The Bio Report

One of the key obstacles to developing new drugs and diagnostics is the lack of access to longitudinal biological and clinical patient data. Culmination Bio, a spin-out of Intermountain Health, is building the largest patient data platform with more than 40 years of de-identified patient electronic health records and biospecimen data. We spoke to Lincoln Nadauld, president and CEO of Culmination Bio, about the data driving the company’s platform, how partners are using its data today, and how it has the potential to accelerate the development of new diagnostics and therapies.

NAMPT is a critical enzyme that regulates how cells use energy. It can also play an important role in the ability of cancer cells to survive, grow, and spread. While it’s been recognized as a potential target to treat certain cancers, developing NAMPT inhibitors have been challenging because they can disrupt energy metabolism in healthy cells. Remedy Plan Therapeutics believes it’s overcome the challenges of NAMPT inhibition by a unique mechanism of action that can avoid the problem of toxicity. We spoke to Greg Crimmins, founder and CEO of Remedy Plan Therapeutics, about the role of NAMPT in cancer, the challenges of developing NAMPT inhibitors without toxicity, and why he believes the company has solved the problem.

The emergence of CRISPR, a powerful tool for gene editing, promises to correct devastating genetic diseases, but it also raises concerns about how it will be used and who will make those decisions. Neal Baer, in his new book “The Promise and Peril of CRISPR,” brings together a series of essays by bioethicists, geneticists, and others who explore ethical and policy considerations raised by the technology. We spoke to Baer, co-director of the master’s degree program in Media, Medicine, and Health at Harvard Medical School; about whether there are unique questions raised by CRISPR as a dual-use technology, the book’s recasting of the case of Chinese scientist He Jiankui, and why he thinks there needs to be public debate now over the use of the technology to make heritable changes to the genome.

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.