New Gut-Brain Signaling Drug Targets Prader-Willi Syndrome with Dr. Tien Lee Aardvark Therapeutics

Dr. Tien Lee, Founder and CEO of Aardvark Therapeutics, draws a clear distinction between appetite and hunger and the implications for treating metabolic conditions and managing weight. The Aardvark lead drug candidate, an oral bitter taste receptor agonist designed to activate the gut-brain connection to turn off hunger, is showing effectiveness in treating Prader-Willi Syndrome and general obesity.  There are also signs that this drug could be effective for those using GLP-1s to avoid nausea and prevent rebound weight gain experienced after discontinuing GLP-1 drugs. Tien explains, "That difference between hunger and appetite is the central thesis for our entire company, and your brain actually regulates how much you should eat. And it's driven by both appetite and hunger. So appetites like the carrot, and hunger is like the stick. Appetite is what you feel when you really enjoy a certain food, like ice cream or cake. And the appeal and the deliciousness of that food is a reward that your brain chases. Hunger is the feeling that you get when you have fasted for a prolonged period of time, and it really bothers you, and you feel real discomfort from not eating. And then at that point, food quality matters less, and you just want to escape that negative sensation. And we believe a lot of the current drugs are good at reducing appetite, but they don't so much address hunger like what our approach is pursuing."  "In obesity, there's probably a combination of both appetite and hunger at play. And they're both important. In fact, your body has both appetite and hunger that are regulated. And when we eat food, our gut releases a number of gut hormones that help tamp down and give us satiety for both appetite and hunger. However, there are certain conditions where hunger is the predominant issue. And with the disease that is our lead indication is a condition called Prader-Willi syndrome. It's a rare genetic disorder that affects about one out of 15,000 live births. And patients with this condition have this unabated, unrelenting hunger that they feel that really starts to manifest when they're about four or seven years old. And then characteristically, patients will even feel compelled to eat garbage to the point of stomach rupture if unregulated with their food access. So it's a very debilitating condition with a lot of suffering for the patients and their families."   "There are actually quite a number of new revelations in the scientific literature, and there's a greater appreciation of gut-brain signaling. So there are actually as many neurons in your gut as there are in your spinal cord, almost as many neurons as in the cat brain. And there's a greater appreciation of a two-way communication between your brain and the gut. So the vagus nerve is the largest nerve in your body, and there's actually a two-way communication between the gut and the brain. About 80% to 90% of the signal is actually from the gut to the brain. And even the drugs that people know currently, the Ozempic and the Zepbound drugs, are working through this gut path hormone. But naturally, a lot of the signals actually come from the gut to the brain through this vagus nerve conduction." #AardvarkTherapeutics #Hunger #Appetite #PraderWilliSyndrome #PWS #Hyperphagia #RareDiseases #BiotechInnovation #ObesityTreatment #GutBrainAxis #TasteReceptors #ClinicalTrials #Therapeutics #MetabolicHealth #PharmaceuticalInnovation  aardvarktherapeutics.com Download the transcript here

Lawrence Blatt, Chairman, President, and CEO of Aligos Therapeutics,  describes the current gaps in treating the hepatitis B virus and how the disease can potentially lead to end-stage liver disease and liver cancer. Current therapies were initially developed for HIV and can suppress the virus but not eliminate or prevent the disease. The lead Aligos drug candidate blocks all steps of viral replication and prevents the virus from integrating into infected liver cells, where it can activate cancer-causing genes. Lawrence explains, "Hepatitis B virus is actually the most prevalent chronic viral infection in the world that makes patients very ill, and they can actually die from this disease. There's almost 250 million, a little bit more than 250 million people infected with Hepatitis B. And it really affects people in all walks of life across many different demographic groups. So there's not a typical HPV patient out there."   "So HBV needs to be treated for life, currently very similar to HIV, and actually HBV and HIV share common features. And early on in the HIV epidemic, patients who were treated with a class of drug called nucleoside analogs, who were also coinfected with HBV, we saw responses to those drugs. So the drugs that worked in HIV, called nucleoside or nucleotide analogs that were purposely built for HIV, worked against HBV, and they worked to a certain degree. They can suppress the virus, but they can't eliminate the virus, and they can't completely suppress all the components of the viral lifecycle that end up causing disease."   "So we're not going to affect the damage that's there initially, but we're blocking that damage from occurring. Now, one thing that's really interesting is that our livers are regenerative organs. So the liver is constantly replacing itself with new healthy hepatocytes or cells that make up the liver. And so if you could block the ongoing disease processes, the liver will have time to heal itself and eventually reverse the scarring. And that's really the only organ in our body that can regenerate. If you get scarring on your lungs or any other part of your body, that is for life. But in the liver, if you block the disease processes, you can reverse that scarring. So it's a very important and unique finding."  #AligosTherapeutics #HepatitisB #Biotechnology #DrugDevelopment #LiverHealth #ClinicalTrials #MedicalBreakthrough #PatientCare #Virology #PharmaceuticalInnovation #Vaccines Aligos.com Download the transcript here  

This roundtable on the role of AI in the biotech sector features Frank Yocca, Senior VP and Chief Scientific Officer at BioXcel Therapeutics, Joanne Taylor, Senior VP for Research at Gain Therapeutics, and Martin Brenner, CEO and Chief Scientific Officer at iBio. The conversation covers the historical adoption of AI in biotech, its current use in drug discovery, and future possibilities.  AI is not a new phenomenon in biotech and has evolved from data processing to sophisticated models that can screen vast amounts of data. There is a critical need for high-quality, structured data to train effective AI models, and these experts caution about the hype surrounding AI-generated discoveries and emphasize the need for real-world biological and human testing. Frank explains, "We are all about AI right from the get-go. We sort of inherited that from the parent company, BioXcel, which is now BioXcel, LLC. The company started by deploying data science on big biomedical and other datasets. Much of the data was unstructured and required significant curation, which at first was largely manual. Later, we began deploying more natural language processing and knowledge graphs to predict whether drugs that initially failed but were safe could be repurposed for other indications. More recently, the latest evolution has really been to use large language models and more agentic workflows to generate hypotheses and insights."   Joanne explains, "So Gain has had for many years, I think 10 years also, a virtual drug discovery platform where we've been able to screen millions of compounds virtually to discover allosteric binding molecules. But about three or so years ago, we made the change from screening millions of compounds to screening, now we're up to the capability of screening trillions of compounds." "We can screen in days, whereas it would take you months and maybe a year to do high-throughput screening. But in terms of having introduced AI into this system, it means that we can do things better because obviously, if you can screen trillions of compounds, you're screening more of the possibilities, you are going to be making better drugs. At least that's the hypothesis than if you are screening fewer compounds. So it's the fact that this is a fast tool set that makes you able to do things that you wouldn't have been otherwise able to do, but it doesn't necessarily make the process itself that much faster because you are doing much more." Martin elaborates, "So we had the good fortune to start from scratch. We're a very small company. We have made from the get-go the decision that our scientists would be bilingual. They're not only data and AI scientists, but they're also biologists. That makes it a lot easier to translate between the two disciplines. We literally started, or Rubrik Therapeutics started, on the hypothesis that would be a model of structure prediction for proteins. So the company was clearly ahead of its time, and we started by making molecules that set up better than existing ones. And that's, I think, a very low hurdle that a lot of people are doing right now. And you hear sometimes this overreaching argument, we make AI drugs. First of all, tomorrow medicines take 10,000 steps, and enabling three of them is not making an AI drug, but making better molecules. This was the first important step." #BioXcel #GainTherapeutics #iBio #AI #ClinicalAI #ArtificialIntelligence #Biotechnology #DrugDiscovery #PersonalizedMedicine #HealthcareInnovation #BiopharmaAI #ClinicalTrials #RareDisease #Neuroscience #PrecisionMedicine #HealthTech #BiotechLeadership #AIinHealthcare #DrugDevelopment #MedicalInnovation bioxceltherapeutics.com  gaintherapeutics.com  ibioinc.com Download the transcript here    

David Dodd, CEO of GeoVax,  highlights the need for next-generation vaccines, specifically multi-antigen and T cell-focused technologies, to provide better protection for immunocompromised populations. Their pipeline includes a COVID-19 vaccine candidate, an Mpox/Smallpox vaccine, and a gene therapy for solid tumors. A priority for GeoVax is to develop new manufacturing processes to significantly accelerate vaccine production, increase yield, and reduce costs. David explains, "Multi-antigen vaccines become critically important, especially for populations for whom the existing approach in vaccines, meaning single-antigen vaccines or antibody-focused or antibody-only vaccines, is inadequate. And to clarify that, there are approximately 40 million adults in the United States, about 10 times that number worldwide, who suffer from various medical conditions, such as blood cancers. They may have renal disease, diabetes, or be HIV positive. They may also have weakened immune systems, they could have multiple sclerosis or lupus. So there are a host of medical conditions that the result is they inhibit or they deplete an individual's immune system from mounting an adequate antibody response. And keep in mind, the antibody system is that first line of defense when an infectious threat occurs. And that's sort of like the frontline soldiers. They throw up a protective guard to respond to that." "That means for those individuals, what we need to do is also address this, as we develop vaccines, and some technologies allow you to do this. The majority of vaccine platforms do not, unfortunately. And that is to also induce a very strong cellular immunity or T cells. And this becomes critically important because T cells are what clear a virus from the body. It's also what drives what is known as memory, and also gives breadth or robustness of protection. So it becomes critically important that if one has the opportunity because of their technology or the platform they're utilizing to enlist and engage both the antibody as well as the cellular side, then one can generally develop a much more robust protective immune response that will reduce the risk of severe infection, hospitalization, and the risk of death against certain infections." #GeoVax #Biotech #Vaccines #PublicHealth #Healthcare #COVID19 #LifeSciences #Biotechnology #Mpox #GlobalHealth  geovax.com Download the transcript here

Rick Davis, patient advocate and Founder of AnCan, is building and operating virtual peer-to-peer support groups to allow patients to connect with others who have direct experience with their condition.  These groups can provide accurate information, foster connections among participants, and serve as a check on medical misinformation. With the growing acceptance of virtual meetings, this approach overcomes geographic, physical, and psychosocial barriers that might otherwise prevent participants from attending on-site meetings. Rick explains, "The mission is to make each person and each patient a better advocate for themselves. That's really what we try to do, and we do that through empowering patients with peer knowledge. We introduce patients to other peers who have been through what these people are facing right now, not only patients, but also their care partners, and through their experience, we hope that these patients and care partners will become more expert in managing their own situation."   "In 2007, when I was first diagnosed with stage three cancer, I attended a physical meeting, and I realized that so many people cannot attend physical meetings because one, they may have a geographical disability, they may have a physical disability, or they may have a psychosocial disability. If we only allow people to exchange views when they're physically in front of each other, it's very limiting. And so I started to look and see what existed in terms of virtual communication. And back in the day, there was very, very little. And that was the motivation that got me started."  "People come into a group, and they hear things that they just wouldn't hear otherwise. And that's why it's so valuable. It's so incredibly valuable. I mean, we had a group last night where a guy came in facing a situation, and by total coincidence, there was somebody from his own city in there who knew the docs that he'd been dealing with, understood the frustration he'd been going through, had been through it himself, and shared his experience. Well, you can't buy that."   #AnCan #AnCanSupport #VirtualSupport #CancerSupport #PeerSupport #PatientAdvocay #DigitalHealth ancan.org Download the transcript here  

Bob Farrell, CEO of mPulse, is using digital technology, data analytics and AI to improve the relationship between health plans and their members in order to improve health outcomes and operational efficiency. Bob introduces the concept of HXI, Health Experience and Insights, as a framework that unites data, intelligence, and personalized communication to provide tools to enage members at the best time and by the preferred methods with appropriate information at the right time. Analyzing claims data enables plans to identify high-risk patients, promote preventive care, and build health literacy. Bob explains, "The mission of mPulse, and this has really been the mission of the company since its founding in 2015, is to improve the health outcomes of our customers' members and patients. So we're looking to close gaps in care. We're looking to increase literacy so that members and patients can understand their health plans. So providers can take charge of healthcare and improve those outcomes. And while we're doing that, we try to help our customers improve their operational efficiencies. Most of our customers are health plans and they range from small community plans to large nationals. The 60 largest plans are our customers. We have a wide array of customers and continue to expand on that base, both with new customers and by doing more with the customers that we have."   "Health plans are not known to be the early adopters of technology. So you're right. A lot of them are still transitioning from older ways of doing things. But in general, health plans have a huge trust issue with their members, and it has really resulted from a lack of engagement, a lack of positive experience. So we see a lot of health plans looking to embrace technology to improve the member experience, make sure that those members are getting outreach. Not just now and then, but during the whole course of their consumer health journey, so that they can be aware of what things they have available to them, so that they can easily adjudicate claims and easily find providers."    #mPulse #HXI #PersonalizedCare #HealthExperienceInsights #DigitalHealth mPulse.com Download the transcript here  

Rick Pierce, Co-Founder and CEO of Decoy Therapeutics. is using AI and machine learning to accelerate drug discovery and is developing broad-acting antivirals using peptide conjugates that target a shared invasion mechanism of hundreds of viruses.  The company is using small language models and a high-speed peptide synthesizer to dramatically reduce drug creation time. Rick predicts that the future of drug discovery will combine AI-driven design with advanced biological models, such as organoids, to better predict drug toxicity and efficacy. Rick explains, "Decoy Therapeutics was founded years ago, during the COVID era. And what we've learned during that was that in order to develop drugs rapidly and scale up their manufacturing, we needed to use machine learning and AI. And the drugs that we're looking at developing today as a result of that are broad-acting antivirals that can be used against multiple viruses. So one drug can be used against multiple viruses like Flu, COVID, and RSV." "So we chose antivirals as a space because viruses have what is called polypharmacology, and in plain layman's terms, what that means is that about 250 of these viruses share the same invasion machinery, meaning the way the virus enters the healthy cells is shared across all those viruses. It's slightly different in each of those viruses, but effectively for drug development, very similar."   "That allows us to use peptides, which are also alpha helices, to be able to design drugs with AI and machine learning that physically block the invasion machinery and thus basically the virus from binding to a healthy cell. Peptides are uniquely positioned as drugs for this set of viral targets. Again, it's a rich set of targets among 250 viruses across multiple viral families."   #DecoyTherapeutics #PeptideConjugates #BroadSpectrumAntiviral #AIinBiotech #NextGenMedicine   decoytx.com Download the transcript here  

Dr. Kumar Dharmarajan, cardiologist and geriatrician and Co-Founder and Chief Medical Officer at World Class Health, is  bringing concierge healthcare to employees of self-insured companies.   The platform includes a global network of top-tier doctors and nurse navigators. Directly negotiating with providers reduces costs and reduces administrative and financial friction for patients seeking planned procedures. The model also reduces friction for physicians by providing them with complete patient records and ensuring prompt payment. Kumar explains, "We are a global, medically led center of excellence platform. So, by that, we have top doctors and top hospitals around the world, including the United States and many other countries, and we help patients access that network. We have pre-negotiated rates via our nurse navigators. We really believe in the power of nurses to help patients make healthcare decisions that may be valuable and important to them. And those nurses will work with the patient before, during, and after their care episode, whether that physician they access is local, in their own communities, or somewhere else around the world. And right now, we are partnering with large self-insured companies around the world and offering our product, in addition to the network they have through their usual insurer." "We are looking for employees of self-insured large companies. Our specific target has been largely knowledge workers, so these are employees in technology, financial services, and other knowledge industries. And the reason we feel that is one, our global network may be really appealing to them because many knowledge workers come from different parts of the world, Asia, Europe, Latin America, etc. And second, our nurses and our strong concierge model, which we built with experts from Stanford and Johns Hopkins International, have created a truly white-glove experience. So not only are they high-quality, highly qualified providers, top 1% doctors, hospitals around the world, but it's also a white glove service to help patients deal with all the administrative minutiae and challenges we all experience in healthcare. And we believe that's well powered and tailored to the knowledge industry." #WorldClassHealth #SelfInsured #ConciergeCare #NurseNavigators #DigitalHealth worldclasshealth.com Download the transcript here

Brent Dial, Founder and CEO of Beek Health, has built a platform that addresses patient information fragmentation by aggregating data from patient portals and providing direct access to lab testing. Health literacy is key to preventing chronic diseases, and AI is being used to scale the delivery of personalized health information. Identifying relevant biomarkers and early warning signs supports proactive health management that can alter long-term health outcomes. Brent explains, "Beek Health is re-imagining healthcare by finally putting the individual at the center of their health journey. While we talk about patient-centric or customer-centric or shared decision-making, it's not real in practice, and it's for good and for very clear reasons. There's information asymmetry, there's information overload, and then information is quite fragmented." "Currently, we have three subscription tiers. The first option is the basic plan, which gives you platform access to synthesize and connect with multiple patient portals, as many as you have. The average individual has at least two patient portals, and it's estimated you'll see 17 different providers in your lifetime. So that's a lot of data spread out across different systems. So, one, you can sync. We have over 40,000 endpoints or provider locations where you can sync your patient portal information in one unified dashboard. All the dashboards look different."  "Second, you'll have access to labs anytime you need them. And so labs are woefully underutilized for health tracking: 70% of diagnoses are based on lab results, so you can access them anytime you need to. We partner with LabCorp, which has over 2,000 locations, and you'll receive your results within 48 hours. In addition, we're adding cost navigation, cost estimate tools, and some more fun features on our roadmap, but that just gives you basic access for a year for $99."   #BeekHealth #HealthInYourHands #OwnYourHealthData #HealthTech #DigitalHealth #PatientEmpowerment #HealthcareReimagined #ConnectedHealth #FutureOfHealth beekhealth.com Download the transcript here

Dr. Asher Eghbali, Co-Founder of Fuerte, has developed a platform to address the significant communication challenges between healthcare providers and pharmaceutical industry representatives. The goal is to streamline this relationship by replacing inefficient scheduling methods, and eliminate miscommunication and missed meetings to reduce frustrations and wasted time. The app is designed to combine professional networking with social media elements, including user profiles and notifications, to help build stronger, long-lasting professional relationships that benefit everyone involved. Asher explains, "Within the life science companies and pharmaceutical reps, as we know, they're working very hard to commercialize medications and new drugs, new therapies that come out there that they want to get into patients' hands. But sometimes they have a very hard time scheduling and putting in time to go to the doctor's office. Traditionally, they conduct a lunch-and-learn session or a coffee consult, where they come on-site to a doctor's office or a hospital setting."   "Right now, to schedule that appointment, it's being done where the medical assistant or the office manager is writing down that individual's name on some kind of paper calendar, at most, maybe some kind of Google sheet, or a Google Meet account that they have within the office section. And that's the way that they're scheduling it. Healthcare reps are sometimes cold walking in, sometimes they're cold calling. They're putting in a lot of effort. They're working very hard to figure out how to get in and educate providers and their staff on new advancements." "What Fuerte hopes to do with a streamlined communication platform is make it very easy for the providers to find the reps and the reps to find providers to keep in touch with each other, to search each other by disease state, by therapeutic drug, by medical advancement, and to have a shared calendar system that they can keep in constant communication and contact." fuerteapp.com Download the transcript here