“The Biotech industry is, by its very nature, a live representation of the trophic cascades and a field that ruled by pure Darwinism,” as I noted at the “start-ups and tech transfer” roundtable session during the American Society for Cell Biology in San Diego, CA last year.
Indeed, small start-up biotech companies, just like zooplanktons in the water of San Francisco Bay, sprout relentlessly in a handful of breeding sites such as the Bay area, New England, and the Triangle in North Carolina. Each small start-up carries their unique gene marker and struggles fiercely for survival. There are only so many financial resources available from venture capitalists and hedge funds, and just like energy from the sun that is insufficient enough to feed all the zooplanktons, most of them succumb to the limited resource and vast R&D challenges within the first two or three years.
Nevertheless, there are winners, whose unique genes enable them to absorb enough resources to own others and stand out of the crowd. Deep below, where the sunshine is scarce and visibility is low, large predators lurk in the dark and constantly watch the surface, trying to identify ideal catches.
However, identifying ideal catches is a challenging and complex process. While extensive efforts have been exerted by the technology scouting firms as well as venture capitals, and numerous point-based systems even algorithms have been developed, the chance of correctly predicting the potential of candidate biotech start-ups remains low.
For example, biospace.com published “Top 30 Life Science Startups to Watch in The U.S.” in October 2014. Out of these 30 start-ups, only one secured its position in their 2016 list of “Top 20 Life Science Startups to Watch in the U.S.” In my opinion, the technology (i.e. research focus) serves as the pivotal factor that determines the transformative potential of biotech start-ups.
From this point, I would like to discuss the seven biotech start-ups to watch in 2016-17.
Founded in 2014 at Burlingame, CA, Corvus Pharmaceuticals has its research focus placed on immuno-oncology to develop novel agents that could treat cancer patients through the interference of the main immunological pathways in clinical settings. Its core technological concept lies on the immuno-suppressive effects of adenosine by preventing its binding to A2A, a membrane-bound receptor that dampens the ability of the immune cells to attack tumours once activated. Rather than monoclonal antibody-based therapies that are currently flourishing in the cancer research and treatment, Corvus focuses on using the more traditional approach of small molecule analogues (checkpoint inhibitors) to block and neutralize the activity of target receptors, which is expected to cost much less and more efficient to be manufactured. Its main checkpoint inhibitors that are currently under clinical trials include Rituxan, Imbruvica, and Zelboraf.
Established in Boston, MA with members from one of the first few groups that developed the much-renowned CRISPR/Cas9 genome editing technique at Harvard University. With George Church, Luhan Yang, and Marc Güell, eGenesis places its main mission in research and development of xenotransplantation (i.e.: culture the organs of animal origin for transplantation into the human host).
In brief, since swine and human share extensive anatomical similarities in internal organs, such as size, shape, and blood vessel pattern, they become an ideal organism as organ donors. However, there is the vehement immune response that swine cells may provoke in human bodies. The swine genome is riddled with multiple copies of porcine endogenous retrovirus (PERV), the remnant of a retrovirus genome inserted in ancient times. PERV still has the potential to produce infectious viral particles, which can infect human cells and therefore becomes the main obstacle in swine-human xenotransplantation.
eGenesis has published results demonstrating the elimination of all PERV copies in swine genome and successful creation of PERV-free swine embryos. The next step of eGenesis is using a similar approach to suppress the expression of swine-human immunoresponsive antigens in such PERV-free breeds, to solve the last barrier between human-swine xenotransplantation.
Founded in 2013 with $30 M in Series A financing from Versant Ventures, 5AM Ventures, and OrbiMed Advisors, Audentes is dedicated to developing adeno-associated virus (AAV)-mediated gene therapy for rare diseases.
While the practice of gene therapy is no longer novel nowadays, much less focus have been put on rare diseases, whose treatment is complicated by the scarcity of available data as well as the lack of purpose-designed medical solutions.
It has been expected that since genetic backgrounds of these rare diseases have been recently documented with specific candidate targets annotated, the highly versatile and customizable AAV-mediated genetic engineering would allow the production of case-specific gene therapy solution to overcome the lack of prior documentation, on which traditional medical approaches relies heavily.
Currently, Audentes has four programs in IND-Enabling stage of development with preliminary data expected in Q4 2017.
Significantly different from the mass of biotech companies whose primary aims focus on the therapeutic and medical field, Zymergen put its main research focus on genetically engineered microbes that use industrial fermentation. Founded in 2013 at Emeryville, CA by a $2 M seed funding and later Zymergen secured a further $44 M funding in 2015.
Drastically different from the traditional, manually-performed strain selection from either working colonies or induced mutagenesis, Zymergen employs a strategy that combines automation, machine learning, and data architecture that allows for the design and improvement of industrial microbial strains at unprecedented scales and speeds.
The key technology that allows such dramatic improvement of efficiency is the full automation of every step of the strain selection and validation process. This not only enables the screening to be performed in a much larger, parallel scale, but also integrates data collected at each step in machine learning and big data analysis to adjust the process of design and screening on the fly. Several industry partners have validated the technology model of Zymergen and proven to be both reliable and efficient.
With current extensive field applications of CRISPR/Cas9 gene editing technology, it would be inappropriate to ignore Editas, founded in 2013 by Feng Zhang, a rival group of CRISPR/Cas9 technology at MIT; Editas was the first demonstration of successful CRISPR/Cas9 editing in mammalian cells. Under the name of Editas Medicine, the Broad Institute and MIT announced their patented CRISPR/Cas9 system that allows researchers to modify genes in living cells as well as organisms.
Unlike eGenesis who put extensive, focused efforts on transformative medicine, Editas Medicine devotes the R&D to develop the underlying foundational and conceptual research that could allow them to be used for optimization and improvement of therapeutic research.
With a much larger patent pool in hand, Editas Medicine is expected to generate its cash flow by licensing its patented technologies to end-users and research facilities with more focus on solving specific issues.
The ever-increasing bacteria resistance to antibiotics is now posing a real challenge to the public health system. To make the situation worse, the development and approval of new antibiotics decrease steadily over the past three decades, limiting treatment options for many patients.
With this issue in mind, Spero Therapeutics was founded in 2014 in Boston, Massachusetts with the specific aim of developing “potentiators” – novel chemical entities that would disrupt the permeability of lipopolysaccharide (LPS) layer in Gram-negative bacteria strains to allow antibiotics traditionally only used against Gram-positive bacteria can be administrated.
Such technology, if demonstrated successful, is expected to expand the current antibiotic spectrum against Gram-negative bacteria strains by at least four fold. Spero Therapeutics has submitted their lead “potentiator” candidate for the investigative new drug (IND), with human-based studies soon following.
Amongst the almost over-saturated R&D market of Alzheimer’s Disease (AD), Alzheon, a Massachusetts-based company that was founded in 2013, holds a distinctive advantage with their ALZ-801 compound.
In short, several beta amyloid-related diseases, such as AD, Down syndrome, and macular degeneration, are all caused by the abnormal aggregation of beta amyloid within the central nervous system. Rather distinctive from the other AD treatment methods and medicines, ALZ-801 is an orally administered precursor of tramiprosate (homotaurine), which has been suggested to have the ability to bind beta-amyloid in its soluble form. ALZ-801 prevents its aggregation and accumulation within the brain, thereby providing an alternative approach to treating such diseases.
The oral administration path as well as its small-molecule properties not only significantly simplifies the treatment process, but also extensively reduces the expected cost and market price comparing to current therapies and medicines. The ALZ-801 is currently in the Phase II stage for AD and Phase I stage for Down syndrome, with other beta amyloid-related indications in pre-clinical stage.
So, what distinguishes these seven biotech start-ups from the masses? For tech scouts and venture capitalists it is crucial to identify “good science” from “bad science” as the recent Theranos scandal clearly demonstrated. Over-ambitious and fancy concepts without solid scientific foundation almost always fail. These seven start-ups were chosen, not for their business models, nor for their ambitious promises, but for their possession of practical, proven technologies and the solid scientific basis standing behind them. While companies may fail, demonstrated scientific concepts will not be affected and can be easily transferred to another business entity (or, alternatively, held to prevent the potential competitors from entering the paucity) through patents.
While this is not a complete list of biotech start-ups to watch; the list reflects my opinion of transformative technologies. Which start-ups are you eyeing based on game-changing biotechnology?
Dr. Siwei Zhang received his BSc degree in biology from Peking University in 2006. Subsequently, he pursued his MPhil degree in Molecular Biology and Haematology at the Chinese University of Hong Kong between 2006-2008 and his PhD degree in Developmental Biology and Neuroscience at the University of Manchester between 2008-2012, each sponsored by a full studentship. After spending a few years in Europe, Siwei moved to Chicago and is currently working as a postdoctoral research associate at the Department of Molecular Biosciences, Northwestern University. His research interests focus on the investigation of molecular mechanisms of cancer metastasis during early embryo development. In his free time, he enjoys writing tech and science commentaries to keep himself with the pace of the modern biotech industry.