# Tolera Bio — Market & Competitive Analysis
*Confidential — for VC / VP discussion. All figures illustrative and assumption-driven; sources noted inline.*

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## 1. Market sizing (US; EU as expansion)

| Layer | Definition | Patients | Basis |
|---|---|---|---|
| **Prevalence** | US EoE (~1 in 2,000) | **~167,500** | Western prevalence 1/2000 (project basis) × 335M US pop |
| **Diagnosed** | Clinically diagnosed | **~100,500** | ~60% diagnosed (EoE is under-diagnosed) |
| **SAM — biologic-eligible** | Moderate–severe / failing conventional therapy | **~55,300** | ~55% of diagnosed |
| **SOM (mature, annual)** | Realistic annual serviceable share | **~6,600 / yr** | ~12% of SAM at maturity (base case) |

- **TAM ≈ $2.2B/yr** if the biologic-eligible pool were treated at ~$40k/yr chronic-biologic pricing (dupilumab-class list economics).
- **Tolera SOM revenue ≈ $1.0B/yr** at maturity (base case), at a **one-course price of ~$150k** on ~6,600 patients/yr. Presented as a scenario range — 8% / 12% / 18% of SAM = $0.66B / $0.99B / $1.49B — reflecting Tzield's real-world, screening-gated ramp.
- **EU roughly doubles** the addressable population; rest-of-world extends further. The individualized model travels internationally because the *process* is exported, not a fixed inventory.

*Pricing logic:* a durable one-course therapy is priced against the **cost it displaces** — ~$40k/yr of lifelong biologic. At $150k it pays for itself in **~3.8 years** and saves a payer **~$250k per patient by year 10** (see figure, panel 3). This is the classic curative-therapy value-based-pricing argument (cf. gene therapies), and it is the payer conversation that anti-cytokine incumbents cannot have.

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## 2. Competitive landscape (2025–2026)

Every approved and pipeline EoE therapy shares one structural feature: **chronic dosing of a broad (non-antigen-specific) mechanism.** None induces durable, antigen-specific tolerance.

| Agent / modality | Company | Mechanism | Dosing | Antigen-specific? | Durable off-therapy? |
|---|---|---|---|---|---|
| **Dupilumab** (Dupixent) | Sanofi/Regeneron | anti-IL-4Rα (Th2 cytokine block) | chronic (q1–2wk injection) | No | No |
| **Budesonide oral susp.** (Eohilia) | Takeda | topical corticosteroid | chronic (BID) | No | No |
| **Cendakimab** | Bristol Myers Squibb | anti-IL-13 | chronic | No | No |
| **Tezepelumab** | AstraZeneca/Amgen | anti-TSLP | chronic | No | No |
| **PPIs** | generic | acid suppression | chronic | No | No |
| **Elimination diet** | — | antigen avoidance | lifelong avoidance | *Antigen-directed but not therapeutic* | No (relapse on reintroduction) |
| **TOL-EoE (Tolera)** | **Tolera Bio** | **antigen-specific pMHC-II tolerance (Tr1 induction)** | **one course** | **Yes** | **Design goal: yes** |

**Signal from the field:** the space is active and well-capitalized (multiple large-pharma programs), which validates the disease's commercial attractiveness — but a recent pipeline agent was **discontinued for EoE after failing to improve the endoscopic reference score (EREFS)** despite a measurable mechanistic effect, underscoring that (a) mechanism alone doesn't win, endpoints do, and (b) even sophisticated cytokine/cell-targeting agents remain palliative. Tolera's differentiation is categorical, not incremental.

**The whitespace (figure, panel 2):** competitors cluster in the *broad-mechanism / chronic-dosing* quadrant. Tolera occupies *antigen-specific / one-course* alone.

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## 3. Why Tolera wins where incumbents can't

1. **Outcome:** durable tolerance vs. indefinite symptom suppression.
2. **Payer economics:** one-course pays back in <4 years and saves ~$250k/patient/decade.
3. **Patient experience:** ends the lifelong-injection / restrictive-diet burden — the lived-experience insight the founder brings.
4. **Platform, not a single asset:** the same PACT engine extends beyond EoE to other food/auto-antigen-driven disease (celiac work already exists in this project), giving investors a pipeline-in-a-product.
5. **Built-in companion diagnostic:** a second, pipeline-independent revenue line (name-the-food blood test).

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## 4. Business model

- **Primary:** personalized tolerance vaccine (TOL-EoE), one-course, value-based priced (~$150k).
- **Secondary:** companion diagnostic (blood-based food-trigger + clonotype assay) — standalone reimbursable test and patient-selection gate.
- **Platform optionality:** PACT extended to celiac, other IgE/T-cell food disease; out-licensing of qualified backbones/cassettes.
- **Revenue timing:** diagnostic can generate revenue pre-therapeutic-approval; therapeutic revenue post-Phase 2/approval.

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## 5. Key assumptions & sensitivities (stated for diligence)

| Assumption | Value used | Sensitivity |
|---|---|---|
| US prevalence | 1/2000 | Rising; upside if trend continues |
| Diagnosed fraction | 60% | Under-diagnosis → upside as awareness grows |
| Biologic-eligible fraction | 55% | Drives SAM directly |
| Mature annual SOM share | 12% (base case; 8%/12%/18% range) | Screening-infrastructure & reimbursement gated (Tzield precedent) |
| One-course price | $150k | Value-based vs. $40k/yr biologic; payer-negotiable |
| Chronic biologic comparator | $40k/yr | Dupilumab-class list economics |

*These are planning assumptions for a Seed-stage company, not guidance. All non-dairy epitope activity is a computational prior pending validation.*
