The National Institutes of Health (NIH) is a household name in the drug discovery and development industry. From regulatory guidelines to its numerous associated institutes, the NIH's impact is widespread in medical research. But that impact is perhaps most visible in the sheer amount of funding that the institute makes available every year in grants to support research studies and small businesses. In 2017 alone, the NIH estimated that it would disperse $18.2 billion—55 percent of its budget for the fiscal year—to finance “a total of 36,440 competitive, peer-reviewed and largely investigator-initiated research project grants.” For 2018, that percentage drops slightly, but still comes in at 53 percent.
Among the NIH's many recipients is South San Francisco, Calif.-based GigaGen, a biotherapeutics company. GigaGen's CEO, Dr. Dave Johnson, took some time to talk with us about how NIH funding and participation in the I-Corps commercialization program helped the company build momentum and secure additional funding and partner support.
DDNews: As an introduction, what is GigaGen’s focus and goal?
Dave Johnson: GigaGen focuses on understanding how immune regulatory pathways work and what causes them to fail so that we can develop novel antibody therapies for patients with cancer and immune deficiency. We have developed a proprietary antibody discovery technology called Surge that quickly characterizes every cell in complex immune systems, powering our selection of drug targets, identification of drug candidates and preclinical assessment of efficacy.
DDNews: Your company was able to focus on its Surge technology at the NIH’s I-Corps commercialization program. Can you give us a quick rundown on your technology platform, and the support framework that the I-Corps program provided GigaGen?
Johnson: The purpose of the I-Corps program is to refine a product strategy, not to refine the technology itself. The idea is that you want your product to solve problems that the market needs to have solved. In other words, you put the problem before the solution. We achieve this by interviewing 100+ "stakeholders" in less than three months. Stakeholders include potential customers or other individuals who might help refine the product. We ask them about the problems that they are facing in their work, and then describe how we would propose to help solve those problems. Eventually, patterns start to emerge, and we are able to specify a clear product-market fit. We have applied this methodology to several products in our portfolio.
For example, we had developed a technology that generates a DNA library of antibody sequences from millions of single B cells. This enabled us to identify the antibody sequences present in a diverse B cell repertoire. We also had a method that reformatted the DNA library into a yeast display library, thereby enabling us to identify specific binders via protein binding assay. Our question was whether it was worth commercializing both the sequencing and the yeast library components, or to just focus on the sequencing component. We quickly found that there were many existing products for repertoire sequencing, and many existing yeast libraries, but there was no product that combined both. The combined technology became a product that solved key problems faced by stakeholders—namely, to identify specific binders in complex antibody repertoires.
DDNews: How did the NIH grants impact GigaGen’s growth?
Johnson: What NIH grants do is allow a company to develop a technology that financially minded investors are not yet ready to finance. For example, most large venture capital deals finance existing technologies that were spun out of other companies or developed for years at research universities. In our case, we wanted to solve problems that did not have existing solutions at other companies or research universities; therefore, we needed to develop the technologies ourselves rather than licensing existing technologies. We turned to NIH to finance the initial development of the technologies.
NIH grants contributed significantly to our early technology development. Once we had preliminary data showing the utility of the technologies, we were able to secure a $50-million equity investment and research collaboration. That deal fueled our growth.
DDNews: What is the company’s current pipeline status? Are there any targets or assets you’re particularly excited about?
Johnson: We are currently advancing a pipeline of first-in-class biotherapeutics, including novel oncology antibody drug combinations and the world’s first recombinant polyclonal hyperimmune gammaglobulin.
Our early work with polyclonal gammaglobulin development resulted in a $50-million equity investment and research collaboration with pharmaceutical company Grifols. Historically, polyclonal drugs have had to be manufactured in living mammals by collecting plasma from humans or other animals and pooling and processing the IgG antibodies from the collections. As you can imagine, this is a laborious and complex process that subject to supply issues and contamination risks. Additionally, consistency is a problem as the products generated through these methods vary from batch to batch, which can result in unpredictable treatment responses. GigaGen’s ability to understand immune system function at the deepest level has enabled us to recreate human immune systems so that we can now engineer these polyclonal drugs to be more consistent and potent.
We are also very excited about the work we are doing in oncology. Last year, we applied our technology to take a close look at how natural immune systems respond to 17 different oncology targets. We uncovered over 1,000 novel, high-affinity antibodies to these targets—antibodies that have been missed with other discovery methods. We are now testing combinations of these drug candidates in different cancer types to identify and develop the best clinical combinations, as the future of cancer treatment lies in attacking the disease from many directions. The other notable accomplishment to our work in this field is the speed of our discovery process—we were able to deep dive into immune systems and generate these candidates within six months, a speed and scale that is unprecedented with prior technologies.
DDNews: What kind of role do you see the NIH playing in the future for other companies such as yours, new startups that are advancing novel technology platforms?
Johnson: It has been exciting to see some institutes place increasing emphasis on product strategy and commercialization. For example, NIH’s National Cancer Institute (NCI) prioritizes projects that are direct responses to discussions with customers. Of course, the scientific plans still must pass muster, but product strategy and commercialization plans are equally important. This is particularly critical for platform projects, because platforms often have many possible applications, product directions and customer profiles. NCI has even been providing supplemental project budgets for I-Corps customer discovery projects, which enables young companies to travel to business development conferences and meet with potential customers in person. These kinds of efforts will help new startups evolve their science projects into commercially relevant businesses. This is a critical transition that companies must go through before they start contributing to the U.S. economy by creating new jobs and novel life-saving medical products.
Over the course of his time at GigaGen, co-founder and CEO Dave Johnson has served as the principal investigator of 16 grants from the National Science Foundation, National Cancer Institute and National Institute of Allergy and Infectious Diseases, including seven Phase 2 projects. These grants led to approximately $52 million in partnerships with established pharmaceutical companies, including Grifols, Novartis and Merck. Prior to his time at GigaGen, Johnson was a founding member and chief operating officer of Natera, and served as a project director at the Stanford Human Genome Center.