A Study To Evaluate The Efficacy, Safety, Pharmacokinetics, And Pharmacodynamic Effects Of GDC-6599 In Patients With Chronic Cough

Inclusion Criteria:

• Previous diagnosis of CRC, despite optimized treatment for asthma or COPD, or UCCfor at least 1 year

• Chest X-ray or computed tomography (CT) scan thorax within 5 years prior toscreening visit that confirms the absence of any clinically significant abnormalitycontributing 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 atscreening"

• Mannitol CDR ≥ 12 coughs/100 mg determined at screening visit mannitol challengetest

• For women of childbearing potential: agreement to remain abstinent or usecontraception For men: agreement to remain abstinent or use a condom, and agreementto 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 oneadditional controller (GINA STEP 3- 5) for ≥ 3 months

• Patients with atopic asthma (n = 20), based upon historic record of positive testfor atopy (if available), or confirmed at screening by positive fluorescence enzymeimmunoassay for specific IgE against at least one of the following five perennialaeroallergens: 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 negativetest for atopy (if available), or confirmed at screening by negative ImmunoCAP testresult 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 suggestingatopy

• Never or former smoker (≥ 6 months prior to screening) with < 20 pack-years orequivalent 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 stableICS therapy for ≥ 12 weeks prior to screening visit

• Former smoker with ≥ 10 pack-years or equivalent history within 6 months ofscreening

• 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 thescreening period (prior to randomization [Study Visit 2]), that confirms the absenceof clinically significant lung disease besides COPD

Exclusion Criteria:

• Pregnant or breastfeeding, or intention of becoming pregnant during the study orwithin 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 CRCasthma 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 priorto screening

• Treatment with any strong inhibitor or inducer of CYP3A within 28 days or 5drug-elimination half-lives, whichever is longer, prior to initiation of study drug

• Treatment with angiotensin-converting enzyme (ACE) inhibitor within 12 weeks priorto 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 (StudyVisit 1) through completion of the study

• Treatment with cough suppressant medication within 2 weeks prior to screening (StudyVisit 1) through completion of the study

• Known coronavirus 2019 (COVID-19) infection, persistent symptoms of known priorCOVID-19 infection, and/or known positive COVID-19 test within at least 8 weeksprior to screening and randomization

• Clinical laboratory value outside the reference range for the test laboratory atscreening

• Any serious medical condition or abnormality in clinical laboratory tests that, inthe investigator's judgment, precludes the patient's safe participation in andcompletion of the study

• History of malignancy within 5 years prior to screening, except for appropriatelytreated carcinoma in situ of the cervix or non-melanoma skin carcinoma