Collaborate, not compete

Posted on 30 Mar 2017 by Bioentrepreneur

Collaboration seems to be the last thing on the mind of bioentrepreneurs. This is based on personal experience as well as feedback from my fellow entrepreneur friends. It is quite disappointing and interesting as the same time, as to why most prefer to compete, and not collaborate.

Historically and traditionally, ecosystems can be built and nurtured by collaborating and not by competing. It is human nature to compete, but the urge to win comes along with jealousy and ego. This can hinder progress of a project that is aimed toward a noble and useful cause.

In 2015, the Alzheimer’s Drug Discovery Foundation (ADDF) and Pfizer’s Centers for Therapeutic Innovation (CTI) announced a collaboration to advance new small-molecule drugs for Alzheimer’s disease and related dementias. Also recently, 500 Startups, a venture capital seed fund, and Echelon, a global series of tech events by e27, have decided to collaborate to showcase Southeast Asia startup ecosystem to corporates. I think this is a brilliant partnership and will definitely help the startup ecosystem in SE Asia and the rest of the world.

Human culture is to celebrate and elevate an individual; this undermines the value of collaboration. Everyone is in it for the money (a fact of life), but this can also be achieved by effective partnership and working together.

Being a two-time entrepreneur, I am not surprised anymore when collaborations do not go through and the entrepreneur on the other side does not understand what he/she is missing out on. For example, if you are a founder of a biotech startup that works on solutions for diagnosis of cardiac failure and your friend has a social enterprise that works in rural areas to make sure people have a healthy heart, would you collaborate with them? Why would you turn down such a request?

The up side of collaboration is new innovations, new product development, expanding the market, enhancing customer satisfaction and a wider network. Collaboration does have its downsides, such as control issues, insecurities and group dynamics. But looking at the positives, it seems it is more effective and beneficial to collaborate than to do your own thing.

There has been a debate as to whether corporates should collaborate with startups, to scale and succeed together. This equation has many factors to consider, but should work if the vision is similar for both the corporate and the startup. They can learn from each other by working together and creating mutual benefits. Startups always take more risks with disruption, things get done faster due to lenient regulations and they like being associated with big corporates.

Sandhya Sriram

The Gene Editing Bazaar

Posted on 10 Mar 2017 by Markus Schmidt

On February 15, 2017, the US patent authorities ended a legal battle over IP rights between University of California at Berkeley and the Boston-based Broad Institute. According to the long awaited decision, Broad keeps its patents allowing them to own the use of CRISPR-Cas9 gene editing technologies in any eukaryotic organisms (including yeast, plants, animals and humans), while Berkeley’s broader patent application, which allows general use of CRISPR-Cas9 in any type of cell (including bacteria), will proceed before the USPTO. Gene editing – the precise and relatively easy deletion, insertion or modification of particular DNA sequences in the genome – is one of the latest innovations aiming to convert genetic engineering into a real engineering discipline. In the past, precise modifications were hard or almost impossible to achieve, frequently leaving genetic marks and requiring rather expensive and time-consuming processes.

The dream of every synthetic biologist, to edit the DNA letters in the genome as if using word processing software, seems not so far fetched anymore. But helping to make genomes easier to engineer is not the only advantage for scientists and the biotech industry. As it turns out, the gene editing process of CRISPR-Cas9 is distinct enough from traditional genetic engineering so that first applications issued in 2016 in the US, like the non-browning mushroom, escape regulations on genetically modified (GM) crops. In the US, GM red tape does not apply to plants or fungi because CRISPR/Cas9 does not involve genetic elements from plant pathogens, and the modifications are in principle indistinguishable from a naturally occurring mutation. The potential for covering the tracks of gene editing (for example to avoid royalty payments) has recently caught the attention of the US Intelligence Advanced Research Projects Activity, which is currently “seeking information on potential tools and methods to detect organisms that have been modified using genome editing techniques.”

Other countries are also lagging behind with decisions on regulatory status. In Europe we see varying reactions. For example, Sweden decided that non-regulation was “crystal clear,” but Austrian government reps announced that CRISPR/Cas9 will be treated just like GMOs.

European countries, however, will have to wait at least until 2018 before the European Court of Justice will announce a presumably legally binding decision for EU member states. Until then, gene editing in Europe (and elsewhere) is in a legal limbo, giving the US (again) a head start on developing and innovating novel biotech applications.

Still, technical obsolescence could soon render ownership of CRISPR/Cas9 irrelevant, given related techniques, such as the CRISPR-Cpf1 where IP rights seem less complicated. There might even be a much greater number of CRISPR or related tools that work at least as well or better and that could even be open source/open access. We will see what happens to initiatives like the do-it-yourself CRISPR kit from Josiah Zayner. And a group of do-it-yourself biologists from all over Europe will for the first time join the Genome Hacking Retreat, beginning March 12, in Germany to exchange ideas and develop new applications using gene editing. It’s possible that in the next 10 years we’ll witness the coming of age of free and ubiquitous gene editing tools for everyone.

Markus Schmidt

Heparin, Brazil and innovation

Posted on 12 Aug 2016 by Luiz Antonio Barreto de Castro

An article published at the Brazilian Journal of Cardiovascular Surgery compared all heparins manufactured by Brazilian companies to Liquemine, manufactured by Hoffman La Roche. Heparin is a complex carbohydrate that was introduced to control thrombosis during extra-corporeal surgeries during the 1930s by Clarence Crafoord. It’s been nearly a century and there is no substitute for the drug. No surgeon performs chest surgery without heparin at hand.

Authors of the article, titled Quality control of the heparins available in Brazil: Implications in cardiovascular surgery, concluded that no heparin manufactured in Brazil met the minimum quality control requirements when compared to Liquemine.

There were issues with purification, and contamination with other carbohydrates resulting in inadequate anti-clotting properties. Structural problems were also detected, which resulted in heparins of variable molecular weights – unacceptable, because these properties equally affect the anti-clotting behavior of the drug.

Fortunately, imported heparins are available in Brazil. We attempted to learn more about this scenario and visited a medium size company that commercializes heparin in Brazil (total revenues: US$300 million/year), at the invitation of a friend of the CEO.

Our objective was to improve quality control at the company and boost innovation. We wanted to speak with a company that had four decades of science dedicated to heparin. To our surprise, the Innovation Director asked us if we had their heparin product. Apparently this was key for us to proceed, and since we did not have it, the meeting was aborted prematurely.

This question surprised me, and I later realized I should have said we were not product makers ourselves, but wanted to discuss quality control. Foreign companies dedicate a lot of work by scientists to assure quality control of heparin and drugs in general, but a lack of quality control at Brazilian companies means we cannot compete internationally, or innovate.

But there is hope. At our meeting, the CEO arrived somewhat late. After listening to a short summary by the Innovation Director about heparin, the CEO said, “Even if we cannot collaborate in the area of heparin, please stay in touch. Innovation is key for us – if we don’t innovate, this company will disappear in 10 years.”

I agree. Particularly if that innovation isn’t around creating new drugs.

Luiz Antonio Barreto de Castro

Clinical trials and beyond

Posted on 25 Jun 2015 by Gayatri Saberwal

For previous blogs on Australian biotech, go here, here and here.

Australia is well developed concerning clinical trials. The regulatory body, the Therapeutic Goods Administration (TGA), trusts the high ethical standards of the doctors and the ethics committees of the hospitals. Therefore, first-in-man trials do not require TGA approval, and can be done after notifying the regulators. Also, the protein for trials can be manufactured in a Good Manufacturing Practices (GMP)-like facility that is not fully GMP. (A GMP facility needs to comply with the regulations and be registered with the TGA in order to obtain the label, but a GMP-like facility doesn’t.) This makes it easy to do clinical trials in Australia. Further, the data generated from clinical trials in Australia are considered to be at par with that from the US or Europe. Clinicians running the trials are also paid much less than their peers in the US.

The country is also fairly innovative. In a 2013 Innovation Survey, Australia was ranked 13^th in the world, and between 2003–2013, the per capita and per GDP dollar IP filings from Australia were more than that of most developed countries.

Yet problems remain. Overall, while human resources in Australia are less of a challenge now than they used to be two decades ago, the pool of people with experience remains small. There is a whole series of missing skills related to IT and data mining, IP, commercialization and regulatory affairs. Once a company has grown it can easily hire people who are accustomed to revenue and know how to increase sales, but in the early stages one has to put together a story and make people believe in it, and this is not easy to do in Australia. The experienced managers, or advisers, are mainly returning Australians or foreigners with commercialization experience in the US or EU. Also, the advisers might be located overseas. Notably, sourcing and retaining Americans is a challenge.

Another problem: the country has not yet produced a first-in-class drug. The only notable commercialization story is that of the key patent behind the cervical cancer vaccine Gardasil. The technology was discovered at the public University of Queensland, and clinical trials were financed through the sale of some of the patents to an Australian medical company, CSL, and later Merck. Currently, Merck has the exclusive global license to sell Gardasil, except in New Zealand and Australia, where CSL owns the license. But generally, a successful company is one that developed a simple product, repositioned existing products or developed new delivery systems for existing molecules, and did not build upon cutting-edge science.

Yes, biotech in Australia has its challenges. However, the science is good, government programs are supportive and clinical trials are relatively easy to initiate. Also, pioneers of earlier years have shown what it takes to build a successful company. Keep in mind that it can be done, but do not expect to go the whole way alone.

Szymon Jarosławski and Gayatri Saberwal

Acknowledgments: This article is based on interviews with 14 senior people in, or associated with, companies in Australia, whose comments have been edited for clarity and brevity. We are extremely grateful to the interviewees, who gave freely of their time and their insights. This work was supported by a grant to GS from the Institut Merieux, France. SJ was supported by France Volontaires, France. Neither organization played any specific role in this study.

3 years in Bogota; a 3-path strategy

Posted on 16 Jan 2014 by Johann Osma

It has been three-and-a-half years since I moved to Bogota as a faculty member at University of los Andes. I remember that when I first started here, almost everybody said my ideas about fabricating microsystems and electronics for biochemical applications were sci-fi, and that there was little hope about their feasibility. Nowadays, we are a successful research team at the microelectronics research center (CMUA) called biomicrosystems, and one of the pioneer groups focused on innovation and entrepreneurship in Colombia.

Our research centers on microsystems, especially those related with microfluidics, along with the development of sensors and biosensors for food monitoring and environmental control. In this field, researchers and students from different backgrounds and expertise work together. It’s common to see engineers from electronics, mechanics, mechatronics, environmental, civil, computing, and beyond working with artists, designers, biologists and microbiologists, physicists, chemists and even anthropologists on any of our projects. Due to the diversity of the group, our strategy is to train each member of our team in one of three paths: Research, development, and industry/market application. The first path is for students and researchers who want to follow a straight scientific career, understanding that about 70% of their results will not solve the problem they are targeting. This path has high risk and is long term, but a high remuneration if the research is successfully translated. The second path, development of equipment and technology, is for those interested in solving inner needs of the group, such as coming up with new and specialized equipment, or discovering methods that ease the work of the people involved in the first path. This path has a medium risk and a middle-term development, but moderate remuneration. The third path is for those eager to bring our new developments and technology to the real world, via the industry or start up. These people aim to transfer inventions or technologies into an attractive product for the industry. It requires an understanding of the industrial sector and the ability to transform our inventions into something solid, tangible and sellable.

This three-path strategy has worked for our group, making it possible to do research and still offer a brochure of products and developments. But behind the scenes, there is a more powerful strategy, one involving know-how transfer. In our research line we have identified those things we know how to do, and we have transferred that knowledge to everyone in the group. Thus, if someone needs to use a certain technique, that technique is then taught to everyone, independent of their background, age, and time in the group. The only commitment after receiving the training is that you will then train others. In that sense, even I, the “boss,” may have to be supervised on certain techniques if I am not fully trained. This model helps us train young students in a short time, and allows them to create a positive impact in our research.

Recently, Sara, a grad student in our development path, trained three 18-year-old undergrads in the use of her in-house microscope equipment and the fabrication of microfluidic channels. These students (guided by Sara), then produced artificial transparent muscle arteries for studying optimal mixing condition of blood and serum. The goal was to produce transparent artificial arteries, which medical researchers could use to explore properly injecting serum or a drug into the bloodstream and tracking the mixing pattern. Our three undergrads were trained in three months and were capable of fabricating and analyzing their results in about the same time. After six months of hard work, they submitted and presented their work at the Pan American Health Care Exchanges, an initiative originally initiated in cooperation with PAHO (Pan American Health Organization) and WHO (World Health Organization). These three students now have a place in our industry/market application path.

These results could not be better: three of our youngest students and future researchers presented their first work at an international conference at the age of 18, our in-house equipment is being used each day by more people, and we are producing a generation of students and researchers who think innovation is a path that anyone can follow in any field.

Johann F. Osma

Not Invented Here

Posted on 06 May 2013 by Rick Jones

Pharma has been accused of not looking beyond the fortress walls. Are VCs now following suit?

Business development professionals have long complained about the difficulty in convincing Big Pharma research groups that a new project from outside their company is worthy of consideration. This is called Not Invented Here (NIH) syndrome and, when displayed by pharma, is characterized by skepticism of novel ideas, a focus on data gaps rather than an assessment of the data that exist, and an unwillingness to abandon internal projects even if corporate portfolio valuation standards favor the external project.

Big Pharma has made strides toward erasing this bias toward internal projects. Even before the recent R&D downsizing inside pharma, an increasing percentage of its pipelines was derived from licensing or acquiring outside projects, and most large companies expect 50% or more of their products to be sourced externally. Business development groups have enlarged and a variety of mechanisms have been set up to access external innovation, such as corporate venture funds, academic center collaborations, “innovation centers” and incubators.

Continue reading →

BGI’s youth movement

Posted on 19 Apr 2013 by Juliana Chan

Prior to meeting BGI Executive Director Dr. Wang Jun, I had been fascinated by the rise of BGI, the Chinese world leader in human, plant, and animal genetics research.

BGI began in 1999 as China’s representative to the International Human Genome Project, where it was responsible for 1% of the output. Since then, it has grown into a genomics powerhouse, making waves for its choice of projects, such as the BGI Cognitive Genetics Project, which is studying the genetic basis for intelligence, and its recent US$118 million acquisition of the California-based whole human genomic sequencing-technology company, Complete Genomics.

I met the 37-year-old executive director at the Plant and Animal Genome Conference (PAG) Asia that took place from March 17-19 in Singapore, and Dr. Wang explained to me how BGI was structured.

“We currently have 4,000-plus employees. BGI is divided into several parts. The first is BGI Research, which is doing a lot of academic non-profit research. Then we have BGI Tech, which is doing a lot of genomics and ‘omics services. Then we have BGI Healthcare, which is trying to deliver healthcare solutions to society. BGI Agriculture develops new breeds. We recently started a project to treat waste water to provide environmental protection. Those are the major parts,” he said.

Continue reading →

Israeli Ag Bio

Posted on 12 Feb 2013 by Bernard Dichek

Israeli biotech comes full circle with the recent Rosetta Green success story. Rosetta Green, a company that specializes in identifying unique genes and developing improved plant traits for the agriculture and biofuel industries, has been purchased by Monsanto for $35 million.

It is the first Israeli biotech in the agriculture sector to make headlines in a long time, but it could be the beginning of a new trend. Today more than 90% of Israel’s life science companies, including well-known ones as Teva Pharmaceuticals and Protalix (developer of a new drug for Gaucher’s disease), are all in the biomedical domain, but it wasn’t always like that, and maybe things are changing.

The country’s first biotech startup, Bio-Technology General (BTG), today known as Savient Pharmaceuticals, was founded more than 30 years ago in order to commercialize a bovine growth hormone invented at the Weizmann Institute. It was typical at that time for talented researchers to be focused on agriculture, which then made up more than 75% of the country’s economy.

But BTG soon realized that there were greater opportunities in the human health market, and that its core growth hormone technology could be readily adapted to treat dwarfism and other disorders. As BTG began to develop the first human growth hormone, more and more researchers from Weizmann Institute and other Israeli universities began to work on drug-related topics, including the inventor of the growth hormones, Prof. Haim Aviv, who became a serial entrepreneur and founded several biopharm startups.

So perhaps it is not surprising that Rosetta Green is a spin-off of a parent human genomics company, Rosetta Genomics. Rosetta Green’s location in Israel works to its advantage, as plant genomics is heavily dependent on skills related to algorithms and other mathematical areas in which there is an interface between high-tech and biotech, and Israel has a growing pool of researchers who have acquired these skills in the country’s dynamic high-tech industry.

There is a second success story in the ag field: Evogene. Like Rosetta Green, it was created as a spin-off from a parent drug development company – Compugen, which specializes in bioinformatics. Evogene has a number of collaborative agreements underway with Monsanto and provided its investors with one of the highest returns for a biotech over the past year, as shares rose about 25%. These two companies might be at the forefront of a wave of successful, ag-biotech Israeli firms.

Bernard Dichek

Biotech, and Dengue

Posted on 07 Dec 2012 by Bioentrepreneur

Our editorial team came across a bit of news on neglected diseases while monitoring the biotech sector and thought we’d pass it along. Neglected diseases earned that collective moniker partially because the major drug developers of the world didn’t see the financial incentive to pursue products in these indications. Over the years, smaller, more nimble biotechs have stepped into the void, and today biotech companies are contributing 41% of products in the pipeline for neglected diseases, according to a new report by BIO Ventures for Global Health (BVGH), a non-profit based in Washington, DC. The report looks at neglected disease drugs and vaccines currently in development worldwide and examined the entities working on them.

The report shows that academia still is responsible for most products in development, with biotech coming in second, but ahead of non-profit-supported developers and pharma companies. Of course, all these groups often collaborate, an example here being Anacor, of Palo Alto, California. The company is working on a slew of neglected diseases while it also pursues its main portfolio. The company began its endeavour by collaborating with the University of California at San Francisco and later drew support from the Geneva-based non-profit Drugs for Neglected Diseases Initiative.

Dengue is the top target for biotechs, the report states. BioMedTracker lists products in development for dengue virus from Sanofi, Merck and Co., and Vical, with Sanofi having acquired its product from Acambis, first through license and then outright buyout; and Merck from Hawaii Biotech via purchase.

Dengue is a global problem, of course. The Centers for Disease Control puts the infection rate worldwide at 100 million annually, and this map shows the areas most affected. Nice to see biotech doing what it can.

Alma As Example

Posted on 28 Nov 2012 by Bernard Dichek

Biotech entrepreneurs looking for new ways to start a company on the global stage may find the example of Alma Bio Therapeutics inspiring and instructive.

The start-up with a platform technology in the field of auto-immune and inflammatory diseases was established in December 2011 by Irun Cohen, a professor emeritus at Israel’s Weizmann Institute; Raanan Margalit, an expert in preclinical drug development; and Dr. Binah Baum, an experienced biotech executive who is well-networked in the European bio-community.

The three Israeli founders established their business in the Basel Biotech Incubator in Switzerland and financed a preclinical trial out of their own pockets. In doing so, they have shown it is possible to establish a company outside of one’s home turf and get to proof-of-concept without relying on outside investors.

Baum explains the choice of the Swiss location as being related to access: several big pharmas that are likely candidates for collaboration are in that area or nearby in Germany, Austria and France. Also, the European venue increases the startup’s visibility among angels and private investors. In Israel, by contrast, she notes that VCs are primarily focused on medical devices rather than early stage biopharma, though she says it’s possible they might establish a presence in Israel later on.

The company’s IP is based on original research by Prof. Cohen at the Weizmann Institute. Several years ago, that IP was reassigned back to the inventor by the Institute’s technology transfer agency.

As a combined result of the previous and current studies, Alma has already obtained six major patents. The company chose inflammatory bowel disease (IBD) as its initial autoimmune indication. At a later stage, it plans to apply its platform to chronic pathological inflammatory diseases.

Alma’s technology is built around leveraging heat shock proteins (HSPs) that are implicated in the immune system’s control over inflammatory diseases. Discoveries made in this area by Prof. Cohen have already led to the development of a drug by Andromeda Biotech for Type I Diabetes; it is currently in Phase III.

Alma’s goal is to treat IBD in a curative and non-toxic manner by introducing heat shock proteins in the patient’s body that can regulate the level of inflammation in a controlled manner. Rather than use recombinant proteins, the HSPs are introduced through changes in the DNA coding.

The entrepreneurs note there is no disease-modifying therapy available for IBD, a condition currently attracting intensive R&D efforts in the pharmaceutical industry.

Upon reaching Phase I/II, Alma’s founders are confident that investors are likely to gain a relatively fast and high multiple return once a deal is made with a pharma company.