Dealing a therapeutic counterblow to traumatic brain injury

The TBI therapy’s delivery mechanism is a customizable, Lego-like strand made of short proteins called peptides, which are composed of amino acids, with a biological agent attached at one end that can survive in the body for weeks and even months. Credit: New Jersey Institute of Technology

A blow to the head or powerful shock wave on the battlefield can cause immediate, significant damage to a person’s skull and the tissue beneath it. But the trauma does not stop there. The impact sets off a chemical reaction in the brain that ravages neurons and the networks that supply them with nutrients and oxygen.

It is the secondary effects of traumatic brain injury (TBI), which can lead to long-term cognitive, psychological and motor system damage, that piqued the interest of a team of NJIT biomedical engineers. To counter them, they are developing a therapy, to be injected at the site of the injury, which shows early indications it can protect neurons and stimulate the regrowth of blood vessels in the damaged tissue.
The challenge, researchers say, is that brain cells don’t regenerate as well as other tissues, such as bone, which may be an evolutionary strategy for preserving the synaptic connections that retain memories. To date, there is no effective treatment for restoring damaged neurons. The body’s protective mechanisms also make it difficult to penetrate the blood-brain barrier, which hampers the delivery of medications.
“Nerve cells respond to trauma by producing excessive amounts of glutamate, a neurotransmitter that under normal conditions facilitates learning and memory, but at toxic levels overexcites cells, causing them to break down. Traumatic brain injury can also result in the activation and recruitment of immune cells, which cause inflammation that can lead to short- and long-term neural deficits by damaging the structure around cells and creating a chronic inflammatory environment,” says Biplab Sarkar, a post-doctoral fellow in biomedical engineering and member of the team that presented this work at a recent American Chemical Society conference.
The team’s treatment consists of a lab-created mimic of ependymin, a protein shown to protect neurons after injury, attached to a delivery platform—a strand of short proteins called peptides, contained in a hydrogel—that was developed by Vivek Kumar, director of NJIT’s Biomaterial Drug Development, Discovery and Delivery Laboratory. After injection, the peptides in the hydrogel reassemble at the localized injury site into a nanofibrous scaffold that mimics extracellular matrix, the supporting structure for cells. These soft materials possess mechanical properties similar to brain tissue, which improves their biocompatibility. They promote rapid infiltration by a variety of stem cells which act as precursors for regeneration and may also provide a biomimetic niche to protect them.
Now in preclinical animal trials, rats injected with the hydrogel retained twice as many functioning neurons at the injury site as compared to the control group. They also formed new blood cells in the region.
“The idea is to intervene at the right time and place to minimize or reverse damage. We do this by generating new blood vessels in the area to restore oxygen exchange, which is reduced in patients with a TBI, and by creating an environment in which neurons that have been damaged in the injury are supported and can thrive,” Kumar says. “While the exact mechanism of action for these materials is currently under study, their efficacy is becoming apparent. Our results need to be expanded, however, into a better understanding of these mechanisms at the cellular level, as well as their long-term efficacy and the resulting behavioral improvements.”
Collaborators James Haorah, an associate professor of biomedical engineering, and his graduate student Xiaotang Ma at NJIT’s Center for Injury Biomechanics, Materials and Medicine have shown how a number of TBI-related chemical effects can disrupt and destroy integral brain vasculature in the blood-brain barrier, the brain’s protective border, promoting chronic inflammation that can lead to symptoms such as post-traumatic stress disorder and anxiety, among others. Their current work provides insights into the potential neuroprotective and regenerative response guided by the Kumar lab’s materials, while future studies will attempt to analyze other mediators of inflammation and blood flow in the brain.
Kumar’s delivery mechanism is a customizable, Lego-like strand made of short proteins called peptides, which are composed of amino acids, with a biological agent attached at one end that can survive in the body for weeks and even months, where other biomaterials degrade quickly. Its self-assembling bonds are designed to be stronger than the body’s dispersive forces; it forms stable fibers, with no signs of inducing inflammation, that rapidly incorporate into specific tissues and collagen, recruiting native cells to infiltrate. The hydrogel, which is also composed of amino acids, is engineered to trigger different biological responses depending on the payload attached. These platforms can deliver drugs and other small cargo over day-, week- or month-long periods. Kumar’s lab has recently published research on applications ranging from therapies to prompt or prevent the creation of new blood vessel networks, to reduce inflammation and to combat microbes.
“The ultimate hope is that that localized delivery of regenerative materials may provide significant benefits for a number of pathologies,” he notes.
For example, the team recently developed a class of materials that may be useful against infection. These novel anti-microbial peptides are capable of disrupting dense bacterial colonies and have shown promise against a number of yeasts. Additionally, they promote human cell proliferation and are currently being studied for wound healing. That work was published this summer in the journal ACS Biomaterials Science and Engineering.
Kumar and his lab have created another hydrogel designed to recruit autologous (a person’s own) dental pulp stem cells directly to the disinfected cavity after root canal therapy. The tooth would be regenerated in part by prompting growth of the necessary blood vessels to support the new tissue. Yet another peptide-based therapy, armed with antiangiogenic capabilities, targets diabetic retinopathy, an ocular disease affecting more than 90 million people worldwide. People with the disease form immature blood vessels in the retina, obstructing their vision. The hydrogel can be injected directly into the vitreous gel of the eye, where the peptide interacts with the endothelial cells in the aberrant blood vessels, causing them to die.
“Conventional biomaterials used in tissue regeneration suffer from a variety of problems with delivery, retention and biocompatibility, which can lead to rejection by the host,” Kumar says. “We’re trying to address these issues with a technology designed to be universal in its application, delivering materials that persist in the tissue and promote their biologic effects for long periods of time.”

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Mice regrow brain tissue after stroke with bioengineered gel

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More information: Biplab Sarkar et al, Membrane-Disrupting Nanofibrous Peptide Hydrogels, ACS Biomaterials Science & Engineering (2019). DOI: 10.1021/acsbiomaterials.9b00967

https://medicalxpress.com/news/2019-10-therapeutic-counterblow-traumatic-brain-injury.html

Paralysed man walks again with brain-controlled exoskeleton

A French man paralysed in a night club accident can walk again thanks to a brain-controlled exoskeleton in what scientists said Wednesday was a breakthrough providing hope to tetraplegics seeking to regain movement.

The patient trained for months, harnessing his brain signals to control a computer-simulated avatar to perform basic movements before using the robot device to walk.
Doctors who conducted the trial cautioned that the device is years away from being publicly available but stressed that it had “the potential to improve patients’ quality of life and autonomy”.
The man involved, identified only as Thibault, a 28-year-old from Lyon, said the technology had given him a new lease of life.
Four years ago that life changed forever when he fell 12 metres (40 feet) from a balcony while on a night out, severing his spinal chord and leaving him paralysed from the shoulders down.
“When you’re in my position, when you can’t do anything with your body… I wanted to do something with my brain,” Thibault told AFP.
Training on a video-game avatar system for months to acquire the skills needed to operate the exoskeleton, he said he had to “relearn” natural movements from scratch.
“I can’t go home tomorrow in my exoskeleton, but I’ve got to a point where I can walk. I walk when I want and I stop when I want.”
Cervical spinal cord injury leaves around 20 percent of patients paralysed in all four limbs and is the most severe injury of its kind.
“The brain is still capable of generating commands that would normally move the arms and legs, there’s just nothing to carry them out,” said Alim-Louis Benabid, professor emeritus at Grenoble and lead author of the study published in The Lancet Neurology.
A team of experts from the Hospital of Grenoble Alpes, biomedical firm Cinatech and the CEA research centre stared by implanting two recording devices either side of Thibault’s head, between the brain and the skin.
These read his sensorimotor cortex—the area that controls motor function.
Each decoder transmits the brain signals which are then translated by an algorithm into the movements the patient thought about. It is this system that sends physical commands that the exoskeleton executes.
Thibault used the avatar and video game to think about performing basic physical tasks such as walking, and reaching out to touch objects.
Using the avatar, video game and exoskeleton combined, he was able to cover the length of one and a half football pitches over the course of many sessions.
‘Repaired not augmented man’
Several previous studies have used implants to stimulate muscles in patients’ own bodies, but the Grenoble study is the first to use brain signals to control a robot exoskeleton.
Experts involved in the research say it could potentially lead to brain-controlled wheelchairs for paralysed patients.
“This isn’t about turning man into machine but about responding to a medical problem,” said Benabid.
“We’re talking about ‘repaired man’, not ‘augmented man’.
In a comment piece on the study, Tom Shakespeare from the London School of Hygiene and Tropical Medicine said the exoskeleton system was “a long way from usable clinical possibility.”
But Thibault said the trial offered a “message of hope to people like me.”
“This is possible, even with our handicap.”

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Pioneering study suggests that an exoskeleton for tetraplegia could be feasible

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More information: Alim Louis Benabid et al, An exoskeleton controlled by an epidural wireless brain–machine interface in a tetraplegic patient: a proof-of-concept demonstration, The Lancet Neurology (2019). DOI: 10.1016/S1474-4422(19)30321-7

https://medicalxpress.com/news/2019-10-paralysed-brain-controlled-exoskeleton.html

Adults with intellectual, developmental disabilities ‘invisible’ in national data

People with intellectual and developmental disabilities (IDD) are often “invisible” in national population surveys that collect only the minimum data for disability, according to researchers at The Ohio State University College of Medicine who are looking into the lack of data.

“Inadequate health surveillance of people with intellectual and developmental disabilities hampers our understanding of their health status, health determinants and health needs,” said Susan M. Havercamp, associate professor in the Department of Psychiatry and Behavioral Health at Ohio State’s College of Medicine.
Havercamp and Gloria L. Krahn of Oregon State University are the guest editors of a special issue of the journal Intellectual and Developmental Disabilities that explores why timely and reliable data is essential to identify health disparities, understand the causes and correlates of disparities and monitor progress in reducing them.
“In 2002, the U.S. Surgeon General’s report, Closing the Gap, highlighted the need for better data on people with intellectual and developmental disabilities. This concern persists today,” said Dr. K. Craig Kent, dean of the College of Medicine. “These researchers explain how public health and policy planning for adults with IDD is imperiled by the lack of ongoing national surveillance data on the prevalence and health status of these individuals, and why this matters.”
The Affordable Care Act of 2010 required establishing minimum data collection standards for disability status as well as for race, ethnicity, sex and primary language in all national population health surveys.
This requirement ensures that these marginalized groups are counted and reported in national data; however, the minimum standards don’t allow for ready identification of persons with IDD within the disability group, said Havercamp, a researcher at The Ohio State University Wexner Medical Center’s Nisonger Center.
Recent changes to two national surveillance systems—National Health Interview Survey and the Survey on Income and Program Participation—eliminated questions that have been used to identify adults with IDD.
“Without specific questions that allow for ready identification of respondents with IDD, this population becomes invisible in the data,” said Havercamp, who is also a member of Ohio State’s Neurological Institute. “Changes to national health surveillance systems provide a challenge and an opportunity.”
Havercamp co-authored three of the nine manuscripts published online in the journal. She also chaired the national surveillance workgroup that recommended four top priority areas and steps to improve health surveillance of adults with IDD. The workgroup encourages federal, state, public and private partners to work together so that adults with IDD will become visible in health surveillance data.
“Once adults with IDD are no longer invisible, empirical data will guide publicly funded services and supports that can better meet their health needs,” Havercamp said.

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Study: Individuals with developmental disabilities experience health care disparities

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More information: Susan M. Havercamp et al. What Matters in Population Health and How We Count It Among People With Intellectual and Developmental Disabilities, Intellectual and Developmental Disabilities (2019). DOI: 10.1352/1934-9556-57.5.347

https://medicalxpress.com/news/2019-10-adults-intellectual-developmental-disabilities-invisible.html

Will clampdown on vaping send users back toward cigarettes?

Only two years ago, electronic cigarettes were viewed as a small industry with big potential to improve public health by offering a path to steer millions of smokers away from deadly cigarettes.

That promise led U.S. regulators to take a hands-off approach to e-cigarette makers, including a Silicon Valley startup named Juul Labs, which was being praised for creating “the iPhone of e-cigarettes.”
Today Juul and hundreds of smaller companies are at the center of a political backlash that threatens to sweep e-cigarettes from store shelves nationwide as politicians scramble to address two separate public health crises tied to vaping: underage use among teenagers and a mysterious and sometimes fatal lung ailment that has affected more than 1,000 people.
New restrictions at the local, state and federal level are poised to wipe out thousands of fruit-, candy- and dessert-flavored vapes that have attracted teens. But experts who study tobacco policy fear the scattershot approach of the clampdown could have damaging, unintended consequences, including driving adults who vape back to cigarette smoking, which remains the nation’s leading preventable cause of death.
“This could take us from potentially the single biggest improvement in public health in the United States toward a public health disaster in which cigarettes continue to be the dominant nicotine product,” said Jonathan Foulds, an addiction researcher and tobacco specialist at Penn State University.
Foulds and many other experts continue to view e-cigarettes as a potential “off-ramp” for smokers, allowing them to continue using nicotine—the addictive chemical in cigarettes—without inhaling all the toxic byproducts of burning tobacco.
But they warn the vaping backlash could do irreparable harm to the public perception of e-cigarettes, while ignoring the riskiest products that are most likely to blame for the recent outbreak.
Federal investigators say that nearly 80 percent of people who have come down with the vaping illness reported using products containing THC, the high-inducing chemical found in marijuana. They have not traced the problem to any single product or ingredient. But investigators are increasingly focused on thickeners and additives found in illegal THC cartridges sold on the black market.
On Friday, the Food and Drug Administration specifically warned the public not to vape THC or purchase any vaping products off the street.
THC vapes are separate from the legal, nicotine-filled e-cigarettes being targeted by President Donald Trump and politicians across the country.
Democratic governors in New York, Michigan, Washington, Rhode Island and Oregon have followed the president’s plan to ban flavored e-cigarettes nationally with their own state-level flavor restrictions. Massachusetts’ Republican governor has gone even further, placing a four-month moratorium on sales of vaping products of any kind.
“The problem here is we have convinced adult America that vaping is as dangerous as smoking—and nothing could be further from the truth,” said Kenneth Warner, professor emeritus at the University of Michigan’s school of public health.
E-cigarettes generally heat a flavored nicotine solution into an inhalable aerosol. There is little research on the long-term effects of inhaling the chemicals in vaping, such as vegetable glycerin. Despite those unknowns, most experts agree e-cigarettes pose a much smaller risk than cigarettes, which cause cancer, lung disease and stroke and account for some 480,000 U.S. deaths each year.

Even before the current uproar over vaping, most adults considered e-cigarettes dangerous. A 2017 government survey found 55 percent of Americans considered e-cigarettes as harmful as regular cigarettes.
And while the flavor bans are likely to curb teen vaping, Warner and others point out that those policies won’t prohibit flavors in traditional tobacco products. That means both teens and adults could wind up switching to deadlier menthol cigarettes or flavored cigars, which come in coffee, raspberry, chocolate and hundreds of other varieties.
WALKING A POLICY TIGHTROPE
The policy debate underscores the challenge of finding the right regulatory scheme for e-cigarettes, products for which there is little high-quality research.
More than 30 countries prohibit vaping products. In contrast, the United Kingdom has fully embraced them as a public health tool, urging doctors to promote them to help smokers quit.
The U.S. FDA has been struggling to find the right approach since it gained authority over e-cigarettes in 2016.
The agency repeatedly delayed its deadline to begin reviewing e-cigarettes, a step that critics say allowed products like Juul to catch on with teenagers. At the same time, e-cigarette companies and proponents say the agency’s new review deadline of next May is too aggressive and will force most companies out of business.
Now the agency is trying to walk a tightrope between keeping e-cigarettes away from teens but preserving them for an estimated 10 million adults who use them, most of whom also smoke.
Further complicating the picture is the fact that no e-cigarette brand has yet been shown to help smokers quit in rigorous studies. But large-scale surveys suggest smokers who use e-cigarettes daily are up to six times more likely to quit than those who don’t use them.
RISK OF SMOKING RELAPSE
The statistics favoring e-cigarettes are bolstered by the experiences of people like Laura Adams, 52, of Battle Creek, Michigan.
A smoker since age 16, Adams was rushed to the hospital in April when a coughing fit left her struggling to breathe. Doctors diagnosed her with chronic obstructive pulmonary disorder, or COPD, and told her she needed to quit cigarettes.
For more than 25 years previously, Adams had smoked clove-flavored cigarettes. When the government banned those in 2009, she switched to flavored cigars.

“I always liked the flavors better than regular tobacco,” Adams said.
After her medical emergency, Adams tried a series of e-cigarettes at a local vape shop before settling on a large, refillable device that allowed her to switch between flavors like blueberry, watermelon and peach.
“As far as I’m concerned, flavored vaping juice saved my life,” Adams said. “It gave me the option of continuing with my nicotine but without destroying my lungs.”
As Michigan stores pull their flavored products to comply with the state ban, Adams has been researching out-of-state suppliers and even do-it-yourself kits for mixing flavors.
But some public health advocates fear less motivated ex-smokers will simply return to cigarettes. Even with the success of Juul, e-cigarettes remain a tiny slice of the U.S. tobacco market, accounting for $8.6 billion in sales compared to $95 billion for cigarettes, according to Euromonitor.
Industry analysts point to early indicators that e-cigarette sales are beginning to flag amid the bans and negative headlines. E-cigarette sales slowed by 11 percent over the four weeks ended Sept. 22, according to retail data tracked by Nielsen.
The trend “could result in improved combustible cigarette” sales “as vapers potentially return” to smoking, Wells Fargo analyst Bonnie Herzog told investors in a recent note.
That’s exactly the opposite of what public health officials have been trying to achieve, noted former FDA Commissioner Scott Gottlieb, who stepped down in April.
As FDA chief, Gottlieb outlined an ambitious anti-smoking plan intended to shift most of the nation’s 34 million smokers away from cigarettes and toward less risky products. The unprecedented plan involved a two-step process: cutting nicotine in traditional cigarettes to make them virtually nonaddictive and then promoting FDA-sanctioned, lower-risk alternatives, such as e-cigarettes.
But the agency has yet to unveil its proposal for cutting nicotine. And a separate proposal to ban menthol cigarettes is still in regulatory limbo.
So as the agency begins sweeping flavored e-cigarettes off the market in coming months, Gottlieb fears smokers may revert to regular cigarettes and cigars, which will still have nicotine levels and flavors designed to addict users.
“This was always a package deal, and it’s become even more critical than ever to advance that entire policy agenda,” he said.
The FDA says it remains committed to Gottlieb’s vision of lower-nicotine cigarettes and less-harmful alternative products. The agency’s regulatory calendar lists this month as the target date to release its proposal for regulating nicotine. But that effort will take years to implement and will almost certainly face lawsuits from tobacco companies.

Meanwhile, it remains unclear which e-cigarettes—if any—will survive the FDA review process set to begin in May.
Under agency standards, only vaping products that represent a net benefit to the nation’s public health are supposed to be permitted. Proving that standard will require companies to submit detailed analysis of their ingredients and population-level estimates of how their products will impact both adult and underage users.
Industry observers say few, if any, of the thousands of vape shops that mix their own custom flavors and solutions will be able to meet the threshold.
“It’s ironic that the vape shops, who really championed e-cigarettes for smoking cessation, are going to be out of business,” said Dr. Neal Benowitz, a nicotine and tobacco researcher at the University of California San Francisco.
That leaves a handful of industry heavyweights such as Juul, which could benefit from billions in research funding from Marlboro-maker Altria, the tobacco company that owns a 35 percent stake in the vaping firm.
But Juul has been besieged by lawsuits and investigations into its alleged role in triggering the explosion of teen vaping. That history could block the company from ever winning FDA approval for its current device, according to former FDA officials.
A THIRD WAY
The uncertainty swirling around vaping could clear the path for another product that is neither a traditional cigarette nor an e-cigarette.
Earlier this year, the FDA authorized the sale of a first-of-a-kind device, IQOS, that heats tobacco without burning it. The approach is designed to mimic the experience of smoking while producing fewer toxic chemicals than paper-and-tobacco cigarettes.
The battery-powered device is getting a preliminary launch this month in Atlanta ahead of a wider rollout. But IQOS’s pedigree underscores the persistence of Big Tobacco companies, even in a world increasingly focused on vaping and other alternative products.
IQOS was developed by Philip Morris International, the global tobacco giant that sells Marlboro cigarettes overseas. It will be sold in the U.S. by the biggest American cigarette maker, Altria, which is also Juul’s biggest investor.

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Walmart to stop selling electronic cigarettes at its stores

https://medicalxpress.com/news/2019-10-clampdown-vaping-users-cigarettes.html

‘Masayoshi Son Is The Walter White Of Money Launderers’

by Scott Galloway
MDMA
The unicorn barn is on fire. Ablaze. A feckless FTC and DOJ, no longer countervailing forces to private power but co-conspirators, have enabled invasive species (Amazon, Apple, Facebook, and Google) to devastate the ecosystem. What to do? No worries, just double up on the MDMA of our economy — charismatic CEOs cut with cheap capital — and the illusion of prosperity party rocks on into the morning. Not that I’ve done a lot of drugs in my life, but they make for gangster metaphors, no?
Unfortunately, the later the lights go on, the uglier the reality. The markets have been dancing and partying with young firms with a seductive rap: “I think of myself as a tech, SaaS kind of guy.”

But as the lights come on, it’s clear he’s a rich kid exiting the bathroom with short-lived confidence from the cheap capital around his nostrils. He doesn’t have a real job (viable business model), and, worse, his parents are fed up and about to cut him off. (If I sound like someone who spent too much time at Pangea, Lotus, Rose Bar, Bungalow 8, and Butter in 2003 NYC, trust your instincts.)
The lights are on, and the market is now discerning between overvalued unicorns:
— Pinterest
— Snap
— Twitter
— Peloton
— Slack
— DoorDash
— Lime
— Palantir
— Uber
— Compass
And those that could lose more than 80 percent of their value or disappear:
— Tesla. Dear Twitter trolls: yes … I’m an idiot, I can’t do, so I teach, and I don’t understand genius. It’s a tech/energy play. I get it… Save your breath. Yes, he is a genius, Tesla has changed the world for the better (I believe this). And … Tesla doesn’t have the scale to compete in a well-run, low-margin business — auto.

— WeWork. Shared workplace concept that’s been in the news lately. Founder has great hair.
— Robinhood. Until yesterday, Robinhood was a disruptor. But Schwab announced they were eliminating commissions on trades, and Robinhood’s top of the funnel (customer acquisition) collapsed. Schwab has other products/revenue streams. Robinhood’s VCs must now fund a company whose $7.6 billion valuation (see above: white powder around nostrils) was cut in half yesterday. Similar to Walmart, Schwab’s leadership will result in multiple expansion. Look for Schwab stock to recover its 8 percent one-day loss within 30 days.
— Lyft. Imagine a shitty business, ride hailing, minus a global brand or Uber Eats. Lyft is all the calories of Uber, with none of the great taste.
— OYO. Just like WeWork, OYO is a REIT with too much SoftBank capital. Masa owns 45 percent, and as one of the lead investors in every round since 2015, he has pushed the valuation from $400 million to $12.5 billion. Smoking their own supply.
To be fair, it’s easy to see why we continue to do this. The stable (the US information economy) produced Secretariat, Seattle Slew, Zenyatta, and Spectacular Bid (awkward equestrian metaphors for Amazon, Apple, Facebook, and Google). We also feel a sense of hope/justification, as Airbnb is just hitting its stride and could be one of the greats.
The Betty White powder was cut with a variety of things: frothy markets, idolatry of innovators/founders, and weak oversight. But the central nervous system stimulant here is cheap capital. And the substance mixed into the fine Columbian has been SoftBank, whose $100 billion Vision Fund was disruptive, on several levels.
The case study we’ll be teaching for decades in b-schools around the world about the Vision 1 disaster (not fair, it’s a total f**king disaster), writes itself. The strategy was (wait for it) capital as a strategy. Specifically, more of it, so you could win deal flow and be the fuel that helps portfolio firms make the jump to light speed, leaving competitors behind and befuddled.
Easy to see how this makes sense. But it doesn’t. Capital is in fact a weapon in private equity, where only a few firms can bid for the truly great, proven assets with enormous cash flows. However, in venture, and growth, the secret sauce is dislocation, a market ripe for disruption, and crazy genius founders who are too stupid to know they will fail. When your ability to deploy heaps of billions into a concept becomes the priority, as it does when you have $100 billion to deploy, your returns go down. This is evident across SoftBank’s portfolio.

Venture is Local
My NYU colleague Professor Pankaj Ghemawat published gangster research showing business and trade are, despite rumors of the death of distance, a function of geography. A retail store’s profitability is correlated with proximity to HQ. Sequoia Capital was the lead investor in my second firm, and the partner on our board told me a key tenet was they would not invest in a firm the partner could not drive to.
Masa and Adam would agree to meet in-between their 13 time zones (I think that’s Hawaii). Similar to when the Japanese acquired US movie studios and golf courses in the eighties, SoftBank will leave with less yen than they came with. If you found the previous sentence uncomfortable, racist even (as I initially did), you’ve fallen victim to the same monoculture PC virus infecting our universities. Japan did buy US golf courses, and their currency is in fact the yen.

Smoking Your Own Supply
Another tenet of venture, expressed by every investor I’ve raised money from (General Catalyst, Maveron, Sequoia, Weston Presidio, JPM, Goldman, and others) is they will not lead subsequent rounds. Good investors resist the temptation to smoke their own supply and require third-party, arms-distance validation of the firm’s value here and now. SoftBank was the only lead investor in WeWork, through multiple rounds, since 2016.

Ironically, the real damage on the capital side will be on SoftBank employees, as they own common stock in Vision 1. Saudi Arabia Public Investment Fund and Mubadala own preferred stock that captures a 7 percent (preferred) return each year, sequestering returns from the few winners in the portfolio. So, Vision 1 has pneumonia, but the common equity holders in Vision 1 are on a ventilator.
The spoon, baking soda, and heat that turns overvalued firms into crack is charisma — people who trade likability and their reputations for hundreds of millions (often billions) to wallpaper over ugly truths about a business and its impact on other people and the commonwealth. Think of it as information economy money laundering. Masayoshi Son is the Walter White of money launderers, washing dirty money and procuring his take.

A question: if the relationship between Saudi Arabia’s Public Investment Fund and SoftBank became strained — as it often does between criminals and money launderers — would Mohammad Bin Salman dispatch operatives to intercept him on foreign soil, strangle him, and then dismember him with a bone saw? And, another question, if they did … would Prime Minister Shinzo Abe do more than ask Mohammad Bin Salman to buy additional weaponry from Mitsubishi Heavy Industries?
Addiction
Addiction is the long-term inability to moderate or cease intake. Someone with an addiction will continue to misuse the substance in spite of the harmful effects. British-Venezuelan scholar Carlota Pérez has written powerfully about the link between technological innovation and extreme income inequality. We see evidence of a Hunger Games economy everywhere. Life has become harder for two of every five Americans.
However, the idolatry of winners, constantly promoted on CNBC and Instagram, creates a high we’re all chasing, the “innovator” badge. Its spoils, coupled with the false narrative that we live in a meritocracy, have dulled our sense of empathy.
We feel it in our gut. We witness immense prosperity, but little progress. A shrinking middle class, depressed teens, and fractured alliances. Still, we continue to look away. As a species, we’re easier to fool than convinced we’ve been fooled. We refuse to face the truth: The innovation industrial complex has ripped at the fabric of our democracy, fomented a caste system, and dulled our sense of empathy.
We’re lying to everyone. We’re lying to ourselves. We’ve lost sight of what’s important. We’ve lost ourselves. We’re addicted.
https://www.zerohedge.com/economics/masayoshi-son-walter-white-money-launderers

Oncology biotech Monopar Therapeutics postpones $40 million IPO

Monopar Therapeutics, which is developing therapies for chemotherapy-induced mucositis and cancers, postponed its IPO on Wednesday, citing market conditions. It had filed to raise $40 million by offering 4.4 million shares at a price range of $8 to $10.

The Wilmette, IL-based company was founded in 2014 and had planned to list on the Nasdaq under the symbol MNPR. JonesTrading, Aegis Capital Corp., and Arcadia Securities were set to be the joint bookrunners on the deal.

Relevant Profile: MNPR

https://www.renaissancecapital.com/IPO-Center/News/65269/Oncology-biotech-Monopar-Therapeutics-postpones-$40-million-IPO

IPO Week Ahead: 2 billion-dollar biotechs

Two of the largest-ever biotech IPOs by market cap are scheduled for the week ahead. They are joined by an Illinois bank. The three deals plan to raise a combined $550 million.
Germany-based BioNTech (BNTX) is targeting $251 million at a fully diluted market cap of $4.45 billion. That would make it the third-largest development-stage biotech ever to list in the US, behind July’s Genmab (GMAB), and December 2018’s Moderna (MRNA). The company’s extensive pipeline includes mRNA therapeutics, engineered cell therapies, antibodies, and small molecule immunomodulators. Its lead mRNA candidate is being co-developed with Genentech in a Phase 2 trial for melanoma, with topline data expected in the 1H20. To date, BioNTech has raised $1.3 billion  privately, most recently $324 million in August 2019.
Infectious disease biotech Vir Biotechnology (VIR) plans to raise $150 million at a $2.4 billion market cap. The company’s pipeline consists of five product candidates targeting hepatitis B virus, influenza A, HIV, and tuberculosis. Backed by ARCH Venture, the company is collaborating with Alnylam Pharmaceuticals to develop siRNA candidate VIR-2218 for hep B, currently in Phase 1/2.
Bloomington, IL-based bank HBT Financial (HBT) is raising $149 million at a market cap of $474 million, in the year’s largest US-based bank by IPO proceeds. Operating as Heartland Bank, HBT has 64 branches spread across central and northeastern Illinois. The company generated adjusted net income of $25 million in the 1H19, with an ROTCE of 21.2% and an efficiency ratio of 54%; it plans $0.15 quarterly dividend (3.3% yield).
Potential launches this week include Post protein-supplement spinoff Bellring Brands (BRBR), commercial-stage biotech Innate Pharma (IPHA), and insurance distributor BRP Group (BRP).
Relevant Profiles: BNTX, VIR
https://www.renaissancecapital.com/IPO-Center/News/65311/US-IPO-Week-Ahead-2-billion-dollar-biotechs-and-a-bank