Top Stories for Week of February 24, 2020

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Aided by machine learning (AI), scientists find novel antibiotic able to kill superbugs.

A powerful antibiotic that kills some of the most dangerous drug-resistant bacteria in the world has been discovered using artificial intelligence. The drug works in a different way to existing antibacterials and is the first of its kind to be found by setting AI loose on vast digital libraries of pharmaceutical compounds. Tests showed that the drug wiped out a range of antibiotic-resistant strains of bacteria, including Acinetobacter baumannii and Enterobacteriaceae, two of the three high-priority pathogens that the World Health Organization (Geneva) ranks as “critical” for new antibiotics to target.

“In terms of antibiotic discovery, this is absolutely a first,” said Regina Barzilay, a senior researcher on the project and specialist in machine learning at Massachusetts Institute of Technology (Cambridge MA).

“I think this is one of the more powerful antibiotics that has been discovered to date,” added James Collins, a bioengineer on the team at MIT. “It has remarkable activity against a broad range of antibiotic-resistant pathogens.”

To find new antibiotics, the researchers first trained a “deep learning” algorithm to identify the sorts of molecules that kill bacteria. To do this, they fed the program information on the atomic and molecular features of nearly 2,500 drugs and natural compounds and how well or not the substance blocked the growth of the bug E coli. Once the algorithm had learned what molecular features made for good antibiotics, the scientists set it working on a library of more than 6,000 compounds under investigation for treating various human diseases.

Rather than looking for any potential antimicrobials, the algorithm focused on compounds that looked effective but unlike existing antibiotics. This boosted the chances that the drugs would work in radical new ways that bugs had yet to develop resistance to. Jonathan Stokes, the first author of the study, said it took a matter of hours for the algorithm to assess the compounds and come up with some promising antibiotics. One, which the researchers named “halicin” after Hal, the astronaut-bothering AI in the film 2001: A Space Odyssey, looked particularly potent.

Writing in the journal Cell, the researchers describe how they treated numerous drug-resistant infections with halicin, a compound that was originally developed to treat diabetes, but which fell by the wayside before it reached the clinic. Tests on bacteria collected from patients showed that halicin killed Mycobacterium tuberculosis, the bug that causes TB, and strains of Enterobacteriaceae that are resistant to carbapenems, a group of antibiotics that are considered the last resort for such infections. Halicin also cleared C difficile and multidrug-resistant Acinetobacter baumannii infections in mice.

Barzilay now wants to use the algorithm to find antibiotics that are more selective in the bacteria they kill. This would mean that taking the antibiotic kills only the bugs causing an infection, and not all the healthy bacteria that live in the gut. More ambitiously, the scientists aim to use the algorithm to design potent new antibiotics from scratch.

Tracking Washington

A single-payer healthcare system would save more than 68,000 lives and $450 billion a year, new research shows. Americans spend more money on health care than people in other wealthy nations, but we live shorter lives, says the Washington Post. A new analysis, published in the journal Lancet, adds some pragmatic bulk to an argument many progressives have been making for years: A national single-payer healthcare system would save tens of thousands of lives each year–and hundreds of billions of dollars.

In last week’s debate in Nevada, Sen. Bernie Sanders (I-VT) cited “a major study [that] came out from Yale epidemiologist[s] in Lancet, one of the leading medical publications in the world” in support of his Medicare-for-all plan. He was talking about this study, which was published last week. The study’s lead author, Alison Galvani, is the director of Yale University’s Center for Infectious Disease Modeling and Analysis. The paper discloses that Galvani served as an “informal, unpaid advisor” to Sanders’ Senate office as it developed the Medicare For All Act. None of the other authors disclosed any outside or competing interests.

Overall, the study concludes, a single-payer system analogous to Sanders’s plan would slash the nation’s healthcare expenditures by 13%, or more than $450 billion, each year. Not only that, “ensuring healthcare access for all Americans would save more than 68,000 lives.” In their breakdown of the numbers, researchers applied the existing Medicare fee structure across the entire healthcare system and found it would save about $100 billion annually.

The Post says to keep in mind that this basically represents less money going to doctors and hospitals, a major sticking point for medical groups that oppose Medicare-for-all. But those declines would be more than offset by several hundred billions in savings from reduced administrative and billing costs, Galvani and her colleagues estimate. The lack of patient billing under a Medicare-for-all system would also eliminate the roughly $35 billion a year that hospitals now pay to chase down unpaid bills.

The authors estimate an additional $219 billion in savings from reduced “administrative overhead” that the current decentralized system creates, including “the elimination of redundant corporate functions and the truncation of the top-heavy salary architecture of health insurance corporations.” For instance, the plan would replace dozens of health insurance executives, with one administrator paid the same salary as the current Secretary of Health and Human Services. Finally, allowing the national Medicare system to negotiate pharmaceutical prices would save about $180 billion, according to the analysis. Add it all up and here’s what you get: a new system that would cost about $3 trillion a year, instead of the $3.5 trillion that is being spent now.

IPO Sector

Preclinical biotech Passage Bio Inc. said it plans to raise $126 million this week by offering 7.4 million shares at a price range of $16 to $18. At the midpoint, Passage Bio would command a market cap of $713 million. The Philadelphia, PA-based company was formed by OrbiMed, Frazier Healthcare, and UPenn’s Gene-Therapy Program and is developing gene therapies for rare central nervous system disorders.

Passage Bio is very early stage, with its drug candidates not expected to start clinical trials until at least the 2H20. But early-stage biotechs have been performing very well this year, averaging an 88.3% return. The company says it will use the IPO funds for development of its three lead gene therapy programs in dementia, Krabbe disease and rare childhood disease GM1 gangliosidosis. Those programs were among five that Passage picked up in its partnership with UPenn’s Gene-Therapy Program in February 2019. At the same time, the biotech brought home a $115.5 million series A round to bankroll the development of those programs, all of which target rare, monogenic CNS diseases.

In addition to its three lead treatments, Passage has three discovery-stage programs. They target metachromatic leukodystrophy, a specific subset of patients with amyotrophic lateral sclerosis and patients with Charcot-Marie-Tooth hereditary neuropathy type 2A stemming from a particular mutation. Passage Bio was founded in 2017 and plans to list on the Nasdaq under the symbol “PASG.” J.P. Morgan, Goldman Sachs and Cowen are the joint bookrunners on the deal. It is expected to price during the week of February 24, 2020.

Elsewhere, Imara Inc., a Phase 2 biotech developing small molecule therapies for rare, genetic blood disorders, filed on Friday with the SEC to raise up to $86 million in an initial public offering. The Cambridge, MA-based company’s filing comes a few weeks after Beam Therapeutics raised $180 million and Black Diamond raised $201 million in the first local biotech IPOs of the year.

Imara is developing a daily pill for two blood disorders: sickle cell disease, which affects approximately 4.4 million people worldwide, and beta thalassemia, which affects roughly 288,000 people worldwide. It is currently running two mid-stage clinical trials of the potential treatment. The four-year-old startup faces competition on both fronts: several companies, including bluebird bio Inc. and Agios Pharmaceuticals Inc., are testing sickle cell therapies. Meanwhile, bluebird and Acceleron Pharma Inc. are currently commercializing beta thalassemia treatments, while CRISPR Therapeutics Inc. and Vertex Pharmaceuticals Inc. are testing a method of removing the gene responsible for the disease.

Imara was founded in 2016 and plans to list on the Nasdaq under the symbol “IMRA.” Morgan Stanley, Citi and SVB Leerink are the joint bookrunners on the deal. No pricing terms were disclosed.

London would be ready to host the 2020 Olympics if the outbreak of the coronavirus forced the Games to be moved from Tokyo, Shaun Bailey, the Conservative candidate for mayor of the British capital, has said. London hosted the Olympics in 2012, but British officials played down the prospect of taking away the Games from Tokyo, which has been planning the event for seven years since its bid won in 2013.

The flu-like coronavirus, which has killed more than 2,000 people in China and infected over 74,000 globally, has had a major impact on the sporting calendar in Asia with a host of events being cancelled and postponed. With the Tokyo Games due to begin on July 24, organizers have set up a task force to coordinate with public health authorities over the epidemic. The International Olympic Committee has said it had been advised by the World Health Organization that there is no case for contingency plans to cancel or relocate the Games.

In Japan, hundreds have been infected by the virus with two deaths confirmed on the Diamond Princess cruise ship off Yokohama port, sparking concerns that the world’s top sporting event may not take place. Despite much of the 2012 infrastructure being repurposed to redevelop parts of east London after the Games, Bailey said the city was well placed to step in for Tokyo if needed and urged the Olympic Committee to consider the city as an alternative. (Ref: Reuters)

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