Pioneering Development in the Treatment of ... · •Developing novel therapeutics to treat gastrointestinal diseases by modulating the gut microbiome •Lead asset, RP‐G28, has

Pioneering Development in the Treatment of Gastrointestinal Diseases

(NASDAQ: RTTR)

Non‐Confidential PresentationAugust 2019

Pioneering Development in the Gut Microbiome for the Treatment of Lactose Intolerancewww.ritterpharma.com

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This presentation contains forward‐looking statements. All statements pertaining to future expectations, beliefs, goals, plans or prospects included in this presentation, constitute “forward‐looking statements.” By their nature, forward‐looking statements involve risks and uncertainties that may cause actual results, performance or achievements to differ materially from any future results, performance or achievements expressed or implied by the forward‐looking statements. The forward‐looking statements in this presentation are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation, risks inherent in the development of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights and other risks discussed in our reports filed with the Securities and Exchange Commission, which are available for review at www.sec.gov.

We have based these forward‐looking statements largely on our current expectations about future events and financial trends that we believe may affect our business, financial condition and results of operations. Any forward‐looking statements that we make in this presentation speak only as of the date of this presentation, and the Company undertakes no obligation to update or revise such statements to reflect events or circumstances after the date of this presentation, except as may be required by law.

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 – Looking Statement

v20


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Stock1

Exchange NASDAQ

Symbol RTTR

Recent Price $0.90

52 Week Range $0.47 - $4.00

Market Cap $8.1 Million(at recent price)

50 Day Avg. DailyVol.

583K Shares

Key Metrics: RTTR

Cash $14.8M2

Common shares 9.0M

Preferred shares 6.5M3

Preferred rights Pari passu to common

Warrants o/s & Strike Price

8.4M @ $1.30

Fully Diluted MarketCap

$22.1 Million4

(at recent price)

Cash/Capitalization

1. Stock analysis based on June 3, 20192. Proforma, based on 2018 10K, includes Cash and cash equivalents and Short term investments3. Assuming all preferred share series were converted to common at their respective conversion rates4. Includes warrants and stock option pools


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• Developing novel therapeutics to treat gastrointestinal diseases by modulating the gut microbiome

• Lead asset, RP‐G28, has potential to become the first FDA‐approved treatment for lactose intolerance (LI)

– LI effects 50M3,4 people in the U.S. and is currently a >$1.5B OTC2 market

– Current treatment options of dairy avoidance and OTC products are only partially effective with high compliance challenges

• RP‐G28 is in Phase 3 development ‐ following two Phase 2 trials demonstrating efficacy and an excellent safety profile

– First pivotal Phase 3 trial (known as “Liberatus”) completed LPLV ‐ data readout expected in early Q4 2019

– Few novel GI assets in development ‐ only 23 GI‐related NCEs1 in Phase 3 development

Ritter Pharmaceuticals: Executive Summary

1. Evaluate Pharma 2018, 2. Derived from lactase market size and CAGR (Persistence Market Research 2018) and lactose free dairy market size and CAGR (Future Market Insights 2018), 3. NICHD 2006, “Lactose Intolerance: Information for Health Care Providers” https://www.nichd.nih.gov/sites/default/files/publications/pubs/documents/NICHD_MM_Lactose_FS_rev.pdf, 4. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. Lactose Intolerance. Retrieved May 14, 2019, from https://www.niddk.nih.gov/health‐information/digestive‐diseases/lactose‐intolerance/definition‐facts


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Global Lactose Intolerance Prevalence: >1B People Worldwide

1. Storhaug 2017 Lancet Gastroenterol. Hapatol.; 2. Schematic from Food‐Intolerance‐Network.com – Lactose Intolerance visited 5/30/19; 3. DelveInsight 2019 – Lactose Intolerance; 4. NICHD 2006, “Lactose Intolerance: Information for Health Care Providers” https://www.nichd.nih.gov/sites/default/files/publications/pubs/documents/NICHD_MM_Lactose_FS_rev.pdf, 5. Calculated based on multiple studies per country, sources available upon request; 6. Calculated as 70% of lactose malabsorbers ‐ 73% LM in Japan (Storhaug 2017). Several studies show 50‐80% of malabsorbers have abdominal symptoms, with 70% as median (Asoka 1990, Korpela 2001, Cavalli‐Sforza 1987, Isokoski 1972, Cloarec 1991, Leis 1997, Bozzani 1986, Burgio 1984)

• LI: condition of lacking the lactase enzyme + GI symptoms• Symptoms include abdominal pain, flatulence, cramping,

bloating and diarrhea – Onset occurs age 5+ into adulthood, symptoms may increase

with age

– LI can occur naturally (primary LI) or be “induced” by another condition (secondary LI)

• Prevalence estimates– 15% in US: 50M3,4

– 12% in EU: 55M5

– 50% in Japan: 63M6

• Prevalence is increasing due to aging populations, and increased awareness

Worldwide Prevalence of Lactose Intolerance in Recent Populations2


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Current Treatment Options are Limited and Have Challenges

Source: JJN Consulting (2019) Lactose Intolerance & RP‐G28 Quantitative Study: Understanding the Universe of Lactose Intolerant Sufferers

61%

34%

20% 19%14% 14%

0%

20%

40%

60%

80%

Reduce dairy Substitutes Pre‐/pro‐biotics Lactase pills Eliminate dairy OTC sxm relief

% of LI Patients % Utilizing Symptom Management Approach

Limita

tions Does not

get rid of all symptoms

Expensive, hard to find when traveling, tastes different

Often has limited efficacy if not validated

Must be taken prior to every encounter with dairy

Difficult to achieve; “hidden” lactose is common

Limited efficacy as only treating symptoms

• Few options available to patients– No Rx option

– Options have limited efficacy and/or are difficult or undesirable to follow

• 85% of all LI sufferers are taking measures to reduce symptoms

– 49% using multiple options ‐ no one approach works in all situations

• Even though 71% of LI sufferers reduce or eliminate dairy, 92% want to eat some dairy


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Lactose Intolerance Overview

• Symptoms: abdominal pain, flatulence, cramping, bloating and diarrhea

• Most patients have multiple symptoms

• 30% have moderate to severe symptoms3

• Main symptom management approaches: dairy avoidance, substitutes, lactase pills

Lactose intolerance is a painful and uncomfortable condition with multiple symptoms, associated with increased health risks and a variety of quality of life challenges

1. JJN Consulting (2019) Lactose Intolerance & RP‐G28 Quantitative Study: Understanding the Universe of Lactose Intolerant Sufferers; 2. Average annual assumptions– Lactaid Purchase 3x Month x 12 Months; 3. DelveInsight 2019 Lactose Intolerance: Market Insights, Epidemiology and Market Forecast‐2028; 4. Peer‐reviewed literature, available upon request

Condition

Impact

Challenge

Health Risks

• 68% indicate a negative impact on their life – such as their mental health, their relationships, or their work productivity1

• Sufferers spend ~$200‐400 / year on lactase pills and dairy substitutes / lactase‐free dairy2

• 66% report it’s really hard to avoid dairy all the time1

• 67% report not getting adequate symptom relief1

• 65% indicate comorbidities with LI (anxiety, IBS, …)1

• 52% have given up talking to their doctor about their LI – given lack of treatment options1

• Dairy avoidance leads to increased health risks

• Linked to low bone density and osteoporosis, increased blood pressure among other conditions, primarily due to dairy avoidance4


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Patient Journey: Diagnosis and Treatment ParadigmGeneral outcome: Patients settle for trade‐off of avoiding dairy vs having symptoms

Origination Diagnosis & Treatment Outcome

Patient

Primary Care

Physician (PCP)1

Gastro‐enterologist

(GE)

Symptoms

Self dx Self‐treat w/ limited options

PCP dx

Treat w/ limited options

GE dx

Revisit PCP; inadequate

relief

Live with trade‐off: avoid dairy vs have

symptoms

Treat w/ limited options

Dairy avoidance nutritional deficiency negative health

consequences

Mild Moderate Severe

~30%

~25%

Patients visit doctor when fed up or symptoms get worse

7%

17%

Source: JJN Consulting (2019) Lactose Intolerance & RP‐G28 Quantitative Study: Understanding the Universe of Lactose Intolerant Sufferers and Cadence (2019) Lactose Intolerance Patient Journey Study; 1. PCP can include OB/GYN or other regularly visited clinician

76%

Management approach results in sufficient outcome

52% ultimately stop discussing LI w/ their HCP due to lack of options available

Dx rate expected to go up upon new treatment availability


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RP‐G28: Novel Lactose Intolerance Treatment

Indication For the treatment of lactose intolerance (LI)

Mechanism of Action (MOA)

Non‐absorbed oligosaccharide, stimulates preferential growth of lactose‐metabolizing colonic bacteria, compensating for lack of endogenous lactase enzyme

Treatment Course

Single course of treatment (30‐day duration) provides long‐lasting symptom relief and ability to eat dairy freely

• Powder (single dose packets) to be mixed with water and drank twice a day

• Palatable sweet taste

Safety and Efficacy

• Generally safe and well tolerated, no serious adverse events in clinical trials

• Treated patients become “lactose tolerant” and report significantly less symptoms, adequate relief, and ability to consume dairy

• Phase 3 study evaluates 90 dof durability, expectation ~70% of patients will maintain effect for >1 year1,2

Dev. Plan Currently in Phase 3 trial

1. Second Phase 3 (G28‐007) study to assess >6 months durability, 2. Estimation based on Phase 2 program data and historical data


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Lactose Intolerance: • Inadequate lactase activity in small intestine results in undigested lactose

• LI symptoms from undigested lactose are the result of:– Bacteria in gut ferments lactose and produces abdominal pain, flatulence and

cramping

– Osmotically active lactose causes water retention in the gut causing bloating and diarrhea

RP‐G28 Mechanism of Action Colonic Microbiome Adaptation

RP‐G28 Promotes Colonic Adaptation:• Preferentially stimulates growth of lactose‐metabolizing bacteria in the GI tract

– Lactose‐metabolizing bacteria compensate for the lack of endogenous lactase activity

– Decrease proportion of gas‐producing bacteria

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

Lactose transits through small intestines

Undigested lactose fermented in colon, producing gas

Mechanism of LI symptoms & RP‐G28

Lactose transits through smallintestines

Lactose is digested by colonic bacteria, no gas or symptoms


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• Phase 2 trials report consistent outcomes supporting RP‐G28’s mode of action

– Increased abundance of intestinal lactose‐metabolizing bacteria

– Increased bifidobacteria was correlated with reduction in abdominal pain and cramps associated with lactose intolerance1

• 82% of subjects on treatment showed significant alterations in their microbiome1

• 90% of treated patients in Phase 2a had a bifidogenic response1

• 78% of treated patients in Phase 2b increased Bifidobacteria (p=<.001)2

Microbiome Data Supports Mechanism

1 Phase 2a Microbiome Data. Azcarate‐Peril et al. PNAS 2017;114:E367‐E375, Andrea Azcarate‐Peril, et al. DDW Conference; 2013 May 18‐21; Orlando, FL.2 Phase 2b Microbiome Data

#2

#7

Principal Component Analysis of Microbiome Shifts1

Amplicon Sequencing of 16S rRNA Gene

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


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RP‐G28 Clinical TrialsExcellent safety, Clear functional and Biological Efficacy

1. Savaiano et al.: “Improving lactose digestion and symptoms of lactose intolerance with a novel galacto‐oligosaccharide (RP‐G28): a randomized, double‐blind clinical trial.” Nutrition Journal, 2013. 12:160.2. M. Azcarate‐Peril et al.: “Impact of short‐chain galactooligosaccharides on the gut microbiome of lactose‐intolerant individuals.” PNAS, 2017. 114 (3) E367‐E375.

• N=62• Established mode of action, identified appropriate endpoints and clarified dosing regimen

• Safety and tolerability supported; No SAEs, AEs similar to placebo

• Lactose digesting bacteria found to increase significantly

• Publications: Nutrition Journal 20131, PNAS 20172, DDW conf. 2016, 2017

PHASETRIAL 2a

• N=377• Established efficacy and selected optimal dose

• Validated well‐defined patient‐reported outcomes tool

• SAEs and AEs similar to placebo

• Efficacy subset: significant improvement in symptoms of LI measured as change in LI SZA score (severity)

• Publications: in submission, DDW conf. 2018

PHASETRIAL 2b

• N=557 (1st Trial)• Two confirmatory clinical trials expected for NDA filing

• Primary endpoint agreed upon with FDA

• First Phase 3 trial (“Liberatus”) enrollment complete (N=557) Q1’19

• LPLV completed (July 2019)• Second Phase 3 trial planned for 2020

PHASEPROGRAM 3PHASE

TRIAL 1• N=14• Evaluated pharmacokinetic (PK) profile of RP‐G28

• No safety signals• < 1% oral dose administered fasted is absorbed– Food reduces plasma exposure by ½

– Drug has short half‐life of approx. 2 hrs


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• N=377

• Design– Double‐blind, placebo‐controlled, multi‐center,

dose ranging study conducted at 15 U.S. clinical sites

– Inclusion/Exclusion: Minimum severity of LI assessed by blinded lactose challenge and lactase deficiency confirmed by standard HBT

Phase 2b (G28‐003): Protocol Design

• Endpoints: Employed a validated patient‐reported outcomes tool

– Primary endpoint: Proportion of subjects who report a clinically meaningful reduction in LI symptoms (abdominal pain, cramping, bloating and gas)

– Endpoints incorporated FDA’s recommendations prior to un‐blinding the data

Screening Phase 30‐Day Treatment Phase 30‐Day Post‐Treatment PhaseReal‐world Assessment

Group A: RP‐G28 Low Dose

Group B: RP‐G28 High Dose

Group C: Placebo

Day 0 lactose challenge

Day 31lactose challenge

1:1:1

Lactose avoidance period Lactose / dairy consumption encouraged

Study Subjects


Protocol Design


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Clinically Meaningful Benefit

• Significant reduction of lactose intolerance symptoms after treatment

• Primary endpoint met statistical significance in efficacy subset analysis2

– Similar response in both doses2: lower dose p=0.043; higher dose p=0.029

• Efficacy Subset mITT population excludes from analysis inconsistent data from one study center

– mITT population of all dosed patients (N= 368), p=0.06

Phase 2b (G28‐003): Primary Endpoint LI Symptom Composite

1. Primary endpoint defined as patients reporting a >4‐point change in LI Symptom Composite Score post‐treatment compared to baseline or a zero LI Symptom Composite Score post‐treatment.2. Efficacy Subset modified intent to treat (mITT) population excludes from analysis inconsistent data from one study center (mITT population represents full data set).

P‐value 0.016(vs. placebo)

Proportion of Patients Reporting Meaningful Improvement in Lactose Intolerance Symptoms1,2

26%

40%

20%

30%

40%

50%

Efficacy Subset mITT (N=296)

% of P

atients Re

porting Re

spon

se

Placebo Treatment


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Treatment patients consumed nearly 2x more milk

Milk Consumption

Patients consistently report symptom relief

Global Assessments

22%

16% 16%

2% 2%

37%35%

30%

16%

13%

0%

10%

20%

30%

40%

AbdominalPain

Cramping Bloating GasMovement

SymptomComposite

Percen

t of P

atients Re

spon

ding

Placebo Treatment*

P‐value 0.0144 0.0020 0.0150 0.0005 0.004(vs. placebo)

0.7

1.3

0.4

0.5

0.6

0.7

0.8

0.9

1

1.1

1.2

1.3

1.4

Cups of M

ilk Con

sumed

Per Day

Placebo Treatment*

P‐value 0.0144(vs. placebo)

64%

52%

25%

82%

66%

40%

20%

30%

40%

50%

60%

70%

80%

90%

No or MildSymptoms

Very or ExtremelySatisfied

Very Much or MuchImprovement

Percen

t of P

atients Re

spon

ding

Placebo Treatment*

P‐value 0.0013 0.0302 0.0343(vs. placebo)

Phase 2b (G28‐003): Compelling Treatment Outcomes

* Efficacy Subset population, excludes from analysis inconsistent data from one study center

Significant percent of treated patients reported elimination of symptoms

Lactose Intolerance Symptoms


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• N=557 (Last patient last visit completed July 2019)• Design

– Double‐blind, placebo‐controlled, multi‐center (>30 U.S. sites)

– Designed with input from the FDA

– Well‐defined LI population and screening methods

– Placebo run‐in and blinded lactose challenge to

ensure LI symptoms

– Validated symptom assessment measures to capture

appropriate clinical outcome endpoints

• Primary Endpoint– Change from baseline to Day 61 (30 days of treatment and 30 days of real‐world lactose exposure) in LI symptoms1

compared to placebo

• On track for topline data readout early Q4 2019

Phase 3 (G28‐006): “Liberatus” Protocol Design

1. “LI symptoms” is defined as a composite score compiling symptoms of abdominal pain, cramping, bloating and gas

14‐Day Run‐in Period

Usual Diet

Day 0 lactose challenge

30‐Day Treatment Phase 90‐Day Post‐Treatment PhaseReal‐world Assessment

RP‐G28

Placebo

2:1

Lactose avoidance period


Lactose / dairy consumption encouraged



Study Subjects

Protocol Design


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Formulation: 14 issued patents with formulation/ dosage form claims in:

• United States (3), Europe (Germany, Spain, France, United Kingdom, Italy, and the Netherlands), Australia (2), the Philippines, Singapore, and South Africa

Methods of Use: 16 issued patents with method of use / method of treatment claims in:

• United States (4), Canada, Europe (Germany, Spain, France, United Kingdom, Italy, and the Netherlands), Australia (2), the Philippines, Singapore, and South Africa

Manufacturing Process: 13 issued patents with manufacturing process claims in:

• United States, Europe (Germany, France, the United Kingdom, Ireland, Italy, Switzerland, and the Netherlands), India, China, Japan (2), and South Korea

Expected NCE Market Exclusivity:

• From date of approval: 5 years in the United States; 8 years in Japan; and 10 years in Europe

Additional Information:

• Most patents will not expire until 2030, with a potential for a Patent Term Extension (PTE) in the US and Supplemental Protection Certificate (SPC) in EU until 2035

• 15+ pending patent applications in the US and other key international markets

Intellectual Property and Regulatory Protections


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• First‐in‐Class ‐ Potentially the first FDA‐approved drug for lactose intolerance

– Few novel GI assets in development ‐ only 23 GI‐related NCEs1 in Phase 3 development

– Well covered IP portfolio

• Large market potential ‐ Low barrier to penetrate target population with few competitors

– 50M sufferers in U.S.3,4 and >1B worldwide

– >$1.5B over‐the‐counter U.S. market2

• Pivotal Phase 3 trial of RP‐G28 underway ‐ data readout expected in early Q4 2019; 2nd Phase 3 trial planned for 2020

– Excellent safety and efficacy results through Phase 2

– Understood regulatory pathway to approval

Summary

1. Evaluate Pharma 2018, 2. Derived from lactase market size and CAGR (Persistence Market Research 2018) and lactose free dairy market size and CAGR (Future Market Insights 2018), 3. NICHD 2006, “Lactose Intolerance: Information for Health Care Providers” https://www.nichd.nih.gov/sites/default/files/publications/pubs/documents/NICHD_MM_Lactose_FS_rev.pdf, 4. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. Lactose Intolerance. Retrieved May 14, 2019, from https://www.niddk.nih.gov/health‐information/digestive‐diseases/lactose‐intolerance/definition‐facts


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John W. BeckChief Financial Officer

Sharron Gargosky, PhDVice President, Clinical Operations

Ira E. RitterChairman, Co‐Founder, Chief Strategic Officer

Andrew J. RitterCo‐founder and Chief Executive Officer Board of Directors

• Ira E. RitterChairman

• Matthew W. FoehrPresident & COO, Ligand Pharmaceuticals

• Paul V. MaierFormer CFO, Sequenom, Inc.

• Michael D. StepFormer Sr. VP Corporate Development, Santarus, Inc.

• Andrew J. RitterCo‐founder and Chief Executive Officer

• Noah J. DoyleManaging Director, Javelin Ventures

• William M. Merino, Ph.D.Former Sr. VP Worldwide Regulatory Affairs at Warner, Lambert Pharmaceuticals

15+ years of research in gastrointestinal diseases• Founder of Ritter Pharmaceuticals. Former President of Ritter Natural Sciences,

developed and marketed digestive healthcare products. Wharton MBA

25+ years of experience in finance, fundraising, and accounting in the pharmaceutical industry

• Former CFO of Ardea Biosciences (acquired by AstraZeneca in 2012); former CFO of Metabasis Therapeutics.

25+ years of global clinical development and operational experience• Experience in the field of pharmaceutical and biologic development having

managed international programs from early research phase through the U.S. Food & Drug Administration approval process.

40+ years serving on Executive Boards; Rockwood, Oak Media, RG Publishing• President and Chairman of Rockwood, produced over 200 private label HBA

products for major national retailers including GNC and K‐Mart

Experienced Leadership and Management

Jennifer TimmermanSenior Director, Regulatory Affairs

13+ years of US and International regulatory strategy• Most recent experience at Medpace, Kedrion Biopharma, Reckitt Benckiser

Andrew ThompsonSenior Advisor, Business Development

35 years of experience in the Pharmaceutical Industry • Held senior commercial and business development roles in both multi‐nationals

and private European companies, specialized in Business Development in the gastrointestinal space


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William J. Sandborn, M.D. Chief, Division of Gastroenterology and Director, University of

California San Diego Inflammatory Bowel Disease

Center

William Chey, M.D.

Director of the GI Physiology Laboratory, Michigan

Co‐Director of the Michigan Bowel Control Program, Michigan Medicine

Anthony J. Lembo, M.D.

Assoc. Professor of Medicine at

Harvard Medical School

Director, GI Motility Laboratory at Beth Israel Deaconess Medical Center

Todd Klaenhammer,

Ph.D.Professor of Food

Science, Microbiology & Genetics at North Carolina State University

National Academy of Science Member

Byron L. Cryer, M.D.

Professor of Digestive & Liver

DiseasesAssociate Dean at the University of

Texas Southwestern Medical Center at

Dallas

Distinguished Medical Advisory Board

Dennis Savaiano, Ph.D.Virginia C. Meredith Professor, Dept of Nutrition Science, Purdue UniversityConsidered one of

the foremost experts on lactose intolerance in the

world

http://www.ritterpharma.com/

Follow us on Twitter: @RitterPharma

Follow us on LinkedIn: www.linkedin.com/company/ritter‐pharmaceuticals‐inc‐/

Thank You

Documents

Pioneering Development in the Treatment of ... · •Developing novel therapeutics to treat gastrointestinal diseases by modulating the gut microbiome •Lead asset, RP‐G28, has