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Lowering the Cost of Failure in Biopharmaceuticals

Tue, 11/11/2014 - 04:00
Court Chilton

In any business, projects fail, but in biopharmaceuticals, the consequences of failure are especially damaging. Projects in the industry tend to be long and expensive—from clinical trials to regulatory approvals to commercial application. At any point in the process, obstacles can derail a project. Failure is most certainly an option, and for companies with many projects in the pipeline, failure is inevitable.

In this environment, large biopharmaceutical firms need to focus less on avoiding failure and more on reducing its costs. Most companies unfortunately do the opposite. The industry suffers from what is known as “inattentional blindness” and “continuation bias.” Inattentional blindness occurs when firms focus primarily on, for example, the biological hypotheses behind a compound early in trials and don’t also focus on downstream clinical risks, patient selection, and commercial hypotheses.

“Continuation bias” occurs because, over the course of lengthy projects, sunk costs accumulate. Even when clinical trials are going badly, no manager wants to be the one to announce to the company that all of the money spent on a project has been wasted.

Managers thus develop approaches to keep projects with thin prospects going. Outsourcing is one way. Firms can be contracted to conduct unpromising trials, thereby distancing managers from the results. Outsourcing tends to slow learning cycles within a biopharmaceutical firm, which also tends to extend projects past their expiration dates.

Another source of continuation bias is that in big firms projects often are understaffed. With many projects under way simultaneously, big and established biopharmaceutical firms try to gain some leverage, some efficiency by staffing projects thinly, which results in projects that are “long and thin.” Startups, counterintuitively, are even more likely to fall into this trap because—even though they can create “short, fat projects”—ending a project often means the end of the firm.

For big biopharmaceuticals, the challenge is this: how to fail fast. Managers need to pay close attention to the results of early stage clinical trials. Sometimes additional tests that are relatively quick and sharply focused can be ordered to determine whether the basic biology of a drug is going to be effective, or whether a patent can be extended. If those results are unfavorable, then projects can be halted before they move into the next, much more expensive phases.

The related challenge: developing cultures in which employees understand that failure is not a career killer. The manager who decides to shut down a project that is going into a downward spiral should be rewarded, perhaps even celebrated, not punished. Instead of hiding failures, biopharma needs to recognize and accept it, then generate wider learning from it and move forward.

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New and Old Models in Grocery Delivery, and Guilt About Good Jobs

Tue, 11/11/2014 - 01:55
Curt Woodward

I’m not really the kind of person who wants to use a grocery-delivery service. I’m glad they’re available, especially for people who might have trouble navigating the aisles of their local supermarket. But while I’m able-bodied, I figure I should really be able to drag myself to the store and buy my own groceries.

Then we brought home our newborn. Within a day or two, as I watched our food stash dwindle, I was imagining the pure joy of having a stranger shop for me. It wasn’t long before I was signing up.

As it turns out, living in the Boston area offers consumers a chance to try out two generations of online grocery delivery services. One of them is Peapod, an original dot-com era company now owned by Dutch grocery company Ahold. In some areas of the U.S., Peapod operates the delivery services for a regional chain of Ahold-owned grocery stores—in my town, for instance, Peapod is connected to Stop & Shop.

The other service available in my city is Instacart, a very young startup that offers its service in a few cities around the country. Instacart deliveries can come from a number of stores in any given area, ranging from everyday supermarkets to more expensive specialty grocers, and even the membership warehouse mecca of Costco.

I tested both services at home over two weeks, and generally liked both of them. They were easy to use and delivered what they promised. I didn’t find any mistakes in any of the handful of orders I placed, and the delivery people were pleasant each time. Even someone like me, who thinks a lot of grocery baggers don’t do it right, was happy with the way things were packed—cold things were kept cold, dry things kept dry.

One major difference, which isn’t obvious if you just start shopping away, is how these two competitors make money. Instacart marks up the price of each the items listed on its website over the in-store price to help pay for everything—the company doesn’t say by how much—and also charges a per-order delivery fee of $3.99 for two-hour delivery and $5.99 for a one-hour turnaround. The minimum order is $35.

Peapod says its prices are “comparable” to what you’d pay in an actual store, with some differences owing to how local grocery-store managers have priced their inventory at a particular store. Instead of sending shoppers into stores to grab things off the shelves, which is what Instacart does, Peapod has warehouses or smaller store-rooms filled with the items it offers, making its operations more centralized. Its delivery fees are a little higher: $9.95 for orders from $60-$100, and $6.95 for orders above $100.

Another big difference is the way your groceries arrive. Peapod sends its drivers out with climate-controlled box trucks to keep things the right temperature. Instacart, on the other hand, uses a workforce of people driving their own cars, so you’re more dependent on their packing abilities and a speedy arrival to ensure freshness.

Instacart definitely has a leg up in the quality of its website—it’s modern, easy to navigate, and pleasant to look at, while Peapod’s is still stuck in the early 2000s, if not earlier, with teeny-tiny fonts and rigidly rectangular navigation bars and drop-down menus.

Instacart also had much quicker turnaround times, which is a pretty crucial difference. Whenever I filled an order on Instacart, I had plenty of options for when I could get my stuff delivered, even if it was within a few hours and right around dinnertime.

With Peapod, the fastest you can get a delivery is the next day. Just about every time I went to the website to place an order, I was too late to get a next-morning delivery, and had to schedule a window for the afternoon or evening.

Both Peapod and Instacart do a good job of keeping you updated on the status of your orders, too. If you give them your phone number, Instacart shoppers can call and run through possible substitutions when the store is out of something you wanted—a complication that comes from Instacart being a separate company, not tied into any particular store’s inventory. They’ll also call or text when they arrive, if you want, and the service texts you afterward to rate the delivery.

Peapod’s service was almost shockingly on point with text messages—I headed down to meet the driver when I was notified he was getting close, and received a text message on my phone literally the same instant the colorful Peapod truck pulled up in front of my stoop. One slightly old-school note: I had to sign for the Peapod delivery on a paper invoice, which is where I filled in my tip.

All in all, the combination of quicker turnaround times, greater store variety, and more pleasant design made me slightly more likely to order from Instacart when I logged in for another re-supply.

But there was something else nagging at me when I did.

Instacart is one of many fast-growing smartphone-based startups that rely on a largely unattached workforce to make its service feasible. Instacart’s shoppers don’t work for the company, officially speaking—they are “independent contractors” wearing Instacart T-shirts and bearing Instacart-branded bags full of groceries.

You can read about this arrangement in Instacart’s terms of service, where the company makes clear that it doesn’t regard those shoppers as employees. Inside that thicket of legalese and carefully worded protections, the integrated, consistently branded grocery delivery service that you’d see from the outside becomes a passive technology service linking up buyers and sellers.

“Instacart is a communications platform for facilitating the connection between individuals seeking to order food and beverage products and other grocery items … and individuals seeking to assist customers by retrieving and delivering the groceries,” it says.

Instacart also claims to have no control over “the quality, timing, legality, failure to provide or any other aspect whatsoever of the Personal Shopper Services,” and uses all-caps to distance itself from any liability should a customer have problems or conflicts with the delivery people.

For the people who fill your orders and drop them at your door, that can mean a level of flexibility that isn’t possible with rigidly scheduled shift work—a benefit that’s often touted as especially well suited for students, retirees, parents of small children, or others seeking part-time work and a little extra cash. The company has said that drivers can make between $15-$30 per hour, depending on how quickly their jobs get finished.

For Instacart, it also means labor costs are about as low as they can get. Unlike the engineers and product managers at Instacart headquarters in San Francisco, the shoppers and drivers aren’t getting any health insurance, free food, or equity in the company. They also have to cover self-employment taxes and their own transportation expenses.

People reviewing the company at job-listings site Glassdoor have complained about the pay pretty consistently, saying there’s sometimes a minimum guarantee of $10 an hour in newer markets, but that it gets eaten up by parking tickets and gas.

Peapod, on the other hand, is a distinctly real-job kind of company. Its ads for delivery drivers list pay of at least $11 per hour, before tips. Drivers can also get a 401(k) retirement plan with an employer match, health, dental, vision, and life insurance coverage, paid days off, and discounted pricing on groceries.

But online reviews of these jobs aren’t fantastic, either. There are plenty of complaints of bad management, stressful schedules, heavy turnover, and difficult-to-predict schedules. If you’ve ever had a blue-collar job making an hourly wage, you’ll recognize most of these gripes.

Let’s just be honest here and say that, no matter what kind of scheduling and pay scheme the employer is using, delivering groceries for other people can be a grueling job that you probably wouldn’t want to do forever. In a slow-recovering economy, with about 9 million Americans still unemployed, people will take what they can get.

It still makes me question my choice when I buy something from Instacart.

There are a great many startups doing pretty interesting things these days at the place where powerful mobile computing and real-world logistics cross paths. The car-hailing service Uber is the headline example here, and yes, Uber also maintains that drivers are contractors and not employees. It’s being sued by drivers who say they’re being shortchanged by that distinction.

If it continues to grow quickly and expand to new cities, it seems pretty easy to imagine that Instacart will have its own reckoning over how it treats the people doing the heavy lifting. As an otherwise happy customer, I frankly wouldn’t mind seeing a judge decide whether the whole system is fair, or a bit of creative accounting that shortchanges working people.

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As Huge Bills Loom, Immunotherapy Pioneer Dendreon Enters Bankruptcy

Mon, 11/10/2014 - 16:54
Alex Lash

After 22 years, one groundbreaking cancer treatment, and even more ups and downs than the volatile biotech industry would consider normal, Seattle-based Dendreon (NASDAQ: DNDN) has filed for bankruptcy.

The company and its prostate-cancer treatment sipuleucel-T (Provenge) could be sold, or it could emerge from bankruptcy court with completely new ownership. From a reading of court documents, creditors would prefer a quick sale by early February. But either way, the firm’s current shareholders will likely be wiped out, and there will likely be more turmoil for the remaining 700 employees, many of whom are in Seattle.

The move is not a surprise. The firm’s massive debt load and lack of revenues have been a red flag for some time. The debt holders, with $620 million coming due in 2016, will be first in line to get paid out, but the big fight—as with all bankruptcies—will be among those lenders to see who gets paid first, and how much.

They want at least $275 million for the company, according to bankruptcy filings released today. Deerfield Management is Dendreon’s largest lender. It holds 36 percent of the notes coming due in 2016.
Provenge received FDA approval in April 2010, and people both in the financial world and the medical world—not to mention patients with hard-to-treat prostate cancer—were eager to see how the new drug would work. It was the first personalized cancer immunotherapy to get the nod from regulators. The process required extracting a patient’s own immune cells, boosting them with extra cancer-fighting powers, and re-infusing them back into the patient.

Under CEO Mitchell Gold, the firm borrowed a massive amount of cash to make the U.S. launch work. (Gold also sold shares worth nearly $27 million in the two days following sipuleucel-T’s approval.)

But it quickly became clear that the potential clamor for Provenge was not materializing, and the problems piled up. The company priced Provenge too high; doctors were confused about reimbursement; key management roles were left vacant.

Meanwhile, Big Pharma competitors with deeper pockets and, arguably, savvier leadership, brought new prostate cancer treatments to market: abiraterone (Zytiga), from Johnson & Johnson (NYSE: JNJ), and enzalutamide (Xtandi) from the partners Astellas Pharma and Medivation (NASDAQ: MDVN).

Cancer immunotherapy has taken big steps since Dendreon’s pioneering approval. Other autologous treatments, which like Provenge use a patient’s own cells, have shown remarkable results against blood-borne cancers in experimental settings. And ipilumumab (Yervoy), an “off the shelf” treatment that doesn’t use a patient’s own cells, was approved for melanoma in 2011.

Once touted as a multibillion-dollar-a-year blockbuster, Provenge netted $284 million in 2013 revenues, with $224 million more in the first nine months of 2014. Dendreon won European Union approval for the treatment in 2013, but the product has not yet launched there.

A series of adjustments ensued—layoffs, facilities shut down, and in 2013, an attempt to find a buyer. None were forthcoming, according to today’s filings. Then there were more layoffs, more strategic consultants and bankers, and ultimately, after much negotiation with Deerfield and other debt holders, the move into Chapter 11, which is the arm of the bankruptcy code that gives companies breathing room to come up with a plan to pay creditors—either by restructuring, or selling assets—while keeping business going. (In Chapter 7, by comparison, a company is liquidated in piecemeal fashion.)

The plan for Dendreon is two-fold. The company will seek a buyer at auction, with the minimum bid set at $275 million. Dendreon has until December 29 to find a “stalking horse” bidder—bankruptcy-speak for a lead bidder to start the process and set a floor for bidding to discourage low-ball bids.

Other bids must be in by January 27, 2015. An auction is slated for February 3 at the latest, according to the court filings. If no buyer steps up, a recapitalization will take place, with debt holders owning 100 percent of the company, and stockholders most likely wiped out.

Gold was replaced as CEO in 2012 and later surrendered his board seat. He now runs a hedge fund with an analyst who once covered Dendreon.

Dendreon now has 700 employees, according to filings. It’s unclear how many of them are in the Seattle area, where Dendreon is headquartered, but the firm has 200,000 square feet of office and laboratory space in the city. The city’s biotech community has already suffered big losses this year with Amgen’s decision to pull up stakes and take 660 jobs with it.

Obligations to those employees, including bonuses, benefits, and other payments, are up in the air in a bankruptcy reorganization, so workers will be watching the proceedings closely. In the court filings, Dendreon general counsel Robert Crotty wrote that “disruption from employee resignations or lack of morale could have devastating effects on [Dendreon’s] restructuring efforts.” He urged that the company be allowed to honor its obligations to employees.

The firm said today it would continue operating during the restructuring.

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Stemina’s Autism Blood Test Shows Early Promise, Has Lots to Prove

Mon, 11/10/2014 - 15:22
Jeff Engel

In the latest attempt to find a better method for diagnosing autism, researchers at Madison, WI-based Stemina Biomarker Discovery and the University of California-Davis’ Mind Institute published study results Friday of an early-stage, blood-based test that they say identified autistic children with 81 percent accuracy.

The study, published in PLOS One, tested blood samples taken over a 13-month period from 82 children—52 with autism spectrum disorder (ASD) and 30 without—who were 4 to 6 years old and mostly white males. Researchers analyzed metabolites in the blood, trying to establish which of these small molecules signal autism. This approach differs from other high-profile blood-based biomarker studies in the past few years that have tried to detect the disorder by examining the activity, or expression, of genes.

Stemina has conducted two additional similar studies that achieved roughly the same results as the paper published Friday: another one in partnership with UC-Davis’ Mind Institute that involved 278 patients, and a 210-patient study with the Arkansas Children’s Hospital Research Institute, Stemina co-founder and CEO Elizabeth Donley says. The results of those two studies have yet to be published, and Stemina’s autism test is still at least three years and one larger-scale study away from commercialization, she says.

“We are very pleased with the result of this first study because it demonstrates that differences in the metabolism of children with ASD are profound enough to distinguish them from typically developing children,” Donley says in a press release. “This will allow us to understand the individual metabolism of children with ASD in a way we never could before, leading to earlier diagnosis and individualized treatment.”

Stemina, founded in 2006, has used its metabolomics technology to perform toxicity tests on compounds for drug developers, cosmetics and consumer products companies, and the U.S. Environmental Protection Agency, among other customers. But a blood test for autism would be the company’s first diagnostic product.

The average age of diagnosis for an autistic child in the U.S. is 4, although certain healthcare facilities with the right expertise can provide reliable diagnoses at age 2, Stemina says. Diagnosing the disorder as early as possible is important because some studies have shown earlier treatment can boost the child’s cognitive and social skills. The challenge is that the current standard for diagnosis is a series of behavioral tests conducted by experts, partly because scientists have yet to crack the code on the biology underpinning autism.

Plenty of research has been done over the past few years to find a reliable blood-based test to diagnose children sooner, with varying degrees of success. Lexington, MA-based SynapDx is one of the more closely watched companies trying to commercialize such a test. It has raised more than $32 million, and last year it launched an 880-patient, 20-site study of its diagnostic that primarily analyzes RNA molecules in the blood, as a way to measure gene expression.

Donley thinks that her company’s test has an advantage by studying metabolites instead of gene expression because they provide “a readout of the organism’s current state in real time,” she says. “Gene expression will also be important, but we don’t believe it will be as predictive,” she adds. (SynapDx may well be able to test that theory directly, as a secondary objective of its study is to look at metabolites, lipids, and DNA, in addition to gene expression.)

While Stemina’s test “doesn’t answer all the questions about the process of how you become autistic,” it “can be very good at diagnosing and understanding what’s different about this child,” Donley says. “That’s where we think the promise is of this particular test and approach,” she adds.

Ultimately, the goal would be to … Next Page »

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From Bluetooth Gloves to Teaching Robots: Gadgets at Expand NY

Mon, 11/10/2014 - 13:05
View the Slideshow João-Pierre S. Ruth

For folks who want free hands while operating mobile devices, the team at Easier to Use hopes the GoGlove will be the right fit.

I met Easier to Use co-founder Ben Harris over the weekend at Engadget Expand New York, a technology show held at the Javits Center. GoGlove is equipped to remotely control Bluetooth-enabled devices such as smartphones by tapping certain fingers together. This was one of the gadgets featured at the event, which included other wearable technology and robots (see slideshow above).

Founded last January, Easier to Use has used the Artisan’s Asylum crafting studio in the Boston area to help develop its idea, Harris said. This bit of wearable tech has sensors in the fingertips that, when touched to the magnet in the thumb, can control certain functions in recent iPhone, iPad, and Android devices. The idea came from Harris’s desire to change music on his smartphone while enjoying winter activities such as skiing—but without fumbling to retrieve the device. The Easier to Use team launched a crowdfunding campaign this month to support development of GoGlove.

“This is our second Kickstarter,” Harris said. The first time around, the team tried pitching its gloves in July, far from the cold weather months. “It was a little bit hard to do,” Harris said. “Now everybody is in winter mode and gloves make a lot more sense.” The tentative plan is for GoGlove to ship in the second quarter of 2015.

With the right gestures, the glove can access certain functions on Bluetooth smartphones, cameras, and other gadgets. It can start a music app, pause, switch tracks, and control volume. GoGlove also can remotely turn GoPro cameras on and off, as well as trigger the shooting of video or pictures.

Robots stood up to be counted at Expand NY as well. Aldebaran Robotics’ “Nao” is a walking, dancing, interactive humanoid robot used in some schools to help teach children; it has some use cases in special education. It can also be used to try and keep Alzheimer’s patients active and engaged with the world, said Alexandra Sugurel, a product manager with Aldebaran, which is headquartered in Paris.

The robot is equipped with cameras, touch sensors, and directional microphones to listen to users. By going under the hood, Nao has also been used to teach coding, said Sugurel.

The first version of Nao was released in 2007, Sugurel said, and the latest model debuted this year. The Nao is not sold in the retail consumer market, she said, but rather is available to certain developers and educational institutions. In addition to its Paris headquarters, Aldebaran has its U.S. headquarters in Boston.

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DMI Diagnostic Device Wins Grand Prize in Nokia Sensing XPrize

Mon, 11/10/2014 - 10:00
Bruce V. Bigelow

The XPrize Foundation returned to San Diego today to announce that a team led by Eugene Y. Chan of the DNA Medicine Institute (DMI) in Cambridge, MA, is the winner of the second $525,000 grand prize in the Nokia Sensing XPrize Challenge.

X Prize founder and chairman Peter Diamandis and Nokia CTO Henry Tirri announced the incentive prize competition during a 2012 digital health conference in San Diego as a way to stimulate innovations in wireless health sensing technologies. Finland’s Nokia provided a $2.25 million pool for awarding a series of prizes through two separate, consecutive competitions.

XPrize organizers plan to honor the DMI team at a lunchtime ceremony today during the Exponential Medicine Conference underway at the Hotel del Coronado, just across the bay from downtown San Diego. In a statement today, Diamandis says the technology DMI submitted “embodies the original goal of the Nokia Sensing XChallenge—to advance sensor technology in a way that will enable faster diagnoses and easier, more sophisticated personal health monitoring.”

An expert panel of judges selected DMI from 11 finalists, giving DMI the highest combined score in accuracy, consistency, demonstration quality, technical innovation, human factors, market opportunity, originality, and user experience. DMI designed portable diagnostic technology that can carry out hundreds of clinical lab tests on a single drop of blood—and provides accurate results within minutes.

Eugene Y. Chan and DMI team.

DMI says just about anyone can use its handheld “rHEALTH” device, or Reusable Handheld Electrolyte and Lab Technology for Humans system. DMI’s rHEALTH system consists of microfluidic technology that mixes diagnostic nanostrips into a drop of blood, and uses a laser to perform rapid cell counts and to measure electrolytes, proteins, and other biomarkers. DMI funded most of the development through grants from NASA, the NIH, and the Gates Foundation.

DMI rHEALTH devices

In a statement, Chan says, “Our hope is that the rHEALTH system, once commercialized, will enable consumers to monitor their own health while on-the-go in a more efficient manner and alert them of more serious medical concerns almost immediately.”

Chan, a physician-innovator, founded DMI in 2004, and serves as CEO and chief scientific officer. The small group specializes in developing advanced biomedical technology and devices, and provides R&D consulting services, among other things.

DMI also is one of 10 finalists selected three months ago for the $10 million Qualcomm Tricorder XPrize, a separate incentive prize competition organized by the XPrize Foundation. The winner will be announced next year.

The first $525,000 grand prize in the Nokia Sensing XPrize Challenge was awarded last year to Nanobiosym, a Boston-area organization led by Anita Goel, for its development of a portable diagnostic device that accurately detects the genetic signature of any pathogenic organism. Nanobiosym Diagnostics’ Gene-RADAR is intended to provide rapid and affordable medical diagnostics, even in developing countries where electricity and water are not widely available.

The 11 finalists, culled from a field of 27 teams in five countries, were announced in October. Of those finalists, the expert panel convened by the X-Prize Foundation also selected five teams for a $120,000 “Distinguished Award.” Those teams are:

Biovotion, a medical device company based in Zurich, Switzerland, is developing a multi-sensor wearable device for monitoring vital signs to provide hospital-quality monitoring to people with chronic medical conditions.

Eigen Lifescience, a Stanford University team engineered a biosensor platform that uses giant magneto-resistive spin valves to detect biomolecules for use in diagnosing individual patients.

Golden Gopher Magnetic Biosensing, a Minneapolis, MN-based team, also created a portable giant magneto-resistive biosensing system to detect biomarkers in human serum and urine samples.

Gues, based in London, England, has developed a sensor and companion mobile app for detecting sleep apnea as well as abnormally low respiratory rates.

Endotronix, a startup founded in Woodridge, IL, uses a biosensor implanted in the pulmonary artery and integrated with a wireless handheld device to monitor people with congestive heart failure.

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Xconomy Healthcare Summit Nov. 18: Last Chance to Request Invite

Mon, 11/10/2014 - 09:42
Editors

Health is a function of genetics, the environment, and what we do with our lives. Everyone knows that. But increasingly the tools are being developed to take more control of all of the above, dramatically affecting what is possible in living longer and healthier lives, even in the face of a previously debilitating illness.

Getting a much more detailed picture of new advances in healthcare is the focus of Xconomy’s second annual Healthcare Summit. The summit will take place on Tuesday, November 18, at the stunning deCordova Sculpture Park and Museum in Lincoln, MA. It’s a special, invitation-only event with some of the top leaders in healthcare, not just from Boston, but from around the country. With the summit just eight days away, this is the last best chance to get your invitation now.

You can view the current lineup for this special event here.

General registration is $795 (you can apply for a discount if you’re from a government organization, non-profit, or startup), and includes breakfast, lunch, and a reception after the event. To request an invitation, please write to: hcsummit@xconomy.com. Just tell us a bit about yourself. If you are a service provider, it is not too late to sponsor this event.

We’ll have a chat with George Church of the Harvard Personal Genome Project, as well as a special session encompassing gene therapy and gene editing that’s called Genomic Medicine: From Science Fiction to Science Reality. At the other end of the spectrum is a panel (with demonstrations) on wearable devices. In between are looks at new ways to connect patients and doctors and big data and healthcare, including a talk from computer guru Stephen Wolfram.

There’s a lot more planned for this special day, and we’ve booked the entire museum. Again, to request your invitation, please write us at hcsummit@xconomy.com.

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Sage’s Drug For Rare Epilepsy Shows Promise in Small Study

Mon, 11/10/2014 - 07:25
Ben Fidler

Sage Therapeutics isn’t the company its founders originally intended.

Third Rock Ventures started Sage in 2011 to develop drugs for big neurological disorders such as schizophrenia and traumatic brain injury. Along the way, however, the Cambridge, MA-based company decided to focus on rare neurological disorders that could be moved quickly through the clinic.

That switch is proving prescient so far: Sage got the full top-line data from its first clinical trial today, and the results are promising.

Sage (NASDAQ: SAGE) reports that SAGE-547, its lead drug, met all primary and secondary goals in a small, 12-patient clinical trial for super-refractory status epilepticus (SRSE), a rare, life-threatening form of epilepsy characterized by continuous or repeating seizures. Patients with the condition are put into anesthesia-induced comas to suppress their seizures when antiepileptic drugs fail. There are no approved therapies for SRSE.

So far, SAGE-547 has proven to be to be safe and allowed clinicians to wean eight of the patients in the small Phase 1/2 trial off those anesthetics, effectively halting their disease. A 12th patient in the study could not be evaluated, so the drug essentially worked in eight of 11 patients, or 73 percent. Sage CEO Jeffrey Jonas (pictured above) says the 12th patient was diagnosed with status epilepticus after taking a lethal overdose of drugs in a suicide attempt; that patient died from the toxins he ingested, not from anything related to SAGE-547.

Jonas says that the company had been looking for a response rate of at least 50 percent: “Even at a 50 percent response rate we think it [would be] very exciting for patients where there are no approved therapies for a condition that’s often life-threatening,” he says. “We’re obviously delighted with the data.”

Sage will now have to recreate these small-sample size results in a larger, longer trial. It hopes to talk to the FDA about starting a pivotal study—the last required before regulatory approval—in the first half of 2015. The company has already been cleared to treat patients as young as two years old by expanding enrollment in the current study, in which the average patient age was 54.

Those patients—eight males and four females— had SRSE for an average of 11 days. In that time, they hadn’t responded to intravenous antiepileptic drugs and couldn’t be taken off anesthesia without suffering continuous seizures. Jonas says the trial was designed to reflect real-world usage. The company enrolled patients with a range of potential underlying conditions, ages, and reasons for developing status epilepticus—be it stroke, cancer, a drug overdose, existing epilepsy, or something else—who were in intensive care and needed interventional treatment to stop their seizures.

They were each given an IV dose of SAGE-547 for five days while being weaned off of the anesthetics, then were monitored for four weeks.

Sage’s main goal was to show the drug was safe, and it says that there were no drug-related serious adverse events in the 12 patients in the trial (it hasn’t yet disclosed data about lesser side effects). Sage also hit a secondary mark to show the drug worked, too. What that means, in a practical sense, is that patients could be taken out of their comas without immediately seizing up. Jonas adds that Sage is seeing this happen regardless of patients’ ages or the cause of their conditions.

“That’s one of the encouraging things,” he says. “These patients may be treated with a myriad of underlying agents, and despite that, the drug has been very well tolerated.”

Separately, five of seven patients who have been permitted to take SAGE-547 under compassionate use (71 percent) were free of SRSE either “during the course or soon after…treatment,” according to a statement from the company. Those data don’t count towards Sage’s trial, but at minimum the data back up the type of response Sage is seeing in its study.

Jonas says Sage will start testing SAGE-547 at higher doses and in longer durations as it expands its current trial, to see the reactions of those who don’t respond to the drug at a lower dose. A pivotal study might require anywhere from 100 to 200 patients, and the main goal would likely be to enable a SRSE patient to wake from his or her coma and stay seizure-free for a certain period of time.

“That’s probably the most clinically relevant endpoint that will drive the use of the drug and will add value to patients’ lives, so that’s probably what we’ll shoot for,” Jonas says. “Happily, if you look at the data that we have so far, the patients meet those endpoints anyway.”

Status epilepticus affects about 150,000 people each year in the U.S. Roughly 25,000 of those patients, Jonas says, are “super refractory,” meaning that they don’t respond to treatment with benzodiazepines (now-generic drugs that have been around for decades) or other anti-seizure drugs, and they can’t be taken out of induced comas without suffering seizures.

SAGE-547 is an allosteric receptor modulator, designed to create equilibrium among the neurotransmitters in the brain and calm the overexcitement of brain signals that are thought to lead to disorders such as status epilepticus. ’547 is supposed to do so for SRSE patients by dialing down the inhibitory transmitter known as GABA.

Well after it launched in 2011 with a $35 million Series A round from Third Rock, Sage shifted its strategy from bigger central nervous system diseases to rare ones, in part due to a fortuitous case of a University of California, Davis doctor who used its experimental drug as a last resort for a status epilepticus patient.

Switching its focus to the rare status epilepticus has paid dividends. All within the space of a few months earlier this year, the FDA granted SAGE-547 a fast-track designation and orphan drug status, and investors carried Sage to a $90 million IPO. At the time, Sage had shown that four SRSE patients dosed with SAGE-547 in the Phase 1/2 study all responded to its drug.

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NV Bots Bets on Schools for Sales of Cloud-Connected 3D Printer

Mon, 11/10/2014 - 04:00
Martin LaMonica

AJ Perez is a young startup executive who thinks about the long term.

As the CEO of New Valence Robotics (NVBots), he’s targeting the company’s 3D printers at schools—not known as big spenders on emerging technology—with an eye towards the next generation of designers. It’s an unconventional approach, but it could help the year-old company get a foothold in a crowded market that’s full of promise—and plenty of hype.

Perez told me how NVBots plans to build a profitable business and also inspire kids to study science and engineering, as a 3D printer whirred away in his Seaport District office in South Boston. The company has raised $1 million in angel funding since April and expects to close another $1 million from angels by the end of the year, he says.

There are hundreds of 3D printing companies—printing giant Hewlett-Packard announced its entry last week—but the market overall is split between high-end machines and those aimed at hobbyists, Perez says.

NVBots is making an easy-to-use printer, but not one necessarily destined for home offices or basements. Instead, it designed a printer that can be shared by a group, whether it’s students or professionals who need tools for making plastic prototypes quickly. Functionally, Perez wants NVBots machines to outperform consumer-oriented 3D printers, yet be less expensive than industrial-grade machines now on the market.

Perez shows the company’s cloud-based software for running 3D printing jobs. Credit: Martin LaMonica

The idea for the company’s products sprang from Perez and his co-founders’ experience with 3D printing while they were students at MIT. They were frustrated by the lack of remote control and “shareability” their machine had, Perez says. “We didn’t set out to be a 3D printing company at all. We just did it by necessity,” he says.

From a Web-based application, people can configure how they want a plastic part to be made, deciding on how quickly it should be made and at what strength. There’s also an administrative console that allows a person to organize print jobs. The printer itself has a robotic arm that removes an object and sets it aside, allowing the next job to start. “When you have all those three things, you can do remote function and automation,” Perez says.

NVBots hopes that the close integration of its software and hardware will help it stand out from the many other 3D printers companies. It’s also developing a curriculum to guide schools on how to use 3D printers as a teaching tool to make learning science fun and hands-on. The curriculum includes making models that represent the inside of cells or simulate how hydrogen and oxygen combine to make water.

But why go after schools as potential customers? After all, school budgets are tight no matter where you are and 3D printing is still a novelty for most educators.

To Perez, schools are a relatively under-served market. More fundamentally, though, he sees students as future customers. They need to learn today how to design for 3D printing—a completely different approach to fabrication and manufacturing— in order to drive demand for professional 3D printers down the road, he says.

“If you believe that 3D printing is going to disrupt manufacturing, is going to disrupt the supply chain, it’s going to happen from a design perspective,” he says. “It’s going to happen because we are thinking about making things from the inside out.”

An arm cuts away 3D printed objects so the next job can run. Credit: Martin LaMonica.

At MIT, Perez teaches design for additive manufacturing—the industrial version of 3D printing—and he and his co-workers teach 3D printing design for 10- to-12 year olds at a local school.

Getting venture capitalists to buy into the idea of selling to schools hasn’t been easy, since they’ve seen the difficulty of selling enterprise software in the education market. But NVBots isn’t expecting schools to actually purchase their machines and pay the yearly subscription fee to its software, which ranges from $3,000 to $5,000. Instead, Perez expects school districts to use grant money available to promote STEM education.

So far, the company has 10 schools using its printers and software and is negotiating what could be a bigger deal of about 100 printers. The key is demonstrating that hands-on learning, aided by 3D printers, can actually enhance education and is not just an expensive toy (the printers themselves cost thousands of dollars).

There’s a lot of hype around 3D printing, particularly for home users. But in industry, 3D printing is already taking hold: General Electric and Rolls Royce, for example, are making metal parts for aircraft with additive manufacturing. The question is how quickly this technology will spread and whether it can be affordable to thousands of smaller companies.

NVBots needs to demonstrate that its first customers have successfully use of 3D printers for education, which could prod other schools to buy in—or at least apply for grants and make room in their curriculum for the technology. And for Perez, students are the key to unleashing the potential of 3D printing more broadly. “It’s the next generation of professional designers that are going to matter,” he says.

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Beg, Borrow, or Steal: Accessing Unaffordable Science Journals

Mon, 11/10/2014 - 04:00
Stewart Lyman

If you work in academia or in Big Pharma, you likely have easy access to the world’s scientific literature. Outside of these places, however, obtaining affordable access to the latest scientific journals is much more problematic. This includes scientists at all but the largest biopharma companies, doctors and other health care professionals, and people wanting to research diseases for themselves or loved ones.

Many journal articles cost $30 to $35 each to download, so it’s easy to run up a big bill in a hurry. Given that Big Pharma is outsourcing much of its early stage R&D to small biotech companies, it’s more important than ever that people working in these places be able to keep up with what’s happening in their fields. Compounding the problem: the worldwide production of scientific literature continues to grow at an overall rate of 2.8 percent each year.

I’ve been exploring ways to obtain cheaper access to articles in the scientific literature for those who can’t afford to purchase them a la carte. I’ve written about this subject in previous articles for Nature Biotechnology and Xconomy, and it’s clear from the response to these stories that I touched on a nerve. People hate it when the dreaded paywall appears when trying to access a link on the Internet. Nothing is more annoying than finding out that you can’t readily access some information that’s been put forth in support of a point made in an online article without a credit card in hand. My back-of-the-envelope calculations show that approximately 73 percent of full-text articles in PubMed are secured behind a paywall (that’s over 10 million papers).

I’ve suggested a new model for gaining access to the literature, based on iTunes, and that I named iPubSci. The idea has been well received by many scientists, but implementation is going to take a sea change in academic publishing business models. One blog writer suggested that the concept has already been discredited simply because it has not yet been adopted. I can’t guarantee that it will ever become a viable business model. The change from purchasing records or CDs to buying individual songs has been a financial calamity for music publishers, as described in Robert Levine’s finely detailed book, Free Ride: How Digital Parasites Are Destroying the Culture Business, and How the Culture Business Can Fight Back. The effects on musical artists, however, are much less clear. Moving to a model where people can purchase individual research articles instead of entire journal issues will likely be anathema to academic publishers as well, as it does not fit in with their current (and highly profitable) business models.

What are the primary ways that people access the scientific literature if you don’t happen to work at a research university? Faced with this lack of access, I’ve found the most common approaches are for people to “beg, borrow, or steal” their way in. According to the online Cambridge Dictionary, this phrase means, “to do whatever is necessary to get something.” Here’s how they do it:

Beg
This approach works pretty well if you’re looking for a recently published paper: simply email one of the authors and ask for a pdf reprint. I keep a blank template loaded in my email program that just requires me to fill in the investigators name and the title of the paper. I’ve found that my success rate using this approach to be pretty high, maybe around 85 percent or so. It also provides an entrée to the author should you have any follow-up questions or comments on the data described in the paper. Getting the investigator’s email address is often easy, but sometimes very hard. Some journals facilitate this process by making the address readily available; others deliberately obfuscate this process by making you contact authors directly through the good graces of the journal. They don’t provide email addresses, and I suspect that requests made here for reprints may somehow not find their way to the author. It’s also a good idea to look at the senior author’s website, because many principal investigators maintain downloadable pdf files of their papers in that location.

Unfortunately, accessing copies of older journal articles via the “beg” approach is very challenging: many authors will have moved on to other institutions, retired, or died since the articles were published, and a substantial percentage of vintage articles may not be readily available in a digital format (e.g. pdf file) that facilitates their rapid transfer.

Borrow
Borrowing is just another way of sharing journals. This is a common approach used within small biotech companies: a number of people each purchase an individual subscription, which is then shared among the group. This process does not readily lend itself to having a significant number of subscriptions, because they would very quickly become unaffordable. Considering that many scientists in biomedicine would want access to at least a hundred journals, this doesn’t work out in a small, industrial setting. Virtual biotech companies (i.e. those that outsource all of their R&D, clinical, and regulatory functions) will be especially challenged in this regard. There are also the usual issues of physically finding older print copies, which may be at a work site or at home. It’s also possible (and maybe even likely) that if someone leaves the company they will take all of their back issues with them.

How else can you “borrow” access to science journals? A second approach is to simply visit your local institution(s) of higher learning and access the materials you need directly from the campus libraries. For those who don’t live near such places this would still be a burden, but for many other folks this is a solid approach. The librarians are usually quite helpful at providing instructions on how to access what you need. Depending on the place, you may be able to print out what you want, email articles home to yourself, or download them and take them away on a flash drive. Additional costs associated with this approach would include transportation, parking, and possibly printing or photocopying costs.

Steal
Got some nice, friendly neighbors who work at the local university and have remote access to their online library? If they are willing to share their access code, you will now have a convenient doorway into the library’s journal articles as well. I harbor no illusions that such an approach is likely illegal and that university administrators (and publishers) will not condone this practice. The success of this approach depends on having an accommodating neighbor as well as a university that makes no effort to ferret out such transgressions. Exactly how many people employ this approach is difficult to say. It’s unlikely that people filling out journal usage surveys, whether from the university or the publishers, would admit to this particular route of access.

Other Handy Tips and Tricks
One of the biggest frustrations associated with purchasing science journal articles is that you can’t preview the paper. Buy it, and only then may you realize that it doesn’t actually contain the information that you were seeking. Abstracts aren’t always composed in a way that allows you to figure out exactly what data are provided in the paper; many are poorly written. I’ve described this situation as being akin to … Next Page »

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What Early Looks From ASH Tell Us About Cancer Immunotherapy

Fri, 11/07/2014 - 17:44
Alex Lash

[Note: Ben Fidler contributed to this report.] Immunotherapy is one of the most promising new ways to fight cancer, and we’ve followed it closely for some time. One of its main proving grounds is in blood-borne cancers, because some of the immunotherapy methods are, at least for now, easier to target in that direction.

That’s one reason why the upcoming American Society for Hematology conference—and the research abstracts, or previews, that were released this week—have garnered so much attention. An important caveat is that abstracts are often not representative of final data sets. What researchers report next month in San Francisco might be different than what the abstracts reveal.

More cancer immunotherapy news will certainly emerge from the massive volume of abstracts between now and December 6, the first day of ASH. For now, there are several interesting developments to note.

Cancer immunotherapy drugs that attack the PD-1 protein on tumor cell surfaces have made headlines for their effects on solid tumors like melanoma. But the ASH abstracts are providing some guidance how they might work against blood cancers.

The initial results seem encouraging: Some 87 percent of Hodgkin’s lymphoma patients who had failed at least three prior therapies responded to nivolumab (Opdivo) from Bristol-Myers Squibb (NYSE: BMY). Pembrolizumab (Keytruda) from Merck (NYSE: MRK) also showed early promise. (Pembrolizumab is approved to treat melanoma in the U.S., nivolumab is approved in Japan but not yet in the U.S.)

One hematological cancer that might not respond as well to PD-1 blockers is multiple myeloma. Bristol-Myers Squibb reported that none of the 27 patients with the disease responded to nivolumab. That’s a boon for Summit, NJ-based Celgene (NASDAQ: CELG), as PD-1 drugs represented a potential competitive threat to its multiple myeloma franchise.

Another kind of immunotherapy is based on a patient’s own immune cells, removed and genetically engineered to be efficient killers of a specific type of tumor, and re-introduced to the patient. It’s called chimeric antigen receptor T-cell, or CAR-T, therapy.

One of the leaders in the field is Seattle’s Juno Therapeutics, which is pushing forward into human trials with CAR-T therapy and another kind of immunotherapy developed at three institutions: Memorial Sloan-Kettering Cancer Center in New York, Fred Hutchinson Cancer Research Center in Seattle, and Seattle Children’s Hospital.

Juno has already made a splash, not just with its prodigious fundraising, but with results of a Phase 1 CAR-T trial in which 20 of 22 acute lymphoblastic leukemia (ALL) patients with a particularly intractable form of the disease—in other words, a very grim prognosis—showed complete remission of the disease.

At ASH, Memorial Sloan-Kettering researchers will present follow-up data from those patients. That’s important because some of the most promising medical technologies have seemed transformative at first—and CAR-T cell therapy, which Juno and others are pursuing, fits that description—only to run into the frustrating intricacies of biology.

From the abstract, here’s the latest on those 20 patients. As of July, 1, five had relapsed. Three of them were re-treated, and two of them “achieved a second CR”—or complete remission. That leaves three of the 20 with uncertain status, but the overall results remain impressive in a patient population with little hope of remedy. We contacted Juno officials for comment, but they did not respond in time for publication.

Another important follow-up with these patients are the data on a known side effect of CAR-T called “cytokine release syndrome,” sometimes called … Next Page »

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How a Big Company Can Run Fast, Like a Startup

Fri, 11/07/2014 - 15:14
Elaine Chen

What does the word “startup” mean to you?

Many words can come to mind: new, exciting, experimental, small, lean, agile, fast. To me, “startup” mostly makes me think of “agile” and “fast.”

In an early stage startup, everybody is focused on the same thing. People are passionate, enthusiastic, hungry for an opportunity to change the world, and they will do whatever it takes to get things done. At a headcount of 5-10 people, coordination comes naturally. There are no legacy processes to slow things down. Without existing customers, the team is free to modify their products and services as they learn more. There is also a shared sense of urgency. So they run fast: because it’s fun, because they can, and because they have to.

Contrast that with an established company with a healthy, mature business. Let’s say the company has a global headcount of 100,000. Suppose one of the business units has 6,000 people. The R&D team may have 450 people. The revenue for this business unit is growing at 5-10 percent year over year.

Now suppose two product leaders in this R&D team come up with an idea for a radically different product offering that can turn things upside down. If things work out, this could quadruple their total addressable market. But these leaders still have responsibilities to the existing business, as do all the potential team members. Under these conditions, how would they get started?

Entrepreneurially minded product leaders in big companies have significant advantages over the average startup founder. They are funded, they have teams, their core technology is solid, and they have deep market knowledge from their existing business. But they still face daunting challenges:

  • Budget Catch-22. They have an existing budget, earmarked for sustaining development for existing products. They need a new budget to support experimentation, which will not be approved until they show progress.
  • Divided attention from product leaders. Founders for a startup can focus single-mindedly on making their new idea work. Leaders of new initiatives in a big company are still responsible for the existing product portfolio.
  • Legacy processes. A team at scale has comprehensive processes that govern how work is managed and coordinated, how information is shared, and how decisions are made. These processes are almost never aligned with “fast” or “agile.”
  • Functional silos. A technical team at scale is often organized by functional disciplines. While this is great for streamlining well-understood work, it is not the best structure to power the amorphous experimentation phase for a new program.
  • Organizational dynamics. A successful company at scale has well defined rules of engagement, as well as incentive systems to optimize productivity for existing work. These rules and systems may discourage team members from working on new, risky, unproven ideas.
  • Pace mismatch. The pace of new product development is much different from that of sustaining engineering. It could be hard for the team to switch from a marathon pace to a sprint.
  • Risk against the status quo. What if the new idea works too well, and it cannibalizes the existing business? This concern could be used to smother a new idea before it gets going.

How can product leaders address these challenges and pursue their ideas, with the speed and agility of a startup?

A lot of the startup magic lies in having a small team that comes together by choice to build something out of nothing. Entrepreneurial teams in big companies can potentially emulate this dynamic. Here is a thought experiment on how product leaders can build an internal startup inside a big company.

  • Get buy-in from senior management. This support is needed to help them delegate their existing responsibilities to free themselves up, recruit people to join their quest, and to operate without hiding the project from everyone.
  • “Secure funding.” Frequently product leaders have a fixed annual budget that is set without their input. They would need to find creative ways to meet existing goals, while freeing up people to work on the idea.
  • Build an A-team. Hand-pick a small, cross-functional team with complementary skills to dedicate to the project. Start small: find a hustler, a hacker, and a designer. Find people who are excited to pursue this new idea. They must choose to join this team, and they must feel energized about adopting a completely new work style and pace.
  • Find office space. Set up the team as a semi-autonomous entity in a location that is psychologically separated from their original teams. This could be as simple as moving people from different departments to sit next to each other.
  • Provide some autonomy. Empower the team to make most of the important decisions about the project independently, without going through normal corporate processes.
  • Define mechanisms for “corporate governance.” Come up with some lightweight mechanism to provide managerial foresight. For instance, there might be a senior management debrief once every month or two.

Now the team is ready to begin, starting with customer development. They will need to get out of the building to find out who their customers and users are. With validated hypotheses about target customers, the team can then work on their minimum viable product. This will launch them into the build-measure-learn cycle until they find product-market fit.

Big companies have financial and domain knowledge advantages over startups. Startups have human systems advantages over big companies. By combining the best of both worlds, entrepreneurial teams in established businesses can very well give startups a run for their money in speed and agility.

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Innovation Hub: The Power of You

Fri, 11/07/2014 - 13:00
Kara Miller

A few decades ago, big companies like GE and IBM controlled product pipelines, meaning that they would likely bring groundbreaking inventions to life. Now, a college junior can have a good idea and build an entire business around it using only a crowdfunding website, open source technology, and a 3D printer.

What effect does this power shift from corporations to individuals have on our larger society? We brought the question to a panel of experts at our recent live event, which included author Nicco Mele and Harvard Business School professor Karim Lakhani.

[This interview has been edited and condensed. For the full conversation, visit innovationhub.org.]

Kara Miller: What is causing innovators to turn their backs on big companies?

Nicco Mele: Technology has, over the last 35 years, pushed power to individuals. In 1820, the vast majority of Americans were self-employed as shopkeepers and subsistence farmers. By 1920, the vast majority of Americans were employed by a corporation. Over the last 20 years, that pendulum has swung back in a significant way to people being self-employed. And, you know, it sure beats having a boss.

KM: Instagram had only 13 employees when it was taken over for a billion dollars. Barnes and Noble is worth approximately the same amount, and it has 33,000 full-time employees. How is this possible?

Karim Lakhani: There’s been a shift in the cost of computation. When I was graduating from MIT, to do a startup you’d need 10 million bucks, 30 engineers, and all this software to get going. Today, if you get half a million bucks, you might be OK. You can get computation from the cloud, open source tools, and scale in ways that weren’t possible before. Instagram was running on Amazon’s Web servers, which made it possible for them to do what they were able to do. Technology is becoming democratized, and access to the technology is becoming widespread.

NM: It begs the question, what are the advantages to scale?

KL: If you’re going to make a 787 airplane, you need scale. Some really important problems require scale, time, coordination, and diversity of expertise. So the question becomes, what’s the organizational form that can sustain this? Is it always going to be the GEs, IBMs, and AT&Ts of the world, or can we have more fluid, distributive forms take place?

KM: When you think about where the creative people are going these days, what happens to everyone else, particularly in regards to the consolidation of money?

NM: I think the world is full of opportunity if you’re a student at an elite university. But the Department of Labor did a study that says between 16 to 19 percent of parking attendants in the U.S. have a four-year college degree, and the debt that comes with it. Broadly speaking, a lot of our institutions are not addressing the challenges we’re facing.

KL: Right now, we’re in a stage where we’re seeing tremendous inequality in the economy. But at the same time, people are inherently problem-solvers. You go, oh my goodness, are we back at the start of the industrial revolution? Maybe, to some degree. But I also believe that adjustments will be made, and we will go after the big problems that we want to be solving in health, energy, food, and so forth.

Mikaela Lefrak contributed to this report.

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Aereo Cuts Back New York & Boston Staff, Says It’s Not Shutting Down

Fri, 11/07/2014 - 12:05
João-Pierre S. Ruth

Still trying to tread water in a hostile sea, streaming television service Aereo is slashing away much of its staff, further casting its future as a company in doubt.

In a brief statement sent to Xconomy, the New York-based startup, which halted its service in the summer, confirmed it is letting employees go, but has not yet turned off the lights.

“In an effort to reduce costs, we made the difficult decision to lay off some of our staff in Boston and New York. We are continuing to conserve resources while we chart our path forward,” senior vice president of communications Virginia Lam says via email. Lam went on to call the cuts “difficult, but necessary” to keep Aereo afloat. The company declined to comment further or state how many employees had been cut.

Other news outlets have reported Aereo’s entire Boston office had been let go and the majority of the New York staff was cut leaving just an executive team.

From the moment Aereo came out of stealth in 2012, there were questions about the legality of its service, which streamed broadcast TV shows to paying subscribers. Aereo presented itself as an alternative to traditional industry models—others called it an attempt to exploit a perceived loophole.

Aereo recently asked regulators to designate the company a service provider comparable to cable companies, whose business model Aereo ironically flouted in the past.

In mid-October, Aereo CEO Chet Kanojia posted an open letter to customers on the company’s homepage describing some of the attempts to remain alive.

Kanojia said the company asked the Federal Communications Commission to get online video services, such as Aereo, placed under the umbrella of multichannel video programming distributors—the same category as cable and satellite television providers. FCC Chairman Tom Wheeler seems open to such a change. Whether or not it would save Aereo, if it happens at all, remains to be seen.

Back in June, Aereo lost its legal battle with television broadcasters in U.S. Supreme Court over allegations of copyright infringement. Broadcasters claimed Aereo’s service was a retransmission of their television signal, which Aereo was not paying for. Aereo offered miniature antennae that viewers could access—for a fee—to stream over-the-air network broadcasts to their devices.

Despite Aereo’s assertions that consumers had a right to use its service to watch over-the-air shows, the high court’s ruling forced the company to suspend those operations.

Since its founding, Aereo raised some $97 million in funding, which includes January’s $34 million in a Series C round that included investors IAC, FirstMark Capital, Highland Capital Partners, and Himalaya Capital Management.

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East Coast Biotech Roundup: Intercept, Idera, Inotek, & More

Fri, 11/07/2014 - 10:31
Ben Fidler

Abstracts from the American Society of Hematology’s coming annual meeting were released yesterday, leading to a feeding frenzy among investors looking to declare biotech’s immediate winners and losers. In many cases, though, those answers won’t be known until the full details are disclosed in December in San Francisco. Here are the rest of this week’s headlines from the East Coast.

—Cambridge, MA-based Aegerion Pharmaceuticals (NASDAQ: AEGR) needed to diversify to help soften the blow from the disappointing launch of its cholesterol drug, lomitapide (Juxtapid). This week, it attempted to do so by paying AstraZeneca $325 million for an FDA-approved drug for a rare fat disease, metreleptin (Myalept). There are lingering questions as to the drug’s market potential, but Aegerion aims to boost the product’s revenue by winning approval in additional countries and more disease types, and hiking its price.

—Lexington, MA-based Inotek Pharmaceuticals filed for an IPO this week, aiming to fund a late-stage trial program for a drug it’s developing for glaucoma. Inotek is chasing Bedminster, NJ-based Aerie Pharmaceuticals (NASDAQ: AERI), which just began a Phase 3 trial for a glaucoma drug of its own in July.

—Cambridge-based Proteostasis Therapeutics inked a deal with Astellas Pharma to try to develop up to three new drugs that modulate what’s known as the unfolded protein response, a cellular stress reaction that occurs when proteins in the endoplasmic reticulum don’t fold properly. Proteostasis got an unspecified upfront payment, and could receive up to $400 million for each program, should all three projects hit a series of development goals. It’s the second industry partnership scored by Proteostasis over the past year; the company formed a partnership with Biogen Idec (NASDAQ: BIIB) last December.

—New York-based Intercept Pharmaceuticals (NASDAQ: ICPT) is once again a Wall Street battleground after investigators published the results of its Phase 2 study of a nonalcoholic steatohepatitis drug, obeticholic acid, in the Lancet on Friday. While the drug improved certain hallmarks of the disease, including the scarring of the liver that accompanies it, investigators concluded that its long-term benefits and safety profile need “further clarification.” Side effects like elevated cholesterol levels and pruritus (itching) were associated with the drug. Shares sank about 17 percent in pre-market trading.

—Cambridge-based Idera Pharmaceuticals (NASDAQ: IDRA) has edged into the Duchenne muscular dystrophy field by forming a collaboration with Parent Project Muscular Dystrophy—a Hackensack, NJ, nonprofit organization that funds Duchenne research—to develop a toll-like, receptor-blocking drug that can curb an inflammatory response that causes muscle damage for patients with the debilitating disorder. Idera didn’t disclose the financial terms of the deal, but it’ll work with Parent Project and researchers from the Children’s National Health System to do preclinical studies.

—Cambridge-based Bind Therapeutics (NASDAQ: BIND) lost Amgen as a partner last year, but this week it added Merck in its place. The two will work together to soup up two investigational Merck drug compounds—a kinesin spindle protein inhibitor and a polo-like kinase 1 inhibitor—with Bind’s nanoparticle technology, which is meant to help distribute a drug more efficiently throughout the body. Bind will conduct the initial research on the drugs, after which time Merck and Bind will alternate in choosing whether to develop them further. Financial terms weren’t disclosed.

—Another week, another deal for New York-based Bristol-Myers Squibb (NYSE: BMY), which picked up an option to acquire Denmark’s Galecto Biotech AB for up to $444 million. Galecto is developing a drug for idiopathic pulmonary fibrosis that is currently in Phase 1 testing. The drug, TD139, targets Galectin-3, a protein thought to play an important role in many types of fibrosis. Bristol can exercise its buyout option within 60 days of the completion of a Phase 1b trial.

—New Brunswick, NJ-based Johnson & Johnson (NYSE: JNJ) won FDA approval to use its hepatitis C drug simeprevir (Olysio) in combination with Gilead Sciences’ (NASDAQ: GILD) sofosbuvir (Sovaldi) as part of an all-oral, interferon-free regimen for the disease.

—Patrick Vink has been named the new chief operating officer of Lexington-based Cubist Pharmaceuticals (NASDAQ: CBST), taking over for Robert Perez, who will become Cubist’s CEO on Jan. 1 when Mike Bonney officially steps down. Vink has been serving as Cubist’s senior vice president and general manager of international business.

Image courtesy of flickr user stu_spivack via Creative Commons.

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PopTech Rebels Rage Against the Tech Machine, From Within

Thu, 11/06/2014 - 15:24
Gregory T. Huang

The coastal town of Camden, Maine, is a beautiful setting in late October, even in a Nor’easter. The drive takes three and a half hours from Boston—a little longer in the pouring rain—but once you get there, it feels very far from the daily rat race.

The Camden Opera House, built in 1894, is the site of the annual PopTech conference—an elite gathering of several hundred technologists, designers, artists, and entrepreneurs. It’s a venerable place full of charm, mystique, and old ghosts.

It’s also far too small for 600 people to mill around in when the weather’s so miserable they can’t go outside. Yet PopTech co-founder Bob Metcalfe said the venue is a key reason why the conference, now in its 18th year, has endured.

Any program that starts off with morning yoga has a high bar to clear. Over the next two days, the audience would hear their share of new-agey, motivational phrases from the stage. We are all human “beings,” not human “doings.” We need to “zerotask,” not multitask. We need “contemplative technologies” that promote concentration, compassion, and wisdom.

My fears were quelled when I talked to some of the other attendees about technology trends. Hoon Joo Lee works in research at Nike and picked my brain about harvesting energy from wearables and apparel. Luke Segars works for Google and gave me a grand tour of the possible futures of virtual/augmented reality and 3D printing.

Instead of people staring at their phones all the time, Segars suggested, they could interact with a virtual screen around them as a mobile interface. Instead of buying stuff in stores or online, they could print more of what they need at home—which could eventually turn the manufacturing and retail industries on their heads. (This has nothing to do with his work at Google, which makes it all the more interesting.)

The big theme of the conference talks, hosted by design guru John Maeda, was “rebellion.” Joi Ito, the tech investor turned MIT Media Lab head, described some connections between rebellion, creativity, and education. At his lab, he said, “I don’t want obedience. I want rebellion as a key factor” in the faculty and students.

Ito lamented the traditional school system that has “stamped out creativity in our kids.” As for education, Ito said he doesn’t even like the word. “‘Education’ feels like something that people do to you. Learning is what you do to yourself.” (For his part, Ito said he dropped out of college three times and got kicked out of kindergarten.)

His take-home message on education: “We need to transform the system to be more rebellious and creative. This is the only way we’re going to survive.”

The irony of a maverick like Ito rising to prominence in the tech industry—and now being part of the machine, where he brings in funding from companies like Fox, Google, Intel, and Twitter—was not lost on Ito or his audience. Or on Maeda, who quipped, “When rebels mature, they make institutions.” (Maeda is the former president of the Rhode Island School of Design and now works at a big venture firm.)

“We all like rebellion, because it’s cool and it reminds us of our childhood and it feels good,” Ito said. “But who pays for all of it, and how does it build itself into the system?”

Indeed, the day’s speakers uncovered a persistent tension between the need for institutions—which provide structure, discipline, a unified message—and the need for rebels to challenge them and make them stronger. Which is hardly a new idea; it’s been said that the best companies, and industries, disrupt themselves.

Anil Dash, a Web entrepreneur and CEO of ThinkUp, took one of the biggest swings at the tech machine. Given that “software influences culture in a deep way,” he said, technologists and companies “have to take responsibility for what’s bad.” That ranges from Web companies’ nefarious terms of service to their being “lousy about civic duties,” to excluding women and minorities from their staffs (actively or not).

What’s more, tech entrepreneurs need to “respect our institutions,” he said, citing Uber as a darling of the startup community that continues to face legal and regulatory hurdles in various markets.

“All of us have to hold app developers accountable,” Dash said emphatically. “We can do better.”

The conference’s greatest selling point, perhaps, is that the hype machine known as the “Internet of Things” was not even mentioned until Day 2. And when it was, it was in the context of the maker movement—and another type of rebellion.

Ayah Bdeir, the CEO of electronics startup littleBits, railed against the fact that people are intellectually out of touch with the systems and devices they use every day. Few of us really understand how our smartphones work, or how the financial industry is run, or what happens when the power grid fails, she said.

“We resign ourselves to being consumers of these technologies, and I believe this is a very dangerous thing,” Bdeir said.

She called for a “coup d’état,” to “rebel against our things, technology, and mental laziness.” For Bdeir, the answer is to “democratize hardware” and make it more modular and self-service. Her company makes electronics kits that provide simple building blocks—circuits, components, and so forth—so that non-technologists can experiment with putting hardware together and creating their own gadgets.

So far this has led to rudimentary projects like a doorbell that sends a message to the owner’s phone, and quirkier ones, like a communication system that lets a pet bunny text a family when he’s hungry.

These are admittedly small steps for a broader tech industry that is starting to have more pockets of self-awareness. It seems constructive, at least, that people at different levels in the system are willing to speak out about their place in society.

All of which is to say, rebellions are a long haul—you have to start somewhere.

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Struggling Aegerion Diversifies With Fat Disease Drug

Thu, 11/06/2014 - 11:09
Ben Fidler

Aegerion Pharmaceuticals has been in the news for all the wrong reasons of late. The launch of its rare disease drug, lomitapide (Juxtapid), has stalled, The company is worth less than a third of what it was last year. Today the Cambridge, MA-based company is trying to turn the conversation elsewhere—to an FDA-approved rare disease drug it is acquiring from pharma giant AstraZeneca.

Aegerion (NASDAQ: AEGR) is paying AstraZeneca $325 million in cash up front to acquire and commercialize metreleptin (Myalept), an injectable drug for generalized lipodystrophy. This ultra-rare condition, characterized by the loss of fat tissue, can lead to a number of severe metabolic disorders, like high triglyceride levels or an inability to break down sugar. The condition is caused by a deficiency of leptin, a hormone that helps regulate appetite, energy expenditure, and the amount of fat stored in the body. Metreleptin is a recombinant form of that hormone.

The drug has been passed around a bit. It was first owned by Amylin Pharmaceuticals, which was developing it as a treatment for obesity and high triglycerides or diabetes in patients with lipodystrophy. Amylin was bought by Bristol-Myers Squibb and AstraZeneca a few years ago (Bristol later divested its stake), and AstraZeneca eventually won FDA approval of the drug in the U.S. in February.

The drug, however, was given a limited label. It’s only approved for complications of general lipodystrophy (“general” referring to a complete loss of fat tissue)—a patient group Aegerion executives calculated as one in a million—partially due to safety concerns.

Nonetheless, buying metreleptin gives Aegerion a chance to diversify beyond its only other drug, lomitapide, a treatment for a rare genetic form of very high cholesterol, and tell a different story to investors. The company’s share price has fallen precipitously over the past year or so, because lomitapide hasn’t lived up to expectations, and competition is looming from a group of drugs from Amgen and Sanofi/Regeneron Pharmaceuticals. Aegerion recently significantly lowered its financial projections for the year, from $180 million-$200 million in sales to $150 million-$160 million. The company was worth close to $90 a share in July 2013; it’s now worth just over $20. CEO Marc Beer was also named in allegations of illegal drug use in the messy divorce proceedings between Jefferies & Co. banker Sage Kelly and his wife (Beer has denied the allegations).

In need of another revenue stream, Aegerion picked up metreleptin. On a conference call with analysts, Aegerion executives projected the drug could generate somewhere between $200 million and $250 million in peak net sales. Those assumptions were based on Aegerion winning approval of metreleptin in Europe, commercializing it in a number of countries, adding an additional indication to its label for patients with a partial loss of fat tissue and severe complications, and hiking up the price of the drug, which currently costs $325,000 per patient, per year. Beer didn’t specify just how much of a price increase Aegerion is contemplating, but said that the company will provide more details on its launch plans and pricing strategy once the deal closes in early January.

Still, there are big questions as to the drug’s potential. Aegerion executives said on the conference call that the company plans to file for approval in Europe based on the drug’s existing data; but neither Amylin nor AstraZeneca were able to do so. Also, while Aegerion aims to expand the market for the drug to included patients partial loss of fat tissue, the FDA didn’t previously approve the drug for that indication because it didn’t feel that safety and efficacy for those patients been satisfactorily demonstrated in clinical trials. (“It’s something we’ll have to demonstrate prospectively,” said chief medical officer Mark Sumeray.)

But at minimum, Aegerion’s investors will no longer just be talking about lomitapide.

“We’re really excited about this critical milestone,” Beer said on the call. “Aegerion, with the close of this transaction, will become a two-product company.”

Aegerion shares were up 11 percent in early trading on Thursday.

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How States Can Build a Cleantech Funding Pipeline

Thu, 11/06/2014 - 04:00
Martin LaMonica

Research universities across the country regularly turn out science and technology that could be kernels for jobs-creating businesses. But many of those ideas have trouble finding bankers or venture investors willing to finance the slow, expensive development of a new company based on science.

Massachusetts has developed one response to the problem of funding hard technology development in the area of clean energy. The goal: fill the gaps left by institutional investors.

The agency, called the Massachusetts Clean Energy Center (MassCEC), was created in 2009 after the state passed a series of landmark laws that helped spark activity in renewable energy projects and clean technology companies. It’s been a priority for outgoing Gov. Deval Patrick, who announced another MassCEC grant program last week.

Although it’s too early to declare this approach a resounding success, the program’s money is helping fuel an active cleantech cluster in the region—something many states are also actively pursuing. For entrepreneurs, the program’s structure reflects the reality that state and federal funding remain crucial in energy and sustainability, where early-stage funding remains difficult to secure .

The MassCEC, which is funded by a charge on electric bills, has created a series of grants for researchers or startup companies that are designed to get technologies out of the lab and to demonstrate products in real-world commercial settings. The program isn’t entirely unique—California, New York, and Connecticut also provide financial incentives for cleantech companies.

But Massachusetts’ funding program is comprehensive, spanning from early-stage proof-of-concept grants to cost sharing with corporate customers for pilot projects. And the state also takes an equity stake in early-stage companies, which is not common.

Barton

The funding programs have been formed in direct reaction to the exit of venture capitalists from cleantech and the challenge of relying on banks to fund innovation-based companies, MassCEC CEO Alicia Barton says. “We definitely have been riding that evolution along with the industry,” she says.

A classic financing gap—sometimes called the Valley of Death—is moving a company from a prototype product to its first commercial deployment. In hardware-based businesses, this can be expensive because there are manufacturing costs. And finding customers willing to take a risk with unproven technology is difficult, particularly among conservative electricity utilities.

Boston-based XL Hybrids, for example, landed a $150,000 state grant to test its hybrid-conversion kits for utility vans and trucks in cities with two corporate partners, which provided $230,000. Energy storage controls company Sparkplug Power received a $150,000 grant with a $223,00 match for testing a grid battery system with a utility in western Massachusetts. Similarly, one of liquid metal battery company Ambri’s first test sites is partially funded by the program.

Last week, the MassCEC announced a partnership with the Department of Energy’s ARPA-E agency to jointly fund pilot-scale commercial projects. ARPA-E funds companies or researchers to create a commercial prototype, but it struggles in finding follow-on funding from industry.

“My biggest worry, including when I was in business, is what I would call pilot-scale capital. It’s is the most difficult capital to get,” said ARPA-E director Cheryl Martin at a cleantech conference in Boston last week. “Because there are still risks even if you have prototypes.”

Early-stage
At the opposite end of the funding spectrum—early-stage financing—MassCEC is providing small grants to researchers or entrepreneurs working on clean-energy technologies (no fossil fuel companies are eligible.) It also provides money to incubators, including Greentown Labs in Somerville, MA.

With the departure of most venture capitalists from energy, these state grants are increasingly important. But seed investments are hard to get in any industry, notes Tibor Toth, the managing director of investments at the MassCEC. Angels and corporate investors are helping fill the gap.

“It’s not just in cleantech. You see in other tech and life sciences, some early-stage risk capital is being taken up by angels,” Toth says.

Are these programs working? MassCEC officials are quick to point out that the number of jobs in clean energy is growing faster than biopharma, although a significant portion of those jobs, such as solar installers and HVAC contractors, are not related to technology development. Officials can also point to a few companies, including MIT spin-off Solid Energy Systems, which received seed funding from the state and then attracted venture money.

On the other hand, these are relatively small sums … Next Page »

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Math Toy Tiggly Counts Emerges, Demos at New York Tech Meetup

Wed, 11/05/2014 - 17:58
View the Slideshow João-Pierre S. Ruth

A dose of physical play can help kids learn, Tiggly CEO Phyl Georgiou says.

In our rush to digitize everything, from books to games, he believes connections to the real world remain important. “There’s a question about how kids use their time,” Georgiou says. “They’re busier and use digital devices more and more. Those two trends result in less physical playtime.”

Counting numbers is a core curriculum for kids, he says, that can be taught more effectively in the real world than with an app on a tablet alone. “If you incorporate physical play with a tablet, you get a powerful way to learn numbers,” Georgiou says.

His New York-based company, born at the Harvard Business School, just introduced its latest product for the education-technology arena. Tiggly Counts, due on shelves at Apple Stores on November 11, is already available through Amazon and other e-tailers.

Georgiou spoke with me in advance of Monday’sNew York Tech Meetup (NYTM), a large monthly gathering that showcases new technology, where he would demo Tiggly Counts. His company develops other apps and physical objects, such as Tiggly Shapes, used in tandem with tablets to help educate children as they play games.

Tiggly Shapes, which debuted last year, teaches shapes and motor skills to preschoolers and younger kids. Georgiou says the arrival of Tiggly Counts helps show that his company is not just a one-trick startup. “We want to create a learning journey from toddler, age of 18 months, all the way to 6 or 7 years old,” he says. “Those are the age groups where physical play is critical to early child development of motor and spatial skills.”

In September, Tiggly raised $4 million in a Series A round led by Habermaass GMBH, a German toy maker and learning company.

Tiggly’s newest product uses objects similar to Cuisenaire colored rods, which are used in schools to help teach math. For example, if the related app asks for a certain number, a child would place the appropriate piece on the tablet screen.

The demos at NYTM often feature technology that may be at such early stages there is no business model to speak of yet. This month, however, investor-backed startups such as Tiggly; Admittedly, an alum of the Entrepreneurs Roundtable Accelerator; and Offerpop, which gathers user-generated content about brands that marketers can use, took the stage as well. (See slideshow above).

Georgiou says competition in the youth edtech space is growing, and there are other math learning apps on the market, but they typically focus on right and wrong answers or feature animated characters that become the center of attention. “They’re not really engaging all the senses of the child,” he says.

With his company’s latest funding, Georgiou says Tiggly could grow its staff of 15 to 20 by mid-2015. The company also plans to scale up production. Furthermore, he says Tiggly is developing new products that he believes can make learning in the real world an integral part of the virtual experience for children. “Tiggly wants to help preserve the idea that physical toys are an important part of the toy box; it’s not just about the app store,” he says.

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How to Replace a Nuke Plant? One Utility Leans on Energy Storage

Wed, 11/05/2014 - 17:22
Martin LaMonica

Energy storage technology from a few California startups will help fill a gap left by the closing of the San Onofre nuclear power plant in southern California. It’s a sign of the dramatic changes happening in some pockets of the U.S. electric grid.

Southern California Edison today detailed how it intends to generate enough power to run nearly one million homes with a mix of technologies, including energy efficiency, renewables, and energy storage. The proposal still needs to be approved by state regulators.

One of the big winners is Millbrae, CA-based Stem, which has been contracted to provide 85 megawatts from a distributed collection of refrigerator size batteries in buildings. The company earlier this year lined up $100 million to finance installation of these batteries in commercial customers, such as hotels and office buildings.

Using Stem’s analytics software, the batteries lower electric bills by providing power to a building during peak hours when prices are highest. Those batteries will act as “dispatchable capacity” in the Los Angeles-area grid, earning money from utilities the way natural gas power plants do today.

San Francisco-based Advanced Microgrid Solutions, which has said little publicly until now, was contracted to provide 50 megawatts of capacity. The company, which was founded last year by a former public utility commissioner in California, intends to install and own battery systems at commercial buildings. The batteries will lower peak-hour charges in those buildings and Advanced Microgrid Solutions will also bid services into the wholesale energy markets.

Another “behind the meter” energy storage provider will be Ice Energy Holdings from Glendale, CA. It makes an air conditioner system that makes ice during off-peak hours and draws on the stored cold energy to lower the air-conditioning load during the hottest hours of the day.

Also part of the plan are more conventional energy sources, including a gas-fired power plants and a giant, 100-megawatt battery plant from AES that will act like a traditional power plant in many ways. Efficiency technologies are also part of the mix, including demand response, which lowers power usage at buildings automatically during peak hours.

It’s often said that the utility industry moves slowly and is averse to adopting new technologies. But because California’s state regulators wrote laws to force utilities to consider alternatives to power plants, these smart grid technologies can demonstrate their worth—or lack of—at large scale.

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