The Bio Report

Realizing the Therapeutic Potential of Cytokines by Making them Context Dependent

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

Targeting Cancer and Autoimmune Conditions with Donor-Derived EBV T Cells

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.

Reprogramming the Tumor Microenviroment to Activate an Immune Response

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.

Making Safer and More Effective Vaccines with Targeted mRNA

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.

Addressing a Global Need with RNA Vaccines and Immunotherapies

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.

Targeting Bacteria in Chronic Diseases

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.

Targeting Solid Tumors with Off-The-Shelf CAR T Therapies

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.

Reimagining the Development of Immunotherapies with a Venture Studio

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.