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The future of AI drug discovery & development in immunology and GPCR research

Alphabet subsidiary and precision health company Verily recently announced a breakthrough in its AI drug discovery GPCR research
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Alphabet subsidiary and precision health company Verily recently announced a breakthrough in its AI drug discovery GPCR research collaboration with Sosei Heptares.

A mere six months ago Verily launched the study with Sosei Heptares – a global leader in GPCR structure-based drug design – with an aim to “prioritise protein targets for therapeutic targeting in immune-mediated disease”. Now, Verily has announced that early results from its “next generation immune mapping technology” Immune Profiler platform have already identified “more effective therapeutic options against G protein-coupled receptors (GPCR) in autoimmune and other immune-mediated diseases”.

The companies hope that in the year to come those data targets will be entered for validation, hit generation, and lead selection. With approximately one third of all current FDA-approved drugs targeting GPCRs, Verily/Sosei Heptares are looking to expedite GPCR research within not only immunology, but also gastroenterology and immuno-oncology as well, and the latest data bodes well for future development of therapeutic options in these areas.

Human-first precision health

Pharmaphorum asked Charlie Kim, head of molecular science at Verily (which takes a “human-first precision approach to drug target discovery”), to expand on the details of the recent collaborative findings and what they mean for the future of the Verily/Sosei Heptares partnership, as well as where he thinks AI’s use in drug discovery and development might lead the industry.

Verily’s Immune Profiler platform is “a discovery engine consisting of proprietary immune profiling lab workflow, growing multi-omic database, and advanced analytical tools”. The purpose of collaborating with Sosei Heptares, Kim told pharmaphorum, was to streamline definition of those GPCR targets worth studying, while substantially reducing human hours spent trawling through data.

Granted, it’s an ambitious scientific undertaking, and one “aimed squarely at developing new and more effective therapeutic options for autoimmune and other immune-mediated diseases.” Essentially, the collaboration brought together both “the right expertise and the right technology”, opening up myriad possibilities for targeting GPCRs within the human genome.

Verily’s Immune Profiler can, Kim asserted, “generate more than 8 million immune measures across 24 immune cell subsets”. What this means is that it lays pretty firm foundations for identifying new drug targets and, coupled with Sosei Heptares’ expertise, researchers have been able to reveal “a number of priority targets with known links to autoimmune diseases that were not high on anyone’s radar until now”.

Next, they need experiential evidence that will support progressing these revealed prioritised targets into the discovery of lead molecules.

Technological breakthroughs in molecular biology

Kim was inspired by the “host of technological breakthroughs in molecular biology in the late 90s”, when he was beginning his PhD at Stanford University. It was a time when “the potential for systematic understanding of complex biology was palpable”, a fascinating terrain wherein the “first bacterial genomes were being sequenced”, when microarray technology was in the early stages of being invented, and ‘genomics’ and ‘big data’ certainly weren’t on the tips of people’s tongues.

Kim recognised then, he said, that better tools for medicine needed to be developed, and that they still do. Citing the transformative therapies available for targets such as tumour necrosis factor (TNF), the pro-inflammatory cytokine interleukin-23 (IL-23), and programmed cell death protein 1 (PD-1) – he explained that “these drugs only achieve the best outcomes in a minority of patients with autoimmunity or cancer”. What, then, is the solution?

Well, Kim believes that “by leveraging the power of genetics and functional genomics, coupled with a ‘human-first’ mindset, innovative analytics, and scalable compute power” there is “the ability to take a fundamentally different approach to drug development”. It also bodes well for improving clinical trial success rates. Indeed, Verily’s Immune Profiler prioritises targets with “multiple lines of evidence” by specifically using “multi-omic integration of evolutionary selected genetic signals and their associated functional impacts to construct models of human immunology”. The company also hopes the platform will be able “to identify better biomarkers and diagnostic tools”.

Efficiency and cost-effectiveness are key drivers in these recent developments in AI drug discovery and development, given that R&D for a new drug can take up to 18 years. The overarching desire to reduce in some way the “translational valley of death” of failed clinical trials is palpable. But mere volition does not enact results. Back in January 2020, Exscientia and Sumitomo Dainippon partnered on the AI-created drug molecule DSP-1181 for obsessive compulsive disorder (OCD): the development had taken their AI only 12 months to go to trial. However, by July 2022 it was revealed that DSP-1181 didn’t even pass the phase 1 study and, furthermore, had exhibited “insufficient novelty” (bearing considerable similarity to haloperidol, the antipsychotic drug FDA-approved in 1967).

AI drug discovery in immunology today, and tomorrow

AI relies on data.  Speed and cost-effectiveness are one thing, but without good data to act upon, results are meaningless. Noting that AI has been used successfully in diagnostic breakthroughs in oncology thus far, Kim reminded us that when it comes to autoimmune diseases, such “predictive and accurate diagnostic tests […] are still in their infancy”.

As Kim makes very clear, “[i]mmune-mediated diseases are highly complex and, oftentimes, therapies that work for one patient may not be effective for another”.  What the Immune Profiler platform does is “broaden the ability to identify potential places where new therapies could be found”. It is the horizon looker, seeing far more – and, at that, far more expediently – than the human researcher alone ever could.

A notable issue with clinical trials is the homogeneity of the patient database. Whilst many are rightly calling for a diversification and equitisation of clinical trial participation, it doesn’t yet change the fact that the pharma industry uses clinical research organisation (CRO)-provided information, which itself can only draw from the patient-provided data available – patient data which isn’t always particularly diverse.

Precision health, then, seeks to create “the greatest number of options possible”, as well as “make sure every patient has the most targeted treatment for their condition, physiology, and more”. The artificial intelligence in Verily/Sosei Heptares’ case uses advanced data analytics to search for molecules to test in the first place. Undertaking that needle-in-a-haystack task, the AI looks for something, anything – until it finds it. As Kim admits, “[n]ot all of them will bear fruit – but some, even maybe many, will – and that’s why it’s so critical for us to be here right now”.

Verily and Sosei Heptares hope their collaboration will eventually help those people currently living with immune-mediated diseases who are dissatisfied with their current treatment, or unable to undergo the currently available therapies for their condition, by “unlocking novel therapeutic options”. It is not a method that will yield tangible results tomorrow, but with further investigation and even molecule generation projected within the next year, as Kim, said: “In pharmaceutical R&D, that is certainly moving at a very fast clip.”


About the interviewee

Dr. Charlie Kim earned his PhD from Microbiology and Immunology at Stanford University and pioneered the application of genomic and bioinformatic approaches to the study of infectious disease. He joined the faculty of the UCSF Department of Medicine in 2011, where he expanded his focus to the application of immunogenomic approaches to translational research. In 2015, he joined Verily to further these goals in the powerful compute environment of the Google ecosystem. In his role as Head of Molecular Science, he leads teams responsible for innovating molecular platforms and applying them in translational research aimed at improving patient outcomes. He is the director of PRESCO, a multi-site observational severe COVID-19 outcomes study, and strives to bring powerful technologies to translational research with the goal of accelerating the development of therapeutics, biomarkers, and diagnostics that can improve patient outcomes through Precision Health.


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Positioning your business for success in all market cycles

Brokers who are embracing this market and taking the time to improve their processes, marketing and client experience will win.



HousingWire recently spoke to Alex Elezaj, chief strategy officer at UWM, about the work independent mortgage brokers can do right now to prepare for when rates drop and how to go above and beyond for clients.

HousingWire: Why should independent mortgage brokers embrace today’s market?

Alex Elezaj: It’s only a matter of time before rates drop, and when they do, there will be a clear difference between those who have been preparing and those who have not.

The way I see it, there are two types of people in the mortgage space right now: those who are simply waiting around for rates to drop and those who are putting in the work to better their business. The winners have spent 2023 focused on strengthening relationships with real estate agents, educating borrowers and improving their marketing strategies.

The reality is, we can’t control the rates, but we can control the service we provide and make sure we stay in front of past clients. Those who are focused on how they can get better and taking the steps to make improvements to their business are the ones who are going to come out stronger and more successful for the long term.

HW: What can independent mortgage brokers do right now to prepare for when rates drop?

AE: It’s important to leverage tools, technology and services that streamline operations and enhance your productivity now so that when volume increases, these steps are already part of the process. At UWM, we ensure our clients have a full suite of resources to help them grow their business in any market.  

For example, PA+ is an option for UWM clients to receive an additional level of loan processing support, with the goal being to ease some of the most time-consuming parts of the loan process from setup through closing. Most recently, we enhanced this service to allow brokers and their processors to choose which part or parts of the loan process they’d like a UWM loan coordinator to handle.

Not only does this give them more flexibility, control and support, allowing them to scale their business immediately, but it also offers brokers and processors additional assistance during busy times and makes them more available to have meaningful touchpoints with borrowers.

Some of UWM’s most successful clients are taking advantage of PA+ today to ensure their businesses are set up for success when rates eventually drop. Preparing is all about using the resources available to you.

HW: Providing a great client experience goes a long way when it comes to referrals and repeat business. What’s the secret to making long-lasting impressions?

AE: The reality is, nobody wants a mortgage. They want the house. This is why, as an independent mortgage broker, providing an elite client experience should be the main priority for every loan. When a borrower looks back at the homebuying process, we don’t want them to think about potentially stressful parts. We want them to remember how seamless and easy their broker made it.

To help with this, UWM recently announced Memory Maker, which allows independent mortgage brokers to send their choice of customized thank you items to borrowers and real estate agents. This includes personalized thank you emails or handwritten notes and gifts for borrowers, such as a cutting board, ice bucket or welcome mat.

It’s these types of gestures that leave a lasting impression in someone’s memory bank that can lead to repeat business down the road. On average, a person will own three homes in their lifetime. That’s a potential for three separate mortgages in addition to refinances. Believe it or not, a handwritten thank you note to a real estate agent or a customized cutting board for a borrower can go a long way in making sure that broker is top of mind when those needs arise. 

HW: We know rates will drop at some point. What will things look like in the wholesale channel when they do?

AE: The wholesale channel reached a new milestone last quarter with the broker market share achieving its highest level in over a decade. We’ve seen a massive shift in retail LOs transitioning to the wholesale channel, and we expect this trend to continue. The broker channel continues to prove it’s resilient and thrives in all market cycles, and we are prepared for the day rates tick down, just like we were prepared when the market shifted to purchases.

Brokers who are embracing this market and taking the time to improve their processes, marketing and client experience will win. It’s easy to get wrapped up in the doom and gloom surrounding the housing industry right now, but if we block out the negativity, outwork the competition and do right by every borrower we interact with, the independent mortgage broker channel will continue to dominate and be the obvious choice for consumers and real estate agents.

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Former Government Officials Say Cannabis Rescheduling Would ‘Supersize’ The Industry

Former DEA chiefs and retired White House drug czars are expressing concerns over the possible cannabis rescheduling. In a letter addressed to U.S. Attorney General Merrick…



Former DEA chiefs and retired White House drug czars are expressing concerns over the possible cannabis rescheduling. In a letter addressed to U.S. Attorney General Merrick Garland and DEA administrator Anne Milgram, the 11 ex-officials argued that reclassifying marijuana would “supersize” the industry through tax relief and normalization, reported Marijuana Moment.

The news comes some six weeks after Health and Human Services (HHS) Secretary Xavier Becerra confirmed his agency had responded to President Biden’s directive to provide cannabis rescheduling recommendations to the DEA. Becerra wrote to Milgram calling for marijuana to be reclassified as a Schedule III drug under the Controlled Substances Act (CSA).

Now, former DEA administrators and directors of the White House Office of National Drug Control Policy are basically recommending the DEA disregard the HHS’s recommendation.

“Schedule I drugs are those with no accepted medical use. The FDA has not approved marijuana for medical use because no double-blind, published studies show safety and efficacy for raw marijuana; thus, it must remain a Schedule I drug,” wrote six former DEA heads and five White House drug czars.

It is important to note that even though the FDA has not approved marijuana for medical use as yet, it did approve one CBD-based medication called Epidiolex, which is helping control seizures for numerous children suffering from rare forms of epilepsy. What’s more, the Schedule 1 status of cannabis was one of the main reasons why there have not been sufficient clinical trials and research on marijuana’s therapeutic effects and benefits.

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‘Supersizing’ The Cannabis Industry

Even though former government officials recognized that cannabis rescheduling as Schedule III does not legalize it nor allow it to be recommended by physicians, they say their main concern is that it would “supersize” the industry.

“Moving marijuana to Schedule III would supersize the cannabis industry in the United States by allowing them to evade IRS Section 280E and deduct business expenses. Not only would this mean that marijuana corporations would be able to deduct expenses for advertisements appealing to youth and the sale of kid-friendly marijuana gummies, but it would also dramatically increase the industry’s commercialization ability,” they wrote.

IRS code 280E stipulates that no deductions or credit be allowed to companies running businesses that sell Schedule I or II controlled substances. Therefore, until cannabis is removed from its outdated classification as a Schedule I drug, no tax deductions or credits will be available to legal cannabis operators.

Criminal Penalties

Signatories to the letter, including Michele Leonhart, Robert C. Bonner, Peter B. Bensinger, R. Gil Kerlikowske, General Barry R. McCaffrey USA (Ret.), William J. Bennett, Karen Tandy, John C. Lawn, John R. Bartels Jr., John P. Walters, and Robert Martinez also raised concerns about criminal penalties.

“Rescheduling marijuana, and thus reducing criminal penalties for marijuana trafficking, removes a key tool federal agents have to prosecute cartels,” they said.

However, Shane Pennington, an attorney who specializes in federal drug policy and litigation against DEA, told the outlet that penalties for various substances are not directly connected to the scheduling status under the CSA. “Unlike other substances where you change the schedule and the criminal penalties change accordingly, for certain substances—marijuana chiefly among them—that is not the case,” Pennington said.

The former officials are not the only ones concerned about HHS’ cannabis rescheduling recommendations. Republican senators recently presented a bill to block cannabis legalization without congressional approval.

The post Former Government Officials Say Cannabis Rescheduling Would ‘Supersize’ The Industry appeared first on The Dales Report.

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Five tips for a sustainable Halloween

Halloween is a sustainability nightmare – but it doesn’t have to be.




More than 8 million pumpkins are thrown away over Halloween each year. Evgeny Atamanenko/Shutterstock

Halloween is the spookiest time of the year. However, as you prepare to send shivers down the spines of your friends and family, you may not have given much thought to the environmental footprint that this holiday conceals.

In the UK alone, more than 8 million pumpkins are thrown away each year over Halloween. This amounts to about 18,000 tonnes of pumpkins going to waste that would have been eaten.

But that’s not the extent of it. Halloween has evolved into a commercial money-spinner, with store shelves brimming with plastic costumes, electronic and disposable decorations, and bags of plastic-wrapped sweets – most of which will eventually find their way into landfills after the festivities end.

If you’re looking to partake in the spooky festivities of Halloween, here are five tips to ensure you can give people a good fright without harming the environment.

1. What to do with your pumpkin

Pumpkin carving isn’t just a problem because of food waste, a huge amount of resources – including fuel for lorries and fertilisers – go into producing the mountain of pumpkins that are used over Halloween.

If you do plan on carving a pumpkin this year, make sure you throw it into a food waste bin. Pumpkins that end up in landfill emit methane as they decompose. Methane is a potent greenhouse gas that contributes to climate change.

Read more: The case for compost: why recycling food waste is so much better than sending it to landfill

A better approach may be to forgo the whole pumpkin thing altogether. Instead, consider investing in a reusable decoration (preferably one that’s not made from plastic) or crafting your own creepy creation out of something you already have in your home to put outside your door.

But if you still want to experience the fun of carving a pumpkin, then make sure it isn’t wasted by baking some pumpkin pie, roasting its seeds in the oven, or simply roasting segments of pumpkin as a savoury treat (even the skin is edible).

A pile of abandoned rotting pumpkins.
Pumpkins emit methane as they decompose. Amanda Wayne/Shutterstock

2. Cut down on buying new

The shops are filled to bursting with Halloween decorations. However, many of these decorations – from cackling witches to vampire bat lights – are electrical. Making these products uses up substantial resources, including endless amounts of copper wiring and some of the rarest materials on the planet, such as lanthanum, an element found in modern television sets, energy saving lamps and optical lenses.

When these decorations are thrown away, they contribute to the growing electrical waste crisis. In 2019, global electrical and electronic waste generation stood at around 54 million tonnes, amounting to around 7.5kg per person. This generation rate is expected to increase significantly in the future.

So consider if you really need to buy new. You may find you already have enough lying around to transform your home into a haunted house. Christmas lights, for example, could double up as a creepy addition to your Halloween decor.

You may also have some other old bits and pieces that you can remake into something suitably spooky. Old dolls can be given unsettling new attire crafted from fabric scraps (although they might be creepy enough by themselves). And bottles can be filled with water and a few drops of food dye to make a collection of witches’ brews.

3. Ditch single-use plastic

We all like being able to hand out some sweet treats to trick-or-treaters. But sweets are often individually wrapped in plastic. Many single-use plastics don’t get recycled and, because plastic doesn’t break down naturally, it can stay in the environment for hundreds of years.

Instead of plastic-wrapped treats, think about getting something in paper packaging. If you have the time, then maybe you could make some sweat treats yourself to hand out.

A group of kids trick or treating.
Sweets are often individually wrapped in plastic that is subsequently thrown away. Sean Locke Photography/Shutterstock

4. Make your own costume

Most of the Halloween costumes you can buy are made out of plastic. In fact, an investigation by Hubbub, an environmental charity, found that about 83% of the materials used to make the seasonal outfits available at 19 supermarkets and retailers in the UK were plastic.

These outfits not only contribute to the accumulation of plastic in landfills, they are also a source of harmful microplastics. These minuscule plastic particles have been found almost everywhere, including in water sources, marine life, human bodies, and now even in the clouds.

Even if you don’t throw away your costume, tiny plastic fibres are released from the fabric every time you wash it. These fibres ultimately find their way into the environment through the wastewater system.

So ditch the plastic wig and look at what you already own. Old clothes can be torn up to give the look of a horrifying zombie. And, although it may be an old standby, everyone has an old sheet somewhere that can be used as a ghost costume.

5. Less is more

Sustainability is all about leaving the world in a way that future generations can enjoy as good a quality of life as we do. A crucial element in making this future a reality is only using what we need instead of an excess.

So, when making choices about how to have a happy Halloween, think before you consume. Do you need to buy a load of prepackaged food? Or can you make your own pumpkin pie? Do you need to get in a car to go trick or treating? Or can you do it locally on foot?

By following these tips, you can have a fun, freaky – but also sustainable – Halloween.

Alice Brock receives funding from The South Coast Doctoral Training Partnership.

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