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: A Champion in GI With A One Tract Mind
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 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 r
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
9 Meters in Circuitous Length - But a Straight-Forward Strategy GI-Centric, Patient-Focused Develop Acquire / Acquire targeted clinical compounds capital efficient Partner Agnostic within GI tract if needs are unmet + regulatory aligned to focus Rare & unmet needs allows for predicates targete
Slide 6: 9 Meters Pipeline in Rare and Unmet Need GI Diseases
9 Meters Pipeline in Rare and Unmet Need GI Diseases PROGRAM INDICATION CLASS ROUTE PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 UPCOMING MILESTONES Larazotide Tight Junction Topline readout Regulator Oral; Gut Restricted Adult Celiac Disease Phase 3 → 2022 NM-002 Initiate Phase 2 → 2Q21 Long-Acting GLP-1 I
Slide 7: Multiple Potential Inflection Points Over Next 12-18 Months
Multiple Potential Inflection Points Over Next 12-18 Months 2Q 2021 3Q 2021 4Q 2021 2022 • Initiate Phase 2 NM-002 • Initiate IND-enabling • Topline Phase 2 • Interim analysis for trial pathway for NM-102 readout of NM-002 larazotide Phase 3 for trial celiac disease • Obtain USAN name for • Initiate
Slide 8: Short Bowel Syndrome (SBS) is a Debilitating Orphan Disease
Short Bowel Syndrome (SBS) is a Debilitating Orphan Disease • Orphan disease (orphan designation Normal SBS Patient Length of GI Tract Length of GI Tract granted) with an underserved market ~ 9.0 m / ~ 30 ft Significantly Shortened • Affects up to 20,000 people in the U.S. with similar prevalence in
Slide 9: NM-002 Target Product Profile
NM-002 Target Product Profile NM-002 (proprietary long-acting GLP-1)* GLP-2 Class Profile ü Long acting GLP-1 receptor agonist – GLP-2 analogue ü Slows gut motility – Expand intestinal mucosa / villous growth ü Increases time for absorption of key nutrients – Limited effect on gut motility Efficacy
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 (SBS) is a Debilitating Orphan Disease
Short Bowel Syndrome (SBS) is a Debilitating Orphan Disease • Severe disease characterized by a near-complete lack of gut motility with significant impact on quality of life Normal SBS Patient Length of GI Tract Length of GI Tract • Impaired intestinal absorption, diarrhea & metabolic ~ 9.0 m / ~ 30
Slide 13: SBS Patient Perspective on Chronic Diarrhea
SBS Patient Perspective on Chronic Diarrhea Indicative of Significant Impact Over the Last Decade The bathroom is probably the most If you want a one-word description [of I’m going so much I have no annoying thing… I always have plastic living with Short-Bowel Syndrome], life. I can’t go anywhere –
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
Treatment Options: GLP-2 Mechanism of Drug Class Trophic gut peptide increases villous height and crypt depth Approved therapy: Endotoxins Nutrients Gut Lumen Bacterial Metabolites • GLP-2 class to promote intestinal growth (teduglutide approved in US Enterocyte L Cell in 2012, long-acting analogues
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
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 SBS p
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
The Clinical Impact of Chronic Diarrhea Importance in SBS Patients Carol Rees Parrish, MS, RDN University of Virginia
Slide 20: Available at no cost to patients & clinicians
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 UVA Health
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
NM-002 Replaces GLP-1 and Restores the “Ileal Brake” Typical Short Short Bowel Syndrome with GLP-1 Bowel Syndrome GLP-1 travels through In a shortened bowel, the blood, which motility is increased, affects gut motility reducing nutrient elsewhere in the body. uptake and causing quicker movement of f
Slide 24: NM-002 is XTENylated Creating Ultra-Long Half-Life
NM-002 is XTENylated™ Creating Ultra-Long Half-Life XTENylation Key Benefits: XTEN e Ex Exenatide 4.2 kDa • Increases exenatide half-life from 2 to ~170 h in PK modelling P HisGlyGluGly ThrPheThrSerAsp Leu • Not PEGylation conjugation Kan R Ser • Fully recombinant process Arg Val Ala GluGluGluMetGln
Slide 25: NM-002 Pharmacokinetics Supports Target Product Profile
NM-002 Pharmacokinetics Supports Target Product Profile 50 mg 100 mg 150 mg Day Parameter Cohort Cohort Cohort (n=3) (n=4) (n=2) Mean AUC0-t 1481465.77 2849924.89 2651203.79 (h*ng/mL) 1 Mean Cmax 13893.92 24894.00 24347.01 Serum concentration (ng/mL) (ng/mL) Mean 144 150 168 Tmax (h) 50 mg 100 mg 15
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 Open label, two-dose, dose escalation study of NM-002 in adult patients with SBS Key secondary outcomes: NM-002 given twice, Doses were Main outcomes: Patients followed for 6 Total stool output(TSO); at 3 different dose administered on Safety & weeks afte
Slide 28: Phase 1b/2a Trial: Treatment Emergent Adverse Events
Phase 1b/2a Trial: Treatment Emergent Adverse Events 50 mg Cohort 100 mg Cohort 150 mg Cohort Any exposure to NM-002 (n=3) (n=4) (n=2) (n=9) # of System Organ Class Preferred # of subjects # of events # of subjects # of events # of subjects # of events # of events subjects Term n (%) n n (%) n n (%)
Slide 29: Phase 1b/2a Efficacy: Total Stool Output (TSO)
Phase 1b/2a Efficacy: Total Stool Output (TSO) NM-002 Dose First 48 Hours Change from First 48 Hours Change from Patient Baseline (mL) (mg) Post Dose 1 (mL) Baseline (mL) Post Dose 2 (mL) Baseline (mL) 1 50 22508 12550 −9958 13950 −8558 2 50 1900 200 −1700 300 −1600 61 50 1175 350 −825 - - 3 100 720
Slide 30: Phase 1b/2a Efficacy: Bowel Movement Frequency
Phase 1b/2a Efficacy: Bowel Movement Frequency NM-002 Dose First 48 Hours Change from First 48 Hours Change from Patient Baseline (#) (mg) Post Dose 1 (#) Baseline (#) Post Dose 2 (#) Baseline (#) 2 50 22 1 −21 4 −18 61 50 5 8 3 - - 4 100 20 20 0 10 −10 5 100 8 11 3 13 5 7 100 22 17 -5 10 -12 8 150
Slide 31: Urine Output Unreliable In This Ambulatory Setting Trial
Urine Output Unreliable In This Ambulatory Setting Trial 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. 31
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 *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 32
Slide 33: SF-36 Quality of Life Questionnaire Results
SF-36 Quality of Life Questionnaire Results Results of the SF-36 Quality of Life instrument show directional improvement in multiple elements of health status over the course of this study. 33
Slide 34: Summary of Study Results
Summary of Study Results 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 month
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 FDA Type C meeting communication supports plan to initiate Phase 2 study with NM-002 for SBS using Total Stool Output (TSO) as the primary efficacy outcome measure Multi-center, double-blind, double-dummy, randomized placebo-controlled trial; FDA has provided
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 Treatment Day Group n 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 finalize
Slide 39: Managing the Phase 2 Program During Covid-19
Managing the Phase 2 Program During Covid-19 • 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 • Monitorin
Slide 40: Informing the NM-002 Phase 3 SBS Clinical Program
Informing the NM-002 Phase 3 SBS Clinical Program teduglutide glepaglutide apraglutide (Phase 3 investigational (phase 3 investigational (approved) agent) agent) Phase 3 patient number 173 129 144 Duration of double- 48 weeks blind treatment 24 weeks 24 weeks (efficacy at 24 weeks) No. of groups 2 (
Slide 41: NM-002 Near Term Inflection Points
NM-002 Near Term Inflection Points Early December April 4Q21 Topline Phase 1b/2a results Pending USAN Name Topline Phase 2 results 2020 2021 March 23 2Q21 4Q21 Phase 2 initiation 9 Meters SBS R & D Day Phase 3 SBS study initiation -22 patient trial starts -Full data set review 41
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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