Cereno Scientific Ab Class B · OMXSTO:CRNO_B
Cereno Scientific Ab Class B — Technical Presentation (September 2024)
57 slides from Cereno Scientific Ab Class B's technical presentation, Sep 30, 2024
Slide 1: Webcast CS1 phase II topline results
Sten R. Sörensen Chief Executive Officer Webcast CS1 phase II topline results September 30th, 2024 @2PM CET
Slide 2: Disclaimer
Disclaimer CS1-003 is a phase IIa trial that is not powered for statistically significant detection of efficacy-related parameters. This presentation has been prepared and produced by Cereno Scientific AB (publ) (“Cereno Scientific”) solely for Cereno Scientific’s investor presentation and may not b
Slide 3: Cereno is led by a group of seasoned professionals with extensive experience
Cereno is led by a group of seasoned professionals with extensive experience Sten R. Dr. Björn Dahlöf Dr. Rahul Agrawal Chief Medical Officer and Sörensen Chief Scientific Officer Head of R&D Chief Executive Officer Eva Jagenheim Chief Financial Nicholas Oakes Julia Fransson Officer Head of Preclini
Slide 4: Cereno develops novel drugs to transform treatment landscape in PAH and other cardiovascular diseases
Cereno develops novel drugs to transform treatment landscape in PAH and other cardiovascular diseases Pioneering epigenetic modulation Pipeline portfolio: through HDAC inhibition (HDACi) with CS1: Phase II HDACi completed, ODD in PAH disease-modifying potential in CVD CS014: Phase I HDACi ongoing CS
Slide 5: Cereno develops its pipeline to become attractive for partners or exit through M&A
Cereno develops its pipeline to become attractive for development with strategic financial/pharma partners or exit through M&A Cereno’s assets can be packaged in three different portfolios for • Co-development • Out-licensing, • Asset trade sale and Portfolio ’s Ass s • M&A • Commercialization PAH p
Slide 6: Cereno Scientific – Latest news!
Cereno Scientific – Latest news! • Compassionate use: First patient dosed • CS014 dose dependent remodeling • Positive CS1 topline results • Fluidda partnership to document the impact of CS1 on reverse remodeling of pulmonary arteries • Capital Markets Day – October 17th @13.30, Posthuset – Sthlm &
Slide 7: CS1-003: A phase IIa trial of CS1 in Pulmonary Arterial Hypertension (PAH)
CS1-003: A phase IIa, prospective, randomized, multicenter trial to investigate the safety, tolerability and explore efficacy of CS1 in Pulmonary Arterial Hypertension (PAH) NCT05224531 Webcast – September 30th, 2024 @2PM CET
Slide 8: CS1 PAH phase IIa trial – Summary results
CS1 PAH phase IIa trial – Summary results • Primary endpoint of safety & tolerability met successfully • Positive impact on exploratory clinical efficacy parameters: • REVEAL risk score: 43% improved; 71% improved or stable • Functional class: 33% improved; 86% improved or stable • mPAP: 67% had sus
Slide 9: CS1 PAH phase IIa trial - Agenda
CS1 PAH phase IIa trial - Agenda • Executive summary • Pulmonary arterial hypertension • PAH management goals • Preclinical data in PAH • Phase IIa clinical trial design and goals • Phase IIa safety data • Compelling signs of efficacy • Summary of findings • In-depth analysis • Conclusions 9
Slide 10: Phase IIa CS1-003 trial recruitment closed July 2024
Phase IIa CS1-003 trial recruitment closed July 2024 • “On June 28, 2024, Cereno announced the decision to close patient recruitment for the Phase IIa CS1-003 trial by July 1, 2024, after the Clinical Steering Committee recommended sufficient data had been gathered to evaluate the next development s
Slide 11: CS1 PAH trial results (1): Primary endpoint of safety & tolerability met
CS1 PAH trial results (1) Primary endpoint of safety & tolerability met successfully CS1 showed good safety & tolerability profile Safety • No CS1-related serious adverse events including hospitalizations/mortality • No CS1-related changes in liver lab values • No CS1-related clinically significant
Slide 12: CS1 PAH trial results (2): Positive impact on exploratory efficacy parameters
CS1 PAH trial results (2) Positive impact on exploratory clinical efficacy parameters Results: • REVEAL risk score: • 43% (9/21) of the patients improved risk score • 71% (15/21) of the patients improved or had stable risk score • Functional Class: • 33% (7/21) of the patients improved functional cl
Slide 13: Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension • Progressive, debilitating & fatal disease • No spontaneous improvement • No cure, except for lung transplantation www.cerenoscientific.com
Slide 14: Pulmonary Arterial Hypertension is a debilitating disease with no spontaneous improvement
Pulmonary Arterial Hypertension is a debilitating disease with no spontaneous improvement • Progressive narrowing of the pulmonary vessels, Healthy ultimately leading to right heart failure and death • Life expectancy is 2.5 years without therapy, 7.5 Pathological vascular years with current therapy
Slide 15: Epigenetic mechanism through HDAC drives PAH progression
Epigenetic mechanism through HDAC drives PAH progression Pathological remodeling of small pulmonary arteries PAH pathophysiology • Endothelial dysfunction Healthy Early-stage PAH Late-stage PAH • Inflammation • Fibrosis • Plexiform lesions • Vasoconstriction • Vascular & RV hypertrophy Clinical cons
Slide 16: PAH management goals
PAH management goals • Improvement of risk score – Measured by REVEAL • Improvement of symptoms and physical capacity – Measured by functional class • Improvement of hemodynamics – Measured by pulmonary pressure CS1 aims to reach the management goals by reversing pathological remodeling www.cerenosc
Slide 17: Goals of PAH treatment and management
Goals of PAH treatment and management • PAH treatment goals are to improve: • Risk score status (e.g., REVEAL) • Functional class • Hemodynamics (e.g., PVR, mPAP)* • Right ventricular function • Survival PVR: Pulmonary Vascular Resistance; mPAP: mean Pulmonary Artery Pressure. 17
Slide 18: Existing treatment options are insufficient in PAH
Existing treatment options are insufficient in PAH Current therapies do not address the root cause of the disease Key unmet needs in PAH: • Therapies that have disease-modifying capacity • Safer and more tolerable treatments CS1 aims to address the unmet medical needs 18
Slide 19: Scientific rationale: Preclinical data in PAH
Scientific rationale for conducting CS1 phase IIa trial: Preclinical data in PAH • Epigenetic modulation through HDAC inhibition provides attractive proposition to address root cause of PAH disease • Documentation of prevention and reversal of pathological remodeling • Documentation of mPAP reductio
Slide 20: Cereno's HDACi portfolio is untapping the potential of epigenetic modulation in CVD
’s HDACi portfolio is untapping the potential of epigenetic modulation in CVD Disease-modifying elements of CVD addressed by HDACi • Histone deacetylase inhibition 1 Reverse pathological remodeling (HDACi) plays important role in epigenetic modulation.1-14 Unpacked DNA (Suitable for gene expression)
Slide 21: CS1 tackles PAH root cause through reverse remodeling
CS1 tackles PAH root cause through reverse remodeling CS1 is developed as a disease-modifying therapy CS1 characteristics in preclinical models Healthy Early-stage PAH Late-stage PAH • Reverse pathological remodeling • Anti-fibrotic • Anti-inflammatory • Pulmonary pressure reduction • Anti-thromboti
Slide 22: PAH preclinical data – Prevention and reversal of pathological remodeling and reduced mPAP
CS1 effect profile: Anti-fibrotic Anti-inflammatory Pulmonary pressure reduction Anti-thrombotic PAH preclinical data – Prevention and reversal of pathological remodeling and reduced mPAP m PAP: Pulmonary artery pressure. VPA – Active substance in CS1 Source: Lan et al PLoS ONE, 2015; 22 Zhao, L. et
Slide 23: Goal of PAH therapy – Prevent and reverse pathological remodeling
Goal of PAH therapy – Prevent and reverse pathological remodeling Clinical goal of therapy: • Improvement of risk score • Improvement of functional class 23
Slide 24: CS1 PAH phase IIa clinical trial design and goals
CS1 PAH phase IIa clinical trial design and goals • Primary endpoint of safety & tolerability • Explore efficacy parameters and signals of reverse remodeling • Prepare to pursue pivotal trial Dr. Rahul Agrawal Chief Medical Officer and Head of R&D 24 www.cerenoscientific.com
Slide 25: CS1 PAH phase IIa trial design
CS1 PAH phase IIa trial design Primary endpoint: Exploratory endpoints: Implanted device for Trial size: 25 patients 10 Safety and Including validated risk score, pulmonary pressures US clinical sites tolerability functional class 0 2 4 6 8 10 12 14 16 18 20 22 Screening Baseline period Treatment pe
Slide 26: CS1 Phase IIa trial – patients randomized for safety analysis
CS1 Phase IIa trial – 25 patients randomized for safety analysis, 21 patients per protocol Screened N= 38 Screen failure N= 13 Randomized N= 25 CS1 480mg CS1 960mg CS1 1920mg N= 9 N= 8 N= 8 Completed study Early termination Completed study Early termination Completed study Early termination N= 8 N=
Slide 27: CS1 Phase IIa trial – Demographic and clinical characteristics at baseline
CS1 Phase IIa trial – Demographic and clinical characteristics at baseline show representative PAH population Variable Overall (N=25) Female Sex 19 (76.0%) Race White 16 (64.0%) Black or african American 4 (16.0%) Asian 1 (4.0%) Native american or alaska native 1 (4.0%) Other 3 (12.0%) NICE Clinical
Slide 28: CS1 – Phase IIa safety data
CS1 – Phase IIa safety data • Primary endpoint successfully met • Good safety and tolerability profile 28 www.cerenoscientific.com
Slide 29: Primary Endpoint met – No serious adverse events related to CS1
Primary Endpoint met – No serious adverse events related to CS1 Treatment-Emergent CS1 480 mg QD CS1 960 mg QD CS1 1920 mg QD Overall Adverse Events (TEAEs) (N=9) (N=8) (N=8) (N=25) Subjects Subjects Subjects Subjects n (%) n (%) n (%) n (%) Any TEAEs 6 (66.7%) 5 (62.5%) 8 (100.0%) 19 (76.0%) Seriou
Slide 30: Primary endpoint of safety & tolerability successfully met
Primary endpoint of safety & tolerability successfully met CS1 showed good safety & tolerability profile Safety • No CS1-related serious adverse events including hospitalizations/mortality • No CS1-related changes in liver lab values • No CS1-related clinically significant platelets decrease or blee
Slide 31: CS1 phase IIa – Compelling positive signs of efficacy
CS1 phase IIa – Compelling positive signs of efficacy • Reduction in REVEAL risk score • Improvement in functional class • Reduction in mean pulmonary arterial pressure (mPAP, AUC) www.cerenoscientific.com
Slide 32: REVEAL risk score predicts survival
REVEAL risk score predicts survival Published data: REVEAL score has the highest prognostic power Published data (Benza et al., 2022): 1-point reduction in risk score in 12 Time from 1 year post-enrollment (months) weeks associated with 23% reduction in relative risk of death at 12 months1 REVEAL ri
Slide 33: Compelling signs of efficacy (1): REVEAL risk score
CS1 phase IIa – Compelling signs of efficacy (1) REVEAL risk score: 43% of the patients improved REVEAL risk score change from baseline 16 • 43% of the patients (9/21) improved by at 14 least 1 point reduction in REVEAL risk score 12 • 71% of the patients (15/21) improved or Number of patients 10 43
Slide 34: Compelling signs of efficacy (2): Functional Class
CS1 phase IIa – Compelling signs of efficacy (2) Functional Class: 86% improved or had stable functional class NYHA Functional Class change from baseline • 33% (7/21) of patients improved 20 functional class 18 • 86% (18/21) improved or had 16 stable functional class Number of patients 14 33% 12 10
Slide 35: CardioMEMS permits daily non-invasive monitoring of pulmonary arterial pressure
CS1 phase IIa trial – CardioMEMS permits daily non-invasive monitoring of pulmonary arterial pressure Mean Pulmonary Arterial Pressure (mPAP) area under the curve (AUC) is a measure of the pressure burden of pulmonary pressure on the right ventricle of the heart 35
Slide 36: Compelling signs of efficacy (3): Sustained reduction of mPAP AUC
CS1 phase IIa trial – Compelling signs of efficacy (3) CardioMEMS: Sustained reduction of mPAP AUC in 67% (14/21) of patients Changes in mPAP from CardioMEMS (AUC Day 1-85) – 21 patients 600 400 mPAP AUC Day 1-85 200 (mmHg x days) 0 -200 -400 Positive hemodynamics outcome: -600 A mean Pulmonary Arte
Slide 37: Even a small change in ePAD is an independent predictor of mortality
Even a small change (3-5mmHg) in pulmonary artery diastolic pressure (ePAD) is an independent predictor of mortality Relationship between change in ePAD and mortality Published data: Decreased ePAD of 3, 4, or 5 mmHg from baseline to 6 months was associated with decreased mortality risk Source: Zile
Slide 38: CS1 PAH phase IIa trial – Summary of results
CS1 PAH phase IIa trial – Summary of results • Primary endpoint of safety & tolerability met successfully • Compelling positive impact on exploratory clinical parameters already over 12-week treatment: • REVEAL risk score: • 43% (9/21) of the patients improved risk score • 71% (15/21) of the patient
Slide 39: CS1 PAH phase IIa trial investigator Dr. Jason Guichard
CS1 PAH phase IIa trial investigator Dr. Jason Guichard: “I am very pleased with the positive outcomes we are seeing in our patients following treatment with CS1. Their improvements in health and well-being are encouraging and reflect the potential effectiveness of the therapy. This progress reaffir
Slide 40: In-depth analysis
In-depth analysis • Recent inhouse evidence of reverse remodeling from preclinical data • Pulmonary Vascular Resistance (PVR) in the CS1 Phase IIa trial • Remarkable responders: evidence consistent with reverse remodeling and improved RV function in the CS1 Phase IIa trial • Overall findings suggest
Slide 41: Preclinical data – Dose-dependent reduction of plexiform lesions
In-depth analysis Preclinical data – Dose-dependent reduction of plexiform lesions Hallmark of PAH vascular remodeling Reduced incidence of plexiform lesions in small pulmonary arteries (<100µm) (%) Healthy Plexiform Lesions Sugen/hypoxia rat model 40 30 20 10 0 Cross sections of arteries (<100 µm)
Slide 42: Reversal of vascular remodeling is expected to result in a reduction of PVR
In-depth analysis CS1 phase IIa trial – Reversal of vascular remodeling is expected to result in a reduction of PVR PVR is the hemodynamic parameter that best reflects CS1 lowers PVR in several patients reverse remodeling from baseline to end of treatment Patients with improved PVR after 12 weeks th
Slide 43: Remarkable responders in PVR mostly in low dose group
In-depth analysis CS1 phase IIa trial – Remarkable responders in PVR mostly in low dose group Pulmonary Vascular Resistance (Woods) PVR remarkable responders: • Reduction in PVR of >30% • 5 patients identified, range 35-51% Treatment End reduction, mean 45% -50% • 4/5 of the PVR-responders are in lo
Slide 44: Inverse relationship between change in stroke volume and PVR
In-depth analysis CS1 phase IIa trial – Inverse relationship between change in stroke volume and PVR in the remarkable responder group Stroke volume vs PVR changes PVR remarkable responders: • Reduction in PVR and increase in stroke volume • Clinically meaningful increase in SV: > 10 mL1 Impact of P
Slide 45: Overall findings suggest lower dose range (480-960mg) optimal
In-depth analysis Overall findings suggest lower dose range (480-960mg) optimal VPA in CS1 patients vs CS014 in preclinical model estimated unbound exposures Preclinical therapeutic range of CS014 1920mg is consistent with phase IIa clinical response • CS014 is an equipotent analog of the active ing
Slide 46: Summary of in-depth analysis – Evidence of vascular remodeling
In-depth analysis Summary of in-depth analysis – Evidence of vascular remodeling • Recently obtained preclinical data with CS014 demonstrates: • Dose-dependent reversal of remodeling of lung resistance arteries in a PAH model • Dose-dependent reduction of plexiform lesions • Reduction of fibrosis as
Slide 47: Conclusions
Conclusions • Positive topline results of Phase IIa trial with lead candidate CS1 in PAH Sten R. Sörensen Chief Executive Officer www.cerenoscientific.com
Slide 48: CS1 PAH phase IIa trial – Summary results
CS1 PAH phase IIa trial – Summary results • Primary endpoint of safety & tolerability met successfully • Positive impact on exploratory clinical efficacy parameters: • REVEAL risk score: 43% improved; 71% improved or stable • Functional class: 33% improved; 86% improved or stable • mPAP: 67% had sus
Slide 49: CS1 PAH – Path forward
CS1 PAH – Path forward • Completing the analysis of the trial • Fluidda study • Compassionate use and long-term data • Regulatory path www.cerenoscientific.com
Slide 50: CS1 – Clear path forward to develop asset as a disease-modifying therapy for PAH
CS1 – Clear path forward to develop asset as a disease-modifying therapy for PAH • Complete analysis of the PAH trial • Regulatory path • Engaging with regulatory authorities for pivotal trial • Compassionate use • Expanded access program (compassionate use) ongoing and will provide long-term data •
Slide 51: Cereno signs agreement with Fluidda to evaluate the impact of CS1
Cereno signs agreement with Fluidda to evaluate the impact of CS1 on reverse remodeling in a clinical setting Source: FLUIDDA company presentation
Slide 52: Cereno Scientific – Path forward
Cereno Scientific – Path forward • Portfolio development • Key upcoming milestones www.cerenoscientific.com
Slide 53: Cereno develops its pipeline to become attractive for partners or exit through M&A
Cereno develops its pipeline to become attractive for development with strategic financial/pharma partners or exit through M&A Cereno’s assets can be packaged in three different portfolios for • Co-development • Out-licensing, • Asset trade sale and Portfolio ’s Ass s • M&A • Commercialization PAH p
Slide 54: Cereno Scientific – Key upcoming milestones 2025
Cereno Scientific – Key upcoming milestones 2025 CS1 compassionate use program long term (H1) CS1 FDA pivotal study approval (H1) Reverse remodeling Fluidda (H1) CS014 phase I completion (H1) CS014 phase II approval (H2) Continued partnering activities 54
Slide 55: Webcast CS1 phase II topline results – Q&A
Webcast CS1 phase II topline results – Q&A Q&A sessions: • Webcast CS1 phase II topline results – Q&A • Send questions to henrik.westdahl@cerenoscientific.com • Capital Markets Day – October 17th @13.30 55
Slide 56: About Cereno Scientific
Cereno Scientific develops innovative treatments for rare and common cardiovascular disease. The lead drug candidate, CS1, is an HDAC (histone deacetylase) inhibitor that acts as an epigenetic modulator with pressure-reducing, reverse-remodeling, anti-inflammatory, anti-fibrotic and anti-thrombotic
Slide 57: Appendices
Appendices www.cerenoscientific.com
Cereno Scientific — Technical Presentation (September 2024) on 6ix