IBC's 18th Annual TIDES is the industry's #1 forum for oligonucleotide and peptide leaders to build successful partnerships and accelerate products from early discovery through late-stage development and commercialization. The TIDES team recently talked to Bruce L. Riser, Ph.D., CEO, BLR-Bio, LLC for an exclusive interview that delves into the topics he plans to discuss at the upcoming Oligonucleotide and Peptide Therapeutics event in Long Beach, CA.
What are the biggest challenges of bringing new agents with novel targets to the market?
BR: There are really two big challenges when bringing new agents with novel targets to the market. First, many investors and potential partners are not familiar with the target, or they do not have the comfort that exists with an established target. Second, there can be misperceptions in the scientific community and in the biopharmaceutical industry where an agent is associated with another type of development creating a negative halo. On the first challenge, it is easy to see a proven target and to line up, jumping on the bandwagon with others trying to either win the race to launch first or to attempt to find a niche in an already established area. The problem of course is that lining up with everyone else does not provide the opportunity to develop and launch a true breakthrough therapy that can change the treatment paradigms and have a breakthrough impact on peoples' lives. Instead, investors and companies that line up for the established target often find they are trailing others to the market and are never able to successfully establish themselves in the market. It really takes a visionary to see the potential of a new target and have the insight and strength to invest in it. The second challenge, dealing with miss-associations of a novel therapy with other developments can be truly vexing. Our peptides target the novel CCN signaling pathway, leveraging the unique qualities of CCN3 to target the control of ECM changes in response to injury, blocking fibrosis and creating an environment for re-establishment of complete tissue homeostasis. By creating peptide libraries and conducting diverse in vitro and in vivo screens we have identified specific regions with the CCN3 protein responsible for blocking single, or multiple, pathways to fibroblast and cancer growth, and fibrosis formation. Unlike other products such as antibodies directed against the pro-fibrotic CCN2, that appear to partially block a single pathway, our novel therapy regulates vs. simply blocking, thus allowing reestablishment of the body's healthy equilibrium.
With several peptide products in the pipeline in preclinical development and a wide range of possible disease applications, how have you selected your lead indication target(s)?
BR: Having several products covering a wide variety of diseases is great and choosing lead indications to pursue is a wonderful challenge to have. In reality, the two lead indications that we have chosen to pursue have as much to do with the research that we have done with my team as it does the extreme health care need. My long background in academia, clinical nephrology/public health, and pharmaceutical drug R&D has driven the way we do drug discovery at BLR Bio. First, working to clearly understand the pathways to disease before selecting a target, and trying not to get caught up by targets in vogue. Then, testing our peptides in multiple related diseases before moving into the clinic. Our pipeline was created out of our long-term interest in fibrosis and the extracellular matrix in biology and disease, particularly in renal fibrosis as a complication of diabetes an area of great medical need. This has led to the selection of diabetic nephropathy as a main target for one of our lead products. Since our target, and the peptide inhibitor of our target, are involved in many other forms of fibrosis and other disease involving the miss-regulation of matricellular signaling, this creates other exciting therapeutic indications down the road. These include NASH, IPF, MD, and scleroderma to name a few.
I began my career in cancer research, and we know now that the extracellular matrix and matricellular signaling proteins such as the CCNs are critical also in the formation and resolution of tumors. The pro-fibrotic CCNs, CCN2 and CCN4 in particular have been shown to be important for the establishment and likely invasion and metastases in numerous tumors. The opportunity to use CCN3-based therapy to, not only halt the cancer, but also to target the microenvironment is an exciting one. Our company is particularly excited about the potential in pancreatic cancer. We have an established relationship with thought leaders in the cancer field and are moving forward with development work, partnering with some of these world experts. To add to the excitement of the therapies, our company also is developing a diagnostic/theranostic based on the same technology platform. It holds the promise of either stand-alone or companion diagnostics for development.
What are the key advantages of peptide therapeutics over small molecules, antibodies and other protein therapeutics?
BR: As you know, peptide-based drugs are one of the most rapidly growing areas in therapeutic development. More than 100 peptide-based drugs are on the market with several effective in cancer treatment. There is good reason for this. In size, falling between small molecule drugs and "biologics", they have many of the benefits of both while shedding many of the deficiencies. For example, because of their small size they gain many delivery benefits over biologics. First, better penetration of tissue at the site of action. This is crucial in fibrotic disease and cancer where there is a very strong barrier to penetration. Second, it allows for many more delivery options, including oral formulation. The earlier assumption of poor metabolic stability of peptides has just not proven to be the case. Although there is often rapid clearance from circulation, the previous assumptions about required PK by classic definition has also proven to be not relevant, since a specific and sustained biological activity at the target receptor is characteristic of many peptides. Unlike small molecules they are based on sequences that have evolved to react with specific receptors and often at very low concentrations. This results in very low off target effects. Last, since they can be chemically synthesized the ease and cost to manufacture are more nearly like that of small molecules. The majority of approved peptides are in the 15 amino acids (aa) range or smaller, and they treat a broad range of diseases.
How do you see academia and industry collaborating in the future to advance promising peptide therapeutics into commercially viable products?
BR: First, we think that academia will play a significant role in the creation of new peptide-based therapies in the future. Since the last decade has seen a decline in the number of newly approved drugs from large pharma, and recently there has been a strong trend for these same companies to dramatically reduce their discovery effort, this creates a large opportunity for novel peptide therapies and academic-initiated translational research. This does not necessarily mean that the new paradigm will be that large strategic companies will license early stage assets directly from Universities. Rather, we anticipate that the most promising discoveries will lead to the creation of start-up companies and the building of defendable IP. Then, large pharmaceuticals will court these start-ups as they progress to become true biotechnology companies with completion of phase I, phase II clinical trials or beyond. We think that the best of these emerging biotech companies will then expand their ability to do discovery and early stage development. They will also be able to clearly evaluate and in-license additional opportunities in academia. These are exactly the skills now lacking in big pharma. These successful discovery biotech's will become the future pipelines for drugs that will go to the mid and large pharma companies centered on late development and marketing. I envision BLR Bio as becoming one of these discovery companies able to contribute significantly to filling this gap.
Want to hear more from Dr. Riser? Join him this May in Long Beach, CA for the 18th annual TIDES - Save $300 when you register using the code B16180BLOG100. Click here to register.
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