Cash-rich startup Rubius to build $155M cell therapy manufacturing site in RI

After closing two mega-rounds of investment within eight months of each other, the booming team at Rubius is now putting some of that cash to work. The Cambridge startup is building out a 135,000 square-foot manufacturing site in Rhode Island for its cell therapies — just months before it files its first IND.

The company plans to renovate an existing property in Smithfield, RI to do the job, investing $155 million over the next 5 years for the project. Back in March, Rubius’ president Torben Straight Nissen told Endpoints News that he was pondering an in-house manufacturing process. Developing a new class of medicine calls early on for some pricey manufacturing capacity.

The big idea at Rubius is that researchers can take red blood cells — designed by nature to transport oxygen — hijack them through genetic engineering tech and get them to carry proteins needed to fight various diseases. It’s an off-the-shelf approach, rather than one personalized for each patient.

It’s a platform play — a particular favorite of Flagship Pioneering, the startup factory that churned out Rubius. Flagship chief Noubar Afeyan has been one of the leading proponents of a move to find new platform companies with big potential for some game-changing technology and then coming up with the big money needed to build a full pipeline of therapies, rather than one or two pilot projects to demonstrate their potential.

Rubius’ platform has already attracted big financial support, raising $220 million in two round since last summer.

The R&D plan at Rubius is to push ahead with some lead enzyme replacement therapies being spawned on a platform that seeks to develop a brand-new class of cell therapies. The company plans to file its first IND for lead candidate RTX-132 in early 2019.

Bursting at the seams, Rubius is also now moving into 45,000 square feet in new digs at 399 Binney. By this summer, Nissen said, the staff should be up to around 100.

https://bit.ly/2KQ5Xiu

Breathing Tubes Fail to Save Many Older Patients

Earlier this year, an ambulance brought a man in his 80s to the emergency room at Brigham and Women’s Hospital in Boston. He had metastatic lung cancer; his family had arranged for hospice care at home.

But when he grew less alert and began struggling to breathe, his son tearfully called 911.

“As soon as I met them, his son said, ‘Put him on a breathing machine,’” recalled Dr. Kei Ouchi, an emergency physician and researcher at the hospital.

Hospice patients know that they’re close to death; they and their families have also been instructed that most distressing symptoms, like shortness of breath, can be eased at home.

But the son kept insisting, “Why can’t you put him on a breathing machine?”

Dr. Ouchi, lead author of a new study of how older people fare after emergency room intubation, knew this would be no simple decision.

 

“I went into emergency medicine thinking I’d be saving lives. I used to be very satisfied putting patients on a ventilator,” he told me in an interview.

But he began to realize that while intubation is indeed lifesaving, most older patients came to the E.R. with serious illnesses. “They sometimes have values and preferences beyond just prolonging their lives,” he said.

Often, he’d see the same people he’d intubated days later, still in the hospital, very ill, even unresponsive. “Many times, a daughter would say, ‘She would never have wanted this.’”

Like all emergency doctors, he’d been trained to perform the procedure — sedating the patient, putting a plastic tube down his throat and then attaching him to a ventilator that would breathe for him.

But, he said, “I was never trained to talk to patients or their families about what this means.”

His study, published in the Journal of the American Geriatrics Society, reveals more about that.

 

 

 

Analyzing 35,000 intubations of adults over age 65, data gathered from 262 hospitals between 2008 and 2015, Dr. Ouchi and his colleagues found that a third of those patients die in the hospital despite intubation (also called “mechanical ventilation”).

Of potentially greater importance to elderly patients — who so often declare they’d rather die than spend their lives in nursing homes — are the discharge statistics.

Only a quarter of intubated patients go home from the hospital. Most survivors, 63 percent, go elsewhere, presumably to nursing facilities.The study doesn’t address whether they face short rehab stays or become permanent residents.

But it does document the crucial role that age plays.

After intubation, 31 percent of patients ages 65 to 74 survive the hospitalization and return home. But for 80- to 84-year-olds, that figure drops to 19 percent; for those over age 90, it slides to 14 percent.

At the same time, the mortality rate climbs sharply, to 50 percent in the eldest cohort from 29 percent in the youngest.

All intubated patients proceed to intensive care, most remaining sedated because intubation is uncomfortable. If they were conscious, patients might try to pull out the tubes or the I.V.’s delivering nutrition and medications. They cannot speak.

Intubation “is not a walk in the park,” Dr. Ouchi said. “This is a significant event for older adults. It can really change your life, if you survive.”

 

A study at Yale University in 2015 following older adults before and after an I.C.U. stay (average age: 83) confirmed what many geriatricians already understood. Depending on how disabled patients are before a critical illness, they’re likely to see a decline in their function afterward, or to die within a year.

Those who underwent intubation had more than twice the mortality risk of other I.C.U. patients. “You don’t get better, most of the time,” said Dr. Ouchi. While outcomes remain hard to predict, “a lot of times, you get worse.”

Intubation rates are projected to increase. But so has the use of alternatives known as “noninvasive ventilation” — primarily the bipap device, short for bi-level positive airway pressure.

A tightfitting mask over the nose and mouth helps patients with certain conditions breathe nearly as well as intubation does. But they remain conscious and can have the mask removed briefly for a sip of water or a short conversation.

When researchers at the Mayo Clinic undertook an analysis of the technique, reviewing 27 studies of noninvasive ventilation in patients with do-not-intubate or comfort-care-only orders, they found that most survived to discharge. Many, treated on ordinary hospital floors, avoided intensive care.

“There are cases where noninvasive ventilation is comparable or even superior to mechanical ventilation,” said Dr. Douglas White, a critical care physician and ethicist at the University of Pittsburgh School of Medicine.

Dr. Ouchi, for instance, explained to his patient’s distraught son that intubation would thwart his father’s desire to remain communicative. The patient, able to see though not to say much, died four days later in a hospital room with bipap and morphine to reduce his “air hunger.”

 

Most patients in the Mayo review died within a year, too. But bipap may provide an interim option, giving families and physicians time to decide together whether to intubate an ailing older patient, who at this point probably can’t direct his own care.

The harried emergency room environment, after all, hardly encourages thoughtful discussions about patients’ prognoses and wishes. Those can become fraught conversations anyway, as Dr. White’s previous research has demonstrated.

His 2016 study showed that when physicians and surrogate decision makers have very different expectations about a critically ill patient’s odds of recovery, it’s not merely because family members fail to grasp what the physician explained.

“Other things get in the way of making good decisions,” Dr. White pointed out. “A lot of this has to do with psychological and emotional factors” — like “optimism bias” (Most people with this condition will die, but not my mom) or “performative optimism” (If we maintain hope, our mom will get better).

In their most recent study, he and his colleagues experimented with a support program for families with relatives in I.C.U.s., nearly all intubated.

When a specially-trained nurse checked in daily to explain developments and answer questions, families rated their communications more highly and felt more satisfied with their loved ones’ care.

The University of Pittsburgh Medical Center’s health system has begun adopting the program in its 40 I.C.U.s.

 

But discussing how aggressively an older person wants to be treated remains a conversation — probably a series of them — best held before a crisis.

Intubation, for instance, is often something a physician can foresee. Older patients who have cardio-respiratory conditions (emphysema, lung cancer, heart failure), or who are prone to pneumonia, or who have entered the later stages of Alzheimer's or Parkinson's disease — any of them may be nearing this crossroads.

When they do, Dr. Michael Wilson, a critical care physician at the Mayo Clinic, opts for a particularly humane approach.

As he recently described in JAMA Internal Medicine, before he inserts the tube, he explains to the patient and family that while he and the staff will do everything they can, people in this circumstance may die.

“You may later wake up and do fine,” he tells his patient. “Or this may be the last time to communicate with your family,” because intubated patients can’t talk.

Since setting up intubation generally takes a few minutes, he encourages people to spend them sharing words of comfort, reassurance and affection. Without that pause, “I have stolen the last words from patients,” he told me.

His editorial has drawn attention from critical care physicians around the world.

Dr. Wilson has used this approach about 50 times in his I.C.U., so he has learned what patients and families, given this opportunity, tell one another.

“It’s nearly always, ‘I love you,’” he said. “‘I hope you do well.’”

https://tinyurl.com/y9o6qjeh

Educational Development 7.7% Holder to Board: ‘Little to No Economic Alignment’

Red Oak Partners, LLC, a long-term investor in Educational Development Corporation (NASDAQ: EDUC) and the largest outside investor with a 7.7% ownership stake, announced today that it has issued a letter to the Board of Directors (“BOD” or the “Board”) of EDUC expressing serious concerns with the Company’s troubling corporate governance practices, Board composition, and misaligned management incentive plan proposal and Red Oak’s intention to oppose the election of the Class II directors and the proposed management equity incentive plan at the upcoming 2018 Annual Meeting scheduled to be held on July 24th. Red Oak has also called upon EDUC’s Board to work with its shareholders to address the significant concerns regarding EDUC’s corporate governance practices.

https://bit.ly/2KYnLF2

Align Tech prevails in legal challenge to Invisalign store pilot program

Align Technology (ALGN -1.7%) has won the first round in a legal spat between the company and SDC Financial LLC and SmileDirectClub LLC regarding its Invisalign stores.

The plaintiffs allege that Align’s pilot program breaches non-compete provisions that apply to members of SDC Financial LLC. Remedies requested include the preliminary and permanent enjoinment of all activities related to the pilot program, including the closure of all Invisalign stores and a prohibition on opening new stores, and allowing SDC entities to exercise their right to repurchase all of Align’s SDC Financial LLC membership interests at a price equal to Align’s current capital account balance.

On Friday, June 29, a Tennessee court denied the SDC entities’ request for a temporary injunction preventing Align from opening new stores. The company says it intends to continue the pilot program and will “vigorously defend itself” in arbitration proceedings currently scheduled for December 2018.

https://bit.ly/2u3ZfMm

Thousands without power in Los Angeles after high demand due to heat wave

Thousands of Los Angeles residents were left without power Saturday morning after a heat wave prompted high electricity demand throughout the city.

“Friday’s record-setting heat led to unprecedented peak electricity demand,” according to the Los Angeles Department of Water and Power (LADWP). High demand caused power outages throughout city and left 34,500 customers in the dark — without fans or air conditioning.

The department said that figure accounts for about 2.5% of their 1.5 million customers.

Scorching heat has descended upon California and parts of the southwest after a heat wave swept across Canada earlier in the week, killing dozens in the province of Quebec, according to Canadian health officials.

Many areas in California on Friday broke their daily high temperature records, according to CNN meteorologists. Downtown Los Angeles reached a high of 108 degrees, breaking its previous daily record of 94 degrees, which was set in 1992.

close dialog

UCLA also broke its previous daily temperature record, where thermometers read 111 degrees.

Since the start of the heat wave on Friday, LADWP has restored power to 14,500 customers, it said in a statement. But LADWP warned customers they should prepare to be without power for 12 to 24 hours, “and possibly even longer due to the high number of small localized outages.”

The peak energy demand level on Friday was 6,256 megawatts, LADWP said, a new record for a day in July, beating out the previous record of 6,165 megawatts, set on July 24, 2006.

LADWP also asked customers to reduce their electricity use throughout Saturday afternoon and into the evening.

“LADWP crews worked throughout the night to restore power and will work around the clock until every affected customer has service restored,” it added.

But according to CNN meteorologists, more daily high temperature records were expected to either be tied or broken on Saturday. Temperatures along the coast could reach up to 100 degrees, while those farther inland could see highs of up to 120 degrees.

More than 15 million people were under excessive heat warnings on Saturday throughout Southern California and Nevada.

The heat is also exacerbating conditions fueling wildfires in California, which have claimed one life and forced hundreds to evacuate from their homes.

https://cnn.it/2N0Fkoj

Predicting vs understanding

I'll be speaking on Tuesday, July 24th at the Traders Expo event in Chicago, and one of the things I'll be covering is how we really know we have an edge in markets.  I'll also share with the group some of the edges I am currently pursuing in my own trading.

In a broad sense, there are two forms of knowing:

*  Predicting - Being able to anticipate future events;

*  Understanding - Being able to explain events.

We can predict without understanding.  We know to anticipate changes in weather without being able to explain the chain of events by which these occur.

We can understand without being able to make specific predictions.  We might understand reasons for a market's behavior without being able to predict when and how the market will move.

This is a bit of a simplification, but a good deal of what we call technical analysis seeks prediction.  A good amount of fundamental analysis seeks understanding.

The vulnerability of much technical analysis is that it finds patterns that appear to be correlated with price changes, but cannot explain the nature of that relationship.  As the video explains, if we look at enough patterns, we can find something that appears to be predictive.  Indeed, with a large enough search space (thanks to powerful computing), we can find things that work in sample and out of sample that still are random!

The principle that makes sense here is that we don't *truly* have an edge unless we can clearly explain why this edge is present.  Prediction without understanding is a frail basis for risking our hard-earned money. 

If we can explain the basis for a predictive relationship, we possess true understanding.  Real conviction and confidence in trading comes from understanding the basis for what you're doing. 

A person with a purpose in life has a "why"--a considered set of reasons for doing what they're doing.  That person is most likely to travel in a coherent direction.  Without a "why", we wander through life.  That's the difference between having a year of experience versus one day of experience repeated 365 times.

So, too, with trading.

Trading psychology is much easier when we have a genuine "why" underlying our actions.  Too many people are pursuing trading because they can't figure out another way to work independently and make enough money to support themselves.  This is understandable, but invariably ends badly.  People setting themselves up as gurus are all too willing to exploit the desire to make a living from trading.  A great question to ask about any idea advanced by a guru is, "Why?"  If you--and they--can't truly explain why an idea works, how do you know you actually have an edge and not just another pattern fit to market data?
https://bit.ly/2MUtX1p

New model for large-scale 3-D facial recognition

Researchers from The University of Western Australia have designed a new system capable of carrying out large-scale 3-D facial recognition that could transform the entire biometrics industry.

The model could be used by any organisation or government agency for more accurate 3-D facial recognition and could lead to widespread applications, and improving security measures while potentially removing the need for personal passwords.

Facial recognition is fast becoming the tool of choice for surveillance, security and IT industries and relies on the ability of computer models to determine whether or not a person is legitimate.

Currently, 2-D facial recognition of photographs is widely used and has seemingly surpassed human accuracy levels however it has several shortcomings that the more advanced 3-D model is able to address.

Unlike 2-D facial recognition software, 3-D models have the potential to address changes in facial texture, expression, poses and scale, yet the data is difficult to gather.

2-D facial data can be obtained simply by searching the internet while 3-D facial data requires physical collection from real subjects thereby limiting its use.

The research team from the UWA Department of Computer Science and Software Engineering created the first-of-its-kind model—called FR3DNet—analysing 3.1 million 3-D scans of more than 100,000 people.

They trained the model to learn the identities of a large dataset of ‘known’ persons and then match a test face to one of those identities.

The 3-D model’s creator, Dr. Syed Zulqarnain Gilani, said the model was a huge step forward in the field of 3-D facial recognition.

“With off-the-shelf 3-D cameras becoming cheap and affordable, the future for pure 3-D face recognition does not seem far away,” Dr. Gilani said.

“Our research shows that recognition performance on 3-D scans is better and more robust. Your 3-D scan could be in any pose, wearing glasses or a face mask, and laughing or just smiling and the deep model can recognise you in an instant.

“We hope that this research will help improve security on devices that use facial recognition to grant access to networks and systems.”

The 3-D Facial Recognition model (FR3DNet) is currently available for research purposes. The paper was published in Computer Vision and Pattern Recognition.

 Explore further: Facial recognition was key in identifying US shooting suspect

https://bit.ly/2Nz6unC