Galmed Pharmaceuticals Ltd. · NASDAQ:GLMD
Galmed Pharmaceuticals — Investor Day (January 2021)
42 slides from Galmed Pharmaceuticals's investor day presentation, Jan 26, 2021
Slide 1: KOL Symposium & Pipeline Update
Leveraging Science for Lifetime Medicine KOL Symposium & Pipeline Update 26 January 2021
Slide 2: Safe Harbor and Disclaimer Statement
2 Safe Harbor and Disclaimer Statement This presentation contains forward - looking statements about our expectations, beliefs or intentions regarding, among other things, our product development efforts, business, financial condition, results of operations, strategies or prospects . In addition, fr
Slide 3: Speakers
Speakers Opening Words: Allen Baharaff , Galmed CEO Program Introduction: Dr. Liat Hayardeny - Brück , Galmed CSO Presenter: Prof. Arun Sanyal, MD Virginia Commonwealth University Medical Center Aramchol for NASH & Fibrosis Presenter MoA : Dr. Liat Hayardeny - Brück Presenter IBD: Prof. Shomron Ben
Slide 4: Galmed at a Glance
4 Galmed at a Glance • Clinical stage biopharma company with two lead assets in development o Aramchol - in Phase 3 for NASH and fibrosis o Amilo - 5 MER - Phase 1 - ready for acute and chronic inflammatory conditions including IBD • Aramchol has potential to be a backbone therapy for NASH and fibro
Slide 5: Galmed Development Team – Small, Experienced and Highly Efficient
Galmed Development Team – Small, Experienced and Highly Efficient 5 Liat Hayardeny - Brück Ph.D., MBA, Chief Scientific Officer + 21 years experience in drug development Prof. Ran Oren, M.D. Previously headed the Institute of Gastroenterology and Liver Diseases at Hadassah Ein Kerem Hospital, Jerusa
Slide 6: Galmed's Pipeline
6 Galmed’s Pipeline * South Korea rights licensed to Samil Pharma ** MBT - Microbiome - Based Technology Product candidate Product description (dosing frequency) Potential indications Stage of development Worldwide commercial rights Aramchol Acid SCD1 modulator 300 mg BID NASH and Fibrosis * Aramcho
Slide 7: Why Aramchol Meglumine?
Why Aramchol Meglumine? • Aramchol’s direct antifibrotic mechanism of action combined with its ability to reduce liver fat has potential to be a backbone therapy for NASH and fibrosis • Aramchol meglumine is a new salt form of Aramchol with an improved target product profile and 2035 IP protection •
Slide 8: Aramchol Meglumine, ARMOR Ph3 Open-Label Segment, Microbiome
• Aramchol – Meglumine • ARMOR Ph3 - Open - Label Segment • Microbiome for NASH & Fibrosis Introduction: Presenter:
Slide 9: Data Support FDA Approval of Change to Aramchol Meglumine
Data Support FDA Approval of Change to Aramchol Meglumine • Aramchol is the active moiety that is measured in plasma following administration of Aramchol Meglumine. • Meglumine is present as a class I counterion in many other oral pharmaceutical products. It is listed in the FDA Inactive Ingredients
Slide 10: New Data: PK Results of Twice Daily Administration of Aramchol and Aramchol Meglumine
New Data: Pk Results of Twice Daily Administration for 10 Days of Aramchol and Aramchol Meglumine in human 0 50 100 150 AUC ss 0-12h A U C [ g * h / m L ] Aramchol 300 mg BID Aramchol Meglumine 383 mg BID **** **** P < 0.0001 Less Aramchol meglumine dose is needed for same exposure of Aramchol
Slide 11: Aramchol Meglumine – Better Than Aramchol and Yet the Same
Aramchol Meglumine – Better Than Aramchol and Yet the Same 11 • Aramchol Meglumine circulates as Aramchol . • Galmed intends to target the desired exposure of Aramchol 300 mg BID currently used in the open label part of ARMOR. • Less Aramchol meglumine dose is needed for same exposure of Aramchol in
Slide 12: ARMOR Ph3 Open-Label Segment, Microbiome for NASH & Fibrosis
• ARMOR Ph3 - Open - Label Segment • Microbiome for NASH & Fibrosis Presenter:
Slide 13: ARMOR Ph3 Open-Label Segment: Efficacy kinetics, Safety and PK
ARMOR Ph 3 - Open - Label Segment: Efficacy kinetics, Safety and PK • The ARMOR protocol was amended to include an Open - Label segment to evaluate the safety, PK and kinetics of histological outcome measures and Non - Invasive Tests (NITs) associated with NASH and fibrosis 13 Visits Schedule NITs a
Slide 14: Open-Label Segment: Rationale, Objective, Population
Open - Label Segment: Rationale, Objective, Population 14 Rationale : Aligned with the advancement of the Aramchol meglumine program, the Open Label segment will allow an informed decision on: • Initial histology data with higher exposure and potential for improved efficacy • Characterizing the kine
Slide 15: Open-Label Segment – Study Groups
Open - Label Segment – Study Groups • All subjects will receive Aramchol 300 mg BID • A total of 150 subjects, including those already randomized to Aramchol 300 mg BID or placebo, will be randomized in a ratio of 1 : 1 : 1 to receive Aramchol 300 mg BID according to the below grouping : • Group A :
Slide 16: Open-Label Segment - Methodologies
Open - Label Segment - Methodologies • Frequent study visits include imaging (Fibroscan), Biomarkers (ProC 3 , ELF and others) and Microbiome profile • The central biopsy reading procedures, DMC and adjudication committees for the Open - Label Part are the same as those of the Randomized, Double - B
Slide 17: The Open Label Segment will De-Risk Aramchol's Clinical Development Program
The Open Label Segment will de - Risk Aramchol’s Clinical Development Program 17 Activity Result Using 300mg twice daily - higher exposure 1. Provide data on efficacy (magnitude of effects) and safety for the higher exposure regimen Broader Population including also: F1, Non diabetes, Different BMI
Slide 18: Microbiome - NASH relationships
Microbiome - NASH relationships 18 Disturbance of the gut – liver axis was shown to play a pivotal role in the pathogenesis of NAFLD and NASH • NAFLD and NASH patients are more likely to have altered gut permeability in comparison with healthy controls • The association of increased intestinal perme
Slide 19: Characterization of gut microbiomes in NASH patients
19 Characterization of gut microbiomes in nonalcoholic steatohepatitis ( NASH) patients: A connection between endogenous alcohol and NASH Zhu, L., Baker, S.S., Gill, C., Liu, W., Alkhouri , R., Baker, R.D. and Gill, S.R., 2013 ., 57 ( 2 ), pp. 601 - 609 .
Slide 20: Mapping of NASH-related microbiome
20 Mapping of NASH - related microbiome Sharpton, S.R., Ajmera, V. and Loomba, R., 2019 Clinical Gastroenterology and Hepatology, 17 ( 2 ), pp. 296 - 306 .
Slide 21: Mediation of microbiome for attenuation of NASH: Precedents
21 Mediation of microbiome for attenuation of NASH: Precedents J Gastroenterol ( 2020 ) 55:142 – 158
Slide 22: Aramchol's effect on the Microbiome
Aramchol’s effect on the Microbiome 22 Bifidobacterium Decrease in NASH Aramchol promotes growth . Collinsella : Increase in NASH Aramchol inhibits growth Relative abundance • Aramchol was tested in 100 mg/L and 300 mg/L for 5 days on healthy donor microbiome in vitro • The results based on 16 S - N
Slide 23: Galmed & MyBiotics Collaboration Highlights
Galmed & MyBiotics Collaboration Highlights 23 • Identification of microbiome repertoire associated with the response to Aramchol based on: - Phase 1 subjects data analysis - Phase 3 subjects data analysis - In depth in vitro studies • Development of microbiome - based therapeutic for combination wi
Slide 24: Amilo5-MER
Amilo5-MER Introduction: Dr. Liat Hayardeny - Briick , Galmed CSO Presenter: Prof. Shomron Ben-Horin, MD. Tel-Aviv University, Sheba Medical Center @Galmed
Slide 25: Amilo-MER Highlights
25 Amilo - 5 MER Highlights Amilo - 5 MER is a Differentiated, Specific and Selective Immune - Modulator 1 • Amilo - 5 MER is a specific amino acid sequence, homologue to the human CD 44 variant which displays an efficient anti - inflammatory effects • Amilo - 5 MER is a penta - peptide that prevent
Slide 26: Mechanism By Which Amilo-MER Interferes With Chronic Inflammation
26 The Mechanism By Which Amilo - 5 MER Interferes With Chronic Inflammation – Interferes With SAA Involvement Pro Inflammatory Cytokines ↑ Inflammation & Tissue Destruction Infection / Stimuli Macrophage SAA Aggregates SAA Monomers Amilo - 5 MER – Interferes with inflammatory vicious cycle by preve
Slide 27: Amilo-MER Prevents SAA Aggregation
27 Amilo - 5 MER Prevents SAA Aggregation, The Main Cause of Chronic Inflammation WITHOUT Amilo - 5 MER WITH Amilo - 5 MER * Research work performed in collaboration with Prof. Mary Cowman from New York University Video recording of nanoparticle tracking analysis of SAA* Number of SAA aggregates abo
Slide 28: Lee et al., 2020, Cell
28 Lee et al., 2020 , Cell 180 , 79 – 91 January 9 , 2020 ª 2019 Elsevier Inc. https://doi.org/ 10.1016 /j.cell. 2019.11.026
Slide 29: Amilo-MER Significantly Reduces Plasma Pro-Inflammatory Cytokines in LPS-induced Mice
29 Amilo - 5 MER Significantly Reduces Plasma Pro - Inflammatory Cytokines in LPS - induced Mice Model – the Gold Standard of Systemic Inflammation 1h 3h 0 2×10 4 4×10 4 6×10 4 2×10 5 4×10 5 6×10 5 IL-6 [ p g / m l , m e a n + / - S E M ] ** *** 1h 3h 0 5×10 2 1×10 3 1.5×10 3 INFg [ p g / m l , m e
Slide 30: Amilo-5MER Affects Histopathological Hallmarks in IBD Animal Model (TNBS)
TNBS + Vehicle TNBS+ Amilo-5MER 3mg/kg TNBS+ Amilo-5MER 15mg/kg TNBS + anti-TNFa 0.1mg 0 10 20 30 40 50 m R N A I L - 6 & I L - 1 b / G A P D H r a t i o IL-6 IL-1b * * Colonic mRNA levels of IL-6 & IL-1b 30 Amilo - 5 MER Significantly Affects Histopathological Hallmarks in IBD animal model (TNBS) *
Slide 31: Amilo-5MER Affects Clinical Symptoms in Rheumatoid Arthritis Model
31 CIA Sick C 57 BL/ 6 Mouse 9 Days after Amilo - 5 MER treatment Immunization with collagen ( 200 μ g/mouse) and CFA Boost: Collagen ( 200 μ g/mouse) and CFA 3 weeks Onset of disease 1 - 3 days 1 2 3 4 5 6 7 8 9 10 Peptide Injections (SC): Days after disease onset Protocol: Assay under blind manner
Slide 32: Amilo-MER Restores the Normal Anatomy of the Inflamed Joint
32 Amilo - 5 MER Restores the Normal Anatomy of the Inflamed Joint Following Amilo - 5 MER treatment Control A representative stained histopathological joint section from a mouse with CIA following 9 days treatment with Amilo - 5 MER). Pathology (blinded) assessment indicate a joint of a normal mous
Slide 33: Amilo-MER Demonstrates Therapeutic Effects in MOG and PLP Induced EAE Models
33 Amilo - 5 MER Demonstrates Therapeutic Effects in MOG and PLP Induced EAE Models in Mice Amilo - 5 MER Demonstrates Anti Inflammatory Effects in Major MS Experimental Models – Oral and in Treatment Mode PLP/ MOG induced EAE EAE boost 2 days 3 days 5 6 7 8 9 10 11 12 13 14 15 16 17 Peptide Injecti
Slide 34: Preclinical Safety Studies in Support of First-in-Human Study Completed
34 Preclinical Safety Studies in Support of First - in - Human Study Completed Maximum Tolerated Dose (MTD) studies in mice and dogs • 7 day MTD in mice at doses up to 1000 mg/kg, in dogs up to 200 mg/kg: No adverse effects were noted • 28 - days in mice at doses up to 175 mg/kg, an in dogs at doses
Slide 35: Clinical Development Plan for Mild to Moderate Ulcerative Colitis
Clinical Development Plan for Mild to Moderate Ulcerative Colitis
Slide 36: Serum Amyloid A (SAA) is Elevated in Active IBD Patients
Serum Amyloid A (SAA) is Elevated in the Site of Inflammation (biopsies); Active IBD Patients Compared to Healthy Individuals 36 CD active CD mucosal healing UC active Healthy 0 10 20 30 40 50 60 70 R e l a t i v e m R N A l e v e l s SAA levels in biopsies E xpression of SAA in intestinal tissue bi
Slide 37: Mild to Moderate Ulcerative Colitis
Mild to Moderate Ulcerative Colitis * Ko et al, 2019 - AGA Clinical Practice Guidelines on the Management of Mild - to - Moderate Ulcerative Colitis; ** https://www.fda.gov/files/drugs/published/Ulcerative - Colitis -- Clinical - Trial - Endpoints - Guidance - for - Industry.pdf Galmed is aiming to
Slide 38: Mild to Moderate Ulcerative Colitis
38 Mild to Moderate Ulcerative Colitis * Ko et al, 2019 - AGA Clinical Practice Guidelines on the Management of Mild - to - Moderate Ulcerative Colitis; ** https://www.fda.gov/files/drugs/published/Ulcerative - Colitis -- Clinical - Trial - Endpoints - Guidance - for - Industry.pdf Galmed is aiming
Slide 39: Amilo-MER Clinical Development Plan - Phase 1
39 Amilo - 5 MER - Clinical Development Plan ( CDP) - Phase 1 • Phase 1 a study in healthy volunteers planned initiation in Q 1 2021 . • Pre - IND meeting with the FDA planned for Q 3 2021 . • 6 weeks Open - label Phase 1 b PoC trial to study the safety and efficacy of Amilo - 5 MER in 20 active UC
Slide 40: Amilo-MER Planned Phase 2/3 & CDP
40 Amilo - 5 MER , Planned Phase 2 & 3 CDP • Phase 2 randomized, double - blind, placebo - controlled, multi - center trial will be performed in a specific UC population (i . e . , mild - to moderate or moderate - to severe), provided a meaningful clinical response is achieved in MS in at least 3 /
Slide 41: 2021, The Year of Change
41 H 1 2021 • Submission of 2 new INDs (Aramchol Meglumine & Amilo 5 - MER) • Data from Aramchol Meglumine Regulatory bioequivalence and food effect studies • Meeting with FDA for approval of Aramchol Meglumine NCE development program • In - vitro and in vivo data from Aramchol / ASC 41 (THR - ß - a
Slide 42: Thank You
THANK YOU