A precision BRAF inhibitor for the tumors that stop responding.
BRAF-Δ is our lead candidate: a small molecule designed to re-engage the MAPK pathway in drug-resistant melanoma and to cross the blood–brain barrier for glioblastoma. We are raising a $100K Phase-1 round to fund wet-lab validation.
Mechanism
Resistance Bypass
Current BRAF inhibitors (vemurafenib, dabrafenib) lose potency as tumors evolve MAPK reactivation. BRAF-Δ is designed to bind an alternate hydrophobic pocket that resistance mutations leave intact.
BBB Permeability
AI-guided lipophilicity and P-gp efflux screening prioritized scaffolds capable of crossing the blood–brain barrier — a prerequisite for treating glioblastoma.
AI × Wet-Lab Loop
Molecular dynamics and docking narrow the candidate set; wet-lab validation on patient-derived cell lines closes the loop. We iterate weekly, not quarterly.
Use of Funds · $100K
Design Pipeline
BRAF-Δ moves through six stages. Every stage has a stop condition — a specific readout that kills the candidate or advances it. Nothing is skipped, and every failed candidate is published as a lab note.
- Stage 01
Target validation
CompleteConfirm the BRAF bypass variant as a driver of relapse in melanoma and GBM via published patient sequencing and literature triangulation.
→ Kill if the variant isn't clinically enriched in resistant tumors.
- Stage 02
In silico screening
ActiveScreen ~120k scaffolds against the alternate hydrophobic pocket with AI-guided docking. Rank on binding pose, pocket coverage, and synthetic accessibility.
→ Advance top 20 scaffolds to molecular dynamics.
- Stage 03
Molecular dynamics + ADMET
Active100 ns MD runs on the shortlist. Predict lipophilicity, P-gp efflux, hERG risk, and BBB permeability. Kill off-target liabilities before spending wet-lab dollars.
→ Advance 4 leads with clean ADMET and stable binding.
- Stage 04
Wet-lab synthesis + biochemical assay
Q2 2026Synthesize the 4 leads via CRO. Measure IC50 against wild-type BRAF, V600E, and the resistance variant. Selectivity is non-negotiable.
→ Kill any lead with IC50 > 500 nM on the resistance variant.
- Stage 05
Patient-derived cell line validation
Q2–Q3 2026Test survivors on melanoma and GBM patient-derived cell lines, including lines resistant to vemurafenib and dabrafenib. Confirm on-target MAPK suppression by Western.
→ Advance leads with >50% growth inhibition on resistant lines.
- Stage 06
BBB permeability + preprint
Q3 2026In vitro BBB model (hCMEC/D3) on the surviving lead. Publish a preprint of the full loop — hits, misses, and the resistance-variant thesis — regardless of outcome.
→ Data package readied for seed round and academic co-development.
How We Optimize
Multi-objective, not single-metric
Every candidate is scored on a weighted composite: potency on the resistance variant, selectivity vs. wild-type BRAF, BBB permeability, ADMET safety, and synthetic tractability. Nothing advances by being brilliant on one axis and broken on another.
Weekly loops, not quarterly reviews
AI proposes → docking ranks → MD filters → wet-lab confirms. The loop closes every week. Each iteration compresses the search space by roughly one order of magnitude.
Kill early, kill loud
Every stage has a hard stop condition written before the data arrives. Sunk-cost bias is the fastest way to burn a $100K round. Failed candidates get published, not buried.
Human-in-the-loop chemistry
AI-generated scaffolds are triaged by a medicinal chemistry advisor before synthesis. Novelty is a feature; unmakeable molecules are not.
Open benchmarks
We benchmark leads against vemurafenib, dabrafenib, and encorafenib on the same resistant cell lines. If we can't beat the standard of care, we say so.
Reproducibility as a first-class metric
Every assay is run in triplicate across two independent operators before it counts. Raw data lands in a public dataset attached to each lab note.
See the two principles in one place.
Live · demo dataMulti-objective scoring and "kill early, kill loud" aren't slogans — they're the weekly stand-up. Move the weights to reflect what you care about (e.g. push BBB up for a GBM-first strategy) and watch the advance/kill list re-sort. The numbers below are illustrative; the mechanic is real.
Score the leads. Watch the decisions move.
- LL-772→ advanceΔ-pyrimidinePOTSELBBBADMSYN8.0compositeLead scaffold — balanced across every axis.
- LL-609→ advanceSulfonamide-quinazolinePOTSELBBBADMSYN7.8compositeCleanest ADMET, highest BBB — potency is the ceiling.
- LL-814watchAza-indazolePOTSELBBBADMSYN7.3compositeBest potency; BBB is marginal — a GBM problem, not a melanoma one.
- LL-931kill · hard stopMacrocyclicPOTSELBBBADMSYN6.6compositeElegant on paper. Unmakeable at CRO scale.
- LL-455kill · hard stopFluoro-pyridinePOTSELBBBADMSYN6.2compositehERG flag + weak selectivity. Killed in stage 3.
- Mon01AI proposes
~30 new scaffolds generated from the current binding-pose priors.
- Tue02Docking ranks
Top 30 → top 10 by pocket fit, pose stability, and synthesizability.
- Wed03MD + ADMET
100 ns MD on top 10 · ADMET model kills anything with a hERG or hepatotox flag.
- Thu04Wet-lab confirms
Survivors go to the biochemical assay bench — IC50 on the resistance variant.
- Fri05Stand-up + kill
This board updates. Advances move to next week's cohort. Kills get published.
Every Friday, this decision board is signed by the medicinal chemistry advisor and posted as a lab note. Advance / watch / kill is on record before the next week begins.
The Vision
BRAF-Δ is the first proof, not the destination.
If we can move a resistance-driven oncology target from thesis to validated wet-lab readout in twelve months for $100K, we've proven a template — one that scales to every abandoned target the field has quietly deprioritized.
The five-year vision is a portfolio of ten such programs, each run as an open notebook, each staffed by a rotating cohort of student researchers who get their first wet-lab publication before their first driver's license. The lab Luella went looking for at thirteen — built at scale.
Phase-1 is a capital-efficient bet on loop speed as the moat. $100K buys a public data package on a validated resistance target, the operational template for the next nine programs, and a first-look position on any lead we out-license. Downside is bounded by publication — we ship the science either way. Upside is a scalable, IP-generating platform priced at the seed-round tier.
- 10 programs
targeting resistance mechanisms in solid tumors the pharma pipeline has passed over. - ≤12 months
from thesis to validated wet-lab readout. The loop is the moat. - 100+ students
with a first-author lab note before they turn eighteen. - 1 licensed asset
handed off to a clinical partner — proof the model produces medicine, not just papers.
KPI Dashboard
The scoreboard we run the lab on. Every metric has a口径 (definition + measurement method) so investors and partners can audit the number, not just admire it.
口径A program is 'active' once it clears Stage 01 (target validation) and has an assigned scaffold cohort. Reviewed at each Friday stand-up.
口径Median days from Monday scaffold generation to Friday advance/kill decision, measured over the trailing 8 weeks. Excludes CRO synthesis lead time.
口径Percent of docked scaffolds that survive MD + ADMET filtering. Rising rate = better proposal priors. Reset each quarter.
口径Percent of MD-advanced leads whose measured biochemical IC50 lands within 3× of the predicted value. Truth check on the model.
口径Percent of ordered scaffolds delivered on-spec (>95% purity) on the first CRO attempt. Below target = medicinal chemistry triage failing.
口径Public write-ups of any decision — wins, kills, inconclusives — with raw data attached. Cadence: minimum one per program per month.
口径Total program spend ÷ number of stage-gated advance/kill decisions. Drops as the loop tightens and CRO batching improves.
口径Under-18 researchers listed as first or co-first author on a public lab note or preprint. Tracked lifetime.
口径Programs handed off under a signed license or academic co-development agreement. The end-state proof the platform produces medicine.
Baseline metrics reflect trailing 8-week rolling averages. The dashboard is regenerated the first Monday of every month and archived under Documents.
Documents
Roadmap
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- Indicative check size and preferred instrument (SAFE / note)
- Time horizon to a decision
- Any conflict / competing programs in your portfolio
Next Steps · Partnership
What we need in the next 90 days — and what you get for showing up early.
First-look rights on subsequent programs. Weekly investor lab note. Named in the preprint acknowledgements.
Board observer seat through Phase-1. Quarterly working session with the scientific advisor. Priority on any out-license conversation.
Co-authorship on the Phase-1 preprint. In-kind credit convertible into program equity at seed valuation. Reference client on resistance-target work.
Small equity grant · monthly 30-min sync · named advisor on the data room. Ideal: MAPK-pathway or GBM clinical background.
Warm intros into any pharma BD desk working on BRAF resistance. We'll credit and share the response in writing.
- Day 0Email or download the one-pager. We reply the same day.
- Day 1–230-min intro call. Full deck + preclinical rationale under NDA.
- Day 3–7Diligence session with the scientific advisor. Q&A in writing.
- Day 8–14SAFE + closing docs. Onboarding to the weekly investor lab note.
Include your check size, timeline, and whether you want board observer rights. We reply within 24 hours.