Unlocking the Secrets of the Six-Base GenomeEpigenetics was somewhat vague when I was an undergraduate ( a long time ago). So I was curious to get an update on how we can investigate it more closely and what we are learning. I talked to Tom Charlesworth, Director of Market Strategy and Corporate Development at biomodal, a sequencing technology company focused on epigenetics. Tom explained how modifications beyond the traditional four DNA bases impact gene expression, development, and disease. What is the Six-Base Genome?Tom introduced biomodal as a sequencing technology company spun out of the University of Cambridge, focused on the interface between genetics and epigenetics. Their technology goes beyond the traditional four-base genome (A, T, G, and C) by adding two epigenetically modified bases: methylcytosine (5-MC) and hydroxymethylcytosine (5-HMC). This “six-base” approach captures critical modifications that play distinct roles in gene regulation.5-MC is associated with repressing gene expression, often keeping certain genes “turned off,” while 5-HMC is linked to opening chromatin and activating gene expression. Understanding these modifications provides a more dynamic picture of how our genes are regulated—not just by the sequence of DNA but also by chemical marks that change over time.Bridging the Gap Between Genetics and FunctionThe traditional four-base genome gives us an invaluable map of our genetic code, but it falls short of explaining how the same genetic sequence could lead to such diverse outcomes—from development to disease. Epigenetic modifications, like 5-MC and 5-HMC, offer another layer of regulation that’s essential for gene expression. Tom highlighted research that illustrates the value of this additional information. He mentioned the work of developmental biologist Emily Hodges, who uses the six-base data to study chromatin accessibility during neuronal stem cell differentiation. Emily found that early changes in 5-HMC could predict chromatin opening, an insight that would be invisible if one only looked at 5-MC. This kind of nuanced view helps us understand the precise moments when genes are primed for activation, offering a clearer picture of developmental biology.Applications From Oncology to NeurologyTom described three main areas where their customers are leveraging the six-base genome: fundamental research, oncology, and neurology.In oncology, there’s a growing recognition that multi-omic data—integrating genetic and epigenetic information—can improve cancer detection and treatment response. Tom shared examples of ongoing projects in Canada and Australia, where researchers are using six-base sequencing to better understand the complex dynamics of tumor evolution. By distinguishing between 5-MC and 5-HMC in circulating tumor DNA, they hope to pinpoint which DNA fragments originate from cancer cells, providing a more accurate snapshot of the disease’s state and progression.The six-base genome also shows promise in neurology. Tom explained that the brain is unique because it has an unusually high level of 5-HMC compared to other tissues, yet we still don’t fully understand why. Early research is exploring this epigenetic landscape to uncover new biomarkers for diseases like Parkinson’s, Alzheimer’s, and various brain tumors. The ability to profile these epigenetic marks could lead to breakthroughs in diagnosing and potentially treating neurological disorders.Are you subscribed yet? If not, let’s fix that.Epigenetics as a “Life Record”: The Developmental and Environmental ContextHere’s another way think about the six-base genome—as a record of a cell’s developmental journey and its responses to the environment. During early development, epigenetic marks guide cells down specific paths, setting up the blueprint for tissues and organs. But later in life, these marks are influenced by external factors like diet, aging, and environmental exposures. This can lead to changes in gene expression that contribute to disease, aging, or even resilience against external stressors.We also touched on how this concept applies to reprogramming cells, such as in induced pluripotent stem cells (IPSCs). When cells are reprogrammed, they don’t just revert to a blank slate; their epigenetic history still influences how they behave. Tom described work showing that successful reprogramming often involves restoring specific epigenetic marks, essentially rewinding the “epigenetic clock” to a more youthful state.Rethinking DNA as the Sole BlueprintTraditionally, DNA has been viewed as the ultimate blueprint for life. But the static genome represents only a portion of the story—it’s the interaction with the adaptable epigenome that truly dictates how our genetic potential is realized. The six-base genome isn’t just a scientific curiosity; it’s another tool for decoding the complexities of life.Tom describes DNA as the “possibility space” of an organism, but it’s the epigenetic modifications that trim and shape this space into the reality we observe. This nuanced view challenges us to look beyond the sequence and consider the rich layers of regulation that determine who we are and how we function.I am most excited to learn how environmental conditions like diet and maybe even experience influence the epigenome. As a bacterial geneticist, my basic model is substance A interacts with some regulatory protein to turn a gene on or off. I want to know how the epigenome records my environment. Do the conversations I have had leave detectable marks on the chromosomes in my brain? What would be the mechanism for that? Regardless of the outcome, it’s fun to see the ever increasing depth of our understanding of biology.Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website.If you appreciate this content, you likely know someone else who will appreciate it too. Please share it with them. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

A year ago, Mark Herbert, VP of Biopharma Business Development at Varda Space Industries, joined me on one of the most popular episodes of this podcast. Today, he’s back with some exciting updates on Varda's latest mission, which involved launching a satellite and conducting pioneering drug manufacturing experiments in space. From overcoming regulatory hurdles to making groundbreaking discoveries, Varda’s journey is a glimpse into the future of pharmaceuticals—and it’s happening above our heads.Launching and Landing: The Mission to SpaceMark began by describing Varda’s June 2023 launch, where they became the first company to send a satellite with re-entry capabilities on a SpaceX Falcon 9 rocket. Varda was one of 35 satellites on the launch, but the only one designed to return to Earth. After orbiting for eight months, the spacecraft re-entered the atmosphere and landed at the Utah Testing and Training Range. The mission took longer than expected due to the complexities of obtaining a re-entry license from the FAA—a groundbreaking process as they were the first to go through it.While in orbit, they reproduced terrestrial experiments using their custom-designed hardware. One of the key achievements was rediscovering a new form of ritonavir, a widely studied HIV drug, which had experienced stability issues in the past. This discovery and the successful replication of these results in orbit demonstrated Varda’s ability to conduct controlled pharmaceutical manufacturing in space—a major leap forward in drug development.Navigating Challenges: The Complexities of Space Re-EntryThe mission wasn’t just about science—it was also a complex regulatory and logistical feat. One doesn’t just bring a satellite back whenever and wherever you like.There is a lot of planning required for the re-entry, from coordinating with the FAA to clearing commercial airspace over the Western United States during their 35-minute descent. The spacecraft re-entered the atmosphere at Mach 25, a speed that necessitated strict safety protocols to avoid any conflicts with other air traffic.Varda’s spacecraft had to endure extreme temperatures during re-entry, reaching three times the surface temperature of the sun. The team licensed the protective shield licensed from NASA, allowing them to maintain a stable internal temperature throughout the process. This ensured that the drug samples remained intact and unchanged during their return to Earth—a critical validation for future missions.Small Capsule, Big Impact: The Benefits of Space ManufacturingThe whole purpose of manufacturing in space is to solve formulation challenges. In microgravity, Varda was able to manipulate ritonavir’s crystal forms in ways that are impossible on Earth. Beyond the chemistry, the technical and logistical challenges of this mission, honestly, blow my mind. The spacecraft’s small size belies the complexity: inside, the “huggable” capsule maintains the temperature within a one-degree range, even while moving from sunlight to shadow multiple times every day in orbit.To ensure they could isolate the effects of microgravity, the team included controls—different forms of ritonavir that were stable on Earth. This careful experimental design allowed Varda to confirm that the re-entry process did not alter the drug samples, proving that drugs manufactured in space could be brought back without compromising their integrity.Are you subscribed yet? If not, let’s fix that.Looking Forward: Expanding Horizons in Space-Based Drug ManufacturingVarda’s success presents new possibilities in space-based manufacturing. Currently, their focus is on small molecule crystallization. By 2025, Varda plans to expand into solvent-based applications, allowing them to test a broader range of small molecules. By 2026, the company hopes to launch biologics—complex molecules used in cutting-edge therapeutics that often face formulation challenges on Earth.Mark spoke about how Varda’s work could eventually transform biologics manufacturing. For instance, many biologics are currently restricted to intravenous administration because of stability issues tied to Earth’s gravity. Microgravity could help overcome these limitations, enabling new formulations that are more convenient and accessible to patients.Hypergravity: A New Tool for Drug DevelopmentHow does one determine that gravity influences the crytallization of any particular molecule? Draw the curve for the effect of increased gravity and extrapolate backward. Varda has developed a hypergravity platform at their El Segundo facility, which allows them to study the effects of increased gravity on pharmaceutical processes. By simulating up to 5G conditions, Varda is able to screen molecules and processes terrestrially, providing valuable data before investing in the high costs of spaceflight. This approach not only maximizes the chances of success in orbit but also adds a new dimension—literally—to pharmaceutical research.Hypergravity serves as a negative dataset, helping researchers anticipate how microgravity might alter their processes. By tweaking the “gravity knob,” Varda can better design experiments that leverage the unique conditions of space to create novel drug formulations.Future Vision: Monthly Missions and New FrontiersVarda’s ultimate goal is to conduct space missions on a regular cadence, with plans to have quarterly launches through 2026 and the potential for monthly missions if the demand arises. Their focus remains on pharmaceuticals, particularly small molecule crystallization and biologics. Varda’s platform is designed to make space accessible for drug development, offering new tools to researchers looking to solve problems that Earth’s 1G environment cannot.Beyond the immediate applications, Varda’s work represents a paradigm shift in how we think about drug development. As Mark pointed out, this technology could enable the creation of entirely new therapeutics that would be impossible under Earth’s gravity. It’s a thrilling prospect—one that could redefine the future of medicine and bring treatments manufactured in orbit into everyday healthcare.Final ThoughtsVarda’s journey is not just about the technology—it’s about opening up new possibilities for researchers and patients alike. As someone who grew up during the space age, I never imagined that some day, we could be receiving treatments that were made in space. This is just the beginning, and Varda is leading the way into a new era of drug manufacturing.Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website.If you appreciate this content, you likely know someone else who will appreciate it too. Please share it with them. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

I spoke with Brian Thomson, HR consultant and leadership coach, about leadership, hiring, retention, and culture in early-stage life science companies. Brian’s practical insights offer a roadmap for building and sustaining a thriving company from the ground up.The Importance of Modeling the Right BehaviorsFrom the beginning, Brian emphasized a key concept: intentionality. In his view, leadership is not just about making the right decisions; it's about being intentional in how you model behaviors and build culture within your organization. This is particularly crucial in the fluid environments of startups, where the pace is fast, and the stakes are high.He pointed out that it’s not about whether a particular culture is right or wrong—what matters is that it’s intentional and authentic. This intentionality shapes hiring, retention, and performance management, all of which are crucial for the long-term success of a company. He argued that strategic planning should not just be a buzzword but a disciplined practice that informs every decision, from the type of culture you want to build to the kind of people you need to hire.The Rule of Threes: Core Competencies in StartupsBrain has a rule of threes when it comes to what founders of early-stage life science companies need to focus on: disruptive science, a strong core team, and a high degree of intentionality around culture. While it’s easy for founders to get fixated on the science—because it’s their passion and it’s measurable—the other two elements are just as critical.This resonated with me, especially considering how often we see startups with groundbreaking science but no clear direction on how to build a team or a culture that can sustain the business. The science might make headlines, but it’s the culture and the team that will drive the long-term success of the company.Strategic Planning: More Than Just a ProcessBrian’s sees strategic planning as more than just a process; it’s a foundational practice that lends clarity, focus, and discipline to an organization. He mentioned that in his role as a coach, he often works with early-stage organizations to develop a strategic plan that is as concrete as possible. The goal? To ensure that at any given moment, everyone in the organization knows the top priorities.Be very disciplined. Be very focused. Make your plan. Make it as concrete as possible. At any given time, if I go and ask two of your employees, anywhere in the organization, “What are the number one and what's the number one and what's the number two topmost priority that the company has at that moment?”If they can't answer that, it indicates to me that you haven't done a good enough job of being very clear and being very focused. This approach to strategic planning directly feeds into the hiring process. By being clear on the values and culture you want to create, you can ensure that the people you bring into the organization are aligned with those goals. Hiring isn’t just about finding people with the right skills; it’s about finding people who will thrive in the specific culture and environment of your company.Like what you see?Hiring: An Internal Competency, Not a Task to OutsourceMany startups make a mistake by outsourcing their hiring processes. Hiring is too critical to be left to an external agency, especially in the early stages of a company’s development. The first 10 to 15 hires set the tone for the entire organization, and if those hires don’t align with the company’s culture and values, it will create long-term issues.Brian argued that hiring should be an internal competency, with the leadership team taking an active role in the process. This ensures that everyone who joins the company is fully aware of the environment they’re stepping into, whether it’s a messy startup with lots of ambiguity or a more structured environment.The Value of Transparency in the Hiring ProcessBrian shared a story from his time as Chief People Officer for a small biotech spinout during the Great Resignation. Despite the mass exodus of employees across industries, his organization navigated that period with zero regrettable turnover and zero R&D turnover. The secret? Radical transparency.From the first conversation with potential hires, Brian and his team were upfront about the realities of the company’s environment. This honesty helped attract the right people—those who were excited about rolling up their sleeves and getting their hands dirty—and it also helped filter out those who weren’t a good fit. Brian emphasized that transparency in the hiring process not only attracts the right talent but also helps candidates self-select out if the environment isn’t right for them.Retention: A Balancing ActWhen it comes to retention, 100 percent retention isn’t the goal, nor is it ideal. A little turnover can be a good thing, as it brings in fresh perspectives and prevents complacency. However, the key is to ensure that the turnover is natural and doesn’t result in the loss of essential talent.Brian talked about the importance of building a talent engine within the organization—an environment where employees are developed and prepared for their next roles, whether within the company or elsewhere. This approach not only boosts retention but also enhances the company’s reputation as a place where people can grow and develop their careers.The Power of a Coaching CultureFinally, we talked about the value of creating a coaching culture within an organization. Brian argued that this is one of the most effective ways to develop talent and increase engagement. Instead of relying on traditional training programs, which can be expensive and often ineffective, he advocates for on-the-job learning and continuous development through coaching.In a coaching culture, managers act as mentors, helping their employees navigate their careers and develop the skills they need to succeed. This not only empowers employees but also creates a more dynamic and engaged workforce. This approach doesn’t require a huge budget—it’s more about a shift in mindset and behavior.Final Thoughts: Intentionality Is KeyAs we wrapped up our conversation, the theme that kept coming back was intentionality. Whether it’s in strategic planning, hiring, or building a coaching culture, being intentional about your decisions and actions is crucial for the success of any startup. The best companies are those that are clear about who they are, what they value, and where they’re going.Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

When I first heard about hydrosomes, I honestly thought, “That can’t be real.” Hydrosomes are microscopic bubbles that stay in water without coalescing and rising to the surface. Then I met Nick Jackowetz, the Senior VP and Principal Scientist and the team from Hydrosome Labs at BIO 2024 in San Diego. They answered my questions and I invited Nick to be a guest on the podcast to share the story with you. Hydrosomes are also known as ultrafine bubbles, and they have incredible potential for many applications. If you’ve ever wondered how something as seemingly simple as a bubble could revolutionize fields like agriculture, cosmetics, and even fermentation, then this episode is definitely one to tune into.Nick started by breaking down the basics of what makes these ultrafine bubbles so unique. We’re talking about bubbles so small that they’re measured in nanometers—around the size of a virus particle. To put that into perspective, imagine a champagne bubble, which is already tiny to the naked eye. Now, pack a trillion of these ultrafine bubbles into that single champagne bubble, and you start to grasp just how small we’re talking about. It’s mind-boggling, right? These bubbles don’t even float like the ones we’re used to; they stay suspended in solution because they’re not governed by the same buoyancy rules. This leads to some pretty wild implications for how they can be used.Even the physics of these bubbles changes at such a small scale. For instance, the pressure inside these bubbles can reach up to 30 atmospheres, which is 30 times the pressure we experience in our everyday environment. This intense pressure doesn’t make them pop as you might expect; instead, it opens up new possibilities for gas delivery in various applications. Imagine being able to deliver oxygen directly to cells in a way that’s more efficient and targeted than ever before. Because the bubbles have an enormous collective surface area, believed to be charged, the team is looking at how they attract and move nutrients around. While the concept has been around since the 1980s, the science has only really taken off in the last decade. The early research mainly came out of Japan, where these bubbles were first studied in applications like agriculture and aquaculture. It turns out that these tiny bubbles can help grow plants more effectively by delivering nutrients and gases directly to the roots. Are you subscribed yet? If not, let’s fix that.I was curious to learn about potential applications. One area that’s particularly exciting is their potential in consumer packaged goods, especially in cosmetics. Imagine being able to deliver active ingredients like vitamin C or retinol more effectively into the skin without the need for added chemicals. That’s exactly what these ultrafine bubbles can do. By improving how these ingredients penetrate the skin, we could see a new wave of cosmetic products that are not only more effective but also safer for consumers.We didn’t stop there. The potential for these bubbles in the beverage industry is another game-changer. Picture your favorite sparkling water, but instead of regular carbonation, the drink is infused with ultrafine bubbles. These tiny bubbles could enhance flavor profiles, reduce the need for added sugars, and even change the overall sensory experience of the drink. Nick mentioned ongoing research into how different gases inside these bubbles—like nitrogen or nitrous oxide—could create new taste sensations and improve the mouthfeel of beverages. The idea that you could enjoy a sweeter taste with less sugar is not just intriguing; it could have significant implications for the health-conscious consumer market.For life sciences, the interesting application is in fermentation processes. These bubbles could play a crucial role in making fermentation more efficient, which is especially important as industries increasingly rely on fermentation not just for food and beverages but also for producing pharmaceuticals, enzymes, and other valuable compounds. The idea that you could boost the growth and productivity of cells in a fermentation tank just by adding these bubbles is something that could have wide-reaching benefits, particularly for biotech companies looking to optimize their production processes without the need for expensive new infrastructure. To be clear, it’s not just putting bubbles in the media. The effect, in addition to transporting oxygen, is enhanced by how the hydrosomes attract and transport nutrients.One of the most exciting projects Nick mentioned is a preclinical study on how these bubbles might affect the gut microbiome. Early evidence suggests that drinking water infused with ultrafine bubbles could positively impact gut health, potentially altering the microbiome in ways that benefit overall health. This could lead to a whole new category of wellness products that deliver health benefits just by changing the way water is consumed.Of course, there are still challenges ahead. One of the biggest hurdles is accurately measuring these bubbles, especially as they get smaller. The equipment needed to detect and analyze these tiny bubbles is still catching up with the science, which makes it difficult to fully understand their potential. But as technology advances, we can expect to see more precise tools that will allow scientists like Nick to push the boundaries even further.Whether it’s improving the efficiency of fermentation, enhancing the delivery of cosmetic ingredients, or even opening up new frontiers in drug delivery and gut health, ultrafine bubbles are something to keep an eye on. I’m excited to see where this technology goes next, and I hope to have Nick back on the podcast in the future to update us on the latest developments. I’m particularly interested in what RNA analysis might tell us about how gene expression might change in cells grown in hydrosome-infused media. Stay tuned. But for now, enjoy the episode. Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website.If you appreciate this content, you likely know someone else who will appreciate it too. Please share it with them. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

Issa Kildani is the founder and principal consultant at Ambrosia Ventures. Our conversation centered on his journey from metabolic and cardiovascular research into the consulting world. Even if you are not planning on becoming a consultant, one can learn a lot from his approach to acquiring skills and building relationships with customers.Transitioning from Research to ConsultingYou don’t need an MBA to become a consultant. I’m sure it helps in some areas, but there is a lot to be said for rolling up your sleeves and figuring it out. Issa started his career in metabolic and cardiovascular research as a graduate student at Vanderbilt University. He eventually realized while working at startups that his longer-term goal was to help people and companies rather than stay at the bench.Transitioning into consulting requires a diverse skill set, including project management, strategic thinking, and analytical skills. There was a lot to learn but he saw a path to make it happen by being self-driven and inquisitive, eager to learn and explore new areas, one of which was strategic thinking. Strategic ThinkingI’m always interested in what it means to think strategically. Issa shared his experience at a neurofeedback and biofeedback startup in Michigan. Working closely with the CEO, he learned the importance of strategic thinking by understanding different markets and thinking ahead about potential expansions. With multiple opportunities for expansion, how do you choose where to focus? Issa considered what were the emerging markets and where that would put them 5 years down the road. So you want to jump on it just now, you know, like the AI and machine learning, things like that in drug discovery.These are hot topics, but which one is going to take you a lot further in the company and what's your long-term vision? Does it align to your long-term vision? Do you plan on selling five years from now or do you plan on growing to a bigger company? Those are the kind of decisions that play into it and help them align to that strategic goal. Understanding Industry DynamicsBeyond understanding markets, one also needs to understand how the industry works. There are many components to the life science ecosystem. Issa talked about the unique challenges faced by biotech companies, such as funding issues, regulatory hurdles, and clinical trial recruitment problems. In the early stages, refining their pitches and helping them communicate their value more effectively is a key for success. At later stages, the focus might be more on regulatory issues or broader strategic goals. My overall impression is that Issa is very good at talking to potential customers and figuring out in detail what their current challenges are. That is a skill in itself.Building Relationships and Winning BusinessIssa takes a very long approach to building relationships and winning business. He emphasized understanding clients' needs, being genuinely interested in their success, and maintaining long-term relationships. It can take a long time to land a client. Issa’s process involves regular check-ins, understanding the client's challenges and milestones, and providing insights so potential clients can understand the value he brings to help them achieve their strategic goals.The Value of MentorshipWe talked about the value of mentorship. He described how his mentor, who was also his boss, played a significant role in his development as a consultant. By being upfront about his desire to learn and improve, Issa received invaluable guidance and feedback that helped him fine-tune his skills. The key thing here was simply to ask. Sometimes this may seem like a bold move. “Can I really ask a senior executive to be my mentor?” (It’s not the only way but as an older parent, I can tell you nothing gets your attention faster or makes you feel better than when a young person asks for your advice.)Even if they don’t have time to be your mentor, it will put you on their radar as someone who is looking to do more for the company. You can’t lose. If you take away nothing else from this message, being curious and asking for advice will take you a long way regardless of your goal. I challenge you to find some one and talk to them this week.Opportunities and Challenges in Smaller Biotech EcosystemsIssa is based in a smaller biotech ecosystem, Ann Arbor, Michigan. While smaller ecosystems may lack the resources and investment opportunities of larger hubs like San Francisco or Boston, they offer a chance for a consultant to make a significant impact. Add to that the possibility of connecting with larger hubs and applying those insights locally, you can make a difference to foster growth and innovation in these emerging ecosystems.The Broader Implications of ConsultingFrom my own experience, the best thing about being a solopreneur or consultant is the opportunity to see what’s happening across all of life science. If you are the person who feels that life at the bench is too slow or too narrow, this may be the path for you. I enjoy the feeling of helping others in life science directly. I may not find the cure that affects millions but I get to build relationships and see the value I bring t people I actually know. At the same time, I know they are helping millions.For anyone considering a career in consulting Issa's journey offers valuable lessons. Check out Issa's website and blog for more insights and resources.Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

In this episode, I spoke to Cassandra Rix, the owner and chief leadership coach at The Resonance Coach. Our conversation centered around understanding individual motivations and expectations within group efforts, especially in the context of company acquisitions. I think you will find the insights applicable to many situations at work and at home.Cass's Background and ExpertiseCass has spent over 20 years working with businesses either in the process of being acquired or on the tail end of an acquisition. She specializes in service agencies selling expertise and time, such as consultancies and communication specialists. Her focus now is on helping founders looking for investment or seeking an exit strategy, and the businesses interested in investing in them. She believes that many acquisitions fail despite thorough due diligence because the underlying human motivations and behaviors of the individuals involved aren't fully understood.Understanding MotivationsWhile people may outwardly agree on a common goal, such as selling a company, their underlying reasons can be very different. These differences will show up during times of significant change (after the investment or acquisition). Everyone’s motivations are influenced by their own personal experiences and beliefs, which drive their decisions and behaviors.Cass's own interest in understanding motivations stems from her background in sales and marketing, where she worked with buyers and wanted to comprehend why people made specific purchasing decisions. Our beliefs drive our behavior, and it's crucial to recognize that we often make assumptions about others' motivations based on our own perspectives. We expect them to act the way we would. I’d like to look deeper into this in future episodes.If you find this helpful, it kind of makes sense to subscribe, doesn’t it?The Challenges of AssumptionsIt’s risky to assume that everyone's motivations are similar. Cass used the analogy of wearing someone else's shoes – just because you're in their shoes doesn't mean you understand their journey. This is especially relevant in business settings, where assuming that all founders or team members share the same motivations can lead to conflicts and dysfunction.Cass illustrated this with an example of how misaligned expectations can derail an acquisition. For instance, if one founder decides they have enough financial security post-acquisition and leaves, the remaining team dynamics can be severely disrupted:So the things that fall apart there is, well, we all think we've agreed to sell this business or invest, have investment in this business so that we can carry on. What does carry on mean? What if that means that one person has generated enough income in the acquisition process, not to need to stay throughout the earn-out. And suddenly you go from a leadership team or founding team of four to three or three to two. What if the other two people in that business were beautifully balanced by that third individual? And so the relationship that they're left with is dysfunctional. They don't really like each other. They don't know how to communicate with each other. They've never had to without that third person as a foil. And probably the most flawed thing is the assumption that the rest of the business, whether you're talking about another twenty people, fifty people or thousands of people, the assumption that those people don't know.This scenario can lead to conflicts and a decline in business performance, which affects everyone's livelihoods.The Role of Vulnerability and Communication As individuals climb the corporate ladder, they often create personas that might not align with their true selves. This can lead to exhaustion and dissatisfaction, as they try to maintain an identity that doesn't reflect their genuine motivations.Cass said that vulnerability is not a weakness but a strength. When leaders and team members are open about their true motivations and feelings, it fosters understanding and empathy. She shared that when people reveal their authentic selves, it often leads to relief and better teamwork. This openness can help teams navigate change more effectively, as everyone understands each other's perspectives and can support one another.Practical Implications and Real-World ExamplesCass pointed out how small habits and cultural norms, such as which hand you use to hold a fork, can shape our perspectives and lead to emotional attachments about how things should be done. If we feel that strongly about cutlery, imagine the intensity of our feelings about approaches to business where the stakes are much higher. Translating this to business settings, she explained how deeply ingrained beliefs about success and behavior can affect decision-making and team dynamics. Differing motivations for making money can lead to misunderstandings. Some people might want to make money to retire early and spend time with family, while others aim to leave a legacy or achieve a prestigious position. These differing goals and expectations can create friction if not openly discussed and understood. Whether you are the acquiring/investing company or the company being invested in, understanding these things can make a huge difference in your long-term happiness (money, legacy…).The Courage to Be DislikedOur conversation concluded with a serious reflection on the importance of self-awareness and the courage to be true to oneself. Cass recommended the book "The Courage to Be Disliked," which explores the concept that what others think of us often reflects their own beliefs and insecurities. She encouraged leaders and individuals to focus on their own motivations and well-being rather than constantly worrying about others' opinions.Her final thought: "The most liberating two words in the English language are 'let them...'" Letting go of the need for external validation and embracing one's true self can lead to greater fulfillment and success, both personally and professionally.Let them.Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

In my recent conversation with Larry Kaplow, we talked about brand strategy in the life sciences, why, when and how.Defining Brand StrategyWe kicked off the discussion with Larry describing the danger of not having a strategy. In a world overloaded with information, a brand has to cut through the noise and make its value clear. Even if a company has groundbreaking technology, it’s easy to be overlooked if the brand strategy isn’t aligned with the audience's needs. People—whether researchers, investors, healthcare professionals, or patients—are primarily concerned with their own interests.A brand is the sum of all associations that audiences have about a company. This definition, which he credited to Uli Applebaum, highlights that every touchpoint, from sales calls to investor decks, contributes to building these associations. As a result, a deliberate and intentional strategy is crucial for creating consistent and meaningful connections with the audience.Simplifying the Brand MessageLarry argued that while nuances might change, the core brand message should remain consistent. He likened it to owning a space in the audience's mind—when they think of your company, they should think of one defining characteristic. This consistency makes it easier for the audience to remember and relate to the brand.Here is a real-world example. Thermo Fisher faced the challenge of convincing diverse audiences to switch from traditional methods to mass spectrometry in toxicology. By identifying two primary audience groups—those looking to grow their business and those pushing the boundaries of research—they could tailor their brand message to resonate broadly. This approach allowed them to lead with a brand-focused message about pushing toxicology forward, which connected with all their target audiences. It took doing some homework to get there. This involves understanding the audience's motivations, barriers, and pain points. Larry shared another example from a different company in the medication management space in hospitals. The initial tech-focused message wasn't resonating. Hospitals were resistant to new technology because new tech often means a lot of work. By shifting the narrative to focus on patient and hospital safety, they aligned their message with what was truly important to their audience. This not only made the brand message more relevant but also helped position the technology with respect to existing budgets for safety initiatives.Personality Archetypes for Commoditized ProductsBrand personality archetypes can differentiate a company in a commoditized market by mirroring what's important to them or by representing something they aspire to be. For instance, McDonald's uses the "Innocent" archetype, creating a sense of happiness and nostalgia. In contrast, Burger King has struggled with consistency, resulting in a less impactful brand presence. As I look at it, BK is focused on the burger, McDonald’s is focused on the experience.Crafting a Long-Term Brand Vision for InvestorsIf we think about smaller biotech firms, even prior to commercialization, crafting a long-term brand vision is crucial, especially when communicating with investors. Larry noted that investors are people too, influenced by compelling narratives. Investors looking for long-term returns want to see a cohesive brand strategy that promises sustainable growth and market relevance. A strong brand story in the investor deck can be as important as the technical details. The other lesson here is knowing what kind of investor you have or are looking for.Brand Architecture - Balancing Messages Across Different LevelsWe wrapped up the conversation by discussing how to balance messages across different levels—company brand, technology, and specific applications. Larry differentiated between brand architecture and communication structure. Brand architecture involves categorizing and integrating different brands, especially post-acquisitions, whereas communication structure focuses on maintaining a consistent brand story across various touchpoints.He highlighted the importance of having a comprehensive brand position that can be communicated at all levels, from the high-level mission and vision to the detailed technical aspects. This consistency not only strengthens the brand but also adds credibility and value over the long term.Final ThoughtsLarry’s insights were a masterclass in brand strategy, particularly for the life sciences sector. His emphasis on consistency, relevance, and the importance of doing the homework provides a clear roadmap for any company looking to strengthen its brand. For me, the takeaway was clear: a well-defined and consistently communicated brand strategy is essential for cutting through the noise and making a lasting impact. And for those in the biotech space, understanding and addressing the needs of all your audiences, including investors, is key to building a strong, sustainable brand.Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

At BIO2024, I spoke Sam Clark, CEO and founder of Terran Biosciences, about their development of new long-duration dosage forms for the treatment of schizophrenia . We discussed the development of prodrugs, the potential of psychedelics, and the journey of founding a biotech company. The Genesis of Terran BiosciencesSam's journey into biotech was personal. Growing up around friends and family members with severe mental illnesses like bipolar disorder and Alzheimer's disease, he saw the limitations of existing treatments. Through his studies at MIT and Columbia, he recognized the slow pace of development and the significant side effects of available medications. Existing treatments for mental illnesses have many unpleasant side effects from cause weight gain to Parkinsonian symptoms and hormonal disruptions. All of that led to his decision to found Terran Biosciences hoping to transform the standard of care.Terran's PipelineTerran's lead asset, TerXT, is a novel combination of prodrugs of xanomeline and trospium, compounds that have been around for a long time, but with less than ideal pharmacokinetics. They also have Idazoxan XR, an adjunctive treatment for schizophrenia, and several new forms of psychedelics like psilocybin and MDMA with differentiated pharmacokinetics aimed at making these treatments more accessible and affordable.Sam explained the significance of prodrugs in their approach. Unlike simple reformulations, prodrugs are entirely new compounds created by attaching a side chain to the original molecule. This attachment improves pharmacokinetics, allowing for more effective absorption and longer-lasting effects. For example, the older compounds xanomeline and trospium, which need to be taken twice daily, have been modified into prodrugs that can be administered once daily or as long-acting injectables with multi-month durations. This innovation not only simplifies the regimen for patients but also leverages the FDA's accelerated 505(b)(2) pathway, potentially bringing these new treatments to market faster.Overcoming Development ChallengesCreating effective prodrugs is no small task. Sam described the extensive process, involving a team of world experts and over 200 FTE chemists working tirelessly. They designed over 10,000 prodrugs, synthesized 700, and conducted 500 preclinical studies to refine their approach. This massive undertaking, though challenging, has led to promising results.Are you subscribed yet? If not, let’s fix that.The Potential of PsychedelicsI also wanted to explore psychedelics, a field that has generated significant interest in recent years. Terran is developing new forms of MDMA, psilocybin, and 5-MeO-DMT, aiming to improve their pharmacokinetics and make these treatments more accessible. Sam highlighted MDMA's potential, currently under FDA review for treating PTSD, with a decision expected soon. (Right after we spoke, the FDA advisory panel recommended rejecting approval for MDMA. The decision has not been made yet.) By creating new forms and leveraging the 505(b)(2) pathway, Terran aims to overcome patent barriers and ensure these treatments are affordable.Insights into Brain FunctionI am particularly curious about anything we can learn about neurobiology from studies around these therapeutic compounds and psychedelics. Here is the challenge: Psychedelics, for example, act on multiple receptors. Teasing out different pathways in the brain is complicated. Functional MRI studies of people undergoing psychedelic trips show reproducible changes in brain pathways, suggesting potential mechanisms but the circuitry is complicated. There are no simple answers yet.The Journey of a First-Time FounderI asked Sam about his experience as a first-time founder. Terran's success is in large part due to its corporate structure, modeled after fast-moving Silicon Valley companies. By avoiding traditional hierarchical structures and instead utilizing a flat organization with world experts leading sub-teams, Terran has managed to solve complex problems efficiently.Team building has been essential to Terran's achievements. Sam's approach involves creating specialized teams for different facets of a problem, ensuring a comprehensive and collaborative effort. “Workflows” for the WinI have seen a pattern in several interviews recently. Changing a process can have as big of an effect on solving a problem (and creating success for a company) as developing a new product. In this case, it’s a bit of both. The problem being solved by TerXT is the patient regimen. Prodrugs with longer-duration pharmacokinetics make adherence easier for the patient. At the same time, I appreciate the enormous amount of development effort that went into creating those prodrugs. A different approach to assembling teams and managing them is also a significant change in the workflow that will have an impact.Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website.If you appreciate this content, you likely know someone else who will appreciate it too. Please share it with them. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

In this episode, recorded at BIO2024 in San Diego, I had the pleasure of speaking with Martin Brenner, the CEO and CSO of iBio. Our focus was the challenges and innovations in developing antibody-based therapeutics, particularly through their AI-driven discovery platform. Martin shared his insights into the current landscape and future directions of antibody therapies, touching on key aspects such as target selection, engineering challenges, and the role of AI in optimizing therapeutic antibodies.The Challenges of Developing Antibody TherapiesAntibodies have revolutionized therapeutic approaches over the past two decades, with numerous successful drugs already approved. However, as Martin pointed out, we've now picked much of the low-hanging fruit. The target space is becoming increasingly complex, with most approved antibodies focusing on a small set of targets. For instance, about 40% of all approved antibodies target PD-1. While anyone can now develop a PD-1 antibody, the real challenge lies in identifying and effectively targeting novel, more complex antigens.Another significant challenge Martin highlighted is improving the safety and therapeutic window of antibodies. Highly potent antibodies, particularly in oncology, can cause severe side effects. Enhancing the safety profile while maintaining efficacy is a critical area of ongoing research.Potency vs. Therapeutic EffectivenessIt turns out that the best-binding antibody isn't always the most effective therapeutic. For example, in bispecific molecules, where one arm binds to a tumor cell and the other to an immune cell, the tightest binding isn't always ideal. Overstimulation can lead to cytokine release and toxicity. Instead, finding the right balance in binding characteristics is crucial to avoid adverse effects.Traditionally, the goal was to find an antibody that binds quickly and stays bound indefinitely. However, this might not always be the best approach. Understanding on and off rates of antibodies is important for delivering the desired response. Novel technologies now allow us to screen for these characteristics early, optimizing therapeutic effectiveness and safety.Are you subscribed yet? If not, let’s fix that.iBio's AI-Driven PlatformiBio focuses on generating small, high-dimensional data sets to train their models. Their technology starts with an epitope steering engine, which creates engineered epitopes that precisely reflect the surface of target proteins. This innovative approach allows for targeted antibody development, even against challenging targets.For example, iBio can create PD-1 agonists that activate receptors instead of merely blocking them. This capability opens up a new realm of possibilities in antibody therapies, particularly for complex and hard-to-target proteins.Discovering New Biology Through TargetingOne of the most exciting parts of our conversation was discussing how iBio's platform not only targets known regions of proteins but also helps uncover new biological functions. By addressing the entire protein surface with engineered epitopes and screening them, iBio can identify antibodies that reveal new aspects of a protein's role. This approach not only enhances therapeutic development but also contributes to our broader understanding of biology.Smart Antibodies and MaskingMartin explained their concept of smart antibodies, which are designed to be inactive until they reach the disease tissue, like a pro-drug. This masking technique, particularly useful in tumor biology, involves connecting a mask to the antibody with a linker that is cleaved off by enzymes in the tumor environment. This method allows for higher precision in targeting and reduces side effects by ensuring the antibody is only active in the intended tissue.For example, targeting the epidermal growth factor receptor (EGFR) can be problematic due to its expression in the skin, leading to side effects. Using a masking approach, iBio can target EGFR in tumors while minimizing impact on the skin, potentially allowing for higher dosing and improved efficacy.Optimization and Rapid DevelopmentiBio's approach to optimization sets them apart. Traditional methods like phage display create large libraries of molecules but require significant time to identify and develop drug-like characteristics. In contrast, iBio uses machine learning to create localized diversity in a smaller, more manageable library. This method mimics the diversity of large libraries while maintaining high developability, drastically reducing optimization time from months to weeks.Focus Areas and Future DirectionsI asked Martin about what areas they are focused on with their pipeline. iBio is currently focusing on cardiometabolic and immuno-oncology areas. Their preclinical pipeline includes promising targets in immuno-oncology, with plans to partner these developments strategically. Additionally, Martin's background in diabetes and obesity research has driven their pivot into cardiometabolic diseases, aiming to develop drugs for those indications that avoid muscle and bone loss, crucial for the aging population.Other molecules, single chain antibodies from sharks or human heavy chain alone may eventually form the basis of new therapies for more complex targets.For me, the attraction of this approach is the broader look at the target molecules to survey all the possibilities beyond developing a small molecule that fits in a binding site and the benefit of everything we learn about biology that may lead to new discoveries in the future.Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website.If you appreciate this content, you likely know someone else who will appreciate it also. Please share it with them. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

In this episode of CC Life Science, I had the pleasure of hosting Neil Spooner, the founder and chair of the Patient-Centric Sampling Interest Group (PCSIG). Neil shared his insights into patient-centric sampling and its potential to revolutionize healthcare and clinical trials.Introduction to Patient-Centric SamplingNeil began by explaining the concept of patient-centric sampling, which prioritizes the patient's needs over traditional methods that often inconvenience them. Traditional methods like venous phlebotomy or standard urine collection are designed with the analytical labs, clinicians, and logistical chains in mind rather than the patients. For patients, that means they have to have to take time out of their day, possibly missing work or school, to visit a clinic for sampling.This is an added burden for patients, particularly those with chronic conditions requiring frequent testing. I shared the example of a family member, who had leukemia and needed to visit the hospital twice a week for tests. This was a significant strain not only on her but also on family members. Neil explained that patient-centric sampling offers a more convenient alternative, allowing samples to be collected at a time and place that suits the patient, whether at home or any other location.Benefits for Clinical Trials and HealthcareI was curious about what this approach would mean for clinical trials and healthcare. Neil pointed out that easier and more flexible sampling methods could improve patient recruitment and retention in clinical trials. It could also help gather data that is currently difficult to obtain, such as samples taken during a clinical event like a migraine. This approach not only enhances data collection but also broadens the patient pool to include those who might otherwise find it difficult to participate due to geographical or physical constraints.Current Research and Stakeholder EngagementBring this concept to life isn’t just about workflows and analytical science. Marketing plays a big role as well. And I don’t just mean promotion. I mean understanding the needs of everyone involved. Neil explained that the PCSIG is actively engaging with various stakeholders to understand their concerns and benefits regarding patient-centric sampling. They are doing market research to identify key stakeholders in different use cases, such as clinical trials, therapeutic drug monitoring, diagnostics, and drug testing in sports. By having conversations with these groups, PCSIG aims to educate and address their concerns while identifying potential benefits and gaps in the current system.Addressing the Resistance to ChangeOne of the significant challenges discussed was the resistance to change within the healthcare and clinical trial sectors. Neil ponted out the importance of finding passionate individuals within organizations who can champion the adoption of new sampling methods. These individuals need the support of their superiors and a network of like-minded professionals to overcome the inevitable hurdles that come with implementing new technologies.Are you subscribed yet? If not, can we fix that?Technological and Logistical InnovationsWe spent a little bit of time discussing sample formats and logistics. Currently labs doing routine analyses operate large analyzers that are set up for huge volumes of a standard set of tubes. Neil provided insights into the technological and logistical innovations required for patient-centric sampling. He mentioned various devices that can collect blood samples through finger pricks or from other body parts like the arm or thigh, often producing dried samples that can be mailed to labs. The COVID-19 pandemic demonstrated the feasibility of such home-based testing, showing that logistical systems can adapt to handle new sampling methods.Impact on Drug Testing in SportsI was surprised to hear about the application of patient-centric sampling in drug testing for sports. Chain of custody is crucial here to ensure the integrity of the samples. Neil explained that while athletes would still need to be witnessed during sample collection, blood sampling could be a more comfortable and less invasive (in terms of witnessing) option compared to urine sampling. Ultimately it’s likely to be complementary to urine testing. It does bring benefits for the athlete. It can make ongoing monitoring more practical for providing valuable data for athletes' training and health.Sponsorship and Future PlansFinally, we touched on the PCSIG's funding and sponsorship. Neil explained that the organization aims to keep sponsorship levels low to encourage broad participation, including startups and companies from less affluent regions ensuring that no one sponsor has outsized influence on the direction of the group. Sponsors benefit from visibility on PCSIG's platforms and involvement in the sponsors' advisory group, which helps shape the group's activities. Sponsors recently voted on nine proposed activities, and the top two priorities would soon be announced.Reducing the burden on patients needing frequent testing alone makes this effort worthwhile in my opinion. The benefits for recruitment and retention in clinical trials and drug/health monitoring in sports are icing on the cake.Your deepest insights are your best branding. I’d love to help you share them. Chat with me about custom content for your life science brand. Or visit my website.If you appreciate this content, you likely know someone else who will appreciate it also. Please share it with them. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com