- Before
- Signs target reviews built from weeks of reading, and answers the committee's questions by going back to the papers.
- Now
- Opens any grade and sees the claims and passages behind it, decides the critic's challenges, and signs with conditions.
One portfolio, the week before the committee
Northwind Bio runs 12 targets across Immunology, Oncology and Neuroscience ahead of the Oct 22 discovery portfolio committee. Dr. Maya Chen, Head of Immunology target discovery, has RKN2 in ulcerative colitis to sign. Here is her week, screen by screen, in the working solution.
- 01Morning
The whole portfolio on one evidence matrix
Dr. Maya Chen · Head of Immunology target discoveryTwelve targets down the side, grouped by therapeutic area; six questions across — genetics, expression, biology, tractability, safety, competition — each graded A to D, with the overall grade and the stage at the right: 53 grades, 851 cited claims behind them. The evidence watch above the matrix already shows two changes: a third oral GPR214 antagonist entered Phase 1, and neutropenia was reported with a kinesin inhibitor related to KIF29.
“Six questions every target must answer, graded A to D. Click a grade to see its evidence.”
- 02One click
RKN2 is a C on safety — and she sees why
Dr. Maya Chen · Head of Immunology target discoveryClicking the RKN2 safety cell opens what is behind the grade. 212 heterozygous loss-of-function carriers show no immune deficiency or serious infection across 1,400 phenotypes, but two siblings with homozygous partial loss of function had chronic mucocutaneous candidiasis from early childhood, and knock-in mice clear oral Candida more slowly. Each claim carries its number, its evidence type and its source.
“Infection risk needs a monitoring plan.”
- 03The assessment
Every section: the question, the grade, the claims, the passages
Safety liability agentRKN2 — oral small molecule, built Oct 5 in 4.6 days from 61 sources and 142 claims. Section 5 of 6 asks what happens when the target is taken away, in people, in animals, in tissues. The safety liability agent wrote it with 81% confidence from four sources, and the source panel highlights the exact passage behind each claim, with a link to open it there.
The safety liability agent never lowers a liability without a cited source, and any human loss-of-function phenotype is flagged.
- 04Critic review
The critic argues the other side
CriticThe critic reads each section as a sceptical committee member. On safety it argues that candidiasis is a known, monitorable effect of IL-17 pathway medicines and that the 212 carriers are healthy, so the risk looks dose-dependent — and proposes raising safety from C to B with a fungal-infection monitoring condition. Maya can accept, keep the grade as is, or ask the agent to look again. A second challenge — RKN1, the closest family member, is expressed in heart, so is there an off-target risk? — is resolved: 40-fold selectivity cited, and a cardiac selectivity check added as an open question for Priya Raman.
The critic proposes only — it never changes a grade itself. A person decides.
- 05Oct 7 · 09:14
New evidence moves a grade, in view
Genetics evidence agentLRRK3 in ALS was signed on Sep 21 as Hold for more evidence: its genetics rested on one small association study, p = 4 × 10⁻⁵, not replicated. “Check for new evidence” re-runs the genetics, safety and competitor searches and reads 214 new papers and preprints. A genome-wide meta-analysis of 29,612 ALS cases and 122,656 controls replicates the locus at p = 2.8 × 10⁻⁹, and the risk allele raises LRRK3 in motor neurons. The cell flips from C to B with a “was C” tag, the citation slides in, and the overall grade moves from B− to B.
It stays a B, not an A, until fine-mapping is published — and Dr. Aiko Tanaka confirms before the committee pack uses it.
- 06A new request
PTPN31 in atopic dermatitis, built while she watches
Sam Patel · Computational biologistSam Patel requested PTPN31 in atopic dermatitis, small molecule or degrader, for the Nov 19 committee. The assessment planner splits the template into 6 sections and 38 research questions; six specialist agents then research in parallel, each lane showing its sources and claims, and the scorecard fills as each grade lands.
The assessment planner sets the evidence bar for every grade and never grades a section itself.
- 07Built
Graded, challenged, assembled and routed
Critic and Assessment assemblerExpression and competition come back A, tractability C — the phosphatase site is shallow and the allosteric pocket has no ligand yet. The critic raises 6 challenges, resolves 5 with the agents and leaves 1 for the owner. The assembler writes 128 cited claims from 54 sources into the assessment, overall B+, and routes it to Dr. Maya Chen.
Only cited claims appear in the assessment.
- 08Committee prep
Three targets, one rubric, side by side
Dr. Maya Chen · Head of Immunology target discoveryFor the Oct 22 committee she compares RKN2, CDH31 and KCNT4 on one radar and a criterion-by-criterion table. RKN2 is strongest on genetics and pathway biology, watch safety; CDH31, an antibody–drug conjugate in gastric cancer, is strongest on expression and tractability; KCNT4 in focal epilepsy is strongest on genetics. One click adds them to the committee pack.
- 09Signed
She signs with conditions; safety gets a co-signature
Dr. Maya Chen and Lena OrtizMaya chooses Advance with conditions over Advance to validation, Hold for more evidence or Stop. The open questions become the conditions — cellular selectivity against RKN1 in human cardiomyocytes, a freedom-to-operate opinion on the allosteric pocket, serum IL-22 as a pharmacodynamic biomarker, the QLS-208 Phase 1 read-out. The two open critic challenges are recorded with her signature, and because safety is graded C, Lena Ortiz co-signs after her.
“Signing as Dr. Maya Chen · Meaning: scientific approval of this assessment.”