Table of Contents

• Overview
• 1. Why: Global Unmet Needs and Market Opportunity
• 2. What: Our Product and Core Innovations
• 3. Who: Stakeholders and Value Propositions
• 4. How: Market Entry and Go-To-Market (GTM) Strategy
• 5. How Big: Market Size and Pricing Assumptions
• 6. Business Model: Revenue Streams and Unit Economics
• 7. Competitive Analysis
• Appendix: Glossary of Key Terms

Overview

Our project presents FoCas, a DNA-based nanotherapeutic platform designed to address the global antimicrobial resistance (AMR) crisis. By integrating synthetic biology tools for precise targeting, membrane permeabilization, and direct resistance-gene disruption, FoCas transforms MRSA back into a "methicillin-sensitive" state, enabling the reuse of low-cost, low-toxicity legacy antibiotics.

1. Why: Global Unmet Needs and Market Opportunity

Antimicrobial resistance (AMR) is one of the most pressing public health challenges worldwide. According to The Lancet, in 2019 there were an estimated 4.95 million deaths associated with bacterial resistance, of which 1.27 million deaths were directly attributable. This trend shows no sign of slowing down; without effective interventions, the annual death toll is projected to reach 8.22 million by 2050, surpassing that of most major cancers.

Among resistant pathogens, methicillin-resistant Staphylococcus aureus (MRSA) stands out as a representative "superbug." The danger of MRSA lies not only in the broad spectrum of infections it causes (skin, respiratory, bloodstream), but also in its tendency to result in longer hospital stays, higher mortality rates, and greater treatment costs.

Patients with MRSA infections typically require 14–21 days of hospitalization, compared to only about 7 days for methicillin-sensitive strains; in immunocompromised populations, mortality is 2–3 times higher, placing heavy burdens on healthcare systems and families alike.

From a cost perspective, the treatment of a single MRSA infection can reach $30,000–50,000, far exceeding the expenses for ordinary infections. Meanwhile, the safety and sustainability of traditional therapies are increasingly concerning: around 30% of patients treated with vancomycin or linezolid experience nephrotoxicity or gastrointestinal adverse effects, and 15% suffer gut microbiota dysbiosis, leading to secondary infections such as C. difficile.

On the industry side, pharmaceutical companies face a significant innovation gap. Developing a brand-new antibiotic requires 10–15 years of R&D and an investment of $1–2 billion, while bacterial resistance evolves much faster than drug pipelines can catch up. This creates a severe supply-demand imbalance—AMR continues to escalate, but effective tools remain scarce.

In summary, under the combined pressures of high incidence, high mortality, high costs, and rapid bacterial evolution, traditional antibiotic strategies are no longer sufficient to address MRSA and other resistant pathogens. There is an urgent need for a new type of solution that is cost-effective, safer, and rapidly adaptable to emerging resistance mechanisms.

Figure. Clinical and economic burden of MRSA compared to MSSA.
Average hospitalization days, relative mortality risk, and treatment costs are shown for methicillin-resistant Staphylococcus aureus (MRSA, red) versus methicillin-sensitive Staphylococcus aureus (MSSA, blue).

2. What: Our Product and Core Innovations

Focas: A Nanotherapeutic Platform

To address the multiple unmet needs of MRSA treatment, we developed a DNA-based nanotherapeutic platform (FoCas). Unlike conventional approaches that merely add another antibiotic to the market, FoCas restores MRSA's sensitivity to methicillin by integrating synthetic biology tools for precise targeting, membrane permeabilization, and direct resistance-gene disruption. In doing so, it does not simply expand the antibiotic pipeline but rather redefines how resistant pathogens can be "re-sensitized" to existing low-cost drugs. For details, please see the Description page.

Innovation 1:

We engineered aptamer-functionalized complexes that selectively bind to the Spa protein on MRSA's surface. Once bound, these complexes induce the generation of reactive oxygen species (ROS) via Fenton-like reactions. This targeted ROS production enhances bacterial membrane permeability by 40–50% in vitro, creating new "entry points" for methicillin while leaving mammalian cells unharmed. This step is critical because it overcomes one of the most fundamental barriers in resistant infections: the inability of antibiotics to effectively reach their bacterial targets.

Innovation 2:

The second innovation is our use of programmable DNA origami carriers. These nanostructures remain stable under normal physiological conditions but unfold specifically in MRSA infection environments, which are characterized by acidic pH (5.5–6.0) and elevated H₂O₂. Upon activation, the carriers release their CRISPR-Cas9 payloads directly into the bacterial microenvironment. In controlled studies, this system achieved >90% targeting efficiency against MRSA, compared with <30% for conventional non-targeted approaches, demonstrating both precision and selectivity.

Innovation 3:

The FoCas platform further incorporates a swappable sgRNA toolkit that can target more than five clinically relevant resistance genes. For instance, mecA (encoding PBP2a, the hallmark of methicillin resistance) and ermA (conferring macrolide resistance) can be cleaved with high efficiency. Thanks to this modular design, when new MRSA subtypes emerge, FoCas can be rapidly reprogrammed within 2–3 weeks—a pace vastly superior to the 5–8 years typically required for new antibiotic R&D.

Value Proposition

FoCas transforms MRSA back into a "methicillin-sensitive" state, enabling the reuse of low-cost, low-toxicity legacy antibiotics (repurposing through re-sensitization).

Technology Readiness Level (TRL)

FoCas is currently at TRL-3 (Experimental Proof-of-Concept), with a roadmap toward TRL-5 (In Vivo Proof-of-Concept):

• M1 (3 months): Demonstrate >80% mecA cleavage efficiency in vitro/cell culture (qPCR + sequencing).
• M2 (6 months): Achieve 3–4 log₁₀ CFU reduction in bacterial load in murine wound infection models.
• M3 (9 months): Complete acute toxicity studies in rats, demonstrating no organ damage at ≥5× therapeutic dose.

Minimal Viable Product (MVP) Metrics

Key performance indicators include:

• ROS induction (DCFH-DA assay);
• Membrane permeabilization (SYTOX Green staining);
• mecA cleavage (qPCR / gel electrophoresis);
• Reduction of MIC (Minimum Inhibitory Concentration) to ≤4 μg/mL (CLSI standard).

3. Who: Stakeholders and Value Propositions

The successful translation and adoption of FoCas requires alignment across multiple stakeholder groups, each with different levels of power and interest. To clarify their roles and the value FoCas brings to each, we mapped them onto a Power–Interest Grid and summarized their respective pain points and incentives.

Figure. Power–Interest Grid of key stakeholders in the adoption of FoCas.

Quadrant Analysis

1. Manage Closely (High Power, High Interest)
   • Hospitals and Clinics (especially tertiary and specialty departments): These stakeholders directly determine clinical adoption, holding both prescribing authority and guideline-setting power. For them, FoCas provides tangible value by reducing MRSA-related treatment costs by 50–60% and shortening hospital stays by 7–10 days, thereby alleviating bed shortages and financial burdens.
   • Public Health Authorities (CDC, health regulators): As key actors in AMR control and "antibiotic reduction" initiatives, they value FoCas as a tool to reduce inappropriate antibiotic use and slow the evolution of resistance, directly supporting policy implementation.
2. Keep Satisfied (High Power, Low Interest)
   • Pharmaceutical and Biotechnology Companies: Although initially less engaged, they hold the manufacturing capacity and distribution channels for scale-up. FoCas offers them opportunities for licensing, co-production, and pipeline expansion, creating new business models in the AMR field.
3. Keep Informed (Low Power, High Interest)
   • Research Institutions: Academics and researchers are highly motivated to explore novel technologies. FoCas provides them with a programmable, modular research platform, enabling validation, publications, and translational collaborations. They also serve as critical partners in preclinical development.
4. Monitor (Low Power, Low Interest)
   • Community Hospitals and Primary Care Facilities: Currently less inclined to adopt cutting-edge therapies, but FoCas can be integrated through demonstration projects, eventually becoming part of antimicrobial stewardship at the local level.
   • Livestock and Farming Sectors: With limited regulatory oversight at present, their immediate interest is low. However, within the One Health framework, FoCas can be piloted in veterinary applications and gradually scaled up.

4. How: Market Entry and Go-To-Market (GTM) Strategy

Our Go-To-Market (GTM) strategy is structured into two phases: a short-term validation stage and a mid-to-long-term scale-up stage. This roadmap balances the scientific validation and regulatory hurdles with commercial expansion and revenue generation. In short: we start with "scientific validation → veterinary applications → exploratory clinical use", then advance to "routine hospital adoption → public health procurement", and finally achieve "pharma partnerships → global distribution."

Short Term (0-3 years): Validation and Early Adoption

• Research Institutes: FoCas will be provided as a research tool to generate validation data, support academic dissemination, and strengthen technical credibility.
• Veterinary and One Health Market: With relatively lower regulatory barriers, FoCas can enter veterinary and livestock infection scenarios early, creating initial revenues and case studies.
• Hospitals (under ethical approval): In severe MRSA cases, FoCas may be adopted under compassionate or exploratory use, generating early clinical evidence and paving the way for future inclusion in Antimicrobial Stewardship Programs (ASP).

Mid-to-Long (3-10 years): Clinical Adoption and Scale-Up

• Hospitals and Clinics: Upon successful completion of clinical trials, FoCas will be positioned as an adjuvant therapy or preventive agent, broadly applied in infectious disease and surgical wards.
• Public Health Agencies: As part of national and regional AMR control strategies, FoCas can be incorporated into centralized procurement programs, enabling large-scale adoption.
• Pharmaceutical and Biotech Companies: Through licensing agreements and co-manufacturing partnerships, FoCas can lower production costs and expand international distribution networks.
• Veterinary and Companion Animal Markets: With the global push for "antibiotic reduction" policies, FoCas can be adapted for multiple animal health applications, extending its One Health potential.

5. How Big: Market Size and Pricing Assumption

We applied the TAM / SAM / SOM framework (Total Addressable Market / Serviceable Available Market / Serviceable Obtainable Market) to estimate the potential market size for FoCas. This layered approach allows us to scale from the macro opportunity down to the realistically accessible market in the near term.

TAM

Since FoCas is primarily intended for human medical applications, our TAM calculation is based on the global healthcare market for AMR. The animal-related AMR market, due to significant policy and statistical variability, is excluded at this stage.

• In the United States, there are approximately 2.8 million new AMR infections annually, leading to more than 35,000 deaths.
• Globally, AMR is already responsible for 4.71 million associated deaths each year, of which 1.27 million are directly attributable. Without interventions, the annual death toll is projected to reach 8.22 million by 2050.
• Based on epidemiological estimates, we assume there are ~50 million new AMR cases worldwide per year.
• Cost data: in the U.S., the total annual cost of community-onset and hospital-onset infections caused by six major resistant pathogens reaches $2.7B and $1.9B, respectively. In China, the median treatment cost of a single MRSA case is $11,450, of which only $1,063 is attributable to antibiotics. The majority of the burden comes from extended hospitalization and complications.
• Taking into account regional variation in costs and access, we set the potential revenue per FoCas-treated patient at $175.

Thus,
TAM = 50,000,000 × $175 = $8.75B.

Figure. Comparative economic burden of antimicrobial resistance (AMR).
(A) Distribution of community-onset infection costs in the United States, showing MRSA as the single largest contributor (42.35%), followed by ESBL-producing Enterobacteriaceae (27.37%) and VRE (11.73%).
(B) Distribution of hospital-onset infection costs in the United States, where MRSA (29.98%) and ESBL (24.31%) remain major drivers of expenditure, alongside multidrug-resistant Pseudomonas (25.44%).
(C) Breakdown of the average per-case hospital cost of MRSA treatment in China, highlighting that antibiotics account for only a small fraction (9.28%) of the total ($11,450 median cost), with the majority arising from medication, hospitalization, and complications.

This figure is highly consistent with independent market research, which values the global AMR market at $8.84B in 2025 and projects growth to $12.86B by 2032, validating the robustness of our assumptions.

SAM

Our initial entry market will be high-tier hospitals in China, focusing on in-hospital treatment of AMR infections where FoCas can be deployed as an adjuvant or for non-invasive indications.

• In 2021, China reported ~711,852 AMR-related deaths.
• A systematic review found that among hospitalized bacterial infections, 27.45% were resistant strains, and 15.77% were multi-drug resistant (MDR).
• According to the National Health Commission, the prevalence of hospital-acquired infections (HAIs) in China has remained 2.3–2.7% since 2014, with 245M hospital admissions in 2023.
• Given FoCas' novel nature and the need for controlled introduction, we restrict our target to public grade-A tertiary hospitals, accounting for ~50% of total admissions.
• For modeling simplicity, we assume an HAI prevalence of 2%, of which 30% are AMR-related.

Calculation:
245,000,000 × 50% × 2% × 30% ≈ 735,000 patients.

For pricing, we assume FoCas can reduce MRSA treatment costs down to the level of MSSA. While median antibiotic costs are $1,062 for MRSA vs. $391 for MSSA, the main difference stems from extended hospitalization. Based on health-economic analysis, we price FoCas at $1,000 per patient.

Thus,
SAM ≈ 735,000 × $1,000 = $735M.

Figure. Comparison of hospital costs for MRSA vs MSSA in China.
Breakdown of average hospitalization costs by category (antibiotics, medications, diagnostics, treatment, materials, and other costs). Median total cost per case is significantly higher for MRSA (~$11,450) compared to MSSA (~$8,300), largely due to extended hospitalization and associated treatments rather than antibiotics alone.

SOM

As AMR therapeutics represent an emerging category, there is little precedent for penetration data. We conservatively assume FoCas can capture ~20% of the SAM in the initial stage.

Thus,
SOM ≈ $735M × 20% = $147M.

Summary:

• TAM ≈ $8.75B (Global AMR medical market).
• SAM ≈ $735M (China tertiary hospitals as initial serviceable market).
• SOM ≈ $147M (with 20% penetration into SAM).

6. Business Model: Revenue Streams and Unit Economics

Revenue Streams

1. Per-episode sales in healthcare settings – FoCas administered as a treatment dose for MRSA infections.
2. Research-use reagent kits – modular FoCas kits marketed to research institutions for validation and exploratory applications.
3. Veterinary / One Health applications – treatment doses adapted for livestock and companion animals.
4. Licensing and milestone payments – partnerships with pharmaceutical and biotech companies for manufacturing and distribution.
5. Technical services – customized solutions including diagnostic assays and sgRNA design-on-demand.

Cost Structure

• Primary cost drivers: DNA synthesis and origami assembly, Cas9/sgRNA production, aptamer functionalization, GMP-grade purification and quality control, as well as cold-chain logistics and insurance.
• Economies of scale: With industrial-scale synthesis and purification, the unit material cost of DNA origami and CRISPR components is expected to decline substantially, enabling competitive pricing relative to high-cost antibiotics.

7. Competitive Analysis

The current antimicrobial resistance (AMR) therapeutic landscape is composed of traditional antibiotics, long-acting agents, and emerging biologics. To clearly position FoCas, we compare it across three layers: product benchmarking, 2×2 positioning, and Porter's Five Forces analysis.

Competitive Landscape

Name	Type	Company/Institution	Key Strengths	Limitations
Vancomycin	Antibiotic	Eli Lilly	Guideline-recommended therapy for severe MRSA infections	Rising resistance; nephrotoxicity; requires drug monitoring
Daptomycin (Cubicin®)	Antibiotic	Merck	Effective in MRSA bacteremia/endocarditis	Not effective in pneumonia; risk of myotoxicity
Linezolid (Zyvox®)	Antibiotic	Pfizer	High oral bioavailability; suitable for lung infections	Bone marrow suppression; neuropathy; bacteriostatic only
Dalbavancin (Dalvance®)	Long-acting lipoglycopeptides	AbbVie	Weekly or single-dose IV; reduces hospital stay and IV use	Limited data for bacteremia/deep infections
Ceftaroline (Teflaro®)	5th-gen cephalosporin	AbbVie	Rare β-lactam active against MRSA; salvage therapy option	Restricted indications; higher risk of adverse events in combination
Afabicin (Debio 1450)	FabI inhibitor	Debiopharm	Staphylococcus-specific; positive Phase II results	Still in Phase II; not yet approved
AP-SA02	Phage therapy	Armata Pharma	Highly specific bacteriophage cocktail; precision therapy	Manufacturing challenges; regulatory uncertainty
Locus crPhage®	CRISPR therapy	Locus Biosciences	First CRISPR-based antibacterial in Phase II/III trials	Complex delivery; ethical and regulatory hurdles
FoCas (iZJU-China)	DNA origami + CRISPR	iGEM Team	Modular, programmable; ROS-assisted; environment-responsive delivery; restores methicillin sensitivity	TRL=3; pending preclinical and clinical validation

2×2 Positioning (Cost × Effectiveness)

• Traditional antibiotics (e.g., Vancomycin): Low cost but limited efficacy, with significant side effects.
• Next-generation antibiotics / long-acting agents (e.g., Dalbavancin, Ceftaroline): Moderate balance of cost and effect but restricted indications.
• Emerging biologics (e.g., phages, CRISPR products): High therapeutic potential but high cost and regulatory barriers.
• FoCas positioning: By restoring MRSA sensitivity to methicillin, FoCas ensures strong efficacy while significantly reducing overall treatment costs (savings of $25k–45k per case, reducing hospital stay by 7–10 days). Thus, FoCas is uniquely placed in the "high efficacy + cost-controllable" quadrant.

Porter's Five Forces

1. Industry Rivalry: Intense competition across antibiotics and novel biologics. FoCas differentiates through modular gene targeting and DNA-origami-based precision delivery.
2. Threat of Substitutes: Vaccines, antibodies, and preventive measures exist, but none can directly "de-resist" pathogens at the gene level. Substitution threat = moderate.
3. Bargaining Power of Suppliers: Early-stage costs for CRISPR proteins and DNA origami materials are high, but synthetic biology scale-up will reduce costs over time. Supplier power = moderate–high.
4. Bargaining Power of Buyers: Hospitals and insurers are highly price-sensitive; demonstrating cost-effectiveness (saving $25k–45k per patient) is critical. Buyer power = strong.
5. Threat of New Entrants: CRISPR-based antimicrobials are attracting new startups, but regulatory and R&D barriers remain high. Threat = moderate.

Strategy Advances of FaCas

Unlike competing directly with antibiotics, FoCas complements and enhances existing treatments by:

• Reactivating legacy drugs (restoring methicillin as a frontline therapy).
• Rapid modular adaptability (2–3 weeks for new subtype vs. 5–8 years for new antibiotics).
• Clear cost-effectiveness ($1,000 per dose vs. $25k–45k savings per case).
• Platform scalability (applicable to other resistant pathogens beyond MRSA).

In essence, FoCas positions itself as a next-generation resistance-reversal platform, establishing a defensible niche in the "high efficacy + cost-controllable" space.

Appendix

• 1. TRL (Technology Readiness Level)
  A widely used scale to evaluate the maturity of a technology, ranging from TRL-1 (basic concept or idea) to TRL-9 (fully validated in clinical or industrial deployment).
  Originally developed by NASA, it is now commonly applied in biomedical innovation and biotech startups to communicate how close a product is to real-world use.
• 2. MVP (Minimum Viable Product)
  Refers to the smallest functional version of a product that delivers core value and allows validation of key performance indicators.
  In the biotech/medtech field, an MVP may not be a "product on the shelf," but rather a simplified experimental prototype (e.g., an in vitro assay) that demonstrates feasibility and attracts early adopters, investors, or regulatory interest.
• 3. TAM / SAM / SOM
  • TAM (Total Addressable Market): the total global revenue opportunity if a product achieved universal adoption.
  • SAM (Serviceable Available Market): the portion of TAM that can realistically be served given product scope, regulations, and geography.
  • SOM (Serviceable Obtainable Market): the share of SAM that a company can actually capture, based on competition, penetration rate, and go-to-market strategy.
    This layered model is a standard tool in business planning for illustrating both the scale of opportunity and the realism of market entry assumptions.
• 4. ASP (Antimicrobial Stewardship Program)
  Hospital-level programs designed to optimize the use of antibiotics and related therapies.
  ASPs aim to balance effective treatment of infections with minimizing resistance evolution, often through prescribing guidelines, dosage optimization, and monitoring.
  For new antimicrobials like FoCas, integration into ASPs is critical for adoption, since they regulate how frontline clinicians can access and prescribe such products.
• 5. Power–Interest Grid
  A stakeholder management tool that categorizes stakeholders based on their relative power (ability to influence outcomes) and interest (degree of involvement or concern).
  The matrix typically includes four quadrants:
  • Manage Closely (high power, high interest),
  • Keep Satisfied (high power, low interest),
  • Keep Informed (low power, high interest),
  • Monitor (low power, low interest).
  In healthcare innovation, this framework helps align strategies for engaging hospitals, regulators, pharma partners, and research collaborators.