Cereno Scientific Ab Class B · OMXSTO:CRNO_B
Cereno Scientific Ab Class B — Investor Day (August 2022)
129 slides from Cereno Scientific Ab Class B's investor day presentation, Aug 30, 2022
Slide 1: Cereno Scientific Capital Markets Day
Cereno Scientific Capital Markets Day August 30, 2022
Slide 2: Welcome and Introduction to Cereno CMD 2022
Welcome and Introduction to Cereno CMD 2022 • Moderator today: Lars Frick, financial journalist at Börsveckan, specialist in Life Science • Agenda – corporate and external speakers with commercial and scientific presentations • Q&A and panel discussion – open for questions from audience in-situ and
Slide 3: Today's program
Today’s program Dr. Raymond L. Benza Sten R. Sörensen Dr. Björn Dahlöf Professor of Medicine, Wexner Chief Executive Chief Medical Officer Medical Center, Officer Ohio State University, SAB, Cereno and PI for CS1’s Phase II study Dr. Phil Adamson Dr. Michael Holinstat Dr. Gunnar Olsson Divisional Vi
Slide 4: Cereno's Commitment to Transforming Cardiovascular Disease Management
Cereno’s Commitment to Transforming Cardiovascular Disease Management Sten R. Sörensen Chief Executive Officer (CEO), Cereno
Slide 5: Disclaimer
Disclaimer This presentation has been prepared and produced by Cereno Scientific AB (publ) (“Cereno Scientific”) solely for Cereno Scientific’s investor presentation and may not be used for any other purpose. Unless otherwise stated, Cereno Scientific is the source for all data contained in this pre
Slide 6: Most deaths worldwide are caused by cardiovascular disease
Most deaths worldwide are caused by cardiovascular disease Cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels. WHY? Most CVD complications happen because of thrombus formation – 22.2 million people blood clots obstructing the are expected to die annually due to CVD b
Slide 7: Cereno develops novel drugs to transform treatments for PAH and other cardiovascular diseases
Cereno develops novel drugs to transform treatments for PAH and other cardiovascular diseases Lead program CS1 currently in US Introducing epigenetic modulation Phase II in PAH with strong rationale through HDAC inhibition with disease and supportive data – topline data modifying potential. expected
Slide 8: Cereno's Scientific Advisory Board are top thought leaders in the field of CVD
Cereno’s Scientific Advisory Board are top thought leaders in the field of CVD Dr. Bertram Pitt Dr. Raymond L. Dr. Deepak Bhatt Dr. Gunnar Olsson Dr. Gordon Dr. Faiez Zannad Chair of Board Benza Prof of Medicine, MD, PhD in Medical Williams Prof of Therapeutics Prof Em in Professor of Medicine, Harv
Slide 9: Promising programs with potential to transform the CVD treatment landscape
Promising programs with potential to transform the CVD treatment landscape Next Program Indication Discovery Preclinical Phase I Phase II Phase III milestone Phase II top- CS1 PAH HDACi with epigenetic effects line data: Q1, 2023 Phase I IND HDACi with CS014 CVD epigenetic effects submission: 2023 P
Slide 10: Growing and strengthening our management team with expertise for next stage
Growing and strengthening our management team with expertise for next stage Sten R. Daniel Brodén Sörensen Chief Financial Chief Executive Officer Officer Nick Oakes Niklas Bergh Björn Dahlöf Head of Preclinical Chief Scientific Chief Medical Development Officer Officer Michael Holinstat Jonas Faije
Slide 11: Merck $11.5 billion acquisition of Acceleron
Merck $11.5 billion acquisition of Acceleron – highlights attractiveness of promising PAH pipeline drugs • Merck acquired Acceleron Pharma Inc., with sotatercept as the key asset, for approximately $11.5 billion in November 2021 • Acceleron had just started Phase III in PAH, composition of matter pa
Slide 12: Leaving a mark in the medical community through abstracts accepted at top congresses
Leaving a mark in the medical community through abstracts accepted at top congresses June 9-12, 2022 June, 22-26 2022 August 26-29, 2022 Investigation of efficacy, safety and CS014 is a novel HDAC inhibitor CS585 is a first-in-class compound optimal dose of CS1 in subjects regulating platelet activi
Slide 13: Overview of Cardiovascular Disease and Cereno's Focus Areas
Overview of Cardiovascular Disease and Cereno’s Focus Areas Björn Dahlöf, MD, PhD, FESC, FACC Chief Medical Officer (CMO) & Board member, Cereno
Slide 14: The cardiovascular epidemic has rapidly grown in recent years
The cardiovascular (CV) epidemic has rapidly grown in recent years Cardiovascular It all started with a disease of epidemic Now no. 1 ”big bang” Man proportions killer in appeared appeared the world 13.8 billion 200,000 –100 2020 -> years ago years ago years ago 14
Slide 15: More than 200 million people at high risk of a cardiovascular event
More than 200 million people in the world today are at high risk of having a cardiovascular event ”Previously we used to work ourselves to death, today we rest ourselves to death while eating easily available food” Inactivity = Smoking 15
Slide 16: Most deaths worldwide are caused by cardiovascular disease
Most deaths worldwide are caused by cardiovascular disease Cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels. WHY? Most CVD complications happen because of thrombus formation – 22.2 million people blood clots obstructing the are expected to die annually due to CVD b
Slide 17: Cardiovascular disease equals exorbitant costs for patients, their families and society
Cardiovascular disease equals exorbitant costs for patients, their families and society • Common and rare CVDs result in significant markets Societal annual cost of CVD due to their mortality threat and adverse effect on the quality of life of patients These numbers are • The global anti-thrombotic
Slide 18: Cereno's promising programs have potential to transform the CVD treatment landscape
Cereno’s promising programs has potential to transform the CVD treatment landscape Next Program Indication Discovery Preclinical Phase I Phase II Phase III milestone Phase II top- CS1 PAH HDACi with epigenetic effects line data: Q1, 2023 Phase I IND HDACi with CS014 CVD epigenetic effects submission
Slide 19: Genetics clearly plays a role in disease, but epigenetics may be the missing link
”Genetics clearly plays a role in disease, but epigenetics may be the missing link between the environment and the transcriptional responses and could explain why some individuals develop CV disease while others do not” Epigenetic Modulation for Cardiovascular Disease
Slide 20: HDACi: Epigenetic modulation for cardiovascular disease
Figure. Potential Therapeutic Epigenetic Targets in Cardiovascular Disease Examples of targeting epigenetic mechanisms in CVD. Possible targets HDACi: Epigenetic modulation include modifying DNA methylation, changing the acetylation or deacytylation of histones, and miRNA or lncRNA modificiations. D
Slide 21: Review article in The Lancet Healthy Longevity supports epigenetic modulation via HDACi
Review article in The Lancet Healthy Longevity supports the potential of epigenetic modulation via HDACi in CVD “Given the pleotropic properties of CS1’s active substance being a HDACi with documented anti-thrombotic, anti-inflammatory, anti- fibrotic and pressure-reducing effects gives it a unique
Slide 22: Pulmonary arterial hypertension is a disease with poor prognosis and unsatisfactory treatment today
Pulmonary arterial hypertension is a disease with poor prognosis and unsatisfactory treatment today Pulmonary arterial hypertension (PAH) is a type of pulmonary hypertension, high blood pressure in the lungs • A rare fatal pulmonary vascular disease with 5-15 / 100,000 people affected. • Patients ex
Slide 23: CS1 aims to offer an effective, safe and disease modifying treatment for PAH
CS1 aims to offer an effective, safe and disease modifying treatment for PAH CS1’s multi-fold efficacy, all relevant for PAH CS1 is a new advanced reformulation and acts as an epigenetic modulator Pulmonary pressure-reduction • Proven good safety and tolerability in Phase I study. Reverse-remodeling
Slide 24: Towards personalized anti-thrombotic therapy
Towards personalized anti- thrombotic therapy • There are many different potential uses of anti- thrombotic treatment as depicted A-L in the illustration to the right. Epigenetic Modulation for Cardiovascular Disease
Slide 25: Current anti-thrombosis treatment involves the risk of serious bleedings
Current anti-thrombosis/blood thinning treatment involves the risk of serious bleedings Waran Brilique Xarelto Trombyl Persantin Plavix Eliquis Depot Pradaxa Efient Systemic inhibition of coagulation/platelet function Increased risk of bleeding Insufficient preventive effect Need for new preventive
Slide 26: Cereno will enter one of the largest pharmaceutical markets
Cereno will enter one of the largest pharmaceutical markets with a profile which will impact thrombosis management NOACs/ Warfarin CS585 CS1, CS014 Antiplatelets Dose monitoring not required Required Anti-thrombotic efficacy Lower risk of Increased Increased bleeding bleeding bleeding Not Not Not ¤
Slide 27: Understanding PAH: Debilitating Rare Disease
Understanding PAH: Debilitating Rare Disease Dr. Raymond Benza Prof. and Director at the Ohio State University Wexner Medical Center; PI of Phase II study with CS1
Slide 28: Pulmonary Hypertension; Focus on Pulmonary Arterial Hypertension
Pulmonary Hypertension; Focus on Pulmonary Arterial Hypertension Raymond L. Benza, MD, FACC Professor of Medicine Division of Cardiovascular Diseases Bob and Corrine Frick Endowed Chair of Heart Failure Department of Medicine The Ohio State University Wexner Medical Center
Slide 29: Normal Human Circulation
Normal Human Circulation Pulmonary arteries
Slide 30: Pulmonary Hypertension: High Pressure in the Pulmonary Arteries
Pulmonary Hypertension: High Pressure in the Pulmonary Arteries Pulmonary hypertension= Mean PAP > 20 mmHg Normal mean pressure = 10-15 mmHg • Mild = Mean PAP 20-40 mmHg • Mod = Mean PAP 41-55 mmHg • Severe = Mean PAP > 55 mmHg Galie N et al European Heart J 2004; 25:2243-78 Khan MG, Lynch JP III ed
Slide 31: PHTN: A Disease of Lung Vessels and the Right Heart
PHTN: A Disease of Lung Vessels and the Right Heart 31
Slide 32: Normal Human Circulation
Normal Human Circulation wide-open Blood Vessels Normal THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER
Slide 33: Definition and Clinical Classification of Pulmonary Hypertension
Definition and Clinical Classification of Pulmonary Hypertension 1. Pulmonary arterial 2. Pulmonary hypertension due to hypertension left heart disease 3. Pulmonary hypertension due to 4. Pulmonary hypertension due to lung diseases and/or hypoxia pulmonary artery obstructions Simonneau, et al. Eur R
Slide 34: Problem
PROBLEM Global Burden of PHTN: It’s a Pandemic! PHTN in the Community ;78 million with some form of PH ;780 million in those aged >650 Nl PASP 18-25 50% with abnormal PASP 25% w/PASP > 30 mmHg 34
Slide 35: Problem
PROBLEM • The Faces of Pulmonary Arterial hypertension: A progressive, chronic disease affecting primarily women (5:1) with a mean age of 50 y.o. • Mean life expectancy is 2.5 years without therapy, now extended to 7.5 years with modern therapeutics • PThere is no Cure for PAH except for Lung Transp
Slide 36: Pathology of Pulmonary Hypertension and PAH
Pathology of Pulmonary Hypertension and PAH Endothelial cells Lumen Smooth Muscle Effector Molecule cells Effector Molecule 41 Adapted from: Humbert, et al. N Engl J Med. 2004;351:1425-1436.
Slide 37: Pathology of Pulmonary Hypertension and PAH
Pathology of Pulmonary Hypertension and PAH 37 Woodcock ; J Cardiovasc Pharmacol Ther. 2019 Jul; 24(4): 334–354.
Slide 38: Three Most Cited Mechanisms of PAH
Three Most Cited Mechanisms of PAH Endothelin pathway Nitric oxide pathway Prostacyclin pathway Endothelial cells Preproendothelin Proendothelin L-arginine Arachidonic acid Prostaglandin I2 NOS sGC Nitric oxide Endothelin-1 stimulator GTP Prostaglandin I2 Endothelin-receptor A cGMP Prostacyclin Endo
Slide 39: Managing PAH
Managing PAH 40
Slide 40: Pharmaceutical Therapies Implemented since 1991 yet Survival still Sub-Optimal
14 Pharmaceutical Therapies Implemented since 1991 yet Survival still Sub-Optimal • Long-term data à observational registries • Median survival has increased ~ 7 vs 3 years in the 80s • Still, 7 year survival rate is unacceptable • Morbid events now outrank mortal events and these predict future Fur
Slide 41: How Does Risk Stratification Help us?
How Does Risk Stratification Help us? PAH – Deadly but unpredictable as to when and how • Sudden cardiac death Short survival • Right heart failure Who is the most vulnerable? Acute • Sepsis exacerbation • Renal failure • Arrythmia Long survival, • Systemic Organ but chronic Damage inadequate CO + •
Slide 42: Risk Stratification in PAH
Risk Stratification in PAH Risk Risk Risk THIS MATERIAL IS BEING PROVIDED FOR INTERNAL EDUCATIONAL AND BACKGROUND PURPOSES ONLY AND IS NOT FOR PROMOTIONAL USE. DO NOT COPY, DISTRIBUTE OR SHARE WITH 5 | PHYSICIANS, STAFF OR PATIENTS.
Slide 43: One test does not tell it all
We also Agree that “One test does not tell it all….We need the complete picture” BNP NYHA 6MWD There is a need for a collective measurement tool to predict survival in the modern era of PAH therapy Supplements Clinical Gestalt in experienced providers Serves as a key decision tool for less experienc
Slide 44: REVEAL Risk Score Calculators
Updated PAH Risk Score REVEAL Risk Score Calculators WHO Group I APAH-CTD APAH-PoPH FPAH Subgroup +1 +3 +2 New risk calculator with better discrimination Males Ages >60yrs (CI 0.76) Demographics +2 eGFR <60 mL/min/1.73m2 or renal inefficiency (if eGFR is unavailable) Existing variables with revised
Slide 45: REVEAL Risk Score Calculators
Updated PAH Risk Score REVEAL Risk Score Calculators WHO Group I APAH-CTD APAH-PoPH FPAH Subgroup +1 +3 +2 New risk calculator with better discrimination Males Ages >60yrs (CI 0.76) Demographics +2 eGFR <60 mL/min/1.73m2 or renal inefficiency (if eGFR is unavailable) Existing variables with revised
Slide 46: PAH Therapeutic Trials: We are Finally Catching up!
PAH Therapeutic Trials: We are Finally Catching up! 3 years 4 years 4 NOVEL 8 years PATHWAYS IP agonist 6-10 years introduced 2020 sGC stimulator introduced 2017 PDE-5i 2013 15 years introduced 2013 2005 ERAs Prostacyclin introduced 2005 Pathway 2001 Prostanoids Nitric Oxide 2001 Pathway introduced
Slide 47: New pathway Development and Clinical Trials
New pathway Development and Clinical Trials Clinical trials with drugs targeting metabolic dysfunction in pulmonary arterial hypertension • Metabolic syndrome: AMPK signalling and metformin • Glycolysis: dichloroacetate • Fatty acid oxidation: ranolazine and trimetazidine Clinical trials with drugs
Slide 48: New Pathway Development: Failed or Neutral Clinical Trials
New Pathway Development: Failed or Neutral Clinical Trials 48 Sitbon, O Eur Respir J. 2019 Jan; 53(1): 1801908.
Slide 49: New Pathways for Treating Pulmonary Arterial Hypertension
New Pathways for Treating Pulmonary Arterial Hypertension • Manipulating BMPR2 • Sotatercept: PULSAR Study1 • Manipulating PDGF • Seralutinib: TORREY Study, a novel small molecule tyrosine kinase inhibitor for inhalation • Iminitab: AV-101-002 Study: Aerovate Therapeutics; Trials of AV-101, an inhal
Slide 50: Role of CS1
Role of CS1 • Anti-thrombotic activity (restoration of tissue-type plasminogen activator in pulmonary blood vessels and reduction of PAI-1) • Anti-inflammatory activity • Anti-fibrotic/remodeling activity • Pulmonary pressure reduction 50
Slide 51: Role of CS1
Role of CS1 • Anti-thrombotic activity (restoration of tissue-type plasminogen activator in pulmonary blood vessels and reduction of PAI-1) A Phase 2, Prospective, Randomized, Open-label, Blinded • Endpoint, Anti-inflammatory activity Multicenter Study to Investigate Safety and Tolerability, PK and
Slide 52: Clinical Phase II Study Design with CS1
Clinical Phase II Study Design with CS1 Dr. Raymond Benza Prof. and Director at the Ohio State University Wexner Medical Center; PI of Phase II study with CS1
Slide 53: CS1 Phase II study aims to evaluate safety, tolerability and exploratory efficacy
CS1 Phase II study aims to evaluate safety, tolerability and exploratory efficacy Phase II study of CS1 in patients with PAH § Primary endpoint: Safety and tolerability. § Other variables including all standard efficacy endpoints for this patient group (6MWT etc.), a calculated validated risk score,
Slide 54: The innovative Phase II study design was presented at top pulmonary congress
The innovative Phase II study design was presented at top pulmonary congress Investigation of efficacy, safety and optimal dose of CS1 in subjects with pulmonary arterial hypertension: a prospective, randomized, multicenter, parallel-group phase II study R. Benza, N. Bergh, P. Adamson, B. Dahlöf Jun
Slide 55: Phase II study: First patient has been randomized
Phase II study: First patient has been randomized and entered the study’s treatment period Update as of Aug 29 § First site activated: 14 Mar 2022 § First patient screened: 5 July 2022 30 patients § First patient randomized: 25 Aug 2022 ~10 US clinical sites § Activation of clinical sites is ongoing
Slide 56: Phase 2 Study of CS1 in Subjects with Pulmonary Arterial Hypertension
Phase 2 Study of CS1 in Subjects with Pulmonary Arterial Hypertension • Novel Compound with Novel Actions • Novel and Innovative Endpoints – REVEAL Risk Score – Cardiac MRI – CardioMEMs device – Novel biomarkers • Traditional Endpoints (efficacy and safety) – 6MWD, hemodynamics, echo, biomarker
Slide 57: Archetypal Progression of Decompensation: Early and Remote Detection is Key
Archetypal Progression of Decompensation: Early and Remote Detection is Key Clinical Congestion RV Failure GAIN IN TIME HOSPITALIZATION NYHA Hemodynamic Congestion Symptoms Hemodynamic Decompensation PE Weight Change Change LABS 6MWD IntrathoracicImaging Biomarker Impedance Autonomic Change Decompen
Slide 58: Right Heart Catheterization: Contemporary Gold Standard
Right Heart Catheterization: Contemporary Gold Standard for Evaluating PAH & RV Function Hemodynamics are the Most Important Piece of HF Management but not Readily Obtainable • Right Heart Cath (RHC) to Measure Pulmonary Artery Pressure Remains the Gold Standard for Cardiac Hemodynamics • Shortcomin
Slide 59: Right Heart Catheterization: Contemporary Gold Standard
Right Heart Catheterization: Contemporary Gold Standard for Evaluating PAH & RV Function Hemodynamics are the Most Important Piece of HF Management but not Readily Obtainable • Right Heart Cath (RHC) to Measure Pulmonary Artery Pressure Remains the Gold Standard for Cardiac Hemodynamics • Shortcomin
Slide 60: Changes in Right Ventricular Function with Management of mPAP
Changes in Right Ventricular Function with Management of mPAP Prostacyclin Prostacyclin
Slide 61: CardioMEMS – Phase II Clinical Collaboration Between Abbott and Cereno
CardioMEMS – Phase II Clinical Collaboration Between Abbott and Cereno Dr. Phil Adamson Divisional Vice President and Chief Medical Office Heart Failure Division, Abbott
Slide 62: CardioMEMS HF Monitoring System
CardioMEMS HF Monitoring System or LAN la r v i a cellu ad Uplo PA SYSTOLIC, DIASTOLIC AND MEAN. HEART RATE
Slide 63: Pressure Sensor
Pressure Waveform Frequency Pressure Sensor Cross section CL. Le ee
Slide 64: Hemodynamic guided heart failure management
Hemodynamic guided heart failure management Insights into the mechanisms of acute decompensation Symptomatic Pre-symptomatic Symptoms Weight Change Hospitalization Intrathoracic Impedance Autonomic Change Changes Filling (BNP) Pressure Change Hemodynamically Stable Hemodynamic Congestion Clinical Co
Slide 65: Totality of evidence - consistent benefit of CardioMEMS guided care
Totality of evidence - consistent benefit of CardioMEMS guided care Reduction Study Type Study N Follow up p-value in HFH RCT GUIDE-HF IDE NYHA Class II-III 1 946 8.6 mo. 32% p < 0.01 RCT CHAMPION IDE 2 550 18 mo. 33% p < 0.0001 Retrospective Propensity Matched Outcomes 3 2,174 12 mo. 24% p < 0.001
Slide 66: CardioMEMS indications
Current USFDA and CE Mark approved CardioMEMS indications February 21, 2022 The CardioMEMS™ HF System is indicated for wirelessly measuring and monitoring pulmonary artery pressure and heart rate in NYHA Class II or III heart failure patients who either have been hospitalized for heart failure US in
Slide 67: Cereno – Abbott Collaboration
Cereno – Abbott Collaboration US Food and Drug Administration Center for Drug Center for Evaluation and Devices and Research Radiological (CEDR) Health (CDRH) Collaborative review Cereno Investigational New Drug (IND) program with Abbott and CardioMEMS
Slide 68: CS1 Phase II study – CardioMEMS Monitoring
CS1 Phase II study – CardioMEMS Monitoring • All centers are experienced CardioMEMS users • Patients upload hemodynamic information daily from home • Investigators review pressures twice weekly during drug titration • Effectiveness described using the targeted lesion – secondary endpoint or LAN la r
Slide 69: Secondary pulmonary hypertension is almost always found in NYHA Class III patients
Secondary pulmonary hypertension is almost always found in NYHA Class III patients Trial Total ≥ 35 mmHg 25-35 mmHg <25 mmHg CHAMPION 550 (545)* 201 192 152 Heywood 2,000 958 692 350 US PAS 1,200 550 434 211 MEMS-HF 234 (227)* 121 106 - Totals 3,984 (3,967)* 1830 1424 713 September 5, 2022 69 % 46%
Slide 70: Clinical assessment and filling pressures - GUIDE-HF
Clinical assessment and filling pressures - GUIDE-HF - Does less symptomatic = less ill? mmHg PCWP PA Diastolic PA Mean PA Systolic 60 50 48,4 44,1 45,1 40 32,2 28,5 29,4 30 21,9 Pulmonary 18,1 18,9 19,1 20 17,3 17,3 Hypertension September 5, 2022 70 10 0 NYHA Class II NYHA Class III NYHA Class IV N
Slide 71: Prognosis in Group 2 pulmonary hypertension
Prognosis in Group 2 pulmonary hypertension Role of right ventricular dysfunction September 5, 2022 Marco Guazzi et al. J Am Coll Cardiol 2017; 69:1718-1734. 71
Slide 72: Unifying the impact of pulmonary hypertension
Unifying the impact of pulmonary hypertension Unstable refractory symptoms Advanced HF Symptoms RV Failure Stable/treatable symptoms RV dysfunction Intervention or death and decoupling Advanced HF Pulmonary Vascular Remodeling – Increased PVR Secondary Pulmonary Hypertension Elevated LV and LA Press
Slide 73: Cereno's Drug Candidate CS1 to Treat PAH and Broader Potential
Cereno’s Drug Candidate CS1 to Treat PAH and Broader Potential Björn Dahlöf, MD, PhD, FESC, FACC Chief Medical Officer (CMO) & Board member, Cereno
Slide 74: ValProic Acid (VPA) an HDAC inhibitor
ValProic Acid (VPA) an HDAC inhibitor Epigenetic modulator for Cardiovascular Disease • First synthesized in 1882 • Globally established treatment for epilepsy (and bipolar disease) – used for the past 52 years • The widest spectrum of all anti-epileptic drugs • Well tolerated in long-term in the ma
Slide 75: Existing treatment options are insufficient in PAH
Existing treatment options are insufficient in PAH Current therapies are vasodilators treating symptoms of PAH rather than the underlying pathophysiology No. of PAH drugs by class • Four main classes of current PAH therapies: sGC • Endothelin receptor agonists (ERA) 2 ERA • Prostacyclin analogues (P
Slide 76: The search for disease-modifying therapies in pulmonary hypertension
The search for disease-modifying therapies in pulmonary hypertension: new direction in epigenetic modulation for PAH
Slide 77: HDACi game-changing with epigenetic modulation of cardiovascular disease
HDACi game-changing with epigenetic modulation of cardiovascular disease CS1 and preclinical CS014 acts as epigenetic modulators • Epigenetic modulation is the alteration of gene expression without altering genetic material. • Epigenetic changes play a significant role in the pathogenesis of many CV
Slide 78: Epigenetic Modulation for Cardiovascular Disease
2020 Epigenetic Modulation for Cardiovascular Disease
Slide 79: Epigenetic Modulation for Cardiovascular Disease
2020 Epigenetic Modulation for Cardiovascular Disease
Slide 80: Cereno's portfolio includes HDAC inhibitors and a PCA with potential in CVD
Cereno’s portfolio includes HDAC inhibitors and a PCA with potential in CVD Next Program Indication Discovery Preclinical Phase I Phase II Phase III milestone Phase II top- CS1 PAH HDACi with epigenetic effects line data: Q1, 2023 Phase I IND HDACi with CS014 CVD epigenetic effects submission: 2023
Slide 81: CS1 vs Sotatercept
CS1 vs Sotatercept Important mechanisms for PAH - Selected preclinical data Comparison characteristics of CS1 vs Sotatercapt1,2,3,4,5,6,7 Pulmonary pressure Reverse- Anti- Anti- Anti- Generic name MoA Phase reduction remodeling fibrotic inflammatory thrombotic CS1 +++ +++ +++ ++ +++ HDACi II Sotater
Slide 82: Characteristics of CS1 vs Sotatercept
Characteristics of CS1 vs Sotatercept CS1 Sotatercept MoA HDACi TGF-β ligand trap (monoclonal antibody) Oral Innovative formulation, Subcutaneous, Administration delayed immediate release every 3 weeks Use patent 2038 2036 ODD ✓ ✓ Potential disease modifying ✓ ✓ Pulmonary pressure reduction ✓ ✓ Reve
Slide 83: CS1 stands strong vs established and pipeline PAH drugs
CS1 stands strong vs established and pipeline PAH drugs based on preclinical data Pulmonary Reverse- Anti- Anti- Anti- MoA Company Generic name pressure remodeling fibrotic inflammatory thrombotic reduction Ambrisentan,Bosentan, ERA Misc Macisentan +++ + + + 0 PDE5i Misc Sildanafil, Taldalafil ++ +?
Slide 84: HDAC inhibitor CS1 aims to offer an effective, safe and disease modifying treatment for PAH
HDAC inhibitor CS1 aims to offer an effective, safe and disease modifying treatment for PAH CS1’s multi-fold efficacy, all relevant for PAH CS1 is a new advanced reformulation and acts as an epigenetic modulator Pulmonary pressure-reduction • Proven good safety and tolerability in Phase I study. Rev
Slide 85: CS1 viewed as potential game-changer in PAH by global thought leader
CS1 viewed as potential game-changer in PAH by global thought leader “CS1 has to definitely be tested in PAH, it could be game-changing for patients.” – Dr Raymond Benza, global thought leader in PAH treatment and PI CS1-003, CS1’s Phase II study in PAH is ongoing with first about Cereno’s CS1. pati
Slide 86: Review article in The Lancet Healthy Longevity supports epigenetic modulation via HDACi
Review article in The Lancet Healthy Longevity supports the potential of epigenetic modulation via HDACi in CVD Accumulating evidence supports the role of epigenetic modulation through HDAC inhibition in the treatment of multiple medical conditions beyond the treatment of epilepsy, which has been do
Slide 87: Beyond PAH: Cereno's robust strategy for cardiovascular disease management
Beyond PAH: Cereno’s robust strategy for cardiovascular disease management Anti-hypertensive Anti-inflammatory Disability Dementia Diabetes Hypertension Anti-fibrotic Fibrosis Reverse remodeling Stroke Diastolic dysfunction Anti-thrombotic (anti-platelet, fibrinolytic, Atrial fibrillation without bl
Slide 88: CS1 active ingredient reduces thrombus formation in vivo without bleedings
CS1 effect profile: Anti-fibrotic Anti-inflammatory Pulmonary pressure reduction Anti-thrombotic CS1 active ingredient – pre-treatment reduces thrombus formation in vivo – without bleedings Fibrin (injury only) Fibrin (injury + Thrombin) Thrombus volume (inj only) Thrombus volume (inj + Thrombin) Th
Slide 89: CS1 – prevention of fibrosis, atrial fibrillation and thrombosis
CS1 – prevention of fibrosis, atrial fibrillation and thrombosis • Atrial fibrillation increases with age • Associated with progressive (fibrotic) remodelling of the atrium • The risk of thrombosis is linked to the size/fibrotic remodelling of the atrium Findings show that CS1 has therapeutic potent
Slide 90: Potential of Cereno's pipeline of HDACi epigenetic modulators
Potential of Cereno’s pipeline of HDACi epigenetic modulators (CS1, CS014, CSXXX) based on unique efficacy profile Efficacy profile of Systemic blood Pulmonary Anti-fibrotic/ HDACi epigentic pressure pressure Anti-inflammatory/ Reverse Cardiovascular disease modulators reduction reduction Anti-throm
Slide 91: Cereno's Preclinical Candidates Potential to Break New Ground
Cereno’s Preclinical Candidates Potential to Break New Ground Dr. Björn Dahlöf Chief Medical Officer (CMO), Cereno
Slide 92: Cereno's portfolio of two pipeline drug candidates in preclinical development
Cereno’s portfolio of two pipeline drug candidates in preclinical development Next Program Indication Discovery Preclinical Phase I Phase II Phase III milestone Phase II top- CS1 PAH HDACi with epigenetic effects line data: Q1, 2023 Phase I IND HDACi with CS014 CVD* epigenetic effects submission: 20
Slide 93: CS014 is a novel HDACi with epigenetic modulation properties
CS014 is a novel HDACi with epigenetic modulation properties Preclinical development program Q2: Collaboration extended with a full preclinical Ready to start Research collaboration Acquired by development program in clinical phase I, Emeriti Bio cardiovascular disease first-in-man studies 2019 2020
Slide 94: CS585 is a prostacyclin receptor agonist
CS585 is a prostacyclin receptor agonist utilizing a well- established drug class and regulatory pathway Preclinical development program Q1: CS585 obtained through Ready to start Research collaboration an option agreement with Q3: First patent clinical phase I, University of Michigan granted in the
Slide 95: Leaving a mark in the medical community through abstracts accepted at top congresses
Leaving a mark in the medical community through abstracts accepted at top congresses June 9-12, 2022 August 26-29, 2022 CS014 is a novel HDAC inhibitor CS585 is a first-in-class compound regulating platelet activity, targeting the IP receptor for fibrinolysis and clot stability for prevention of thr
Slide 96: CS585 – A First-In-Class Compound Targeting the IP Receptor
CS585 – A First-In-Class Compound Targeting the IP Receptor for Prevention of Thrombosis Without Increased Risk of Bleeding Dr. Michael Holinstat Ass. Prof. at University of Michigan Medical School; and Director Translation Research, Cereno
Slide 97: CS585 is a first-in-class compound targeting the IP receptor
CS585 IS A FIRST-IN-CLASS COMPOUND TARGETING THE IP RECEPTOR FOR PREVENTION OF THROMBOSIS WITHOUT INCREASED RISK OF BLEEDING Michael Holinstat, PhD, FAHA Departments of Pharmacology, Internal Medicine (Division of Cardiovascular Medicine), and Vascular Surgery University of Michigan Contributing aut
Slide 98: Conflict of Interest Disclosure Slide
Conflict of Interest Disclosure Slide: Consulting: • I am a consultant and equity holder in Cereno Scientific and Veralox Therapeutics. I am also an inventor for the patents on CS585 and VLX-1005. Grants: • I receive research grants from the NIH, Cayman Biomedical Research Institute (CaBRI), Cereno
Slide 99: Platelet physiology and pathophysiology
Platelet physiology and pathophysiology Hemostasis Thrombosis
Slide 100: Platelet physiology and pathophysiology
Platelet physiology and pathophysiology Hemostasis
Slide 101: Platelet physiology and pathophysiology
Platelet physiology and pathophysiology Hemostasis Thrombosis
Slide 102: Regulation of human platelet function
Regulation of human platelet function • Currently approved Anti-platelet drug • While current anti-platelet therapy has therapy has reduced the risk of morbidity significant health benefits, morbidity and and mortality by more than 26%. death due to thrombotic events and bleeding still remains a sig
Slide 103: Eicosanoids function as negative regulators for platelet activation
Eicosanoids function as negative regulators for platelet activation: (DGLA) • 12-lipoxygenase oxidizes fatty acids to form bioactive lipids • 12-LOX bioactive lipids represent novel targets for development of antiplatelet therapeutics • Little is known about the Substrate Product Name Reduced Produc
Slide 104: 12(S)-HETrE protects vessel from Thrombosis
12(S)-HETrE protects vessel from Thrombosis 100 WT 12(S)-HETrE IP-/- 80 Control Vessel Aggregation (%) 60 Platelets 40 Gαs Fibrin 20 AC 0 cAMP DMSO 12-HETrE (10µM) 12-HETrE (20µM) PKA 12-HETrE DMSO FORSK 12-HETE 10 µM 20 µM VASP P-VASP Vessel treated with 12(S)-HETrE P-VASP Yeung et al. ATVB 2016; T
Slide 105: 12-HETrE signals through the IP receptor in human platelets
12-HETrE signals through the IP receptor in human platelets 12-HETrE PGI2 PGI2 RO3244794 RO3244794 PAR4 IP receptor Inhibition Aggregation Aggregation Inhibition Aggregation (IP receptor (IP receptor Independent) Dependent) IP receptor IP Receptor Antagonist PGI2 PAR4-AP Tourdot et al. Blood Adv 201
Slide 106: CS585 developed as a high potency analog of 12(S)-HETrE
CS585 developed as a high potency analog of 12(S)-HETrE (human platelets) 250 kDa CS585 regulates Platelet function through: Veh. Control 100pM 250pM 500pM 100nM 10pM 25pM 50pM 10nM 25nM 50nM 75 kDa 1nM Unstimulated v VASP phosphorylation (IP receptor) pVASP 50 kDa Vehicle Stimulated 37 kDa GAPDH v
Slide 107: CS585 selectively signals through IP receptor
CS585 selectively signals through IP receptor IP receptor DMSO DP receptor DMSO EP2/EP4 receptor DMSO RO118542 TG4-155/CJ42794 100 100 100 MK0524 *** 90 80 ** *** 80 80 Aggregation (%) Aggregation (%) Aggregation (%) 70 60 60 60 50 40 40 40 30 20 20 20 10 0 0 0 0 0.050.25 0.5 0.75 1 25 50 100 0 0.05
Slide 108: CS585 inhibits platelet clot formation following injury
CS585 inhibits platelet clot formation following injury Vehicle control CS585 3mg/kg CS585 6mg/kg
Slide 109: CS585 delays clotting and occlusion time in the carotid artery
CS585 delays clotting and occlusion time in the carotid artery ns ns ✱✱ ✱ Carotid Artery Occlusion Time (mins) 30 20 10 0 kg kg kg kg ol tr g/ g/ g/ g/ on 6m 5m 5m 1m C 1. 0. 0.
Slide 110: CS585 doesn't affect coagulation or bleeding
CS585 doesn’t affect coagulation or bleeding ns ns Control 600 CS585 Tail Bleeding time (sec) 250ng/mL Rivaroxaban 500 250ng/mL Rivaroxaban + CS585 400 300 200 100 0 g l g 7UDFLQJVIURPWRSWRERWWRP ro k k g/ g/ nt 6m 5m co HT &KDQQHO 3DWLHQW 67 6DPSOHGHVFULSWLRQ 2SHUDWRU $QDO\]HU61 0. le 85 c 85 S5 hi
Slide 111: Summary: CS585
Summary: CS585 • 12(S)-HETrE potently and selectively inhibits platelet activity and IP receptor thrombosis through activation of the IP receptor • CS585 is a novel IP agonist derived from 12(S)-HETrE Ø Stable in human plasma and blood • CS585 selectively activates the IP receptor resulting in phosp
Slide 112: Acknowledgements
Current Holinstat Lab: Acknowledgements: • Sylviane Lambert, PhD-Research Specialist • Livia Stanger-PhD-Graduate Student Support: • Raymond Adili, MD-Associate Research Scientist • Antonela Rodriguez, PhD-Graduate Student • Adriana Yamaguchi, PhD-Postdoctoral Fellow • Eliana Botta, PhD-Postdoctoral
Slide 113: CS014 – A Novel HDAC Inhibitor Regulating Platelet Activity
CS014 – A Novel HDAC Inhibitor Regulating Platelet Activity, Fbrinolysis and Clot Stability for Prevention of Thrombosis Without Increased Risk of Bleeding Dr. Michael Holinstat Ass. Prof. at University of Michigan Medical School; and Director Translation Research, Cereno
Slide 114: CS014 is a novel HDAC inhibitor regulating platelet activity, fibrinolysis and clot stability
CS014 is a novel HDAC inhibitor regulating platelet activity, fibrinolysis and clot stability for prevention of thrombosis without increased risk of bleeding Michael Holinstat, PhD, FAHA Departments of Pharmacology, Internal Medicine (Division of Cardiovascular Medicine), and Vascular Surgery, Unive
Slide 115: Regulation of human platelet function
Regulation of human platelet function • Currently approved anti-platelet drug therapy • While current anti-platelet therapy has significant has reduced the risk of morbidity and mortality health benefits, morbidity and death due to by more than 26%. thrombotic events and bleeding still remains a Clo
Slide 116: CS014 inhibits platelet clot formation following vascular injury
CS014 developed as an HDAC inhibitor with the ability to inhibit platelet clot formation following vascular injury Control *** 9000 CS014 100 mg/kg Pre-injury 1 min 2 min 3 min 8000 7000 Platelet MFI 6000 Saline 5000 control 4000 3000 2000 1000 0 0 1 2 3 4 CS014 Time (mins) 100 mg/kg 600 Control ***
Slide 117: CS014 delays carotid artery occlusion time
CS014 delays carotid artery occlusion time 35 * Carotid artery occlusion time 30 25 (mins) 20 15 10 5 0 Control CS014 100 mg/kg • CS014 significantly delays time to full • Destroying the vessel wall with 10% FeCl3 results in full occlusion of the carotid artery occlusion of the vessel in 15 minutes
Slide 118: CS014 prevents low shear clot formation and fibrin formation
CS014 prevents low shear clot formation and fibrin formation 16000 2250 *** Saline control *** Saline control 14000 CS014 100mg/kg CS014 100mg/kg 2000 12000 10000 1750 Platelet MFI Fibrin MFI 8000 1500 6000 4000 1250 2000 1000 0 0 5 10 15 0 5 10 15 Time (mins) Time (mins) • CS014 prevents platelet c
Slide 119: CS014 does not alter tail vein bleeding time
CS014 does not alter tail vein bleeding time 600 Tail bleeding time (sec) 500 • CS014 has no increased time to cessation 400 of bleeding compared to control mice following resection of tail 300 • CS014 does not demonstrate any increased risk for bleeding even at elevated levels 200 of drug (tested o
Slide 120: CS014 does not alter coagulation activity in the blood
CS014 does not alter coagulation activity in the blood Reaction time • CS014 did not alter reaction time in whole blood as assessed by TEG CS014 100 mg/kg + • Rivaroxaban (an FXa inhibitor) significantly rivaroxaban 100 mg/mL delays reaction time for clot formation in blood CS014 100 mg/kg • Reactio
Slide 121: Conclusions
Conclusions: • HDACi CS014 inhibits both small and large vessel clotting and fibrin formation • CS014 prevents high shear arterial platelet clot formation and fibrin formation following vascular injury • CS014 significantly delays vessel occlusion in high shear large vessels. • CS014 prevents platel
Slide 122: Panel: The Need for True Innovation in CVD Management
Panel: The Need for True Innovation in CVD Management – Focus on PAH and Thrombosis Dr. Björn Dahlöf Dr. Phil Adamson Dr. Michael Holinstat Dr. Gunnar Olsson Chief Medical Officer, Divisional Vice President and Ass. Prof. at University of MD, Prof, KI; SAB Cereno Chief Medical Officer Michigan Medic
Slide 123: Questions from Audience
Cereno Scientific Questions from Audience
Slide 124: Concluding Words
Concluding Words Sten R. Sörensen Chief Executive Officer (CEO), Cereno
Slide 125: Full steam ahead in 2022
Full steam ahead in 2022 Key 2022 achievements and upcoming milestones ü CS585 and CS014 nominated in Q2 as CDs for further development towards IND submission for clinical programs ü CS585 thrombosis data (prevention of thrombosis without increased risk of bleeding) accepted for EHA June 2022 ü CS01
Slide 126: Cereno's strategy to provide value for patients and stakeholders
Cereno’s strategy to provide value for patients and stakeholders Cereno’s key objectives 2024 Utilizing the project portfolio’s full potential on 2023 profitable markets within cardiovascular disease. 2022 Clinical phase Clinical phase Initiated Phase IIb/III study in PAH with CS1 Topline data Phase
Slide 127: Warrants of series TO2
Warrants of series TO2 • The warrants of series TO2 were issued in Oct Terms of the warrants: 2020 in connection to a directed share issue • Each warrant give the holder the right • In total, 34.5 million warrants of series TO2 are to subscribe for one new share in outstanding and are trading on Spo
Slide 128: Cereno is well-positioned to become a leader in developing innovative treatments for cardiovascular disease
Cereno is well-positioned to become a leader in developing innovative treatments for cardiovascular disease Global presence Offices in biotech hot spots Gothenburg, Sweden and Boston, MA, US and significant R&D collaboration with University of Michigan, MI, US. Inherently profitable market Rare dise
Slide 129: About Cereno Scientific
Cereno Scientific is a clinical stage biotech company within cardiovascular diseases. The lead drug candidate, CS1, is a Phase II candidate in development for the treatment of the rare disease pulmonary arterial hypertension (PAH). CS1 is an HDAC (histone deacetylase) inhibitor that acts as an epige