Obesity Innovator

© Life Sciences & Healthcare Collaborative, LLC APRIL 2025 AI & Digital Health Innovation & Personalized Medicine LIFE SCIENCES Innovator Executive Profile Kendra Bence, VP Obesity & Metabolism Pfizer Obesity Innovator Cancer Link Research and Insights Market Trends Access, Coverage, and Investments 1 OBESITY INNOVATOR Download and Share articles Look for this Icon to share individual articles 25 JOB SEARCH 27 Upcoming Events 28 Puzzle 29 EXPLORE MORE IN THIS ISSUE 2 THE NEXT WAVE Where Science, Market Trends, and Data Collide 7 DIGITAL INNOVATION AI and GLP-1s 11 EXECUTIVE PROFILE Meet Pfizer's Dr. Kendra Bence 15 adipose Tissue & CANCER Decoding the Obesity-Cancer Link 17 INVESTING IN OBESITY Coverage, Access, & Funding 22 PERSONALIZING CARE Phenotypes and Care Management April 2025 MARKET INFLECTION By Katerina Grigoriou Obesity treatment is one of the most exciting frontiers in drug development today, and the unmet need is staggering. According to the World Obesity Atlas 2023, over 1 billion people globally live with obesity (BMI > 30kg/m2), a number expected to double by 2035. The economic impact? Nearly $2 trillion in 2020, projected to exceed $4 trillion by 2035, factoring in healthcare costs and lost productivity. Despite its prevalence, obesity care has been historically overlooked. The establishment of the American Board of Obesity Medicine in 2011 was a step toward closing this gap. Yet, even as obesity prevalence doubled from 1990 to 2022, treatment innovation struggled to gain traction. Between 1990 and 2020, seven new weight-loss drugs were approved, but three were later withdrawn due to safety concerns, and another is not intended for long-term use. This history of setbacks reinforced skepticism around pharmacological interventions, creating an additional hurdle for market adoption. The breakthrough success of Wegovy and Zepbound has begun shifting this narrative, but overcoming historical biases remains critical for future progress. . The NEXT WAVE of obesity innovation 2 OBESITY INNOVATOR Where Science, Market Trends, and Data Collide MariTide (Amgen) The first GIP antagonist set to enter Phase 3 trials, offering robust weight loss and once monthly dosing for improved adherence WHAT'S IN THE PIPELINE "The future...will be defined by personalized, holistic approaches" MET-097i (Metsera) A next generation GLP-1RA designed for once-monthly dosing without the need for dose titration – potentially a game-changer for patient adherence and access Near-Term Injectables: More Than Just Weight Loss "Science tells us we can do even better" 3 OBESITY INNOVATOR Wegovy and Zepound have cemented GLP-1 receptor agonists (GLP-1 RAs) as the backbone of Obesity treatment. But science tells us we can do even better. What’s next? Cagrisema (Novo Nordisk) GLP-1 + amylin analog, demonstrating strong weight loss, though lower than expected Retatrutide (Eli Lilly) A triple agonist (GLP-1 + GIP + glucagon) promising bariatric surgery-like weight loss and potential benefits for people with severe obesity Near-Term Orals: Breaking the Injection Barrier 4 OBESITY INNOVATOR Danuglipron (Pfizer) Now reformulated for once daily dosing after overcoming early hurdles Orforglipron (Eli Lilly) No food intake restrictions, promising injection-like efficacy Oral formulations could expand the obesity treatment market significantly, addressing the needs of patients hesitant about injections while offering manufacturing and logistical benefits that improve global access. The Next Scientific Frontiers The future of obesity treatment isn’t just about more weight loss; it’s about better weight loss. Emerging mechanisms include: Leptin Sensitization & Amylin Agonists: Addressing metabolic adaptation and lean mass preservation Activin Antagonism: Exploring bone and muscle health alongside weight loss Fat Composition Modulation (e.g. Adipo Therapeutics): Investigating adipose tissue remodeling for improved metabolic health Genetic Medicine: Long-term solutions aiming to correct the metabolic dysregulation at the root of obesity Weight Loss Maintenance: Innovations targeting long-term metabolic adaptation to prevent weight regain, an area where current therapies fall short These developments signal a shift from simply achieving weight loss to sustaining it while preserving overall health. As we move beyond GLP-1s, the future of obesity treatment will be defined by personalized, holistic approaches that address the complexity of the disease. Rybelsus (Novo Nordisk) Oral semaglutide in development for obesity, though its stringent dosing requirements may limit adoption Severity of Disease Early-stage metabolic dysfunction vs advanced obesity with comorbidities Weight Loss Needs Patients needing moderate vs significant weight reduction Age & Gender Addressing muscle and bone health in older populations, particularly postmenopausal women, and tackling the unique challenges of pediatric obesity, where early intervention could have lifelong benefits Comorbidities Developing therapies that specifically target cardiovascular health, type 2 diabetes, or metabolic dysfunction in tandem with obesity treatment "This next era of obesity care is about more than just shedding pounds - it's about transforming lives." 5 OBESITY INNOVATOR Obesity is not a one-size-fits-all disease. It is a highly complex, multi-factorial condition driven by a dynamic interplay of metabolic, genetic, environmental, and behavioral factors. Multiple metabolic pathways regulate weight, and these pathways are not static – they shift and adapt in response to weight loss, diet, and treatment interventions. The next wave of obesity therapies must account for these complexities, tailoring treatment approaches to individual patient needs. Obesity specialists already approach treatment this way, but emerging science and new tools will accelerate precision medicine across the broader healthcare landscape. As research advances, treatment strategies will likely segment by: PRECISION OBESITY MEDICINE Written by Katerina Grigoriou, a life sciences strategist obsessed with bringing commercial thinking into early drug development. Read more of her insights at Queen of NPP. Clinical trials provide a foundation, but real-world data (RWD) is essential for understanding long-term obesity treatment outcomes. We’re already seeing broader data collection on the impact of anti-obesity medications (AOMs) on cardiovascular disease, metabolic dysfunction, and sleep apnea. However, significant weight bias remains. Many healthcare providers still view obesity as a lifestyle choice rather than a chronic disease. The lack of emphasis on long-term prevention in healthcare systems means payers remain hesitant to cover AOMs. RWD can provide the evidence necessary to shift policy and reframe obesity treatment as essential, not elective. REAL-WORLD DATA 6 OBESITY INNOVATOR THE PATH FORWARD The dedication of scientists over the decades have brought us to an exciting place with an obesity pipeline rich with potential. As a result, the obesity treatment landscape is evolving rapidly. We stand at a pivotal moment, where the right decisions today will shape the future of obesity care for generations. The industry must move beyond a singular focus on weight loss and embrace a broader vision of metabolic health. To truly redefine obesity care: We must innovate beyond GLP-1s, targeting diverse pathways that personalize treatment and address long-term metabolic adaptation We must break barriers to access by leveraging real-world data to shift policy and overcome outdated biases We must champion a new paradigm – one where obesity treatment is proactive, personalized, and fully integrated into healthcare This next era of obesity care is about more than just shedding pounds – it’s about transforming lives. The science is advancing, the market is shifting, and the momentum is undeniable. Now is the time to seize the opportunity and reimagine what’s possible in obesity treatment! The convergence of artificial intelligence (AI) and GLP-1 receptor agonists (GLP1-RA) is reshaping obesity treatment, creating unprecedented opportunities for innovation in clinical research, healthcare delivery, and patient care. This transformation comes at a crucial time as the obesity treatment landscape undergoes rapid evolution with analysts projecting the GLP-1 market to exceed $100 billion by 2030.1 AI and GLP-1s: Transforming Obesity Care Through Digital Innovation By Brian Conyer 7 OBESITY INNOVATOR "AI is fundamentally changing how we conduct and optimize clinical trials for GLP-1 therapies." The unprecedented demand for GLP-1 drugs has created unique market access challenges. With over 120 anti-obesity drugs in development, roughly 35% being GLP-1 agonists, healthcare systems are grappling with coverage decisions and resource allocation. Industry analysts note that GLP-1 medications are seen as disruptive innovations in healthcare, comparable to the advent of statins for heart disease and cholesterol, highlighting the scale of their potential impact on healthcare systems.1,5 AI-powered analytics are being used to predict treatment outcomes and cost-effectiveness across different patient populations, helping inform coverage policies. These tools can identify which patients are most likely to benefit from GLP-1 therapy, potentially allowing for more targeted coverage criteria that optimize both clinical outcomes and healthcare resources.1,5 REVOLUTIONIZING CLINICAL TRIALS AND REAL-WORLD RESEARCH AI is fundamentally changing how we conduct and optimize clinical trials for GLP-1 therapies. Traditional obesity drug trials are often costly and time-consuming, but AI-driven approaches are streamlining these processes. In 2024, Dandelion Health launched an AI-powered real-world data platform focused on GLP-1 receptor agonists, aggregating de-identified patient health records to generate valuable insights.2 "We can evaluate points like, is this candidate more effective in men or women? Are there certain age ranges where this works best? That level of investigation is normally not done unless you're running a clinical trial," explains Dandelion Health's CEO, Elliott Green.2 This platform enables researchers to explore drug effectiveness across diverse populations and comorbidities without launching new trials, potentially accelerating the development pipeline.2 Machine learning algorithms are also enhancing trial efficiency through improved patient selection and monitoring. AI can analyze electronic health records to identify eligible participants more accurately and quickly than manual screening.3 For GLP-1 trials specifically, AI can help identify patients at higher risk of obesity-related complications who might benefit most from the therapy, ensuring trials enroll those most likely to show meaningful responses. The integration of wearable devices and remote monitoring provides real-time efficacy signals, such as continuous glucose measurements and weight tracking, while promptly flagging safety concerns.4 8 OBESITY INNOVATOR MARKET ACCESS AND COVERAGE CHALLENGES PRECISION MEDICINE AND AI INNOVATION An emerging focus in the field is understanding and managing the psychological aspects of GLP-1 therapy. AI-driven platforms are being developed to monitor and support patients' mental health throughout their weight loss journey. A 2024 commentary in JMIR Diabetes highlighted that as millions more patients start GLP-1 therapy, the "frequent communication, titration, and administrative interactions" could overwhelm healthcare providers, making AI support crucial for comprehensive care.8 Digital health companies are incorporating mood tracking and behavioral health support into their GLP-1 management platforms, using AI to identify patterns that might indicate psychological challenges or needed interventions.4 For example, Lark Health's GLP-1 Companion Program employs AI to provide 24/7 emotional support and coaching, helping patients navigate the psychological aspects of rapid weight loss and lifestyle changes.9 9 OBESITY INNOVATOR The integration of AI in GLP-1 therapy is advancing precision medicine in obesity treatment. While these medications work broadly, individual responses and tolerances vary significantly. As one health data expert noted, with growing datasets and AI tools, providers should soon be able to predict which patients will benefit most from a specific weight-loss drug.6 This precision approach is particularly evident in new digital health solutions. For instance, Allurion Technologies' AllurionMeds program, launched in 2024, features Coach Iris, an AI behavioral coach trained on data from over 150,000 patients. Additionally, the remote patient monitoring platform integrated into the program offers personalized guidance and syncs with smart devices to track not only weight but also body composition and activity levels, providing personalized guidance and addressing challenges such as weight regain. Allurion founder and CEO Dr. Shantanu Gaur commented: “Real-world use of GLP-1s has highlighted three critical issues: poor medication adherence and wrap-around support, muscle and bone mass loss, and untenable cost to the healthcare system”.7 ADDRESSING MENTAL HEALTH IMPACT Written by Brian Conyer, VP of Digital Health, Allurion Technologies FUTURE DIRECTIONS AND IMPLICATIONS "Real-world use of GLP-1s has highlighted three critical issues: poor medication adherence and wrap-around support, muscle and bone mass loss, and untenable cost to the healthcare system." The integration of AI with GLP-1 therapy represents a significant step toward more personalized and effective obesity treatment. As experts emphasize, to truly capitalize on this opportunity, we need robust, unbiased data and careful validation of AI tools.6 Looking ahead, several key developments are likely to shape the field: Advanced predictive modeling for patient response and side effects Integration of digital twins for metabolic modeling and treatment optimization Expanded use of real-world evidence to inform treatment decisions Development of AI-driven support systems for long-term maintenance For healthcare providers and policy professionals, these innovations offer new tools to optimize treatment decisions and resource allocation. For researchers, AI-enhanced platforms provide unprecedented opportunities to understand treatment responses and develop more effective interventions. The success of this technological integration will depend on continued collaboration between healthcare providers, technology developers, and policy makers to ensure that these innovations enhance rather than complicate patient care. As we move forward, maintaining focus on evidence-based implementation and equitable access will be crucial for realizing the full potential of AI-enhanced GLP-1 therapy in obesity treatment.7 10 OBESITY INNOVATOR By Renee Hurley With the critical shift towards recognizing obesity as a complex, chronic, multi-factorial disease and the spotlight brightly shining on GLP-1s, scientists and researchers are empowered to continue searching for new therapies that fill existing treatment gaps and address restrictive side effects of current treatments. Part of our mission at the Life Sciences Obesity Collaborative is to recognize and honor those who are pushing the boundaries of what’s possible in obesity care and treatments, especially those who are inspired by patient journeys and lead with a patient-centric mindset. With that, I’m honored to recognize Dr. Kendra Bence as our first Obesity Innovator. Dr. Bence is currently the Vice President, Obesity & Metabolism in the Internal Medicine Research Unit at Pfizer. Soon after I launched the Collaborative, Dr. Bence reached out to me to connect and learn more about the initiative. From the first moment we spoke, she emanated passion, empathy and dedication. In that initial chat, she led with stories of patient advocates and how they inspired the work she and her team do. She had every opportunity to self-promote and yet she didn’t. I’m hoping to do a bit of that on her behalf. So, I invited Dr. Bence to chat with me again to learn more about her current role, how she got into the obesity field, and what excites her about the future of this space. In your current role as Vice President, Obesity & Metabolism, what are your primary responsibilities? I lead a talented group of scientists focused on developing therapies for obesity and cardiometabolic diseases. In addition, I work with academic collaborators and biotech innovators to develop the most promising ideas and technologies to accelerate delivery of medicines to patients. You earned your doctorate in physiology and biophysics and began your career with a fellowship at Beth Israel Deaconess Medical Center and as an associate professor at the University of Pennsylvania. What led you into the field of pharmaceutical clinical development? The biggest driver for my decision to join a pharmaceutical company was the opportunity to lead larger basic science teams and ultimately have a greater impact in moving the field forward. Being able to see an early discovery translate into a clinically successful pharmacotherapy for patients is humbling and inspiring. With so many therapeutic options, what influenced your decision to focus on obesity and metabolism? My PhD thesis research focused on the basic mechanics of cellular signaling pathways and was agnostic to any particular disease. During my post-doctoral research, a mouse model I was working on developed resistance to weight gain on a high-fat diet and my project was to figure out why. In a full-circle moment, it turned out that obesity protection arose from alterations in key signaling pathways in the brain (a great example of a basic science discovery leading to a breakthrough in understanding disease mechanisms)! What fascinates me about metabolism is the complex crosstalk between organs system (the brain, gut, adipose tissue, liver, muscle, immune system, etc). It is a great time for young scientists to enter the obesity field given the excitement around emerging incretin therapies and the need for additional novel approaches to treating this complex metabolic disease. We have a lot more work to do. Can you share an example of research your team has published and/or is leading that excites you? One of our Pfizer postdoctoral fellows, John Griffin (who is now a Senior Scientist), worked with our Obesity team to publish an interesting story in Molecular Metabolism examining the relationship between the hepatokine Activin E and adipose tissue metabolism, testing the hypothesis that Activin E functions as part of a liver-adipose, inter-organ feedback loop to suppress adipose tissue lipolysis. This work is particularly insightful as human genome wide association studies (GWAS) indicate that a predicted loss-of-function variant in the Inhibin βE gene (INHBE), which encodes Activin E, is associated with reduced abdominal fat mass and cardiometabolic disease risk. Following clues from human genetics can give us insight into pathways associated with risk for chronic metabolic diseases and can provide some level of confidence that the pathway being studied is relevant to human physiology. See Reference With so much progress happening, it’s easy for some to forget that clinical development also consists of many roadblocks. What do you foresee as the biggest challenges in clinical development in obesity? A challenge in obesity clinical development is the high bar/precedence that has been set for demonstrating a dramatic percentage of body weight loss in a relatively short amount of time for leading obesity assets. While these robust levels of weight loss are transforming the obesity field, most patients will benefit from sustained, clinically meaningful body weight loss over longer periods of time. My hope is that we allow the space for development of novel therapies that can deliver on clinically meaningful weight loss efficacy while providing additional benefits to the patient, such as improved body composition and reduced cardiovascular & renal disease risk in the longer term. The development of oral options for obesity therapies will also be important in order to have a global impact on the obesity epidemic. Despite these challenges, there are clearly many opportunities in this field. What keeps you motivated and excited to continue pushing the boundaries? I am inspired by the dedication and excellence of the scientists and colleagues I have the pleasure of working with every day. Research can be fraught with setbacks, but when an elusive breakthrough arises, it is exhilarating to know that your work might help patients someday. It is important to remember that basic science discoveries lay the foundation for subsequent development of medicines. We must continue to support essential basic science, both in industry and academia. I am also proud of being a mentor and giving back to early career scientists & inspiring them to persevere in the face of challenges. Disclaimer: The views and opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views, opinions, or position of their employer. 11 OBESITY INNOVATOR INNOVATOR PROFILE Meet Pfizer's Dr. Kendra Bence 12 OBESITY INNOVATOR 13 OBESITY INNOVATOR Written by Renee Hurley, Founder, Life Sciences Obesity Collaborative Decoding the Obesity Cancer Link 14 OBESITY INNOVATOR Obesity affects just about every system in the human body - due in part to chronic inflammation, hormone dysregulation and other factors - leading to subsequent conditions, such diabetes, kidney disease, and heart failure. Among the possible life-altering conditions is cancer. In fact, 40% of all cancers diagnosed in the United States each year are attributed or have some relation to obesity.1 Although, epidemiological data clearly shows the increase in cancer risk, more research is needed to better understand causation, the pathways attributing to the increased risks, and if and what can be done to reduce those risks in addition to weight loss. Currently, there are 123 active studies listed on ClinicalTrials.gov that are investigating the link between obesity and different types of cancer, including breast, ovarian, endometrial, prostate, rectal, gastrointestinal, pancreatic and liver. In addition, factors such as nutrition, physical activity, and mental health are being studied.2 To explore this further, we reached out to Dr. Kristy Brown to learn more about her research focus around the obesity-cancer link. METABOLIC-PATHWAYS, ADIPOSE TISSUE AND CANCER 15 OBESITY INNOVATOR There is strong epidemiological data linking obesity to the development of at least 13 different cancers. Obesity-related liver cancer is unique among these as it occurs in a highly metabolic tissue that when dysfunctional, is associated with lipid accumulation in cells susceptible to tumorigenesis. Other obesity-related cancers are supported by host metabolic dysfunction through systemic and microenvironment changes that drive tumor growth. Hyperinsulinemia and hyperglycemia, associated with diabetes and obesity, stimulate signaling pathways involved in regulating cell proliferation through protein synthesis, energy metabolism and various other pathways. The adipose is also a major driver of cancer through the production of adipokines, like leptin, low-grade chronic inflammation and local biosynthesis of estrogens. These various factors have been shown to converge to stimulate the proliferation of cancer cells. The development of estrogen receptor positive breast and endometrial cancers with obesity, and occurrence after menopause when gonadal estrogen production has ceased, speak to the importance of adipose-derived steroid hormones. How estrogen production is regulated in the adipose is a major focus of our research, and we have discovered the convergence of obesity-associated factors with dysregulated cell metabolism as major drivers of the adipose expression of aromatase, a key enzyme in the biosynthesis of estrogens and target of current endocrine therapy for the treatment of breast cancer. Obesity is also associated with fibrosis in the microenvironment of many tumors that occurs as a result of tissue injury, including breast and liver. These changes in the extracellular matrix are associated with worse disease outcomes. Our recent work also highlights a role for obesity to cause cancer, with poor metabolic health being associated with more damage to breast epithelium and fallopian tube (origin of ovarian cancer) DNA. Given the important interaction between many obesity-associated factors, it is still not clear whether targeting one will be sufficient to prevent cancer development. The most effective approach will likely involve restoration of metabolic health through weight loss and exercise. In fact, exercise alone, independent of obesity, is associated with reduced risk of cancer. It remains to be determined whether anti-obesity medications will be effective at reducing cancer risk, although recent data point significant benefit. How cessation of these medications and incorporation of healthy lifestyle affect risk and cancer-related outcomes is still unknown. 16 OBESITY INNOVATOR Written by Kristy A. Brown, PhD, Associate Professor of Metabolism and Cancer, Department of Cell Biology & Physiology, KUMC Co-Program Leader, Cancer Prevention and Control, University of Kansas Cancer Center Resources Shared by Dr. Brown Investing in Obesity - Coverage, Access, & Funding 17 OBESITY INNOVATOR By Renee Hurley An estimated 40,000 deaths per year in the United States could be prevented by expanding access to GLP-1 anti obesity medications (AOMs).1 Yet, many employer, private and government health plans do not provide coverage of these drugs for weight loss or if they do, restricted criteria, such as requiring another condition (such as diabetes), meeting with a psychiatrist, or enrolling in a weight-loss program, further limit access and expand coverage gaps. With GLP-1 drugs ranging between $350 and $499 monthly in out-of-pocket costs for uninsured or underinsured patients, these medications are still out of reach for many despite new manufacturer direct-to consumer programs, patient assistance programs, and other cost-lowering efforts. Coverage gaps also expand health inequities and care discrepancies in certain patient populations, socioeconomic groups, and regions. For example. In the U.S, states that have higher obesity and diabetes rates coupled with lower median household income, such as Arkansas, West Virginia, Mississippi and Oklahoma, serve to be most impacted by expanding coverage, and as result “could lead to the largest per capita reductions in mortality”.1 In late 2024, then U.S. President Biden proposed a rule to allow Medicare and to require Medicaid to cover drugs intended for weight loss for obese patients.2 Currently, only 13 states cover GLP1-s for obesity.3 Unfortunately, the U.S. administration change derailed this proposal. In early April, President Trump announced the government would not move forward with these policies. If they had been enacted, they potentially could have applied more pressure to private and employer-based health plans to expand their coverage. According to KFF analysis, most companies with more than 200 employees do not currently cover GLP-1 drugs for weight loss – only 18% reportedly do.4 For those patients who do have access to GLP-1 drugs, high cost and gastrointestinal side effects appear to be the two biggest challenges to patient persistence. DNB /// Back Bay reported, that according to a survey of physicians, 33% of patients discontinue these medications after just six months – even though these are now considered life-time disease-modifying medications. Of the reasons for discontinuation, 54% reported lack of or limited coverage as the number one reason.5 While GLP-1s continue to lead the headlines around weight loss treatments, lack of coverage and access also impact other effective and complementary weight loss therapies, including bariatric procedures. In fact, only 1% of qualified patients undergo bariatric surgery, with insurance denial being the primary reason patients don’t have bariatric procedures.6 Yet, the reduction in overall patient healthcare costs are estimated at 29% within five years of bariatric surgery.7 . ACCESS & COVERAGE SOCIETAL IMPACT 18 OBESITY INNOVATOR Globally, obesity prevalence continues to rise despite decades of increased focus on lifestyle changes and public health policies. With that, the impact on society is reflected in growing healthcare resource utilization and economic burden as well as in lower quality of life and increasing mortality rates. When considering societal impact, critical indirect economic costs are also related to lower workplace productivity due to disability, reduced personal income, reduced workforce participation, and premature deaths. Countries across the globe are working towards estimating the overall cost of obesity to help better quantify the potential economic benefits of enabling greater access to AOMs. For example, estimates for the cost of inaction and societal burden in treating obesity in Canada is $21 billion8, $116.85 billion (US) in the Kingdom of Saudi Arabia9, and £98 billion in the United Kingdom annually10. If current trends continue by 2060, the economic impacts from overweight and obesity (OAO) are projected to rise from 1% in 2020 to more than 3% of Gross Domestic Product (GDP) globally. Within the same time frame, reducing OAO prevalence by just 5% may equate to annual cost reductions of $2.2 trillion globally.11 In the U.S., some estimates of Medicare AOM covered costs (assuming the changes were to take effect in 2026) range from $250 billion to $1 trillion.12 However, a recent study by the Leonard D. Schaeffer Center for Health Policy & Economics, notes that these estimates don’t include price rebates and ignore the medical cost-offsets of treating obesity, explaining that “prior research suggests that Medicare coverage of weight-loss therapies could save federal taxpayers as much as $245 billion in the first 10 years in reduced medical spending.”13 The paper also addresses the huge potential if access were expanded to additional subgroups, such as younger patients, low and medium risk diabetes groups, and those in the moderate BMI categories. Expanded access to these groups and all AOM treatment eligible patients could not only reduce or delay obesity-related comorbidities, such as diabetes, increasing quality of life and life expectancy, but it could also generate $10 trillion in lifetime net social value.13 Read the full white paper and see full figures here. Competition may also help drive down costs. While significant progress has been made with the current GLP-1 AOMs, the race is on to find the next blockbuster. Current GLP-1 drugs are forecasted to surpass $158 billion in sales by 2032.14 In conjunction with and beyond GLP-1s, biopharmaceutical manufacturers are investing in and targeting the current challenges with convenience (i.e. oral formulation instead of injectables), tolerability (ex: GI distress), and effects on body composition, such as lean mass loss. Towards the end of 2024, there were more than 700 active trials and studies on obesity and weight loss in the U.S. and more than 120 weight loss agents being developed by more than 60 companies.15 Strategic deals, including licensing, partnering, co-development, and acquisitions, have ramped up significantly over the past year, with the number of strategic deals in 2024 in the obesity space matching those of the previous three years combined. Tellingly, 72% of those deals were around products still in the discovery and pre-clinical stages.5 Some companies are creating wrap-around care services or partnering with telehealth or digital health providers to differentiate themselves, to improve weight loss treatment effectiveness and maintenance, and to reduce access barriers. In January 2024, Eli Lilly launched LillyDirect to offer Zepound through direct-to-consumer services and partnerships, including collaborations with wellness and telehealth companies, such as Ro and Form Health and care providers like Knownwell. Allurion, which has a proprietary gastric balloon, offers programmatic approach that includes nutritional support and digital tools to monitor progress. R&D PROGRESS 19 OBESITY INNOVATOR 20 OBESITY INNOVATOR In 2024, Venture Capitalists invested more than $1.8 billion into private companies in this space.5 As investments heat up and more companies focus on early obesity R&D, we asked BMO Capital Market's Evan Seigerman to share some insights into what investors are looking for in the next generation of weight-loss drugs. Evan is BMO's Managing Director, Senior Biotechnology & Pharmaceutical Equity Research Analyst. What do you want to see from early-stage development companies as they look to raise capital for new obesity treatments? We like to see differentiation on areas such as mechanism of action (vs. what we have now) — as me-too single agonist GLP1 therapeutics are not going to be competitive. One or two small molecule GLP1s will be successful, we do not need 30. We’re interested in novel mechanisms that solve for limitations with currently available therapies, such as tolerability, quality of weight loss, durability of weight loss, and so on. We also want to see clean clinical data (no off-target toxicities), with improved tolerability and quality of weight loss. What should we expect for M&A activity in the obesity treatment market? While we still believe that the U.S. remains the center of Biotech innovation, we’ve seen a recent uptick in licensing deals from China, including AstraZeneca/ Eccogene, Merck/Hansoh, and Novo Nordisk/United Labs. Time will tell whether these investments pay off, but to my previous point, differentiation vs leaders in the space is important. We could see other large players like Pfizer potentially do a deal in obesity if they decide not to move their oral GLP-1 asset Danuglipron forward. Industry’s interest in the space remains high, but again differentiation is likely to drive deal activity. What are the risk factors to watch for that might hinder growth in the obesity drug market? The number one concern that I am focused on is expanding patient access. Approval of secondary indications like Obstructive Sleep Apnea (OSA) could help drive broader coverage. However, policy changes, such as passage of TROA (Treat to Reduce Obesity Act, which would open up broad Medicare coverage) would make the largest difference here. Any obesity market predictions for 2025 that you would like to share? 2025 is going to be all about oral small molecules (data for Orforglipron expected by mid-year), next generation targets, like amylin, and growing patient access with innovative approaches, like direct-to-consumer (DTC) programs, for example Lilly’s collaboration with Ro Health. "Medicare coverage of weight-loss therapies could save federal taxpayers as much as $245 billion in the first 10 years in reduced medical spending."13 FUNDING Q&A 21 OBESITY INNOVATOR By Leon Katz, MD Applying AI & Phenotypes to Obesity Care Management The application of Artificial Intelligence (AI) and Precision Medicine (PM) is having a monumental effect on how patients are getting their care now and in the near future. Numerous models of AI have been introduced, too many for us to discuss in this article. Before starting a discussion about the use of AI for precision medicine as applied to the treatment of obesity, let’s take a look at the scope of the problem. In 2022, there were approximately 890 million obese adults worldwide.1 With the enormous prevalence of the disease – estimated at 20% of women and 14% of men worldwide by 2030 – the global obesity epidemic is causing tremendous strain on healthcare systems worldwide.2 The goal of this article is to discuss the potential use of AI to improve precision medicine as applied to the treatment of obesity and to explore opportunities to improve care and reduce healthcare utilization. Discussing AI and precision medicine requires a few basic definitions. AI is sometimes defined as a system’s ability to correctly interpret external data, learn from such data, and use those learnings to achieve specific goals and tasks through flexible adaptation.3 Precision medicine has been defined as any medical intervention targeted to population subgroups categorized on common genetic patterns, lifestyles, drug responses and/or environmental and cultural factors.4 The application of AI in medicine has been used extensively in the field of radiology where AI can assist a radiologist in recognition of subtle abnormalities that could easily be missed even by a highly trained professional. The current standard of care for obesity management utilizes a step wise approach with behavior modification as a first step, followed by anti-obesity medication and then bariatric surgery for people with severe obesity or comorbidities. The challenge is how to recognize which treatment modality would provide the best results depending on the patient’s etiology of obesity. Clinical data from obesity research is very difficult to interpret because many variables are based on questionnaires, which can introduce bias and lack of consistency. Dr. Andres Acosta of Mayo Clinic and his colleagues looked to tackle these challenges by classifying obesity based on four pathophysiological and behavioral phenotypes. Their study demonstrated that a phenotype-guided approach showed a 1.75 fold greater weight loss after 12 months compared to non-phenotype guided therapy, which translated to a mean weight loss of 15.9% compared to 9%.5 Additional research has been done to identify and review AI applications in obesity research and care. Dr. Ruopeng An of Washington University Brown School and colleagues reviewed 46 studies that used various AI models and found that the combination of artificial intelligence and precision medicine allowed for recognition of clinically significant patterns of obesity or relationships between specific covariates and weight outcomes.6 AI can assist at every step of obesity management. For example, the initial integration of AI would include the assessment of data in the medical chart, blood work and anthropomorphic data. From there, aggregation of the data would assist with predictive models of future disease burden for the individual patient. This data would be used to create a personalized eating plan that takes into account food availability, preference of the individual and the unique cultural factors involved in choosing food. Traditional methods of food intake depend on people keeping track of individual foods and recording data on paper or in a digital app. By using images of foods consumed, AI may be able to create a more accurate assessment of portion size and caloric intake. Furthermore, exercise and physical activity represent an excellent example of integrating data from wearables and allowing AI to have a comprehensive understanding of the optimal time of the day for achieving the greatest benefit from physical activity. The response of the individual to different types of exercise, the duration that they can achieve, and the pleasure they derive from specific exercise can provide necessary data so that AI can further improve recommended exercise regimens. Additionally, a smart chatbot can assist the person by providing motivational messages, but unlike current simplistic models that simply send a message of encouragement, an AI driven chatbot can take the discussion to a higher level by providing real-time responses to the person’s unique thoughts and feelings. The virtuous cycle repeats as the improvement in comorbidities leads to further refinement of recommended treatment. In these ways, the future of AI in the treatment of obesity is exciting and encouraging. With continued research, we will have an improved understanding of the interaction of genes that contribute to different forms of obesity. New anti-obesity medications will be developed and have improved specificity for differing obesity phenotypes. With the help of AI, aggregated data will provide personalized treatment modalities. Before concluding, consideration of the importance of explainable artificial intelligence is critical. The future of personalized developments in the medical treatment of obesity depend on excellent AI models. Yet, one of the biggest challenges with AI is the difficulty explaining the manner in which the application derived the recommendation, even for the computer scientists who programmed the original AI code. Use of AI by clinicians and the acceptance of its use by patients will depend on our ability to understand how the data and recommendations were derived.7 There will always be a need for Human In The Loop (HITL) protocols. This approach demonstrates the importance of having human oversight in applying AI for medical management. HITL will help ensure that clinical standards, patient needs, and ethical considerations help provide the safest and most effective treatment for human beings. 22 OBESITY INNOVATOR 23 OBESITY INNOVATOR Phenotypes Identified by Acosta et al5 Abnormal Satiation Associated with Abnormal Hypothalamic Brain Perfusion Abnormal Satiety Associated with Intestinal Enteroendocrine Cell Dysfunction Abnormal Emotional Eating Characterized by Uncontrolled Hedonic Eating and Associated with Abnormal Nucleus Accumbens Perfusion Abnormal Resting Energy Expenditure Associated with Decreased REE by Indirect Calorimetry 24 OBESITY INNOVATOR Written by Dr. Leon Katz, Medical Weight Loss Specialist & Diplomat, American Board of Obesity Medicine TALENT 25 OBESITY INNOVATOR TALENT & JOB OPPORTUNITIES We've partnered with SJLife Sciences to highlight obesity and cardiometabolic life sciences and healthcare job seekers and role opportunities. Executive Director, Strategy Pharma leader with 20+ years in brand strategy, marketing, sales, and market access. Expert in obesity, diabetes, and billion-dollar brand growth. Vice President, Medical Affairs Experienced Medical Affairs leader, specializing in various areas, including nutrition and weight regulation, with a strong focus on understanding cardiovascular disease, obesity prevention, and the management of diabetes and other metabolic disorders. Sr. Obesity Manager Experienced professional with 20+ years in healthcare, leading teams and driving strategic initiatives to improve outcomes in health systems and ambulatory care. Director, Patient Engagement With over 15 years in pharma, biotech, and med devices, this professional is a strategic leader focused on improving patient engagement in clinical trials and commercial initiatives. Cardiologist Dynamic life sciences leader with broad experience across biopharma and academia, including clinical development, regulatory strategy, medical affairs, product launches, scientific advisory, and M&A. Vice President, Clinical Operations Experienced Clinical Operations Leader with global drug development expertise, adept at managing all aspects of clinical programs. Skilled in designing and executing global trials across therapeutic areas like, obesity, depression, diabetes, neurology, GI, and lipid lowering. Obesity Medical Liaison Board-certified pharmacist with 10+ years of experience, focused on improving patient outcomes through personalized care and education. Senior Director Medical Affairs Seeking a Senior Medical Director for Obesity to join my Medical Affairs team. This role provides leadership, market preparation, and medical insights. Sr. Medical Director The Sr. Medical Director will lead medical oversight for clinical trials, collaborate on study design, and engage with health authorities, with 3-5+ years of clinical drug development experience preferred. Senior Manager, Strategy Seeking a Strategy & Operations Senior Manager to lead the launch and optimization of new product lines. Director of Medical Education The Director of Medical Education in Boston will lead and implement medical training programs, compliance, and team development. 26 OBESITY INNOVATOR To learn more about the talent and roles listed, please reach out to SJLife Sciences. Stay informed about new talent and roles by Subscribing to their newsletter The Obesity Bulletin. ROLES Industry EVENTS If you would like to see your event listed, email us the details! April 23-27 | National Harbor, MD Annual Obesity Medicine April 24-26 | Toronto, Canada DUO25 April 29-May 1 | Boston, MA GLP-1 Based Therapeutics Summit May 11-14 | Malaga, Spain European Congress on Obesity July 14-16 | Boston, MA Obesity and Weight Loss Drug Development Summit September 19-20 | Rome, Italy International Conference on Weight and Obesity Management October 2-4| Cedar Creek, TX Obesity Summit 2025 October 23-25 | Orlando, FL World Obesity and Weight Management Congress November 4-7 | Atlanta, GA OBESITYWEEK November 20-22 | Singapore International Conference on Obesity December | San Diego Innovation in Obesity Therapeutics Summit 27 OBESITY INNOVATOR Please note: We share the following event listings solely for reference. The Life Sciences Obesity Collaborative and Obesity Innovator do not endorse or manage these events. Hint: All clues and word answers are pulled from the articles in this issue of Obesity Innovator. Please print out this page to complete the crossword and check here for the answer key. 28 OBESITY INNOVATOR Treating obesity is serious business, but that doesn't mean we can't have a bit of fun as we work. We hope you enjoy the crossword puzzle as much as we did with creating it. FOR FUN CROSSWORD SOCIAL NETWORKING Read this issue and all articles online FEEDBACK VIRTUAL PANEL We want to hear from you on areas of interest or ways to improve. > Share Feedback > Connect > Contribute EXPLORE MORE Byline Articles Expert Perspectives Innovator Profile Nominations Partners 29 OBESITY INNOVATOR > Watch Recording OBESITY INNOVATOR We're looking for: © Life Sciences & Healthcare Collaborative, LLC Obesity Innovator is a publication of the Life Sciences Obesity Collaborative.