Pioneering Development in the Gut Microbiome

(NASDAQ: RTTR)

Corporate Presentation: November 2016

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This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, adopted pursuant to the Private Securities Litigation Reform Act of 1995. Statements other than statements of historical fact contained in this presentation, including statements regarding strategy, future operations, future financial position, future revenue, projected costs, prospects, plans, objectives of management and expected market growth are forward-looking statements. The words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward- looking statements, although not all forward-looking statements contain these identifying words.

 

Forward-looking statements involve known and unknown risks, uncertainties and other important factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to: our ability to obtain additional financing; our use of the net proceeds from our initial public offering; the accuracy of our estimates regarding expenses, future revenues and capital requirements; the success and timing of our preclinical studies and clinical trials; our ability to obtain and maintain regulatory approval of RP-G28 and any other product candidates we may develop, and the labeling under any approval we may obtain; regulatory developments in the United States and other countries; the performance of third-party manufacturers; our plans to develop and commercialize our product candidates; our ability to obtain and maintain intellectual property protection for our product candidates; the successful development of our sales and marketing capabilities; the potential markets for our product candidates and our ability to serve those markets; the rate and degree of market acceptance of any future products; the success of competing drugs that are or become available; and the loss of key scientific or management personnel. For a discussion of these and other factors that could cause actual results to differ from those contemplated in the forward-looking statements, please see the discussion under ‘‘Risk Factors’’ and other information contained in our Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2016 and in our publicly available filings with the Securities and Exchange Commission.

 

The forward-looking statements in this presentation represent our views as of the date of this presentation. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make, so you should not place undue reliance on our forward-looking statements. We do not undertake any responsibility to update or revise any of these factors or to announce publicly any revisions to forward-looking statements, whether as a result of new information, future events or otherwise.

This presentation may contain references to our trademark and to trademarks belonging to other entities. Solely for convenience, trademarks and trade names referred to in this presentation, including logos, artwork and other visual displays, may appear without the ® or TM symbols, but such references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. We do not intend our use or display of other companies’ trade names or trademarks to imply a relationship with, or endorsement or sponsorship of us by, any other company.

Forward-LookingStatement

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FinancialSnapshot–NASDAQ:RTTR

*As of November 1, 2016

StockInformaAon*Exchange NASDAQ

Symbol RTTR

Recent Price $2.35

52 Week Range $0.98 - $3.26

Market Cap $20.17 Million

Shares Outstanding

10,730,362

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•  Lead product candidate, RP-G28, has the potential to become the first FDA-approved Rx for lactose intolerance

•  Significant specialty market with unmet need

–  9 million with moderate/severe lactose intolerance in the U.S.

–  >$1.2 billion U.S. market opportunity for an Rx treatment

•  Phase 2b/3 ready, potential pivotal trial

–  Last patient completed (Oct. 17, 2016)

–  Data readout expected in Q1 2017

•  Colonic adaptation technology has potential in multiple

orphan and other indications

•  Strong intellectual property portfolio and NCE status

Highlights

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•  Company Mission: Developing novel therapeutics that selectively modulate the human gut microbiome

–  RP-G28, a first-in-class treatment for lactose intolerance suffered by >1 billion worldwide

–  Technology involves colonic adaptation of gut bacteria to facilitate lactose digestion

•  One of the most advanced therapeutics in microbiome research & development

–  Proof-of-concept demonstrated in 62 subject - Phase 2a study

–  Reasonable, low cost clinical development program

•  Founded by Andrew and Ira Ritter to develop a treatment for Andrew’s lactose intolerance

–  Proof-of-concept achieved through first-generation OTC formulation (Lactagen®)

–  Clinical trial and three consumer studies confirmed symptom reduction in 80% of patients1 (>15,000 patients)

•  World-renowned scientific advisors and strong executive leadership

•  Exploring proof-of-concept in additional orphan uses and higher prevalence diseases of significant unmet need

EstablishedLeadershipintheMicrobiome

1. Lactagen Clinical Data and Customer Experience Analysis

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•  >1 billion global lactose intolerant population

•  40 million U.S. lactose intolerant population

•  9 million moderate/severe

•  $2.45 billion annual U.S. OTC lactose intolerant market sales

•  NIH Symposium raised awareness and health concerns related to lactose intolerance1

•  Unmet need with no FDA-approved drugs

•  Limited physician and user satisfaction with current therapies

Global Penetration Rates of Lactose Intolerance2

1.  NIH Consensus Statement, Lactose Intolerance and Health, Vol 27, Number 2, February 22-24, 2010.

2.  Bouwma A., Crawford D., Malladi S., Mirabito P., Oleksiak M., Osborn J., & Seawell P. (2010). Worldwide Distribution of Lactose Intolerance. Case Study.

LactoseIntoleranceMarketOpportunity

Population Condition Prevalence Rates: •  90% Asian descent •  85% African descent •  75% Hispanic descent

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Lactase Supplements: Inconvenient and not reliable; need to take pills prior to consuming dairy

Dairy Substitutes / Lactose-Free Products:

Not always available and altered taste

Dairy Avoidance: Challenging to avoid all dairy & “hidden” lactose can cause unexpected symptoms

PaAentsareDissaAsfiedwithCurrentManagementOpAons1

66%

65%

70%

46%

29%

54%

Dairy

Sub

sAtutes

LactaseSupp

lemen

ts

Dairy

Avoidan

ce

Pa,entSa,sfac,onn=1,000Pa,ents

PhysicianRecommenda,onn=40Physicians

UnsaAsfactoryTreatmentOpAons

1. Objective Insights, “Market Research Analysis and Forecasts on Lactose Intolerance and RP-G28.” June, 2012.

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•  Modulates the gut microbiome

–  Stimulates growth of beneficial colonic bacteria (specifically lactose metabolizing bacteria)

•  Novel, non-digestible oligosaccharide

–  Ultra high-purity

–  Not absorbed during transit through GI tract/ non-systemic

•  Delivered in a sachet powder formulation, mixed with water

•  Expected one-time, 30-day course of treatment

–  Substantial durability of treatment effect expected (years)

–  Patients can be re-treated if needed

RP-G28forLactoseIntolerance

Target claim:

For the treatment of moderate to severe lactose intolerance

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MechanismofAcAonLactose Intolerance:

•  Inadequate lactase activity, lactose not broken down properly

•  Bacteria in GI tract ferments lactose, causing gas

•  Leads to gastric symptoms: abdominal pain, gas, cramping, bloating, diarrhea

  RP-G28 Promotes Colonic Adaptation

•  Stimulates and adapts the bacteria in GI tract to metabolize lactose

•  Increase lactose-metabolizing bacteria

•  Decrease gas producing bacteria

•  Lactose is broken down, reducing gas production and gastric symptoms

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Pre-Clinical

• No additional non-clinical studies to support phase 2b/3

• Minor toxicology / animal bridging studies (not required for P2 or P3)

Phase 1

•  Proven safety enabled bypass of phase 1; The family of compounds is generally regarded as safe (GRAS) by regulators

Phase 2a

(n = 62)

•  Explored mode of action and endpoints, supporting meaningful patient benefit

• Clarified dosing regimen

• Consultation from FDA (Type C Meeting), completed

Phase 2b/3 (n = 377)

•  Establish efficacy with statistical significance with pain as primary end point

•  Explore optimal dose

Pre-Clinical/ClinicalDevelopmentProgramLast Patient Completed

(October 2016)

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Baseline 25g Lactose

Challenge, HBT Stool Collection

Placebo (Sweetose) (n=20)

RP-G28 (n=42)

Post-Treatment 25g Lactose

Challenge, HBT Stool Collection

30 Days No Dosing

Day 0

Follow-up 25g Lactose

Challenge, HBT Stool Collection

Day 36 Day 66 Dairy Avoidance Diet

35 Days Dosing

Dairy Encouraged

Phase2a:StudyDesign&ProtocolOverview•  Inclusion criteria to validate lactose intolerance

–  Positive hydrogen breath test (20 ppm HBT > baseline) & moderate to severe current symptoms based on a lactose challenge (>12 on total symptoms)

•  62 subjects randomized 2-to-1 (drug-to-placebo)

–  Dosed 1.5g/d increased forced titration to 15g/d over 35 days BID

•  Endpoints

–  Lactose digestion (measured by breath hydrogen)

–  Lactose intolerance symptoms (after a 25g lactose challenge)

–  Microbiome sequencing and genetic analysis of colonic microflora

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Global Assessment1 Placebo (n=18), RP-G28 (n=40)

No Abdominal Pain2

Placebo (n=19), RP-G28 (n=36)

Phase2a:Results

Results

•  Well tolerated, no SAEs reported

•  Treated patients 6x more likely to be lactose tolerant (p=0.039)

•  Durable reduction in abdominal pain at Day 36 & Day 66 (p=0.019)

•  70% reduction in abdominal pain at Day 36

Mechanism of Action Validated

•  Composition and abundance of bacteria in the microbiome shifted

•  Increases in lactose metabolizing bacteria were found

P=0.039

P=0.019

0%

10%

20%

30%

40%

50%

60%

70%

LactoseTolerantDay66 NoPainDay36&66

Percen

tofSub

jects

RP-G28 Placebo

1. Patients reporting “tolerance to dairy foods” at day 66 2. Abdominal pain responder defined as patients that reported NO pain at both Day 36 & Day 66 time points

Data presented at DDW May 2012 and ISAPP Conference 2013, published in Nutrition Journal Dec. 2013

Demonstrated Safety and Efficacy

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Fecal sample analysis performed in labs of:

M. Andrea Azcarate-Peril, Ph.D., Director, Microbiome Core Facility, University of North Carolina Todd R. Klaenhammer, Departments of Food, Bioprocessing and Nutrition Sciences, North Carolina State University

OTU = Operational Transcription Unit by TRFLP analysis identifies bacteria

Changes in Operational Taxonomic Units (OTUs) by Terminal Restriction Fragment Length

Polymorphism (TRFLP) Analysis

•  82% of subjects on treatment showed significant alterations in their microbiome

•  Bacterial populations continued to mature once dairy added to the diet (Day 66)

•  No similar significant changes demonstrated in placebo patients

0

50

100

150

200

250

300

350

400

Day0 Day36 Day66

RP-G28(n=35) Placebo(n=17)

MicrobiomeChangesDemonstrated

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•  Fecal microbiome at Day 66 changed significantly

•  Two distinct clusters #2 and #7

•  Highly bifidogenic

•  Lactose metabolizing bacteria increased:

–  Lactose fermenting genera Faecalibacterium1

–  Roseburia (butyrate producer, increases metabolizing activity)

–  Lactobacilli and streptococci

•  Gas producing bacteria reduced:

–  Prevotella (promoted by rich carbohydrate diets2)

ComposiAon&AbundanceChanges

#2

#7

Principal Component Analysis of Microbiome Shifts

Amplicon Sequencing of 16S rRNA Gene (Day 0 v. Day 66)

1 Anti-inflammatory, butyrate producer 2 Wu et al., Science 2011

n=35 (treatment group only) Red: Day 0, Blue: Day 36, Gold: Day 66

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•  Double-blind, placebo-controlled, multicenter trial, n=377

•  Determine maximum tolerated dose & optimal dose-escalation schedule –  3 arms: Low dose, High dose and Placebo

•  Potential classification as a pivotal trial

•  Inclusion / Exclusion –  Blinded lactose challenge, cardinal symptoms measured by 11-point numerical rating scale and Bristol

stool test

–  Patients with moderate to severe lactose intolerance symptoms

•  End points –  Primary endpoint: Reduction in abdominal pain

–  Secondary endpoints: gas, bloating, diarrhea, cramping, quality of life, global assessment

•  Optional open-label 12-month durability extension study

Phase2b/3ClinicalTrialProtocolP

roto

co

l D

esi

gn

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IndicaAonDevelopmentPipeline•  Designing clinical & pre-clinical development efforts in the

microbiome

–  Establishing the role modulation of the gut microbiome has on health and a variety of diseases: metabolic, gastrointestinal, infant and liver

–  Partnering with renowned academic centers

Preclinical IND Clinical

Lactose Intolerance

Liver Disease (NASH & NAFLD)

Metabolic Syndrome

Environmental Enteropathy

Immunology / Oncology

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IntellectualProperty:9IssuedPatents

IP Counsel: Knobbe, Martens Olson & Bear LLP

•  Composition & Methods of Use patents

–  1 issued patent1: The composition of a solid oral unit dosage

–  4 issued patents2: Using RP-G28 to treat lactose intolerance symptoms and other GI diseases

–  Claims cover broad range of oligosaccharides and purity ranges

–  Specific formulations, regimens, product profile and application use

•  Manufacturing patents

–  4 issued patents3: Process of producing high-purity API (U.S. and U.K.) and patent applications in other jurisdictions

•  NCE market exclusivity (supplemental to patents)

–  Estimate 5 years from date of approval in U.S., 8 years from date of approval in Europe

•  Additional information

–  Patents expiring in 2030

–  24 pending patent applications in the U.S. and other key markets

–  RP-G28 is not absorbed into the bloodstream, thus formulation options for follow-on/generic products may be limited

1.  Composition Claim Patent: GB2480042 2.  Issued Use Patents: US 8,486,668, US 8,492,124, US 8,785,160, US 9,370,532 3.  Manufacturing Patents: US 9,200,303, EP 2462234, IT 1395068, ZL 201080035013.2

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IraE.RiWerChairman,Co-Founder,ChiefStrategicOfficer

40+yearsservingonExecu,veBoards;Rockwood,OakMedia,RGPublishing•  PresidentandChairmanofRockwood,producedover200privatelabelHBAproducts

formajorna,onalretailersincludingGNCandK-Mart

MichaelD.StepChiefExecu,veOfficer

25+yearsofexperienceinthepharmaceu,calindustry•  Recently,Sr.VPCorp.DevelopmentatSantarus(acquiredbySalixin2014);formerlyVP

Corp.DevelopmentatAmylinPharmaceu,calsandposi,onsatDuraPharmaceu,cals,Hoffmann-LaRoche&SyntexLabs

AndrewJ.RiWerCo-founderandPresident

15+yearsofresearchingastrointes,naldiseases•  FormerPresidentofRiderNaturalSciences,developedandmarketeddiges,ve

healthcareproducts.WhartonMBA

EllenMochizukiVicePresidentofFinance

27+yearsoffinancialaccoun,ngexperience•  Consultedwithvariousbiopharmaceu,calcompanies;formerlytheDir.OfAccoun,ng

forNorthropGrummanCorp.,andSr.VPatIndyMacBank

WilliamGannon,M.D.MedicalMonitor

25+ years of drug development experience •  Extensive regulatory, medical and scientific knowledge in GI, Oncology, Rheumatology among other diseases •  Former Chief Medical Officer at Apthera

ErikaJonesDirectorofClinicalOpera,ons

18+ years of clinical drug development experience, managing Phase I, II, III; globally •  Held clinical development roles at Illumina, GE Healthcare, Pfizer, Elan

BillMerinoSr.AdvisorClinical&Regulatory

30+yearsinU.S.andworldwidedrugregistra,on,qualityassurance,qualitycontrolanddrugsafety.•  FormerSr.VPofWorldwideRegulatoryAffairsatWarnerLambert.

LeadershipandManagementBoardofDirectors

IraE.RiWerChairman

MaWhewW.FoehrPresident&COO,Ligand

Pharmaceu,cals

GeraldT.ProehlPresident&CEO,Dermata

FormerPresident&CEO,Santarus

PaulV.MaierFormerCFO,Sequenom,Inc.

MichaelD.StepChiefExecu,veOfficer

AndrewJ.RiWerCo-founderandPresident

NoahJ.DoyleManagingDirector,Javelin

Ventures

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DennisSavaiano,Ph.D.Chair

ProfessorofFoods&Nutri,on&AssociateProvostatPurdueUniversityConsideredoneoftheforemostexpertsonlactoseintoleranceintheworld

W.AllanWalker,M.D. DirectoroftheDivisionofNutri,onatHarvardMedicalSchool

WilliamJ.Sandborn,M.D.Chief,DivisionofGastroenterologyandDirectoratUniversityofCaliforniaSanDiegoInflammatoryBowelDiseaseCenterandProfessorofClinicalMedicine

ToddKlaenhammer,Ph.D. DirectoroftheSoutheastDairyFoodsResearchCenter&ProfessorofFoodScience,Microbiology&Gene,csatNorthCarolinaStateUniversity;Na,onalAcademyofScienceMember

ByronL.Cryer,M.D. ProfessorofMedicineinDiges,ve&LiverDiseasesandAssociateDeanattheUniversityofTexasSouthwesternMedicalCenteratDallas&theNorthTexasVAHealthCareSystem

WarrenGrundfest,M.D.,FACS ProfessorattheUniversityofCaliforniaLosAngeles

HarryGreene,M.D. FormerChief,DivisionofPediatricGastroenterology/Nutri,onandDirectoroftheNIHsponsoredClinicalNutri,onResearchUnit

RogerClemens,Ph.D. AssociateDirectoroftheRegulatoryScienceProgramattheUniversityofSouthernCalifornia’sSchoolofPharmacy

MedicalAdvisoryBoard

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•  Lead product candidate has potential to become the first FDA-approved drug for lactose intolerance, a condition that

affects more than one billion people worldwide.

•  Phase 2b/3 underway, potential pivotal trial

–  Last patient completed – Data readout expected in Q1 2017

•  Colonic adaptation technology has potential in multiple

orphan and other indications

•  Strong intellectual property portfolio and NCE status

InvestmentHighlightsSummary

Thank You Ritter Pharmaceuticals, Inc.

www.RitterPharma.com