PROPRIETARY AND CONFIDENTIAL

Vaxchora®

Vaccine -

Pediatric 

Dose 

Development

James McCarty, MD

Clinical Professor of Pediatrics, Stanford University

Consultant, Emergent BioSolutions

12 January, 2022
PROPRIETARY AND CONFIDENTIAL

Vaxchora vaccine is comprised of two packets 

(sachets) that are reconstituted in 100 mL of water*

• Buffer Component packet:

• Contents: 4.5 g of white to off-white 

powder

• Active Component packet:

• Contents: 2.0 g of white to beige powder

• V. cholerae CVD 103-HgR 

attenuated vaccine strain

Vaxchora® (Cholera Vaccine, Live, Oral)

10Jan2022; VAX-US-00001 2

*For children under 6 years of age: following reconstitution of the buffer in 100 mL of water, discard half of the buffer solution prior to addition of the active component.

VAXCHORA [package insert]. Redwood City, CA: Emergent BioSolutions; December 2020
PROPRIETARY AND CONFIDENTIAL

Vaxchora Vaccine: Clinical Development Program

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Study Age Range Dose # Subjects*(Active) Objectives Results

Phase 1

0021

18 to 50 4.4 x 108 CFU 66 (55)

Safety

Immunogenicity

Kinetics (shedding)

Well-tolerated

SVA 88.9%(D14)

Stool+ 11% (throughD7)

Challenge 

Phase 3

0032

18 to 45 5 x 108 CFU 197 (95)

Efficacy (challenge)

Immunogenicity

SVA 79.8% (D8)

SVA 89.4% (D11)

Efficacy 90.3%(D11)

Efficacy 79.5% (D91)

Lot Consistency 

Phase 3

0043

18 to 45 1 x 109 CFU 3146 (2795)

Lot consistency

Safety

Immunogenicity

Met consistencycriteria

Well-tolerated

SVA: 93.5% (D11)

Older Adult 

Phase 3

0054

46 to 64 1 x 109 CFU 398 (299)

Safety

Immunogenicity

Bridging

Well-tolerated

SVA 90.4%(D11)

Non-inferior to 004

Pediatric

Phase 4

0065,6

2 to 17 1 x 109 CFU 550 (468)

Safety

Immunogenicity

Bridging

Well-tolerated

SVA 98.5%(D11)

Non-inferior to 004

*Placebo in the phase 1 trial was lactose powder in water. Placebo was physiological saline in all other trials. 

CFU=colony-forming unit; SVA=serum vibriocidal antibody

1. Chen WH, et al. Clin Vaccine Immunol. 2014;21(1):66-73. 2. Chen WH, et al. Clin Infect Dis. 2016;62(11):1329-1335. 3. McCarty JM, et al. Vaccine. 2018;36:833-840. 4. McCarty JM, et al. Vaccine. 2019;37:1389-1397. 5. McCarty JM, 

et al. Am J Trop Med Hyg. 2020;102(1):48-57. 6. McCarty JM, et al. Am J Trop Med Hyg. 2020;104(5):1758-1760.
PROPRIETARY AND CONFIDENTIAL

Vaxchora Vaccine Pediatric Development Goals:

• Use existing, approved Vaxchora vaccine formulation

• Adapt Vaxchora vaccine to children 2 to 6 years of age

• Reduce volume

• Flavor/mask taste

Pediatric Study: Dose Development

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PROPRIETARY AND CONFIDENTIAL

Vaxchora Vaccine Pediatric Study: Volume Reduction

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Reconstitution 

volume (mL) T=0 T=15 min

100 11.6 x 108 8.99 x 108

50 4.68 x 108 3.52 x 108

100 (Discard 50 mL) 5.49 x 108 5.30 x 108

Buffer reconstitution volume (mL) pH* Buffer capacity

(ml, 1M HCl)†

100 7.00 25.1

50 7.16 24.3

100 (50 mL discard) 7.02 12.2‡

*pH release specification: 6.7 – 7.1

†Buffer Capacity release specification: >21.0 mL 1M HCl neutralized

‡Buffer capacity is below specification. Children have smaller stomachs and 

higher gastric pH2

CFU=colony forming units

1. Data on file, Emergent BioSolutions Inc, Duffin P, 2020. 2. Nagita A, et al. Pediatr Res 1996;40(4):528-532.

Conclusions:

• Keep buffer concentration the same as approved formulation

• Vaxchora vaccine is stable when reconstituted in 50 mL of buffered water

Vaccine Potency Specification: 4 x 108to 2 x 109 CFU/Dose
PROPRIETARY AND CONFIDENTIAL

Vaxchora Vaccine: Key Steps for Pediatric Administration

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Empty buffer component 

packet contents into 100 mL 

of water and stir until 

completely dissolved

For children less than 6 years of 

age, discard half (50 mL) of the 

buffer solution

Empty active component 

packet contents into the cup 

and stir for 30 seconds.

If desired, sugar (sucrose) (4 

grams or 1 teaspoon) or stevia

(1 gram or 1⁄4 teaspoon) may be 

stirred into the suspension*

Vaxchora vaccine must be 

consumed within 15 minutes of 

reconstitution

*Proposed added step and language, to be 

reviewed by FDA

Data on file, Emergent BioSolutions Inc, Duffin P, 2020
PROPRIETARY AND CONFIDENTIAL

• Typical sugar (sucrose) packet contains 4g, typical Stevia packet contains 1g

• Stevia is much sweeter than sugar (sucrose), so ‘fillers’ (>95% by weight) are used 

to bulk stevia extract (<5%)

• Strategy: choose stevia brands that

• Are available worldwide

• Market is consolidated and dominated by a few major players including 

Cargill, Inc. (Truvia®) and Tate & Lyle (Splenda®)

• Contain the most commonly used ‘fillers’

• Most common ‘fillers’ by survey of popular brands: inulin, erythritol, 

maltodextrin, dextrose

Sugar (Sucrose) and Stevia Sweeteners

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Data on file, Emergent BioSolutions Inc, Duffin P, 2020
PROPRIETARY AND CONFIDENTIAL

• Study setup:

• 1g to 4g sweetener + 50ml reconstituted Vaxchora vaccine

• Potency tested at 0 and 15 minutes

• Vaxchora vaccine potency specification: 4 x 108to 2 x 109

CFU/dose

• Brands were chosen as representative of ‘stevia powder’ or ‘stevia 

crystals’

Sugar (Sucrose) and Stevia Studies

10Jan2022; VAX-US-00001 8

Sweetener

CFU/Dose Post Reconstitution 

(Min)

0 15

Sugar (Sucrose)

1g 7.3 x 108 6.0 x 108

4g 7.0 x 108 6.4 x 108

Stevia Brand (1g)

Pure Via®

4.9 x 108 4.3 x 108

12 x 108 11 x 108

5.6 x 108 5.6 x 108

Truvia® 7.1 x 108 6.3 x 108

Splenda® Naturals 7.1 x 108 6.0 x 108

SweetLeaf® 6.8 x 108 6.2 x 108

Sweet Additions® 7.5 x 108 6.3 x 108

Stevia Brand Filler

Pure Via® Dextrose

Sweet Additions® Maltodextrin

Truvia®, Splenda® Naturals Erythritol

SweetLeaf®Inulin

CFU=colony forming units

Data on file, Emergent BioSolutions Inc, Duffin P, 2020
PROPRIETARY AND CONFIDENTIAL

• Vaxchora is well tolerated and effective in children age 2 to 17 years

• Vaxchora vaccine is compatible with both sugar (sucrose) and stevia powder/crystals

• Vaxchora vaccine is compatible with

• ≥50 mL reconstitution volume

• Sugar (Sucrose) (4 g)

• Stevia (1 g)

• Tested brands that are available around the globe

• Tested most common stevia ‘fillers’: inulin, erythritol, maltodextrin, and dextrose

• Vaxchora vaccine should not be used with:

• Medicine flavorings (FLAVORx®, Yummy Meds®) due to the presence of propylene glycol

Conclusion

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Data on file, Emergent BioSolutions Inc, Duffin P, 2020
www.emergentbiosolutions.com
PROPRIETARY AND CONFIDENTIAL

50ml Pediatric Dose Reconstitution Study: Flavoring

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Category Material T0(CFU/dose) Feasible? Considerations

Flavoring Agents

Stevia (1g) 6.36 x 108 Yes FLAVORx® contains propylene glycol, is not compatible with CVD 103-

OTC medicine flavoring HgR 5.30 x 108 No

Baby Formula

Similac® 6.41 x 108 Maybe

Pro: High t0 potency, stays above potency limit for at least 30 minutes

Con: Complicated reconstitution process Gerber® 7.32 x 108 Maybe

Enfamil® 7.82 x 108 Maybe

Other Foods/ 

Drinks

Applesauce 6.41 x 108 No

Pro: High T0 potency, stays above potency limit for 30 minutes

Con: Excessive foaming/overflow when buffer added. Not suitable for 

the clinic.

Apple Juice 7.47 x 108 No

Rice Cereal 7.69 x 108 No

• Challenges with specific formulations:

– Baby formula: Buffer effervescence caused excessive foaming and sample overflowed unless buffer was added 

first.

– Foods and Drinks: Buffer effervescence caused excessive foaming and sample overflowed. Not suitable for the 

clinic.

CFU=colony forming units; OTC=over the counter.

Data on file, Emergent BioSolutions Inc, Duffin P, 2020.
PROPRIETARY AND CONFIDENTIAL

• Study setup:

• 1g to 4g sweetener + 50ml reconstituted Vaxchora vaccine

• Potency tested at 0 and 15 minutes

• Vaxchora vaccine potency specification: 4 x 108to 2 x 109 CFU/dose

• Brands were chosen as representative of ‘stevia powder’ or ‘stevia crystals’

Sugar (Sucrose) and Stevia Studies

10Jan2022; VAX-US-00001 12

Stevia Brand (1g)

CFU/Dose Post 

Reconstitution (Min)

0 15

Pure Via®

4.9 x 108 4.3 x 108

12 x 108 11 x 108

5.6 x 108 5.6 x 108

Truvia® 7.1 x 108 6.3 x 108

Splenda® Naturals 7.1 x 108 6.0 x 108

SweetLeaf® 6.8 x 108 6.2 x 108

Sweet Additions® 7.5 x 108 6.3 x 108

Sugar 

(sucrose)

CFU/Dose Post 

Reconstitution (Min)

0 15

1g 7.3 x 108 6.0 x 108

4g 7.0 x 108 6.4 x 108

Stevia Brand Filler

Pure Via® Dextrose

Sweet Additions® Maltodextrin

Truvia®, Splenda® Naturals Erythritol

SweetLeaf®Inulin

CFU=colony forming units

Data on file, Emergent BioSolutions Inc, Duffin P, 2020