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David Baker’s lab shows generative AI can design antibodies. But are they good enough to become drugs?

The promise of using artificial intelligence to design biologic drugs from scratch is starting to look a lot less abstract.
This week, scientists led by…

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The promise of using artificial intelligence to design biologic drugs from scratch is starting to look a lot less abstract.

This week, scientists led by David Baker at the University of Washington revealed work showing that they have created therapeutically active proteins from scratch. Using the lab’s generative AI model they created an antibody that neutralizes a bacterial toxin and three that target the viruses responsible for Covid-19, RSV and the flu.

The study, which was posted Monday on bioRxiv and has not been peer-reviewed, showcases the potential power of using AI to make antibodies that target proteins just as their designers intended, rather than trawling through the blood of mice or humans in hopes of finding just the right one.

Yet it also suggests that AI-designed antibodies aren’t yet good enough to pass muster as drugs, at least not at the touch of a button. Scientists not involved in the study told Endpoints News that the work was a step in the right direction, but said the antibodies didn’t stick strongly enough to their targets to become real drug candidates, a point that Baker conceded.

“They’re just too weak for primetime,” Baker told Endpoints in an interview. “I think this is showing what the way of the future is going to be. But these things are not yet tight enough to be used as drugs.”

Making antibodies entirely on computers could become one of the most useful and lucrative applications of the growing de novo protein design field, in which scientists generate proteins never before seen in nature. While Baker’s Institute for Protein Design in Seattle has created other binding proteins before, they were simpler and more alien than the standard antibodies that pharma companies know and love.

Baker’s new preprint shows how his lab’s software, called RFdiffusion, can generate the structures of antibodies that mesh neatly with a specific surface on a bacterial or viral protein. It suggests that AI could help target the Achilles heel of such proteins. “Normally, you can’t really control that,” Baker said. “But in our approach, you specify where on the target you want to bind.”

When the lab tested its antibodies on the viral proteins and used high-powered microscopes to see the results, the structures and interactions were “basically identical” to what their computer program predicted, Baker said. “That was the wow moment.”

Big investments and blockbuster dreams

Many of biopharma’s best-selling drugs are antibodies, and the race is on to tap the AI technologies underpinning text and image generators like ChatGPT to create antibodies. Generate:Biomedicines, an AI startup just outside of Boston, has raised nearly $750 million to make therapeutic proteins, with an initial focus on antibodies. Absci, BigHat Biosciences, and Nabla Bio are also focused on making antibodies with AI.

Nicholas Polizzi

“Deep learning is making previously difficult design problems now tractable,” Nicholas Polizzi, a protein scientist at Dana-Farber Cancer Institute told Endpoints in an email. But like many problems in using AI for biology, “we are running up against a wall of not-enough-training-data,” he said.

The four targets chosen for Baker’s paper weren’t especially tough nuts to crack, since there are already many existing antibodies for those bacteria and viruses. Polizzi noted that the antibodies also targeted surfaces of those proteins for which strong binders already exist, a lower-hanging fruit than targeting a novel surface.

But Baker said that the structures of the antibodies were different enough from existing ones found in the Protein Data Bank — used as the training source for RFdiffusion — that he’s confident the model is coming up with new solutions and not just regurgitating what it’s been fed.

In addition to improving the AI model to make better antibodies, the lab is also working towards making antibodies against more difficult drug targets. Although RFdiffusion is open source, he also wants to make an easier-to-use text interface where scientists can ask the program to generate the amino acid sequence of an antibody that binds to specific sites of a protein.

“We’re not there yet,” Baker said. “But I don’t think we’re far away.”

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Visionary $15 million gift from Wayne & Wendy Holman to NYU Langone Health ensures continued excellence in newly named Holman Division of Endocrinology, Diabetes & Metabolism

NYU Langone Health has received a $15 million gift from innovators and philanthropists Wayne G. Holman, MD, and Wendy Holman to further elevate the world-class…

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March 20, 2024

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NYU Langone Health has received a $15 million gift from innovators and philanthropists Wayne G. Holman, MD, and Wendy Holman to further elevate the world-class treatment and study of endocrine disorders in the newly named and endowed Holman Division of Endocrinology, Diabetes & Metabolism.

Credit: Mateo Salcedo / NYU Langone Health

NYU Langone Health has received a $15 million gift from innovators and philanthropists Wayne G. Holman, MD, and Wendy Holman to further elevate the world-class treatment and study of endocrine disorders in the newly named and endowed Holman Division of Endocrinology, Diabetes & Metabolism.

“Wayne and Wendy’s generosity in this important area of medicine will help NYU Langone further enhance our exceptional research, education and clinical care within the Holman Division of Endocrinology, Diabetes & Metabolism,” said Robert I. Grossman, MD, dean and CEO, NYU Langone. “NYU Langone has a rich history of developing novel treatment options to provide superior outcomes for the most complex cases, and thanks to this endowment, we can sustain these efforts over time.”

“This impactful gift will propel the division into its next phase of growth by establishing new translational research, clinical trials, academic forums, and advancing clinical care, among other initiatives,” said Steven Abramson, MD, Frederick H. King Professor of Internal Medicine and chair of the Department of Medicine at NYU Grossman School of Medicine. “I am excited for the medical advances that will undoubtedly come about because of the Holmans’ deep investment.”

The Holman Division of Endocrinology, Diabetes, & Metabolism, part of the Department of Medicine at NYU Grossman School of Medicine, is among the best in the country, ranked No. 2 U.S. News & World Report’s specialty rankings for 2023-24. The division’s robust research program has made major contributions to the studies of diabetes care, thyroid disease, obesity, neuroendocrinology, lipid disorders, and bone health.

Dr. Holman was recently elected to NYU Langone’s Board of Trustees. His gift is the largest ever given to the NYU Grossman School of Medicine by an alumnus.

“NYU Langone and its medical school gave me the gifts of knowledge, experience, and lifelong friendships. Wendy and I are happy to give back by supporting the dedicated and innovative researchers, physicians, and caregivers in the Holman Division of Endocrinology, Metabolism, and Diabetes who care for patients and advance work toward new treatments and cures,” said Dr. Holman. “We look forward to the achievements. Many thanks to those working so hard on these endeavors.”

For more than 18 years, Dr. Holman has served as founder and CEO of Ridgeback Capital, a private investment firm focusing on the life sciences. Dr. Holman’s work at Ridgeback Capital has provided funding to companies that have developed medicines for various cancers, infectious diseases, rare pediatric diseases, and more. In 2016, the Holmans founded Ridgeback Biotherapeutics, a biotech company focused on developing life-saving medications to treat diseases with limited or no treatment options. Ridgeback Biotherapeutics has brought two medicines—for Ebola and COVID-19—to regulatory approvals around the world. For decades, Dr. Holman and Mrs. Holman have leveraged their own success to help vulnerable populations, facilitating drug research and development at over a hundred biopharmaceutical companies.

“Wayne and I are happy to support advancements in collaboration with NYU Langone that will have a tangible positive effect on health and alleviate human suffering,” said Mrs. Holman. “We are confident the division will continue to make a significant impact on the field and benefit countless individuals, and we are proud to be part of that.”

“Wendy and Wayne are people who have dedicated every aspect of their lives to helping others. They see NYU Langone as an institution with the ability to magnify every dollar, and through which they can have exponential impact,” said Kenneth G. Langone, chair of the NYU Langone Board of Trustees. “And they’re right.”

Media Inquiries

Katie Ullman
Phone: 646-483-3984
Kathryn.ullman@nyulangone.org

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COVID-19 Infection Increases Risk Of Autoimmune Diseases By Up To 30 Percent: Study

COVID-19 Infection Increases Risk Of Autoimmune Diseases By Up To 30 Percent: Study

Authored by George Citroner via The Epoch Times (emphasis…

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March 20, 2024

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COVID-19 Infection Increases Risk Of Autoimmune Diseases By Up To 30 Percent: Study

Authored by George Citroner via The Epoch Times (emphasis ours),

(Juan Gaertner/Shutterstock)

Surviving COVID-19 may leave you at heightened risk of developing debilitating autoimmune diseases like rheumatoid arthritis and lupus for up to a year after infection, according to new research.

However, the study also found that vaccinating against the virus could significantly lower your chances of developing these potentially life-altering inflammatory conditions.

COVID-19 Infection Severity Plays a Big Role

The study, published in Annals of Internal Medicine, analyzed national claims data from over 10 million Korean and 12 million Japanese patients aged 20 and above diagnosed with COVID-19 between January 2020 and December 2021. The dominant strains were the wild-type virus and the delta variant during this period. COVID-19 patients were compared with matched flu patients and uninfected controls.

A little less than 4 percent of Korean participants had a history of COVID-19, and about 1 percent had a history of flu. Among Japanese participants, about 8 percent had been infected with COVID-19, and slightly less than 1 percent had been infected with flu.

Researchers found that COVID-19 patients had a 25 percent to 30 percent increased risk of new-onset autoimmune rheumatic diseases (AIRDs) 30 days after infection compared to uninfected individuals.

More severe COVID-19 was linked to a greater risk of new-onset, untreated, and treated AIRD, with both wild-type and delta variants associated with AIRD risk. The risk of new-onset AIRD seemed to decline over time and trailed off after the first year.

COVID-19 infection is associated with numerous autoimmune disorders, Dr. Jacob Teitelbaum, a board-certified internist specializing in the treatment of chronic fatigue syndrome and fibromyalgia, told The Epoch Times. “For example, there is a marked increase in hyperthyroidism after COVID caused by autoimmune attack on the thyroid glands,” he said. With the immune system already on high alert from the virus and “having trouble shutting down,” it is not surprising that the body’s own tissues will often become collateral damage, he noted.

“So this new study simply confirms what is already expected,” Dr. Teitelbaum added.

Vaccines Reduce Autoimmune Risk, but Only in Mild Cases

The findings also suggest that COVID-19 vaccination reduced the rate of AIRDs among patients who received one to two or more doses. This reduced risk was observed whether the vaccine used was mRNA-based or viral-vector type.

However, the reduced AIRD risk was only linked to patients with mild COVID-19 infection, not those with moderate or severe infection.

This is noteworthy, given growing evidence suggesting that COVID-19 vaccination could cause new-onset autoimmune diseases, including autoimmune glomerulonephritis, autoimmune hepatitis, and AIRDs.

AIRDs Increase Risk of Other Severe Conditions

AIRDs involve inflammation of the joints or connective tissue caused by attacks from the body’s immune system. These diseases can affect multiple organs and systems, leading to a wide range of symptoms and complications.

Some common AIRDs include:

  • Rheumatoid arthritis (RA): RA is a chronic autoimmune disorder that primarily affects joints, causing inflammation, pain, stiffness, and swelling. Untreated RA can lead to joint damage, deformities, disability, cardiovascular disease, osteoporosis, and lung problems over time.
  • Systemic lupus erythematosus (SLE): SLE is a systemic autoimmune disease affecting various organs and tissues like skin, joints, kidneys, heart, lungs, and brain. Symptoms may include fatigue, joint pain, skin rashes, fever, and organ inflammation. Complications involve kidney damage, cardiovascular disease, neurological disorders, and increased infection susceptibility.
  • Ankylosing spondylitis (AS): AS primarily affects the spine and sacroiliac joints, causing inflammation and eventual vertebrae fusion, leading to spinal stiffness and limited mobility. It can also impact other joints, eyes, and organs. Complications may include spinal deformities, eye inflammation, and cardiovascular problems.
  • Psoriatic arthritis (PsA): PsA is an autoimmune condition with joint inflammation and skin lesions (psoriasis). In addition to joint pain, swelling, and stiffness, PsA can cause nail changes, eye inflammation, and tendon inflammation (enthesitis). Complications could include diabetes and high blood pressure.
  • Sjögren’s syndrome: Sjögren’s syndrome primarily affects moisture-producing glands, leading to dry eyes and mouth. However, it can also cause systemic issues like joint pain, fatigue, and organ involvement of the kidneys, lungs, or nervous system. It increases the risk of lymphoma and other autoimmune diseases.
  • Systemic sclerosis (scleroderma): Scleroderma is characterized by excessive collagen production, causing thickening and hardening of skin and connective tissues. It can also affect internal organs like the lungs, heart, kidneys, and gastrointestinal tract. Complications may include gastrointestinal bleeding, lung and heart problems, and bowel obstruction.

Inexpensive Treatment Available but Ignored: Expert

AIRDs significantly impact quality of life and require long-term management with medications, physical therapy, and lifestyle modifications. Regular monitoring and comprehensive care from health care professionals are essential for managing these conditions and minimizing health risks.

However, effective yet inexpensive treatments for these conditions are largely ignored, Dr. Teitelbaum said.

Low-dose naltrexone, costing less than $1 a day, has been shown to help chronic pain or autoimmune conditions, he added. Additionally, highly absorbed curcumin and Boswellia serrata, found in curcumin, were proven as effective as Celebrex in treating rheumatic arthritis in a head-to-head study, he noted.

Tyler Durden Wed, 03/20/2024 - 02:45

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Apartment permits are back to recession lows. Will mortgage rates follow?

If housing leads us into a recession in the near future, that means mortgage rates have stayed too high for too long.

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9 hours ago

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March 19, 2024

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In Tuesday’s report, the 5-unit housing permits data hit the same levels we saw in the COVID-19 recession. Once the backlog of apartments is finished, those jobs will be at risk, which traditionally means mortgage rates would fall soon after, as they have in previous economic cycles.

However, this is happening while single-family permits are still rising as the rate of builder buy-downs and the backlog of single-family homes push single-family permits and starts higher. It is a tale of two markets — something I brought up on CNBC earlier this year to explain why this trend matters with housing starts data because the two marketplaces are heading in opposite directions.

The question is: Will the uptick in single-family permits keep mortgage rates higher than usual? As long as jobless claims stay low, the falling 5-unit apartment permit data might not lead to lower mortgage rates as it has in previous cycles.

From Census: Building Permits: Privately‐owned housing units authorized by building permits in February were at a seasonally adjusted annual rate of 1,518,000. This is 1.9 percent above the revised January rate of 1,489,000 and 2.4 percent above the February 2023 rate of 1,482,000.

When people say housing leads us in and out of a recession, it is a valid premise and that is why people carefully track housing permits. However, this housing cycle has been unique. Unfortunately, many people who have tracked this housing cycle are still stuck on 2008, believing that what happened during COVID-19 was rampant demand speculation that would lead to a massive supply of homes once home sales crashed. This would mean the builders couldn’t sell more new homes or have housing permits rise.

Housing permits, starts and new home sales were falling for a while, and in 2022, the data looked recessionary. However, new home sales were never near the 2005 peak, and the builders found a workable bottom in sales by paying down mortgage rates to boost demand. The first level of job loss recessionary data has been averted for now. Below is the chart of the building permits.



On the other hand, the apartment boom and bust has already happened. Permits are already back to the levels of the COVID-19 recession and have legs to move lower. Traditionally, when this data line gets this negative, a recession isn’t far off. But, as you can see in the chart below, there’s a big gap between the housing permit data for single-family and five units. Looking at this chart, the recession would only happen after single-family and 5-unit permits fall together, not when we have a gap like we see today.

From Census: Housing completions: Privately‐owned housing completions in February were at a seasonally adjusted annual rate of 1,729,000.

As we can see in the chart below, we had a solid month of housing completions. This was driven by 5-unit completions, which have been in the works for a while now. Also, this month’s report show a weather impact as progress in building was held up due to bad weather. However, the good news is that more supply of rental units will mean the fight against rent inflation will be positive as more supply is the best way to deal with inflation. In time, that is also good news for mortgage rates.



Housing Starts: Privately‐owned housing starts in February were at a seasonally adjusted annual rate of 1,521,000. This is 10.7 percent (±14.2 percent)* above the revised January estimate of 1,374,000 and is 5.9 percent (±10.0 percent)* above the February 2023 rate of 1,436,000.

Housing starts data beat to the upside, but the real story is that the marketplace has diverged into two different directions. The apartment boom is over and permits are heading below the COVID-19 recession, but as long as the builders can keep rates low enough to sell more new homes, single-family permits and starts can slowly move forward.

If we lose the single-family marketplace, expect the chart below to look like it always does before a recession — meaning residential construction workers lose their jobs. For now, the apartment construction workers are at the most risk once they finish the backlog of apartments under construction.

Overall, the housing starts beat to the upside. Still, the report’s internals show a marketplace with early recessionary data lines, which traditionally mean mortgage rates should go lower soon. If housing leads us into a recession in the near future, that means mortgage rates have stayed too high for too long and restrictive policy by the Fed created a recession as we have seen in previous economic cycles.

The builders have been paying down rates to keep construction workers employed, but if rates go higher, it will get more and more challenging to do this because not all builders have the capacity to buy down rates. Last year, we saw what 8% mortgage rates did to new home sales; they dropped before rates fell. So, this is something to keep track of, especially with a critical Federal Reserve meeting this week.

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