5 Women to Watch in Boston Biotech

Less than five percent of the CEOs in Fortune 500 companies are women (just one is an African-American woman) but in Boston, several of the most influential biotech executives are women. Perhaps it is the fact that startups with at least one female founder simply perform better. To honor the accomplishments of these pioneering executives, here’s a snapshot at the contributions of five notable women to biotech in Boston.

Susan Windham-Bannister, President and CEO of Biomedical Growth Strategies and the Managing Partner of Biomedical Innovation Advisors

Susan Windham-Bannister was the first President and CEO of the Massachusetts Life Sciences Center where she oversaw a $1 billion investment to accelerate the growth of biotech in Massachusetts. A trail-blazer, she was the first African-American woman to lead a life sciences growth initiative of this scale. Named one of the 10 Most Influential Women in Biotech by the Boston Globe, Windham-Bannister took the reins at the Massachusetts Life Sciences Center in 2008 at a particularly difficult time in the US economy. Windham-Bannister turned this potential disadvantage into a creative force for opportunity, partnering with the private sector to, as a 2013 Northeastern University report found: “attract $3 in outside investment for every public dollar spent, turning just over $300 million in state funds into more than $1 billion worth of backing for the local life sciences sector.”

Susan Windham-Bannister will be the keynote for the Women’s Leadership Symposium and Dinner at part of our Biotech Week Boston event this October.



Mary Lynne Hedley, Ph.D. Co-Founder, President and Board Member, Tesaro

Named “Life Science Entrepreneur of the Year” by the New England Venture Capital Association this past spring, Mary Lynne Hedley Ph.D. has been rightly called a pharmacology pioneer as she has been developing cancer drugs since 1996. Hedley began her career as the co-founder of Zycos, Inc. (which later became MGI Pharma, then Eisai Co Ltd.) moving on in 2009 to become EVP of Operations and Chief Scientific Officer of Abraxis Bioscience. In 2010 Hedley co-founded (with partner Lonnie Moulder) Boston biotech Tesaro, an oncology-focused biopharmaceutical company. The first drug Tesaro brought to the market, called Varubi, manages the side effects of chemotherapy to alleviate suffering and therefore bring some normalcy to the lives of oncology patients. Tesaro is also developing cancer drug Niraparib which we wrote about here. Late last year, Don Seiffert of Boston Business Journal asked Hedley what it was like being one of a tiny minority of women in biotech. Hedley offered: “It’s probably like being a guy in biotech.” Relatively, that rings true – biotech is a tough industry for anyone, with 9 out of 10 companies that begin clinical trials unable to succeed in bringing those drugs to the market.



Katrine Bosley, Chief Executive Officer, Editas Medicine

In 2016, even the least scientifically minded among us cannot have missed the buzz about “CRISPR” technology. Katrine Bosley is at the front row and center of this pioneering technology as the CEO of Editas Medicine. This June Bloomberg called CRISPR “the genetic tool that will modify humanity” and Editas’ mission is to successfully use CRISPR to repair genes that cause mutations that cause a broad range of diseases. In 2014, when Bosley joined Editas, Alex Lash called her one of the “highest profile CEOs of the biotech scene” and her profile has only gotten higher since then. Bosley began her career at Alkermes, moved on to Highland Capital Partners, then Biogen, and then Adnexus (which was bought by Bristol-Myers Squibb).  In her first CEO role, Bosley led Avila Therapeutics into a buyout from Celgene. Prior to Editas, from 2013-2014 she was an Entrepreneur in Residence at the Broad Institute. This May, Fast Company wrote: “Five years ago this was a medical pipedream…With an aggressive timeline and a giant war chest, the Editas CEO may be the first to treat genetic mutations using CRISPR technology…as soon as next year.”



Hannah Mamuszka, Founder Alva10

You may not have heard of Alva10 – yet – but I'll take a bet that you will soon. From stints at some of the most well known Boston based and Global biotechs - Organogenisis, Takeda and ArQule as a researcher and scientist - to almost twelve years as a Director of Pharmaceutical Alliances at Exiqon (previously Oncotech) and most recently VP of Business Development at Exosome, Hannah Mamuszka’s career “has evolved based on the intersections of biotechnology and business development”. The name of her new company Alva10 was inspired by Thomas Edison - whose middle name was, of course, Alva. Mamuszka explains: "Edison was an amazing inventor and thinker, who thought about challenges completely differently than everyone else at the time, and produced radically different results as a product of that thinking. With Alva10, we are emphasizing the value that diagnostics play in personalized, precision medicine, and approaching that value from a completely different perspective than anyone else (that I've seen) in the industry.” The diagnostics she is talking about can analyze “both DNA and RNA in a molecular liquid biopsy”. This ability to translate Big Data into “well validated, broadly distributed diagnostics that are valued in the healthcare system” Mamuszka says is key to precision medicine being realized.



Barbara Fox, Ph.D. Entrepreneur in Residence at Partners Innovation Fund

With a career spanning almost thirty years that started as a Professor of Medicine at the University of Maryland and led to her current role as Founder and CEO of Avaxia Biologics, Barbara Fox has honed her networking skills into a fine art, enabling her companies to compete and win in the highly competitive world of biotech. Prior to Avaxia, Fox was an Affiliated Entrepreneur at Oxford Bioscience Partners, before that President and Chief Scientific Officer of Recovery Pharmaceuticals (now Shire) - a company she founded that develops medicines for the treatment of addiction. Her first position after teaching was Senior Scientist at Immulogic Pharmaceuticals where she quickly moved from that role into Vice President of Discovery Research. At Immulogic Fox directed programs into vaccine development, allergy, autoimmune disease and substance abuse research.

We are pleased to have Barbara Fox speak at Biotech Week Boston’s Bioprocessing International Conference and Exhibition. She will be presenting “Funding a Therapeutic-Focused Company through Angels: The Good, The Bad and the Ugly”. Fox will also be a panelist for: ”How to Overcome the Funding Gap for Biotech Start-ups and Emerging Companies”. Fox will be joined by Joshua Speidel, Latham Biopharm Group and Ohad Karnieli of Karnieli, Ltd.


Got any more women in Boston biotech you think we need to write about? We’d love to share them with our audience so Tweet to us at @BiotechWkBoston. And don’t forget to check in every week for our Biotech Week Boston blog series. Biotech Week Boston is a hub for life sciences, technology, and business and fosters cross-disciplinary interaction and collaboration to break down silos and spark change. Biotech Week Boston will showcase the most comprehensive science and innovative technologies while fostering partnerships to unlock the full potential of what science and business can achieve. Learn more by clicking the link below.

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Gene Editing in CHO Cells

The team behind Cell Line Development & Engineering event have recently produced an exclusive whitepaper titled "Gene Editing in CHO Cells". Below you will find a brief summary of the whitepaper and download the complete whitepaper now.

Whitepaper Summary:

Recently, several exciting advances in CHO cell line engineering have received significant media and research attention due to efforts in genome sequencing, systems biology, and bioinformatics combined with the relatively new field of targeted gene editing platforms. Three key gene editing technologies have been at the forefront of the recent developments in CHO cell line engineering. Early efforts to introduce targeted site specific edits to the CHO genome focused on implementing the zinc finger nucleases (ZFNs) and the transcription activator-like effector nucleases (TALENs). The ZFN platform has been successfully deployed in a variety of post translational modification applications aimed at increasing specificity of recombinant protein production, but the efficiency of this platform can be limited in mammalian cell lines.

The clustered regularly interspaced short palindromic repeats associated 9 (CRISPR/Cas9) targeted gene editing system has recently exploded onto the research scene in almost every organism. This targeted gene editing platform allows for the creation of multiplexed edits in a single cost-effective step with a specificity previously unachievable in the genome editing arena. This complex is composed of short guide RNAs (sgRNAs) and a CRISPR-RNA that form a site specific construct that is complimentary to the target DNA, which introduces a double stranded DNA break upon binding. Repair of the break site by endogenous enzymes then creates a highly specific change to the DNA which can be customized for a variety of applications.

These advances in genome editing have helped enable high-throughput development of CHO cell lines that can be utilized as economically viable commercial expression vectors. The CRISPR/cas9 gene editing system has shown to be an extremely useful tool for customizing the metabolic pathways of CHO cell lines for use in biopharmaceutical production. One of the most useful applications of this exciting technology has been the creation of multiplexed targeted knock out screening systems. Previously, knock out experiments had to rely on mutagenesis, drug knock out, or media screening to identify the effect of a mutation on a desired cell type. These methods are inefficient and sometimes lead to less desirable off-target effects. It is now possible to develop very large gene knockout libraries to be targeted by CRISPR/cas9 using bioinformatics software specific to this platform.

Customizing metabolic pathways in CHO cell lines is of paramount importance for developing “cell factories” capable of biopharmaceutical production. Reducing the energy expenditure associated with mitochondria production and oxidative metabolism is one approach that has been shown to increase the efficiency of the cell by directing metabolism towards production of the target product. Modulating these pathways has traditionally been accomplished using interfering RNAs, but the specificity of the CRISPR/cas9 platform offers another tool with which researcher can customize the energy profile of CHO cell lines destined for biopharmaceutical production.

Future efforts in the field will be focused on increasing the efficiency of the CRISPR/cas9 system, as this platform is poised to become the model for the majority of biopharmaceutical development. Currently, 60 to 70% of all biopharmaceutical production is accomplished with recombinant mammalian cell lines, and this market share is expected to grow. Multiplexed editing efforts will also continue to increase the rate at which specific customizable CHO cell lines can be produced, as this process is highly critical to increasing the rate at which CHO cell line engineering moves forward.

Download the Complete Whitepaper

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New Tools for Genome-Wide Functional Screens Needed to Develop New Drugs

Guest Post: Paul Diehl, PhD, Director of Business Development at Cellecta - Paul will be speaking at IBC's Genome Editing Applications conference March 18-19 in Boston.


Despite the need for new innovative therapies, the rate of novel drug development has remained level with about 35-40 new approvals each year (see figure below). One crucial factor restricting the rate of new drug discovery is the limited set of therapeutic gene targets. There are approximately 1,500 approved therapeutic compounds, but they target only about 300 gene products. Most new compounds in testing are directed toward these same known targets.

However, the potential number of drug targets is at least an order of magnitude greater. DrugBank associates over 4,000 targets with the 7,500 compounds in its database, and GeneCards catalogues over 10,000 genes that have data indicating they “cause, predispose, or protect from diseases.” Why does the current pharmacopeia only exploit less than 10 percent of the potentially targetable gene products then?

The problem is that there is still too much unknown about how most gene products actually work. A tremendous amount of genetic information has been amassed and deposited into online databases. Data about how, under certain conditions in some systems, transcription of certain genes increase or decrease, proteins that interact, and genes that are mutated more frequently in certain systems. Almost all of this data, however, is simply correlative. These massive databases simply do not contain the key information required to really understand how genes produce biology. No amount of deep and thorough analysis of the massive amount of information currently stocked away can illuminate how most genes function because there is a critical dearth of information indicating which genes actually drive the biology.

This lack of information about which genes are responsible for biological responses and disease progression stems from the difficulty in obtaining this data experimentally. Data is needed that causally links gene products to phenotypic changes. This requires assays that assess how the perturbation of certain genes changes the responses or characteristics of cells in a model system, and there are few experimental approaches to generate this sort of data efficiently.

Some techniques, such as genomic recombination technologies like transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs), can provide the needed data by disrupting or otherwise altering genetic targets in a precise manner. However, functional analysis tools must be able to assay the roles of large numbers of genes simultaneously. Collecting data on this scale requires parallel measurements in genome-wide functional assays, which is difficult with these gene manipulation techniques.

There are really only two technologies that currently form the basis of techniques for broad-based genetic screens that assess the functions of large numbers of genes in a single assay: RNA interference (RNAi) and CRISPR knockout screens.

Although RNAi and CRISPR loss-of-function screening approaches are effective, their potential to elucidate gene function remains somewhat limited. One limitation is that either approach only looks at the effects produced by the disruption of a single gene within the system. In reality, though, it is rare that one gene produces one trait. Most phenotypes are caused by multiple interacting genes. While loss-of-function screens can be designed to look for interacting genes, such as Bassik, et al. has shown, paired gene screens can only be run on a limited set of a few hundred genes, so efficient combinatorial assessments of interacting genes across the genome is really out of reach at the moment.

Also, disruption of gene function by knockdown or knockout provides only a limited range of functional assays. Genes may also be activated or otherwise functionally modulated to produce biological responses. Although RNAi can only be used for loss-of-function screens, CRISPR has shown some potential in screening for the activation or gain of genetic function. There is the potential, then, for the development of more sophisticated CRISPR-based screens that assay for genetic changes activating new pathways or bringing about novel biological transformations that may well elucidate disease development.

Thus, while RNAi and CRISPR loss-of-function screens provide one of the few effective approaches currently available for genome-wide functional screening, they are not sufficient to meet the daunting challenge of understanding how genes produce biology. Progress in identifying novel therapeutic targets will continue at a glacial pace until more advanced techniques are developed to address the challenge of teasing out the complex genetic networks that drive and control cellular responses and processes.

  
New Drug Approvals and R&D Expenditures on Annual Basis. The number of new drugs with novel mechanisms approved each year by the FDA (left axis) as compared with the annual expenditures reported by pharmaceutical companies in the 2014 Biopharmaceutical Research Industry Profile published by PhRMA (http://www.phrma.org/profiles-reports).

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