Study in Healthy Adults Challenged With Enterotoxigenic E. Coli, of the Safety, Tolerability and Anti-Diarrheal Activity of VENBETA6890, an Orally Administered, Human Monoclonal IgA

Inclusion Criteria:

1. Male or female ages 18-45 years, inclusive at screening 2. Body weight 50 to 105 kg, inclusive at screening 3. Provide written informed consent beforeinitiation of any study procedures. 4. Willing and able to complete all studyrequirements, restrictions, confinement to the Research Isolation ward, visitsand procedures 5. Completion of a training session and demonstration ofcomprehension of the protocol procedures and knowledge of ETEC-associatedillness by passing a written examination (passing grade is at least 70%).

2. Healthy as judged by the Principal Investigator (PI) and determined by medicalhistory, physical examination, medication history, and laboratory assessments.

3. At Screening: Normal to Grade 1 values14 for the following laboratorydeterminations:

• Complete Blood Count: WBC, absolute neutrophil count (ANC), hemoglobin, andplatelet count

• IgA

• Comprehensive Metabolic Panel: creatinine, alanine aminotransferase (ALT), andtotal bilirubin

• Urine protein and urine glucose

• Urine illicit drug (positive cannabis allowed) and serum alcohol screening

• Willingness to comply with COVID-19 screening PCR testing prior to dosing 8.Female subjects must be of non-childbearing potential (as defined as surgicallysterile or postmenopausal for more than 1 year), or if of childbearingpotential must be practicing abstinence or using an effective licensed methodof birth control (e.g., history of hysterectomy or tubal ligation; use hormonalor barrier birth control such as implants, injectables, combined oralcontraceptives, contraceptive patches, some intrauterine devices (IUDs),cervical sponges, diaphragms, condoms with spermicidal agents; or must have avasectomized partner) within 28-days prior to the administration of VENBETA6890or placebo and must agree to continue such precautions for 28 days after thelast dose. A woman is eligible if she is monogamous with a vasectomized male.

Male subjects with female sexual partner(s) of reproductive potential must fall into one of the following categories to qualify for enrollment:

• Documented to be surgically sterilized (defined as having successfully undergonevasectomy at least 90 days prior to Screening)

• Must agree to use a physical barrier method of contraception (e.g., a male condom)in addition to their partner's use (if partner is a WOCBP) of a birth control methodfrom the time of Screening until 90 days after the last dose of study drug. Thefollowing methods of contraception are acceptable for use by female partners (ifWOCBP) of male subjects:

1. Oral, implantable, transdermal, injectable, or intravaginal hormonalcontraception taken for at least 90 days prior to Screening

2. Intrauterine device (IUD [copper or hormonal])

3. Contraceptive sponge with condom Male subjects must agree not to donate spermfrom the time of Check-in through 90 days after the final dose of study drug 9.Agrees to avoid live-culture yogurt and other probiotics for at least 14 daysprior to the first dose of VENBETA6890 and during the study.

4. Agrees not to participate in another clinical trial during the studyperiod.

Exclusion Criteria:

1. Positive pregnancy test at Screening or within 24 h prior to VENBETA6890 orplacebo dosing 2. Breastfeeding 3. Poor venous access, as defined by inabilityto obtain venous blood, for screening labs, after 3 venipuncture attempts 4.Abnormal vital signs, defined as:

• Systolic BP >150 mmHg or Diastolic BP >90 mmHg

• Resting heart rate >100 bpm

• Temperature ≥38.0°C 5. Abnormal electrocardiogram (ECG) parameters, defined as:

• PR>220 msec

• QRS>120 msec

• QTcF>450 msec for males or >460 msec for females 6. IgA deficiency 7. Evidenceof current or past infection with testing for human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody, or Hepatitis B triple screening panel (Hepatitis B surface antigen, Hepatitis B surface antibody, Hepatitis B totalcore antibody) with confirmatory testing as indicated.

8. Having received prior vaccines for or have had prior infection with ETEC,Heat-Labile Toxin (LT), cholera, Campylobacter, or Shigella, within thepast 3 years 9. History of diarrhea during travel to a developing countrywithin the past 3 years 10. History of chronic gastrointestinal illness,including severe dyspepsia, lactose intolerance, or another significantgastrointestinal tract disease (e.g., irritable bowel syndrome,inflammatory bowel syndrome, gastric ulcer disease) 11. Regular use (≥once weekly) of laxatives, anti-diarrheal agents, anti-constipationagents, or antacid therapies 12. History of major gastrointestinal surgery (uncomplicated laparoscopic appendectomy or cholecystectomy >1-year prioris permitted) 13. Abnormal bowel habits, as defined by <3 stools per weekor >2 stools per day in the past 6 months 14. Use of systemic antibioticswithin the past 2 weeks prior to Day 1 15. Use of topical (skin), otic, orophthalmic antibiotics is acceptable, if those doses are not expected toresult in significant systemic absorption levels 16. Use of oral,parenteral or high-dose inhaled steroids within 30 days. High-dose oral orparenteral steroids is defined as ≥20 mg total daily dose, or equivalentdose of other glucocorticoids; high-dose inhaled steroids is defined as >800 μg/day of beclomethasone dipropionate or equivalent.
9. Use of any medication which might affect immune function* within 30 days *Examples include anti-cancer drugs, immunomodulating monoclonal antibodytherapeutics, and rheumatologic therapies 18. Diagnosis of schizophrenia orother major psychiatric disease 19. Alcohol or drug abuse within last 5 years;current smokers or use of nicotine in any form within 6 months prior toscreening and until after end of study.
10. Presence of immunosuppression, which could be due to active neoplasticdisease or a history of any hematologic malignancy (excluding resolvednon-melanoma skin cancers), radiation therapy, or primary or secondaryimmunodeficiencies 21. History of allergy to quinolone (e.g.,ciprofloxacin) or sulfa drugs (e.g., trimethoprim-sulfamethoxazole) 22.Known history of seizure disorder (remote history of a childhood seizuredisorder which has completely resolved is acceptable) 23. Has consumed anynutrients or drugs with known strong cytochrome P450 3A4/5 (CYP3A4/5)inhibitors or inducers or P-glycoprotein inhibitors or inducers, startingfrom 14 days prior to Day 1 until the completion of study procedures atthe end of study 24. Another investigational medication within 60 days or 5 half-lives, whichever is longer prior to Day 1 25. Participation in aninvestigational device study within 60 days prior to Day 1 26. Consumptionof prescription and over-the-counter medication (including topicalmedications), traditional Chinese medicine, or herbal medicine, vitamin,mineral, plant, and other dietary supplements within 14 days or 5half-lives, whichever is longer, prior to Day 1 and throughout the study
11. Consumption of liquids or foods containing grapefruit or cranberryfrom 7 days prior to Day 1 (Part A) or Check-in (Part B) and throughoutthe study 28. Consumption of any food containing poppy seeds from 48 hprior to Day 1 (Part A) or Check-in (Part B) and throughout the study 29.Donation of bone marrow or peripheral stem cells within 90 days prior toDay 1 or blood or plasma within 60 days prior to Day 1 30. Participationin strenuous exercise within 72 h prior to Day 1 (Part A) or Check-in (Part B) 31. Consumption of caffeine-containing substances within 72 hprior to Day 1 (Part A) or Check-in (Part B) 32. Occupation involving thehandling of ETEC, cholera, or Shigella bacteria 33. Occupation in foodhandling industry or care of: very young children (<2 years old), elderly (≥70 years) or immunocompromised 34. Any other criteria which, in theinvestigator's opinion, would compromise the safety of the study, theability of a subject to participate, or the results of the study