The Bio Report

Speeding Protein Engineering with Whether it’s the development of new biotherapeutics, or replacing hydrocarbons from their role in industrial manufacturing, engineering proteins suited for a task is a time consuming and expensive process. Cradle Bio has developed generative AI technology to accelerate protein engineering by reducing the number of experiments needed to arrive at a product candidate and enable the optimization of multiple properties at once. We spoke to Elise de Reus, co-founder of Cradle, about the company's generative AI technology, how it works, and how it’s changing the process of protein engineering.

With the emergence of GLP-1 agonists to treat obesity, there has been growing interest in the use of peptide-based medicines. Protagonist Therapeutics has developed technology that can take these target specific and potent therapies and allow them to be delivered orally. The company has a collaboration with Johnson & Johnson for an oral peptide that blocks the IL-23 receptor that’s in development to treat psoriasis and ulcerative colitis. We spoke to Dinesh Patel, CEO of Protagonist, about the company’s platform technology, the benefits of orally delivered peptide therapies, and where he sees the biggest opportunities for this approach.

While there have been a parade of novel therapeutic modalities in recent years, many of them are constrained by delivery challenges. Vesigen Therapeutics is developing novel drug delivery technology known as ARMMs that can transport a wide range of therapeutic payloads directly into the cytoplasm of target cells. We spoke to Paulash Mohsen, CEO of Vesigen, about the company’s delivery technology, its advantages over viral vectors and liquid nanoparticles, and how it enables the targeting of previously undruggable targets.

The body has a natural mechanism for breaking down and clearing proteins. Arvinas is among a group of companies that’s seeking to harness this mechanism for therapeutic purposes. It has platform technology that enables the development of targeted protein degraders to breakdown disease-causing proteins. Among the benefits of this approach is that it offers a way to target so-called undruggable proteins that conventional drugs are not able to bind with in a strong enough way. We spoke to Randy Teel, chief business officer and interim chief financial officer of Arvinas, about protein degradation, its evolution as a therapeutic strategy, and the range of indications the company is pursuing.

The traditional approach to treating autoimmune disease has relied on ways to suppress the immune system. COUR Pharmaceuticals is developing first-in-class therapies that instead seek to reprogram the immune system to create antigen-specific tolerance. We spoke to COUR CEO John Puisis and COUR Vice President of Research Adam Elhofy, about how the company’s immune-modifying nanoparticles work, how the approach preserves the immune response, and its partnership with Takeda focused on celiac disease.

The next blockbuster drug may already be in production by bacteria within your body. Bacteria produce unique chemical compounds that are bioactive and may have great therapeutic potential, but this chemical space has largely not been mined. Empress Therapeutics, a Flagship Pioneering company, is searching for such molecules by exploring the genes of bacteria that live in the human body to search for the molecules they produce and identify compelling drug candidates. Since its founding in 2020, the company has already identified 15 novel candidates. We spoke to Sabrina Yang, chief innovation officer for Empress and a principal at Flagship Pioneering, about how exploring the bacterial metagenome in the human body can point the way to the next blockbuster drug, the role AI plays in its platform, and how this approach can accelerate the time and reduce the cost of drug development.

In most cases, the immune system detects and destroys cells that could become cancerous every day. For cancer to ravage the body, it needs to evade the immune system by shutting off its response. SIRPant Immunotherapeutics is seeking to address cancer by activating and modifying a patient’s own macrophages to awaken the immune system to cancer. The activated macrophages are able to recognize and directly attack cancer cells throughout the body and stimulate other parts of the immune system to sustain a prolonged attack. We spoke to Robert Towarnicki, CEO of SIRPant, about the company’s immunotherapies, the advantages they offer over other approaches, and why its platform can be applied to other diseases involving immune dysfunction beyond cancer.

As the founder of SynBioBeta, John Cumbers has long evangelized to investors, entrepreneurs, and forward-thinking industrialists about the emergence of the bioeconomy. Cumbers, however, wants to share his sense of wonder about molecular biology with a broader audience through his new venture, Biological Enlightenment Studios. His ambition is for the studio to become a Pixar for curious-minded youngsters. The studio’s first effort will be Lee's Lab, an animated series that follows the 12-year-old title protagonist through the jungles of Borneo as she seeks to understand the secrets of molecular biology and the splendors of biodiversity. We spoke to Cumbers about Biological Enlightenment Studios, his desire to spark the imagination of a new generation about the marvels of biology, and why bioliteracy matters for the growth and health of the bioeconomy.  

Electronic health records are a rich source of real-world data that can provide insights into health and wellness. Neal Meropol, head of research oncology at Flatiron Health, said they not only have value as a research tool for retrospective studies, but can be a treasure trove of information for prospective studies as well. We spoke to Meropol about how real-world evidence can inform better clinical trial designs and accelerate drug development, how Flatiron works with its clients, and a recent study he was involved in that suggest drug developers who want to increase the diversity of clinical trials participants should consider broadening their inclusion criteria.

Earlier this year, Profluent announced it had edited the human genome with OpenCRISPR-1, the world’s first AI-created and open-source gene editor. Though the open-source aspect helped garner attention for Profluent, it also served as a demonstration of the company’s generative AI platform to create novel CRISPR gene editors. We spoke to Hilary Eaton, chief business officer for Profluent, about how the company’s generative AI engine works, its business model, and why its platform has the potential to create other protein therapeutics of varying modalities.

About 500,000 people suffer from a spinal cord injury each year. Treatments can involve surgical procedures to stabilize the spine and physical rehabilitation, which can have limited benefits. There are currently no FDA-approved therapies that can promote repair and improve function following a spinal cord injury. NervGen Pharma is seeking to change that by developing therapies that allow the nervous system to repair itself. We spoke to Mike Kelly, CEO of NervGen, about the potential for using therapies designed to allow the nervous system to repair itself, how the company’s lead experimental candidate for spinal cord injury works, and why the same approach holds promise in treating a range of neurodegenerative diseases.

One of the challenges of treating neurodegenerative diseases is delivering therapies across the blood-brain barrier. Aliada Therapeutics is developing therapies that use its platform technology that enables the delivery of large molecules, like antibodies, across that barrier. Its lead program is in development to treat Alzheimer’s disease. We spoke to John Dunlop, chief scientific officer of Aliada, about its platform technology, its origins at Johnson & Johnson’s Janssen, and the company’s partnering strategy for leveraging the technology.

SalubrisBio, rather than shy away from complexity, embraces it. The company’s lead experimental therapy is an antibody fusion protein in development for both heart failure and the rare, neurodevelopmental condition amyotrophic lateral sclerosis. We spoke to Sam Murphy, CEO of SalubrisBio, about the challenges of pursuing complex diseases with complex therapies, its pipeline, and how its China-based parent has provided it financial freedom from the vagaries of the capital markets.

One of the challenges facing genetic medicines is delivering payloads across the human cell membrane and inside cells both effectively and with high tolerability. Aegis Life is capitalizing on its parent Entos Pharmaceuticals’ nucleic acid delivery platform technology to address infectious diseases. It recently secured investment from the Bill & Melinda Gates Foundation to help in the fight against malaria, HIV, and other conditions. We spoke to John Lewis, founder and CEO of Aegis Life, about the need it is addressing, the company’s platform technology, and how it is leveraging that to address the barriers to the delivery of vaccines and antibody therapies in developing economies.

The idea of developing cancer vaccines that harness dendritic cells is not new, but Diakonos Oncology thinks it’s been able to solve the lack of efficacy that has plagued this approach. The company combines its vaccines with RNA and proteins from a patient’s tumor to trigger a robust response by tricking the immune system to recognize cancer cells as being virally infected. We spoke to Jay Hartenbach, chief operating officer of Diakonos, about its dendritic cell cancer vaccine technology, how it works, and why its lead indication is an aggressive form of brain cancer.

Kinase inhibitors have given rise to an era of precision medicine for the treatment of cancer, but the ability of cancer cells to mutate enables tumors to develop resistance to existing therapies. Nuvalent is developing therapies that both target the original tumor as well tumors with emergent resistance. We spoke to James Porter, CEO of Nuvalent, about how it designs drugs that address the challenges of both kinase resistance and selectivity, its pipeline in development, and why it’s critical that its experimental therapy for non-small cell lung cancer can penetrate the brain.

Each year, an estimated 400,000 people in the United States will be diagnosed with Lyme disease, a billion-dollar healthcare problem caused by a bacterial infection that is transmitted through the bite of a tick. The condition can cause joint pain and fatigue, but is treatable with antibiotics. Left untreated, though, it can progress and cause more serious symptoms including facial palsy, an irregular heartbeat, and nerve pain. Tarsus Pharmaceuticals is developing a human formulation of the antiparasitic lotilaner, to prevent Lyme disease. We spoke to Bobby Azamian, CEO of Tarsus, about Lyme disease, the case for the company’s experimental prophylactic drug TP-05, and why you may already have been using a form of the drug to protect a four-legged member of your household.

In February, the U.S. Food and Drug Administration approved the first tumor-infiltrating lymphocyte, or TIL therapy, for solid tumors. The approval was hailed as a milestone that points the path forward for a new class of cell therapies for solid tumors. We spoke to Jason Bock, CEO of CMTC, the joint venture between Resilience and MD Anderson Cancer Center, about the emerging area of TIL therapies, the significance of the first approved therapy in the class, and how they may address existing limitations of CAR-T therapies.  

Lipids have long been used as drug delivery vehicles, but HighField Biopharmaceutics is repurposing lipids as drugs to fight cancer. The company’s technology platform is seeking to change the immunotherapy landscape with new treatments that are better targeted, more potent, and less toxic. We spoke to Don Wyatt, chief business officer for HighField Biopharmaceuticals, about the tumor microenvironment, HighField’s platform technology, and how it is developing lipid-based medicines to overcome challenges of existing immunotherapies.

Jeremiah Robison’s daughter Sofia was born with cerebral palsy, a congenital movement disorder. Watching her physicians use body monitors to measure her gait, and later apply functional electrical stimulation as physical therapy, gave him an idea to combine the two to create a sleeve that could be worn on her leg to improve her ability to walk. Now Cionic, the company he co-founded, is producing its Neural Sleeves to help people with a variety of mobility impairments better navigate the world. We spoke to Robison, CEO of Cionic, about the Neural Sleeve, how functional electronical stimulation helps people with movement disorders walk, and how the use of adaptive algorithms continuously optimizes the stimulation it delivers.

Physicians treating people with burns typically incorrectly assess the depth of burn wounds in about 25 to 30 percent of cases. That, in part, is due to a lack of diagnostic tools to assess the severity of a burn and to determine the best approach to treatment. Spectral AI has developed the DeepView System, a predictive device that offers clinicians an objective and immediate assessment of a wound’s healing potential prior to treatment or other medical interventions. We spoke to Pete Carlson, CEO of Spectral AI, about the company’s AI-driven DeepView System, how it works, and how it changes outcomes for patients.

New York City is not the first place that comes to mind when thinking of biotech clusters, but the Big Apple has been a growing center of biomedical innovation with its mix of academic research hospitals, finance, and growing number of biopharmaceutical companies. One place that’s seeking to serve as both a home to innovative companies and facilitate collaborations is Cure, which describes itself as a healthcare innovation campus. We spoke to Seema Kumar, CEO of Cure, about how it operates, its various initiatives, and what can be done to accelerate the movement of innovative technologies from the lab to the marketplace.

Funding levels, drug launches, and R&D success rates all grew in 2023, according to a new report from the IQVIA Institute for Human Data Science. Global funding of biopharmaceutical research and development increased to $72 billion, up from $61 billion in 2022. M&A activity jumped to $140 billion from $78 billion during the same period. We spoke to Murray Aitken, executive director of the IQVIA Institute for Human Data Science, about its Global Trends in R&D 2024 report, what he’s watching, and why the new patent cliff for the industry will be less threatening than the last one.

In January 2023, AstraZeneca agreed to acquire CinCor Pharma, the CinRx cardio-renal disease therapy subsidiary, for $1.3 billion. The deal included a potential additional $500 million milestone payment. The price represented a 121 percent premium to CinCor’s market value at the time and could grow to more than a 200 percent premium if the milestone is met. The sale represented validation of CinRX’s portfolio approach to build multiple biotech companies supported with a dedicated funding mechanism. We spoke to Jon Isaacsohn, founder and CEO of CinRx, about the company’s portfolio approach, how its business model allows it to accelerate the development of needed medicines, and its efforts to develop new obesity therapies.

Antibody-drug conjugates can deliver chemotherapy directly to tumors but more than 95 percent of the dose often ends up in healthy tissues, decreasing efficacy and increasing toxicity. Mythic Therapeutics FateControl technology improves the uptake of ADCs in cancerous cells while avoiding the release of their toxic payloads in healthy ones. This promises to increase efficacy of these therapies in a wide range of cancers without causing unacceptable side-effects. We spoke to Brian Fiske, co-founder, chief scientific officer of Mythic, about the challenges that have held back the benefits of ADCs, how the company’s FateControl technology addresses those, and how it is thinking of building a pipeline of ADCs across indications.

The HGF/MET neurotrophic system plays a critical role in the maintenance and repair of connections in the brain. Enhanced signaling along this pathway has the potential to reduce inflammation, slow neurodegeneration, and provide neuroprotection. Athira Pharma is pursuing small molecule drugs that target this pathway to address a range of neurodegenerative conditions. The company is currently conducting a phase 2/3 study of its lead therapeutic candidate, fosgonimeton, in mild-to-moderate Alzheimer’s disease. But the study comes after the experimental therapy failed to meet its primary endpoint in a phase 2 study in Alzheimer’s disease and a phase 2 study in Parkinson’s disease dementia and dementia with Lewy bodies. We spoke to Rachel Lenington, chief operating officer of Athira Pharma, about the case for targeting the HGF/MET neurotrophic system in neurodegenerative diseases, how its experimental therapy fosgonimeton works, and why its continuing to pursue the therapy despite earlier failures.

The advent of induced pluripotent stem cells, cells that can be coaxed into becoming virtually any type of cell within the body, promised to usher in a new era of regenerative medicine and improved drug discovery. In practice, though, the ability to use these cells to develop desired cell types has proved challenging to do in a predictable way and at scale. Bit.bio, has developed a synthetic biology platform that it says allows it to industrialize this process and produce desired cells in a consistent manner. We spoke to Mark Kotter, founder and CEO of Bit.Bio, about the company’s platform technology, its effort to develop cell therapies, and its growing offering of precision reprogramed human cells for drug development.  

Some 100 trillion gigabytes of data are created and consumed each year, an amount that is expected to double by 2025. The demand for data storage carries the need for significant physical space and power requirements in the form of digital data centers. DNA, though, may represent a solution to what some see as unsustainable growth with environmental consequences. DNA, it turns out, is a dense and durable way to store information. At the end of last year, Paris-based Biomemory launched its DNA Cards, the first DNA data storage ever offered to the general public. The DNA memory cards, about the size of a credit card-sized today may seem more like a curiosity than a viable solution. At $1,000 each, they can store a kilobyte of data, enough to store a single, brief email. We spoke to Erfane Awani, founder and CEO of Biomemory, about the use of DNA for data storage, how it works, and how quickly the technology can scale to where it competes with today’s data storage infrastructure.

People tend to think of each person having their own unique genome. Quotient Therapeutics is taking an approach to drug discovery based on the reality that from cell to cell within a given individual, there can be trillions of divergent genomes. Changes in cells throughout the body can alter how a cell responds to disease and point to new ways to cure, treat, or prevent conditions. We spoke to Jacob Rubens, president of Quotient, about the company’s platform technology, how it uncovers genetic mutations at a cellular level, and its efforts to build a pipeline of therapies around the insights it gains.

Regardless of the cause of a disease, most diseases involve gene dysregulation. Omega Therapeutics is developing a new class of programmable, epigenomic, mRNA medicines designed to make specific epigenetic changes and correct abnormal gene expression to treat or cure diseases. We spoke to Mahesh Karande, president and CEO of Omega Therapeutics, about its pipeline of mRNA therapies, how they work, and its recently announced collaboration with Novo Nordisk to develop an epigenomic controller to treat obesity.

The effects of spinal cord injury extend beyond the loss of mobility. They can include a toll on mental health, a feeling of exclusion, and a general decline in the quality of life as a result of being able to stand and interact eye-to-eye with others. ReWalk Robotics’ Personal Exoskeleton is configured to an individual’s body and enables someone who has suffered a spinal cord injury to stand, walk, and even climb up and down stairs. We spoke to Larry Jasinski, CEO of ReWalk Robotics, about the company’s Personal Exoskeleton, how it works, and the impact it can have on the quality of life for someone with a spinal cord injury.

Mitochondria are often referred to as the “powerhouses” of the cell, but as scientists gain a greater understanding of these essential organelles, they are coming to discover they play a more expansive role in health and disease. The Foundation for the National Institutes of Health named Navdeep Chandel a co-recipient of the 2023 Lurie Prize in Biomedical Sciences for his research that revealed how mitochondria function as signaling organelles that control the body’s normal functions and impact diseases, including cancer and inflammation. We spoke to Chandel, professor of medicine in the Division of Pulmonary and Critical Care and of biochemistry and molecular genetics at the Feinberg School of Medicine, about the state of our understanding of mitochondria, why drug developers are pursuing therapies to target mitochondria across a broad range of diseases, and the need for a concerted effort to conduct fundamental research to better understand the biology of this organelle.

Sandbox AQ, the Alphabet spin-out backed with $500 million in investment, in June 2023 unveiled it AQBioSim division. The division is working to bring SandoxAQ’s AI and quantum-inspired computing to develop new treatments for intractable medical conditions including neurodegenerative diseases and cancer. The company is working with leading drug developers and university medical centers to accelerate drug development, reduce costs, and improve the rate of clinical success. We spoke to Nadia Harhen, general manager of simulation and optimization for SandboxAQ, about the challenges of drug development it is seeking to address, how Sandbox AQ is leveraging quantum technologies, and why it is seeking to tackle an intractable set of diseases. One note: As we were preparing to publish this episode, Sandbox AQ announced it acquired Good Chemistry, a computational chemistry company that leverages AI, quantum, and other advanced technologies to accelerate drug discovery. The deal is expected to enhance SandboxAQ’s existing computational chemistry and simulation capabilities, adding talent, technologies, and industry insights.

It’s long been understood that chromosomal instability (CIN) is a characteristic of cancer cells, but it also represents a key difference between cancer cells and healthy cells that can be exploited. Volastra is developing medicines for a wide range of difficult-to-treat cancers that target the vulnerabilities of these cells. We spoke to Charles Hugh-Jones, CEO of Volastra, about chromosomal instability in cancer cells, how the company is developing a pipeline of therapies to exploit this, and its expanding relationships with Big Pharma.

Though the year began with a banking crisis and has been marked with layoffs and restructurings, we have managed to avoid a feared recession. It’s been a big year for new drug approvals, M&A activity has been brisk, and biotech stocks have rallied in recent weeks pushing the widely watched S&P biotech index into positive territory. We continue our annual tradition to look back across the year in biotech and ahead to JPMorgan and beyond with Adam Feuerstein, Polk award-winning journalist and senior biotech writer for STAT. We spoke to Feuerstein about the biotech news that shaped 2023, the year’s best and worst CEOs, and what’s ahead in 2024.

Vik Bajaj has long lived at the intersection of physical sciences, engineering, data science, and the life sciences—first as an academic working to improve diagnostic imaging at Stanford University and later as a chief scientific officer at GRAIL and Verily. Now, as a founder and CEO of Foresite Labs, the technologist turned venture capitalist is using his experience to create new companies that are leveraging AI and other technologies to transform healthcare. We spoke to Bajaj about the changing data landscape around healthcare, the potential for technology to improve health outcomes, and what it takes for an entrepreneur to get his attention today.   

Interleukin-2 therapies have been seen as promising ways to treat solid tumors, but they have proven challenging because of the ability of IL-2 to both activate and suppress the immune system. Their effectiveness has been limited because of potentially toxic side effects, which have included vascular leak syndrome and pulmonary edema. Aulos Biosciences believes the AI-based approach to computational drug design used for its lead experimental therapy allows it to unlock the power of IL-2 without triggering the concerning side effects of existing therapies. We spoke to Aron Knickerbocker, president and CEO of Aulos Bioscience, about the potential for IL-2 therapies to treat solid tumors, the limits of today's IL-2 therapies, and the AI-based design behind its experimental IL-2 therapy in development.

Real-world data promises to provide insights that lead to better therapies, change how we treat diseases, and improve outcomes for patients. One of the limits of realizing benefits from all of the health information we are swimming in is the lack of access to high-quality data in a usable format. Verana Health has built partnerships with medical societies to provide access to exclusive, real-world data from a network of more than 20,000 clinicians. We spoke to Sujay Jadhav, CEO of Verana Health, about the potential for real-world data to improve our understanding of health, how Verana is addressing challenges these data can present, and the areas of medicine on which it is focused.

Artificial intelligence promises to reshape the healthcare landscape and deliver new insights into the molecular drivers of health and wellness, provide rapid diagnoses of patients, and discover and design therapies that extend beyond human imagination. Swaroop ‘Kittu’ Kolluri, founder and managing director of Neotribe Ventures, is using his experience as a Silicon Valley entrepreneur to invest in the emerging TechBio space. We spoke to Kolluri about the state of AI, the potential of technology to transform healthcare, and Neotribe’s approach to investing.

Though many drug developers are harnessing AI to create novel chemical compounds, Iambic Therapeutic’s generative AI is leveraging quantum mechanics to get to better drugs. It says its physics-informed machine learning approach has yielded promising lead candidates with superior profiles in record time. In October, Iambic completed a $100 million series B financing round to support development of its platform and to advance multiple candidates into clinical development. We spoke to Tom Miller, co-founder and CEO of Iambic, about its AI platform,, the insights Iambic gains from using a quantum mechanics-based approach to drug discovery, and its growing pipeline of cancer therapies.

One of the challenges with treating Alzheimer’s disease is diagnosing patients early enough in the course of its progression to have a meaningful impact with treatments. Sunbird Bio said it can accurately detect and differentiate specific proteins that aggregate and signal the presence of Alzheimer's disease, with a simple blood draw. It said its test in development could address the growing need for more sensitive, reliable, non-invasive diagnostic tests to accelerate drug development and enhance patient care. We spoke to John McDonough, executive chair and CEO of Sunbird Bio, about its diagnostic test for Alzheimer’s disease, how it has the potential to impact treatments and outcomes for millions of patients with the condition, and how its merger with Glympse Bio is expected to push it into new markets.

About 40 percent of all drugs in the Western world are derived from plants. But challenges with producing a reliable supply inherent with materials derived from agricultural processes can lead to drug shortages as climate events, pests, and plant diseases can affect yields. Antheia is harnessing synthetic biology to produce active pharmaceutical ingredients as an alternative to reliance on crop production. We spoke to Christina Smolke, co-founder and CEO of Antheia, about the supply-chain challenges underlying drug shortages, how the company is using synthetic biology to create a reliable supply of active pharmaceutical ingredients, and its growing pipeline of products in development.

The COVID 19 pandemic provided a painful reminder of the global need to protect people against the threat of existing and emerging infectious diseases. Emergex Vaccines is developing fully synthetic vaccines that provide advantages over live attenuated and RNA-based vaccines. The company says its vaccines can provide long-lasting T cell immunity, are cost effective, and stable at room temperature. We spoke to Thomas Rademacher, co-founder and CEO of Emergex Vaccines, about the company’s platform technologies, the manufacturing advantages they offer, and the company’s pursuit of universal coronavirus and influenza vaccines that work across variants.

The advent of targeted therapies has contributed to notable progress in the fight against cancer, but the ability of cancers to develop resistance to these precision medicines continues to leave patients in need of new approaches. Concarlo Therapeutics is developing therapies that target a critical driver of cell proliferation that is reactivated once a cancer grows resistant to certain targeted therapies. We spoke to Stacy Blain, co-founder and chief scientific officer of Concarlo, about the development of drug resistance in cancer, the company’s initial focus on breast cancer, and her own journey from academia to biopharma.

There have been significant advances to immunotherapies since their first introduction, but challenges remain to realizing their full potential in solid tumors. That’s because of the ability of tumors to use multiple mechanisms to evade the immune system. Akamis Bio is developing tumor gene therapies that are capable of targeting tumors and driving expression of multiple immunologically active biomolecules and therapeutic proteins to create a robust, antitumor immune responses. We spoke to Howard Davis, CEO of Akamis Bio, about the challenges immunotherapies have faced in addressing solid tumors, the company’s tumor gene therapy platform, and how it turns tumors against themselves to stimulate an immune response.

Mini-proteins have the power and performance of an antibody with the ability to bind tightly to a target. But because of their small size, it can penetrate into places where small molecules can go. Ordaōs Bio is leveraging its generative AI platform to develop a pipeline of mini-protein therapeutics. We spoke to David Longo, co-founder and CEO of Ordaōs, about the company’s focus on mini-proteins, its generative AI platform, and why its building its own pipeline around rare disease indications and partnering with other drug developers on other indications.

The Fas signaling pathway plays a central role in activating cell death. As such, it is implicated in a range of conditions and has been associated with ophthalmic diseases. ONL Therapeutics is developing therapies that target Fas signaling to address a range of retinal conditions. We spoke to Connie Chang, chief operating officer for ONL Therapeutics, about the role Fas-signaling plays in cell death, how this underlies a number of retinal diseases, and the company’s experimental therapy to inhibit Fas signaling.

Antibody discovery is a long, costly, and complex process. LabGenius is reinventing that process by using its platform technology that combines AI with robotic systems capable of designing, conducting, and learning from its own experiments. Its platform not only has the potential to accelerate the drug discovery process but can generate high-performing molecules that likely would not have been found through conventional discovery methods. We spoke to James Field, founder and CEO of LabGenius, about the company’s use of generative AI to discover new therapeutic antibodies, its initial focus on immunotherapies, why he thinks the data the company is generating to train its AI system is a significant point of differentiation.

Opioid overdose, abuse, and addiction affect an estimated 3 million Americans and accounts for $35 billion in U.S. healthcare costs every year. Tris Pharma is developing the opioid Cebranopadol, as an effective pain management therapy without the addictive potential of FDA-approved opioids. We spoke to Ketan Mehta, founder and CEO of Tris Pharma, about Cebranopadol, how it modulates the addictive potential by targeting two receptors at once, and its potential to address the opioid crisis. An editor’s note: since recording this podcast, the National Institute on Drug Abuse, part of the National Institutes of Health, awarded Tris a five-year, $16.6 million grant to advance Cebranopadol.

With the rapid advances in cancer research, it can be difficult for physicians to stay on top of all of the emerging treatments in clinical development. Leal Health has developed an AI-powered platform that provides a personalized list of treatment options to match a patient’s precise diagnosis to advanced therapies in clinical testing. We spoke to Tzvia Bader, co-founder and CEO of Leal Health, about her own experience with cancer, how that led to the creation of Leal Health, and how it is harnessing AI to connect patients to clinical trials based on their exact diagnoses.  

Earlier this year, the venture capital firm SR One closed a $600 million fund, its second since spinning out from the pharmaceutical giant GSK. Despite the difficult investment landscape today for biotechs, it’s a reminder that significant capital is available to be deployed. We spoke to Simeon George, CEO and managing partner for SR One, about the firm’s investment approach, how the current landscape is causing venture capitalists and therapeutics developers to think differently, and what advice he’d offer entrepreneurs seeking to raise money today.  

Cytokines, which play an essential role in immune cell signaling, have long been recognized as having great therapeutic potential, but efforts to harness them have been hampered by their toxicity. Bonum Therapeutics is overcoming this limitation by engineering cytokines with a sensor domain that makes their activity dependent on their environment. While the company is focusing its efforts to develop regulated cytokine to treat cancer, it also has potential as an approach to autoimmune, metabolic, and other conditions. We spoke to Bonum Therapeutics Chief Scientific Officer Diane Hollenbaugh and Bonum Chief Business Officer Neela Patel about the therapeutic potential of cytokines, the challenges of using them as therapeutics, and why Bonum’s context-dependent cytokines may enable wider use of these proteins to treat a range of diseases

The Epstein-Barr virus is among the most common viruses associated diseases including multiple sclerosis and certain cancers. Atara Biotherapeutics is developing off-the-shelf, T-cell immunotherapies designed to target cancers and autoimmune conditions driven by the Epstein-Barr virus. It is also using its EBV T-cell platform to develop next-generation allogenic CAR T therapies to target a range of non-EBV associated diseases. We spoke to Pascal Touchon, president and CEO of Atara, about the role of the Epstein-Barr virus in certain cancers and autoimmune conditions, the company’s platform technology for allogenic CAR T therapies, and why it has implications beyond EBV-driven diseases.

Myeloid cells can stimulate anti-tumor effects in the body and recruit additional immune system cells to turn a cold tumor hot. Bolt Biotherapeutics is developing a new category of immunotherapies that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. By activating and recruiting myeloid cells, the company’s experimental therapies are designed to re-program the tumor microenvironment and invoke an anti-tumor immune response. We spoke to Randy Schatzman, CEO of Bolt Biotherapeutics, about the company’s immune-stimulating antibody conjugates, the case for activating both the innate and adaptive immune systems to fight cancer, and the company’s lead experimental therapy for HER2 positive cancers.

The development of mRNA-based vaccines has represented a major advance in the field of vaccine development. Rather than using weakened or inactivated viruses to stimulate an immune response to generate protective antibodies, mRNA-based vaccines provide a potentially safer and more effective approach. mRNA vaccines work by introducing a small piece of mRNA into the body, which encodes instructions to produce a specific viral protein for the cell to manufacture. This protein then triggers an immune response, leading to the production of antibodies that can protect against specific diseases. Combined Therapeutics has designed a modified mRNA-based vaccine platform that allows for the inhibition of protein expression in specific tissues, enabling targeted vaccine treatment and preventing off-target side effects. It’s designed to be adaptable and efficient, which makes possible rapid production of vaccines for a wide range of diseases and disease variants. We spoke to Thomas VanCott, chief scientific officer of Combined Therapeutics, about the company’s mRNA platform for vaccines, the advantages it provides, and its potential to use the same approach to train the immune system on specific mutations in a tumor.

Infectious diseases and microbial resistance represent major concerns in developing nations. The combination of globalization with the expanded use of antibiotics in resource-constrained environments is worsening the problem. In fact, hospital acquired infection rates in some regions are three times greater than in the United States and as much as 30 percent of all such infections are antimicrobial resistant. HDT Bio is developing immune activators and RNA-based vaccines to address this challenge with cost-effective and accessible medicines. We spoke to Chris Pirie, co-founder and chief operating officer of HDT Bio, about the problem the company is seeking to address, its platform technology for producing safe and stable RNA vaccines, and the potential to use the same platform to produce immunotherapies for cancer.

Bacteriophage are viruses that target bacteria. Though they emerged in the 1920s as treatments for infectious diseases, because of their high level of specificity, they fell out of favor with the advent of broad-spectrum antibiotics. BiomX is developing both natural and engineered phage cocktails designed to target and destroy harmful bacteria in chronic diseases, such as cystic fibrosis, inflammatory bowel disease, and atopic dermatitis. We spoke to Jonathan Solomon, CEO of BiomX, about the case for phage therapies, the company’s approach to creating a phage cocktail that could effectively target a population of patients, and why it's focusing on chronic diseases.

CytoMed, a spin out of A*STAR—Singapore’s Agency for Science, Technology, and Research—is developing novel cell-based immunotherapies that can go beyond the limitations of existing CAR T therapies. The company is focused on the development of off-the-shelf therapies derived from the delta gamma T cells from healthy donors. We spoke to Wee Kiat Tan, chief operating officer of CytoMed, about the company’s platform technology for off-the-shelf CAR T therapies, the advantages they provide over existing autologous CAR T therapies, and why he believes they will be successful at treating solid tumors.

For academic scientists who make groundbreaking discoveries that can lead to new medicines, bridging the so-called valley of death—the gulf between the lab and having a validated candidate that is ready to begin human clinical trials—continues to be daunting. Foundery Innovations, which bills itself as a venture studio, sees a big opportunity in partnering with academic researchers to carry promising new immunotherapies through to the clinic. Its team has deep experience in immunotherapy development and brings a wide range of skills and cutting-edge platform technologies to de-risk development and accelerate the time to the clinic. We spoke to Max Krummel, founder and managing member of Foundery Innovations, about the venture studio’s business model, the resources it brings to bear, and how it works with academic researchers and universities.

Vericel, which acquired Sanofi’s cell therapy and regenerative medicine unit, markets advanced cell therapy products for sports medicine and severe burn care. The company’s MACI is an autologous cellularized scaffold used in the repair of cartilage defects of the knee. Epicel, its cultured epidermal autografts, are a permanent skin replacement for the treatment of patients with deep dermal or full thickness burns greater than or equal to 30 percent of total body surface area. We spoke to Nick Colangelo, president and CEO of Vericel, about the markets the company is targeting, how its products are changing outcomes for patients, and the company’s plans for growth.

Understanding the physical relationship of cells and how they interact can provide new understanding of diseases and help improve drug development and clinical treatment decisions. Nucleai uses its AI-powered spatial biology platform to transform pathology data into insights. The digital assays it develops enhances drug development, supports treatment decisions, and helps stratify patients to improve care. We spoke to Ken Bloom, head of pathology for Nucleai, about the company’s AI spatial biology platform, how it works, and the potential it has to advance precision medicine.

Vaccitech first gained attention as co-inventor of the Covid-19 vaccine licensed to AstraZeneca. The University of Oxford spin-out is developing a pipeline of T cell immunotherapies to treat and cure chronic infectious diseases, autoimmune diseases, and cancers. The company’s lead experimental therapy is a potentially curative monotherapy for chronic hepatitis B viral infection. We spoke to Bill Enright, CEO of Vaccitech, about the company’s platform technologies, how they work, and how they enable the development of more effective immunotherapies.

One reason that CAR T therapies haven’t been more effective at treating solid tumors is their reliance on targeting antigens on the surface of cells, which can often be present on healthy cells as well. Affini-T Therapeutics is addressing this weakness in current cell therapies by using its platform technology to develop T cell receptor engineered T cells. Its so-called TCR-T cells are able to recognize intracellular targets and attack the drivers of mutations that are inaccessible to CAR-T therapies. We spoke to Jak Knowles, CEO of Affini-T Therapeutics, about the company’s TCR-T cell therapies, how they are engineered, and why they have the potential to be effective at treating solid tumors that have evaded the power of CAR T therapies.

More than 138,000 people in the United States and 1.4 million people worldwide are struggling with malignant brain tumors. The average five-year survival rate of people with the most common malignant brain tumor—glioblastoma multiforme—is less than 5 percent and there have been no notable improvements in the last three decades. The Ivy Brain Tumor Center is using phase 0 clinical trials to provide individualized treatment to patients with brain tumors. The U.S. Food and Drug Administration introduced phase 0 trials in 2004 to address concerns about the slow pace and high cost of drug development. The phase 0 trial is used to quickly identify how a drug works in a patient and whether it should be fast-tracked for further development. We spoke to Nader Sanai, director of the Ivy Brain Tumor Center and chief of neurosurgical oncology at the Barrow Neurological Institute, about phase 0 clinical trials, how they work, and how they are allowing the center to take a precision medicine approach to treating patients with brain tumors.

Traumatic injuries and surgical procedures can damage peripheral nerves and cause the loss of muscle or organ function, pain, and the loss of sensation. Axogen has a portfolio of regenerative medicine products to enable surgeons to repair peripheral nerves without the need to harvest nerves from a patient’s own body. We spoke to Karen Zaderej, CEO of Axogen, about peripheral nerve injuries, the company’s portfolio of products, and how it is changing the way surgeons can repair and regenerate damaged nerves.

About 20 years ago, the number of people dying from chronic diseases surpassed the number of people dying from infectious ones. Though vaccines have contributed to this shift, they’ve generally not been harnessed to address chronic conditions. Vaxxinity is seeking to change that by using vaccine technology to address the growing burden of chronic diseases. It’s advancing a new class of synthetic, peptide-based vaccines designed to activate the body’s immune system to produce antibodies to neurodegenerative, cardiovascular and other chronic diseases. The company’s pipeline includes experimental therapies for Alzheimer’s disease, Parkinson’s disease, and hypercholesterolemia. We spoke to Mei Mei Hu, CEO of Vaxxinity, about the case for using vaccines to address chronic diseases, the benefits this approach provides, and how its platform technology activates the immune system to battle non-communicable diseases.      

Developing therapies that work by degrading disease-causing proteins has shown promise, but first-generation approaches have been limited to targeting intracellular proteins and can’t reach membrane and extracellular proteins that represent about 40 percent of the proteome. EpiBiologics is working to expand protein degradation therapies to include membrane and extracellular targets with the goal of eliminating disease-causing proteins that were previously not addressable by traditional therapeutic approaches. We spoke to Rami Hannoush co-founder and interim CEO and president of EpiBiologics, about the company’s platform technology, how its protein degradation approach expands the potential targets for its therapies; and how its built an atlas of tissue-specific degrader antibodies to target proteins involved in cancer, immunologic-, and neurologic-related conditions.

While many people think of biotechnology in terms of its impact on medicine, it’s expected to transform the economy as its power reaches across industries. As biology increasingly becomes an engineering discipline, it is not only reshaping the way we produce food, but a wide range of industrial products as well. Bio-based processes are replacing petroleum-based ones and giving life to new biomaterials, bioplastics, and biofuels. As the SynBioBeta Global Synthetic Biology Conference returns to Oakland, California May 23 to May 25, we spoke to SynBioBeta Founder and CEO John Cumbers, about the state of the emerging bioeconomy, how biotechnology is being embraced across industries, and the unexpected places biotechnology is already showing up.

One reason that cancers can be difficult to treat is that the tumor microenvironment can hamper the ability of drugs to penetrate the tumor and facilitate the development of resistance to medicines. AUM Biosciences is developing targeted therapies that address genetic drivers of a cancer and can disable defenses that hide tumors from the immune system. The company’s lead experimental therapy is being tested in combination with immunotherapies to treat colorectal cancer and other solid tumors. We spoke to Vishal Doshi, chairman and CEO of AUM, about the development of resistance in cancers, the case of combining precision therapies with immunotherapies, and why he believes we can transform cancer from a deadly condition to a chronic disease.

While there has been great interest in harvesting and targeting the microbiome to treat disease, Federation Bio believes for durable benefits its necessary to provide a rich ecosystem of microbes in a single therapy. The company has developed a platform for producing synthetic microbial cell therapies to treat a range of diseases from metabolic disorders to metastatic cancers. Unlike earlier approaches, the company said it is generating potent, reproducible, and complete microbial consortia that stably engraft to provide predictable and durable responses. We spoke to Emily Drabant Conley, CEO of Federation Bio, about its platform technology, how it determines what to include or exclude in a given therapy, and what makes a disease a good candidate for its living therapeutics approach.

One of the challenges of treating traumatic injuries and degenerative conditions is that while there are therapeutic proteins that can promote repair, they can be difficult to deliver to the site of damage and get them to stay there long enough to provide benefit. Therapdaptive has developed platform technology that enables it to produce variants of recombinant proteins that can bind to the surface of implants, devices, and injectable carriers to allow for precision delivery anywhere in the body. We spoke to Luis Alvarez, CEO of Theradaptive, about the company’s platform technology to produce recombinant proteins that bind to materials, the broad applications for the technology, and how the roots of the company go back to a need he saw during his service in the Iraq war.

In 2022, investment in biopharmaceutical companies, pipeline activity, and the launch of novel medicines all dropped from the previous year. A new report from IQVIA’s Institute for Human Data Sciences argues the downturn, after two record-setting years, is a post pandemic return to longer-term trends. We spoke to Murray Aitken, executive director of the IQVIA Institute for Human Data Science, about what happened to the biopharmaceutical sector in 2022, how to make sense of the data, and the shifting landscape in therapeutic and geographic investments.

The aging process is associated with the development of diseases. BioAge Labs is seeking to expand healthy lifespans by developing therapies for aging-related diseases that target key pathways involved in the aging process. The company has built a platform that combines systems biology and AI to leverage extensive data sets to uncover molecular drivers of aging-related diseases. We spoke to Kristen Fortney, CEO of BioAge, about the company's approach to identifying targets for aging-related diseases, its therapeutic pipeline, and whether it's pursuing any novel targets yet.

Cell therapies are revolutionizing the way cancers are treated, but existing cell therapies have their limits. They have been more successful at treating hematologic tumors than solid tumors, and they can sometimes cause serious side effects, such as the destruction of antibodies or what’s known a cytokine storms in which the immune system gets over-revved and attacks healthy cells. Triumvira Immunologics is developing autologous and allogenic T cell therapies that it believes can address the limitations of existing cell therapies and be used to treat both liquid and solid tumors. We spoke to Paul Lammers, CEO of Triumvira, about the company’s platform technology, why it’s robust and versatile, and why its lead indication is for a cancer where effective treatments already exist.

A complex of proteins that play an essential role in regulating the innate immune system known as the NLRP3 inflammasome is becoming a growing target of interest among drug developers to disrupt immune cell signaling. Halia Therapeutics is developing a pipeline of therapies that target the NLRP3 inflammasome to address not only inflammatory disorders like psoriasis and colitis, but neurologic conditions such as Alzheimer’s disease. We spoke to David Bearss, president and CEO of Halia, about the NLRP3 inflammasome, the role it plays in Alzheimer’s and other neurologic conditions, and the case for this therapeutic approach.

Though the transplantation of insulin-producing islet cells has been used to treat people with type 1 diabetes, such procedures require the use of immunosuppressive drugs to prevent the immune system from rejecting the cells. iTolerance is developing platform technology that can be used with tissue, organoid, and cell therapies without the need for life-long immunosuppression. We spoke to Anthony Japour, president and CEO of iTolerance, about the company’s platform technology that eliminates the need for immunosuppressive drugs with tissue and cell transplantation, the company’s lead experimental cell therapy for type 1 diabetes, and the broad range of regenerative therapies that could benefit from the technology.

Dyadic is working to bridge the gap between high-yield, low-cost, and large-scale industrial biotechnology, and low-yield, high-cost, small-scale biopharmaceuticals. It’s C1 technology, which is a fungal expression system, can efficiently produce enzymes and other proteins. Earlier this year, the company achieved a milestone when it began dosing patients in a phase 1 clinical trial in South Africa of its COVID-19 booster vaccine. The company expects the first-in-human trial to accelerate the adoption of the C-1 production platform for vaccine and therapeutic candidates. We spoke to Mark Emalfarb, president and CEO of Dyadic, about the company’s fungal-based manufacturing platform, how it can product large volumes of enzymes and other proteins in a fast and cost-effective manner, and the potential this has to change the way biologics are manufactured.    

Sam Gambhir understood the ravages of cancer. His wife developed breast cancer and survived. His son later developed brain cancer at the age 15 and died. And in 2020, Gambhir himself succumbed to cancer. Before he died, though, Gambhir, who served as division chief of the Canary Center for Early Cancer Detection and Molecular Imaging at Stanford University, hit upon an idea. Rather than hunt for cancers in the hopes of making an early diagnosis, he devised a way for them to produce synthetic biomarkers to cause them to reveal themselves. He co-founded Earli, which seeks to enable the diagnosis cancers when they are most treatable. We spoke to David Suhy, co-founder and chief scientific officer of Earli, about the company’s synthetic biomarker technology that makes cancers visible with a PET scan, how it works, and how this has the potential to alter outcomes for patients by enabling treatments of patients before their disease progresses.

Finding diverse groups of qualified participants for clinical studies can slow the development of needed medicines. The difficulty in attracting racial and ethnic minorities, women, and the elderly also creates concerns that trial results will fail to reflect what would happen in the real world. Some 80 percent of clinical trials fail to meet enrollment deadlines and an average of 30 percent of participants drop out in part because of the location and duration of these studies. CVS Health in 2021 launched CVS Clinical Trial Services, which capitalizes on CVS’ rich database of patients and its large footprint that puts a CVS location within 10 miles of 85 percent of the U.S. population. We spoke to Owen Garrick, chief medical officer of Clinical Trial Services at CVS Health, about the company’s push into clinical trials, the need to expand the diversity of participants in these studies, and how CVS is leveraging its resources to increase access to and participation in clinical trials.

The microbial world has been a rich source of medicines, but our ability to explore the full potential of the microbes both in us and around us has been limited by technology and the difficulty of culturing most microbes in a lab. Biosortia Microbiomics has developed a platform for finding, amplifying, and screening microbes as a potential source of novel, small molecule drugs. We spoke to Ross Youngs, CEO and founder of Biosortia, about the case for exploring various microbiomes to discover new small molecule drugs, how the company’s platform technology enables it to investigate a much broader range of microbes, and its business model for capitalizing on the discoveries it makes.

One of the underlying limitations of most cancer therapies is the fact that only about 1 to 2 percent of the drug that’s administered ever reaches tumors. That limits the dose because of the potential for unwanted side effects, and limits the efficacy by delivering less than ideal amounts of drug to tumors. Shasqi is developing cancer therapies that use click chemistry to activate agents at the site of tumors to reduce systemic toxicity and increase the anti-tumor activity of its medicines. We spoke to José Mejía Oneto, founder and CEO of Shasqi, about the company platform technology, how it works, and why this can lead to safer and more powerful cancer therapies.