Dr. Janine Sengstack and Rob Cahill, founders of the startup Junevity, are on a mission to extend lifespan and healthspan by combining AI and large scale omics data with genetic medicines known as “siRNAs”. Their cellular reset platform promises to create medicines that can reset each of your organs back to a healthy and youthful state.
This year, Junevity successfully restored “18-year-old metabolism” in animal models allowing mice on a high-fat diet to lose fat while retaining muscle. This candidate therapy may become the first known drug to rejuvenate metabolism. Since our recording, Junevity doubled their seed round funding up to $20M to advance this work into human clinical trials, which means we might see their first rejuvenating medicine in the clinic as soon as the second half of next year.
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Timestamps
1:24 Junevity’s Cell Reset Platform
2:42 The science behind the platform
7:20 Rob’s transition from exited tech founder to biology student
11:43 What makes for good co-founder relationships
14:57 Why right now is the moment for longevity biotech
16:50 Black box AI vs traditional biology
20:28 Advantages of siRNAs for cell reset
35:27 The primary challenge in all preclinical work today
47:49 Timing for achieving longevity escape velocity
54:01 The Ozempic or ChatGPT moment for longevity
1:01:40 Bottlenecks to accelerating longevity
1:06:14 What’s next for Junevity
Transcript
00:00 Intro
Daniel 00:00:00
Welcome to the Free Radicals podcast. We interview the scientists and builders working to revolutionize biotech, dramatically extend human lifespan, and bring about a sci-fi future where humanity has full control over biology. I am your host, Daniel Shur, and my co-host is Eric Dai.
Today’s guests are Dr. Janine Sengstack and Rob Cahill, founders of the startup Junevity. Their company is on a mission to extend lifespan and healthspan by combining AI and large-scale omics data with genetic medicines known as siRNAs. Their cellular reset platform promises to create medicines that can reset each of your organs back to a healthy and youthful state.
This year, Junevity successfully restored 18-year-old metabolism in animal models. This allowed mice on a high-fat diet to lose fat while retaining muscle. This candidate therapy may become the first known drug to rejuvenate metabolism.
Since our recording, Junevity doubled their seed round funding up to $20 million to advance this work into human clinical trials. This means we might see their first rejuvenating medicine in the clinic as soon as the second half of 2026.
I hope you enjoy this interview. Thank you for joining us on the podcast, Dr. Janine Sengstack and Rob Cahill. Janine, can you tell us what Junevity’s cell reset platform is?
01:24 Junevity’s Cell Reset Platform
Dr. Janine Sengstack 00:01:24
Absolutely. The cell reset platform focuses on developing new therapeutics to transform cells from a disease state back to a healthy state. We achieve this by combining siRNA, AI, and large-scale omics data.
By bringing these three technologies together, we can pursue the idea of rejuvenating metabolism. We aim to identify the key regulatory gene, specifically a transcription factor, that controls this process. Our drug, an siRNA, then represses this gene to restore cells and tissue to health, thereby treating the disease.
Daniel 00:02:01
Excellent. Is Junevity a longevity company, and what does that entail?
Dr. Janine Sengstack 00:02:06
I view longevity companies as those aiming to increase healthspan and lifespan. Our mission at Junevity is precisely that, making us a longevity company.
Our long-term approach is to create a specific medicine for each tissue. We do not believe one drug will restore the entire body to health. Instead, we anticipate developing therapies such as a liver drug, a heart drug, or a brain drug. Our cell reset platform allows us to tune the system, moving a tissue from a diseased state back to a healthy state.
02:42 The science behind the platform
Daniel 00:02:42
I would love to understand the science behind the platform. Could you provide an overview of your PhD research, which I found very interesting, and explain how it forms the basis for Junevity?
Dr. Janine Sengstack 00:02:58
The underlying hypothesis is that the transcriptional state of a cell or tissue defines its identity and behavior, including which proteins are expressed or suppressed. If you can revert a disease state or an aged state to a different state, this can undo damage and restore health.
The first proof point of this concept is the Yamanaka factors. Overexpressing these three or four transcription factors can dedifferentiate a cell, effectively turning back time to a stem cell state. While remarkable, applying this clinically is challenging because overexpression is difficult to achieve safely and manufacturing is complex.
Our goal was to identify new transcription factors that could be targeted individually, avoiding combinations for simplicity and safety. Ideally, we wanted to repress these transcription factors, which is generally a safer approach. Repression means fewer molecules are present in the system, reducing the chance of incorrect interactions. Furthermore, transcription factors are often overexpressed in cancer, making repression a safer option.
My PhD work focused on developing the reset platform to identify such transcription factors. We searched for those that, when repressed, could revert cells to a healthier state. After creating and proving this system in a cell culture model, its success prompted us to spin out Junevity. Our aim was to accelerate the technology’s path to patients and expand the reset platform into the broader system it is today.
Daniel 00:04:34
Regarding your PhD research, we’ve hosted several partial reprogramming companies on the podcast. I’m always interested in understanding how these experiments are designed to discover transcription factors.
My understanding is that you run large-scale perturbation experiments on cells, activating or inhibiting various transcription factors, and then observe the resulting readouts for aging or other biomarkers.
When different teams, whether companies or academic labs, are building these platforms and researching partial reprogramming, how do their approaches differ? What are the critical factors that determine success in finding the right therapies?
Dr. Janine Sengstack 00:05:24
There are multiple paths to success in this area. Different companies and academic labs are approaching partial reprogramming in various ways, and I hope they all succeed.
Some approaches involve using small molecules to activate or inhibit different pathways. While this is promising, it is challenging to make a small molecule highly specific for a single transcription factor. Others are pursuing cell therapy, which involves extracting cells, engineering them, and reintroducing them into a system. This is an exciting approach, but also presents challenges in terms of complexity. Additionally, some researchers are using CRISPR screens to knock out genes and assess the benefits.
The field is actively exploring partial reprogramming from many angles, and this is just the beginning of its therapeutic potential. Aging and rejuvenation biology has been building for years, but it is truly taking off now.
Our approach at Junevity focuses on repressing single transcription factors. From a safety perspective, repressing a gene is generally safer. Physically, fewer molecules in the system mean fewer chances for incorrect interactions. Furthermore, transcription factors are often overexpressed in cancer states, making repression a safer option.
From a drug development perspective, siRNAs offer a well-established pathway to the clinic. There are currently seven FDA-approved siRNAs, demonstrating their ability to safely and specifically repress target genes.
07:20 Rob’s transition from exited tech founder to biology student
Daniel 00:07:20
Amazing. I have several follow-up questions about siRNAs and their clinical timeline. However, I want to introduce Rob first. We can save those questions for later.
Rob, could you tell us about your background, how you met Janine, and what excited you about Junevity?
Rob Cahill 00:07:36
I was in tech for the first 15 years of my career, perhaps somewhat similar to you, Daniel. I had built a company, sold it, and was working at the acquiring company. At that time, my godfather developed Parkinson’s, and my mom began falling and experiencing breaks. I realized that aging and these diseases are coming for all of us. This experience inspired many people, including me, to work on aging.
I questioned whether I wanted to build the next software product or address the inevitable challenge of aging. With young children, I wanted to ensure I would be there for them long-term. I made a full career switch into biotech.
A challenge in biotech is the difficulty of entry without specific subject matter expertise. Unlike tech, where generalist roles are common, biotech offers few such opportunities. I returned to academia, taking numerous classes, including organic chemistry, and worked at UCSF. I also completed Johns Hopkins bioinformatics training. I loved it.
I transitioned from leading a 120-person team to coding all day. It felt like I was in grad school or college again. While enjoying the research, I also sought to connect with aging-focused professors at Stanford, UCSF, the Buck Institute, Berkeley, and other institutions. I was introduced to Hal Lee, a professor at UCSF and an expert in transcription factors.
I spoke with him, expressing my admiration for his research and my desire to collaborate. He suggested I meet his grad student, Janine, who was starting a company, noting my prior experience in company building. Hal introduced us. We met for numerous coffees in Mission Bay, walking and getting to know each other while I learned about Janine’s science and vision.
I realized I could spend four or five years on research, but Janine’s work was more impactful than anything I could achieve independently. She was the first person to show that repressing a single transcription factor can reset a cell state from a diseased age to a healthy state. Nobody had ever shown that before. This seemed like a high-risk, high-reward opportunity worth pursuing. We decided to pursue it, and that was about two years ago.
Daniel 00:10:03
Janine, when you met Rob, what aspects of his company-building experience made you excited about him as a co-founder?
Dr. Janine Sengstack 00:10:11
I had been considering starting a company for over a year. I knew I needed a co-founder to enhance the experience and significantly improve my chances of success. I possessed the scientific background, but I sought someone with expertise in business, company building, and operations. Starting a company involves many layers beyond what is learned in grad school. I even tried co-founder dating apps, which proved to be a complete failure.
Then, at the perfect time, Rob was introduced to me. I immediately recognized he was an ideal fit. Our working styles meshed well, our communication was effective, and our enthusiasm, intensity, and pace for advancing science and longevity were perfectly aligned with our mission. We spent countless hours getting to know each other over coffee walks, discussing our life goals, ambitions, career aspirations, and how to integrate these elements to ensure a strong partnership. It became clear that this was a perfect partnership.
As I was finishing my PhD, we decided to try raising funds. The week I graduated, we secured our first check and were off to the races.
11:43 What makes for good co-founder relationships
Daniel 00:11:43
Eric, you were an investor for a while. You have seen many co-founders and founders. What makes for a good co-founder pairing in biotech?
Eric 00:11:55
It’s a great question, Daniel. Ultimately, any company must accomplish its mission objectives, which include transforming investor capital into an enterprise that delivers exceptional value. For a biotech company, the ability to navigate the various stages of therapy development is crucial. This ranges from forming the therapeutic hypothesis and establishing preclinical R&D programs to understanding how to translate those into an Investigational New Drug (IND) application and a Phase 1 trial. Each stage of this business requires very distinct skill sets.
A strong co-founder pairing possesses the comprehensive skills needed for every business stage, along with the resilience and personal rapport to evolve as the business progresses. Phase 1, Phase 2, and Phase 3 trials differ significantly, as do preclinical R&D, animal models, and in vitro models. These stages are dramatically different. Founders must collectively possess the necessary skills and be willing to evolve and grow together.
Dr. Janine Sengstack 00:12:56
That’s totally right. I’d also like to mention our third co-founder, John Hookman, who is our CEO. John successfully navigated his PhD project from concept to FDA approval, raised several hundred million dollars, and took a company public. He is the first person I’ve met to achieve this feat with a PhD project. He is the perfect complement to our diverse skill sets.
The three of us collaborate effectively as a team. Each of us excels in different areas, allowing us to collectively strengthen the company and advance our goals. It’s a great partnership.
Rob Cahill 00:13:37
It is interesting. I have seen that three co-founders can be an unstable equilibrium. This has not been the case for us. I believe it is due to the right combination of skills, as Janine mentioned. John’s unique ability to bring ideas from conception through the clinic, having done so with multiple programs, is particularly unique. The three of us truly work well together.
Another point about Janine: when I first met her, HAO invited me to their lab meeting. I arrived, never having met Janine, to a lab meeting filled with very senior scientists. Janine was leading the meeting. I wondered, “Who is this PhD student leading the entire session?” All the scientists agreed to her direction. I realized Janine was not only brilliant but also possessed strong communication and leadership skills. She excels at public speaking; you might have seen some of her early YouTube videos from high school.
This unique combination defines our mission. Our goal is to develop medicines that extend healthspan and lifespan, ideally within 30 or 40 years, if not sooner. The mission, combined with her intelligence and leadership ability, made me realize she would be a prominent leader in biotech for a long time.
Dr. Janine Sengstack 00:14:55
Thanks, Rob.
14:57 Why right now is the moment for longevity biotech
Daniel 00:14:57
Rob, you made a significant pivot from tech into longevity. What gave you the conviction to jump into longevity now? What made you believe you could make a tangible impact?
Rob Cahill 00:15:11
I did not know at first. I only knew it was a problem I wanted to solve. If you fall in love with the problem, everything else becomes clear. To impact the problem, I knew I could find a way to support the work.
I contacted college peers in academia, science, biotech, and pharma, asking if it was truly possible to extend healthspan and lifespan. After reading numerous papers, I learned that this is an opportune time. We can anticipate real healthspan and lifespan therapies coming to market within the next 10 to 20 years. This is due to the exponential growth of omics data combined with AI, new delivery modalities like siRNA, CRISPR, and mRNA, and a foundational understanding of aging. Thirty years of robust foundational biology work underpins this progress. When these factors combine, numerous exponential curves converge, and significant advancements are possible.
For me, having a mission makes it easier to push through difficulties. I took a 90% pay cut and returned to a very different situation, often confused as I learned new concepts. That mission provides the drive to persevere. Currently, the biggest constraint in longevity is talent and energy. We need people willing to dedicate their careers and time to this field. When such individuals enter the industry, funding, talent, and drugs follow. Anyone interested in longevity, I am happy to discuss how to make that transition. We need more people willing to make that shift and work on this important mission.
16:50 Black box AI vs traditional biology
Daniel 00:16:50
Regarding the trends you described that make this an opportune moment, I see two distinct approaches: first, the fundamental understanding of aging biology, which is traditional biology. Second, there is the AI approach. This involves understanding biological processes, or using AI as a “black box” where a transcription factor leads to a desired result through an unknown cascade. We do not necessarily know how it works.
Of course, these approaches are connected; aging biology informs our experimental design, and our experiments then deepen our understanding. Would you view these as opposing viewpoints? Does Junevity prioritize good experiment design and data, letting AI provide the answers, without much concern for fundamental biology? What are your thoughts?
Dr. Janine Sengstack 00:17:48
I definitely care about fundamental biology. That is the short answer. I view them as paired, not necessarily opposing. While they could be set up as opposing, that is not Junevity’s approach. We integrate AI into each step of our process, but we avoid a “magical black box” approach where AI simply dictates a gene without explanation.
We aim to understand why a specific transcription factor is highly predicted. What pathway is it related to? Is it driving inflammation? We know, for example, that neuroinflammation can be a driving cause of certain CNS diseases. Alternatively, this factor might be crucial in lipid or glucose metabolism. If we are resetting metabolism, perhaps for type 2 diabetes, back to a healthier state, that factor and its regulators could be critical.
AI is a critical aspect across multiple steps of our process. However, understanding the fundamental biology and genetic links of each factor to the disease of interest is crucial for several reasons. First, we want to understand why a specific drug or gene is a viable therapeutic target. Additionally, a deeper understanding of the underlying genetics and biological connections significantly increases the chance of successful translation from in-silico ideas to cells in a dish, to animals, and ultimately to people. This translation is critical. Combining underlying biology with AI predictions, applications, and genetic links leads to the translation we seek.
Eric 00:19:26
I believe AI is not necessarily distinct from fundamental biology. AI allows us to generate different mechanistic or statistical insights from very large datasets. Traditional molecular biology, or what some call fundamental biology, involves a long, integrated history of literature asserting that specific pathways are important for certain diseases. However, modern biology recognizes that these processes occur as systems of pathways and complex molecular networks, not isolated events.
AI does not seek to rewrite all of fundamental or traditional molecular biology. Instead, AI highlights that traditional molecular biology represents a narrow slice of the total integrated view of biology. AI enables a more systemic understanding of how biology truly functions. Sometimes, AI generates non-traditional therapeutic hypotheses or viewpoints that humans might not otherwise discover. Nevertheless, it remains fundamentally rooted in data and molecular biology at its core.
20:28 Advantages of siRNAs for cell reset
Rob Cahill 00:20:28
One interesting aspect for us, concerning transcription factors and siRNA, is that the technology is roughly there today. We do not need huge breakthroughs in AI, measurement, or delivery to create cell-reset drugs for most major tissues in the body.
Imagine what the world could be like in 20 years. You visit your doctor and receive measurements of your tissues. For instance, they might tell you your liver is aging in a certain way, your skin looks unhealthy, or your brain is aging. You then receive a cocktail of cell-reset drugs delivered by siRNA. These drugs target the correct cell type and tissue, and you take them every six to twelve months under your doctor’s supervision. This process resets the tissue and cells.
Transcription factors have been challenging to target for several reasons. First, they were considered undruggable because they are floppy proteins, making it difficult for small molecules to bind. Pharma companies largely avoided them, even though they represent the most powerful genes in the body. Second, understanding their full range of effects and potential off-target effects was difficult. Two years ago, when we approached pharmaceutical companies, their response was often, “Transcription factors are too risky. Stay away.”
This perception is changing due to the abundance of exponentially growing data. AI allows us to decode this information, as Eric mentioned, leading to an open target space where many previously undruggable targets are now accessible. Therefore, we do not need the most advanced AI models or data that does not exist today to identify excellent initial targets.
Daniel 00:22:07
Can you explain what siRNAs are?
Dr. Janine Sengstack 00:22:09
Certainly. To explain siRNAs, it helps to first consider mRNA, which many people know from the COVID vaccine. mRNA is essentially an instruction manual telling your cells to make more of a certain protein.
siRNA, or short interfering RNA, is the mirror image. It is a silencing RNA that tells your cells to make less of something. It is an instruction to your cell: “If you see this sequence, bind to it and reduce the production of that protein.” siRNAs are an elegant and highly specific way to repress or turn off genes.
The mechanism involves an RNA strand approximately 20 nucleotides long. This strand binds to a protein complex called RISC, which then patrols the cell to find a matching mRNA sequence. Once found, RISC labels that mRNA for degradation, preventing it from being translated into a protein.
siRNA has been in development for 15 to 20 years by large pharmaceutical companies. This extensive research was crucial because they had to solve many challenging issues to make it a viable drug. For instance, if you simply introduce siRNA into the system, it degrades quickly. However, over the years, chemists and biologists developed chemical modifications to stabilize siRNA. Now, a single dose of siRNA can last three to twelve months in the body, which is remarkable.
Compared to small molecules that clear quickly, siRNA’s durability is exceptional, and they are also highly specific. They entirely overcome the transcription factor specificity problem we discussed. Instead of targeting the floppy protein directly, which presents a difficult binding pocket for drugs, siRNA targets the mRNA before it even becomes a protein. This allows for highly specific and durable knockdown.
Additionally, there have been advancements in tissue-specific delivery. For example, a modification called GalNAc allows siRNA to specifically target hepatocytes. Many FDA-approved drugs use this liver-specific delivery. Significant advancements are also being made in CNS and other tissue deliveries.
Daniel 00:24:23
As you spoke, I made a note about tissue targeting, which you immediately addressed.
Eric 00:24:29
One grand challenge with siRNAs, which I would like to explore further, is identifying the correct target initially. The second challenge is ensuring sufficient therapeutic siRNA payload reaches the target cell containing the mRNA. How are you innovating in these two areas, or are you leveraging existing innovations from literature or other companies?
Dr. Janine Sengstack 00:24:55
It is a mixture. At Junevity, we specialize in developing siRNAs for transcription factors, ensuring they are highly specific and safe. However, the methodology for designing effective siRNA sequences has been well-established over the past 20 years through the work of various companies and academic researchers.
For instance, starting with a gene identified through our reset platform, we rapidly narrowed it down to the top three siRNA candidates that are highly potent, specific, and safe. These are now being developed further as potential human drugs for patients. We accomplished this in under a year. Our speed is a key strength at Junevity, enabling rapid progress in both drug development and gene selection via the reset platform. This includes creating the siRNA drug itself.
Rob Cahill 00:25:53
Your question also relates to how we select our first indication and the level of risk we are willing to take on a program. Targeting a novel transcription factor is inherently risky and unconventional. Therefore, we minimized risk concerning siRNA delivery initially.
Our first indication is diabetes, where we target the liver with GalNAc. This delivery method has existed for over 20 years and has seven FDA approvals, effectively making it an off-the-shelf solution. It is widely accepted that this approach will work. Our primary focus is demonstrating that the transcription factor can reset liver health, thereby improving glucose control and insulin sensitivity. As we develop future programs, we can gradually increase the level of risk on each.
Daniel 00:26:41
If the diabetes program is successful in clinical trials, would it be a cure for virtually all type 2 diabetes?
Dr. Janine Sengstack 00:26:50
It would significantly impact insulin sensitivity. Diabetes patients often take many different medications, and they would likely still take some other medication. Our mouse studies show that when they take our drug, they become much better at sensing insulin. Their glucose levels decrease, and their insulin levels either decrease or remain stable. This means their body’s ability to use its own insulin is greatly improved.
This addresses a high unmet need for diabetes patients. They currently self-administer insulin frequently to compensate for their body’s poor insulin sensing. There is only one true insulin sensitizer available, but it has significant side effects and a black box warning. This makes doctors hesitant to prescribe it, even though it remains a successful and effective drug.
Our drug offers the potential advantage of lacking these negative side effects and providing great durability. Type 2 diabetes patients would appreciate this, as managing multiple medications is challenging. A dosing regimen of every three or six months with SiRNA could significantly improve their daily lives.
Daniel 00:28:05
When I consider diseases of aging, Alzheimer’s comes to mind, which some refer to as type 3 diabetes. There’s a hypothesis connecting them. Are you also exploring Alzheimer’s with the same treatment?
Dr. Janine Sengstack 00:28:17
We are not yet, but we are very interested in the CNS space and are beginning more CNS explorations with our RESET platform. Our CEO, John, previously ran a CNS company, where he received FDA approval and conducted multiple trials, including a Parkinson’s clinical trial.
We are excited to leverage his background and skillset in the CNS field to address more CNS diseases. There’s a high unmet need; Parkinson’s and Alzheimer’s disease are devastating. Interesting data also suggests semaglutide could be beneficial in CNS diseases.
Rob Cahill 00:28:56
Our hypothesis is that Alzheimer’s and Parkinson’s will require different targets. Since each disease involves different cell types and tissues, a distinct transcription factor will likely be necessary.
Regarding delivery, SiRNA has recently been shown to be injected subcutaneously, systemically, and reach the brain to cause deep brain knockdown. This is amazing, as it opens up many potential drug programs. We are very excited to pursue this direction.
Daniel 00:29:25
When you refer to deep brain knockdown, you mean it’s capable of inhibiting RNA gene expression deep inside the brain?
Dr. Janine Sengstack 00:29:33
Yes, exactly. It involves SiRNA passing the blood-brain barrier via a transferrin receptor. An IV dose allows it to reach and cross the blood-brain barrier. Then, it achieves knockdown in various brain regions, which is therapeutically exciting. This avoids invasive injections directly into the brain or intrathecal administration, which would be much better for patients.
Eric 00:30:01
What innovations in molecular development were necessary to enable SiRNA penetration of the blood-brain barrier?
Dr. Janine Sengstack 00:30:08
Decades of amazing science by other researchers made this possible; it is not our specific work. Other scientists figured out many complicated aspects.
One aspect is that for cell-type specificity, you need to identify a receptor highly expressed on the target cell and minimally on other cells. This allows for specific targeting if you attach an antibody or a ligand that binds to that receptor. For example, with the GalNAc receptor, hepatocytes are essentially the only cells that express the receptor it binds to. This allows for highly specific uptake of that type of SiRNA.
Rob Cahill 00:30:54
I’ve heard experienced biotech professionals say that every new tissue unlocked for oligos, such as SiRNA or ASOs, could lead to 20 new FDA approvals. Each tissue has numerous associated diseases. Consequently, there’s a rush among companies to develop cell-specific targeting for other major tissues. This is a very exciting tailwind for us.
31:17 Junevity’s secret sauce
Eric 00:31:17
Is it fair to say that Junevity is best positioned by using the RESET platform to investigate complex and previously overlooked or risky disease biology, while leveraging the tissue-targeting capabilities developed by other players in the field?
Dr. Janine Sengstack 00:31:27
Yes, our ‘secret sauce’ is our ability, as you mentioned, to analyze large-scale, complicated, non-monogenic diseases. These are not driven by a single mutation, but by numerous genes changing their expression. We then identify the correct transcription factor and use SiRNA to repress it.
As Rob mentioned, our initial programs utilize off-the-shelf delivery methods. As we grow and develop, we plan to expand into other methods. There’s an exciting tailwind of advanced cell-type delivery technologies being developed by others that we could potentially integrate.
Rob Cahill 00:31:37
Our diabetes program, for example, is based on an unusual hypothesis. We didn’t specifically search for a target to improve insulin sensitivity. Instead, we reasoned that if we could make the liver act younger, it would likely be better at insulin sensitivity, as a younger liver inherently performs better. This approach has proven successful: we target the liver, gene expression globally returns to a healthy state, and we observe numerous beneficial effects.
This is the proof of concept we aim to demonstrate. In the current generation of biotechs, the focus is on rapidly advancing programs to the clinic. We have kept this in mind, believing that the sooner we can bring a successful program to the clinic and validate our hypothesis, the more it will inspire the next generation of biotechs and pharmaceutical companies to apply this approach to many other tissues.
Daniel 00:32:12
Earlier, I asked about fundamental biological understanding versus the AI ‘black box’. Using the liver example with type 2 diabetes, you mentioned your focus is on non-monogenic diseases. These involve a transcription factor modulating many genes.
Dr. Janine Sengstack 00:33:04
Yes.
Daniel 00:33:21
How well do you understand the pathology of non-monogenic diseases? Can you explain what happens in the liver as it ages and becomes less insulin-sensitive?
Dr. Janine Sengstack 00:33:22
Yes. We conduct a wide range of analyses to fully understand the mechanism at play when we target our transcription factor. We perform RNA sequencing, comparing diseased, healthy, and treated samples to examine different pathways. We also conduct extensive histopathology, where trained pathologists analyze images to assess conditions like fibrosis levels.
With our treatment, we observe a decrease in fat buildup in the livers. There’s also a reduction in gluconeogenesis—the liver’s glucose production. The liver makes less glucose and appears to break down less glycogen, both contributing to lower glucose levels. Additionally, there are many other beneficial changes.
Dr. Janine Sengstack 00:34:22
Hormonal changes can lead to changes in distal tissues. If something changes in the liver, it might secrete a molecule that talks to the adipose tissue. Then the adipose tissue changes to a healthier state, processing lipids better or handling their uptake better, preventing them from bursting open and leading to more lipids going elsewhere. This is multi-organ communication. Even when you target just one tissue, it can have broad effects on other tissues, leading to a healthier overall state.
Rob Cahill 00:34:55
This is something we have learned from your PhD and other work. We thought cell models could provide the clues needed to figure out the right regulatory networks, but they lack the signaling complexity found in actual live humans with disease. We have focused much more on the in-vivo state for our data. I wonder when and how virtual cell efforts will be able to incorporate disease data, as they are currently heavily reliant on in vitro data.
Eric 00:35:25
I have strong thoughts on this.
Rob Cahill 00:35:26
Let’s hear them.
35:27 The primary challenge in all preclinical work today
Eric 00:35:27
One of the primary challenges of all preclinical work today is that in vitro models and animal models are fundamentally disconnected as simulations of human biology from the actual clinical performance of disease biology or an asset in a human. The big disconnect we have been unable to bridge is this divide between the preclinical and clinical worlds.
Whenever you enter a clinical trial, you are relying on previous clinical data, and only minimally on preclinical data, as it is not a good representation of clinical biology. One of the big breakthroughs we will see in the next decade will involve bridging preclinical human models—derived from organoids, IPSCs, or organs-on-chips—with actual patient biology. How can a patient be modeled onto a dish that is not just slightly representative, but completely representative of total human physiology?
Rob Cahill 00:36:38
You are exactly right. This is why we focus on human disease data in our target prediction. We are not using in vitro data; we are not using mouse data to inform our original predictions. We then look for mouse models where the networks appear to be conserved, which means you are likely to find something that would translate to humans. That will be one of the great breakthroughs: harmonizing in vitro cell models with actual human data. This presents a significant challenge for AI.
Eric 00:37:07
Tell us about the Reset platform. What is the core of the platform, and how do you ensure you are mapping real disease biology in an in silico or in-dish context?
Dr. Janine Sengstack 00:37:19
The Reset platform always starts with human disease biology. That is its core underlying data, and we always start there. We examine large-scale omics, such as transcriptomics, from the tissues of patients with the disease versus healthy individuals—for instance, livers of diabetic patients versus healthy patients. Thousands of genes are turned on or off at different levels.
Just looking at which gene is most overexpressed is not sufficient. We need to find the true regulatory transcription factor driving the disease state. Our Reset AI algorithm and machine learning tools analyze gene expression changes between healthy and diseased states. They identify the upstream manager gene—the transcription factor regulating these differences—to determine if targeting it can push the disease back to a healthy state.
We also consider whether this factor, or the genes it regulates, have genetic linkages to the disease. This further supports the underlying biology, confirming that targeting this factor and its associated pathways is a viable strategy. From this analysis, we can conclude that repressing this transcription factor will likely return the disease state to a healthier one. We then test it in in vitro and in vivo models, aiming to best model the disease and progress it forward. Once we are confident in this gene, we create the human siRNA and develop the drug.
39:01 siRNAs for obesity
Daniel 00:39:01
Let’s discuss some of your specific programs. We have covered the liver and type 2 diabetes. I understand obesity is another target. Can you elaborate on that?
Dr. Janine Sengstack 00:39:11
The obesity program aims to restore healthy metabolism. There have been significant improvements in the obesity space recently, with drugs like Ozempic and other GLP-1s. However, they have drawbacks. If you stop taking them, you regain weight quickly. Additionally, many experience discomfort while on these medications.
We searched for a transcription factor that could be targeted to restore metabolism to a healthier state, potentially resetting the body’s metabolic set point for long-term health. This is exactly what we observe in our animal models. For example, in very chunky, adorable mice. They eat a 60% high-fat diet, which is basically french fries all day, every day. With our drug, they gradually and steadily lose weight over time, shedding fat without losing muscle, which is crucial for healthy weight loss.
Notably, they achieve the same amount of weight loss as semaglutide. With semaglutide (a GLP-1), you lose weight rapidly, similar to starvation, but then it gradually returns. Semaglutide will likely be used for many years; it is an amazing drug. Its pathway is entirely separate from our factor’s. We observe exciting additive effects when a mouse is given GLP-1 plus our drug: they look phenomenal and can eat french fries daily while maintaining the weight of a normal mouse.
Rob Cahill 00:39:31
It is like they get their 18-year-old metabolism back; they can eat pizza all day and not work out, yet still stay in good shape.
Dr. Janine Sengstack 00:39:11
The durability is also exciting: if you stop giving them the drug, they maintain their healthy weight for long periods.
Daniel 00:40:50
Do you also see improvements in other health indicators, even if they eat french fries and pizza daily?
Dr. Janine Sengstack 00:41:15
Their blood markers look phenomenal. Their muscle-to-fat ratio looks phenomenal. This is very exciting because it represents some of the best preclinical obesity data we have seen. Every Friday, we would receive an update on their weight, and everyone in our company would crowd around the computer, exclaiming about the flat line and how they hadn’t gained weight. There is a lot of enthusiasm and excitement around this program.
Daniel 00:42:01
How much do you care about lifestyle interventions anymore? When you think about therapies like that coming down the pipeline, does it make you not worry about diet, exercise?
Dr. Janine Sengstack 00:42:15
As someone who loves exercise, it is a little hard to imagine. However, the mouse is the extreme version. They do not care about their health; they simply eat french fries and do not need to exercise.
In humans, I imagine they will care more about their overall health and other interventions. One option could be taking a GLP1-esque drug. Incorporate lifestyle changes during this period. You might then be able to stop taking the GLP1 and use our drug over time. Perhaps every six months, a booster dose could help maintain that healthy weight, complemented by lifestyle changes.
Daniel 00:43:01
Can you speak to in what way is obesity, with a focus on longevity, a disease of aging or is it?
Rob Cahill 00:43:10
Obesity is partly a disease of aging, and partly due to diet and lifestyle. We initially chose obesity because we were inspired by caloric restriction, one of the best-known longevity interventions. It makes tissues younger and has great systemic effects. We knew we could target the SIRNA to that area. We had good human data, and it is a large market. In recent years, it has become one of the hottest markets.
Companies are asking what comes after GLP1s. GLP1s are effective, will become ubiquitous, and soon generic. Pharmaceutical companies seek the next generation of obesity drugs. A successful rejuvenating drug in metabolism could mark a pivotal moment for longevity. If it reaches the clinic, making people’s metabolism younger and having these effects, people will begin to see the potential of rejuvenating drugs.
Dr. Janine Sengstack 00:44:04
Obesity can be considered an accelerated form of aging in many ways. The phenotypes observed in obesity are very similar to those seen in aging, but they occur at an accelerated rate. There are many overlaps. As Rob mentioned, caloric restriction significantly improves healthspan and lifespan. This makes it an exciting way to apply aging biology to metabolism.
Daniel 00:44:35
I appreciate the framing of having the metabolism of an 18-year-old again. Often, discussions focus on disease and treating disease, or with longevity, on healthspan.
Daniel 00:44:48
Lifespan. I prefer the framing of imagining how you felt at 18. You had boundless energy. You could eat anything and did not need much sleep. This is a very powerful image.
Rob Cahill 00:45:02
People might prefer the metabolism of someone aged 25 or 30, as at 18, one can be quite hormonal. Perhaps 25 or 30 is a better age to target.
Daniel 00:45:10
I am 30, and I would prefer to feel how I did when I was 18, or perhaps 25.
Eric 00:45:16
What are some of the challenges with getting this drug to market? What challenges lie ahead as you plan to convert this from a mouse model to human application?
Rob Cahill 00:45:26
The next step is demonstrating this works in non-human primates. While mouse data is encouraging, its efficacy in humans is uncertain. However, metabolism is so similar between humans and primates that if it demonstrates efficacy and safety in a non-human primate, it is believed it will work in humans.
That is our current stage. We have conducted a successful knockdown study in monkeys, achieving target engagement, good knockdown, and no safety signals. We have also completed toxicology studies. If progress continues, we could be in the clinic by the second half of next year.
Daniel 00:46:05
Is that the diabetes one?
Rob Cahill 00:46:07
It is both. They are both at the same stage. We have been progressing them in parallel.
Dr. Janine Sengstack 00:46:11
What is the official name for the monkey study?
Rob Cahill 00:46:19
The Chunky Monkey study.
Daniel 00:46:20
If the chunky monkeys are as cute as the chunky mice.
Dr. Janine Sengstack 00:46:25
The mice are very spherical and top-tier cute. The monkeys, however, really need some help.
Rob Cahill 00:46:32
They have these big beer bellies.
Dr. Janine Sengstack 00:46:34
Their bellies cascade over their feet. The Chunky Monkey study is what we call it.
Rob Cahill 00:46:40
One benefit of starting the company when we did is that raising money has been challenging. Many companies have struggled to get started. There isn’t much funding for preclinical work. Consequently, the cost of development has decreased. We have made significant progress toward the clinic without extensive funding.
Dr. Janine Sengstack 00:46:56
We have also moved very quickly. I am proud of Junevity’s cultural emphasis on intensity and pace to pursue our mission. The team is small but mighty, achieving significant results. This is because our strong mission alignment drives people to do whatever it takes to reach the next step. This fosters much creative problem-solving and parallel execution to advance quickly.
The entire team collaborates and communicates effectively, allowing us to move quickly. Our team ranges from recent graduates to those with 20 years of pharmaceutical experience, blending big pharma and tech backgrounds.
47:49 Timing for achieving longevity escape velocity
Daniel 00:47:49
What is Junevity’s ethos regarding aging? Does Junevity believe longevity escape velocity is imminent, or do you have more tempered expectations?
Dr. Janine Sengstack 00:48:06
From my perspective, we aim to treat aging-related diseases by developing tissue-specific drugs. As a company, we are not focused on reaching 160 years old tomorrow. Instead, we concentrate on a clear pharmaceutical approach to create drugs that address diseases related to healthspan and lifespan.
Rob Cahill 00:48:34
We do not believe there is a single drug for longevity, nor do we think AI will discover one in the next few years, even if it existed. However, resetting multiple tissues is a realistic path using currently available technology. We likely have varying views on how long we want to live.
When I first joined, I thought I might live until 80, so longevity escape velocity would need to be achieved by then. That would be around 2062, so I worked backward to identify the necessary steps. I would love to live a very long time, and I believe it is possible for our generation.
Dr. Janine Sengstack 00:49:17
I am smiling just thinking about how methodical Rob is. He determines the target year, then works backward to create a daily plan of what needs to be done to accomplish the goal.
Eric 00:49:30
My general view, after speaking with many people, including Daniel, Rob, and Janine, increasingly aligns with the idea that there are many different independent modes of aging. These modes are linked in certain ways, but if you can independently address them, you will see small, 5-15% benefits to health span or lifespan. The integrated collection of many of these happening simultaneously will get us to something that approaches longevity escape velocity. It is unlikely in our lifetime that we will reach 200 years old, but perhaps I am being too sober.
Daniel 00:50:05
Come on, you are kicked off the podcast.
Eric 00:50:08
We can edit that out.
Rob Cahill 00:50:09
This is a good debate. My view is that when exponential curves are happening, it is difficult to make predictions, especially with two exponential curves of data generation in biology and AI. We are just scratching the surface on data. Every second, one of our cells creates unfathomable amounts of data, which we are not currently measuring. As we improve our measurement capabilities, things could progress in a very exciting way.
We debated a scenario: if metabolism remained young, the brain stayed young, and cancer death rates continued their current downward trend, how much longer would people live in 40 years? I do not know the answer, but what are your thoughts?
Eric 00:50:58
Probably 110.
Daniel 00:51:01
Eric, Rob is embracing longevity. You should be more like him.
There is an interesting question. My fear is that if many independent pathologies progress, even if 95% are resolved, one will still be fatal. This is the issue: if we cured all cancer, it would only add about two years to lifespan on average, because people would still die from heart disease or other causes.
However, it is exciting that all these pathologies appear related. If you treat one organ, it often helps the rest of the system. Recent research supports this. For example, young cells in an aged environment also age. Is the interconnectedness of these pathologies a reason for optimism?
Dr. Janine Sengstack 00:51:50
Clinical evidence for this includes GLP-1s, which lead to weight loss and many other positive outcomes. Caloric restriction, for instance, shows that sleep apnea improves, Alzheimer’s potentially improves, and heart disease. Many things are connected.
Certain biological aspects, when addressed and improved, likely lead to improvements in many other parts of biology, organs, and tissues.
Rob Cahill 00:52:22
The cancer statistic assumes the current other causes of death. However, if cardiovascular and neurodegeneration were removed from the causes of death, cancer would likely become more prevalent. It would then represent a much larger share of fatalities.
My view is that addressing those big three – cancer, cardiovascular disease, and neurodegeneration – would lead to very significant extensions in life, far beyond two or three years.
Daniel 00:52:45
That is really interesting. I was considering other high-leverage issues we could solve. As people age, their sleep quality declines significantly. The exact mechanisms are not fully understood, but if we could target the tissues responsible, perhaps the part of the brain that releases melatonin?
Daniel 00:53:07
Yes.
Dr. Janine Sengstack 00:53:07
Great, thank you. I do not know much about brain biology, so that is a good point.
Rob Cahill 00:53:12
I watch my kids sleep at night. They sleep 10 hours without issue. It is amazing. You can talk to them, and they do not wake up. It seems rejuvenation might help with sleep.
Daniel 00:53:23
I wonder if anyone is working on that. If older people could consistently get a good night’s rest, it would undoubtedly improve every tissue in the body.
Rob Cahill 00:53:32
Musculoskeletal health is another major area. I have observed it with my parents. Muscle mass decreases, leading to less body control, increased fall risk, and brittle bones. The resulting loss of quality of life, along with conditions like arthritis, is a significant concern. We are conducting early work in osteoarthritis and sarcopenia.
Daniel 00:53:41
Discussing this makes me very optimistic.
54:01 The Ozempic or ChatGPT moment for longevity
Daniel 00:54:01
If we can target a few of these tissue-specific diseases, there is clearly significant benefit for everyone.
However, I believe most people are unaware of the topics we are discussing. This is why we are excited to do this podcast. When people hear “longevity,” they typically think of lifestyle improvements, not these types of therapies coming down the pipeline. How do you feel about the current public discourse around longevity?
Rob Cahill 00:54:01
Deep down, people know longevity is a good thing, but the prevalence of snake oil, false promises, and supplements has created an expectation that it will not happen. By revealed preference, however, people generally want to live longer and healthier lives.
What will change is the “Ozempic moment” or “ChatGPT moment” for longevity. Perhaps Ozempic is already that moment for longevity. As soon as a drug in clinical trials gains public attention, people will start to see the potential. Part of our hope is to move rapidly to the clinic and generate something that excites the public imagination.
Currently, there are only about 200-300 VC-funded longevity companies. There could be 10,000. Every biotech and pharma company could become a longevity company. Eli Lilly, for example, is already becoming a longevity company in many respects.
Dr. Janine Sengstack 00:54:29
I agree with Rob. There are many ways to apply disease identification and treatment to the longevity space. As you said, an Ozempic moment for longevity may be coming, or perhaps Ozempic itself will demonstrate its significant impact on health span and lifespan.
Daniel 00:55:30
This also makes me consider the powerful images in longevity and biology. With SpaceX and Elon Musk, rocket launches are tangible, visible events that inspire people. In biology, however, there are not as many exciting visual developments.
If something goes to the clinic and we see a rejuvenated human—someone who visibly looks younger—or if we see significant weight loss, Ozempic provides an example. You see everyone around you become thinner. Perhaps it is these types of obvious health improvements that will create impactful imagery.
Dr. Janine Sengstack 00:55:47
I do not have a compelling, rocket-launching idea at the moment, but I will consider it.
Rob Cahill 00:56:30
I know what it is: skin.
Daniel 00:56:37
I was going to ask.
Rob Cahill 00:56:41
Janine’s PhD focused on skin fibroblasts. We have some good skin targets. The problem getting this to the clinic is the lack of good animal models for skin, and the ex vivo models are not effective.
If celebrities suddenly embrace this, consider how 60-year-olds already look like what 40-year-olds used to. This could accelerate the trend. If celebrities started taking a drug that makes their skin plump and young, like an 18-year-old’s, rather than just preventing movement like Botox, that would be transformative.
It’s interesting; I discussed this with my wife. She isn’t excited about the idea of living forever, but she said, “Wait, you’ll make my skin look younger? My friends and I are completely on board for that.”
Dr. Janine Sengstack 00:57:28
We already have a clinical trial waiting list. Many would want to sign up.
Eric 00:57:32
I know a company you might want to meet. It was started by a very famous singer and her fiancé. They utilize skin explant organ-on-chip models. This technology allows them to take actual skin explants from patients worldwide and keep them viable for significantly longer periods. This enables testing the effects of various bioactive molecules on the skin, measuring aspects like wrinkle density.
Rob Cahill 00:57:59
That would be great. We previously received skin chunks from tummy tuck surgeries; the centers would place them on ice and send them to us.
Dr. Janine Sengstack 00:58:09
We would receive small skin samples in our lab. One time, a small hair was growing out of a sample. It was a bit gross, but it emphasized how real the tissue was.
Rob Cahill 00:58:18
But they didn’t live long enough.
Dr. Janine Sengstack 00:58:19
No, they didn’t live long enough.
Rob Cahill 00:58:20
They were like flowers in a vase, living only for a few days.
Daniel 00:58:23
My hypothesis is that solving skin aging would be challenging. I’m not very familiar with the pathology of skin aging. However, I believe a lot of extracellular matrix components are involved, which seems difficult to target with current approaches.
Dr. Janine Sengstack 00:58:41
There is hope for it. A benefit is its accessibility; we don’t have to worry about targeting as much as with complex internal organs. Another reason I believe it’s possible is the existing knowledge regarding collagen expression and water retention in the tissue.
Initially, it was challenging because a clinical trial is required, and the product would compete with readily available over-the-counter options. Therefore, cost presents another challenge. However, as our platform develops and proves its efficacy, this becomes a viable option. I believe everyone wants this to happen, but we haven’t achieved it yet.
Rob Cahill 00:59:27
I’m also interested in replacement therapies as another path to longevity. I recall seeing early studies at UCSF where neurons were grown in a dish, then injected into mice with Parkinson’s. These neurons were integrated into the brain’s substantia nigra, where neurons were dying, improving symptoms.
To me, that’s a very exciting route, alongside partial reprogramming. This technology just completed a phase one trial, demonstrating safety and successful uptake.
I’m unsure if skin would be suitable for this. When explants were mentioned, I wondered about transplanting younger skin. However, for livers, it makes sense.
Eric 01:00:09
That reminds me of the movie, Silence of the Lambs.
Rob Cahill 01:00:12
That’s not the image we want to evoke.
Eric 01:00:16
It puts the lotion on.
Dr. Janine Sengstack 01:00:18
God.
Eric 01:00:20
Regarding IPSCs, there is exciting work happening, and I agree we are in the early stages, perhaps at a GPT-1 or GPT-2 level for IPSC-derived replacement therapies. My graduate studies in tissue engineering focused on primary stem cells, primarily mesenchymal progenitor cells. I have always been fascinated with the idea of replacing tissues using stem cell-based platforms.
Now, data from companies like Neurona and BlueRock Therapeutics show that IPSCs can create seemingly functional dopaminergic neurons. These can be implanted into patients, reconstituting the original function of lost dopamine-producing neurons. This is a really exciting proof of principle.
Research from China also demonstrates that IPSC-derived pancreatic beta islet cells can reconstitute, effectively curing many insulin resistance effects of Type 1 diabetes. We now have multiple proof points from independent labs and clinical trials worldwide. Therefore, we are at a post-existence proof stage, where IPSCs appear to recapitulate the foundational biology of how cells should behave. This is very exciting.
1:01:40 Bottlenecks to accelerating longevity
Rob Cahill 01:01:40
More reasons to be optimistic. There are significant tailwinds behind aging, driven by economies, governments, and the population. The global population is aging considerably. Most of the world’s wealth is held by people aged 50 or older. When people are 50 or older, they often think about knee pain or neurodegeneration. Consequently, money will continue to flow into this industry.
A question I’ve always had is: what are the current bottlenecks? Is it people, money, or science? What can we do to accelerate the industry?
Daniel 01:02:20
That’s the big question. One of our podcast goals is to address this. I agree that talent is consistently a problem. We simply need more talent and more funding.
More broadly, I believe people are not optimistic about the future in general. There are many negative events, and people fear what might happen with AI. I think we need something positive to anticipate. This is why it’s exciting to me: the image of someone remaining young and healthy, with the metabolism of an 18-year-old. That could be our future, as opposed to decline and death. We need optimistic goals to work towards.
Eric 01:03:07
We need to make it less risky to be in biotech and longevity. Everyone is subjected to and can select from different tiers of risk. Currently, we have relatively low confidence for any therapeutic program or biotech company to succeed, purely from a statistical basis. If Ozempic-like moments—representing both clinical and commercial breakthroughs—occur regularly, as they already do in tech, it will feel less risky. People would be more willing to work at a startup or what could become the Google or Meta of life sciences. We do not have many examples of companies where you can build an entire career and become phenomenally wealthy in life sciences. It needs to be less financially risky to enter life science, which means we need commercial breakthroughs.
Daniel 01:03:55
Related to that, what was the experience like fundraising? Was it really hard to raise money for this idea, or was it easy?
Rob Cahill 01:04:08
It was both. We have raised money in three tranches so far. The first raise happened in a few weeks, even before Janine finished her PhD, with just petri dish data and a dream. That was fast because the potential was huge; an early seed round made sense for a venture investor. We then expanded that to a $10 million round once we had early data. If it were a really hot time, we might have raised a huge Series A by now. With John’s experience, having gotten FDA approval from his PhD project, we probably would have raised a big Series A by now. However, preclinical Series A rounds were not very difficult in the last couple of years, and we were able to raise funds. We have not announced our latest funding, but we raised money recently to give ourselves a runway for almost four years at this point. We can run our first clinical trial if we need to, without raising more money or needing a pharma partner. We have had a good team, and we hit so many of the big buzzwords like longevity, AI, obesity, and metabolism, which made it easier.
Dr. Janine Sengstack 01:04:26
siRNA has gotten hotter recently. Two years ago, when we spoke to people, we had to do more convincing, explaining why it was a good idea. Now, when I say “siRNA,” they immediately respond, “Oh yeah, great idea. Moving on.” There has been more excitement and momentum in that space as well.
Daniel 01:05:26
Related to hitting all the right buzzwords, you included longevity. Is longevity a buzzword that helps get funding in this environment?
Rob Cahill 01:05:48
It depends on who you are talking to, of course. For a traditional biotech VC, maybe. People look at the market size and see pharma companies starting to set up programs for it. It is becoming more and more of a positive, especially with crossover investors or tech-style investors, where it is a big positive.
1:06:14 What’s next for Junevity
Daniel 01:06:14
What is on the horizon for Junevity? Do you have clinical trials coming up next year or further in the future?
Dr. Janine Sengstack 01:06:15
Our current “Chunky Monkey” study is for type 2 diabetes and obesity. We will get data for that by the end of this year, which will inform if we move forward into clinical development right away. We have several other programs we are excited about and are moving into, like the CNS program we mentioned earlier, diving into that more. The RESET platform is always running. We are constantly discovering new exciting candidates and targets for new indications. We want to pursue leads, but we also want our platform to be robust and pursue a wide range of diseases related to longevity.
Rob Cahill 01:06:23
I have wondered why there are no really big biotech companies. There are a few examples like Alnylam and Regeneron that have grown. It seems like tech companies achieve economies of scale, positive momentum, and reinforcing loops that you do not quite get in biotech with each new clinical program. There is not much synergy, advantage, or data advantage. How do you build a biotech company that has those benefits? It probably involves some form of data or measurement combined with AI. Imagine building a company that becomes the best at measuring human tissue health, enabling the development of personalized RESET therapies—the right cocktail for each person at the right time—with an in-vivo, blood-based transcriptomic monitor. That would provide a real advantage to run multiple programs. I think we will start seeing companies like that built in the next five to ten years.
Eric 01:07:09
I agree. I have been contemplating the concept of “platform escape velocity” for the past couple of years. All biotech companies are typically categorized as either asset-focused or platform-focused. The perennial challenge we have observed is that platform-focused biotechs are incredibly sensitive to the macro-environment. They capitalize on richer, more liquid ecosystems when fundraising is easier. The hope is that if you raise enough capital and your platform works, you can reach this point of escape velocity, enabling you to deliver on the platform’s promise: endlessly generating assets with increasing marginal benefit, one after another. The reality is that very few platforms have ever truly delivered on that promise. Prime examples might be Amgen, Regeneron, Alnylam, or Vertex. While there are a few successes, we have mostly seen more failures than real success stories. Where the future is going, if we can realize even one instance of this platform concept working, we achieve the escape velocity of the platform. This is built on a moat of progressive and integrated data generation. As you said, this leads to an improved probability of success from identifying and prosecuting a target, with that process resulting in an even better probability of success for the next program. That would be incredible to see, but I do not know if we have truly seen that yet, to be honest.
Dr. Janine Sengstack 01:08:14
Agreed. It is really tricky.
Daniel 01:09:40
But there are some trends around measurement and AI that indicate it is possible. I want to end on a positive note.
Dr. Janine Sengstack 01:09:42
We are going in that general direction.
Eric 01:09:50
I am bullish.
Rob Cahill 01:09:54
We could each say what the next company we would start, or perhaps a company we would start within Junevity if we get big enough.
Rob Cahill 01:10:00
Do you want to start, or should I?
Dr. Janine Sengstack 01:10:01
You start.
Rob Cahill 01:10:02
I have always thought about a measurement company. There is a growing belief that glucose monitoring might be possible through an Apple Watch, for example. The focus would be on measuring human data in real time, specific to diseases. Companies like InsideTracker or Function are already starting in this area, but the goal would be to use that data for drug development. This is probably not the most original idea, but it is something I would love to work on.
Dr. Janine Sengstack 01:10:32
I love animals, and animal testing pains me. While it’s necessary now to ensure drug safety for people, I envision a better future.
In an ideal world, I would establish a retirement farm where animals could live out their lives. Alternatively, and more realistically, we could improve our modeling and expand our genetics knowledge. This would involve enhancing in vitro or ex vivo models to reduce the need for animal testing. Animal testing will likely still be necessary for many years, but reducing reliance on it would make the animal lover in me very happy.
Daniel 01:11:12
Where can people learn more about both of you and Junevity?
Dr. Janine Sengstack 01:11:16
They can visit Junevity.com. They can also read an article we recently wrote titled “Unlocking Transcription Factor Therapeutics,” and explore various other podcasts and content we have produced.
Daniel 01:11:31
Thank you for joining us.
Eric 01:11:33
Thank you.
Dr. Janine Sengstack 01:11:34
Thank you for having us.
Daniel 01:11:35
Thank you for listening to this episode of the Free Radicals podcast.
If you enjoyed this episode and would like to support us, please share it with a friend who might also enjoy it. Also, leave us a five-star review on Spotify and Apple Podcasts, and like and subscribe on YouTube. Your support means a lot.
I’m Daniel Shur, and my co-host is Eric Dai. Thanks for listening.
