Series Seed · $8M · Personalized antigen-specific tolerance for eosinophilic esophagitis

Tolera /ˈtoʊ.lɛr.ə/ · “TOE-lair-uh”

Ruth-Anne Pai, PhD — Founder & CEO · immunologist and person living with EoE

THE PROBLEM

EoE is antigen-specific. Every therapy treating it is not.

Eosinophilic esophagitis (EoE): chronic, food-driven immune disease of the esophagus — dysphagia, food impaction, strictures.
~1 in 2,000 people; ~167,500 in the US and rising.
Driven by a defined triad: a food peptide, presented on an MHC-II molecule, to a pathogenic effector-Th2 (peTH2) T-cell clone.
Every approved and pipeline therapy blocks a downstream cytokine or cell — and must be taken indefinitely:
- Dupilumab, cendakimab, tezepelumab — chronic biologics
- Budesonide (Eohilia), PPIs — chronic symptom control
- Elimination diets — restrictive, relapse on reintroduction
No approved therapy is antigen-specific. None induces durable tolerance.

The lived reality

"At diagnosis, a patient is handed a lifetime of steroids, injections, or a shrinking list of foods they're allowed to eat — managing symptoms, never resolving the cause. We are building the company that changes that answer."

— Founder, living with EoE

THE SOLUTION

A personalized vaccine that retires the disease-driving T-cell clone

From a single biopsy + blood draw at diagnosis, Tolera manufactures a patient-specific pMHC-II tolerance vaccine that silences only the food-reactive clone — leaving the rest of the immune system intact.

Antigen-specific

Targets the patient's own food peptide on their own MHC-II — not broad immunosuppression.

Durable

Induces tolerance (anergy + Tr1/IL-10 regulation) — designed as one course, not lifelong dosing.

Personalized N-of-1

Each vaccine is built for one patient's HLA + trigger — the neoantigen-vaccine model, for food antigens.

Precedent: teplizumab (Tzield) validated disease-modifying tolerance in autoimmunity; individualized neoantigen vaccines validated per-patient manufacturing.

INFLECTION

Why now

Regulatory precedent exists

Tzield (2022) proved the FDA approves antigen-directed, disease-modifying immune therapy; neoantigen vaccines proved individualized CMC is tractable.

The biology is pinned down

Dilollo/Spergel/Hill (2025) functionally validated the first EoE food-antigen TCR (eoeTCR-4): β-casein, HLA-DRB1*07:01, tetramer-confirmed.

The design already computes

A 9-construct pMHC-II panel is designed and GPU-validated (ipTM ≥ 0.87) on a shared, swappable-cassette backbone.

AI protein design collapsed timelines

Structure prediction + epitope selection make N-of-1 design a compute step, not a research project.

THE PLATFORM

PACT™ — from clinic to vaccine in one workflow

PERSONALIZATION

Every walk-in patient gets a vaccine; the evidence tier sets the route

VALIDATION DATA

The science is designed and GPU-validated

What's validated

Dairy anchor is tetramer-validated (β-casein aa59–78, DR7)
All 3 complexes fold at ipTM 0.87–0.90, 15/15 peptide in groove
One shared DR7 backbone; only the peptide cassette swaps
Wheat & soy are computational priors — wet-lab validation is a funded milestone

POPULATION COVERAGE

Coverage: N-of-1 reaches every patient; the library compounds

MARKET

A ~$2B unmet-need market with no antigen-specific competitor

COMPETITIVE LANDSCAPE

Competition: everyone else suppresses; we tolerize

Agent	Mechanism	Dosing	Antigen-specific?	Durable?
Dupilumab (Sanofi/Regeneron)	anti-IL-4Rα	chronic	No	No
Cendakimab (BMS)	anti-IL-13	chronic	No	No
Tezepelumab (AZ/Amgen)	anti-TSLP	chronic	No	No
Budesonide / Eohilia (Takeda)	topical steroid	chronic	No	No
Elimination diet	antigen avoidance	lifelong	directed, not therapeutic	No
TOL-EoE (Tolera Bio)	antigen-specific pMHC-II tolerance	one course	Yes	Design goal: yes

The field is well-capitalized (validating the market) — but a recent pipeline agent was discontinued for EoE after failing to move endoscopic scores. Mechanism alone doesn't win; durable, antigen-specific disease modification is the open category.

BUSINESS MODEL

Business model: therapeutic + companion diagnostic

Personalized tolerance vaccine (TOL-EoE)

One-course, value-based price ~$150k — priced against the ~$40k/yr lifelong biologic it displaces. Pays back in <4 years; saves payers ~$250k/patient over a decade.

Companion diagnostic (blood assay)

Names the causal food + clonotype from a blood draw. Patient-selection gate for the vaccine AND a standalone, earlier-revenue reimbursable test.

Platform optionality (PACT)

Same engine extends to celiac and other food/auto-antigen disease — a pipeline-in-a-product, plus backbone/cassette out-licensing.

MARKET ACCESS

Why payers cover it: solving the plan-churn problem

The wrong-pocket problem: US commercial plan tenure averages ~3 yrs, so a one-time cure can benefit a payer that didn't fund it. Three contracting models address this — an outcomes-based annuity, a one-time price with an outcomes warranty, and a front-loaded value model. We keep all three open and finalize the price architecture with our lead payer partner, matched to each channel (capitated / commercial / Medicaid).

REGULATORY STRATEGY

Regulatory: one platform IND, not one per patient

Individualized-product framework (à la neoantigen vaccines): qualify the platform + selection algorithm once; release each patient's product against it.
Orphan Drug (US <200k) → Fast Track → Breakthrough → test RMAT eligibility. Endpoints already validated: histologic remission, EREFS, DSQ.
Companion diagnostic co-developed under FDA CDx framework. FTO note: the food-trigger assay concept is patented (Hill/Spergel) — license or design-around.

ROADMAP

Value-inflection milestones

THE ASK

The ask: $8M Seed → cleared IND + first-in-human

$8M Seed buys the single largest de-risking step available now: computational designs → human-validated, IND-enabling data + first-in-human dosing, plus a revenue-generating companion diagnostic. A $35M Series A then funds through the Phase 2 durable-remission proof-of-concept.

TEAM

Team & founding advantage

Ruth-Anne Pai, PhD

Founder & CEO

Immunologist; designed and computationally validated the full pMHC-II platform.
Lives with EoE — the patient-scientist advantage in trial design, recruitment, endpoints, and community trust.
Drove the work from literature to GPU-validated constructs to preclinical roadmap.

Building out (seed hires)

VP / Head of CMC — individualized biologic manufacturing & release
Head of Translational Immunology — functional validation, Tr1 assays
Regulatory lead — CBER individualized-product & CDx experience
Clinical advisors — EoE KOLs (GI + allergy/immunology)
SAB — pMHC/tolerance and neoantigen-vaccine veterans

VISION

Make durable, antigen-specific tolerance the standard of care for food-driven immune disease.

Start with EoE: turn a lifetime of suppression into a one-course, personalized vaccine.
Extend PACT to celiac and other food/auto-antigen disease — the same engine, new cassettes.
Build the company that a patient at diagnosis is sent to — the one I wish existed for me.

CONTACT

Contact & disclosures

Ruth-Anne Pai, PhD — Founder & CEO, Tolera Bio

Series Seed · $8M · seeking lead investor

Tolera /ˈtoʊ.lɛr.ə/ · “TOE-lair-uh”

Disclosures & disclaimer

This deck describes a preclinical-stage design platform. The dairy epitope (β-casein aa59–78, HLA-DRB1*07:01) is tetramer-validated in the literature; all other epitope binding values are computational priors pending wet-lab validation. Fold-quality metrics (ipTM/pLDDT) are from GPU structure prediction, not experimental structures.

Market, financial, coverage, and payer/pricing figures are planning assumptions grounded in public data and stated explicitly in the accompanying analyses; they are not guidance or projections of returns. Contracting models are illustrative and subject to payer negotiation. Regulatory pathways described require formal FDA interaction and are not commitments.

The food-trigger T-cell-assay concept is patented (Hill/Spergel); commercial use requires licensing or design-around. Nothing herein is medical advice.