Molecure Sa · GPW:MOC
Molecure Sa — Investor Day (December 2022)
115 slides from Molecure Sa's investor day presentation, Dec 7, 2022
Slide 1: R&D Day
R&D Day December 7, 2022 Fate can be altered
Slide 2: Disclaimer
Molecure SA (”MOC") and its Board and employees make no warranties or assurances regarding the accuracy or completeness of any representations or other materials contained herein. The information and data contained herein reflect the current conditions and assessments of the market situation as at t
Slide 3: Speakers
Speakers Marcin Szumowski Nicolas Beuzen PhD, MBA PhD, MBA Chairman of the Board & CEO Business Development Director Entrepreneur and investor with 20-year 20 years of experience working with high experience in the life science industry. performance, international R&D teams. R&D leaders Samson Fung
Slide 4: Speakers: Clinical Experts
Speakers Clinical Experts Professor Rafał Krenke Professor Cezary Szczylik Head of Department of Internal Medicine, Pulmonary Head of the Department of Clinical Oncology and Diseases & Allergy, Medical University of Warsaw Chemotherapy European Health Center Otwock Member of the European Respiratory
Slide 5: Agenda
Agenda Welcome and Agenda OATD-02: Clinical Development Katarzyna Mucha, CCGroup in a Broad Range of Cancers (Part 2) S. Fung CMO, Z. Zasłona VP Biology, Prof. Cezary Szczylik Oncologist Introduction to Molecure Marcin Szumowski CEO USP7, YKL-40, UoM, RNA (Part 3) OATD-01: Sarcoidosis Market Opportu
Slide 6: Molecure history 2012-2022
Molecure history 2012-2022 CORPORATE Seed Round and Exclusive President’s IPO on the Global License Option to First Drug License from Award for Best Warsaw Stock for OATD-01 License Discovery Yale and Series R&D Company Exchange with Galapagos from the U. of Program A Investment in Poland (WSE) NV M
Slide 7: High Value Pipeline
High Value Pipeline Current status Clinical Candidate 2023 estimate Selection Molecular Target Lead In Vivo Preclinical Regulatory Target Indications Validation Optimization POC Development Process Phase I Phase II Hit-to-lead PROTEIN TARGETS OATD-01 Sarcoidosis, other OATD-01 OATD-01 CHIT1/AMCASE I
Slide 8: Our Main Achievements to Date
Our Main Achievements to Date Accelerating clinical development • Delivering on value generating strategy as a Significant pipeline momentum: focused small molecule company • Lead proprietary candidate, OATD-01 a novel • Ongoing commitment to focus on discovery and chitinase inhibitor in sarcoidosis
Slide 9: Developing first-in-class small molecule drugs to address challenging protein targets
Developing first-in-class small molecule drugs to address challenging protein targets 07/12/2022 9
Slide 10: OATD-01: disease modifying potential in sarcoidosis
OATD-01: disease modifying potential in sarcoidosis
Slide 11: OATD-01 in sarcoidosis on-track to enter Phase II in 2023
OATD-01 in sarcoidosis on-track to enter Phase II in 2023 Clinical Trial Application submission package filing expected Q1 2023 Key Opinion Clinical Trial First Patient Last Patient Clinical Study Scientific Advice Leader Application First Visit Last Visit Report Consultations Submission Q1-Q2 Q2-Q4
Slide 12: OATD-01 Targets CHIT1 (Chitotriosidase 1)
OATD-01 Targets CHIT1 (Chitotriosidase 1) Biological & Medical Significance of this novel target 07/12/2022 12/7/2022 12 12
Slide 13: Targeting CHIT1
Targeting CHIT1 Healthy IPF BALF Cells - IPF •CHIT1 is the most prominent chitinase in humans, can cleave chitin, participates in the body's immune response and is associated with inflammation, CHIT1 tissue damage and remodeling processes •CHIT1 is expressed mostly by activated macrophages 07/12/202
Slide 14: CHIT1 is highly expressed in lungs of patients with sarcoidosis
CHIT1 is highly expressed in lungs of patients with sarcoidosis F Expression of CHIT1 in lungs Lung sarcoidosis and serum of patients with confirmed sarcoidosis Biopsy 1. diseased lungs with Lung biopsies from sarcoidosis patients granulomas show very strong expression of CHIT1 specifically restrict
Slide 15: CHIT1 is expressed in a subset of fibrosis-specific lung macrophages of IPF patients
Lung cell clusters CHIT1 CHIT1 is expressed in a subset of fibrosis-specific lung macrophages of IPF patients Fibrosis Donor In a differential single cell atlas of pulmonary fibrosis, CHIT1 is expressed in profibrotic alveolar macrophages exclusively present in patients with fibrosis and not in heal
Slide 16: Role of profibrotic macrophages in the pathogenesis of pulmonary fibrosis
Role of profibrotic macrophages in the pathogenesis of pulmonary fibrosis Macrophages are long lived cells capable of shaping the inflammatory microenvironment with plasticity allowing for therapeutic interventions Macrophage polarization determines the phenotype of fibroblasts in progressive pulmon
Slide 17: Translational Biomarker Studies
Translational Biomarker Studies CHIT1 activity in serum, induced sputum and BAL fluid samples from IPF and sarcoidosis patients Serum Induced sputum BALf Normal IPF Sarcoidosis Normal control IPF Sarcoidosis IPF Sarcoidosis control The analysis of chitinolytic activity in samples collected from Thes
Slide 18: Reduced Pulmonary Fibrosis and Inflammation in Bleomycin-Induced IPF Model in CHIT1 Knock-Out Mice
Reduced Pulmonary Fibrosis and Inflammation in Bleomycin-Induced IPF Model in CHIT1 Knock-Out Mice Inflammation Pulmonary Fibrosis 300000 **** * Total BAL (CD45+) cell number **** ** 7 Fibrosis: Ashcroft Score (mean with SEM) 200000 6 5 100000 4 4 0 0 CHIT1 CHIT1 WT saline CHIT1 WT CHIT1 KO C WT CHI
Slide 19: Creating Significant Value with OATD-01
Creating Significant Value with OATD-01 Supportive pre-clinical data 07/12/2022 19
Slide 20: Efficacy of OATD-01 in MWCNT-induced granulomatous inflammation model in mice
Efficacy of OATD-01 in MWCNT-induced granulomatous inflammation model in mice OATD-01 suppressed development of the organized granulomatous structures in lungs and CCL4 levels in BALF in the MWCNT (multi wall carbon nanotubes) + ESAT-6-induced model of sarcoidosis 40 days post Day 10 Organized granu
Slide 21: OATD-01 attenuates lung fibrosis in mice
OATD-01 attenuates lung fibrosis in mice Bleomycin OATD-01 Pirfenidone Control (2 U/kg) (30 mg/kg, b.i.d) (250 mg/kg, b.i.d) A OATD-01 reduces features of pulmonary fibrosis in bleomycin induced model B C D Control Bleomycin OATD-01 Pirfenidone Control Bleomycin OATD-01 Pirfenidone Control Bleomycin
Slide 22: Efficacy of OATD-01 in multiple models of NASH in mice and rats
C on tr ol (n NAFLD activity score 0 2 4 6 o di 07/12/2022 se ST as A Controle) M (no disease) STAM + ST O A A M TD ✱✱✱✱ ST ve A -0 1 . h M + 30 STAM veh. O m A and rats TD g/ kg ✱✱✱ -0 1 + OATD-01 STAM qd 1030 mg/kg qd 0 ✱✱✱✱ m g/ kg STAM + OATD-01 qd 100 mg/kg qd N W D NAS score [scale 0-9] 0 2 4
Slide 23: Top processes regulated in NASH model involve macrophage activation and migration
Top processes regulated in NASH model involve macrophage activation and migration Most up-regulated pathways Most down-regulated pathways regulation of macrophage migration acetyl-CoA metabolic process regulation of triglyceride metabolic regulatory T cell differentiation process neutrophil chemotax
Slide 24: Major pathways regulated by OATD-01 in NASH model
Major pathways regulated by OATD-01 in NASH model Most up-regulated pathways Most down-regulated pathways xenobiotic metabolic process collagen fibril organization thioester metabolic process extracellular matrix organization mitochondrial respiratory chain collagen metabolic process complex assembl
Slide 25: Common pathways and genes regulated by OATD-01
Common pathways and genes regulated by OATD-01 NASH vs control OATD-01 vs NASH Most regulated pathways Most regulated pathways acetyl-CoA metabolic process acetyl-CoA metabolic process Collagen fibril organisation Collagen fibril organisation Macrophage migration Macrophage migration OATD01 NASH Com
Slide 26: OATD-01: A first in class small molecule chitinase inhibitor for inflammatory and fibrotic diseases
OATD-01: A first in class small molecule chitinase inhibitor for inflammatory and fibrotic diseases 07/12/2022 26
Slide 27: Unique Attributes of OATD-01
Unique Attributes of OATD-01 • OATD-01 is potentially disease modifying agent for interstitial lung diseases, starting with sarcoidosis • OATD-01 is a novel, single-digit nM, first-in-class small molecule chitinase (CHIT1) inhibitor targeting a key mechanistic pathway involved in inflammation and ti
Slide 28: OATD-01 – Promising clinical data
OATD-01 – Promising clinical data Compelling Data •Efficacy proven in multiple animal models of sarcoidosis, chronic and acute asthma, idiopathic pulmonary fibrosis, (IPF) and non-alcoholic steatohepatitis (NASH) •Compelling translational data •Excellent pharmacological profile •Demonstrated safety
Slide 29: International Key Opinion Leaders supportive of the clinical development of OATD-01 in sarcoidosis
International Key Opinion Leaders supportive of the clinical development of OATD-01 in sarcoidosis Marlies Wijsenbeek Michael Kreuter MD Vincent Cottin MD Daniel Culver MD Mark Judson MD Lourens MD PhD - NL PhD - DE PhD - FR PhD - US PhD - US Pulmonologist, Chair Head of the Center for Hospices Civi
Slide 30: Clinical Development of OATD-01
Clinical Development of OATD-01 A potential disease modifying agent for sarcoidosis 07/12/2022 30
Slide 31: OATD-01 – Translational and clinical data to support a PoC study in sarcoidosis
OATD-01 – Translational and clinical data to support a PoC study in sarcoidosis Very strong clinical Unmet medical need: no Clinical Phase I results correlation of CHIT1 activity effective therapy, advanced with the disease process disease is debilitating with •Full and sustained pharmacodynamic (PD
Slide 32: OATD-01 Phase I conclusions
OATD-01 Phase I conclusions • Clinical phase I completed ▪ Single ascending doses of 25 mg, 50 mg, 100 mg, 200 mg, 400 mg and 600 mg ▪ Multiple ascending dose of 25 mg and 50 mg for 12 days • OATD-01 was generally well tolerated ▪ No treatment-related Serious Adverse Events (SAE) ▪ No alerting safet
Slide 33: Positive results of Drug Drug Interaction (DDI) studies
Positive results of Drug Drug Interaction (DDI) studies When co-administered with other drugs commonly used in patients with fibrotic conditions, and midazolam, OATD-01 was well tolerated and did not significantly change the exposure of either drugs When co-administered When co-administered Repeated
Slide 34: OATD-01 on-track to enter Phase II in 2023
OATD-01 on-track to enter Phase II in 2023 Trial Design & Sites Objectives: Major Endpoints: Patients: •Double-blind, randomized, placebo- •Imaging response by PET/CT to a • ~90 male and female patients with controlled multicenter study to 12-week treatment as a reduction of active pulmonary sarcoid
Slide 35: OATD-01: Potential indications beyond sarcoidosis
OATD-01: Potential indications beyond sarcoidosis Sarcoidosis is the entry point to proving the clinical utility of targeting CHIT1 Positive results in the phase IIa proof of concept could pave the way to multiple other indications where chronic inflammation drive tissue remodelling, and where the e
Slide 36: Prof. Rafał Krenke, pulmonologist
Prof. Rafał Krenke, pulmonologist Head of Department of Internal Medicine, Pulmonary Diseases & Allergy, Medical University of Warsaw His scientific interest are focused on obstructive pulmonary diseases, pulmonary infections, pleural disorders and endoscopic techniques used in the diagnosis and tre
Slide 37: What is sarcoidosis
What is sarcoidosis • Systemic inflammatory disease characterized by formation of immune granulomas in various organs • Granulomas are tight aggregates of immune cells consisting of centrally located, pathologically activated macrophages, epithelioid and giant cells, Crouser ED, et al. Am J Respir C
Slide 38: Burden of sarcoidosis
Burden of sarcoidosis • Sarcoidosis is classified as a rare disease • The incidence of sarcoidosis is ➢ 0.5 to 1.3 per 100,000 in East Asia, ➢ 11.3-14.8 per 100,000 in Scandinavian countries ➢ 7 to 11 per 100,000 in the United States and Canada. • Overall, the prevalence of sarcoidosis is 60 to 77 p
Slide 39: Organ involvement in sarcoidosis (ACCESS study)
Organ involvement in sarcoidosis (ACCESS study) Sarcoidosis is a multiorgan disease that may present with a numer of different faces!! Baughman, RP, Teirstein, AS, Judson, MA, et al. Am J Respir Crit Care Med 2001;164:1885 07/12/2022 39
Slide 40: Clinical features and organ involvement in sarcoidosis
Clinical features and organ involvement in sarcoidosis Features and frequency of pulmonary sarcoidosis stages Frequency at Stage Radiographic features presentation (%) I Medistinal and hilar adenopathy with no pulmonary infiltrates 40-50 II Medistinal and hilar adenopathy with pulmonary infiltrates
Slide 41: Clinical features and organ involvement in sarcoidosis
Clinical features and organ involvement in sarcoidosis Shlobin AO, Nathan SD. Eur Respir J 2012, 39: 1520-1533 Patients with sarcoidosis may show very different stages of pulmonary involvement! 07/12/2022 41
Slide 42: Clinical features and organ involvement in sarcoidosis
Clinical features and organ involvement in sarcoidosis Drent M, et al. N Engl J Med 2021;385:1018-32. 07/12/2022 42
Slide 43: The clinical course of sarcoidosis
The clinical course of sarcoidosis Not easily predictable Spontaneous remission in patients with stage I - 60-80% but only approximately 30% in patients with stage II and III Ungprasert P, et al. Sarcoidosis Vasc Diffuse Lung Dis. 2018; 35(2): 123–128. 07/12/2022 43
Slide 44: The clinical course of sarcoidosis
The clinical course of sarcoidosis (Rochester Epidemiology Project (REP), Olmsted Country, MN, US) Stages at diagnosis: stage I disease (54%), stage II (29%), III (15%) and IV (2%). The median length of follow-up 13.8 years. The 10-year chronic respiratory failure rate = 4.4% (95% CI, 1.9.-6.9) The
Slide 45: Risk factors and favorable factors in sarcoidosis
Risk factors and favorable factors in sarcoidosis 07/12/2022 45
Slide 46: Sarcoidosis consequences and complications
Sarcoidosis consequences and complications • Pulmonary fibrosis is the most severe complication of sarcoidosis • Usually associated with chronic dyspnea and impairment of pulmonary function • Pulmonary fibrosis is the most frequent cause of respiratory failure and results in the majority of deaths r
Slide 47: Patients presenting with sarcoidosis
Patients presenting with sarcoidosis Three fourths of these patients would require treatment The main aim of treatment is to preserve organ function and improve patient symptoms. Steroids and immunosuppressants are the preferred treatments Treatment goals # Approximately 26% of On average, 74% of ▪
Slide 48: Current ERS guidelines
Current ERS guidelines 07/12/2022 48
Slide 49: Decision making on sarcoidosis treatment
Decision making on sarcoidosis treatment The decision of who and when to treat an individual sarcoidosis patient depends on two major factors: • risk for death or organ failure, • impairment of quality of life (QoL). About 5% of patients die from the disease and pulmonary and cardiac disease are the
Slide 50: Decision making on sarcoidosis treatment
Decision making on sarcoidosis treatment • Fatigue is a very common symptom in sarcoidosis (reported in up to 90% of patients) and is strongly associated with a lower QoL. • It is not always related to organ involvement induced bysarcoidosis and may persist for many years, even after apparent remiss
Slide 51: Current algorithm for sarcoidosis treatment
Current algorithm for sarcoidosis treatment Drent M, et al. N Engl J Med 2021;385:1018-32. 07/12/2022 51
Slide 52: Current algorithm for sarcoidosis treatment
Current algorithm for sarcoidosis treatment 07/12/2022 Drent M, et al. N Engl J Med 2021;385:1018-32. 52
Slide 53: Current treatment paradigms
Current treatment paradigms • No cure for sarcoidosis, treatments only modify the granulomatous process and its clinical consequences - major opportunity for a new disease modifying therapy • Little data to guide therapy strategies despite guidelines • Systemic corticosteroids remain the standard of
Slide 54: Current immunsuppressive therapies for sarcoidosis
Current immunsuppressive therapies for sarcoidosis Baughman RP, et al. Eur Respir J. 2021; 58: 2004079 07/12/2022 54
Slide 55: OATD-01 Opportunity Assessment
OATD-01 Opportunity Assessment A potential disease modifying agent for sarcoidosis 07/12/2022 55
Slide 56: Opportunity assessment – Citeline study
Opportunity assessment – Citeline study Objectives KOL interviews 45-60 min virtual discussions Current treatment Opportunity assessment paradigms and unmet needs and pricing considerations KOL requirements •Understand the main treatment goals •Document KOL and payer opinions •Treat sarcoidosis pati
Slide 57: Significant unmet needs, a KOL perspective
Significant unmet needs, a KOL perspective The main need in sarcoidosis is a safer treatment that could halt disease progression, whilst still being cost-effective Satisfactory score for current options: 6/10 Most significant unmet needs Very high Safety 6.3 unmet need •Need for quick, accurate & no
Slide 58: Disease modifying therapies in sarcoidosis are eagerly awaited
Disease modifying therapies in sarcoidosis are eagerly awaited As well as stopping disease progression, KOLs hope that new disease-modifying therapies can offer a safe and effective alternative to steroids Key desirable disease-modifying Of patients would be Up to Of patients would be drug attribute
Slide 59: Significant market opportunity for disease-modifying profile
Significant market opportunity for disease-modifying profile Global sarcoidosis market is currently catered for with old, genericized drugs such as steroids and other immunosuppressive drugs are inexpensive However, the market is likely to completely change in the coming years. The two most advanced
Slide 60: Significant market opportunity for Sarcoidosis alone
Significant market opportunity for Sarcoidosis alone US 200,000 patients EU / UK 150,000 patients JP 20,000 patients Patients Treatment Segmentation Antimetabolite Anti-TNFs No treatment Oral Corticosteroids alone immunosupressants Approx. Approx. 25% Approx. 45% Approx. 20% 10% Core target Upside t
Slide 61: OATD-01 a potential major step forward in therapy
OATD-01 a potential major step forward in therapy Molecure is committed to Demonstrated safety in IND filing with the FDA solving unmet medical Phase I studies in human expected in 1Q 2023 needs of patients with volunteers interstitial lung diseases, Efficacy proven in multiple starting with sarcoid
Slide 62: Q&A
Q&A
Slide 63: OATD-02: A first in class dual arginase inhibitor for cancer applications
OATD-02: A first in class dual arginase inhibitor for cancer applications
Slide 64: High Value Pipeline
High Value Pipeline Current status Clinical Candidate 2023 estimate Selection Molecular Target Lead In Vivo Preclinical Regulatory Target Indications Validation Optimization POC Development Process Phase I Phase II Hit-to-lead PROTEIN TARGETS OATD-01 Sarcoidosis, other OATD-01 OATD-01 CHIT1/AMCASE I
Slide 65: OATD-02 targeting a broad range of solid tumors
OATD-02 targeting a broad range of solid tumors Pursuing first in class dual arginase inhibitor (Arginase 1 and Arginase 2) targeting solid tumors Leadership position in arginase discovery, in particular modulating the intra-cellular ARG2 High arginase activity has been found in patients with a wide
Slide 66: Favorable Competitive landscape
Favorable Competitive landscape 3 main competitors in Oncology with small molecules. •Incyte / Calithera INCB001158 – Phase II •AstraZeneca AZD-0011 – Preclinical •Merck & Co – Discovery 2 companies also developing small molecule arginase inhibitors in other indications •Calithera – CB280 – Phase Ib
Slide 67: OATD-02 Key Milestones, 2022-2024
OATD-02 Key Milestones, 2022-2024 Clinical Trial Drug product First Patient Last Patient *Clinical Study Scientific advice Application manufacturing First Visit Last Visit Report Granted Q1 Q2 Q4 Q1 H2 H2 2022 2022 2022 2023 2024 2024 *Clinical Study Report 07/12/2022 67
Slide 68: OATD-02: Unique mechanism of action
OATD-02: Unique mechanism of action
Slide 69: OATD-02 is a first-in-class dual ARG1-ARG2 inhibitor
OATD-02 is a first-in-class dual ARG1-ARG2 inhibitor Molecure is the only company offering a dual arginase inhibitor with high intracellular activity Highly potent, orally active Significant anticancer efficacy as dual ARG1/ARG2 inhibitor monotherapy and in combinations in with intracellular activit
Slide 70: Increased ARG1 & ARG2 suppress anti-tumor immune responses
Increased of ARG1 & ARG2 suppress anti-tumor immune responses CD4 T cell 07/12/2022 70
Slide 71: OATD-02 restores effective anti-tumor immune responses via inhibition of ARG1 and ARG2
0ATD-02 restores effective anti-tumor immune responses via inhibition of ARG1 and ARG2 07/12/2022 71
Slide 72: OATD-02 Compelling pre-clinical data
OATD-02 Compelling pre- clinical data 07/12/2022 72
Slide 73: OATD-02 demonstrated dose-dependent therapeutic effect in colorectal cancer model
OATD-02 demonstrated dose-dependent therapeutic effect in colorectal cancer model Significant dose-dependent effect was demonstrated in the CT26 model* High concentrations of OATD-02 detected in plasma and tumors correlated with dose OATD-02 induced significant PD effect – arginine levels were eleva
Slide 74: OATD-02 improved the efficacy of immune checkpoint inhibitors
OATD-02 improved the efficacy of immune checkpoint inhibitors OATD-02 enhanced the efficacy of anti-PD-L1 antibodies in colorectal cancer model Vehicle OATD-02 (50 mg/kg, PO, BID) Syngeneic Syngeneic CT26 model CT26 model Anti-PD-L1 (2.5 mg/kg, IP, 4 doses) OATD-02 + anti-PD-L1 OATD-02 OATD-02 ++ant
Slide 75: OATD-02 showed superior activity in a triple therapy combined with anti-PD-L1 antibody & epacadostat
OATD-02 showed superior activity in a triple therapy combined with anti-PD-L1 antibody & epacadostat (IDO inhibitor) OATD-02 showed superior antitumor Syngeneic CT26 model activity in combination with IDO OATD-02 + anti-PD-L1 + IDO inhibitor inhibitor (TGI 61% vs. 33% for EPA TGI TGI TGI TGI TGI TGI
Slide 76: OATD-02 combined with PD-1 antibody reduced the growth of syngeneic GL216 glioma
OATD-02 combined with PD-1 antibody reduced the growth of syngeneic GL216 glioma in the orthotopic model Days post intracranial tumor implantation CCL5 is highly OATD-02 combined 14 21 28 expressed in glioma CCL5 (Rantes) in plasma with PD-1 antibody Vehicle and is associated with ✱✱✱✱ reduced the g
Slide 77: OATD-02 compelling efficacy in animal studies
OATD-02 compelling efficacy in animal studies •Demonstrates dose-dependent therapeutic effect & immune activation response in a C26 tumor model – CRC •Improved the efficacy of immune checkpoint inhibitors •Enhanced the efficacy of anti-PD-1 and anti-PD-L1 antibodies •Showed a superior activity in a
Slide 78: OATD-02 displays an attractive target product profile
OATD-02 displays an attractive target product profile Biological effect INCB001158 OATD-02 Extracellular activity hARG1 80 nM hARG1 20 nM Intracellular Activity Low/none Tregs, ARG2 dependent cancer cells, tumor associated fibroblasts Efficacy in syngeneic models average high Efficacy in xenograft m
Slide 79: Clinical Development Plan
Clinical Development Plan 07/12/2022 79
Slide 80: Professor Cezary Szczylik, Oncologist
Professor Cezary Szczylik, Oncologist Head of the Department of Clinical Oncology and Chemotherapy European Health Center Otwock His scientific interest concentrates on hematology and clinical oncology. Prof. Szczylik is a President of the Foundation for Experimental and Clinical Oncology, co-founde
Slide 81: Unmet need in oncology
Unmet need in oncology •Recent advances in diagnosis and treatment of cancer diseases have resulted in declining cancer death rates 215 across most developed countries 29% •In particular immunotherapies such as checkpoint inhibitors have led to increase in treatment responses and survival 152 Declin
Slide 82: Tumor types with particular unmet need
Tumor types with particular unmet need Pancreatic ductal cancer (advanced, inoperable) •current standard treatments comprise chemotherapy combinations (taxanes, gemcitabine, platinum derivates, irinotecan etc.) •ICIs have not yet demonstrated significant efficacy Metastatic colorectal cancer •ICI ef
Slide 83: State of oncology in Poland – Statistics
State of oncology in Poland – Statistics According to the Polish National Cancer Registry (2019): • Cancer is the second cause of death in Poland and a significant health problem primarily in young and middle-aged people (25-64 years) •171,218 have been diagnosed, and 100,300 died of cancer • 85,559
Slide 84: State of oncology in Poland – common cancers
State of oncology in Poland – common cancers ♂ ♀ • the most common cancer in men is prostate • in the female population, the leading cancers are: cancer (almost 21%) breast, lung and colorectal • lung cancer is the second leading cancer in • the incidence of breast cancers, which are men, accounting
Slide 85: State of oncology in Poland - treatments
State of oncology in Poland - treatments Pancreatic cancer •Treatment of pancreatic cancer is one of the most difficult and still poses a big challenge for oncologists . o Results of the treatment remain unsatisfactory, despite undoubted progress, o Mortality rates meet the morbidity rates. o Overal
Slide 86: State of oncology in Poland - treatments
State of oncology in Poland - treatments Ovarian cancer • In ovarian cancer, prevention is impossible, and the symptoms are not characteristic. o The surgical treatment should take place in experienced centers. o Comprehensive care for patients is also needed. o Genetic tests are performed too rarel
Slide 87: OATD-02 on-track to enter the clinic in 2023
OATD-02 on-track to enter the clinic in 2023 CTA granted. Study initiation with first patient first visit expected Q1 2023 Potential best-in-class profile: •First dual ARG1/ARG2 inhibitor •Favorable therapeutic window of OATD-02 for improved safety and tolerability •Better infiltration in tumor micr
Slide 88: OATD-02 FIH Phase I/II study (1)
OATD-02 FIH Phase I/II study (1) Design •Open-label single-arm dose-escalation monotherapy study (Bayesian design) Patient population (30-40 patients) •Relapsed/refractory advanced and/or metastatic solid tumours •Colorectal cancer, platinum-resistant serous ovarian cancer, pancreatic ductal cancer,
Slide 89: OATD-02 FIH Phase I/II study (2)
OATD-02 FIH Phase I/II study (2) Study Objectives: •Primary outcomes: safety and tolerability, determination of MTD/RP2D •Secondary outcomes: PK, PD (biomarkers), anti-cancer activity (response, survival endpoints) Data generated will inform design of future additional studies across multiple tumor
Slide 90: Key highlights of OATD-02
Key highlights of OATD-02 First in class OATD-02 dual arginase demonstrates therapy robust efficacy in animal studies First in human clinical study to Novel approach start in early with very limited 2023 competition Potential to Potential as a treat a broad mono and range of cancer combination patie
Slide 91: Q&A
Q&A
Slide 92: 10 minute break
10 minute break 07/12/2022 92
Slide 93: Next session starts at 15:40
Next session starts at 15:40
Slide 94: Our vision
Our vision Our goal is to become a leading biotechnology company, globally recognized for discovering and developing breakthrough small molecule drugs acting on unexplored protein and novel RNA targets to help patients in need of innovative therapeutic solutions 07/12/2022 94
Slide 95: Early programs
Early programs
Slide 96: High Value Pipeline
High Value Pipeline Current status Clinical Candidate 2023 estimate Selection Molecular Target Lead In Vivo Preclinical Regulatory Target Indications Validation Optimization POC Development Process Phase I Phase II Hit-to-lead PROTEIN TARGETS OATD-01 Sarcoidosis, other OATD-01 OATD-01 CHIT1/AMCASE I
Slide 97: Ubiquitin pathway – focus on post-translational modifications
Ubiquitin pathway – focus on post-translational modifications • Ubiquitination is a post translational modification covalently attaching ubiquitin to targeted proteins • Ubiquitination determines or alters protein’s biological activity, stability or sub-cellular localization 07/12/2022 97
Slide 98: Significance of deubiquitinase inhibition
Significance of deubiquitinase inhibition • Deubiquitinating enzymes (DUBs), are proteases that reverse the post translational modification of proteins by removing ubiquitin or remodeling ub-chains on target proteins Molecure is developing • As a result, DUBs have a great inhibitors of DUBs, includi
Slide 99: Significant tumor size reduction in CT26 model after USP7i (OAT-4828) treatment
Significant tumor size reduction in CT26 model after USP7i (OAT-4828) treatment CT26 tumor growth kinetics CT26 tumor weight at day 20 07/12/2022 99
Slide 100: OAT-4828 treatment induces CD8 T cells
OAT-4828 treatment induces CD8 T cells OAT-4828 increases cytotoxic OAT-4828 increases cytotoxicity of CD8+ T by CD8+ T cells in tumor and spleen increasing the expression of Granzyme B and INFg Tumor Stimulated splenocytes from OAT-4828 treated mice 07/12/2022 100
Slide 101: Increased killing of CT26 cells by effector cells from OAT-4828 treated mice
Increased killing of CT26 cells by effector cells from OAT-4828 treated mice Live CT26 OAT-4828 Green dye + Live CT26 Mice-treated splenocytes 36h co-culture Effector cells isolated from the spleen of mice treated with OAT-4828 Live/Dead staining And for 20 days bear the potential to induce cell dea
Slide 102: Significant survival increase in CT26 model after OAT-4828 treatment in combination with αPD-1
Significant survival increase in CT26 model after OAT-4828 treatment in combination with αPD-1 Survival analysis (mono) Survival analysis (combo) OAT-4828 increases the survival of animals by 14% vs. control (stand alone) and by 26% in combination with an aPD- 1 vs. aPD-1 alone at 100 mg/kg PO, BID.
Slide 103: OAT-4828 shows efficacy in B16F10 melanoma cancer model
OAT-4828 shows efficacy in B16F10 melanoma cancer model Tumour growthTumorTumour growthgrowth Subc. B16F10 model, treatment from day 7 B16F10 model, treatment from day 7 Subc. Subc. B16F10 model, treatment from day 7 ✱ OAT-4828: 1500 1500 Vehicle •decreases tumor (mm3, median, day 18th) 1500 growth
Slide 104: Human primary co-cultures validates anti-tumor and immunomodulatory properties of OAT-4828
Human primary co-cultures validates anti-tumor and immunomodulatory properties of OAT-4828 In human primary co-culture of Fibroblasts Venular endothelial cells + PBMCs + HT-29 (CRC) + PBMCs + HT-29 (CRC) fibroblasts (stromal model) or venular endothelial cells (immune model) with PBMC and colorectal
Slide 105: YKL-40 binders
YKL-40 binders Status •Advanced lead stage •Selective YKL-40 binder •Favorable pharmacokinetic profile •No significant off-target activity Research Focus in 2023 •Reveal the mechanism of action of YKL40 and its binder through scientific collaboration(s) 07/12/2022 105
Slide 106: License option agreement to develop small molecule assets against a novel target for fibrotic diseases
License option agreement to develop small molecule assets against a novel target for the treatment of fibrotic diseases Status •Constant know-how transfer, screening cascade set up and lead optimization •Verification of the therapeutic efficacy in various fibrosis models •Aiming for first-in-class s
Slide 107: Our small molecule mRNA discovery platform
Our small molecule mRNA discovery platform The potential to disrupt mRNA targeting approaches
Slide 108: High Value Pipeline
High Value Pipeline Current status Clinical Candidate 2023 estimate Selection Molecular Target Lead In Vivo Preclinical Regulatory Target Indications Validation Optimization POC Development Process Phase I Phase II Hit-to-lead PROTEIN TARGETS OATD-01 Sarcoidosis, other OATD-01 OATD-01 CHIT1/AMCASE I
Slide 109: Discovering medicines of the future
Discovering medicines of the future Small molecules targeting RNA to prevent downstream RNA translation 3D CONFORMATION PREDICTION GENE OF INTEREST BOUND SMALL MOLECULE 2D RNA STRUCTURE - NO TRANSLATION - NO PATHOLOGICAL PROTEIN Selection of functional 1 targets, with unique properties UNIQUE ALGORI
Slide 110: Our mRNA platform discovery workflow
Our mRNA platform discovery workflow We are here Docking Validation in NMR (virtual 3D In silico Druggable In silico 3D wet lab Active X-ray screening) Small structure Sequence Secondary structure Small molecule of the shape structures NMR of DNA molecule complex X-ray Docking Hit (virtual screening
Slide 111: Q&A
Q&A
Slide 112: Molecure 3-year goals
Molecure 3-year goals Potential milestones targeted by 2025 Protein Targets BD/Financial/Operational RNA Platform 2023-2024 2023-2024 2023-2024 •Two clinical assets in PhI/II multi •At least one clinical stage program •In vitro PoC reached for 2-3 high center clinical trials in patients partnered in
Slide 113: Value creation potential based on our key strengths
Value creation potential based on our key strengths World class medicinal chemistry Bold & smart target selection – Multiple academic partnerships to and biology expertise both mRNA and proteins access the target biology Validated discovery & development Undrugged, limited competition, Allows us to
Slide 114: Thank you
Thank you
Slide 115: Abbreviations used
Abbreviations used: •ADME: Absorption, Distribution, Metabolism, And Excretion •IND: Investigational New Drug •BALF: Broncho-alveolar Lavage Fluid •IPF: Idiopathic Pulmonary Fibrosis •BID: Bis In Die – Twice A Day •KOL: Key Opinion Leader •CHIT1: Chitotriosidase •LPLV: Last Patient Last Visit •CSR: