Inclusion Criteria:
- Previous diagnosis of CRC, despite optimized treatment for asthma or COPD, or UCC for
at least 1 year
- Chest X-ray or computed tomography (CT) scan thorax within 5 years prior to screening
visit that confirms the absence of any clinically significant abnormality contributing
to the chronic cough in the opinion of the investigator
- Cough severity VAS score ≥ 40 at screening visit
- Pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥ 60% of predicted at
screening"
- Mannitol CDR ≥ 12 coughs/100 mg determined at screening visit mannitol challenge test
- For women of childbearing potential: agreement to remain abstinent or use
contraception For men: agreement to remain abstinent or use a condom, and agreement to
refrain from donating sperm

Inclusion Criteria for Patients with CRC with Atopic Asthma or Patients with CRC with
Non-Atopic Asthma (Part A)

- Physician diagnosis of asthma for ≥ 12 months based upon GINA STEP 2-5
- Stable treatment with ICS therapy (GINA STEP 2) or ICS therapy and at least one
additional controller (GINA STEP 3- 5) for ≥ 3 months
- Patients with atopic asthma (n = 20), based upon historic record of positive test for
atopy (if available), or confirmed at screening by positive fluorescence enzyme
immunoassay for specific IgE against at least one of the following five perennial
aeroallergens: animal (cat dander, dog dander, cockroach), dust mite (Dermatophagoides
farinae, Dermatophagoides pteronyssinus), and mold mix
- Patients with non-atopic asthma (n = 20), based upon historic record of negative test
for atopy (if available), or confirmed at screening by negative ImmunoCAP test result
for all five perennial aeroallergens: animal (cat dander, dog dander, cockroach), dust
mite (Dermatophagoides farinae, Dermatophagoides pteronyssinus), and mold mix, and
relevant local allergens, and no history of symptoms suggesting atopy
- Never or former smoker (≥ 6 months prior to screening) with < 20 pack-years or
equivalent history

Inclusion Criteria for Patients with CRC COPD-CB or Patients with CRC COPD (Part B)

- Diagnosis of COPD GOLD I-II ± CB
- Stable background treatment consisting of a bronchodilator medication and or stable
ICS therapy for ≥ 12 weeks prior to screening visit
- Former smoker with ≥ 10 pack-years or equivalent history within 6 months of screening
- Post-bronchodilator FEV1/ forced vital capacity (FVC) ratio ≤ 0.70 at screening
- Chest X-ray or CT scan within 6 months prior to screening visit or during the
screening period (prior to randomization [Study Visit 2]), that confirms the absence
of clinically significant lung disease besides COPD

Exclusion Criteria:
- Pregnant or breastfeeding, or intention of becoming pregnant during the study or
within 28 days after the final dose of GDC-6599
- History of diagnosed bleeding diathesis or easy bruising or bleeding
- Post-bronchodilator FEV1/ FVC ratio < 0.60 at screening visit (patients with CRC
asthma and UCC only: Part A)
- History of significant hepatic impairment
- History of aspiration or recurrent pneumonia
- Respiratory infection (including upper respiratory infection) within 8 weeks prior to
screening
- Treatment with any strong inhibitor or inducer of CYP3A within 28 days or 5
drug-elimination half-lives, whichever is longer, prior to initiation of study drug
- Treatment with angiotensin-converting enzyme (ACE) inhibitor within 12 weeks prior to
screening (Study Visit 1) through completion of the study
- Treatment with opioids (including codeine), pregabalin, gabapentin, amitriptyline, or
nortriptyline for the treatment of cough within 2 weeks prior to screening (Study
Visit 1) through completion of the study
- Treatment with cough suppressant medication within 2 weeks prior to screening (Study
Visit 1) through completion of the study
- Known coronavirus 2019 (COVID-19) infection, persistent symptoms of known prior
COVID-19 infection, and/or known positive COVID-19 test within at least 8 weeks prior
to screening and randomization
- Clinical laboratory value outside the reference range for the test laboratory at
screening
- Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator's judgment, precludes the patient's safe participation in and completion
of the study
- History of malignancy within 5 years prior to screening, except for appropriately
treated carcinoma in situ of the cervix or non-melanoma skin carcinoma

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/3/2024. Questions regarding updates should be directed to the study team contact.