A Study To Evaluate The Safety Of CMTX-101 In People With Cystic Fibrosis

Inclusion Criteria:

1. Adults ≥18 years of age at the time of screening.

2. If enrolled in the CFF Patient Registry, must provide registry information.

3. Confirmed CF diagnosis based on current CF Foundation (CFF)-sponsored guidelines.

4. For participants on modulator therapy, they must be on a stable dose of modulatortherapy for at least 3 months.

5. Willing and capable of providing induced sputum for evaluation at defined studytimepoints.

6. Positive P. aeruginosa growth of ≥104 CFU/gram from a sample of induced sputum atthe screening visit.

7. FEV1 ≥50% (Part1) or ≥35% (Part 2) of predicted normal value at screening.

8. Currently receiving inhaled antibiotic therapy, either tobramycin or aztreonamalone, or as part of CAT. At least one 28-day cycle completed within 8 weeks priorto screening visit.

9. Women of childbearing potential (WOCBP) must have a negative serum beta-humanchorionic gonadotropin test during screening and agree to use an effective method ofcontraception for the duration of the study and for 4 months after the last infusionof study drug. A female participant is considered of childbearing potential unlesspostmenopausal or surgically sterilized and at least 3 months has passed sincesterilization procedure. Female surgical sterilization procedures include tuballigation, bilateral salpingectomy, hysterectomy, or bilateral oophorectomy. A femaleparticipant is considered postmenopausal if she has had spontaneous amenorrhea forat least 2 years with an appropriate clinical profile (e.g., age appropriate,history of vasomotor symptoms).

• Effective methods of contraception include (a) abstinence, (b) partner vasectomy, (c) intrauterine devices, (d) hormonal implants (such as Implanon), or (e) otherhormonal methods (birth control pills, injections, patches, vaginal rings).

10. Male participants with a female partner must use a medically accepted contraceptiveregimen during his participation in the study and for 4 months after study druginfusion.

• Acceptable methods of contraception for male participants include condoms withspermicide, surgical sterilization of the participant (i.e., vasectomy) at least 26weeks before screening, or sexual abstinence (i.e., refraining from heterosexualintercourse) if that is the preferred and usual lifestyle of the participant.

• Males with infertility documentation are not required to use contraception.

11. Male participants must agree to abstain from sperm donation through 4 months afterstudy drug administration.

12. Capable of providing informed consent.

13. Capable and willing to complete all study visits and perform all procedures requiredby the protocol.

Exclusion Criteria:

1. Body mass index (BMI) <14 at screening and baseline.

2. Has a known history or evidence of human immunodeficiency virus (HIV) infection orchronic hepatitis B screening.

3. Tests positive for hepatitis C virus (HCV) RNA at screening.

4. Pulmonary exacerbation within 28 days of baseline.

5. Requirement for continuous (24 hour/day) oxygen supplementation; periodic use ispermitted.

6. Participation in smoking or vaping activity in the last 6 months.

7. History of, or planned, organ transplantation.

8. Elevated liver function tests obtained at screening.

9. ALT >5 × ULN or AST >5 × ULN, or

10. Total bilirubin >3 × ULN or Total bilirubin >1.5 × ULN combined with either ALT >3 × ULN or AST >3 × ULN. ULN reflects local laboratory ranges.

11. Greater than 5 ml of hemoptysis on one occasion or >30 mL of hemoptysis in a 24-hourperiod within 28 days of baseline.

12. Infection with other more pathogenic organisms such as Mycobacterium abscessus orBurkholderia spp., where the investigator feels that the participant either is notor will not remain clinically stable throughout the duration of the study.

13. Acute clinical illness requiring a new (oral, parenteral, or inhaled) antibiotic(s) ≤30 days prior to the baseline visit. Does not include chronic suppressivemedications or cyclic dosing medications such as inhaled antibiotics.

14. Women who are pregnant, planning to become pregnant during the study period or for 4months following last infusion of study drug, or breastfeeding.

15. Active treatment of any mycobacterial or fungal organisms ≤30 days prior to baselinevisit. Chronic treatment for suppression of fungal populations is allowable.

16. Anticipated need to change chronic (either inhaled or oral) antibiotic regimensduring the study period. Participants must agree to maintain their current chronicantibiotic regimen from the screening visit for the duration of the follow-up period (approximately 30 days).

17. Known allergy to any component of the study drug.

18. Participant with an estimated glomerular filtration rate <60 mL/min/1.73 m2.

19. Any significant finding that, in the opinion of the investigator, would make itunsafe for the participant to participate in this study or would not be in the bestinterest of the participant.

20. Enrolled in an interventional clinical study within ≤60 days of the baseline visit,or participating in a clinical study while enrolled in this clinical study (inclusive of vaccine studies).

21. Currently or previously enrolled in this study.