Welcome to Partnology’s Biotech Leader Spotlight Series, where we highlight the remarkable accomplishments and visionary leadership of biotech industry pioneers. This series is about showcasing the groundbreaking strides made by exceptional leaders who have transformed scientific possibilities into tangible realities. Through insightful interviews, we invite you to join us in following the inspiring journeys of these executives who continue to shape the landscape of the biotech industry. This week we are recognizing:
Pranav Sharma is the Founder and CEO of Xosomix, a biotechnology company focused on the use of exosome based platform technology for drug delivery, diagnostics, and therapeutics with a focus on neurological disorders and endometriosis. Previously, during his time at Scripps Research Institute, he made critical scientific contributions towards understanding the role of exosomes in neural circuit development and synaptic plasticity, how neuronal circuit activity regulates integration of new neurons from stem cells inside the brain, discovered a novel pathway of endocytosis, and developed an advanced nanoscale microscopy to elucidate the ultrastructure of lipid rafts in live cells. He obtained Ph.D. in biophysics and cell biology from National Centre for Biological Sciences, Bangalore, India with postdoctoral work at CSHL, Cold Spring Harbor, NY and Scripps Research, San Diego, CA.
You spent over a decade in academia building foundational discoveries in neuroscience and extracellular vesicles. What was the specific moment when you realized this science had to live outside academia—and become a company?
There wasn’t really a single “aha” moment or defining turning point. It was something that built gradually over time, slowly but surely, pulling me in a particular direction. The drive that fuels our direction in life is almost always personal. I don’t have courage to talk about it publicly yet but my career shift into neuroscience itself was fueled by personal reasons to do something about neurological disorders, specifically developmental neurological disorders. With this background, there were a few factors that nudged me along the way.
First, I genuinely love academia. Academia is the foundation of everything we do in translational research, and one of the things that makes it great is that it’s slow—you have time to think, explore, and let ideas wander. But that also means that discoveries made in academia often take a long time to move into translational research. At a certain point, especially when you’re motivated to see real-world impact, you start to feel that you’ve made meaningful, landmark discoveries and that it’s time to push them forward more quickly. The question becomes: how do you make that happen faster?
The second—and equally important—nudge came from interactions with industry. When I spoke at meetings, people from industry would often come up to me afterward and say, “This is such a nascent field. We really wish someone like you were working on these early problems with us.” Hearing that repeatedly made an impression.
And the final, most important aspect is feasibility and logistics. I had deep technical expertise, platform technology and scientifically sound roadmap to transform therapeutics in neurological disorder. However, no matter how sound scientific and business plans are, we need money to realize it.
When all of these factors came together—along with a moment when someone was ready to sign a contract to use our platform technology in an area far removed from our core focus—it felt like a compelling reason to found a company and make the jump to the other side.
You worked on Rett Syndrome years before exosomes were “hot.” What did you see early that the broader field initially underestimated or misunderstood?
In my opinion, it’s not underestimated or misunderstood—if anything, it’s the other way around. After an initial slow start, the exosomes or extracellular vesicle field expanded too fast, which is a good problem to have. I have a long background in biophysics, cell biology, and vesicle biology in particular. In fact, one lesser-known aspect of my work is that I co-discovered a novel pathway of endocytosis. Because of that, I was deeply familiar with how vesicles move inside cells—but, to be honest, I had never really looked outside the cell.
So when I first came across reports suggesting that vesicles could shuttle between cells, I was both surprised and intrigued. Neuroscience, as a field, tends to adopt new ideas last because of its sheer complexity—new concepts have to be extremely robust before they’re accepted. Still, as a cell biologist who had spent years studying vesicles intracellularly, I immediately saw the potential of vesicles functioning as long range intercellular messengers carrying complex messages.
Around the same time, there were key discoveries in immunology and cancer biology pointing to important roles for exosomes. That combination made a compelling case in my mind that I needed to at least test the idea. I didn’t have unlimited time or resources, so I designed a very simple, clean experiment. In a developing brain, neuronal stem cells produce essentially all major cell types including neurons to form a neuronal circuit. If exosomes play a fundamental role, then treating neuronal stem cells with exosomes should impact this process.
The question was straightforward: if neural stem cells form neural circuits in a dish under highly controlled conditions, would introducing exosomes affect that process in any way? Would it slow it down, speed it up, or do nothing at all? The outcome would tell us whether exosomes played any role in neural circuit development.
I ran the experiment, and it turned out to be one of those rare moments in biology where you don’t need complex analysis and fancy statistics to see the result. You take a peek under a microscope and it’s clear as a day. Simply treating neural stem cells with neural exosomes caused them to differentiate into neurons about 2.5 times faster than in the absence of exosomes. Even more striking was the specificity: the neural exosomes enhanced neuronal differentiation, but had no effect on the formation of glial cells, the other major cell type in the brain.
The magnitude and specificity of the effect were remarkable. I wasn’t just surprised—I was genuinely excited. Once I became invested in the role of exosomes in neural circuit development, I started looking for a real-world disease context in which to apply these findings.
Neuroscience doesn’t offer many clean disease models. Most neurological disorders are extraordinarily complex, with poorly understood underlying causes. Rett syndrome stood out. While my personal drive was to work on conditions like autism, it’s highly heterogeneous with no clear understanding of underlying cases. But Rett syndrome is monogenic—caused by a mutation in a single gene. Rett Syndrome is also a neural developmental disorder. In fact, it was previously classified within the autism spectrum and has since been recognized as a distinct disorder. As a proof of concept case, the key advantage was that a single genetic cause gave us much tighter control over the conclusions we could draw.
That decision shaped the next phase of our research. Our brain works like a musical ensemble. The neurons fire to produce a pattern of activity very much like an ensemble of musicians playing together to produce a melody. Historically, a vast majority of studies directed towards understanding brain function focused on the skills of the individual neurons or their training together in producing a melody. We found that when these musicians in our brain, called neurons, hang together and socialize, they use exosomes to communicate between themselves. These exosomes contained messages that provided them great collective motivation and were extremely helpful in their training and performance. Extending this analogy to the case of Rett Syndrome, Rett neurons practice very hard but are unable to play together and produce a melody. Rett neurons not only lacked some music skills, they had problems coordinating their music with each other. We found that the Rett exosome no longer contained motivating messages to help the neurons with their music skills and coordination.
We thought that maybe if we take exosomes from healthy neurons and give them to Rett neurons, it will provide them the message they are lacking and help motivate them to play a melody. Remarkably, the exosome message from healthy neurons lets Rett Syndrome neurons overcome their shortcomings and fire together in a synchronous way to produce a melody.
Hence, we went on to show not only that exosomes play a fundamental role in neural circuit development, but that their communication is disrupted in Rett syndrome. The deficient Rett syndrome exosomes failed to drive differentiation of neurons, synaptic growth and circuit function. Importantly, introducing healthy exosomes carrying the correct signals could reverse disease phenotypes.
Around that time, interest in exosomes exploded. In many ways, the opposite of being overlooked happened—thousands of researchers and companies entered the field, and began to realize that it is not very easy to work with exosomes. That surge helped create an important role for people like me, who had been working on vesicle biology for years, to stay actively involved and help guide the field in the right direction.
The graveyard of CNS drug development is filled with therapies that failed at the blood–brain barrier. From a mechanistic standpoint, why do exosomes fundamentally change that equation rather than incrementally improve it?
If you look at neuroscience drug discovery, it is arguably one of the most challenging areas of translational research—not to compare one kind of pain with another, but simply to take a high-level view of the problem. There are three core challenges that define the field.
The first is understanding the underlying cause of neurological diseases. For many conditions, we still don’t have a clear picture of what’s actually driving pathology. The field is now moving in the right direction with focus on all cell types of the brain instead of just neurons. The essential element in this is the intercellular communication between all these diverse cell types via exosomes. With Rett Syndrome work, we have demonstrated that restoring deficient exosomes communication with innate exosomes can be used to cure a disease.
The second challenge is getting drugs into the brain. The brain is a uniquely protected organ because of the blood–brain barrier, which prevents most molecules in the bloodstream from freely diffusing into brain tissue. In other organs, metabolites, antibodies, and therapeutics can often access tissue relatively easily. That simply isn’t the case in the brain. The blood–brain barrier acts as a gatekeeper, and any effective therapy has to navigate around or through it.
The third challenge is the lack of good models to test new drugs and, critically, to quantitatively measure how effective those drugs are in treating the disease. In neuroscience, quantitatively assessing treatment efficacy is especially difficult.
Across these three pillars of neuroscience drug discovery, exosomes can make meaningful contributions. Their role in helping us understand disease biology will take time, but where they have immediate and exciting impact is in drug delivery. Exosomes can transport complex therapeutics that would otherwise be unable to cross the blood–brain barrier, giving those drugs direct access to the brain. In addition, most exosomes also elicit minimal immune responses, which means like Trojan horse, they can safely carry molecules that might otherwise trigger immune activation, especially after redosing.
A third—and often overlooked—application of exosomes is in measuring treatment efficacy. Today, many efficacy readouts in neuroscience are essentially binary: either you see a clear recovery, or you see no effect at all. This creates a major problem. A drug that achieves, say, sub optimal 80% efficacy may be classified as a failure simply because it doesn’t meet a rigid threshold, even though modest optimization could turn it into a successful therapy. Without more sensitive tools, we have no way of distinguishing between a drug that is truly ineffective and one that is highly promising but not yet optimized.
If exosomes can help reveal that level of nuance—showing that a therapy produces meaningful but incomplete benefit—it could fundamentally change how we prioritize and develop neuroscience drugs. In that sense, exosomes can directly impact two of the three major pillars of neuroscience drug discovery today, and over time, contribute to the third as well.
From a CEO perspective, what are the tradeoffs between building a single lead program versus advancing a multi-asset platform in a field as complex as neuroscience?
To be honest, it’s very challenging. The complexity isn’t just about scaling up a new technology—that part is actually becoming more common again. Five to ten years ago, platform companies were in vogue, and now we’re seeing some return to that model, where a single platform generates multiple therapeutic programs.
The real challenge with exosomes at this stage is that the field is expanding extremely rapidly. New and exciting discoveries are happening all the time, alongside a set of technical challenges that are actively being worked through. Some of these hurdles—such as consistent manufacturing of exosomes at commercial scale—we’ve already made significant progress on. Many of the early manufacturing challenges have largely been addressed.
Other issues, like exosome heterogeneity, will take longer to fully resolve. That said, we now understand these parameters well enough to work within them. Importantly, while heterogeneity is critical for scientific understanding and more potent versions of therapeutic products in the future, it’s not expected to prevent effective therapeutic use of exosomes and initial FDA approvals. Remember, at the other extreme, many successful modern medicines started as plant extracts. From an FDA standpoint, the batch to batch consistency and clear demonstration of treatment efficacy are the central issues. The field has made critical progress on both aspects.
The biggest challenge, however, comes from the breadth of exosome biology. Exosomes are not limited to neuroscience. As the field has evolved, it’s become clear that they play critical roles in multiple diseases, including most cancers and conditions like endometriosis—one of our programs that sits outside of neuroscience.
Managing programs across such diverse therapeutic areas, each requiring deep and distinct domain expertise, is inherently difficult. Over the longer term, that reality likely points toward spinning out separate companies or entities that can focus more deeply on these individual areas while continuing to leverage the same underlying exosome platform.
Brain disorders represent a ~$100B market, yet patient reach and efficacy remain limited. What has to change—scientifically or structurally—for that market to finally unlock its full potential?
As we touched on earlier, the neuroscience drug discovery landscape is only going to continue expanding. We are living longer than at any point in human history, and that longevity is exposing us to large-scale neurological disorders that were far less common in the past simply because people didn’t live long enough to experience them.
At the other end of the spectrum, neurodevelopmental disorders are also on the rise, partly due to better diagnostics and understanding of disease. As a result, we face challenges on both ends of the age spectrum. In younger populations, we’re seeing increasing diagnoses of ADHD and autism, trends that are likely to persist. In older populations, Alzheimer’s disease, dementias, and other neurodegenerative disorders represent an enormous and growing burden.
The most defining—and unavoidable—challenge in neuroscience is understanding the underlying causes of these diseases. This is extraordinarily difficult, in large part because the brain is unique in being a complex, highly interconnected organ with built- in redundancies. Hence, small changes that could be hard to detect, can have widespread non linear consequences. Neurons are resistant to cell death compared to other cell types because we need to keep most of them for our entire lifetime. This combined with redundancy means, by the time clinical symptoms appear, the underlying pathology may be widespread or hard to detect, obscuring cause-effect relationships. Hence, in many neurological conditions, something may go wrong 20 or 30 years before any outward signs are visible.
Then comes the heterogeneity. Most neurological disorders were historically defined by clinical symptoms, in some cases aided by postmortem pathology, rather than underlying biology. For example, patients are diagnosed with Alzheimer’s disease based on cognitive decline that commonly starts as short term memory loss and neuronal loss and presence of plaques and tangles in postmortem histology of the brain. This is just the end point that could arise from multiple distinct underlying biological causes. In fact, there is growing consensus that what we call “Alzheimer’s” may actually represent three or four different diseases that share similar clinical and pathological outcomes.
This challenge is further intensified by the lack of robust animal models.
In cardiovascular disease, for example, the heart functions as a pump, and that function is remarkably conserved across species. A pig heart, a rodent heart, and a human heart share similar cellular and molecular features. The human brain is fundamentally unique. And I am not talking about cognitive function alone. Historically, there was this naive understanding that a large frontal cortex alone could explain our unique cognitive function. That would mean it’s just a scale up version of simpler cortices. You can understand one and scale up to another. It turns out that our brain is unique starting with unique molecular complexity leading all the way up to neuronal complexity and architecture. So, there is no animal model that can truly represent the human brain.
Even at the level of sensory processing, the differences are profound. Rodents rely primarily on smell and whisker-based touch, while humans are predominantly visual and hearing with finger based touch. While rodents are extremely useful at testing hypotheses and understanding fundamental concepts in neuroscience, they are a poor representation of human neurological disorders and treatment efficacy. When the only truly relevant model system is the human brain itself, understanding disease—and developing effective therapies—becomes an exceptional challenge. The rise of human iPSC derived brain organoids are a step in the right direction and carving an important niche, I still expect this aspect of neurological drug discovery to remain a challenge in future.
If exosome therapeutics succeed, how do you envision the competitive landscape evolving over the next 5–10 years?
In the case of Alzheimer’s disease, it is one of the most competitive areas in drug development. We see FDA approvals emerging regularly, sometimes more than one in a given year, and companies of all sizes are pursuing a wide range of approaches—from traditional small molecules to increasingly complex biologics. It’s a fast-moving, highly dynamic field.
The real question, however, isn’t which approach will succeed next. It’s that, despite decades of effort and many programs advancing all the way through Phase III clinical trials, none have demonstrated the kind of efficacy that would make us say, “We’ve finally solved this.” Small molecules have been tried extensively, and for the most part, failed to achieve this. They are mostly targeting a particular clinical symptom rather than altering or reversing the course of disease.
This gloomy picture may deter most people from entering the field itself. In my view, this is precisely the kind of field where we need to take more risk and advance next-generation ideas sooner rather than later. We need to accelerate new approaches—whether that’s exosomes, novel biologics, or strategies that engage other cell types in the brain. These newer technologies are inherently higher risk, but they also offer much higher potential reward.
Another important point is that exosomes don’t have to be exclusive from other solutions. They can be therapeutic themselves, once there is more understanding about the underlying biology of the disease, but they can also enable existing molecular approaches that fail simply because they can’t access the brain or are immunogenic. Given their innate capability, they can act like a “force multiplier” for any other solution. For that reason, I believe exosomes will ultimately be part of the therapeutic solution for Alzheimer’s, either directly, indirectly or both. Whether through our company or others, exosomes are very likely to play an essential role.
When it comes to endometriosis—our other major program—the situation is almost the opposite. It’s a remarkably small and underdeveloped field, especially given the scale of unmet need. Endometriosis affects roughly 11% of women, and yet the only FDA-approved diagnostic today is surgery. Women—and in many cases girls as young as 12—begin experiencing symptoms like widespread pelvic pain early in life and often live with the disease for decades. There is no cure.
The consequences can be devastating, including pain and inflammation, infertility and lesions that grow throughout the body outside the uterus. In severe cases, those lesions can even extend into the thoracic cavity. I often refer to endometriosis as a “silent pandemic”—it is widespread, deeply impactful, and historically under-discussed and underfunded. Compared to cancer or Alzheimer’s disease, the level of investment and attention has been disproportionately low, and there has also been a lack of high-quality academic and translational research.
That said, things are beginning to change. I’m seeing more interest, investment, and momentum in the field, which is encouraging. But it’s still nowhere near sufficient given the scale and severity of the problem. If anything, I wish there were far more companies, investors, and academic labs working on endometriosis. The unmet need is enormous, and the opportunity to make a real difference is just as compelling as in any other major disease area.
Is there anything you’d like to add that we did not cover?
I’d actually like to spend a bit more time highlighting endometriosis. Alzheimer’s disease doesn’t really need additional spotlight—it already receives extensive attention and coverage. Endometriosis, on the other hand, does not.
Even basic awareness is lacking. Many people don’t realize how many women are affected, how long they suffer without a diagnosis, and that there are currently no effective, non-invasive diagnostic tools or curative therapies. There have been studies showing that the productivity lost due to endometriosis alone is staggering—running into billions of dollars. Because of chronic pain and other symptoms, many women are unable to fully participate in the workforce, while the healthcare system is left managing symptoms rather than addressing the root cause.
The societal cost is already extraordinarily high, yet endometriosis remains under recognized and under prioritized. It’s still not widely understood that this is a condition with an unmet need that is at least on par with diseases like Alzheimer’s—if not greater.
