Exploratory scores, visible weights.

Pursue diligence · N5 · CFRD / diabetes and metabolism

Worth a closer look — not a mandate to form a company

Adult CFRD is common and the reviewed industry drug map is empty.

Would have to be true. CFRD remains prevalent on HEMT; generic SGLT2/GLP-1/metformin are insufficient or poorly tolerated in CF; a CF-specific mechanism or formulation has a feasible endpoint (CGM time-in-range or pulmonary co-benefit).

Kill criteria. Kill if academic SGLT2/GLP-1 studies show off-the-shelf drugs close the gap or if HEMT cohorts show CFRD incidence collapsing toward background.

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Pursue diligence · N1 · Mutation-agnostic CFTR restoration

Worth a closer look — not a mandate to form a company

Nucleic-acid restoration is crowded; a bypass mechanism is the differentiated N1 bet.

Would have to be true. ABCI-class ionophores restore airway anion transport without CFTR protein; safety and chronic dosing work in people with CF including nonsense/rare genotypes; nucleic-acid programs do not fully cover the ineligible group first.

Kill criteria. Kill if ABCI safety/tolerability fails or if a mutation-agnostic mRNA/gene therapy demonstrates clinically meaningful restoration in ineligible genotypes.

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Pursue diligence · N4 · Chronic infection

Worth a closer look — not a mandate to form a company

Approved inhaled antibiotics remain SoC; novel CF infection programs are thin after review.

Would have to be true. Chronic PA or NTM still drives residual lung disease on HEMT; phage or another modality can be manufactured and regulated; culture-ascertainment decline is not the whole PA story.

Kill criteria. Kill if BX004 or similar phage succeeds as a broad incumbent or if PA/NTM prevalence and inhaled-antibiotic use keep collapsing without a new product.

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Watch adjacent · N3 · Residual lung disease

A drug for a nearby disease might close this gap first

CF-specific industry anti-inflammatories are absent; NCFB DPP1 programs are the adjacent crowding risk.

Would have to be true. Residual PEx and FEV1 impairment on HEMT are inflammatory enough to treat; a CF-specific mechanism or CF trial is required because NCFB drugs do not automatically translate.

Kill criteria. Kill if brensocatib-class DPP1 works in CF or if residual disease is mostly structural damage and infection rather than treatable inflammation.

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Pursue diligence · N6 · GI and CF liver disease

Worth a closer look — not a mandate to form a company

PERT is a solved product class; advanced CFLD is small severe and untreated by a disease-modifying drug.

Would have to be true. Cirrhosis/portal-hypertension endpoints can be studied; the 861-person cirrhosis group is large enough for a development path; UDCA-negative guidance leaves a real gap.

Kill criteria. Kill if the addressable advanced-CFLD population is too small for a trial or if a feasible endpoint cannot be defined.

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Services, not a drug · N8 · Treatment burden and care delivery

A clinic or operations problem, not a new medicine

Do not force a drug score onto a services problem. Clinic visits and inhaled-therapy burden remain after modulators.

Would have to be true. A services or digital product can reduce visit burden inhaled-therapy time or adult-care coordination with a measurable CF-clinic workflow; reimbursement is plausible without inventing a TAM from 33989 people.

Kill criteria. Kill if the only residual is clinic operations that health systems will absorb or if Registry time-use evidence never materializes.

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Watch incumbents · N1 · Mutation-agnostic CFTR restoration

Large companies are already in this race

This remains the causal remaining restoration problem and it is the crowded investigational column.

Would have to be true. A new delivery or editing approach is differentiated from 4D-710 VX-522 ARCT-032 RCT2100 KB407 SP-101 SPL84 and related listings; ineligible genotypes still lack restoration after those programs read out.

Kill criteria. Kill as a company-formation default if current clinical nucleic-acid programs show meaningful restoration. Keep as a watch-incumbents card not a me-too newco.

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