$87M in Hand, Beam Therapeutics Launches CRISPR Base Editing Plan

Beam Therapeutics, a new precision genetic medicines company, launched this morning with $87 million in a Series A funding round backed by F-Prime Capital Partners and ARCH Venture Partners.

Although Beam did not lay out any specifics regarding its primary disease research, the company said it will focus its research on multiple DNA base editor platforms that were developed in the Harvard University lab of David Liu, as well as on the RNA base editor platform developed by Feng Zhang at the Broad Institute of MIT and Harvard. Beam said it will be the first company to pursue development of new therapies using CRISPR base editing technology.

DNA, Beam said, is made up of billions of nucleobases, or “bases,” each represented by a single letter (A, G, T, C). These letters are subsequently encoded in RNA messages for expression by the cell. Base editors are capable of precisely targeting and directly editing just one base out of billions within the genome, without cutting the DNA or RNA, the company said. The method is more precise than the more common CRISPR programs that cut and edit, or correct, disease-associated DNA in a cell. The base editing technology allows for the rewriting of a mutation in the DNA.

In its coming out announcement, Beam said it will use the different technologies to “generate a broad pipeline of precision genetic medicines that repair disease-causing point mutations, write in protective genetic variations, or modulate the expression or function of disease-causing genes.”

Chief Executive Officer John Evans, most recently head of Corporate Development and Portfolio Leadership at Agios Pharmaceuticals, said base editors are capable of making single-base changes with high efficiency and unprecedented control. Beam, Evans said, has put together the base editing technologies and intends to establish them as a “new therapeutic option for patients with serious diseases.”

Out of the gate Beam Therapeutics has established several licensing agreements. Its first agreement is with Harvard that covers two base editing platforms developed in Liu’s lab. The first is the C base editor, which features Cas9 linked to a cytidine deaminase to deliver programmable C-to-T or G-to-A edits in DNA. The second is the A base editor, which features Cas9 linked to an evolved form of adenosine deaminase capable of editing DNA to deliver programmable A-to-G or T-to-C edits.

The second license is with the Broad Institute for RNA base editing technologies from Zhang’s lab. This includes the RNA editor platform, which features Cas13 linked to an adenosine deaminase to deliver single base A-to-G editing of RNA transcripts, the company said.

Additionally, Beam entered into a third licensing and option agreement with Editas Medicine. Under terms of this agreement Beam secured an exclusive sublicense to patent filings by Harvard for base editing technologies and patent filings by MGH for CRISPR technology. The company also gained an exclusive option for future sublicensing of additional Cas9 patent families and Cpf1 patent families in the field of base editing. In return, Editas Medicine has received an equity stake in Beam and will be eligible for royalties on medicines utilizing the related intellectual property and technologies.

In addition to Evans, Beam’s leadership team includes Chief Scientific Officer Giuseppe Ciaramella, who most recently served as CSO of Moderna Therapeutics’ Infectious Disease division.

https://bit.ly/2kvxRkU

Celsius Therapeutics Launches with $65 Million Series A Financing

Celsius Therapeutics launched in Cambridge, Massachusetts with a Series A financing round worth $65 million. The financing was led by Third Rock Ventures with participation from GV(formerly Google Ventures), Heritage Provider Network, Casdin Capital, Alexandria Venture Investments and others.

The new company will focus on developing single-cell genomic research into precision therapeutics for autoimmune diseases and cancer. It links computational algorithms in order to identify first-in-class precision therapies. The company indicates it will begin with single-cell sequencing on defined patient samples to identify individual cells and their interactions that cause disease.

Celsius was co-founded by Aviv Regev, director of the Klarman Cell Observatory at the Broad Institute of MIT and Harvard, professor of Biology at MIT and an investigator at the Howard Hughes Medical Institute.

Jeffrey Bluestone is the co-founder, president and chief executive officer. He is with the Parker Institute for Cancer Immunotherapy, University of California, San Francisco and the A.W. and Mary Margaret Clausen Distinguished Professor.

Vijay Kuchroo is a co-founder. Kuchroo is the Samuel L. Wasserstrom professor of neurology, Harvard Medical School, senior scientist in neurology at Brigham and Women’s Hospital, associate member of the Broad Institute, and director of the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women’s Hospital.

Christoph Lengauer is a co-founder and president. A venture partner at Third Rock Ventures, he is also adjunct associate professor, Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University School of Medicine.

Ramnik Xavier is also a co-founder. Xavier is chief of gastroenterology, Massachusetts General Hospital, an institute member with the Broad Institute, and the Kurt Isselbacher professor of medicine, Harvard Medical School.

“When first meeting with Aviv and her colleagues and learning about the significance of this new technology, we knew this had to become a company,” said Lengauer, in a statement. “We formed Celsius with the goal of bringing a novel precision medicine approach to underserved patients with autoimmune diseases and certain cancers. With the new level of clarity provided by single-cell sequencing, our team will be able to address many of the challenges of the current treatments and introduce a new class of medicines that will lead to better outcomes and potential cures.”

Celsius licensed technologies from the Broad Institute based on work by Regev and Kuchroo, as well as non-exclusive licenses to single-cell technologies. It also obtained an exclusive license to early-stage therapies.

“Each of us is made up of tens of trillions of cells,” said Alexis Borisy, partner at Third Rock Ventures and chairman of Celsius Therapeutics, in a statement. “At the core of founding Celsius was the new ability to see something we could not see before. We can now see the dysfunction of key cells and their interactions within their neighborhood. Diseases that we have struggled to understand now can become crystal clear. With that clarity, we hope to create novel precision medicines.”

What differentiates Celcius’ approach is that is believes it has a way of isolating single cells and their interactions with each other. A more typical approach is to study aggregates of cells. Or as Xconomy writes, traditionally a bunch of cells are stuck in a blender, ground up into a slurry, then the DNA and RNA is extracted, which provides an average of the group. “Details about differences between individual cells, and how those cells interact, get lost in the blender.”

Celsius will use high-resolution sequencing technologies to evaluate the RNA of an individual cell. By doing so, the company believes it can identify so-far unidentified genes and biological pathways involved in various diseases.

Regev told Xconomy, “One key challenge is the analysis of data sets of unprecedented size and complexity to identify key cells and genes.”

The company hopes the $65 million will be enough to take the company into clinical trials in the next five years.

https://bit.ly/2GUz1Q5

Accent Therapeutics Launches with $40 Million: Focus on RNA-Modifying Proteins

Accent Therapeutics, headquartered in Cambridge, Massachusetts, closed on a $40 million Series A financing. The round was funded by The Column Group, Atlas Venture and EcoR1 Capital.
Accent will focus on the fairly new area of epitranscriptomics—how RNA structure, stability, function and translation is involved in various diseases. In short, investigating how genes are turned on and off and how their activity is regulated.
RNA, especially messenger RNA (mRNA) function as go-betweens for DNA and the cells’ protein-manufacturing processes. Xconomy writes, “But before the cell makes proteins from RNA, it harnesses a variety of enzymes to attach or remove chemical groups from the RNA. These chemical modifications don’t affect the sequence of the RNA molecule, but they do change the RNA’s molecular structure, stability and function. This can ultimately affect how much protein is made from a particular mRNA. This gives the cell another control knob to turn when it wants to fine-tune the activity of a gene.”
Researchers with Accent recently published an overview of their work in Nature Reviews Drug Discovery with the title, “RNA-Modifying Proteins as Anticancer Drug Targets.” RNA-Modifying Proteins are referred to as RMPs.
The company’s founders include Howard Chang, Standford University; Chuan He, the University of Chicago; and Robert Copeland, president and chief scientific officer of Accent. Copeland said in a statement, “Epitranscriptomics opens a rich new target space, including RMPs that are associated with specific cancers, many with poor patient prognoses. We plan to treat patients by precisely targeting cancers that are uniquely dependent on these specific RMPs.”
Maps of the human epitranscriptome, which show the spots on mRNA molecules where there have been chemical modifications, only first began to be published in 2012. What these changes do, specifically, are still being determined, and are thought to be potential targets for disease modifying therapeutics. Some have already been impliciated in cancer.
The science is very new, which will leave Accent Therapeutics with plenty of basic research to do as it works to develop possible therapeutics. In addition to determining specific mRNA sites and what they do, it will work to identify and develop small molecule drugs that inhibit RNA-modifying enzymes and proteins associated with cancer.
“I like working on the cutting edge of new biology,” Copeland told Xconomy.
The company will use a variety of laboratory techniques, including a CRISPR-based system that, writes Xconomy, “allows them to systematically knock out genes involved in RNA modification one by one, in a wide range of cancer cell types.”
So far Accent has identified approximately 20 targets and has prioritized four. It hopes to identify more.
Copeland launched Epizyme in 2008 as its first chief scientific officer. He was there for nine years, launched an initial public offering, and pushed three drugs into the clinic. Epizyme is also an epigenetics company, focused on drugs that inhibit enzymes that alter DNA. The difference between epigenetics and epitranscriptomic drugs is that epitranscriptomic drug target RNA modifications instead of DNA modifications. The thinking on the part of Copeland and Accent is that the focus on RNA will be more precise.
https://bit.ly/2LzBAdy

Bloom Science Launches from Exclusive UCLA Tech License

San Diego-based Bloom Science launched to develop epilepsy treatments based on a new class of neuroprotective drugs. The company, whose research was published in the journal Cell today, focuses on gut bacteria involved in the anti-seizure effects of the ketogenic diet.

The ketogenic diet was developed in the 1920s to treat epilepsy. In rare types of epilepsy, and in patients who don’t respond to other therapeutics, the diet has positive effects, but because it is low carbohydrate, high fat, compliance is usually a problem. Until recently, it wasn’t clear why the diet worked.

Elaine Hsiao, assistant professor in the Department of Integrative Biology and Physiology in the Life Sciences Division of the UCLA College, and the UCLA David Geffen School of Medicine,as well as co-founder of Bloom, is the senior author of the article, which shows in two preclinical mouse models that the diet increases the growth of certain but bacteria. These specific strains of bacteria are necessary to offer seizure protection. They regulate circulating metabolites that stimulate neurotransmitters in the brain, specifically gamma aminobutyric acid (GABA).

The company will focus on developing products from these bacteria that modulate GABA.

“Despite the introduction of 20 new anti-epilepsy drugs in recent decades, a third of patients with epilepsy never achieve seizure control, and half of those who respond to treatment report negative side effects that limit compliance and negatively impact their quality of life,” said Anthony Colasin, Bloom’s chief executive officer, in a statement. “New and better approaches to managing epilepsy are urgently needed. At Bloom, we are addressing that need by hacking the ketogenic diet to identify microbes with therapeutic potential, and then leveraging a unique business model to develop those microbes as neuroprotective therapies for orphan epilepsy indications in an accelerated time frame.”

The UCLA Technology Development Group has filed a patent on the technology and exclusively licensed it to Bloom.

Colasin is the co-founder, chief executive officer and director of Bloom. Prior to founding Bloom, he was chief business officer of Bionomics, and before that, vice president of Business Development for Ironwood Pharmaceuticals.

Christopher Reyes is the company’s co-founder, chief scientific officer and director. He is also the co-founder and director of Hove. From September 2012 to December 2015 he was vice president of Research and Development Biologics at Bionomics. Before that he was co-founder, chief scientific officer and director of Eclipse Therapeutics.

Hsiao said in a statement, “The human body is comprised of trillions of resident microbes that are important for normal biology, including brain health. The discovery has the potential to impact the many conditions that are associated with alterations in GABA and shown to be modified by the ketogenic diet, such as epilepsy, Alzheimer’s disease, Parkinson’s disease, autism, anxiety and schizophrenia.”

Bloom will be working in the booming area of microbiome research and development, working to develop drugs that exploit the effects of gut bacteria on various diseases. Other companies working in the area include Synthetic Biologics, Microbiota, Sciota Biosciences, and the University of California San Diego School of Medicine, which is running the American Gut Project, a crowdsourced project focused on the human microbiome.

https://bit.ly/2s8IcHZ

Kaplan, CBLA Collaborate on 1st Official Occupational English Test Study Guide

Cambridge Boxhill Language Assessment (CBLA), the owners of the Occupational English Test (OET), and Kaplan Test Prep, the world leader in test preparation, today announced a collaboration on publishing “Official Guide to OET”, the first official study guide for the healthcare-specific exam.

OET assesses the English language skills of healthcare professionals seeking to register and practice in an English-speaking environment. Unlike general English tests, OET test materials are based on real healthcare scenarios so employers can be confident that successful candidates have the right level of English to provide safe, high-quality patient care.

OET results are recognized by healthcare boards and councils globally, including in the UK, Ireland, Australia, New Zealand, Singapore and Dubai as proof of English language proficiency.

The book, available by August, will be the first guide to prepare students for the updated OET, which launches in September.

The OET has gained popularity, with double-digit growth annually, as healthcare professionals increasingly look to this exam as most appropriate for assessing their English language ability.

“We are delighted to have worked with Kaplan Test Prep to create the first official OET study guide. The new book is relevant, an excellent study resource, and will no doubt assist our candidates in developing both the English language skills and confidence to deliver patient safety and quality care in a variety of healthcare settings,” said Sujata Stead, CEO of CBLA.

”The collaboration with CBLA to create this official guide allows us to produce a world-class preparation resource that combines Kaplan’s unparalleled expertise in proven test-taking strategies with verified test-like content vetted by CBLA,” said Steven Marietti, President, Licensure division, Kaplan Test Prep.

https://bit.ly/2J6ZzT8

Med Students Still Do Pelvic Exams on Women Under Anesthesia

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU School of Medicine. How many of you watching learned to do a pelvic exam in medical school or residency on an anesthetized woman, who was getting ready to undergo a surgical procedure for some sort of obstetrical/gynecologic condition? Many people did. I thought the practice was over. After all, many groups, including the American College of Obstetricians and Gynecologists, have issued statements that that should not happen; no one should be using a woman to learn how to do a pelvic exam without consent before that teaching practice is undertaken.

However, when Phoebe Friesen, a former student of mine, was at NYU, she found out that in other parts of the country, and in other nations, there are still women who are being used as teaching subjects for these exams without their permission, without any consent. The practice is just unethical. It’s wrong. It should not be happening. Pointedly, it is because the women themselves have the right to and deserve the respect of giving their permission. Obviously, it is an intimate bodily contact, and more than one person might be involved in these exams.

Think about people like Larry Nassar, who was convicted of molesting young women by touching them without their permission in the name of a therapeutic intervention. Nassar is an extreme case—I understand that. He was a deviant who was getting sexual pleasure from molesting women in the name of medical practice. Nonetheless, part of the outrage about what he was doing is nonconsensual touching in intimate areas on women. We don’t want to see that practice even extended for the noble reason of trying to learn and teach about pelvic exams. I think we should be asking the women, because they have every right to say yes or no, to say whether it’s okay to do that. Some may say yes, some may say no.

If too many people say no, I think the other option is to pay women or find women who would allow people to examine them. Interestingly enough, you may learn better on a conscious woman than on an unconscious woman. Many schools have moved to the practice of hiring women to take on this particular role to help students learn. The other reason it is very important not to do any type of nonconsensual touching is that it teaches students the wrong message. What we want to be saying is, get consent when you touch somebody. Don’t treat somebody as an object or a thing; get their permission. It’s very important to have informed consent.

Sometimes informed consent is a difficult thing to obtain, but it isn’t in this area. People can understand very well what they are being asked. You want to teach the students to respect their patients when they are going to do something like this. It’s very important to send the right message if you’re going to use a patient in a teaching or research role, and to get their permission.

At the end of the day, this is a practice that should come to an abrupt and immediate halt. There should be no teaching on unconscious women without their permission. It’s a violation of their privacy, their dignity, their right not to be touched without their consent. Continuing the practice sends the absolutely wrong message to medical students about how they should be relating to their patients.

https://wb.md/2sjoMiF

LA’s people walker is beating loneliness, one step at a time

Chuck McCarthy’s walking service provides fresh air, exercise and companionship for $30 an hour—but peeing on trees is an absolute no-no.

The Los Angeles-based entrepreneur works with humans, not animals, and is striking a blow for health and social inclusion as the founder of the famously car-friendly city’s first people-walking business.

“I was thinking about becoming a dog walker. But I’ve never had a dog in the city, so I’ve never had to pick up dog poop,” McCarthy told AFP on a recent leisurely saunter in the Hollywood Hills.

“I was also seeing a lot of personal trainer ads. And so I kind of said to my girlfriend, ‘Maybe I’ll just become a people walker.’”

McCarthy was joking but the more he thought about it, the more he realized there was a need for the kind of comradeship he could provide.

The People Walker started as a one-man operation two years ago. But demand was so high that McCarthy now has a roster of 35 walkers, and a website where people can choose routes and walking partners.

Social disconnection has been linked in various studies to depression, heart disease, diabetes and cancer, and can shorten life as profoundly as regular smoking, according to some estimates.

Eric Klinenberg, a professor of sociology at New York University, identified a major cause of loneliness in a recent column in The New York Times: a growing global culture of individualism.

‘Human connection’

It’s not that people have fewer friends, say experts, but rather that the “gig economy” has produced a generation of freelancers with none of the routines or social bonds that traditionally connected workers.

“I’ve walked people that are married with kids that have tons of friends. It’s about convenience and it’s about location and basically having things your way,” McCarthy says.

Meanwhile smartphones and social media have deepened divisions, replacing real human relationships with the ersatz companionship of a social media following.

Instead of “screaming into the void of Twitter or Facebook,” McCarthy’s clients get to enjoy real human connections with people that don’t know them and won’t judge or gossip.

“It seems like something new but it’s very similar to going to confession, to a bar, to a therapist, or going to a hairstylist,” he tells AFP.

McCarthy is an aspiring actor, which makes him coy about revealing his exact age—”I guess I’m in my 30s,” he concedes—but auditions have taken a back seat to the business recently.

“I still wouldn’t turn down a starring role opposite George Clooney,” he adds, just for the record.

The business is on the cusp of making the kind of money McCarthy could call a living, with an app about to launch and grand plans for expansion across California, the US and, eventually, the world.

All shapes and sizes

McCarthy has no idea how far his feet have taken him in the last two years but he walks clients four or five times a week, typically for an hour, and describes himself as more of a listener than a talker.

“It’s less of a confession and more of a conversation. So I wouldn’t say that I’m getting the deepest darkest secrets and nobody is breaking down crying on our walks,” he says.

McCarthy’s clients come in all shapes and sizes, and walk for a variety of reasons.

Anie Dee, a Wisconsinite in her late 20s who decamped to LA seven years ago, had been driving for a ride share service, sitting down all day, and decided last year to get out more.

“I have some health issues so walking long distances is very difficult for me. And so having somebody with me, we walk a lot further than I ever thought I could,” she told AFP.

The freelance theater box office manager noticed as she began going out with McCarthy that her mood and outlook were noticeably more positive.

“When you’re working a lot of desk jobs and you’re by yourself, you don’t really have that social aspect,” she said.

“So when you go for a long walk it’s like, ‘I feel refreshed—this is really nice.’”.

https://bit.ly/2IPmH9B