Team:UniGE-Geneva/Entrepreneurship
Entrepreneurship
« Our vision to improve drug testing efficiency
and biological relevance led to the development of Fluosphera,
an in vitro method to recapitulate the interactions
between multiple human tissues »
Market analysis
Literature search
• Peer-reviewed journals
We performed an academic literature search using NCBI Pubmed to compile primary research and review articles related to encapsulated spheroids and in vitro drug testing. We also reviewed the literature related to the microfluidics device that is used to encapsulate spheroids in our host laboratory to identify literature about previous applications related to the technology.
It became clear that 3D cell culture is currently an intensely-researched topic with applications in fundamental cell biology, precision medicine, as well as high-throughput or high-content drug screening. The increasing number of academic research articles in recent years is mirrored by the adaptation of this technology into the commercial sector, and some of these peer-reviewed articles were published by commercial entities, allowing the initial identification of existing companies in our field of interest.
• Internet search
Google.com was used to obtain a general understanding of the competitor and collaborator landscape. For example, we identified many local (Swiss) companies with cell spheroid products or services, as well as potential collaborators at our own university or within Romandie - the French-speaking western region of Switzerland.
‘Prior Art’ (search of existing patents)
Our Technology Transfer Supervisor, David Pejoski, was trained at the University of Geneva Patent and Commercialization unit, Unitec, to perform an extended prior art patent search using Espacenet beta and Google Patents.
The resulting prior art search indicated that there were an extremely high number of patents existing in the field of in vitro drug testing, many existing patents in the field of 3D spheroid co-culture, and a low number of patents existing in the encapsulated-spheroid field. Importantly, and despite extensive searching, no patent was identified which combined the multiple characteristics we intended to incorporate into a single new drug screening methodology. These in vitro drug testing features we combined in FluoSphera include the capacity to identify different cell populations using fluorescently labeled encapsulation material, as well as different biological processes such as tumor growth, cell death, inflammation, and hormone responses – all within the same test.
In the future, we intend to perform a ‘guided prior-art search’, as recommended by Unitec. This will involve sending one or more representative team members to the Federal Patent Office in Bern. For a relatively small fee compared to outsourced legal costs, a patent specialist from the federal office is assigned to facilitate an in-depth comprehensive patent search. If no overlapping prior art is found, i.e. if our invention or process appears to be novel and not require the negotiation of a license or payment of royalties, the federal office can issue a 'freedom-to-operate' document. The freedom to operate status aims to protect the operations of the startup, by ensuring they are not infringing any external patents, and that any intellectual property linked to the current invention is being used in a lawful manner, i.e. via an agreement with other patent owners, or via licensing.
Collaboration and Competitor analysis
We identified the following competitors and attempted to better understand their products and business models by contacting them by phone, email, or in person, and also by viewing their websites, product promotional material, publications, and posters. These businesses or research entities were identified using the online searches described above, in person via the attendance of conferences (the MipTec session at Basel Life 2019, and the CRTOH Unige Symposium, Geneva, 2019), by word of mouth during coaching sessions with pharmaceutical entrepreneurs, or directly via members of translational research units from the University and local biotech incubators :
ACCESS Unit, Unige. A university drug-screening platform based at the Faculty of Science, Unige. We reached out to this platform because of their specialization in image-based drug discovery, and subsequently performed most of the preliminary experiments there (ACCESS)
READS Unit. A university drug-screening platform based at the Faculty of Medicine, Unige, with a focus on biochemical readouts and roboticized assays. (READS Unit).
InSphero. A Zurich-based 3D cell culture platform for metabolic disease and oncology discovery, as well as liver toxicology (InSphero).
TreeFrog Therapeutics. High-throughput and cGMP-compatible 3D stem cell culture based in Bordeaux, France (TreeFrog Therapeutics).
Capsum. Tailor-made encapsulated cosmetics that uses the same microfluidics encapsulation device as InSphero (Capsum).
IDEA Bio-Medical Ltd. (IDEA Bio-Medical Ltd.)
Questionnaires
A preliminary questionnaire was launched on social media to identify researcher and student perceptions towards in vitro testing and the desire to replace some animal experimentation with translational in vitro models.
The initial results indicated a clear desire to reduce drug testing in animals, echoing the 3R guidelines (3R guidelines) and recommendations issued by the regional animal experimentation office RESAL. In the near future we aim to develop and conduct new questionnaires with the guidance of bioethics experts, with a greater number of questions and participants to confirm our preliminary findings. Tailored questionnaires are intended to be used during future market research with potential customers to identify additional needs and develop an approach to improve our product using customer-focused market research.
Expert advice and coaching
- Mentorship of Aurélien Roux, Director of Biochemistry Department, Faculty of Science, Unige, and advisor of the iGEM Geneva Group in 2019. Prof. Roux provided invaluable background information about the encapsulation device – especially its commercialization and patent history, as well as details of previous and ongoing parallel commercial projects involving encapsulated spheroids, which were instrumental in shaping the direction of the novel research.
- Meetings with pharmaceutical entrepreneur Sylvain Lengacher, CEO of GliaPharm, Geneva. Through the comments and suggestions of a biotech insider, we understood that an important feature of drug screening or testing technologies is cost and time-effectiveness, to ensure competitiveness in relation to tests using small animal-derived cells or industry-standard monolayer cell line methods. Dr. Lengacher provided coaching on how to effectively market our business concept, and also offered the potential to collaborate.
- Project pitches with the Translational Accelerator director, Vincent Wagner, functioned as coaching sessions as well as market research thanks to Dr. Wagner’s expertise in biomedical industry. His suggestions and critical questions about FluoSphera contributed to the conception of a viable product idea.
- Spheroid company representatives : biotech representatives for spheroid products or services were actively contacted by email, or in person during numerous trade displays or technology demonstration events - including those mentioned in the Collaborators and Competitor section. Our communication with these representatives allowed us to better understand the capabilities of similar technologies to FluoSphera, gaps in the market, customer needs and expectations, as well as understand their business operational model and ask for advice about the spheroid market in general, including pricing.
- Conference attendees:
While presenting our poster at the CRTOH Symposium to an audience of mostly cancer researchers and clinicians, we were able to gauge the level of interest and improve our understanding of how our technology might be used for fundamental research in academia or as a tool that Oncologists could use to screen drugs on spheroids made from patient-derived tumor cells (patient-derived organoids; PDOs) i.e. a personalized or precision medicine approach. Several researchers who approached us were interested in this second potential application of FluoSphera. These conversations reinforced our speculation that drug screening of PDOs using Fluosphera could be an additional viable application of our business, and also allowed us to understand desirable product features from a clinical perspective. However, a cost analysis indicated that ready-to-use plates for drug testing of cell lines was much more financially lucrative.
- Dr. Dimitri Moreau, director of the ACCESS Drug screening platform. Dr. Moreau provided advice about the best instruments and fluorophores to use, and also insights into industry and academic standards, i.e. what customers of his screening platform often use, and what he could foresee as useful improvements to their drug testing methodologies.
- Market Size and Growth
External market analysis by Grand View Research predicts that the 3D cell culture market size will expand by several fold in the 11 years between 2013 to 2014. The market already represented 151.3 Million USD in 2013, and is expected to grow rapidly in all sub-sectors, including cancer research and drug development, see Figure.
- Market Segment and Future Clients
Together, the various aspects of our own market analysis indicated a high demand for in vitro drug testing that features enhanced biological relevance, such as the presence of hepatocytes to metabolize drugs, or multiple tissue types to recapitulate sophisticated multi-organ biological systems. The use of ‘translational’ in vitro assays, such as Fluosphera, is likely to be at the ‘lead optimization’ or ‘hit downselection’ phases of the drug screening process.
Fluosphera’s features allow for downselection of hits that are no longer efficacious after metabolism by hepatocytes, or additionally, hits that are metabolized to highly reactive compounds which result in toxicity to critical organs such as the liver, kidneys, and brain. Similarly, based on our data with Tamoxifen, a drug that requires metabolism by hepatocytes before acquiring more potent anti-cancer properties, could also be identified using FluoSphera early in a drug screen pipeline i.e. Fluosphera is specifically designed to identify small molecules pro-drugs which become more efficacious after metabolism by hepatocytes. These features make Fluosphera ideal for companies that are looking to streamline their hit/lead validation phase, by multiplexing critical readouts of optimal drug candidates such as hepatoxicity and efficacity after liver metabolism.
The reason for opting for a more niche market segment rather than ultra-high throughput screening assays using very large molecule libraries ( >100,000 chemical entities) is that cell encapsulation and spheroid-based drug testing approaches are currently more amenable to small or midsized assays. For example, a more realistic experiment size for 3D-tissue screening would be to investigate the effects of up to 2000 molecules (22 plates testing approximately 90 molecules each). These kinds of screens are routinely performed by small to large pharmaceutical companies, as well as academic researchers working on applied drug development projects.
SWOT
Information garnered from the market analysis was combined and used by team members to develop a S.W.O.T. analysis (Strengths - Weaknesses - Opportunities - Threats), with the aim of capturing the technology’s unique features and weaknesses. The SWOT analysis can be used to help place the FluoSphera concept in the broader context of all drug testing approaches, rectify weaknesses, avoid current and future threats, and maximise opportunities.
Value proposition
The multifaceted market analysis resulted in the development and refinement of a ‘Value Proposition’, in other words, what our product is, and how it can add value to, or improve the world.
FluoSphera’s Value Proposition is to
provide an enhanced method to test drugs in vitro that:
Marketing and branding
Notable examples of business exposure with the aim of marketing our ideas are described briefly below, and also in the human practices section (Human practices)
We adapted our presentation slide decks and posters to communicate our goals and findings in an audience-appropriate manner during each opportunity:
- Pitch presentation to Sylvan Lengacher (CEO of GliaPharm) resulted in obtaining professional contact details of 3rd party partners with which could establish a future collaboration.
- Pitch presentation to the directors (Vincent Wagner and Guillaume Rey) of the Translational Accelerator unit at the Faculty of Medicine, University of Geneva, Switzerland.
We took part in the annual symposium for the University of Geneva’s Centre for Research in Translational OncoHematology CRTOH, held at a large biotech hub called Campus Biotech, Geneva. Our poster presentation was well-received and we used this opportunity to make connections with potential future clients.
Branding
We shortlisted and investigated the availability of appropriate names for the startup company as well as the minimal viable product that is currently in development. This involved checking the business name registry and trademark listings, as well as internet domain names that correspond to the intended business and product names. Registering trademarks for products is likely to be managed after finalizing the MVP, see below.
Logo development included brainstorming and selection of a simple and recognizable logo. Many attempts were made to optimize the logo, see images. :
To create commercial presence and advertise our business concept, we printed both the Fluosphera logo and iGEM Geneva 2019 logo on Polo shirts to wear at promotional or scientific meetings. Additional promotional material including stickers of our various logos have also been printed for distribution during the presentation of our poster at future events, including the iGEM Jamboree in Boston.
Intellectual property
- Legal advice and patent filing with Unitec, the University of Geneva Technology Transfer Office.
Raluca Flükiger and Julien Levallois provided excellent advice that allowed us to position our novel methodology in the current biotechnology landscape, as well as provided critical feedback to some of research ideas and directions in an attempt to increase our chance of success at both the scientific and legal level. Unitec provided invaluable feedback after reviewing the Prior Art database compiled by our commercialization advisor, Dr. David Pejoski.
Dr. Flükiger assisted us in developing a set of ‘claims’ for a provisional patent. Claims are discrete phrases that describe precise elements of an invention, and in our case, the novel drug testing methodology. This process took several weeks and helped define our MVP definition and which experiments are required in the upcoming year .
- A provisional patent (EP19199296.5) was filed at the European Patent Office on the 24th September 2019 after extensive collaboration with Unitec in addition to a patent officer from the legal enterprise Katzarov. The patent describes a multiplexed and encapsulated 3D cell co-culture drug testing method, including an in vitro drug testing kit suitable for testing the effect of one or more drugs of interest on multiple biological processes in one or more target cell types. Finally, we aim to file a complete patent application before 24/9/2020.
- InnoGap (Unige) and innovation funding from other sources, such as the RESAL 3RCC Open Call, or InnoSuisse Bridge Funding is pending approval or being drafted, and will be used to consolidate our experimental findings that refine the claims of our provisional patent, and incorporate a startup, depending on the amount of funding that is secured.
The claims of the provisional patent cover a broad range of applications, and explicitly lists numerous examples of potential uses for the technology. We believe that FluoSphera has potential in many other fields where co-culture of tissue-like spheroids are used, and therefore additional patents may be filed in upcoming years to protect distinct I.P.
- Attesting ‘Freedom to Operate’ is necessary to proceed with commercial operations, including sale of an MVP which is produced using an already-patented and commercially-developed microfluidic device.
Minimal Viable Product (MVP)
Our MVP, or minimal viable product, is an easy-to-use, adaptable, multiplexed, and physiologically-relevant, in vitro drug testing method.
The MVP is a mixture of encapsulated cell spheroids that represents multiple human organs or tumors in a single well of multi-well plate, intended for use in high-content efficacy and toxicity studies of existing and novel pharmaceuticals candidates. Individual cell types can be identified using fluorescent microscopy, and fluorescent reporter genes allow multiplexed simultaneous readout of biological processes such as tumor growth, hepatotoxicity, apoptosis, and inflammation.
Pre-dispensed mixtures of pre-grown encapsulated cell spheroids in microwell plates can be rapidly sent to clients, and then used within 3 days. Other MVPs are also possible and are under investigation, for example precision or personalized medicine using encapsulated patient-derived organoids, which is produced using tumor cells provided by the hospital after surgical removal of malignancies from cancer patients. Additional data is needed to make informed decisions about the precise composition of the MVP, and determine the limits of storage, shipment, and best combination of organs to recapitulate in vitro.
The MVP is more suited to secondary or tertiary drug screens, as described in our market research section. The appropriate funding, precise definition of the best spheroid tissue type combinations, and optimization of scalable production of MVPs could make our invention accessible to the first customers as early as Q1 of 2020. These initial customers include small and mid-sized biotechs, and big pharma, who are focused on therapeutic development for a range of diseases including cancer.
Additional proof of principle studies are required to consolidate the provisional patent claims, and refine the patents scope as well as help define the best MVP because technical feasibility and production aspects.
Commercialization perspectives
- ‘Assisted’ Prior-Art Search at the National Patent Office, Bern. The Unige technology transfer office, Unitec provides funding for a representative from their current University projects to travel to Bern and work for a day with a patent specialist. The aim will be to define ‘prior art’ (related patents) that have overlapping features with our provisional patent. Also, obtaining a freedom-to-operate status will ensure we have the required legal permission or licence agreements to use the patented microfluidic encapsulation device within our own commercial operations.
- Future funding we have applied for, detailed above, is intended to be used to: complete experiments to improve and finalize the patent claims, perform an assisted prior-art search with a qualified patent officer – allowing ‘freedom-to-operate’, and importantly to conduct additional optimization experiments that allow the co-culture of more diverse cell subtypes in the same well. These legal and technical milestones will allow the optimization of our minimal viable product (MVP) and facilitate our fundraising efforts, towards our global aims of launching a startup and generating income via product sales to our first customers.
Finance/Funding
Budget projection
Sponsors
Unige-iGEM 2019
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