1. MSRU, Allergy, Probiotics, Prebiotics…..

2. Medical Scientific and Regulatory Unit
Successful Transition to new IN Headquarters
One half Nestlé and one half Gerber legacy teams
Interdisciplinary approach… to help YOU

3. The “NEW” MSRU Heidi Storm Cheryl Callen Kathleen Novak
Melanie Fairchild
Lynn Bellote
Jillian Rado
Melanie Esock
Susan Eberhardt
Stacie Martinek
Heidi Storm
Kathleen Novak
Linda Hsieh
Pamela Cekola
Jami Boccella
Rachel Buchanan

4. Success in Infant Nutrition
Science
Education
Innovation

5. Innovation is “CLAIMS – BASED”

6. Medical Scientific & Regulatory Unit
Nestlé Nutrition, North America
What can
we claim
MSU
What we are allowed to claim
Who claims it with us & for us 6

7. Medical Scientific & Regulatory Unit
Nestlé Nutrition, North America
Medical & Scientific
Substantiation
What can
we claim
Supporting
Claims – Based Innovation
MSU
What we are allowed to claim
Who claims it with us & for us
Regulatory
Affairs
Professional
Relationships 7

8. Medical Scientific & Regulatory Unit
Nestlé Nutrition, North America
Medical & Scientific
Substantiation
What can
we claim
Supporting
Claims – Based Innovation
MSU
What we are allowed to claim
Who claims it with us & for us
Regulatory
Affairs
Professional
Relationships 8

10. Infant Formula Claim Territories
Growth
Digestion
Brain and eye Development

11. Infant Formula Claim Territories
Growth
Digestion
Brain and eye Development
Immunity

12. YOU Changed the game

13. Immunity : The new frontier
Abbott: Similac “Early Shield”
Prebiotics
Nucleotides
Lutein, Lycopene, Antioxidants
PBM
Formula with B. lactis
Mead Johnson
Nutramigen with LGG

14. Immunity : The new frontier
Abbott: Similac “Early Shield”
Prebiotics
Nucleotides
Lutein, Lycopene, Antioxidants
PBM
Formula with B. lactis
Mead Johnson
Nutramigen with LGG
FOLLOWERS

16. Allergy: State of Affairs

17. FACT
The use of certain hydrolyzed infant formulas, instead of intact cow protein formulas can reduce the incidence of atopic dermatitis in infants with a positive history of allergy

18. GINI 6

28. GINI 3: Cumulative Incidence of Atopic Dermatitis at 36 mos* * * *
The Key Point from the 3 year results from the GINI study: It indicated primary prevention of AD extended from 12 months to 36 months of life. * *
*p < 0.05 vs Intact Cow Milk
Von Berg et al., 2007 J Allergy Clin Immunol 119(3):

29. GINI 6: Cumulative Incidence of Atopic Dermatitis at 6 y* * * * *
The Key Point from the 3 year results from the GINI study: It indicated primary prevention of AD extended from 12 months to 36 months of life. *
*p < 0.05 vs Intact Cow Milk
Von Berg et al., 2007 J Allergy Clin Immunol 119(3):

30. GINI 1: Risk of AD at 12 Mos – Odds Ratio
1.0
0.81
19% risk reduction vs. CMF
CI ( ) *
0.56
44% risk reduction vs. CMF
CI ( )
The Key Points from GINI 1 were that it was the largest infant formula study that was double-blinded, prospective, and randomized --looking at infant nutrition and incidence of AD in the 1st year of life. The results were quite compelling. A 100% whey, phF used instead of a standard whole-protein formula, offers significant protection against allergic disease such as AD.
0.42 *
58% risk reduction vs. CMF
CI ( )
*p < 0.05 vs Intact Cow Milk
Von Berg et al., 2003 J Allergy Clin Immunol 111(3):

31. GINI 6: Risk of AD at 6 Years – Odds Ratio
1.0
0.64
0.55
36% risk reduction vs CMF
45% risk reduction vs CMF
0.74
26% risk reduction vs CMF
CI ( )
CI ( )
CI ( ) * * *
Key Points from the GINI 6 include: The intent to treat analysis was based on all 2,252 infants, and per protocol analysis was based on all 988 infants fed the fully or partially hydrolyzed study formulas that were compliant with the feeding recommendations. In the first 4 months of life, which was considered the study’s “strict intervention period”. Of the 988 infants included in the per protocol analysis at year 6, 39% (384) were diagnosed with an allergic manifestation and 26% (253) were diagnosed with atopic dermatitis.Significant risk reduction from birth to 6 years for atopic dermatitis: pHF-W (36%) and eHF-C (45%); all allergic manifestations: pHF-W (25%) and eHF-C (33%).
Extensively hydrolyzed whey formula (eHF-W) did not have an effect up to 3 years of age; however it did start to show an effect at 6 years of age with a risk reduction of 22% on all allergic manifestations and 26% risk reduction of AD. *
*p < 0.05 vs Intact Cow Milk
Von Berg et al., 2008 J Allergy Clin Immunol 121(6):

32. Summary
“…there is modest evidence that atopic dermatitis may be delayed or prevented by the use of extensively or partially hydrolyzed formulas, compared with cow milk formulas, in early childhood.”
“Comparative studies of the various hydrolyzed formulas have also indicated that not all formulas have the same protective benefit. Extensively hydrolyzed may be more effective than partially hydrolyzed in the prevention of atopic disease…The higher cost of hydrolyzed formulas must be considered in any decision-making process for their use.”
In January of 2008 the AAP published a Clinical Report focusing on allergy risk reduction. Though not a position statement, this clinical report replaces any previous positions and reports done by the Academy on allergy risk reduction.
Pediatrics 2008;121:

33. Role of Formula
“While some studies show a slightly more protective effect of certain extensively hydrolyzed formulas as compared to partially hydrolyzed whey-based formula, the clinical relevance of this small difference is uncertain at this time.”
Conclusion
“In summary, …for families with an infant at risk for atopic disease, exclusive breastfeeding for at least four months or the use of particular extensively or partially hydrolyzed infant formulas may prevent or delay several atopic diseases, when compared to using a whole cow’s milk or soy based formula.”
The same authors then published a shorter article based on the report in AAP News, also in January. The AAP News article actually uses more favorable language regarding partially hydrolyzed formulas and allergy risk reduction.
NESTLÉ® GOOD START® is the only partially hydrolyzed, 100% whey formula currently available in the US.
AAP News 2008;29:12

34. AAP Nutrition Handbook:
Countrywide
11/15/2018 8:49 AM
AAP Nutrition Handbook:
States that partially hydrolyzed formulas may reduce the risk of allergy really is “controversial.”
Handbook is five years behind on data
It does not include: GINI 3, 6, or the AAP Clinical Report on allergy risk reduction
We have VERY strong evidence from numerous clinical trials and now GINI 6 year results from the largest pediatric allergy prevention study ever done that our 100% whey, partially hydrolyzed formula does reduce the risk of allergy.
Again, the AAP can not endorse a product, so favoring a “100% whey, partially hydrolyzed formula” would be unethical since we are the only one on the market.
Review the curds picture and discuss the fact that bovine whey does not form the large, hard curds that bovine casein does. Review the protein quality piece pointing out that on every measure bovine whey is scores higher than bovine casein.
Also, point out that both cow’s milk casein and whey are highly antigenic to a newborn with an immature immune system. That is exactly why we hydrolyze the protein.
CMD 34

35. Allergy Claim Update
FDA denied a claim (food allergy), that was not petitioned, instead of claim on atopic dermatitis risk reduction
Ongoing discussion with FDA
Agreement on new filing with right to withdrawal
Filing expected early this year

37. Prebiotics & Probiotics
The are the Pre….
we are the PROS

40. Prebiotic vs Probiotic Safety and Efficacy Misconceptions
“Prebiotics are safer than probiotics”
“Prebiotics support the infant’s natural flora, and are better than probiotics”
“Prebiotics work by increasing the infants native probiotics”
“Prebiotics have less side effects because they are not live bacteria”

41. Prebiotic vs Probiotic Safety and Efficacy Misconceptions
“Prebiotics” are many types of oligosaccharides- and similar to probiotics each one needs to be studied independently for safety and efficacy
There is no parameters to indicate bovine galacto oligosaccharides have the same effect or are similarly tolerated than human oligosaccharides
Prebiotics are not food for probiotics (ingested bacteria); they are food for colonic (not ingested) bacteria

42. Prebiotic vs Probiotic Safety and Efficacy Misconceptions
Prebiotics: preferentially fermented by bifidobacteria already present in the colon; but also serve as substrate to other species
Prebiotic effects on flora are less predictable in modulating colonic flora than providing a specific known probiotic

43. Prebiotic vs Probiotic Safety and Efficacy Misconceptions
Prebiotic fibers work by being fermented and produce gas, water and acid, in the colon and can lead to dose-dependent intolerance (as with any non-absorbed carbohydrate)
Probiotics have no dose-dependent adverse effects

44. Prebiotic vs Probiotic Safety and Efficacy Misconceptions
Prebiotics stimulate colonic bacteria; but do not have the benefit of reverting the problems associated to “sterile environments and sterile diets” leading to poor protection and immune related conditions
Prebiotics do not take the “hygiene” out of the “hypothesis”
Certain probiotics shorten the course of rotavirus diarrhea. Non absorbed carbohydrates (prebiotics) may increase intolerance in acute diarrhea.

45. Prebiotic vs Probiotic Safety and Efficacy Misconceptions
Human Milk:
More than 130 different types of oligosaccharides
All complex, with multiple types of sugars
Early Shield:
One type of oligosaccharide
Rarely found in human milk, in trace amounts

46. Exclusive Breast Feeding Means EXCLUSIVE Breast Feeding
(basically –to prevent the problems associated with not breastfeeding)
If a partially hydrolyzed, 100% whey infant formula is given from the beginning, we can reduce the risk of developing atopic manifestations like atopic dermatitis.
Nutritional intervention with hydrolyzed infant formulas in the first 4 months of life has a long-lasting primary-preventive effect on atopic dermatitis in high-risk children. We can now see that there is not just a delay in the appearance of allergy, but that hydrolyzed formulas can truly reduce the risk of ever developing them.
The relative risk of AD up to 6 years is significantly reduced in partially hydrolyzed whey formula (pHF-W) (36%), extensively hydrolyzed whey formula (eHF-W) (26%) and extensively hydrolyzed casein (eHF-C) (45%) groups
“The data of the 6-year follow-up of the GINI study confirm a persistent preventive effect of eHF-C and pHF-W on AM and AD” (p. 1446, 2nd column, last paragraph)
The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.” (p. 1442,Abstract, Conclusion)
GOOD START uses 100% whey for its protein source and applies a unique [patented-delete b/c we are no longer patented] partial hydrolysis process to break the whey protein down into smaller peptides to help reduce allergic risk vs. intact cow’s milk whey and casein protein formula.
Cow casein-free to facilitate easy digestion.
Faster gastric emptying may help reduce the potential for reflux and spitting up.
Promotes soft stools similar to those of the breastfed infant.
DHA and ARA are at levels shown to support visual and cognitive development
Good Start formulas support healthy growth and development and are approved by the FDA.
When discussing Good Start benefits, we must be mindful that breast milk is the gold standard for growth and development, avoidance of allergy and digestive tolerance. We are simply trying to prevent the problems that may be associated with not breastfeeding

50. November 15, 2018
GINI – 3 year results
November 15, 2018

51. November 15, 2018
Abstract
November 15, 2018

52. November 15, 2018
GINI – 3 year results
November 15, 2018

53. November 15, 2018
Abstract
November 15, 2018

54. Population studied Example: Intent to Treat (ITT) vs
November 15, 2018
Population studied
Example:
Intent to Treat (ITT) vs
Per protocol (PP) analysis
for all groups
1172 got some formula +
191 early dropout = 1363
ITT:
Cumulative incidence of AD at 3 y=
206 / 1363 = 15% PP
206 / 904 = 22%
November 15, 2018

55. Intent to treat (ITT) results
November 15, 2018
Intent to treat (ITT) results
November 15, 2018

56. Cumulative incidence results
November 15, 2018
Cumulative incidence results
November 15, 2018

57. Per protocol (PP) analysis
November 15, 2018
Per protocol (PP) analysis
November 15, 2018

58. Results & Family hx of Atopic dermatitis
November 15, 2018
Results & Family hx of Atopic dermatitis
November 15, 2018

59. Discussion highlights
November 15, 2018
Discussion highlights
November 15, 2018

60. Discussion highlights
November 15, 2018
Discussion highlights
November 15, 2018

61. Discussion highlights
November 15, 2018
Discussion highlights
November 15, 2018

69. Branded Allergy Leave Behind
Purpose
To Persuade healthcare professionals to recommend Nestle GOOD START Gentle Plus when formula is initiated for primary prevention of allergic manifestations.
Educate them on the latest research findings on allergy prevention, including GINI I, 3 and 6.
(basically –to prevent the problems associated with not breastfeeding)
If a partially hydrolyzed, 100% whey infant formula is given from the beginning, we can reduce the risk of developing atopic manifestations like atopic dermatitis.
Nutritional intervention with hydrolyzed infant formulas in the first 4 months of life has a long-lasting primary-preventive effect on atopic dermatitis in high-risk children. We can now see that there is not just a delay in the appearance of allergy, but that hydrolyzed formulas can truly reduce the risk of ever developing them.
The relative risk of AD up to 6 years is significantly reduced in partially hydrolyzed whey formula (pHF-W) (36%), extensively hydrolyzed whey formula (eHF-W) (26%) and extensively hydrolyzed casein (eHF-C) (45%) groups
“The data of the 6-year follow-up of the GINI study confirm a persistent preventive effect of eHF-C and pHF-W on AM and AD” (p. 1446, 2nd column, last paragraph)
The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.” (p. 1442,Abstract, Conclusion)
GOOD START uses 100% whey for its protein source and applies a unique [patented-delete b/c we are no longer patented] partial hydrolysis process to break the whey protein down into smaller peptides to help reduce allergic risk vs. intact cow’s milk whey and casein protein formula.
Cow casein-free to facilitate easy digestion.
Faster gastric emptying may help reduce the potential for reflux and spitting up.
Promotes soft stools similar to those of the breastfed infant.
DHA and ARA are at levels shown to support visual and cognitive development
Good Start formulas support healthy growth and development and are approved by the FDA.
When discussing Good Start benefits, we must be mindful that breast milk is the gold standard for growth and development, avoidance of allergy and digestive tolerance. We are simply trying to prevent the problems that may be associated with not breastfeeding

70. The GINI Timeline: A History of Clinical Efficacy
2008
Jan AAP: GINI citation in AAP Clinical Report
GINI 6: 6-year follow-up, 36% RR in AD in pHF-W. “Data confirms a long-term, allergy-prevention effect…”
2007
GINI 3: 3-year follow-up to GINI % RR using pHF-W for AD. Demonstrates real disease reduction
Today
INR Sales Force Grows! Speaker Programs spread the clinical message to HealthCare Professionals
2003
GINI 1: Largest Independent study conducted with focus on allergy reduction. INRs begin communicating a 44% RR in AD using pHF-W to MDs
2003 was an exciting time for INRs. The German Infant Nutritional Intervention Study was published in The Journal of Allergy and Clinical Immunology. We were able to bring a stronger clinical message and move from the “protein sensitization” discussion to “risk reduction of allergy manifestation”. Pediatricians responded positively to a study that was an independent, prospective, double-blind RCT. At the same time, the message was further validated by Osborn, et. al., 2003 published by The Cochrane Library.
In 2004, the INR sales force was expanded and MSU began to develop the Speakers Bureau. Speakers presented “ Pediatric Allergy: Prevalence and Prevention”. Later, a DVD featuring several presentations with Dr.Yinka Davies and Lynn Mattis, Clinical Nurse Specialist, was developed. This allowed INRs to bring an abbreviated allergy presentation discussing the GINI findings into the clinic or hospital setting. Again, the message was more powerful for physicians and nurses when presented by their peer group.
In 2007, GINI 3 was published, demonstrating that feeding a hydrolyzed formula vs intact cow milk formula in the first 4 months of age does have significant impact on the presence of allergic disease at 3 years of age. The preventive effect observed in the first year persisted into the 3rd year. This provided validation and continued to help tell the story of the benefit of feeding Good Start as a routine starter formula or supplement to BF.
In January of 2008, the American Academy of Pediatrics published the Clinical Report “Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants & Children: The Role of Maternal Dietary Restriction, Breastfeeding, Timing of Introduction of Solid Foods, and Hydrolyzed Formulas”. While not a strong endorsement of the role of
pHF-W in risk reduction of allergy, stronger verbiage was used, stating “modest evidence” of allergy risk reduction with hydrolyzed formulas. This report and the corresponding AAP News report provided additional talking points and validation on the subject.
Most recently, GINI 6 was published in True risk reduction of AD in the first 6 years of life in infants with a familial risk for atopy is possible when feeding a pHF-W in place of CMF. It is important to note that the studies – which were follow-up studies to the original study design – showed long-lasting primary-preventive effects. All were published in the Journal of Allergy and Clniical Immunology.
And the story continues….

71. Population studied Example: Intent to Treat (ITT) vs
November 15, 2018
Population studied
Example:
Intent to Treat (ITT) vs
Per protocol (PP) analysis
for all groups
1172 got some formula +
191 early dropout = 1363
ITT:
Cumulative incidence of AD at 3 y=
206 / 1363 = 15% PP
206 / 904 = 22%
November 15, 2018

72. Intent to treat (ITT) results
November 15, 2018
Intent to treat (ITT) results
November 15, 2018

73. Cumulative incidence results
November 15, 2018
Cumulative incidence results
November 15, 2018

74. Per protocol (PP) analysis
November 15, 2018
Per protocol (PP) analysis
November 15, 2018

75. Results & Family hx of Atopic dermatitis
November 15, 2018
Results & Family hx of Atopic dermatitis
November 15, 2018

76. Discussion highlights
November 15, 2018
Discussion highlights
November 15, 2018

77. Discussion highlights
November 15, 2018
Discussion highlights
November 15, 2018

78. Discussion highlights
November 15, 2018
Discussion highlights
November 15, 2018