Entrepreneurship

Our first steps towards a business model

Our Product

SilenshR is a synthetic biology solution that leverages the innate capacity of bacteria to colonize the hypoxic and immune-privileged cores of tumors conferring specificity to a systemic therapeutic approach. Once the SilenshR E. coli reach a cell density of 2*10^11 colony forming units (cfu) per milliliter within the tumor, genetic circuits are activated allowing SilenshR recombinants to invade cancer cells and release a short hairpin RNA (shRNA) targeting an expressed oncogene thereby halting the unchecked cellular proliferation of cancer. By circumventing the need for systemic delivery of chemotherapy and the inevitable off-target cytotoxicity, SilenshR keeps the immune system intact, spares the digestive epithelial lining from damage and relieves anxiety surrounding hair loss.

Mission Statement

We are committed to exercising our curiosity and improve medicine by applying synthetic biology to enhance health and well-being.

Future Generation Products

SilenshR is not just one recombinant bacterial strain or one sequence of DNA: SilenshR is a revised approach to cancer treatment with greater specificity and less discomfort. Just as different chemotherapeutics might be prescribed depending on the affected organ, the therapeutically active component of SilenshR, the shRNA sequence, can be altered depending on the particular gene promoting tumor growth. The engineered bacteria would have a significant application to human health particularly in conditions characterized by aberrant gene expression, such as with oncogenes in cancer, cytokines in inflammation, and many others. For cancer applications, the engineered bacteria can be taken as an oral probiotic, which will then selectively localize in tumor cells to prove gene therapy.

Technical Implementation Plan

Here we list what tasks need to be accomplished in order to complete our first round of product design. The list is ordered by level of priority for evaluating the commercial potential of our technology. As such, the order represents the relative risk of each experiment, where failure to achieve good results could significantly impact the time and cost estimates for the research and development.

Final characterization of our first generation sensing organism
Transferring our electrochemical system into Nissle
Transitioning our first product into the final prototyping stages
Further screening for future generation products
Further multiplexing of our gene therapy system
In vivo trials in test animals
Clinical trials

Patent Protection

The technology that we have developed, for the purpose of IP protection can be placed into two categories: 1) a method for treating cancer in mammals using bacteria that deliver a therapeutically effective amount of an RNAi agent to reduce the expression or biological activity of target proteins or biologically active fragments 2) Also encompasses a high-throughput, cell-based screening assay for identification of agents that knock down oncogenes, in which bacteria are incubated in conditions suitable for production or release of the therapeutic agent, and test agents that produce a greater amount of gene knockdown than in the control population are selected for. Despite pending public disclosures, we filed for a patent on our technology through Columbia Technology Ventures. Columbia Technology Ventures is the technology transfer office for Columbia University and a central location for many of the technology development initiatives, entrepreneurial activities, external industry collaborations, and commercially-oriented multidisciplinary technology innovations across the university. CTV offers the following services to Columbia associates: Patent filing and IP management, Technology marketing, Technology license agreements, Material and data transfer agreements, Confidentiality agreements, Inter-institutional collaborations, Investment opportunities, mentoring opportunities, Pitch events, and more. Some examples of related patents to ours can be seen below:

Source: Columbia Technology Ventures

We hope that our example will become the accepted means for teams to protect their innovation while still making their parts available for use by others. Although the registry is dependent on the willingness of teams to both utilize its resources and submit their own additions, there is no reason why this philosophy should be incompatible with entrepreneurial development, as with any other open-source system.

(source: Clatech HP 2010)

We believe that the BioBrick™ Public Agreement is a good step in the direction of a sustainable Registry and we hope future teams wishing to protect their work will consider doing so in a way that does not inhibit future iGEM innovation. That is, we hope they avoid patenting primary gene sequences whenever possible. Rather, teams should work to patent only their particularly innovative process.

In order to protect our IP, we have chosen to hold the IP as a group of eight members from the iGEM Entrepreneurial team and license this IP to any legal body which we are involved with and require that IP to grow. To ensure that this technology is not disclosed we have asked all parties involved with our technology development to sign non-disclosure agreements to ensure all information remains patentable.

Regulatory Hurdles (Safety Approval, Standards Approval, Costs)

Three federal agencies, the EPA, USDA and FDA, regulate the use and commercial production of genetically modified microbes, plants, and food and drugs. Our product thus falls under regulation set out by the latter.

Probiotics, also referred to as live biotherapeutic products (LBP), are products that contain live organisms, such as bacteria, that are found naturally in humans. If a probiotic is intended to diagnose, cure, mitigate, treat or prevent a human disease, it is regulated as a drug and a biological product by the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research and an Investigational New Drug application is required to pursue clinical studies in human volunteers. While over-the-counter probiotics are generally viewed as safe, at least in healthy individuals, clinical studies to assess these products may be conducted in individuals whose defenses are compromised, such as through a disease process, immunosuppressive clinical treatment, or an immature or aging immune system.

Additional characterizations that we need for regulatory commercial approval include developing a Methodology to identify a SilenshR microorganism and a protocol development for accidental release. Processing fees can cost up to $30,000.

Manufacturing Cost and Analysis Timeline

Activity	Required Items	Cost
Design	Reagents, Modeling	$1000
Assembly	Characterization, therapy testing, stability studies	$5000

Cost of the design cycle is shown below:

Item	Price/capsule
Gelatin capsule	$0.001
Bacteria	$0.005
Total	$0.006

Market Analysis

As our project is a novel cancer therapeutic, our models appropriately assume that we will capture a majority of the Total Available Market involved in clinical trials through our conservative sensitivity analysis, we've shown that our project has the potential to generate $17M of revenue, suggesting that our project is financially feasible and worth investing in:

Competitors

Marketed Products

MiniVector (Twister Biotech). MiniVectors are supercoiled DNA minicircles containing only the sequence of interest. Experiments have demonstrated that MiniVectors are a safe and effective platform for getting DNA into difficult-to- transfect cells, such as primary and stem cells. This product is currently available for research use only.

Products in development

LADD (Aduro Biotech). Phase II. Aduro’s Live, Attenuated Double-Deleted Listeria (LADD) platform is based on proprietary attenuated strains of Listeria monocytogenes engineered to express tumor antigens to induce specific and targeted immune responses. Deletion of two virulence genes, which control the infection of hepatocytes and bacterial spread, enables the safe administration of the Listeria. CRS-207, Aduro’s most advanced LADD product candidate, is engineered to stimulate an immune response to mesothelin, a tumor-associated antigen expressed by multiple tumor types
T3 Protein Delivery Platform (T3 Pharmaceuticals). Preclinical. T3 Pharmaceuticals has developed a proprietary technology that allows for fast and efficient protein delivery into eukaryotic cells using live bacteria. The method is based on a bacterial protein delivery nanomachine that candeliver specific bacterial proteins directly into eukaryotic host cells.
Monoclonal Microbials (Evelo). Preclinical. This company is harnessing the therapeutic potential of specific strains of naturally occurring microbes to develop a new class of medicines, monoclonal microbials. Evelo is exploring the use of monoclonal microbials for the treatment of autoimmune, immunoinflammatory, metabolic, neurological, neuroinflammatory diseases and cancer. It has been shown that monoclonal microbials can impact specific immunomodulatory pathways, including activation of dendritic cell subtypes, activation of pro-inflammatory macrophages, and infiltration of T-cells in the tumor microenvironment.
Immulytic Platform (Replimune). Preclinical. The Immulytic oncolytic immunotherapy platform is designed to maximize systemic immune activation against tumor neoantigens in conjunction with immune checkpoint blockade. The Immulytic platform produces a universal neo-antigen vaccine, directly in situ in the patient, generates an inflamed tumor, and triggers innate immunity. Its lead product RP1 is based on a proprietary strain of herpes simplex virus engineered for tumor selectivity and enhanced systemic potency

Milestones (edited from Calgary 2013)

Pending

Grants
Preliminary prototype design
Provisional patent
Initiating Partnerships
Market Assessment
Technology Implementation Plan

1 year

Angel Investment
Prototype development
Licensing Agreements/Partnerships

3 year

Venture Capital Funding
Prototype optimization/ field test
Manufacturing and distribution contracts
Product demonstration

5 year

Regulatory assessment and approval
Expansion

Team:ColumbiaNYC/Entrepreneurship