The Bio Report

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 Co

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 w

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.