#240 Dr. David Fajgenbaum - Can AI Find Cures to Rare Diseases Using Existing Medicine?
In this episode of the Shawn Ryan Show, Dr. David Fajgenbaum shares his journey from medical student to physician-scientist after being diagnosed with Castleman's disease. Through his own research, he discovered that sirolimus, a transplant medication, could treat his condition—leading him to establish the Castleman Disease Collaborative Network and EveryCure, a non-profit drug company focused on repurposing existing medications.
The episode explores how Fajgenbaum's team at EveryCure uses AI technology to analyze millions of potential drug-disease combinations. Their platform examines how 4,000 existing drugs might treat 18,000 different diseases, with medical experts reviewing the most promising matches for further research. The discussion covers the challenges of drug repurposing, including financial disincentives that often prevent pharmaceutical companies from exploring new uses for generic medications.
This is a preview of the Shortform summary of the Sep 29, 2025 episode of the Shawn Ryan Show
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Fajgenbaum's Personal Journey and Motivation
David Fajgenbaum's path to becoming a physician-scientist was deeply personal. After losing his mother to brain cancer, he was inspired by her resilient spirit to pursue medicine. His journey took an unexpected turn when he was diagnosed with Castleman's disease, facing death five times. Through his own research, Fajgenbaum discovered that [restricted term], a drug used for organ transplantation, could treat his condition. This discovery has kept him in remission for over a decade and led him to establish the Castleman Disease Collaborative Network.
Drug Repurposing For New Medical Indications
Fajgenbaum advocates for exploring new uses of existing medications through his organization, EveryCure. His lab at the University of Pennsylvania has successfully repurposed 14 drugs for conditions they weren't originally designed to treat, including rare cancers and inflammatory diseases. However, Fajgenbaum points out that financial disincentives often prevent pharmaceutical companies from researching new uses for generic drugs, which make up about 80% of all medications. To address this, EveryCure operates as a non-profit drug company, prioritizing patient care over profit.
AI & ML in Drug Discovery & Repurposing
Fajgenbaum's team at EveryCure employs an innovative AI platform that evaluates approximately 75 million drug-disease pairings, analyzing how 4,000 existing drugs might treat 18,000 different diseases. The AI assigns scores to potential matches, which Fajgenbaum's team of medical experts then reviews. Out of over 6,000 top AI matches, they prioritize 60-70 for detailed research and potential clinical trials. Through a federal contract with ARPA-H, EveryCure continues to leverage AI technology to efficiently identify promising drug repurposing opportunities.
1-Page Summary
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Clarifications
- Castleman's disease is a rare disorder of the lymph nodes that can lead to multiple organ failure. [restricted term], originally used for preventing organ transplant rejection, has shown promise in treating Castleman's disease by targeting abnormal immune responses. David Fajgenbaum's personal experience with Castleman's disease and his successful treatment with [restricted term] have driven his advocacy and research efforts in this field. [restricted term] works by inhibiting a specific pathway involved in the overactive immune response seen in Castleman's disease, helping to manage the condition and improve patient outcomes.
- Drug repurposing involves finding new medical uses for existing medications. Financial disincentives in pharmaceutical research can hinder exploring new uses for generic drugs due to limited profit potential. This challenge arises because generic drugs, which form a significant portion of medications, may not offer substantial financial returns for companies. To address this issue, initiatives like EveryCure operate as non-profit entities, prioritizing patient care over profit.
- In drug discovery and repurposing, AI (Artificial Intelligence) and ML (Machine Learning) technologies are used to analyze vast amounts of data to identify potential new uses for existing drugs. These technologies can evaluate numerous drug-disease pairings to predict how specific drugs might be effective in treating different diseases. By assigning scores to these pairings, AI helps researchers prioritize which combinations to investigate further for potential clinical trials, streamlining the drug development process. Leveraging AI and ML in this way can lead to the discovery of novel treatment options and accelerate the identification of promising drug candidates for various medical conditions.
- EveryCure operates as a non-profit drug company, prioritizing patient care over profit. This means that their primary focus is on advancing medical research and providing affordable treatments rather than maximizing financial gains. By functioning as a non-profit entity, EveryCure can dedicate resources to drug repurposing efforts that may not be financially attractive to traditional for-profit pharmaceutical companies. Their mission is to explore new uses for existing medications to address unmet medical needs, especially for rare diseases and conditions.
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Fajgenbaum's Personal Journey and Motivation
David Fajgenbaum has become a renowned physician-scientist and professor, directing his expertise toward combating elusive diseases after profound personal experiences shaped his resolve and commitment to medical research and patient care.
Fajgenbaum Inspired to Pursue Medicine After Losing Mother To Brain Cancer
Fajgenbaum Inspired by Mother's Humor During Her Tough Brain Surgery to Help Others
David Fajgenbaum was deeply affected by the loss of his mother to brain cancer, an event that propelled him to dedicate his life to combatting diseases. Fajgenbaum recalls a specific moment during his mother's brain surgery recovery when she humorously referred to herself as the Chiquita Banana lady, showing her resilient spirit. This memory of his mother's humor and her concern for family even in dire circumstances inspired him to help others dealing with medical challenges.
Facing Death From Castleman's, Fajgenbaum Discovers Life-Saving Repurposed Drug
Fajgenbaum faced his own mortality when diagnosed with Castleman's disease, a rare condition that nearly took his life five times. Despite numerous near-death experiences and being told he wouldn't survive, Fajgenbaum was motivated by his desire to marry his girlfriend, Caitlin, and build a future. This strong resolve led Fajgenbaum to identify a life-saving repurposed drug. Fajgenbaum found that a drug used for organ transplantation could inhibit an overactive communication line in his immune system, which he believed might treat his Castleman's. Despite initial hesitation due to potential risks, his doctor prescribed the drug, and it has kept Fajgenbaum in remission for over a decade.
Fajgenbaum's Drive to Find Cures in Existing Drugs and Help Patients
The struggle with Castleman's disease strengthened Fajgenbaum's resolve to find treatments for people like his mother and for his own condition. He has since founded the Castleman Disease Collaborative Network, a ...
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Fajgenbaum's Personal Journey and Motivation
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Actionables
- You can channel personal challenges into motivation by writing a "Resilience Diary" where you document daily struggles and how you overcome them, turning adversity into a source of strength.
- Keeping a diary like this helps you to recognize patterns in how you deal with difficulties and can inspire you to take proactive steps in other areas of your life. For example, if you notice that you're particularly good at problem-solving when under stress, you might volunteer for a crisis hotline to help others.
- Start a "Repurpose with Purpose" club with friends or community members to share and discuss ways to use everyday items or skills in unconventional, beneficial ways.
- This club could meet monthly to brainstorm creative uses for household items or discuss skills that could be transferred to new hobbies or community services. For instance, someone with knitting skills might start making prosthetics for injured wildlife.
- Create a "Hope Mosaic" project where you collect and display stories of people who h ...
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Drug Repurposing For New Medical Indications
David Fajgenbaum is an advocate for reexamining existing medications for new uses, understanding that there is untapped potential in the drugs we already possess.
Fajgenbaum Discovered Many Existing Drugs Effectively Treat Diseases Off-label
Fajgenbaum highlights the need to ensure that the approximately 4,000 FDA-approved drugs are evaluated for all possible disease treatments. He shares his vision through EveryCure, a mission-focused entity to relieve suffering by finding new purposes for these medications. Using his own experience as a starting point, Fajgenbaum delved into research on immunosuppressants and, most notably, found that [restricted term], an existing drug, effectively treated his own rare condition, Castleman's disease. This drug is an mTOR inhibitor, sometimes used for its anti-aging properties, proving to be a lifesaver for Fajgenbaum. It has since seen success in treating other patients as well, although it was originally developed to prevent organ transplant rejection.
Fajgenbaum’s lab at the University of Pennsylvania has furthered this initiative by advancing 14 drugs for diseases they were not originally intended for, focusing on rare cancers and inflammatory diseases. These successful examples highlight the vital practice of drug repurposing. For instance, [restricted term] has been effective for about a quarter of the Castleman's disease patients treated, and lidocaine, commonly used for numbing during dental procedures, has been repurposed in India to help reduce breast cancer recurrence and mortality.
[restricted term], an Immunosuppressant, Effectively Treats Fajgenbaum's Castleman's Disease
Fajgenbaum’s life was saved by [restricted term], a medication he decide to take despite limited existing data on its efficacy for Castleman's disease. After beginning treatment with [restricted term], Fajgenbaum saw improvements and, over time, witnessed the remission of his disease, a triumph that came into sharp focus as he felt notably better and regrew his hair by the time he got married in May 2014.
Fajgenbaum's Team Repurposes 14 Drugs For Other Diseases
Building on the success with [restricted term] and a JAK inhibitor, Fajgenbaum's lab has set out to repurpose existing drugs for conditions beyond Castleman's disease. Discoveries have already led to meaningful treatments, such as a child with DADA2 syndrome who experienced halted strokes after off-label drug treatment; this solution came about through similarities with another disease profile and has since been shared and applied globally.
Addressing the Financial Disincentives For Drug Companies to Repurpose Generi ...
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Drug Repurposing For New Medical Indications
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Clarifications
- mTOR inhibitors are drugs that block a specific protein called mammalian target of rapamycin, which plays a role in cell growth and metabolism. These inhibitors are used in treating various diseases like cancer and autoimmune conditions by interfering with abnormal cell growth. The most common mTOR inhibitors are rapalogs, which have shown effectiveness in clinical trials against different types of tumors. The discovery of mTOR and its inhibitor, rapamycin, dates back to the 1990s, leading to significant advancements in understanding their mechanisms and potential therapeutic applications.
- A JAK inhibitor is a type of medication that targets Janus kinases, enzymes involved in immune responses and inflammation regulation. These inhibitors are used to treat various autoimmune diseases and certain types of cancers by blocking the activity of specific JAK enzymes. JAK inhibitors work by interfering with signaling pathways that contribute to disease progression, offering a targeted approach to managing these conditions. ...
Counterarguments
- The process of drug repurposing, while beneficial, may not always be straightforward or safe; drugs may have side effects or interactions that are not well-understood in the context of new diseases.
- There may be regulatory and safety concerns with repurposing drugs without thorough clinical trials, which can be time-consuming and expensive.
- The suggestion to offer additional patent life or allow repurposed drugs to regain patent protection could lead to monopolistic practices and may not necessarily align with the goal of making healthcare more affordable.
- While EveryCure's non-profit model is commendable, it may not have the resources or reach of larger pharmaceutical companies, potentially limiting the impact of its drug repurposing efforts.
- The focus on repurposing drugs for rare diseases, though important, may divert attention and resources from developing new drugs that could be more effective or have fewer side effects.
- Incentivizing pharmaceutical companies with patent extensions might not be the most cost-effective way ...
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AI & ML in Drug Discovery & Repurposing
David Fajgenbaum, co-founder of EveryCure, is at the forefront of employing Artificial Intelligence (AI) and Machine Learning (ML) in drug discovery and repurposing. Fajgenbaum highlights the vast potential of AI to find new uses for existing medications to treat a variety of previously intractable conditions.
AI Platform Finds Promising Drug-Disease Matches in Biomedical Knowledge
Fajgenbaum discusses an AI database that evaluates the effectiveness of every drug against every disease, covering all 4,000 drugs and all 18,000 diseases. This AI platform assesses drug-disease pairings, giving them a score from zero to one to identify potentially significant matches.
AI Evaluates 75 Million Drug-Disease Pairings for Likely Effectiveness
Machine learning algorithms analyze known treatments to score how likely it is for any given drug to treat any disease, reviewing an astounding 75 million drug-disease pairings. The AI system simulates the effectiveness of the 4,000 drugs against the 18,000 diseases to identify potential treatment matches with high scores. Fajgenbaum describes the biomedical knowledge graph mapping all medicine and bioscience-related elements to enhance these evaluations.
Fajgenbaum's Team Reviews AI Matches to Find Promising Research and Trial Opportunities
After the AI identifies the most promising drug-disease matches, Fajgenbaum's team, comprising qualified MDs, PhDs, and individuals with combined degrees, steps in. They conduct a thorough review of the AI’s findings, focusing on the top scores to identify treatments with substantial potential. They carefully analyze over 6,000 top AI matches, prioritizing approximately 60 to 70 for in-depth research, lab tests, and possibly clinical trials to prove their efficacy.
AI and Machine Learning Enable Everycure to Repurpose Existing Drugs For Various Diseases
Fajgenbaum’s work with EveryCure highlights the benefits of leveraging AI and ML for identifying repurposing opportunities, streamlining the process of finding existing drugs that can treat various diseases.
AI Boosts Everycure In Identifying Promising Drug R ...
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AI & ML in Drug Discovery & Repurposing
Additional Materials
Clarifications
- The AI platform evaluates drug-disease pairings by analyzing known treatments to score the likelihood of a drug effectively treating a specific disease. It reviews an extensive number of drug-disease combinations to simulate the effectiveness of various drugs against different diseases. The platform assigns scores to these pairings, with higher scores indicating potentially significant matches for further investigation. This evaluation process helps identify promising drug-disease matches for potential research and clinical trials.
- When the AI system identifies potential drug-disease matches, Fajgenbaum's team, consisting of medical professionals and experts, thoroughly assesses these matches. They focus on the top-scoring matches to pinpoint treatments with significant potential for further investigation. Approximately 60 to 70 of the top matches are selected for detailed research, laboratory testing, and potential clinical trials to validate their effectiveness. This rigorous review process ensures that only the most promising matches progress to the next stages of research and development.
- AI and ML are used to analyze vast amounts of data on drugs and diseases to predict potential matches for repurposing existing medications. By evaluating drug-disease pairings and assigning scores based on effectiveness, AI can identify promising treatment opportunities. This technology accelerates the process of identifying new uses for drugs, leading to quicker experimentation and discovery of repurposing opportunities. Collaborative efforts between researchers and AI systems streamline the identification of drug repurposing candidates, potentially saving time and resources in drug discovery and development.
- The collaboration with Grant Mitchell and Tracy Zecora involves their partnership with David Fajgenbaum in co-founding EveryCure. Together, they work on leveraging AI and ML technologies for drug discovery and repurposing. Grant Mitchell and Tracy ...
Counterarguments
- AI's ability to score drug-disease pairings from zero to one may oversimplify complex biological interactions and may not always capture the nuances of drug efficacy and safety profiles.
- While machine learning algorithms can analyze vast numbers of drug-disease pairings, the quality of the underlying data is critical, and poor-quality data can lead to inaccurate predictions.
- The review process by Fajgenbaum's team is crucial, but it may introduce human biases and is dependent on the expertise and judgment of the reviewers.
- Repurposing existing drugs for various diseases is promising, but it may sometimes overlook the development of novel drugs that could be more effective or have fewer side effects.
- Identifying drug repurposing opportunities through AI is a significant advancement, but it is only the first step, and the subsequent validation and clinical trial processes are resource-intensive and can still fail.
- Collaboration and federal contracts such as the one EveryCure holds with ARPA-H are essential for funding, but they may also come with specific expectations and deliverables that ...
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