Yellow Pigment
Therapeutics
Pre-Seed Round · Confidential · 2026
Turning a protective
human molecule
into medicine.
human molecule
into medicine.
Therapeutics for inflammatory and metabolic disease, built on the natural protective biology of bilirubin and biliverdin.
AI-native drug discovery · Biliverdin-ester prodrug platform · Oral, chronic, daily
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The Opportunity
Metabolic and inflammatory disease is a billion-person market still chasing downstream targets.
Obesity, cardiometabolic risk and age-related inflammation share the same underlying oxidative and inflammatory biology. Most current drugs act on the symptoms. We are targeting the biology that sits upstream of them.
Chronic inflammation
$128B+
anti-inflammatory market by 2030
Estimates run from $128B to $152B by 2030. Current drugs target downstream pathways. Few reach the underlying oxidative and inflammatory biology.
Inflammatory bowel disease is where we start. About 7 million patients worldwide, a $22 to $30B market, and roughly 40% of patients who fail or lose response to current biologics.
Obesity & cardiometabolic
1B+
people affected globally
Anti-obesity market heading toward $95 to $130B by 2030. GLP-1s dominate, yet roughly 60% of lost weight returns within a year of discontinuation.
STEP-1 trial extension, Wilding et al. 2022
Age-related inflammation
1 in 6
will be 60+ by 2030
Chronic low-grade inflammation is a central driver of age-related functional decline, and an aging population keeps expanding demand.
There is a better target hiding in human biology itself.
The Opportunity
Gilbert syndrome is a well-documented natural experiment
Gilbert syndrome is a well-documented natural experiment
in protective biology.
Five to ten percent of people carry a variant that keeps bilirubin mildly elevated for life. Across very large cohorts, they are measurably healthier. The finding has been replicated for two decades and across several disease areas.
504,206
Mortality, COPD, lung cancer
Per 0.1 mg/dL of bilirubin: 3% lower all-cause mortality, 6% lower COPD, 8% lower lung cancer in men
Horsfall 2011, JAMA · 504,206 adults
−7%
Cardiovascular disease
Lower risk per 1 SD of total bilirubin, pooled across 12 prospective studies and 9,378 incident CVD cases
Meta-analysis of 12 prospective studies
Lower BMI
Overweight and obesity
Lower BMI and lower fat mass in carriers of the Gilbert variant
Seyed Khoei 2018
Lower
Oxidative stress
Lower oxidative stress biomarkers
Wagner 2021
Key insight
We ran our own machine-learning Mendelian randomization study across more than 850,000 people in FinnGen and UK Biobank, together with published GWAS meta-analyses, to test which of these associations hold up as causal. The exposure is real and measurable, and the results told us which indications to prioritise. What none of this evidence provides is a way to give someone mildly elevated bilirubin. That is the problem we are solving, and it is a delivery problem rather than a target problem.
The evidence is strong and well replicated. The step nobody has solved is turning it into something a patient can take.
The Science
A validated human pathway can be
A validated human pathway can be
translated into medicine.
Human genetics supports targeting the bilirubin pathway with drugs. The molecular target and mechanism are well understood, and the therapeutic window is defined, with a substantial safety margin.
Precursor
Heme
HO-1 / HO-2
Intermediate
Biliverdin
BLVRA / BLVRB
⭑ Therapeutic Target
Bilirubin
⚑ broad protective window
UGT1A1
↓ in Gilbert
Excreted
BR-Glucuronide
Bilirubin Concentration by Clinical State
Plasma bilirubin (µM)
Normal
3.4 – 17 µM
broad protective window
★ YPT therapeutic window
★ YPT therapeutic window
15 – 100 µM
Crigler-Najjar II
100 – 350 µM
Crigler-Najjar I
350 – 900 µM
Normal
★ YPT therapeutic target
★ YPT
CN-II
CN-I
0
15
100
350
900
µM →
Safety Margin
From the top of the normal range (~17 µM) to the first pathological state (~100 µM, the onset of Crigler-Najjar type II), there is roughly a 6× distance. We do not yet know the right dose. The headroom available to find it is wide.
The aim is controlled access to the protective range, with a wide margin below the levels that cause harm.
Mechanism of Action
Why bilirubin and biliverdin work,
Why bilirubin and biliverdin work,
and how they do it.
Bilirubin acts through four characterized biological pathways whose effects overlap. This helps explain why the benefits extend across cardiovascular, metabolic and inflammatory outcomes, as well as mortality, rather than being confined to a single disease.
01
PPARα modulation
Bilirubin is an endogenous PPARα ligand. It activates fatty acid oxidation and regulates lipid homeostasis, which is the mechanistic basis for the metabolic protection seen in Gilbert carriers.
Metabolic axis
02
Lipophilic antioxidant
Bilirubin intercepts peroxyl radicals inside lipid membranes, a compartment water-soluble antioxidants cannot reach. The BV → BR → BV redox cycle regenerates the molecule, so capacity far exceeds a one-to-one stoichiometry.
Oxidative stress
03
BLVRA signaling
Biliverdin reductase A is a dual-function kinase. Beyond reducing biliverdin, it modulates insulin receptor signaling through IRS-1 and PI3K and acts on NF-κB, placing it at the junction of metabolic and inflammatory control.
Signaling axis
04
Anti-inflammatory signaling
Bilirubin suppresses NF-κB-driven transcription and dampens immune cell activation at epithelial and vascular barriers. This is the axis that converts the antioxidant and metabolic effects into measurable anti-inflammatory outcomes.
Inflammatory axis
Already in clinical testing
Bilix has advanced intravenous PEGylated bilirubin into Phase 2 trials for inflammatory conditions, bringing the approach into clinical testing. The next challenge is an oral form that people can take daily for years, making it practical for long-term treatment of chronic disease.
Four mechanisms, one upstream molecule, and no oral format available yet.
Platform
Why bilirubin has not yet become
Why bilirubin has not yet become
a practical drug.
The therapeutic signal is real. But bilirubin itself has been difficult to translate into a scalable, orally delivered medicine.
01 · Signal
Compelling biology
Strong epidemiological evidence across mortality, cardiovascular, metabolic, and inflammatory disease. Multiple mechanisms. Clear human phenotype. The biology works.
Validated in humans
→
02 · Problem
Delivery bottleneck
Bilirubin itself is chemically difficult. Most published attempts use injectable, infusion, or nanoparticle approaches that limit utility for chronic disease.
A.Poor aqueous solubility
B.Chemical instability
C.Hard formulation
D.Rapid degradation by gut microbiome
→
03 · Opportunity
Oral prodrug strategy
A drug design strategy that masks the problematic chemical features of bilirubin while preserving access to its biology. Delivered orally. Suitable for chronic use.
YPT's approach
The biology is settled. What has been missing is a way to make it druggable.
Platform
Yellow Pigment is building
Yellow Pigment is building
biliverdin-ester prodrugs.
Biliverdin-esters are a practical drug design strategy to access bilirubin biology in a tractable, developable format suitable for oral delivery and chronic use.
BV-Ester
Prodrug
Prodrug
Oral dose
GI lumen
GI lumen
Esterase
Biliverdin
BV
BV
Absorbed
Systemic
Systemic
BLVRA/B
Bilirubin
BR
BR
Active
Pharmacology
Pharmacology
UGT1A1
Therapeutic
Effect
Effect
Gilbert-range
biology
biology
Improved absorption
Ester groups increase lipophilicity, enabling passive GI uptake
Endogenous activation
Esterases regenerate BV → BLVRA/B converts to BR
Better CMC profile
Improved formulation path vs. bilirubin free acid
IP-protected space
Composition-of-matter filings in preparation. Specific ester structures are shared under NDA, not in this deck.
A chemistry strategy designed for druggability, oral delivery and mechanistic relevance. The specific candidate structures are available under NDA.
Platform
What we have already shown.
We have run the pathway end to end ourselves. Conversion works, the enzyme responsible is confirmed, two early safety questions are answered, and the screening cascade that selects a candidate is built and running.
Published Precedent
Biliverdin dimethyl ester shows improved membrane passage versus unmodified biliverdin in published permeability studies
Biliverdin dimethyl ester is a substrate for serum and cellular esterases in vitro and in vivo, supporting the bioactivation mechanism
The protective human phenotype is replicated across very large independent cohorts, including 504,206 adults in Horsfall 2011 and twelve prospective cardiovascular cohorts
Our Data
Conversion confirmed. Extracellular biliverdin to bilirubin conversion demonstrated in monocyte cell culture, in a biologically relevant setting
Mechanism confirmed. BLVRA knockout slows conversion, which establishes that the reaction depends on the enzyme rather than on a non-specific chemical effect
No heme loading. Dosing biliverdin does not load cells with heme or disturb heme homeostasis, answering one of the first safety objections raised against this approach
Respiration intact. Cellular respiration is unchanged at active concentrations, with no mitochondrial liability signal
Cascade operational. HPLC, fluorescence (iRFP and eUnaG) and permeability assays are built in-house and running. The screening campaign can start immediately
Five in-house readouts give consistent results, supporting the chemistry behind the platform.
Platform
A known molecule on a de-risked path.
The hard problem here is delivery rather than target discovery. That removes much of the risk that makes early drug development slow and expensive, and it is why a small team can run this program.
01
Known, endogenous payload
Biliverdin and bilirubin are human metabolites with characterised safety and a well-studied cytoprotective, anti-inflammatory and antioxidant profile. We are not introducing a foreign molecule into human biology.
Safety anchor
02
Direction of effect pre-validated in humans
Gilbert syndrome and elevated serum bilirubin associate with lower cardiometabolic and inflammatory disease risk across millions of people, giving directional human evidence before a single patient is dosed.
Human genetics
03
Regulatory path anchored in known biology
The planned route is a 505(b)(1) NDA for a new chemical entity, supported by extensive human safety and epidemiological literature on the active molecule. The prodrug is new, while the underlying pharmacology is already studied.
505(b)(1) route
04
A lean team that compresses the cycle
Three founders across technology, business and science. Computational work comes first. Candidate design, structure-property filtering and large-scale human genetics analysis are run in-house at low cost, while synthesis and assays run through external labs we have already partnered with.
Computational first
Delivery is the problem we solve. It carries far less risk than discovering a new target, and we are set up to do it cheaply.
Pipeline & Go-to-Market
One engine,
One engine,
a sequenced set of programs.
The same chemistry and biology underpin several disease programs. Our next experimental result will determine which we pursue first.
Lead Program
Inflammatory Bowel Disease
The gut is both the target tissue and the first tissue the drug reaches, so a locally acting anti-inflammatory is what this indication needs
Around 40% of patients fail or lose response to current biologics, and oral small molecules in this space carry class safety warnings
Colonic-release formulation is an established, de-risked delivery technology
Market Opportunity
$22–30B
~7M patients worldwide · growing ~5% a year
Clinical Entry
Antiphospholipid Syndrome
Focused orphan indication with a clear mechanism and a short, legible development path
No approved disease-modifying therapy beyond anticoagulation
Human APS data links lower bilirubin to higher inflammatory burden, supporting the mechanism directly
Market Opportunity
Orphan
Focused entry · orphan incentives · credible bridge to broader autoimmune
Gated Expansion
Metabolic & Obesity
PPARα agonism and antioxidant activity, mechanisms already linked to lower adiposity and better metabolic health
GLP-1 adjunct positioning for lifelong weight control, where only around 20% of patients remain on therapy after two years
Opens if the in vitro campaign shows systemic absorption. We treat this as a gated expansion rather than a committed program
Market Opportunity
>1B
patients worldwide · multi-$10B+ annual market
How we decide the order
The in vitro permeability results will help determine which program we pursue first. Evidence of systemic absorption would support development for metabolic disease and obesity. If the esters remain largely in the gut, we could pursue them as local treatments for inflammatory bowel disease. Either result gives us a development path to test, allowing several programs to emerge from the same platform.
One platform, a lead indication chosen for where the chemistry is strongest, and an expansion that depends on results we are about to generate.
Pipeline
A faster consumer-health path to early revenue.
The same platform, IP, and manufacturing base extend into consumer health, where regulatory timelines are far shorter and revenue can arrive years ahead of the therapeutics.
Cosmetics
Anti-aging night serum
Biliverdin ester paired with retinol, stabilized with vitamin E and provitamin B5, in a squalane or hyaluronic acid base.
Mild skin yellowing reads as visible proof that the product is working, and consumers treat it as a feature.
Supplement
Gut and microbiome support
Oral natural biliverdin, not the ester, complexed with chlorophyll, phycocyanobilin, and vitamin B12.
Structure and function claims across gut health, intestinal barrier, antioxidant defense, healthy inflammatory balance, and the microbiome.
$122 to $193B
Global skincare, 2025
$8 to $10B
Nutricosmetics, 2025, fast growing
$200 to $210B
Dietary supplements, 2025
First to large-scale CMC
Branched, separately licensable IP
Visible signal as a consumer benefit
Short regulatory timelines and shared IP turn the platform into revenue while the drug programs mature.
Path to Value
A capital-efficient path to
A capital-efficient path to
candidate nomination.
A staged 18–30 month workflow from designed library to nominated candidate, with explicit go/no-go criteria at every gate. The second step matters most, because the permeability data decides which program leads.
1
Library Design & CRO Synthesis
Rational design of biliverdin-ester variants with computational prioritisation on structure and physicochemical properties. CRO synthesis of an initial 20 to 40 compound library.
Go criterion: ≥20 synthesizable candidates with verified purity ≥95%.
4–6 mo
2
In Vitro Screening Campaign, the decision gate
Human serum esterase activity, membrane permeability in HepG2 and Caco-2, PPARα reporter activity, intracellular and extracellular BLVRA/BLVRB activity, and bilirubin secretion. This step decides which program leads. Systemic absorption opens the metabolic program. Gut retention confirms the IBD program.
Milestone 1
Go criterion: ≥3 compounds clearing permeability, esterase and PPARα thresholds, with a defined absorption profile.
3–6 mo
3
In Vivo Proof-of-Concept
Disease-model efficacy in the indication the gate selects: colitis models for the gut-restricted branch, APS models (MRL/lpr and aPL antibody induction) for the systemic inflammatory branch.
Milestone 2
Go criterion: Statistically significant disease-marker reduction versus vehicle control.
6–12 mo
4
IND-Enabling Package & Series A Position
Formulation lock, GLP toxicology and PK in the species the selected program requires, and composition-of-matter plus method-of-use filings. Positions the company for Series A or strategic partnering.
Milestone 3
Go criterion: Development candidate nominated with an acceptable preclinical safety margin and a defined clinical entry indication.
6–12 mo
This round takes a well-evidenced biological thesis to a nominated candidate and a Series A position.
Path to Value
A staged path from near-term revenue to exit.
Two complementary engines. Consumer products generate early cash on a short regulatory path. Therapeutic programs are advanced to the point where they are most valuable to an acquirer or partner.
Program
Regulatory path
Time to value
Primary value realization
Consumer
Cosmetics & supplements
Cosmetic dossier, NDI
~2 yrs to first revenue
Direct product revenue or partnership
Dermatology
Topical
505(b)(1), rapid PoC
Phase 1 to 2
Asset sale or partnership
Inflammatory bowel disease
Lead program, gut-restricted
505(b)(1), colonic-release
Phase 1 to 2
Asset sale or partnership
Metabolism
Gated on absorption data
Maintenance Phase 2, 6-month endpoint
~4 yrs to Phase 2
Asset sale or partnership
Autoimmune
Orphan first
Orphan (APS), then lupus
Phase 1 to 2
Asset sale or partnership
Acquisition
$4.0B
Takeda bought Nimbus Therapeutics' oral TYK2 inflammation program upfront in 2022, at Phase 2b
Public re-rating
~10×
Abivax, an oral ulcerative colitis drug, went from roughly $1B to over $10B in market value on a single Phase 3 readout in 2025
Comparables are illustrative of how this asset class is valued, not projections. Timelines are internal planning estimates contingent on funding, trial design, and regulatory feedback, not commitments. The metabolic Phase 2 timeline assumes a six-month primary endpoint.
Consumer revenue in roughly two years funds and validates the platform, while the therapeutics are built to sell or partner after clinical proof of concept.
Competitive Landscape
Validated biology
Validated biology
despite limited direct competition.
The biology is increasingly validated, but the field remains open when it comes to building a chronic, oral therapy designed to safely recreate the protective bilirubin phenotype.
01 · Existing Approaches
Direct Bilirubin Therapeutics
External validation of the biology, in a format that limits utility for chronic disease.
Bilix / BRIXELLE platform: PEGylated bilirubin, i.v., early clinical
Focused primarily on acute inflammatory indications
No approved or clinical-stage oral bilirubin-elevating therapy
02 · Unmet Need
Gap in the Field
In inflammatory bowel disease specifically, the gap is a safe oral option for the patients biologics have failed.
Around 40% of IBD patients fail or lose response to current biologics, and existing oral small molecules carry class safety warnings
i.v. and nanoparticle bilirubin formats are not suited to daily, long-duration administration
Oral prodrug chemistry not pursued by existing players
03 · Yellow Pigment
First-in-class oral approach
Pharmacologically recreating the Gilbert protective phenotype, designed for daily, chronic use.
Oral BV-ester prodrug platform with unique chemistry approach
Designed for chronic disease settings where duration and daily dosing matter
Human genetics-validated target with Gilbert syndrome as natural proof of concept
Existing field
Yellow Pigment
i.v. · acute · nanoparticle · early clinical
oral · chronic · prodrug · daily dosing
Strong external validation of the biology, with a clear gap around oral chronic-disease therapeutics.
Why Yellow Pigment
A platform built to convert protective biology
A platform built to convert protective biology
into category-defining medicines.
Yellow Pigment turns one of the strongest human protective phenotypes into a controlled, oral pharmacology platform, positioned to address some of medicine's largest unmet markets through three reinforcing pillars.
I
Human protective biology insight
A hypothesis grounded in one of the most replicated protective phenotypes in human genetics, already validated in millions of Gilbert carriers and not derived from cell lines or animal models alone.
Human genetics-validated target
Decades of consistent cohort evidence
Pleiotropic protection across disease areas
II
Controlled pharmacology through BV-ester prodrugs
A proprietary chemistry strategy that recreates the broad protective window with controlled, oral, daily pharmacology, solving the delivery and formulation problem that has blocked prior bilirubin approaches.
BV-ester design library (40+ compounds)
Composition-of-matter IP opportunity
Oral, chronic, daily-dose format
III
Platform for major chronic-disease markets
A staged development engine that moves efficiently from screening cascade to validated candidate, with shared infrastructure unlocking commercial reach into multi-$10B+ metabolic, autoimmune, and inflammatory markets.
IBD lead program · APS clinical entry · metabolic expansion
Cross-applicable tox and translational learnings
Capital-efficient path to Series A and partnership
IV · How we operate
Three founders spanning technology, business and science. Computational work comes first, so candidate design, structure-property filtering and large-scale human genetics analysis are done in-house at low cost. Synthesis and assays run through external labs we have already partnered with. The result is a cost and time profile much closer to a software company than to a traditional discovery lab.
Protective human biology, controlled oral pharmacology, several large chronic-disease markets, and a small team set up to reach them efficiently.
Team & The Ask
Experienced founders raising seed capital
Experienced founders raising seed capital
to reach a major inflection point.
Nikola Ivica, PhD
Chief Scientific Officer
MIT PhD, Harvard BA. Heme metabolism, bilirubin biology and therapeutic platform design. Scientific founder of the ester hypothesis.
Ivan Posavec
Chief Executive Officer
Harvard BA. Repeat founder and experienced CEO across multiple domains.
Luka Babić
Chief Operating Officer
Harvard BA. Exited founder and operator, running execution systems and the computational work.
Advisors
Staša Stanković, PhD
OvartiX CEO, Cambridge PhD, AstraZeneca consultant, women's health scientist
Nenad Grmuša
DEM BioPharma CEO, former Takeda R&D strategy and external innovation leader
Pre-Seed Round
3 x $500k
Milestone-tranched SAFEs
Tranche 1
$500K
Unlocks Milestone 1
In Vitro Screening Campaign
Resolves the permeability question and sets the lead program
Tranche 2
$500K
Unlocks Milestone 2
In Vivo Proof-of-Concept
Efficacy in the disease model the gate selects
Tranche 3
$500K
Unlocks Milestone 3
IND-Enabling Package
Takes one target toward clinical stage
A small first check that scales in as risk retires, with each tranche gated to an objective milestone. Burn stays low: three founders, computational work in-house, and wet lab through external CROs we have already scoped.
Goal: Nominate a Yellow Pigment development candidate, settle the lead indication on data, and take one target toward clinical stage, positioning the company for Series A financing or strategic partnering.