For millions of years, parasites have perfected an improbable balancing act: they suppress their host's immune system just enough to survive without killing the organism keeping them alive. A three-person Y Combinator startup called Ditto Bio is now betting that this evolutionary tightrope walk contains pharmaceutical gold—proteins from ticks, worms, and viruses that could recalibrate the misfiring immune systems behind autoimmune disease.
It's audacious, certainly. Whether it's realistic is another question entirely.
The company arrives at a curious inflection point for autoimmune therapeutics. The market is projected to swell from roughly $79.76 billion in 2025 to $108.07 billion by 2031, according to Mordor Intelligence. AbbVie's Skyrizi alone pulled in approximately $17.56 billion last year, with the company forecasting combined Skyrizi and Rinvoq revenues topping $31 billion by 2027. Yet Medicare's drug price negotiation program—with the first negotiated prices taking effect in 2026 following negotiations announced in August 2024—now includes stalwarts like Enbrel and Stelara. FDA guidance from late 2025 continues to streamline the biosimilar pathway that could erode pricing power faster than anyone anticipated.
Against that backdrop, a growing cohort of companies is chasing something more ambitious than incremental improvements in immunosuppression. They want immune tolerance—the holy grail of turning off disease at its source rather than indefinitely dampening inflammation. Ditto's twist? Instead of synthetic constructs or engineered human proteins, the founders are proposing to harness molecules that evolution already stress-tested over geological timescales.
When Suppression Isn't Enough
The current standard of care in autoimmunity amounts to controlled suppression, broadly speaking. Anti-TNFs, IL-23 and IL-17 inhibitors, JAK inhibitors, B-cell depletion therapies—all dampen inflammation, often quite effectively. But none restore physiologic immune balance. Patients remain on indefinite treatment, vulnerable to infections, sometimes facing laboratory monitoring or concerns about long-term malignancy risk.
That gap has catalyzed what looks increasingly like a modality shift. In March 2026, Quell Therapeutics dosed the first patient in its CHILL Phase 1/2 basket trial of QEL-005, a CAR-Treg therapy targeting rheumatoid arthritis and systemic sclerosis. Sonoma Biotherapeutics reported interim Phase 1 RA data for its engineered Treg platform in October 2025, backed by a Regeneron collaboration that triggered a $45 million milestone payment.
COUR Pharmaceuticals released one-year Phase IIa results for its antigen-specific tolerizing nanoparticle CNP-104 in primary biliary cholangitis on March 3, 2026. The accompanying Science Advances paper, published February 28, detailed how the nanoparticle engages STING and Type I interferon pathways to induce CD4+ T-cell tolerance. Anokion announced positive symptom data from its Phase 2 celiac trial (KAN-101) in January 2025, though subsequent program updates have been scarce.
These aren't fringe players. They represent substantial capital, clinical traction, and a shared conviction that the next decade of autoimmune therapeutics will hinge on precision immune reprogramming rather than broad suppression. A 2025 Nature Reviews Rheumatology survey catalogued the expanding armamentarium of antigen-specific immunotherapies—tolerogenic vaccines, nanoparticles, antigen-coupling strategies—as evidence of a paradigm gaining momentum.
Ditto Bio wants in on that wave. But it's proposing a fundamentally different starting point.
Evolution's Medicine Cabinet
The scientific rationale leans on millions of years of host-pathogen co-evolution. Parasites—helminths, ticks, certain viruses—evolved to evade or modulate mammalian immunity with exquisite specificity. They secrete proteins that suppress dendritic cell activation, dampen T-cell proliferation, induce regulatory T cells, or manipulate cytokine signaling. Often with picomolar to nanomolar potency.
These molecules were refined under intense selective pressure: too weak, the parasite gets cleared. Too strong, the host dies. The result, in theory, is a natural library of immunomodulators that hit clinically validated targets without the baggage of synthetic design.
The preclinical literature offers intriguing, if scattered, proof points. Tick salivary protein Salp15 suppresses dendritic cells and CD4+ T-cell activation in multiple studies spanning 2006 to 2020, with mixed but notable outcomes in experimental autoimmune encephalomyelitis models. The helminth Heligmosomoides polygyrus secretes Hp-TGM, a TGF-β mimic identified in 2017 that potently induces Foxp3+ Tregs; a 2024 update confirmed its functional TGF-β-like signaling. ES-62, a phosphorylcholine-containing protein from Acanthocheilonema viteae, reduced arthritis and lupus-associated features in mice via TLR4/MyD88 and IL-17 modulation. Hookworm-derived AIP-2 suppressed asthma in preclinical models.
Reviews published in 2024 and 2025 catalogued helminth excretory-secretory protein families—SCP/TAPS/val-like, complement control proteins, apyrases—and their effects on pattern recognition receptors and cytokine cascades, with particular relevance to inflammatory bowel disease models.
Most of that work remains confined to academic labs, however. The leap from mouse colitis to human rheumatoid arthritis is notoriously treacherous. And attempts to bring parasites themselves to patients have largely faltered.
From Parasitology PhD to YC Pitch
Ditto Bio's co-founders—Adair Borges, Dennis Sun, and Emily Weiss—are betting the answer lies not in live worms or eggs, but in purified, engineered proteins.
Borges holds a UCSF PhD in parasitology, virology, and genomics, with over 50 publications and a notable stint as co-inventor of anti-CRISPR systems. She was a Miller Fellow at UC Berkeley before founding Ditto in May 2025. Sun brings Harvard and UC Berkeley training plus operational experience from early-stage biotech chief-of-staff and scientific operations roles. Weiss, a PhD microbiologist with genomics and plant genetics expertise, spent time at Illumina and DuPont building computational and wet-lab platforms.
According to their YC Launch post—published roughly a month before March 12, 2026—the team analyzed over one million proteins from viruses, ticks, and worms in the seven months since founding. They claim to have identified thousands of proteins predicted to hit clinically validated targets, with early experimental evidence showing binding in the 1–2 nanomolar range. They're also building a tissue biobank to map real-world immune memory to parasite proteins, aiming to engineer out immunogenicity before candidate molecules ever reach patients.
That last piece may prove critical. Parasites may have evolved immunomodulatory prowess, but they're profoundly foreign to the human immune system. Introducing a tick or worm protein into a patient carries the risk of triggering anti-drug antibodies, hypersensitivity, or neutralizing immune responses that render the therapeutic ineffective.
FDA guidance dating to 2014—still referenced in 2026—alongside updated EU and TGA immunogenicity guidelines adopted in 2024–2025, emphasizes risk-based immunogenicity assessment for novel proteins. For first-in-class parasite-derived scaffolds, that bar is high.
Ditto's stated strategy of mapping immune memory—presumably drawing on patient exposure histories and serological profiles—suggests they intend to identify and remove T-cell epitopes or otherwise de-risk immunogenicity through rational protein engineering. The tooling for that work has matured rapidly. UnifyImmun, a 2024 cross-attention model for HLA/TCR binding, and PredIG, a 2025 interpretable T-cell epitope immunogenicity predictor, are among a growing suite of machine learning tools for epitope prediction. Multiple papers from 2025 detail advances in modeling peptide-MHC-TCR triads and MHC-II presentation. AlphaFold has limitations—recent research highlights hallucinations in intrinsically disordered proteins and complex modeling—but the broader proteomics and computational infrastructure is more capable than it was even three years ago.
Still. Ditto is a three-person, sub-Series A company listing broad disease targets on its website: RA, IBD, psoriasis, SLE, MS, type 1 diabetes, asthma, celiac, vitiligo, thyroid autoimmunity. No peer-reviewed datasets. No disclosed in vivo efficacy, PK/PD, or toxicology. No announced lead candidate or IND timelines.
As of March 2026, the public information amounts to a YC directory page, a Launch post, and founder LinkedIn updates. That's typical for a company seven months old, but it also means investors and industry watchers are evaluating a thesis more than data.
The Cautionary Tale of Nomacopan
There is one notable precedent for bringing a parasite-derived protein into late-stage development: Akari Therapeutics' nomacopan, a tick-derived complement C5 and LTB4 inhibitor.
By 2022–2023, the company had advanced nomacopan into Phase 3 Part A for pediatric hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), securing EU and US orphan drug, fast track, and rare pediatric disease designations. A genuine milestone—a molecule evolved in an Ornithodoros tick, recombinantly produced, dosed in children with life-threatening disease.
Then the program stopped.
Akari's October 2024 merger prospectus revealed the discontinuation of the HSCT-TMA indication and a pivot to PAS-nomacopan, a long-acting formulation targeting geographic atrophy in ophthalmology. Whether the decision reflected efficacy, safety, manufacturing complexity, or capital constraints remains unclear from public filings. But it illustrates the chasm between compelling biology and commercial execution. Even with strong preclinical rationale, regulatory designations, and human dosing, a tick-derived therapeutic can fail to reach the finish line.
Live-helminth approaches have faced even steeper headwinds. Trichuris suis ova (TSO)—pig whipworm eggs—showed safety in early trials for Crohn's disease and multiple sclerosis over a decade ago, but efficacy signals remained elusive. A randomized, double-blind, placebo-controlled ulcerative colitis study published in December 2024 found variable outcomes, and a 2026 review summarized the translational challenges: inconsistent manufacturing, unpredictable immune responses, regulatory hurdles.
The FDA Import Alert 57-21, revised May 31, 2023 and still active in 2026, detains whipworms, hookworms, and TSO products at the border unless they're covered by an active IND or BLA, effectively blocking commercial live-helminth strategies in the United States.
That regulatory stance underscores the strategic logic of Ditto's protein-first approach. Recombinant proteins are standard fare in biopharma. They can be characterized, dosed precisely, scaled in standard CHO or E. coli systems. They don't carry viable organisms across borders or into patients' intestines.
But they also lack the mechanistic redundancy of a living parasite. Ditto is betting on single or small combinations of proteins hitting defined targets, not a cocktail of thousands of co-evolved factors working in concert.
A Crowded Field, Higher Stakes
Ditto is entering a competitive landscape that has compressed and clarified over the past eighteen months. The tolerance thesis is no longer speculative; it has capital, clinical milestones, and peer-reviewed mechanistic data behind it.
Quell's March 2026 dosing in the CHILL basket trial marks the first-in-human deployment of CAR-Treg technology in RA and systemic sclerosis. The company had presented preclinical QEL-005 data at ACR Convergence in October 2025, showing robust suppression of autoreactive T-cell responses. A separate Quell program, partnered with AstraZeneca and focused on IBD, selected a lead candidate in June 2025.
Sonoma Biotherapeutics, backed by a March 2023 Regeneron collaboration and a 2025 G-Rex manufacturing grant, is advancing engineered Tregs with positive interim Phase 1 RA data announced in October 2025. Both companies are betting on autologous or allogeneic cellular therapy—expensive, logistically complex, but potentially disease-modifying.
COUR Pharmaceuticals is pursuing a different vector: biodegradable PLGA nanoparticles loaded with disease-relevant antigens to induce antigen-specific tolerance. CNP-104 for PBC showed durable improvements at one year in the Phase IIa data released March 3, 2026, and the mechanistic Science Advances paper detailed STING/Type I interferon pathway contributions to induced CD4+ T-cell tolerance. COUR raised a $105 million Series A in January 2024 and is enrolling CNP-106 in myasthenia gravis. Anokion's KAN-101, a liver-targeted antigen-coupled approach for celiac disease, reported positive symptom data in January 2025, though further updates remain unpublished.
These modalities—CAR-Tregs, tolerizing nanoparticles, antigen-coupled constructs—share a unifying goal: restoring immune tolerance without chronic immunosuppression. They differ sharply in mechanism, manufacturing, cost, and regulatory path.
Ditto's parasite-derived proteins would slot into yet another category: recombinant biologics targeting immunomodulatory pathways identified through evolutionary mining. If successful, that approach could scale more like a traditional antibody or fusion protein than a cell therapy or nanoparticle platform.
But it also inherits the competitive burden of biologics. It will be benchmarked against IL-23s, JAKs, and emerging biosimilars on efficacy, safety, and cost.
The Bar Is High
The entrenched incumbents set a formidable standard. Skyrizi achieved approximately $17.56 billion in sales in 2025, driven by psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis indications, with robust PASI90 and endoscopic remission data. Cosentyx and Taltz dominate IL-17-driven diseases. Dupixent, a type 2 inflammation blockbuster, continues rapid expansion. JAK inhibitors like Rinvoq offer oral convenience and broad efficacy, albeit with boxed warnings and lab monitoring. Biosimilars are eroding the oldest biologics—Humira, Enbrel, Remicade—but the newer classes remain protected and growing.
For Ditto to compete, parasite-derived proteins will need to demonstrate not just efficacy, but differentiation.
Can they induce remission as reliably as an IL-23 inhibitor? Can they durably modulate disease without triggering infections at the rate seen with broad immunosuppressants? Can they be dosed less frequently, or discontinued after tolerance is established? And critically, can they avoid the immunogenicity that would neutralize efficacy or trigger hypersensitivity?
That last question is particularly acute. FDA and European regulators emphasize risk-based immunogenicity assessment, with validated ADA assays, neutralizing antibody testing, and longitudinal clinical monitoring. Ditto's tissue biobank strategy suggests they're attempting to engineer out high-risk epitopes before first-in-human dosing. But the proof will be in Phase 1 safety and pharmacokinetics. A parasite protein with 1–2 nanomolar target binding that elicits a robust neutralizing antibody response by Week 4 of dosing is no therapeutic.
The regulatory path is well-trodden for recombinant proteins, but that cuts both ways. Precedent exists—Akari's nomacopan reached Phase 3 with tick biology—but so does the expectation of rigorous non-clinical toxicology, GLP manufacturing, and robust Phase 2 efficacy signals before large pivotal trials. Ditto will need to move from in silico predictions and early binding data to cell-based assays, animal models, and eventually human proof-of-concept.
That timeline, even with YC velocity and AI-enabled screening, is measured in years, not quarters.
Pricing and payer dynamics add another layer of complexity. Medicare's drug price negotiation program launched in 2026 with immunology drugs on the list, and the January 2026 announcement of the 2028 negotiation cycle added more Part B and Part D products. The FDA's October/November 2025 draft guidance suggesting many biosimilar programs may no longer need comparative efficacy studies will likely accelerate biosimilar approvals in immunology classes, increasing payer leverage and price pressure.
Any novel therapeutic entering clinical trials today will launch into a market where payers demand differentiation on outcomes—steroid-sparing, mucosal healing, disease modification—not just mechanism novelty.
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Ditto Bio is seven months old. It has a compelling scientific premise, impressive founder credentials, and the backing of Y Combinator. It also has no lead candidate, no in vivo data, and years of development ahead before the first patient receives a dose.
Perhaps that's fitting. Evolution works on deep time, after all. Whether Ditto can compress millions of years of natural selection into a viable therapeutic pipeline—and do so faster than competitors pursuing tolerance through other means—remains to be seen. The parasites perfected immune evasion over millennia. The startup has considerably less time to prove the strategy translates to the clinic.
Human investors, unlike ticks, tend to be impatient.
