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Watch out Moderna: John Maraganore, ARCH and Beam are hatching a platform play ‘to lead the future of RNA therapies’

Giuseppe Ciaramella joined Moderna in 2014, back when the mRNA specialist only employed about 70 people. There, as CSO of the infectious disease division,…

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Giuseppe Ciaramella joined Moderna in 2014, back when the mRNA specialist only employed about 70 people. There, as CSO of the infectious disease division, he helped build the initial mRNA vaccine pipeline and steered Moderna’s first vaccine program toward an IND.

He left for Beam Therapeutics four years later, before a wildly successful Covid-19 vaccine propelled Moderna to the biotech hall of fame.

After immersing himself in base editing for the past several years, the biotech vet is making a return to the RNA world — and, with the backing of ARCH, a16z and Newpath Partners, he wants to build the next big thing.

John Maraganore is coming on board as a co-founder of Orbital Therapeutics. The Alnylam founder and former CEO told Endpoints News in an email that he started getting involved soon after becoming a venture partner at ARCH last year. Notably, while Ciaramella believes Orbital has put together the most complex and comprehensive toolbox in the RNA space, it’s conspicuously steering clear of RNA interference — the field Alnylam made its name in.

“My vision for Orbital is to lead the future of RNA therapies (outside of RNAi),” Maraganore wrote.

Kristina Burow

ARCH’s Kristina Burow and Carol Suh are also playing a part in putting the company together, while Ciaramella brought together a quartet of star researchers to be his scientific co-founders: Stanford’s Howard Chang and Ravi Majeti; Drew Weissman at the University of Pennsylvania; and Gene Yeo out at UC-San Diego.

Ciaramella isn’t leaving Beam. In fact, Beam is providing the tools, infrastructure and even personnel to bootstrap Orbital — including the know-how for making, purifying and characterizing linear RNA as well as the lipid nanoparticles to deliver it. Some of the top leadership at Beam will also double as Orbital execs. Ciaramella is serving as Orbital’s interim CEO while continuing his day job as Beam’s president and CSO; Beam CFO Terry-Ann Burrell will also assist while CEO John Evans is on Orbital’s board.

The discussions with ARCH started, he said, as Beam realized that as it worked on its core promise of making therapies out of base editing — the gene editing technique where scientists can chemically change DNA one letter at a time — the biotech was developing a whole host of complementary technologies that can potentially be applied broadly outside gene editing.

Orbital is grabbing rights to all of that, with certain areas mapped out for exclusivity. In exchange, Beam will grab an equity stake in Orbital and access to the newer technologies Orbital has introduced from its scientific co-founders, such as circular RNA and virus-like particles.

“The idea is really to take the state-of-the-art of what is currently available as far as delivery and RNA technology and put them all under one roof,” Ciaramella said. “And the reason why that, we think, is really essential is because it creates, first of all, a critical mass of technologies that are needed to realize the full potential of RNA medicine. This is basically behind the foundation of Orbital — it’s really to finally achieve the potential that RNA has always had since the very beginning. But some technical limitations were preventing this from happening.”

One of those limitations, he added, was a short half-life that prevented companies from making protein replacement therapies out of RNA, akin to what’s currently done with one-shot gene therapies. From autoimmunity to blood disorders to regenerative medicines, he sees Orbital making medicines that have “never been possible to make before.”

If you think about it, the beauty of RNA is its programmability. The same chemical can actually make many different proteins. And so potentially you can combine, let’s say a cytokine with a receptor or an intracellular protein, which will be very, very difficult to do with traditional technology. Imagine a drug product that binds maybe a peptide or cellular component or a receptor — it’s very difficult to manufacture. In this case, it’s always the same thing. So you manufacture exactly the same polymer, which is the RNA, you can potentially even co-formulate it in the same LNP. And now you’re instructing the body to really manipulate a disease system in a very sophisticated and complex way. And so you’re not just relying on a single point of intervention, but potentially — imagine if there is a signaling cascade, modulated at the beginning or at the end, you can really now develop therapeutic modalities that it’s never been possible to do before. And that was the dream of RNA and I think the technology that is emerging is providing line of sight to doing that. And that’s why you really need that critical mass of all of the available technology.

With some of the newer tools, Ciaramella would go so far as to say Orbital’s technology suite is probably competitive with what Moderna has now, at least based on publicly available information. And just like Moderna, he envisions Orbital to be a platform company that will push forward multiple projects simultaneously.

The deal with Beam provides Orbital access to its tech exclusively for vaccines and protein replacement therapies, and non-exclusively for other uses. For Beam, the exclusive terms are limited to gene editing and conditioning for transplants, while the rest is all non-exclusive.

At this stage of the company build, Ciaramella is reluctant to go into timelines. But with a funding round on the horizon — to be unveiled soon — he wants to stay on the faster side of an IND by identifying some programs that are relatively quick to the clinic. The goal is not only to generate buzz on the tech, but also to train the organization.

“Really what we want to create is what I call momentum,” he said.

The company’s headcount is at 15 now, and Ciaramella pointed to Beam — which is five years into launch and has about 500 employees — as a reference point for the speed and scale he’s shooting for. A fellow Moderna vet, Gilles Besin, will soon jump from Affinivax to become Orbital’s CSO.

So you can expect plenty of cash for the showdown at a time the whole field is bubbling with excitement.

“Having spent 20 years advancing RNAi therapeutics as a whole new class of medicines, I’m a huge believer in the potential of RNA-based therapies as one of the most important frontiers of medicine,” Maraganore wrote. “Excluding RNAi and ASOs, RNA therapies are in the 1st few innings of their potential for disease impact.”

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Homes listed for sale in early June sell for $7,700 more

New Zillow research suggests the spring home shopping season may see a second wave this summer if mortgage rates fall
The post Homes listed for sale in…

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March 11, 2024

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  • A Zillow analysis of 2023 home sales finds homes listed in the first two weeks of June sold for 2.3% more. 
  • The best time to list a home for sale is a month later than it was in 2019, likely driven by mortgage rates.
  • The best time to list can be as early as the second half of February in San Francisco, and as late as the first half of July in New York and Philadelphia. 

Spring home sellers looking to maximize their sale price may want to wait it out and list their home for sale in the first half of June. A new Zillow® analysis of 2023 sales found that homes listed in the first two weeks of June sold for 2.3% more, a $7,700 boost on a typical U.S. home.  

The best time to list consistently had been early May in the years leading up to the pandemic. The shift to June suggests mortgage rates are strongly influencing demand on top of the usual seasonality that brings buyers to the market in the spring. This home-shopping season is poised to follow a similar pattern as that in 2023, with the potential for a second wave if the Federal Reserve lowers interest rates midyear or later. 

The 2.3% sale price premium registered last June followed the first spring in more than 15 years with mortgage rates over 6% on a 30-year fixed-rate loan. The high rates put home buyers on the back foot, and as rates continued upward through May, they were still reassessing and less likely to bid boldly. In June, however, rates pulled back a little from 6.79% to 6.67%, which likely presented an opportunity for determined buyers heading into summer. More buyers understood their market position and could afford to transact, boosting competition and sale prices.

The old logic was that sellers could earn a premium by listing in late spring, when search activity hit its peak. Now, with persistently low inventory, mortgage rate fluctuations make their own seasonality. First-time home buyers who are on the edge of qualifying for a home loan may dip in and out of the market, depending on what’s happening with rates. It is almost certain the Federal Reserve will push back any interest-rate cuts to mid-2024 at the earliest. If mortgage rates follow, that could bring another surge of buyers later this year.

Mortgage rates have been impacting affordability and sale prices since they began rising rapidly two years ago. In 2022, sellers nationwide saw the highest sale premium when they listed their home in late March, right before rates barreled past 5% and continued climbing. 

Zillow’s research finds the best time to list can vary widely by metropolitan area. In 2023, it was as early as the second half of February in San Francisco, and as late as the first half of July in New York. Thirty of the top 35 largest metro areas saw for-sale listings command the highest sale prices between May and early July last year. 

Zillow also found a wide range in the sale price premiums associated with homes listed during those peak periods. At the hottest time of the year in San Jose, homes sold for 5.5% more, a $88,000 boost on a typical home. Meanwhile, homes in San Antonio sold for 1.9% more during that same time period.  

 

Metropolitan Area Best Time to List Price Premium Dollar Boost
United States First half of June 2.3% $7,700
New York, NY First half of July 2.4% $15,500
Los Angeles, CA First half of May 4.1% $39,300
Chicago, IL First half of June 2.8% $8,800
Dallas, TX First half of June 2.5% $9,200
Houston, TX Second half of April 2.0% $6,200
Washington, DC Second half of June 2.2% $12,700
Philadelphia, PA First half of July 2.4% $8,200
Miami, FL First half of June 2.3% $12,900
Atlanta, GA Second half of June 2.3% $8,700
Boston, MA Second half of May 3.5% $23,600
Phoenix, AZ First half of June 3.2% $14,700
San Francisco, CA Second half of February 4.2% $50,300
Riverside, CA First half of May 2.7% $15,600
Detroit, MI First half of July 3.3% $7,900
Seattle, WA First half of June 4.3% $31,500
Minneapolis, MN Second half of May 3.7% $13,400
San Diego, CA Second half of April 3.1% $29,600
Tampa, FL Second half of June 2.1% $8,000
Denver, CO Second half of May 2.9% $16,900
Baltimore, MD First half of July 2.2% $8,200
St. Louis, MO First half of June 2.9% $7,000
Orlando, FL First half of June 2.2% $8,700
Charlotte, NC Second half of May 3.0% $11,000
San Antonio, TX First half of June 1.9% $5,400
Portland, OR Second half of April 2.6% $14,300
Sacramento, CA First half of June 3.2% $17,900
Pittsburgh, PA Second half of June 2.3% $4,700
Cincinnati, OH Second half of April 2.7% $7,500
Austin, TX Second half of May 2.8% $12,600
Las Vegas, NV First half of June 3.4% $14,600
Kansas City, MO Second half of May 2.5% $7,300
Columbus, OH Second half of June 3.3% $10,400
Indianapolis, IN First half of July 3.0% $8,100
Cleveland, OH First half of July  3.4% $7,400
San Jose, CA First half of June 5.5% $88,400

 

The post Homes listed for sale in early June sell for $7,700 more appeared first on Zillow Research.

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Survey Shows Declining Concerns Among Americans About COVID-19

Survey Shows Declining Concerns Among Americans About COVID-19

A new survey reveals that only 20% of Americans view covid-19 as "a major threat"…

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March 11, 2024

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Survey Shows Declining Concerns Among Americans About COVID-19

A new survey reveals that only 20% of Americans view covid-19 as "a major threat" to the health of the US population - a sharp decline from a high of 67% in July 2020.

(SARMDY/Shutterstock)

What's more, the Pew Research Center survey conducted from Feb. 7 to Feb. 11 showed that just 10% of Americans are concerned that they will  catch the disease and require hospitalization.

"This data represents a low ebb of public concern about the virus that reached its height in the summer and fall of 2020, when as many as two-thirds of Americans viewed COVID-19 as a major threat to public health," reads the report, which was published March 7.

According to the survey, half of the participants understand the significance of researchers and healthcare providers in understanding and treating long COVID - however 27% of participants consider this issue less important, while 22% of Americans are unaware of long COVID.

What's more, while Democrats were far more worried than Republicans in the past, that gap has narrowed significantly.

"In the pandemic’s first year, Democrats were routinely about 40 points more likely than Republicans to view the coronavirus as a major threat to the health of the U.S. population. This gap has waned as overall levels of concern have fallen," reads the report.

More via the Epoch Times;

The survey found that three in ten Democrats under 50 have received an updated COVID-19 vaccine, compared with 66 percent of Democrats ages 65 and older.

Moreover, 66 percent of Democrats ages 65 and older have received the updated COVID-19 vaccine, while only 24 percent of Republicans ages 65 and older have done so.

“This 42-point partisan gap is much wider now than at other points since the start of the outbreak. For instance, in August 2021, 93 percent of older Democrats and 78 percent of older Republicans said they had received all the shots needed to be fully vaccinated (a 15-point gap),” it noted.

COVID-19 No Longer an Emergency

The U.S. Centers for Disease Control and Prevention (CDC) recently issued its updated recommendations for the virus, which no longer require people to stay home for five days after testing positive for COVID-19.

The updated guidance recommends that people who contracted a respiratory virus stay home, and they can resume normal activities when their symptoms improve overall and their fever subsides for 24 hours without medication.

“We still must use the commonsense solutions we know work to protect ourselves and others from serious illness from respiratory viruses, this includes vaccination, treatment, and staying home when we get sick,” CDC director Dr. Mandy Cohen said in a statement.

The CDC said that while the virus remains a threat, it is now less likely to cause severe illness because of widespread immunity and improved tools to prevent and treat the disease.

“Importantly, states and countries that have already adjusted recommended isolation times have not seen increased hospitalizations or deaths related to COVID-19,” it stated.

The federal government suspended its free at-home COVID-19 test program on March 8, according to a website set up by the government, following a decrease in COVID-19-related hospitalizations.

According to the CDC, hospitalization rates for COVID-19 and influenza diseases remain “elevated” but are decreasing in some parts of the United States.

Tyler Durden Sun, 03/10/2024 - 22:45

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Rand Paul Teases Senate GOP Leader Run – Musk Says “I Would Support”

Rand Paul Teases Senate GOP Leader Run – Musk Says "I Would Support"

Republican Kentucky Senator Rand Paul on Friday hinted that he may jump…

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12 hours ago

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March 10, 2024

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Rand Paul Teases Senate GOP Leader Run - Musk Says "I Would Support"

Republican Kentucky Senator Rand Paul on Friday hinted that he may jump into the race to become the next Senate GOP leader, and Elon Musk was quick to support the idea. Republicans must find a successor for periodically malfunctioning Mitch McConnell, who recently announced he'll step down in November, though intending to keep his Senate seat until his term ends in January 2027, when he'd be within weeks of turning 86. 

So far, the announced field consists of two quintessential establishment types: John Cornyn of Texas and John Thune of South Dakota. While John Barrasso's name had been thrown around as one of "The Three Johns" considered top contenders, the Wyoming senator on Tuesday said he'll instead seek the number two slot as party whip. 

Paul used X to tease his potential bid for the position which -- if the GOP takes back the upper chamber in November -- could graduate from Minority Leader to Majority Leader. He started by telling his 5.1 million followers he'd had lots of people asking him about his interest in running...

...then followed up with a poll in which he predictably annihilated Cornyn and Thune, taking a 96% share as of Friday night, with the other two below 2% each. 

Elon Musk was quick to back the idea of Paul as GOP leader, while daring Cornyn and Thune to follow Paul's lead by throwing their names out for consideration by the Twitter-verse X-verse. 

Paul has been a stalwart opponent of security-state mass surveillance, foreign interventionism -- to include shoveling billions of dollars into the proxy war in Ukraine -- and out-of-control spending in general. He demonstrated the latter passion on the Senate floor this week as he ridiculed the latest kick-the-can spending package:   

In February, Paul used Senate rules to force his colleagues into a grueling Super Bowl weekend of votes, as he worked to derail a $95 billion foreign aid bill. "I think we should stay here as long as it takes,” said Paul. “If it takes a week or a month, I’ll force them to stay here to discuss why they think the border of Ukraine is more important than the US border.”

Don't expect a Majority Leader Paul to ditch the filibuster -- he's been a hardy user of the legislative delay tactic. In 2013, he spoke for 13 hours to fight the nomination of John Brennan as CIA director. In 2015, he orated for 10-and-a-half-hours to oppose extension of the Patriot Act. 

Rand Paul amid his 10 1/2 hour filibuster in 2015

Among the general public, Paul is probably best known as Capitol Hill's chief tormentor of Dr. Anthony Fauci, who was director of the National Institute of Allergy and Infectious Disease during the Covid-19 pandemic. Paul says the evidence indicates the virus emerged from China's Wuhan Institute of Virology. He's accused Fauci and other members of the US government public health apparatus of evading questions about their funding of the Chinese lab's "gain of function" research, which takes natural viruses and morphs them into something more dangerous. Paul has pointedly said that Fauci committed perjury in congressional hearings and that he belongs in jail "without question."   

Musk is neither the only nor the first noteworthy figure to back Paul for party leader. Just hours after McConnell announced his upcoming step-down from leadership, independent 2024 presidential candidate Robert F. Kennedy, Jr voiced his support: 

In a testament to the extent to which the establishment recoils at the libertarian-minded Paul, mainstream media outlets -- which have been quick to report on other developments in the majority leader race -- pretended not to notice that Paul had signaled his interest in the job. More than 24 hours after Paul's test-the-waters tweet-fest began, not a single major outlet had brought it to the attention of their audience. 

That may be his strongest endorsement yet. 

Tyler Durden Sun, 03/10/2024 - 20:25

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