9 Meters Biopharma, Inc. · OTC:NMTRQ
9 Meters Biopharma — Technical Presentation (March 2021)
42 slides from 9 Meters Biopharma's technical presentation, Mar 23, 2021
Slide 1: Short Bowel Syndrome R&D Day: NM-002 Long-Acting GLP-1 Agonist
A Champion in GI With A One Tract Mind Focused on Rare and Unmet Needs in Gastroenterology Short Bowel Syndrome R&D Day NM-002: Proprietary Long-Acting GLP-1 Agonist March 23, 2021
Slide 2: Forward Looking Statements
Forward Looking Statements 2 This presentation includes forward-looking statements based upon the Company's current expectations. Forward-looking statements include, but are not limited to, statements that express our intentions, beliefs, expectations, strategies, predictions or any other statements
Slide 3: R&D Day Agenda
R&D Day Agenda • Introduction - John Temperato, President & CEO • Short Bowel Syndrome Overview & Management – Patrick H. Griffin, MD, CMO • Clinical Impact of Chronic Diarrhea in SBS Patients – Carol Rees Parrish, MS, RDN, University of Virginia Health System • Paradigm Shift to GLP-1 – Patrick H.
Slide 4: Introduction
Introduction John Temperato, President and CEO
Slide 5: 9 Meters in Circuitous Length - But a Straight-Forward Strategy
Capital efficient development pathway Market protection enhancements Capital efficient commercialization Payer leverage Acquire targeted clinical compounds Agnostic within GI tract if needs are unmet Rare & unmet needs allows for targeted patient profiling within GI 9 Meters in Circuit
Slide 6: 9 Meters Pipeline in Rare and Unmet Need GI Diseases
9 Meters Pipeline in Rare and Unmet Need GI Diseases 6 NOTE: All programs are New Chemical Entities. NOTE: All programs are globally licensed except NM-004, which excludes Asia, except for Japan. PROGRAM INDICATION CLASS ROUTE PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 UPCOMING MILESTONES Topline readout
Slide 7: Multiple Potential Inflection Points Over Next 12-18 Months
Multiple Potential Inflection Points Over Next 12-18 Months 7 • Initiate Phase 2 NM-002 trial • Obtain USAN name for NM-002 • Attendance at Digestive Disease Week (DDW) conference 2Q 2021 • Initiate IND-enabling pathway for NM-102 • Initiate IND-enabling pathway for NM-003 3Q 2021 • Topline Phase 2
Slide 8: Short Bowel Syndrome is a Debilitating Orphan Disease
8 1Jeppesen P. Expert Opin Orphan Drugs; 1:515-25; 2Transparency Market Research; Short Bowel Syndrome Market, 2019 Normal Length of GI Tract ~ 9.0 m / ~ 30 ft SBS Patient Length of GI Tract Significantly Shortened Short Bowel Syndrome (SBS) is a Debilitating Orphan Disease • Orphan disease (orphan
Slide 9: NM-002 vs GLP-2 Class Profile
9 NM-002 (proprietary long-acting GLP-1)* GLP-2 Class Profile Long acting GLP-1 receptor agonist Slows gut motility Increases time for absorption of key nutrients – GLP-2 analogue – Expand intestinal mucosa / villous growth – Limited effect on gut motility Efficacy Improvements in total stoo
Slide 10: Patrick H. Griffin MD, FACP – Chief Medical Officer
Patrick H. Griffin MD, FACP – Chief Medical Officer Dr. Griffin became our chief medical officer in February 2019. Previously, Dr. Griffin served as executive vice president and chief medical officer of Synergy Pharmaceuticals from January 2015 through November 2018, and senior vice president and ch
Slide 11: Short Bowel Syndrome Overview & Management
Short Bowel Syndrome Overview & Management Patrick H. Griffin, MD, FACP, CMO
Slide 12: Short Bowel Syndrome is a Debilitating Orphan Disease
12 1Amiot A et al. Clin Nutr 2013;32:368–74; Boland E et al. Am J Surg 2010;200:690–3; 2Bielawska B. Nutrients 2017;9:466–79; Pironi L et al. Clin Nutr 2016;352:247–307; Hofstetter S et al. Curr Med Res Opin 2013;29:495– 504. 3 Jeppesen 2014 Normal Length of GI Tract ~ 9.0 m / ~ 30 ft SBS Patient Le
Slide 13: SBS Patient Perspective on Chronic Diarrhea
SBS Patient Perspective on Chronic Diarrhea Indicative of Significant Impact Over the Last Decade 13 Patient quotes from NPS market research; Source: SEC 8-k April 2010 NPS Pharmaceuticals Inc. If you want a one-word description [of living with Short-Bowel Syndrome], it’s ’hell’. It changes your who
Slide 14: Treatment Options: Nutrition and Hydration
Treatment Options: Nutrition and Hydration • Absorption capacity for nutrition, fluid, and electrolytes is proportional to: ‒ Length of small bowel ‒ Segments of the intact bowel ‒ Absorptive quality of remnant bowel ‒ Individual capacity for GI mucosal adaptation • PN/IV support provides the nutrit
Slide 15: Treatment Options: GLP-2 Mechanism of Drug Class
15 Treatment Options: GLP-2 Mechanism of Drug Class Trophic gut peptide increases villous height and crypt depth Control GLP-2 Murine model of GLP-2 effects on gastrointestinal villus/crypt architecture adapted from Drucker DJ, Erlich P, et al. Proc Natl Acad Sci U S A. 1996; 93:7911. National Acade
Slide 16: Treatment Options: Supportive Care
Treatment Options: Supportive Care • SBS supportive symptom care: ‒ Growth hormone and glutamine (approved) ‒ Antidiarrheals: loperamide, diphenoxylate/atropine, diluted tincture of opium, codeine ‒ Antiemetics for chronic nausea (e.g. 5HT3 antagonists) ‒ Acid suppressors: PPI, H2RA ‒ Antibiotics: s
Slide 17: Patients With SBS Typically Have No Natural GLP-1
17 Patients With SBS Typically Have No Natural GLP-1 • GLP-1 is naturally produced in a portion of ileum that is removed during surgical resection • Natural GLP-1 prevents the GI tract from moving rapidly: known as an “ileal brake” • Without this brake, there is a lack of gut motility, causing an SB
Slide 18: Speaker: Carol Rees Parrish, MS, RDN
Speaker: Carol Rees Parrish, MS, RDN Carol Parrish has 30 years of clinical experience, the past 20 of which have been spent specializing in nutrition support and GI disorders at the University of Virginia Health System (UVAHS), Digestive Health Center of Excellence. Carol founded the Medicine Nutri
Slide 19: The Clinical Impact of Chronic Diarrhea in SBS Patients
The Clinical Impact of Chronic Diarrhea Importance in SBS Patients Carol Rees Parrish, MS, RDN University of Virginia
Slide 20: UVA Health
UVA Health Available at no cost to patients & clinicians @ www.shortbowelsyndrome.com under “sign up at top” NOTE: New 2021 version will be available this summer 20
Slide 21: Paradigm Shift to GLP-1
Paradigm Shift to GLP-1 NM-002: Proprietary Long-Acting GLP-1 Agonist Patrick H. Griffin, MD, FACP, CMO
Slide 22: Why is a paradigm shift needed?
Why is a paradigm shift needed? • Chronic diarrhea due to malabsorption in SBS has not been fully addressed with current treatments. • Relief from incessant diarrhea continues to be a high unmet need and requires a solution for all SBS patients, independent of parenteral requirements. • NM-002 is a
Slide 23: NM-002 Replaces GLP-1 and Restores the Ileal Brake
In a shortened bowel, motility is increased, reducing nutrient uptake and causing quicker movement of food through the bowel. Typical Short Bowel Syndrome Short Bowel Syndrome with GLP-1 GLP-1 travels through the blood, which affects gut motility elsewhere in the body. Motility is slowed, allowing m
Slide 24: XTENylation technology behind NM-002
24 Asp HisGly Thr ThrSerPheGluGly Asp Leu Ser LysGlnMetGluGluAlaVal GluArg Phe Leu Ile GluTrpLeu ProLys GlyGly Ser Ser Gly GlyAlaProProSer • Dipeptidyl peptidase 4 cleaves native GLP- 1 and GLP-2 in minutes • Exenatide still limited by half-life (2.5 h) • Long-acting depot formulation (Bydureon®) no
Slide 25: NM-002 Pharmacokinetics Supports Target Product Profile
25 NM-002 Pharmacokinetics Supports Target Product Profile All parameters are mean values. 1. One 50 mg dose patient did not receive a 2nd dose Source: Pharmacokinetic data from NM-002 Phase 1b/2a trial in short bowel syndrome Day Parameter 50 mg Cohort (n=3) 100 mg Cohort (n=4) 150 mg Cohort (n=2)
Slide 26: NM-002 Phase 1b/2a Results
Short Bowel Syndrome NM-002 Phase 1b/2a Results Patrick H. Griffin, MD, FACP, CMO
Slide 27: Phase 1b/2a Study: SBS Clinical Trial Design
Phase 1b/2a Study: SBS Clinical Trial Design 27 Screening 50 mg cohort n = 2 100 mg Cohort n = 2 50 mg Cohort n = 1 100 mg Cohort n = 2 Total n=9 7 Day Safety Assessment 150 mg Cohort n = 1 150 mg Cohort N = 1 7 Day Safety Assessment 7 Day Safety Assessment Open label, two-dose, dose escalation stud
Slide 28: Phase 1b/2a Trial: Treatment Emergent Adverse Events
50 mg Cohort (n=3) 100 mg Cohort (n=4) 150 mg Cohort (n=2) Any exposure to NM-002 (n=9) System Organ Class Preferred Term # of subjects n (%) # of events n # of subjects n (%) # of events n # of subjects n (%) # of events n # of subjects n (%) # of events n TEAEs 3 (100.0) 7 3 (75.0) 6 2 (100.0) 4 8
Slide 29: Phase 1b/2a Efficacy: Total Stool Output
Patient NM-002 Dose (mg) Baseline (mL) First 48 Hours Post Dose 1 (mL) Change from Baseline (mL) First 48 Hours Post Dose 2 (mL) Change from Baseline (mL) 1 50 22508 12550 −9958 13950 −8558 2 50 1900 200 −1700 300 −1600 61 50 1175 350 −825 - - 3 100 720 615 −105 325 −395 4 100 1285 420 -865 24502 11
Slide 30: Phase 1b/2a Efficacy: Bowel Movement Frequency
Patients 1 & 3 have an ostomy, therefore missing from the bowel frequency table; total stool output (previous slide) more relevant in these patients 30 Phase 1b/2a Efficacy: Bowel Movement Frequency Patient NM-002 Dose (mg) Baseline (#) First 48 Hours Post Dose 1 (#) Change from Baseline (#) First 4
Slide 31: Urine Output Unreliable In This Ambulatory Setting Trial
Urine Output Unreliable In This Ambulatory Setting Trial 31 To date, urine output has not been an efficacy endpoint for any SBS development program and there are currently no plans to use this as an end measure in our go-forward clinical and regulatory path.
Slide 32: Parenteral Support: Data from 2/5 Patients on NM-002
Parenteral Support: Data from 2/5* Patients on NM-002 After Only Two Doses 32 *5 of 9 total patients in the trial were on PS; the remaining 3 patients (not shown) had no worsening of PS values and were stable on baseline PS
Slide 33: SF-36 Quality of Life Questionnaire Results
SF-36 Quality of Life Questionnaire Results 33 Results of the SF-36 Quality of Life instrument show directional improvement in multiple elements of health status over the course of this study.
Slide 34: Summary of Study Results
Summary of Study Results 34 Study met its primary objective: NM-002 demonstrated an excellent safety and tolerability profile NM-002 demonstrated a clinically relevant improvement in total stool output (TSO) volume, supporting a clear “GO” decision for next phase of development Data support twice mo
Slide 35: Clinical and Regulatory Path Forward
Clinical and Regulatory Path Forward Patrick H. Griffin, MD, FACP, CMO
Slide 36: FDA Response on Planned Phase 2 Program
FDA Response on Planned Phase 2 Program 36 Secondary endpoints will include parenteral requirements, diarrhea impact, meal-related stool output, nocturnal stool output, sleep quality and quality of life FDA Type C meeting communication supports plan to initiate Phase 2 study with NM-002 for SBS usin
Slide 37: Goals of Phase 2 Trial
Goals of Phase 2 Trial • Remote trial execution in Covid-19 environment (Telehealth, remote outcome assessments, e.g., oral intake & TSO) • Remote outcome measurements ‒ stool output volume ‒ oral intake volume ‒ body weight ‒ vital signs, etc. • Identify most efficacious, safe dose compared to plac
Slide 38: Proposed NM-002 Study Design & Timeline
Proposed NM-002 Study Design & Timeline 38 Group n Treatment Day 0 7 14 21 28 1 6 50 mg PBO 50 mg PBO 50 mg 2 6 100 mg PBO 100 mg PBO 100 mg 3 6 50 mg 50 mg 50 mg 50 mg 50 mg 4 4 PBO PBO PBO PBO PBO • Study population: all comers (regardless of phenotype and/or PS requirement) • Site selection final
Slide 39: Managing the Phase 2 Program During Covid-19
Managing the Phase 2 Program During Covid-19 39 • Data collection considerations • Training, communication and management of the trial team • Patient recruitment • Patient retention during the trial • Managing investigational drug product & matching placebo • Patient study sample management • Monito
Slide 40: Informing the NM-002 Phase 3 SBS Clinical Program
Informing the NM-002 Phase 3 SBS Clinical Program 40 Based on current data we project a double-blind treatment period of 12 weeks enrolling 80-100 patients followed by adequate long-term safety timeline to be determined. teduglutide (approved) glepaglutide (Phase 3 investigational agent) apraglutide
Slide 41: NM-002 Near Term Inflection Points
April Pending USAN Name NM-002 Near Term Inflection Points 41 March 23 9 Meters SBS R & D Day -Full data set review 2020 2021 2Q21 Phase 2 initiation -22 patient trial starts 4Q21 Topline Phase 2 results 4Q21 Phase 3 SBS study initiation Early December Topline Phase 1b/2a results
Slide 42: Thank You
Thank You John Temperato President & CEO jtemperato@9meters.com Edward Sitar Chief Financial Officer esitar@9meters.com 8480 Honeycutt Road, Suite 120 Raleigh, NC 27615 Telephone: 1-919-275-1933 info@9meters.com www.9meters.com Twitter LinkedIn
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