Safety, Tolerability, and Pharmacokinetics of RCS-21 in Healthy Volunteers.

Inclusion Criteria:

1. Able and willing to give written informed consent.

2. Male or female aged 18 to 64 years (inclusive).

3. Women will be considered for inclusion if they are:

• Not pregnant, as confirmed by pregnancy test (see assess- ment schedule), andnot breastfeeding. AND

• WOCBP must use one of the following highly effective methods of birth controlthat result in a low failure rate of less than 1% per year when usedconsistently and correctly

• according to recommendations by the European Heads of Medicines Agencies -from at least 14 days before the first administration of study medicationuntil 30 days after the last administration of study medication:

• combined (estrogen and progestogen containing) hormonal contraceptionassociated with inhibition of ovulation:

• oral

• intravaginal

• transdermal

• progestogen-only hormonal contraception associated with inhibition ofovulation:

• oral

• injectable

• implantable

• intrauterine device (IUD)

• intrauterine hormone-releasing system (IUS)

• bilateral tubal occlusion

• vasectomized partner (provided that this partner is the sole sexualpartner of the WOCBP participant and that the vasectomized partnerhas received medical as- sessment of the surgical success)

• sexual abstinence (defined as refraining from hetero- sexualintercourse during the entire study period, be- ginning 2 weeks priorto the screening visit) OR

• Of non-childbearing potential defined according to the Clinical TrialFacilitation Group (CTFG) document "Recommendations related to contraceptionand pregnancy testing in clinical trials"

4. Male participants with female partner(s) of childbearing potential are eligible toparticipate in the study if they agree to the following during treatment and until 30 days after the last administra- tion of study medication:

• Inform any and all partner(s) of their participation in a clinical drug studyand the need to comply with contraception instructions as directed by theinvestigator.

• Male participants are required to use a condom during treatment and until 30days after the last administration of study medication.

• Female partners of male participants who have not undergone a vasectomy withthe absence of sperm confirmed or a bilateral orchiectomy should consider useof effective methods of contraception during treatment and until 30 days afterthe last administration of study medication.

• Sperm donation is not allowed during treatment and until 30 days after the lastadministration of study medication.

5. Healthy participants according to the assessment of the investigator, as based on acomplete medical history including a physical examination, vital signs, 12-leadElectrocardiogram (ECG), pulmonary function testing and clinical laboratory tests.

6. Body Mass Index (BMI) of 18.5 to 31.9 kg/m2 (inclusive).

7. Ability to inhale in an appropriate manner (e.g. as confirmed in the inhalationtraining using the PARI eFlow® device with a pla- cebo medication at the screeningvisit).

8. Non-smokers (including e-cigarette) or ex-smokers (with less than 10 pack years andstopped smoking for at least 5 years prior to screening visit).

9. Normal pulmonary function with Forced Expiratory Volume in the first second (FEV1) ≥ 80 % of predicted normal at screening visit. Calculations will be based on theGlobal Lung Function Initiative (GLI 2012) formula.

Exclusion Criteria:

1. Any clinically relevant abnormal findings in physical examination, clinicalchemistry, hematology, urinalysis, vital signs, lung function or ECG at screeningvisit, which, in the opinion of the investigator, may either put the participant atrisk because of participation in the study or may influence the results of thestudy, or the participant's ability to participate in the study.

2. Past or present disease, which as judged by the investigator, may affect the outcomeof this study. These diseases include, but are not limited to, cardiovasculardisease, malignancy, he- patic disease (asymptomatic Gilbert syndrome is allowed),renal disease, hematological disease, neurological disease, endo- crine disease (stable and asymptomatic hypothyroidism with or without Hormone Replacement Therapy (HRT) is allowed) or pulmonary disease (including but not confined to chronicbronchitis, emphysema, tuberculosis, bronchiectasis or cystic fibrosis).

3. Having received any vaccination within the last 2 weeks before the first screeningvisit.

4. History or current evidence of clinically relevant allergies or idiosyncrasy to anydrug or food.

5. History of allergic reactions to any active or inactive component of the studymedication (including medication for bronchoscopy, e.g. salbutamol, lidocaine,midazolam or propofol).

6. Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg,diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outsidethe range of 50 to 90 beats per minute (bpm).

7. Proneness to orthostatic dysregulation, fainting, or blackouts.

8. History or presence of any malignancy except for basalioma.

9. Chronic or acute infections or history of an acute infection during the four weeksbefore the first screening visit.

10. Positive results in any of the following virology tests: human im- munodeficiencyvirus (HIV) antibodies and antigen, Anti-hepati- tis B-core antibody (HBc-Ab),hepatitis B-surface antigen (HBs- Ag) and anti-hepatitis C virus antibody (HCV-Ab).

11. Positive drug screen (amphetamines, barbiturates, benzodiaze- pines, cannabinoids,cocaine, methadone, methamphetamine, opiates, phencyclidine, or tricyclicantidepressants).

12. History of previous administration of any registered or investiga- tionaloligonucleotide-based drug.

13. History or presence of alcohol or drug abuse.

14. Use of any medication (including over-the-counter medication, herbal products)except allowed concomitant medication within 2 weeks (for biologics: 6 months)before administration of IMP or within < 10 times the elimination half-lifeof the respective drug, or the duration of the pharmacodynamic effect, whatever islonger.

15. Positive breath alcohol test.

16. Planned donation of oocytes, blood, organs, bone marrow dur- ing the course of thestudy or within 6 months after the last screening visit.

17. Participation in another clinical study with an investigational drug or devicewithin the last 3 months or during the course of the study. For biologics, theminimum exclusion period is at least 6 months or the time of duration of thepharmacodynamic effect or 10 times the half-life of the respective drug whatever islonger before inclusion in this study.

18. Blood donation of more than 250 ml within the last 30 days before the firstscreening visit.

19. Anticipated non-availability for study visits/procedures.

20. Anticipated lack of willingness or inability to cooperate adequately.

21. Vulnerable participants.