had no extra help or were only trained to monitor their blood pressure at home.

The new findings suggest some of those benefits may hold up over the long run - even after patients stop messaging with their pharmacists, researchers said.

Hayden Bosworth, who studies treatment adherence at Duke University Medical Center in Durham, North Carolina, said there's been a lot of interest in how to help patients stick more closely to their blood pressure and cholesterol medications, for example.

"From a health care plan perspective, these interventions are expensive and we need to look more at the sustainability of the effects and look at it long term," said Bosworth, who wasn't involved in the new research.

"We need to look at it from a (return on investment) perspective."

The new study took place at Group Health, a Seattle-based health care system. Patients there already had online access to parts of their medical records and could email with their doctors through a secure website.

Researchers led by Dr. Beverly Green randomly assigned 778 people in the system with high blood pressure to one of three groups.

One group received usual care, a second was trained in how to monitor blood pressure at home and a third received the monitoring instruction and was able to communicate online with pharmacists.

A year after the intervention ended, 618 patients remained in the study. Blood pressure was controlled - meaning less than 140/90 milliliters of mercury (mm/Hg) - for 60 percent of people who had online access to pharmacists, compared to 48 to 52 percent of those in the other groups.

Average systolic blood pressure - the top number - was 134 in the pharmacy group versus 138 among usual care participants and 141 for the blood pressure monitoring only group. There was no difference between groups when it came to diastolic blood pressure, the study team reported in JAMA Internal Medicine.

"We thought that since the patients were used to taking care of their blood pressure and communicating with their pharmacists, now they would do that with their provider," Green told Reuters Health.

She said a formal cost analysis of the program is in the works, but that online pharmacist access cost about $400 per patient.

Given the improvement in blood pressure, "I believe it is very inexpensive," Green said.

But current reimbursement plans make it difficult to make these types of programs work, she said. For example, doctors typically don't get paid for communicating with patients online or over the phone - only in person.

Bosworth said online access to pharmacists is just one way to improve adherence to blood pressure medicines. Texts and emails from case managers are other strategies, he said.

"These kinds of interventions - patients are extremely satisfied with them," Green said.

"They really appreciate being able to get a hold of their provider when they need it. And they also like that they can get their questions answered when they need it and they don't have to come in," she added.

"I think we're at a point where we can do these self-management programs relatively well for at least med adherence," Bosworth told Reuters Health.

"The important part now is how do we take these, package them, and implement them in the real world?"

SOURCE: http://bit.ly/10lllFn JAMA Internal Medicine, online May 20, 2013.

NEW YORK (Reuters) - Little known biotechnology company Merrimack Pharmaceuticals Inc has quietly built a large pipeline of experimental cancer treatments that it aims to deliver at a fraction of the cost spent by larger rivals.

That could translate into lower-cost treatments for large unmet needs, such as pancreatic cancer, at precisely the time when pressure is mounting to reduce runaway healthcare spending.

Despite six drugs in clinical development - one of them in late-stage trials - and two more about to advance to human testing, Merrimack is burning only about $20 million a quarter.

"For the size and scale of what we do, that's eye poppingly low," Merrimack Chief Executive Robert Mulroy told Reuters.

"Our cost structure is orders of magnitude lower than anybody to date in this business. Our cost from starting a discovery program to getting into the clinic is less than $20 million, and the industry average is close to half a billion per molecule," he said in an interview this week.

"Hopefully, we're going to get to less expensive drugs because our capital costs to be successful with them will be so much lower."

That would be music to the ears of payers and the overtaxed U.S. Medicare system contending with new cancer treatments that can exceed $100,000 per patient.

Started by six professors from Harvard and the Massachusetts Institute of Technology in 2000, Merrimack is nearing the finish line with what could be its first commercial product, a nanotherapeutic treatment for pancreatic cancer - a disease for which patients currently have few options.

Shares of Merrimack, which has a market value of about $500 million, are down nearly 16 percent this year, while the biotech sector overall has been on the rise.

Brean Capital analyst Gene Mack said investors have been wary about the prospects for the company's lead drug because the failure rate for pancreatic cancer drugs has been high and Merrimack is testing its drug in patients that have failed prior treatment - a population with a very poor prognosis.

"Investors don't realize how much progress has been made in the last year," Mack said. "Fundamentally, this is my favorite company (worth) under a billion dollars."

Late-stage trial data on the lead drug candidate, known as MM-398, is expected the second half of this year. If the study succeeds, the company could file for approval late this year or early in 2014.

MM-398 is designed to treat a particular type of tumor - hypoxic tumors - that tend to be resistant to standard therapies because of poor blood flow to the tumor.

"You don't have a lot of highways to the tumor so you don't get a lot of drug there," Mulroy explained.

The Merrimack technology is designed to deliver cancer-killing therapy directly into the tumor and have it work for far longer than other new medicines that directly target tumors.

"Our technology keeps the drug in the tumor for over a week as opposed to just a few hours," Mulroy said.

Hypoxic tumors are very common in pancreatic cancer, making it notoriously difficult to treat, but are also present in many other types of solid tumors.

Merrimack is developing a companion diagnostic test that uses a radioactive imaging agent to identify hypoxic tumors. If the test works as intended, MM-398 could also eventually treat lung, breast, colon and other cancers if patients are found to have the right type of tumor, giving it a huge potential market. The company plans to test MM-398 in combination with chemotherapies and targeted biotech medicines.

Merrimack also has a drug, MM-111, in Phase II testing for gastric cancer, for which there is an enormous unmet need, particularly in China and Asia.

The company has enough cash to fund its numerous clinical trials for the rest of this year and take MM-398 through to approval and commercialization, Mulroy said.

The company has full rights to seven of the eight drugs in clinical development and hopes to retain them for the U.S. and European markets while looking for partners to sell the medicines in other parts of the world, the CEO said.

French drugmaker Sanofi acquired global rights to the Merrimack drug MM-121, being tested in lung, breast and ovarian cancer. Merrimack, which will get milestone payments and royalties on future sales of the medicine, expects data from four Phase II trials of MM-121 later this year.

In another vote of confidence, Sanofi is the company's second-largest shareholder with more than a 5 percent stake, according to Thomson Reuters data.

Merrimack's share performance over the second half of the year will hinge on a steady flow of clinical data, with four Phase II studies and the pivotal Phase III on MM-398 expected to be reported in the coming months.

"There will be plenty of opportunities to show that the technology works," Mulroy said. "We're in a big transition year for us."

(Reporting by Bill Berkrot; editing by Ed Tobin and John Wallace)

The pharmaceutical company’s Discovery Fast Track program is designed to identify and collaborate with academic researchers developing novel therapeutics and help advance their work.

Applicants submit a therapeutic hypothesis and target information and the status of the biological screen. Judging criteria for the submissions, according to the contest website, includes:

• Strength of the therapeutic hypothesis
• The degree of originality of the work presented
• Level of completeness of the target/screening assay
• Potential impact or benefit of the target to medicine (unmet medical need)
• Investigator’s and institution’s capabilities to support entry into the Discovery Fast Track Competition and for joint execution of a DPAc project

In August 2013, an expert panel of judges will select up to 20 finalists, who will then submit an expanded application including confidential supporting data and present their proposal to GSK. Winners will be selected in October 2013.

Those academic researchers who are chosen will get access to some of the vast resources of the big pharma business, such as high throughput screening. That means that they can test millions of pure compounds (1.8 million to be exact) using a diverse set of technologies in biochemical and cellular assays of different complexity. It also has proprietary software for validation.

The deadline for submissions is July 19. Applicants can apply here.

Winning researchers will partner with investigators on GSK’s Discovery Partnerships with Academia team to develop viable, research-stage drug candidates into innovative medicines, according to a company statement. The three year old Discovery Partnerships program got its start in the UK and to date has led GSK to initiate nine collaborations, including two in the U.S. — one with Vanderbilt University to deveop a group of drugs to treat severe obesity and the other with the Fred Hutchinson Cancer Research Center to develop muscular dystrophy therapeutics.

Other drug developers have used innovation challenges to crowdsource ways to improve chronic conditions and help solve painpoints in healthcare like Sanofi with its Data Design Diabetes challenge and Janssen’s Connected Care challenge.

A spinoff of Epitomics (now owned by Abcam) that’s using the biotech’s rabbit monoclonal antibody technology to discover and develop new cancer drugs has raised at least $15 million.

According to a recent U.S. Securities and Exchange Commission filing, Apexigen could continue raising up to $20 million in an equity round that’s already seen participation from 30 investors. The company’s VP of business development couldn’t be reached for more information.

The Burlingame, California, startup was spun out of Epitomics in 2010 with the rights to use the company’s monoclonal antibody and humanization technologies to develop biopharmaceuticals for diseases that are difficult to treat.

Many companies develop monoclonal antibody drugs for cancer. Apexigen is doing it based on rabbit-derived, humanized monoclonal antibodies rather than mouse or human-derived antibodies. It says the rabbit immune system creates more diverse antibodies to a target because of a unique mechanism called gene conversion.

The startup’s most advanced internal candidate, APX005, targets the CD40 protein and is under preclinical development for the treatment of difficult to treat cancers such as pancreatic cancer. Apexigen also has at least four other drug candidates being developed through licensing deals, mostly in China.

Other ongoing collaborations include a deal with Boehringer Ingelheim under which the Big Pharma will develop cell lines for APX005.

[Photo from Flickr user Daniel Hall]

May 21 (Reuters) - A new type of asthma drug meant to attack the underlying causes of the respiratory disease slashed episodes by 87 percent in a mid-stage trial, making it a potential game changer for patients with moderate to severe disease, researchers said on Tuesday.

"Overall, these are the most exciting data we've seen in asthma in 20 years," said Dr. Sally Wenzel, lead investigator for the 104-patient study of dupilumab, an injectable treatment being developed by Regeneron Pharmaceuticals Inc and French drugmaker Sanofi.

The drug also met all its secondary goals, such as improving symptoms and lung function and reducing the need for standard drugs called beta agonists.

Although far larger trials will be needed to confirm findings from the "proof of concept" study, researchers expressed optimism. They noted that dupilumab has also shown the ability to tame atopic dermatitis, or severe eczema, an allergic condition that is not well controlled by current treatments.

Results of the 12-week asthma study are being presented on Tuesday at the annual scientific meeting of the American Thoracic Society in Philadelphia.

The medicine, if approved, could hold promise for patients with moderate to severe persistent asthma that is not well controlled by standard drugs.

"We have been treating asthma with sort of Band-Aid therapies that didn't get at the underlying causes," Wenzel said in an interview, adding that dupilumab could be an important step in going to the root of the problem.

The drug works by simultaneously blocking proteins that have been linked to inflammation, interleukin-4 (IL-4) and interleukin-13 (IL-13).

HITS ELUSIVE TARGETS

Wenzel, director of the Asthma Institute at the University of Pittsburgh, said other drugmakers have tested medicines that block one or both of the proteins, but without success.

The trial recruited patients with high levels of eosinophils, a biomarker that shows immune system cells called type 2 helper T cells (Th2 cells) associated with allergy and asthma have been activated.

Such patients were deemed likely to benefit from treatment.

All patients initially stayed on their standard asthma treatments, meaning medium-to-high doses of inhaled glucocorticoids, as well as long-acting beta agonists. But patients gradually tapered off on those drugs and were no longer taking either of them after 9 weeks.

Throughout the Phase IIa trial, half the patients also received weekly injections of dupilumab, while half received placebo injections.

After the ninth week, about 25 percent of those on placebos had experienced exacerbations, a catch-all term that included the need to take a beta agonist, a decrease in lung function, the need for an oral or inhaled corticosteroid, or if the patient went to the hospital or emergency room for worsening asthma.

"By end of the trial, after 12 weeks, 44 percent of those in the placebo group had exacerbations, compared with 5 percent of those on dupilumab," Wenzel said.

That represented an overall 87 percent reduction in exacerbations, which Wenzel said was highly statistically significant.

Wenzel said dupilumab was well tolerated, with side effects similar to placebo. But she cautioned that longer trials are needed to fully assess the drug.

Regeneron and Sanofi said standard drugs are unable to control asthma well in 10 to 20 percent of patients. They estimate that inflammation caused by Th2 cells - the type of inflammation among patients they tested - plays a role in half of those moderate to severe cases and affects as many as 2.5 million people in the United States and up to 30 million worldwide.

Dupilumab has also shown strong hints of safety and effectiveness in two early-stage trials that involved 67 patients with atopic dermatitis. Larger studies are slated to begin later this year.

Atopic dermatitis is inherited and involves patches of highly itchy skin on any part of the body. Patients, many of whom also have asthma and hay fever, have compared the sensation to having unending poison ivy.

"This asthma data and the data we already have in atopic dermatitis really raises the possibility the scientific community has finally hit upon the key pathway across all these allergic diseases," George Yancopoulos, Regeneron's research chief, said in an interview.

Regeneron has become one of the world's biggest biotechnology companies in the past 18 months, following the U.S. approval in late 2011 of its Eylea treatment, developed with Bayer AG. It is used to treat the "wet" form of macular degeneration, the leading cause of blindness in the elderly.

The company and partner Sanofi are also developing promising treatments for cholesterol and rheumatoid arthritis.

Pfizer said it would continue to study the experimental drug, inotuzumab ozogamicin, in other hematologic cancers.

"Hematologic cancers are a complex group of diseases, with more than 70 different types of lymphomas, leukemias or myelomas that require unique treatment options," Mace Rothenberg, Pfizer's senior vice president of clinical development and medical affairs for its oncology business unit, said in a statement.

No new or unexpected safety problems were identified by the independent monitors, Pfizer said.

Inotuzumab is not a particularly high-profile drug in Pfizer's developmental pipeline, but had reached the final stage of human trials before the company would have applied for FDA approval.

Analysts at Cowen & Co had forecast sales of $100 million in 2016 for the drug.

The study tested inotuzumab in combination with Roche Holding's Rituxan in patients with relapsed or refractory aggressive non-Hodgkin lymphoma who were not candidates for intensive high-dose chemotherapy. That combination was compared with patients who got either Rituxan and Teva's Treanda or Rituxan and the chemotherapy drug, gemcitabine.

During a planned interim analysis, an independent Data Monitoring Committee concluded that inotuzumab ozogamicin plus Rituxan would not improve overall survival compared with the other drug regimens.

(Reporting by Bill Berkrot; Editing by Jan Paschal)

The Open Research Exchange is currently looking for researchers to use the hub. It’s also named members of a scientific advisory board for the OpenDNS site.

PatientsLikeMe developed the hub with backing from the Robert Wood Johnson Foundation, which provided a $1.9 million grant. It reflects a view in the patient-centered care movement that the way the U.S. Food and Drug Administration and drug developers in particular define a successful drug is not necessarily the same as how a patient taking that medication would define it.

Jamie Heywood, co-founder of Cambridge, Massachusetts-based PatientsLikeMe, said at the time of that announcement: “If we can develop a measurement system that is openly shared and centered on the patient, we will move our knowledge forward and bring medicine to a new and important level.”

Researchers have free access to the platform and in exchange, data indicating the validity and performance of their products will be publicly available on the website, according to a page detailing how the hub works. It will function like an open-source platform in that health outcome measures developed in the hub will be licensed under terms that allow others to use and extend them at no cost.

PatientsLikeMe is an online patient community to help patients connect with each other as well as giving access to treatment and outcomes reports. It’s has been successful at attracting a combination of Big Pharma companies such as Merck and Sanofi, and at least one payer – Aetna.

Karyopharm’s approach, in phase 1 development, targets a group of proteins associated with cancer. These proteins, referred to as Exportin 1, thwart tumor suppressor proteins from doing their job by “escorting” them from the cell’s nucleus into the cytoplasm.

If tumor suppressor proteins remain in the cell’s nucleus they can program the cancer cells to self-destruct.

Karyopharm’s selective inhibitors of nuclear export will treat advanced hematologic and solid tumors.

The financing round included Delphi Ventures, which will get a seat on Karyopharm’s board in return for its investment. Deepa R. Pakianathan will represent Delphi on the board.

In a CEOCFO interview earlier this year, CEO Dr. Michael Kauffman said the company’s plan is to take the drug through to the approval stage in the U.S. and Europe “largely on [its] own,” though it would look for a partner for Asia.

It is presenting data from its phase 1 trial at the upcoming American Society of Clinical Oncology’s annual meeting in Chicago next week.

UPDATE: In a phone interview with MedCity News, Sharon Shacham, Karyopharm’s chief scientific officer, said its fundraising has been helped by “robust preclinical validation” as well as by the clinical data it has collected so far. Although the mechanics of cancer cells have been known for years, a previous effort to develop a treatment proved too toxic for noncancer cells. Among the indications it is evaluating for its therapeutics are hematological indications — acute myeloid leukemia, chronic lymphocytic leukemia and Waldenström’s macroglobulinemia — as well as non-Hodgkin’s lymphoma and myeloma.  Although it currently employs 23, it expects to grow its staff to under 30 in the next two years, mainly with lower- and middle-management roles.

[Photo Credit: freedigitalphotos user Salvatore Vuono]

Lundbeck said in a statement that the trial showed safety levels consistent with previously completed studies at lower doses.

Lundbeck and Takeda submitted vortioxetine, also known as Brintellix, for regulatory approval in the United States and Europe at the end of last year.

Industry analysts at Deutsche Bank see the new drug having sales potential in excess of $1.5 billion and possibly up to $3 billion a year, although consensus forecasts for 2016 are a more modest $500 million, according to Thomson Reuters Pharma.

Lundbeck hopes the new drug will provide a new source of revenue as its existing antidepressant, Cipralex, sold as Lexapro in the United States and Japan, comes off patent protection.

(Reporting by Mette Fraende, Editing by Mark Trevelyan)

Researchers from Brigham and Women’s Hospital made the discovery that the clay known as synthetic silicate nanoplatelets could be induce stem cells to become bone cells without the addition of other materials was published in Advanced Materials this week. Akhilesh Gaharwar of the BWH division of Biomedical Engineering, the study’s first author, said it could be used to develop therapeutics for bioengineering and eventually speed up recovery times.

The National Institutes of Health, U.S. Army Engineer Research and Development Center, Institute for Soldier Nanotechnologies, and the National Science Foundation. funded the research, according to the Harvard Gazette.

With more baby boomers reaching retirement age and beyond there’s a need for a new generation of devices and therapeutics that can improve recovery times from fractures. Having an organic source of bone, albeit in the very early stages of development could also be appealing to the medical device industry which has been plagued by lawsuits over problems with metal hip implants.

Another bone related innovation occurred earlier this year, when a a skull implant developed by Oxford Performance Materials with the help of 3-D printing was used to replace 75 percent of a man’s skull. The OsteoFab Patient Specific Cranial Device is made from a high performance polymer that’s biocompatible and mechanically similar to bone.

[Photo credit BigStock Photo surface cracked clay]

The “virtual” business models that have become common in many biotech startups may allow companies to operate with less capital, but they also present their own set of challenges.

One of those is finding quality vendors to conduct research and development, clinical trials and other services, and managing those relationships.

“There’s high turnover in the vendor market, there’s high fragmentation in the vendor market, and there’s a lot of paperwork that goes into protecting your assets any time you’re doing something for life science,” said Cliff Culver, founder of a health IT startup aimed at making the process of outsourcing services less cumbersome.

Culver, who was previously working for a publicly traded healthcare consulting company on healthcare IT initiatives, joined up with a few former Pfizer executives in late 2011 to form the online platform OnDeckBiotech. It’s got two components for biotech companies to use: a directory of service providers (CROs, CMOs, consultants, etc.) and a set of administrative tools to manage both new and existing relationships.

On the platform, vendors maintain a free company profile that includes an overview of services, background documents and client testimonials. Biotechs that use the platform can search for services, communicate with vendors and compare proposals. Service providers pay a fee if and when they receive new business.

OnDeckBiotech launched in beta in February of last year. According to Culver, the company has now assembled a network of a few hundred vendors, a couple of VC-backed biotechs and a large pharmaceutical company using the platform.

It’s also recently partnered with trade organization MassBio to create a version of the platform that contains MassBio member vendors. “One interesting thing is that a lot of the startups in this space are actually service providers, but they’re very small and don’t necessarily have a way to get out there,” he said.

Culver said the next steps for the Boston-based company are finalizing more of those kinds of partnerships, which will likely include a national-scale rollout of the platform.

[Photo Credit: freedigitalphotos user sheelamohan]

STOCKHOLM (Reuters) - Sweden's Recipharm has hired UBS to advise on either a partial sale of the pharmaceutical company or a listing on the Stockholm exchange, a source close to the process told Reuters on Thursday.

The source said a part-sale or a listing were equally likely. If a listing were the preferred outcome, it would happen in the second half of 2013.

Recipharm, which is a contract manufacturer and developer of drugs for the pharmaceutical industry, has around 1,500 employees and made earnings before interest, tax, depreciation and amortization (EBITDA) of 281 million Swedish crowns ($42.32 million) in 2012 on sales of 2.07 billion crowns. Its core profit margin was 13.5 percent, up from 9.6 percent in 2011.

German drug firm Aenova, whose business is similar to Recipharm's, was bought by private equity firm BC Partners from Bridgepoint last year at between 10 and 11 times EBITDA, a person familiar with that transaction said.

Applying that multiple to Recipharm would give it an enterprise value of 2.8 to 3.1 billion Swedish crowns.

Recipharm had net debt of 420 million crowns at the end of 2012.

Recipharm was founded in 1995 by Lars Backsell, currently chairman of the board, and Thomas Eldered, who serves as its chief executive. They jointly own 100 percent of Recipharm's shares.

Recipharm and UBS both declined to comment.

($1 = 6.6406 Swedish crowns)

(Reporting by Sven Nordenstam. Editing by Alistair Scrutton and Jane Merriman)

The La Jolla, California, biotech formerly known as Anaphore is looking a little different these days. Under the leadership of former Fate Therapeutics CEO Paul Grayson, Anaphore changed its name to RuiYi Inc., honed its focus from developing broader classes of proteins to new biologic drugs for the Chinese market,  and set up a four-way collaboration to bring its first rheumatoid arthritis drug to market.

Biotech is growing fast in China, but most of that effort has been in biosimilars and biobetters, Grayson said. That’s a great place to start because those drug classes are generally less risky to develop, but RuiYi wanted to do something that would make it stand out. “We wanted to be novel without being too novel or we would get back into a different risk bucket,” Grayson said.

So it set its focus on a biologic drug for the Chinese market, and went to work evaluating hundreds of different candidates. Near the end of last year, it licensed its first candidate, RYI-008, from biopharmaceutical company arGEN-X BV. The biologic drug is a monoclonal antibody that’s selective to IL-6, a cytokine associated with inflammation and cancer.

“There’s already an approved antibody that targets the receptor; ours targets the cytokine, so you can actually use a lot less,” Grayson said. “It’s a known biologic mechanism, and there’s a lot of data showing that it’s safe and it has the potential to be a big therapeutic in terms of medical need.”

The antibody also has a long half-life, so patients don’t have to take it very frequently, Grayson said. The company is targeting a once-monthly injection to treat rheumatoid arthritis.

RuiYi’s market strategy starts with commercializing the therapeutic in China, where Grayson said the addressable patient population is nearly four times what it is in the U.S. And, only a small percentage of those patients have ever used a biologic therapeutic for RA, instead being treated with NSAIDs, DMARDs and natural remedies instead. Grayson said these factors not only create a solid market opportunity for RuiYi to establish itself in China, but also set the stage for quick enrollment in clinical trials.

Now that it’s got its strategy in line, the company is working with Shanghai company Genor Biopharma to develop the antibody and with biomanufacturer CMC Biologics to develop a cell line that will be used to manufacture it. Grayson said he’s anticipating filing an IND in China within 18 to 26 months.

The company has set up a lab in China with about 15 employees, who are also working on some of RuiYi’s own pre-clinical drug candidates. It’s operating with the $38 million it raised a few years back from investors including Merck Serono Ventures, 5AM Ventures and Versant Ventures.

Bristol released preliminary data from the early-stage trial on Wednesday, with more detailed results expected to highlight the American Society of Clinical Oncology's annual meeting in Chicago that starts at the end of the month.

Patients in the study received Bristol's immunotherapy Yervoy, which is already on the market, and an experimental treatment called Nivolumab that attacks an immune-system-inhibiting protein called PD-1. The combined treatment shrank tumors in a majority of patients.

"We have never seen this with immunotherapy before," said Dr Jedd Wolchok of New York's Memorial Sloan-Kettering Cancer Center. "The vast majority of patients have a decrease in tumor burden. In melanoma, we're used to seeing the opposite," he said of the notoriously difficult-to-treat form of skin cancer.

Investors have been eager to see results of the study, with Bristol shares reaching a 10-year high on Wednesday in advance of the data release.

Both drugs are designed to target different parts of the immune system that act as brakes even when cancer is present, preventing immune cells from attacking tumors. By gumming up these brakes, the drugs free the immune system to attack and kill tumor cells.

Approved in 2011, Yervoy, or ipilimumab, was the first drug to significantly extend survival in patients with advanced melanoma, the most deadly form of skin cancer. It boosts the immune system by blocking the action of a protein called CTLA-4.

Nivolumab, which is in late-stage testing, targets a protein called PD-1, or Programmed Death receptor, a new class of immune-system drugs that shows promise not only in melanoma but also in lung and kidney cancer.

Typically, only about 11 percent of patients respond to Yervoy, and recent studies in melanoma suggest Nivolumab produces a response rate of about 41 percent, Wolchok told a news briefing.

The current study looked at the combination of the two drugs based on animal studies suggesting that together they might work better than either drug alone.

Wolchok reported results for 86 patients in the trial as of February 2013, including 52 patients who were on both drugs at the same time. In one of the treatment groups, which will likely advance to late-stage trials, 53 percent of patients treated with both Yervoy and Nivolumab simultaneously had an objective response - defined as at least a 50 percent reduction in tumor size.

RAPID RESPONSE

Dr Sandra Swain, president of ASCO, called the findings remarkable. "This combination treatment led to a very rapid and profound lasting tumor shrinkage. Ninety percent of patients are still responding," she said.

Three out of four patients who responded to the dual treatment had tumor shrinkage in the first three months.

Among the most advanced melanoma patients, Wolchok said the combination of the two drugs produced "rapid and deep regressions, with many showing more than 80 percent tumor regression by the time of the first scan."

Overall, most patients had some decrease in tumor size. In 31 percent of all patients taking the dual therapy, tumors shrank by greater than 80 percent, Wolchok said.

In 18 percent of patients, the drug combination produced a complete response, meaning tumors were no longer detectable, Wolchok said in an interview. He said they do not yet have any data on relapse because 90 percent of patients who responded to the treatment are continuing to benefit.

The combination also appeared to be safe. About half of patients who got both treatments had a drug-related side effect, but in most cases it was linked to elevations in enzymes related to the pancreas and liver.

"These are reversible, sometimes without treatment," Wolchok said, although some patients did need a short course of the steroid prednisone. There were no drug-related deaths.

"We really didn't see anything new with the combination" related to safety, he said.

Bristol-Myers plans a late-stage clinical trial that looks at both drugs in combination, as well as each separately, in patients with melanoma. It has also begun testing the same combination in lung cancer and renal-cell cancer.

"We view the combination of immunotherapy as a significant one that we'll be pursuing," Michael Giordano, Bristol-Myers' senior vice president of global development for oncology and immunology, said in an interview.

So far, Bristol-Myers is furthest ahead in its development of a PD-1 inhibitor, but Merck & Co Inc last month won designation from the U.S. Food and Drug Administration as a "breakthrough therapy," which could speed development and regulatory review of the product.

In a recent note, Bernstein Research analyst Tim Anderson said Bristol's anti-cancer drug PD-1 "is the major driver of investor interest at the moment," but said awareness is building that competitors "may not be very far behind."

Last November, Merck reported results from a trial of its drug in patients with advanced melanoma and saw a 47 percent response rate. In that trial, the drug benefited patients who had previously been treated with ipilimumab but had not responded, said Dr. Gary Gilliland, a Merck senior vice president for oncology.

Merck plans to present an update of this study on June 2 at the ASCO meeting. Gilliland said the company also is studying its treatment in so-called triple-negative breast cancer, a hard-to-treat form of the disease, as well as head and neck cancer and bladder cancer.

Other companies pursuing the PD-1 or related pathways include Roche, GlaxoSmithKline and Teva.

"PD-1 is arguably the most exciting breakthrough in cancer therapy in a decade," said ISI Group analyst Mark Schoenebaum. "There is speculation that it might offer a cure for some patients with solid tumors. This is unprecedented."

(Additional reporting by Bill Berkrot in New York; Editing by Michele Gershberg and Prudence Crowther)