©2015 Bayer HealthCare LLC, Animal Health, Shawnee Mission, Kansas 66201Bayer (reg’d), the Bayer Cross (reg’d), Baytril®, Zelnate™ and It’s not an

antibiotic. It’s not a vaccine. It’s Zelnate.™ are trademarks of Bayer.Micotil is a registered trademark of Eli Lily and Company. Advocin and Draxxin are registered trademarks of Zoetis.

ZNT151087

The goal of this study was to evaluate the efficacy

of Zelnate™ DNA Immunostimulant versus a

currently approved antibiotic, Micotil® (tilmicosin)

Injection, when administered to feedlot cattle at

medium risk of developing BRD. A head-to-head

study was conducted and effects were measured

over 56 days.1

Gilcrest Feedlot (JBS) in eastern Colorado.

AnimalsA total of 2,004 cattle were enrolled in the study.

Enrolled calves were classified as being at medium

risk of BRD, as defined by: heavy weight, ranch/

farm origin (5 Montana and 4 South Dakota

ranches), and relatively short transport distances.

Inclusion criteria required that each calf

present with a BRD score ≤ 1 (as defined in

Study Procedures — see page 2) at the time of

enrollment. Otherwise, all enrolled calves were

in good health with no complicating injuries

at enrollment.

Eligible animals were randomly assigned to two

treatment groups: Group 1 received Micotil

(n=1,002), and Group 2 received Zelnate (n=1,002).

Bodyweight was collected on Day 1, with Group 1

(Micotil) weighing an average of 591 lbs and

Group 2 (Zelnate) weighing an average of

589.4 lbs. All cattle were given access to standard

feedlot rations and free-choice water.

Objective

Study Location

A Clinical Efficacy Study of Versus Micotil® (tilmicosin) Injection for the Treatment of Bovine Respiratory Disease in Medium-Risk Cattle.

For Intramuscular Administration to Cattle

FOR VETERINARY USE ONLY

DNA Immunostimulant

02293

READ IN FULL

DESCRIPTION

ZELNATE™ is a bacterial-produced plasmid DNA with a liposome carrier that stimulates the innate immune system in cattle. The innate immune system has been shown to provide a potent, rapid, nonspecific, protective response to infectious agents, such as those that can lead to Bovine Respiratory Disease (BRD). BRD is a serious condition that commonly causes lung lesions, reduced lung capacity and mortality.

The freeze-dried (desiccate) product is packaged with two different sterile diluents. The First Sterile Rehydrator (vial 1) is used to reconstitute the desiccate cake (vial 2), and then transferred to the Final Sterile Solution (vial 3) to achieve the proper concentration for administration.

INDICATION

ZELNATE™ is indicated for use as an aid in the treatment of Bovine Respiratory Disease due to Mannheimia haemolytica in cattle 4 months of age or older, when administered at the time of, or within 24 hours after, a perceived stressful event.

IMPORTANT STORAGE CONDITIONS

Store Refrigerated 2°C to 8°C (35°F to 46°F) DO NOT FREEZE.

STUDY DATA

In Study A, 3- to 4-month-old steers were randomly allocated to receive either ZELNATE™ or a negative control (N=32 per group). On Day 0, each group of healthy calves was intramuscularly administered their respective treatment and challenged (intratracheally) with Mannheimia haemolytica. Lung lesion scores were obtained on Day 5. ZELNATE™ significantly (p<0.05) reduced lung lesion scores compared to the control group (Figure A).1

In Study B, 3- to 4-month-old steers were randomly allocated to receive either ZELNATE™ or a negative control (N=40 per group). On Day 0, each group was challenged (intratracheally) with Mannheimia haemolytica. Twenty four hours post-challenge (i.e., Day 1), BRD morbidity was observed to be 67.5%. At this time, each group was intramuscularly administered their respective treatment (i.e., in the face of clinical BRD). Lung lesion scores were obtained on Day 5. Among calves that lived until Day 5, ZELNATE™ numerically reduced lung lesion scores compared to the control group (data not shown). The cumulative incidence of death, associated with BRD, was 11.3%. The lung lesion scores among dead calves and those living to Day 5 were observed to be 55.3% and 17.6%, respectively. ZELNATE™ significantly (p<0.05) reduced mortality compared to the control group (Figure B).2

MANUFACTURED BY: Diamond Animal Health, Inc. Des Moines, IA 50237U.S. Veterinary License No. 213Made in U.S.A.

DISTRIBUTED BY: Bayer HealthCare LLC, Animal Health Division P.O. Box 390Shawnee Mission, KS66201 U.S.A.1-800-633-3796

This product is based on technology developed by Juvaris BioTherapeutics and is patent protected. Animal health applications are being exclusively developed by Bayer HealthCare Animal Health and are protected by Bayer patent applications.

©2014 Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas 66201 U.S.A.

Bayer (reg’d), the Bayer Cross (reg’d) and ZELNATE™ are trademarks of Bayer. 52405B

In conclusion, ZELNATE™, as a stand-alone therapy, has been shown to: 1) significantly reduce lung lesion scores associated with BRD when administered in the face of disease challenge (Study A), and 2) significantly reduce the risk of mortality when administered in the face of clinical BRD (Study B).1Data on file. Bayer HealthCare Animal Health.2Data on file. Bayer HealthCare Animal Health.

Figure A: Average lung lesion scores between calves receiving either ZELNATE™ or a negative control at the same time as an intratracheal Mannheimia haemolytica challenge. Lung lesion scores reflect those observed on Day 5 post-challenge.

Figure B: Cumulative incidence of mortality between calves receiving either ZELNATE™ or a negative control 24 hours after an intratracheal Mannheimia haemolytica challenge. Mortality estimates reflect those observed from the Day of challenge (Day 0) to Day 5 post-challenge.

* = statistically significant reduction (p<0.05)

83944706, R.0 83944722, R.0 83944730, R.0

METHOD OF ADMINISTRATIONInject 2 mL intramuscularly at the time of, or within 24 hours after, a perceived stressful event (for example: weaning, shipping, commingling or adverse environmental conditions). Use entire contents of vial once first opened.

PRECAUTIONDo not administer within 21 days of slaughter.

OTHER INFORMATIONContains no antibiotics and no preservatives. ZELNATE™ has shown no detectable lesions at the site of intramuscular injection.

HOW SUPPLIED Vials of 5, 10 and 50 doses.

2 31Mixing process must be completed in the appropriate order. Transfer needle must be fully inserted to prevent spillage.  

1Data on file. Bayer HealthCare Animal Health.

Zelnate.com

Calves at medium risk of developing BRD that

were administered Zelnate performed in a

comparable manner to those that received

Micotil. There were no statistical differences

between treatment groups across all clinical and

performance parameters as shown in the chart

on this page. In this study, the performance of

Zelnate was similar to Micotil.

On Day 1, all enrolled calves received an MLV

5-way vaccine, deworming agent, steroid implant

and 7-way clostridial vaccine along with their

assigned treatment:

Over the next 56 days, calves were assessed

daily to ensure proper animal husbandry and

for non-BRD related issues. For three days,

each animal was not evaluated for BRD, allowing

time for the respective treatments to work.

Following the three-day moratorium period,

calves were assessed for BRD daily according

to BRD scoring criteria.

■ BRD score of 0 = Clinically normal

■ BRD score of 1 = Mild BRD that includes

Study ProceduresSummary of clinical efficacy study

Results

Parameter Micotil Group

Zelnate Group P-value

BRD morbidity 7.65% 13.84%Non-inferior (confidence

interval of delta within -10%)

Time to BRD Dx 28.1 days 22.6 days <0.0001

BRD repulls 17.90% 11.10% 0.5929

BRD chronicity 27.90% 29.10% 0.9942

Overall BRD mortality 0.44% 0.50% 0.7643

BRD case-fatality 3.95% 2.99% 0.7287

ADG 2.96 lbs 2.91 lbs 0.6759

DMI 12.96 lbs 12.81 lbs 0.3768

Feed:Gain 4.50 4.55 0.7302

See product label for complete product information, indications and application instructions.

one or more of the following signs:

• Elevated respiratory rate for the

environmental conditions

• Serous or mucoid nasal discharge

• Mild to moderate gauntness

■ BRD score of 2 = Moderate BRD that

includes one or more of the

following signs:

• Mild or moderate depression

• Mild to moderate muscle weakness

• Moderate to extreme gauntness

• Dyspnea

■ BRD score of 3 = Severe BRD that includes

one or more of the following signs:

• Severe dyspnea that may include open-

mouth breathing

• Severe depression

■ BRD score of 4 = Moribund

A calf was defined as having BRD if it met one of

the following sets of criteria:

• A BRD score = 1 or 2 with a rectal

temperature ≥ 104°F, or

• A BRD score = 3, regardless of rectal temperature

Throughout the study, three BRD diagnoses were

allowed per calf. After each pull, a different BRD

therapy was administered to calves that met the

criteria for BRD diagnosis: Draxxin® (tulathromycin)

Injectable Solution at first pull, Baytril® 100

(enrofloxacin) Injectable at second pull and

Advocin® (danofloxacin injection) at third pull.

After the third pull, a calf was determined to have

“chronic” BRD and no further antimicrobial

therapy was provided. Bodyweights were obtained

on dead calves.

On Day 56, final bodyweight measurements of

remaining calves were taken for use in the

calculation of various performance parameters.

Micotil Group: 2 mL/100 lbs subcutaneous (SC) injection

(n=1,002) Avg. 591 lbs

Zelnate Group: 2 mL/animal intramuscular (IM) injection

(n=1,002) Avg. 589.4 lbs

Zelnate.com

Calves at medium risk of developing BRD that

were administered Zelnate performed in a

comparable manner to those that received

Micotil. There were no statistical differences

between treatment groups across all clinical and

performance parameters as shown in the chart

on this page. In this study, the performance of

Zelnate was similar to Micotil.

On Day 1, all enrolled calves received an MLV

5-way vaccine, deworming agent, steroid implant

and 7-way clostridial vaccine along with their

assigned treatment:

Over the next 56 days, calves were assessed

daily to ensure proper animal husbandry and

for non-BRD related issues. For three days,

each animal was not evaluated for BRD, allowing

time for the respective treatments to work.

Following the three-day moratorium period,

calves were assessed for BRD daily according

to BRD scoring criteria.

■ BRD score of 0 = Clinically normal

■ BRD score of 1 = Mild BRD that includes

Study ProceduresSummary of clinical efficacy study

Results

Parameter Micotil Group

Zelnate Group P-value

BRD morbidity 7.65% 13.84%Non-inferior (confidence

interval of delta within -10%)

Time to BRD Dx 28.1 days 22.6 days <0.0001

BRD repulls 17.90% 11.10% 0.5929

BRD chronicity 27.90% 29.10% 0.9942

Overall BRD mortality 0.44% 0.50% 0.7643

BRD case-fatality 3.95% 2.99% 0.7287

ADG 2.96 lbs 2.91 lbs 0.6759

DMI 12.96 lbs 12.81 lbs 0.3768

Feed:Gain 4.50 4.55 0.7302

See product label for complete product information, indications and application instructions.

one or more of the following signs:

• Elevated respiratory rate for the

environmental conditions

• Serous or mucoid nasal discharge

• Mild to moderate gauntness

■ BRD score of 2 = Moderate BRD that

includes one or more of the

following signs:

• Mild or moderate depression

• Mild to moderate muscle weakness

• Moderate to extreme gauntness

• Dyspnea

■ BRD score of 3 = Severe BRD that includes

one or more of the following signs:

• Severe dyspnea that may include open-

mouth breathing

• Severe depression

■ BRD score of 4 = Moribund

A calf was defined as having BRD if it met one of

the following sets of criteria:

• A BRD score = 1 or 2 with a rectal

temperature ≥ 104°F, or

• A BRD score = 3, regardless of rectal temperature

Throughout the study, three BRD diagnoses were

allowed per calf. After each pull, a different BRD

therapy was administered to calves that met the

criteria for BRD diagnosis: Draxxin® (tulathromycin)

Injectable Solution at first pull, Baytril® 100

(enrofloxacin) Injectable at second pull and

Advocin® (danofloxacin injection) at third pull.

After the third pull, a calf was determined to have

“chronic” BRD and no further antimicrobial

therapy was provided. Bodyweights were obtained

on dead calves.

On Day 56, final bodyweight measurements of

remaining calves were taken for use in the

calculation of various performance parameters.

Micotil Group: 2 mL/100 lbs subcutaneous (SC) injection

(n=1,002) Avg. 591 lbs

Zelnate Group: 2 mL/animal intramuscular (IM) injection

(n=1,002) Avg. 589.4 lbs

©2015 Bayer HealthCare LLC, Animal Health, Shawnee Mission, Kansas 66201Bayer (reg’d), the Bayer Cross (reg’d), Baytril®, Zelnate™ and It’s not an

antibiotic. It’s not a vaccine. It’s Zelnate.™ are trademarks of Bayer.Micotil is a registered trademark of Eli Lily and Company. Advocin and Draxxin are registered trademarks of Zoetis.

ZNT151087

The goal of this study was to evaluate the efficacy

of Zelnate™ DNA Immunostimulant versus a

currently approved antibiotic, Micotil® (tilmicosin)

Injection, when administered to feedlot cattle at

medium risk of developing BRD. A head-to-head

study was conducted and effects were measured

over 56 days.1

Gilcrest Feedlot (JBS) in eastern Colorado.

AnimalsA total of 2,004 cattle were enrolled in the study.

Enrolled calves were classified as being at medium

risk of BRD, as defined by: heavy weight, ranch/

farm origin (5 Montana and 4 South Dakota

ranches), and relatively short transport distances.

Inclusion criteria required that each calf

present with a BRD score ≤ 1 (as defined in

Study Procedures — see page 2) at the time of

enrollment. Otherwise, all enrolled calves were

in good health with no complicating injuries

at enrollment.

Eligible animals were randomly assigned to two

treatment groups: Group 1 received Micotil

(n=1,002), and Group 2 received Zelnate (n=1,002).

Bodyweight was collected on Day 1, with Group 1

(Micotil) weighing an average of 591 lbs and

Group 2 (Zelnate) weighing an average of

589.4 lbs. All cattle were given access to standard

feedlot rations and free-choice water.

Objective

Study Location

A Clinical Efficacy Study of Versus Micotil® (tilmicosin) Injection for the Treatment of Bovine Respiratory Disease in Medium-Risk Cattle.

For Intramuscular Administration to Cattle

FOR VETERINARY USE ONLY

DNA Immunostimulant

02293

READ IN FULL

DESCRIPTION

ZELNATE™ is a bacterial-produced plasmid DNA with a liposome carrier that stimulates the innate immune system in cattle. The innate immune system has been shown to provide a potent, rapid, nonspecific, protective response to infectious agents, such as those that can lead to Bovine Respiratory Disease (BRD). BRD is a serious condition that commonly causes lung lesions, reduced lung capacity and mortality.

The freeze-dried (desiccate) product is packaged with two different sterile diluents. The First Sterile Rehydrator (vial 1) is used to reconstitute the desiccate cake (vial 2), and then transferred to the Final Sterile Solution (vial 3) to achieve the proper concentration for administration.

INDICATION

ZELNATE™ is indicated for use as an aid in the treatment of Bovine Respiratory Disease due to Mannheimia haemolytica in cattle 4 months of age or older, when administered at the time of, or within 24 hours after, a perceived stressful event.

IMPORTANT STORAGE CONDITIONS

Store Refrigerated 2°C to 8°C (35°F to 46°F) DO NOT FREEZE.

STUDY DATA

In Study A, 3- to 4-month-old steers were randomly allocated to receive either ZELNATE™ or a negative control (N=32 per group). On Day 0, each group of healthy calves was intramuscularly administered their respective treatment and challenged (intratracheally) with Mannheimia haemolytica. Lung lesion scores were obtained on Day 5. ZELNATE™ significantly (p<0.05) reduced lung lesion scores compared to the control group (Figure A).1

In Study B, 3- to 4-month-old steers were randomly allocated to receive either ZELNATE™ or a negative control (N=40 per group). On Day 0, each group was challenged (intratracheally) with Mannheimia haemolytica. Twenty four hours post-challenge (i.e., Day 1), BRD morbidity was observed to be 67.5%. At this time, each group was intramuscularly administered their respective treatment (i.e., in the face of clinical BRD). Lung lesion scores were obtained on Day 5. Among calves that lived until Day 5, ZELNATE™ numerically reduced lung lesion scores compared to the control group (data not shown). The cumulative incidence of death, associated with BRD, was 11.3%. The lung lesion scores among dead calves and those living to Day 5 were observed to be 55.3% and 17.6%, respectively. ZELNATE™ significantly (p<0.05) reduced mortality compared to the control group (Figure B).2

MANUFACTURED BY: Diamond Animal Health, Inc. Des Moines, IA 50237U.S. Veterinary License No. 213Made in U.S.A.

DISTRIBUTED BY: Bayer HealthCare LLC, Animal Health Division P.O. Box 390Shawnee Mission, KS66201 U.S.A.1-800-633-3796

This product is based on technology developed by Juvaris BioTherapeutics and is patent protected. Animal health applications are being exclusively developed by Bayer HealthCare Animal Health and are protected by Bayer patent applications.

©2014 Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas 66201 U.S.A.

Bayer (reg’d), the Bayer Cross (reg’d) and ZELNATE™ are trademarks of Bayer. 52405B

In conclusion, ZELNATE™, as a stand-alone therapy, has been shown to: 1) significantly reduce lung lesion scores associated with BRD when administered in the face of disease challenge (Study A), and 2) significantly reduce the risk of mortality when administered in the face of clinical BRD (Study B).1Data on file. Bayer HealthCare Animal Health.2Data on file. Bayer HealthCare Animal Health.

Figure A: Average lung lesion scores between calves receiving either ZELNATE™ or a negative control at the same time as an intratracheal Mannheimia haemolytica challenge. Lung lesion scores reflect those observed on Day 5 post-challenge.

Figure B: Cumulative incidence of mortality between calves receiving either ZELNATE™ or a negative control 24 hours after an intratracheal Mannheimia haemolytica challenge. Mortality estimates reflect those observed from the Day of challenge (Day 0) to Day 5 post-challenge.

* = statistically significant reduction (p<0.05)

83944706, R.0 83944722, R.0 83944730, R.0

METHOD OF ADMINISTRATIONInject 2 mL intramuscularly at the time of, or within 24 hours after, a perceived stressful event (for example: weaning, shipping, commingling or adverse environmental conditions). Use entire contents of vial once first opened.

PRECAUTIONDo not administer within 21 days of slaughter.

OTHER INFORMATIONContains no antibiotics and no preservatives. ZELNATE™ has shown no detectable lesions at the site of intramuscular injection.

HOW SUPPLIED Vials of 5, 10 and 50 doses.

2 31Mixing process must be completed in the appropriate order. Transfer needle must be fully inserted to prevent spillage.  

1Data on file. Bayer HealthCare Animal Health.