🚀 Entrepreneurship

Our Mission

Our mission is to accelerate the field of synthetic biology through the development of accessible and sustainable cell-free systems. We strive to create a future where cell-free synthetic biology tools are within the reach of researchers, educators, and innovators worldwide, catalyzing groundbreaking discoveries and delivering sustainable solutions to some of the world’s most pressing challenges.

Cell-Free Systems have the potential to transform a diverse range of bioprocesses, from small-scale synthesis of protein for research purposes to mass production of medicines and industrial enzymes [1]. However, the high cost of entry, complex logistics, and specialized equipment required to utilize cell-free systems have still left many researchers in academia and early-stage biotech unable to fully leverage this powerful technology. Opportunity Cell-free Protein Synthesis is an incredibly versatile, powerful process that can be used to produce many different biomolecules. However, its use, thus far, is mainly focused in lab work, primarily in academic settings. The Cell-Free Transcription and Translation (TX-TL) technology is mainly used by well-equipped academic research laboratories, for example to prototype gene circuits to be implemented in traditional cell-based systems [2]. For the technology to mature and become widely adopted in industry, innovation reducing cost while increasing scale must take place. We believe in a future where safe, accessible, affordable synthetic biology tools are available to a wide audience of innovators, with an accessible Cell-Free platform as an important part of our vision.

Our Beginnings

We saw something exciting in the lab and imagined it entering into the commercial world in a blaze of glory. Proteins with powerful protective properties from a charismatic creature known for its resilience? Popularizing the cutting-edge TX-TL technology? Fantastic! Our project solves a key problem for SynBio practitioners across the world; who doesn't want a shelf-stable cell-lysate? We entered into the prospective entrepreneurial landscape as a team full of hope and dreams, ready to make a difference with this tardigrade-protein infused lysate.

Fundraising and Pitching

As the first iGEM team from our campus, resources for startups and entrepreneurship have been greatly helpful as we developed our project.

We were fortunate to receive a non-dilutive prototyping grant from UnternehmerTUM, the largest startup accelerator in Europe, following consultation with Florian Lintl, the head of our campus Venture Lab. To qualify for this grant, we had to show our potential to form a deep-tech startup that could potentially move forward through the venture capital ecosystem. Getting here required an education in pitch-building.

Initially, our "pitch deck" was a word-heavy PDF explaining all of our scientific aspirations in excruciating detail while glossing over practical applications of the research. We also didn't include any financial projections or tangible commercial benefits of cell-free technology, since we lacked the knowledge how to prepare a pitch talk in general. Upon presenting the project to a commercially minded audience (Patrick Grossman, CEO of Invitris), we received a lot of helpful advice and constructive criticism. He offered us to try using the Y Combinator tools for pitch building and not to forget to include important segments such as financial market analysis and projections. We had the opportunity to improve our pitch and present our ideas a few more times to stakeholders. Each pitch was an exercise in the iterative DBTL cycle. Received feedback was implemented multiple times, and we adapted our presentation to different audiences:, from biotech accelerator members at ValleyDAO to non-technical startup consultants at Venture Labs. Some of the most insightful feedback we received was to:

• Tell a story!
• Keep it short and direct
• Make it easy to understand!
• But don't compromise the technicals

This is one of our slide decks, built for a non-technical audience, that we would like to share as example for other iGEM teams:

Intellectual Property

While connecting to these entrepreneurial resources, the question of IP began to emerge. Of course, none of us had ever dealt with patents before, as we’re student’s with limited industry experience. We discussed IP with connections at ValleyDAO (decentralized climate-tech accelerator), TUM VentureLabs (University entrepreneurship support), and SynBio IP Lawyer Sara Holland. With the help of our advisors and research, a picture was painted of the road to defensible intellectual property in Germany; it became increasingly clear that it is well-paved with paperwork.

Due to the open-source nature of the iGEM competition and the source of our project's inspiration (Imre Banlaki, our PhD advisor, proposed the tardigrade protein-protected cell-lysate), the tardigrade-related elements of the project were meant to be published openly as part of the iGEM project. But what of the other advances, such as the energy buffer optimization? Could we become pioneers in the field of tardigrade proteins? Where could this research take us?

The Needs of Industry

As we explored the ins and outs of the Cell-Free sector, we realized that there wasn't really a commercial need for tardigrade-stabilized lysate; it's an interesting proof of concept and foundational advance into the integration of disordered proteins into synthetic biological systems, but there's already similar things that perform the same function. Trehalose, for example, has already been used to stabilize cell-lysate[3] during lyophilization, and the lyophilization that we're avoiding by using the proteins isn't the largest cost factor in operating a Cell-Free system. In the laboratory setting, energy buffer components are the costliest part of a reaction [2]. The deeper we looked into the industrial aspects, and the closer our project was inspected by interested parties, the more work to be done revealed itself.

Intellectual Property

During our exploration of the entrepreneurial path and collaborations with UnternehmerTUM and TUM Venture Labs, we considered filing a preliminary patent application surrounding the optimization of our energy buffer. Ultimately, due to the extensive (and expensive!) processes surrounding German patent law, all results from these procedures are published openly here on the wiki, and no patent was filed. While meeting with potential coopetitors, Invitris and Insempra, both independently raised the point that our main process didn't really have a great deal of commercial value; it would be complicated from a legal perspective to express the tardigrade genes in an autolysing strain, and if we're actually using the E.coli for production, it would be better practice to use a standard non-autolysing strain of something like BL21, and simply add purified tardigrade proteins to that. Our main lab workflow also didn't actually measure the concentration of tardigrade proteins expressed in the lysate, so we have no idea how much or little is needed to effectively stabilize lysate.

Even if our experimentation was more robustly carried out, the functions of intrinsically disordered proteins still aren't fully understood (posing regulatory risks for pharma synthesis) and, compared to something like Trehalose (a simple, inexpensive chemical lyoprotectant), are unlikely to offer any distinct advantages in the preservation of cell-lysate. Tardigrade proteins are fascinating, and understanding the roles that intrinsically disordered protein segments have evolved to take on can offer new insights into the foundational building blocks of life. But foundational advances don't pay the bills.

We realized that the commercial path we'd considered was not realistic. Between German IP laws andlack of commercial potential, our path forward into the wilderness of the free market was looking more disordered than a tardigrade's proteins.

But like the mighty waterbear from which we draw our inspiration, we survive and move on. In part because of the competition, in part because of the prototyping grant we received, and in part because we harbor a secret dream of wanting to make the world just a tiny bit better. There are so many challenges out there, so many problems, and we'd like to be part of a solution.

Commercial Research

Moving forward with a commercial mindset, it makes more sense to enter into a contractually protected Sponsored Research Agreement if the research is to take place in a public academic lab. However, IP is much easier to manage if developed in a privately owned lab.

Maria Castano, our connection at Sartorius, forwarded us to Invitris, a startup that successfully spun off from a Munich iGEM team, who provided valuable insights into what it takes to be a startup in this space. They explained that small biotech companies aren't generally supporting themselves by selling physical products, like reaction kits. Products are important, but more for showing a proof of concept than as a main revenue stream; the true value comes from showing your unique edge and collaborations with others. For a small, flexible, private research lab, there are several potential sources of funding:

• Product Sales
• Sponsored research
• IP Sales
• Codevelopment
• Investors
• Grants
• Acquisition

A company succeeding in the space must take a multi-pronged approach to business. Selling reaction kits might be part of a firm's portfolio, but ultimately they should be there as a signifier that this is an active, innovative environment that produces useful things. Kits should be sold at a low profit margin, or even at a loss, to expand outreach and brand awareness. By selling products targeting other labs, we will be expanding our network of potential collaborators. We will simulate this working relationship by sending kits to other iGEMers.

Coopetition

There are many companies working with cell-free systems. We see our potential relationship with these companies through the lens of coopetition; by working together, we can accelerate the development of cell-free systems and make them more widely available to the scientific community, expanding the market for all companies involved. Here are examples of some companies working in this field space:

• Invitris
• Tierra Biosciences
• Twist Bioscience
• B4pt
• Lenio Biotech

Ultimately, we realize that tardigrade protein-infused lysate does not have a significant market value. A new niche must be found.

(re)Consultants

Another collaboration came in the form of student organization Reconsult. As a sustainability-focused business consulting club, they were happy to support us in developing a better understanding of the market from a business-focused perspective. They helped us to prototype a business model that leaned on the strengths of a flexible young research group.

SWOT Analysis

The SWOT analysis is a strategic planning tool used to evaluate the Strengths, Weaknesses, Opportunities, and Threats involved in a project or business venture.

Expanded SWOT Analysis

Strengths

• Strategic Partnerships: Collaborations with Invitris, UnternehmerTUM, TUM Venture Labs, and other industry partners provide valuable support and resources.

• Cost-Effective Solution: The focus on producing cheap lysate with low storage and transportation costs addresses a significant market need.

• Location Advantage: Straubing's growing biotech scene and underutilized talent pool offer a unique opportunity for growth.

Weaknesses

• Initial IP Limitations: The open-source nature of the iGEM competition and the project's inspiration have limited patentability of core technologies.

• Early Stage: As a startup, Bluebear Bio may face challenges in scaling production and establishing market presence.

• High Fixed Costs: The business model indicates high fixed costs, which could be a challenge in the early stages of the company.

Opportunities

• Growing Biotech Market: The expanding field of synthetic biology offers numerous applications for cell-free lysate technology.

• Educational Market: Potential to tap into the educational sector by providing accessible synthetic biology tools to schools and universities.

• Customization Potential: Ability to develop specialized lysate varieties to meet diverse industry needs as the company grows.

• Codevelopment Projects: Opportunity to engage in codevelopment projects with larger companies in private industry.

Threats

• Competition: Established players in the biotech industry may have more resources and market share.

• Regulatory Challenges: Potential regulatory hurdles in scaling up production and commercializing biotechnology products.

• Funding Uncertainty: Dependence on research grants and venture capital could pose challenges if funding becomes scarce.

• Technological Advancements: Rapid advancements in the field might require constant innovation to stay relevant.

Bluebear Bio has the potential to disrupt the cell-free synthetic biology market with our innovative and cost-effective solutions. Our strategic partnerships and location advantages position it well for growth. However, careful navigation of IP issues, scaling challenges, and market competition will be crucial for long-term success. Leveraging educational markets and pursuing customization opportunities could provide significant avenues for expansion.

Business Model

The Lean Canvas is a business model canvas specifically designed for startups

Bluebear Bio will produce, develop, and sell cell lysates. Our company will reach two main customer groups at the beginning of its natural lifespan; small academic and private industry labs. As we develop our lab further, scaling our process of lysate production and guiding our research through meeting the priorities of these two key customer groups, our intellectual property will develop and we will be in a position to codevelop projects for larger companies in private industry.

Cell-Free TxTl has an incredible range of potential commercial applications. By studying and solving a few of its core limitations, we will find our niche in the bioeconomy developing and scaling cell-free systems.

The core of our business will remain the same (providing cell-free reactions optimized for cost without compromising on activity), but we will meet the needs of different industry segments as we expand our product lines and deliver more specialized varieties of lysate.

Expanded Business Model

The Problem

Cell-free synthetic biology is on the verge of breaking through to the wider ecosystem, but several weak points still hold it back. The primary obstacle is the high cost and limited accessibility of cell-free tools, which restricts its widespread adoption across various industries. This barrier is further compounded by a prevailing niche focus on academic research, which often overlooks the commercial scaling potential necessary for broader industrial applications. As a result, many potential users, particularly in small labs and startups, are unable to leverage the benefits of cell-free systems.

Our Solution

We will dismantle these barriers by offering affordable, scalable, and user-friendly cell-free lysate solutions. Our approach focuses on reducing costs through optimized production processes and strategic partnerships, enhancing accessibility for a broader audience. By prioritizing the development of low-cost lysate and streamlining distribution through our automated online shopfront, we empower researchers and innovators to conduct advanced experiments without the need for extensive resources or specialized equipment. Our commitment to democratizing synthetic biology is reflected in our efforts to provide high-quality lysates that are cost-effective and versatile enough to meet a wide range of research needs.

Unique Value Proposition

In a market where cost and accessibility often hinder widespread adoption of developing bioengineering tools, Bluebear Bio stands out by offering a unique focus and source of value: affordable, accessible cell-free lysates that do not compromise on quality. Our focus on reducing costs of storage and transportation, alongside our commitment to lowering the barriers to entry, positions us uniquely to democratize synthetic biology. By leveraging strategic partnerships with industry leaders and academic institutions, we are able to deliver a product that meets the needs of both academic and industrial researchers, while continuously optimizing for efficiency and cost-effectiveness.

Unfair Advantage

Bluebear Bio's unfair advantage lies in our strategic collaborations and geographical positioning. Our partnerships with industry frontrunners like Invitris and UnternehmerTUM provide us with unprecedented access to resources, expertise, and market insights that are difficult for competitors to replicate. Additionally, our location in Straubing, a town rich with underutilized talent and a burgeoning biotech scene, grants us an advantageous position to harness local resources while maintaining operational flexibility. This unique blend of alliances and location offers us a competitive edge in driving innovation and scaling our operations effectively.

Customer Segments

Bluebear Bio targets diverse customer segments, each with distinct needs that align perfectly with our product offerings. Our primary customers comprise small academic labs and private industry labs that require cost-effective, efficient solutions for conducting advanced biological research without the complexities of traditional cell-based systems. As we progress, we aim to expand our reach to include pharmaceutical researchers and educational institutions, providing them with customized solutions that facilitate cutting-edge research and learning. Our commitment to understanding and addressing the specific challenges faced by each customer segment ensures that we deliver solutions that are not only innovative but also deeply aligned with the evolving needs of the synthetic biology landscape.

Channels

Our multi-faceted approach to reaching our customer base is a testament to our dedication to accessibility and engagement. Bluebear Bio utilizes an automated online shopfront to streamline the purchase process for our cell-free reaction kits, ensuring ease and convenience for our customers. We actively participate in conferences and trade shows, enhancing our visibility and fostering connections within the synthetic biology community. Additionally, we build our social network through targeted publications and partnerships with iGEM teams, reinforcing our presence in the synthetic biology space and extending our reach to new audiences.

Revenue Streams

Bluebear Bio's revenue streams are strategically diversified to ensure a resilient and scalable business model. Our primary revenue is generated through the sale of our cell-free lysate kits, which cater to academic and industry labs seeking cost-effective solutions. As we expand our capabilities, we anticipate additional revenue from codevelopment projects with larger companies, leveraging our expertise to deliver customized solutions. Furthermore, our intellectual property presents opportunities for licensing agreements, allowing us to capitalize on our innovations while fostering collaboration and growth within the synthetic biology landscape.

Customer Profile

• Researcher in a Biology lab, moderately well-funded, does frequent high-throughput screening
• Chemists who wants to express genes without growing a cell culture
• Educators who want to teach cell-free systems
• Industry researchers who want to optimize their protein expression

Proof of Concept

We realized that we need to think big; if we're to accomplish our mission of expanding cell-free synthetic biology, we should seek to solve some of the world's pressing sustainability concerns while going about and expanding our operations.

Potentially, one of the most commercially practical applications of cell-free TX-TL is enzyme/protein manufacturing. Additionally, complicated metabolic pathways that place a large burden on living cells can be more easilyeasiliy implemented in cell-free systems, even thougheventhough cell-free systems are expensive to maintain. Interestingly, at scale, the largest cost factor for cell-free systems isn't generally the energy buffer; the cost of DNA templates adds up quickly. Properly scaling a cell-free system thus requires careful optimization of variables like magnesium content that promote the recycling of DNA through the TX-TL process. Scale-up is a field unto itself, and a field that we began to explore.

A Process Flow Diagram (PFD) is a graphical representation of the process flow of a chemical or biochemical process. It is used to visualize the flow of materials and energy through the process, and to identify the key components and equipment required.

After designing a series of experiments to scale up our lysate production, and modeling the process, we received approval to operate in the Bioverfahrenstechnik (bioprocess engineering) lab at our campus. By moving from a flask to a bioreactor, we gained a more realistic idea of what it takes to produce commercial quantities of cell lysate. Read about this process more on our upscaling page, where we show the iGEM community the benefits and challenges of increasing production volume. While we only physically tested a 2l reactor size, the process flow that we calculated allows for much more accurate data on what it would take to produce enough cell-lysate to make an impact in the market.

Location

Connecting and working with other student groups is one of the advantages of our geographic location in a small but rapidly expanding biotech hub.

Map of Biotech Hub Straubing

The TGZ Biolab at the Hafen Straubing-Sand leases suitable lab space for our purposes, while local life science companies and labs have the potential to become stakeholders and partners.

References

1. Catherine, C., Lee, K. H., Oh, S. J., & Kim, D. M. (2013). Cell-free platforms for flexible expression and screening of enzymes. Biotechnology advances, 31(6), 797-803.
2. Marshall, R., & Noireaux, V. (2019). Quantitative modeling of transcription and translation of an all-E. coli cell-free system. Scientific reports, 9(1), 11980.
3. Marshall, R., & Noireaux, V. (2019). Quantitative modeling of transcription and translation of an all-E. coli cell-free system. Scientific reports, 9(1), 11980.