The emergence of tyrosine kinase inhibitors represented a major advance in the fight against cancer, but the ability of tumors to mutate and develop resistance to these therapies remains a challenge. Theseus Pharmaceuticals is developing what it calls “pan-variant” kinase inhibitors in the hopes of outsmarting tumors by anticipating the range of kinases that may drive their spread and growth as they change. We spoke to Tim Clackson, president and CEO of Theseus Pharmaceuticals, about its structural-based approach to drug development, how it determines the appropriate targets for its pan-variant kinase inhibitors, and why it believes its next-generation TKIs can overcome the challenge of drug resistance.

The emerging understanding of the role the microbiome plays in wellness and disease is opening up a large number of potential therapeutic targets in the millions of genes that drive the microorganisms that live within the body. Eligo Bioscience is developing a new class of precision medicines that uses gene editing to address the expression of pathogenic genes in the microbiome to treat not only infectious disease, but other conditions such as inflammatory diseases and cancer as well. We spoke to Xavier Duportet, CEO of Eligo Bioscience, about the company’s use of synthetic DNA to target bacterial genes, its platform technology, and the wide range of conditions that can be addressed through this approach.

While cancer immunotherapies have been promising, CAR T cell therapies have been costly, effective on less than half of patients, and focused on hematologic cancers. Cytovia Therapeutics is enlisting natural killer cells, part of the innate immune system, to develop off-the-shelf immunotherapies to treat liquid and solid tumors. The company is leveraging a cluster of technologies to produce CAR NK cell therapies, edited NK cells to enhance their targeting, and NK engagers to redirect NK cells toward tumor targets. We spoke to Daniel Teper, co-founder and CEO of Cytovia, about the case for NK immunotherapies, Cytovia’s platform technologies, and the company’s pipeline of therapies in preclinical development.

Neurodegenerative diseases such as ALS, Alzheimer’s disease, and frontotemporal dementia have been difficult conditions for drug developers to target. Coya Therapeutics is approaching these conditions as diseases of immune system dysfunction to address the neuroinflammation that underlies them We spoke to Adrian Hepner, president and chief medical officer of Coya, about the role a hyper immune response plays in the progress of neurodegenerative diseases, how the company’s experimental regulatory T cell therapy works to halt that, and its pipeline in development.

The introduction of precision medicine has revolutionized the treatment of cancer and other diseases, but mental health conditions have not benefitted from the same type of treatment innovation. Alto Neuroscience is working to move psychiatry away from a trial-and-error approach to develop targeted medicines with the use of biomarkers to match the right drug to the right patient. We spoke to Amit Etkin, founder and CEO of Alto Neuroscience, about its efforts to develop precision medicines for mental health disorders, its AI platform for biomarker discovery, and its therapeutic pipeline in development.

The use of protein degraders is a promising area of emerging small molecule therapies. Rather than inhibit disease-causing proteins, degraders use a natural cellular process to break them down. Origami Therapeutics is using its proprietary drug discovery platform to develop novel protein degraders to target neurodegenerative diseases. The approach allows the company to target proteins that are considered undruggable because they lack an identified binding site. We spoke to Beth Hoffman, founder and CEO of Origami, about its platform for developing degraders, its focus on neurodegenerative diseases, and how its looking to potential partners to exploit the full potential of its platform technology.

Cancer immunotherapies have shown great promise, but many tumors can develop resistance as the changing tumor microenvironment can help cancers evade detection and allow cancer cells to proliferate. Teon Therapeutics is developing immno-oncology therapies for difficult to treat cancers that are designed to have the dual effect of restoring immune activity while suppressing cancer cell proliferation. We spoke to Serge Messerlian, CEO of Teon Therapeutics, about what happens when immunotherapies fail, the unique approach Teon is taking, and how the dual activity of its cancer therapies can restore immune activity while suppressing cancer cell proliferation.

Existing anticoagulants can prevent life-threatening blood clots for people with cardiovascular and metabolic diseases. The problem is that because of their mechanism of action, they also work to suppress the body’s ability to stop bleeding as it should. As a result, these therapies can be under utilized by patients who need them. Anthos Therapeutics is developing an experimental monoclonal antibody that can suppress coagulation without disrupting hemostasis, the biological process of stopping bleeding. We spoke to John Glasspool, CEO of Anthos, about the problems of existing anticoagulants, the novel target its monoclonal antibody acts on, and how it is able to uncouple the pathways for thrombosis and hemostasis.

Though the search for eternal youth has long been the fodder for myths and legends, science has been pushing us closer toward extending healthy years of life and has set some people off on efforts to defy death altogether. Peter Ward, in his new book The Price of Immortality: The Race to Live Forever, explores a subculture of immortality seekers who have turned to cryonics, as well as efforts to merge man with technology as a way to escape death. The growing understanding of the biology of aging and advances in regenerative medicine, though, are creating the potential to alter notions of human lifespans. We spoke to Ward about his book, distinguishing science fact from science fiction, and the growing understanding of the biology of aging that offers the potential for extending healthy years of life.

About 15 years ago, Harvard Business School professor Gary Pisano took at look at how small entrepreneurial biotechs fared against large and mature pharmaceutical companies and found the two sectors were about the same when it came to R&D productivity. Now, a new book From Breakthrough to Blockbuster: The Business of Biotechnology finds that the biotechnology industry is far more effective at bringing innovative therapies to market than Big Pharma and offers a prescription for large drug companies to decentralize decision-making to improve their ability to innovate. We spoke to venture investor and former biotech executive Don Drakeman, co-author of the book, about its findings, how decentralized decision-making can produce greater innovation, and lessons from COVID-19.