Attached files
| file | filename |
|---|---|
| EX-99.1 - EX-99.1 - PhaseBio Pharmaceuticals Inc | ex991-earningsreleaseq.htm |
| 8-K - 8-K - PhaseBio Pharmaceuticals Inc | axearningsreleaseq32020.htm |
Corporate Overview November 2020
Legal Disclaimer This presentation includes forward-looking statements. All statements contained in this presentation other than statements of historical facts, including statements regarding future results of operations and financial position of PhaseBio Pharmaceuticals, Inc. (“we,” “us” or “our”) our business strategy and plans, the preclinical and clinical development of our product candidates and our objectives for future operations, are forward-looking statements. The words “anticipate,” believe,” “continue,” “estimate,” “expect,” “intend,” “may,” “will” and similar expressions are intended to identify forward-looking statements. We have based these forward- looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our financial condition, results of operations, business strategy, clinical development, short-term and long-term business operations and objectives and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions. Risks regarding our business are described in detail in our Securities and Exchange Commission filings, including in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2020. Moreover, we operate in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the future events and trends discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, achievements or events and circumstances reflected in the forward-looking statements will occur. We are under no duty to update any of these forward-looking statements after the date of this presentation to conform these statements to actual results or revised expectations, except as required by law. You should, therefore, not rely on these forward- looking statements as representing our views as of any date subsequent to the date of this presentation. Moreover, except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements contained in this presentation. 2
Company Overview Clinical-stage biopharma company focused on the development and commercialization of novel therapies to treat cardiopulmonary Therapeutic Focus diseases Bentracimab Novel agent in Phase 3 development for immediate and sustained reversal of ticagrelor, the preferred antiplatelet (PB245) therapy of the American College of Cardiology, the American Heart Association and the European Society of Cardiology Novel, once-weekly, subcutaneously-injected vasoactive intestinal peptide (VIP) receptor agonist that targets VPAC Pemziviptadil Product Candidates receptors in the cardiovascular, pulmonary and immune systems. Pemziviptadil is in Phase 2b development as a (PB1046) potential treatment for patients with pulmonary arterial hypertension (PAH) PB6440 Oral aldosterone synthase inhibitor in early development for treatment-resistant hypertension • Extends circulating half-life of proteins and peptides, enhances solubility, stability and bioavailability while ELP providing a sustained-release mechanism Platform Technology Technology • Enables product candidates that are straightforward to manufacture and administer Recent Milestones & Upcoming Catalysts Completed Phase 2a trial in older/elderly subjects, and InitiatedInitiated PhasePhase 33 trialtrial basedbased onon planplan toto pursuepursue Bentracimab Q3 2019 healthy subjects receiving supratherapeutic doses of BentracimabBentracimab Q1Q1 20202020 ✓ ✓✓ acceleratedaccelerated approvalapproval pathwaypathway ticagrelor Initiated Phase 2b trial in older/elderly subjects to support Bentracimab Q4 2019 Bentracimab 2H 2020 Target for publication of Phase 2a trial results ✓ Biologics License Application (BLA) safety database Bentracimab 2H 2020 Target for publication of Phase 2a trial results Executed Bentracimab funding and co-development Expected to report Phase 2b data from PAH Bentracimab Q1 2020 Pemziviptadil 2H 2021 ✓ agreement with SFJ Pharmaceuticals trialExpected to report Phase 2b data from PAH Pemziviptadil 2H 2021 Granted PRIority MEdicines (PRIME) designation by trial Bentracimab Q1 2020 ✓ European Medicines Agency (EMA) 3
A Clinical Stage, Cardiopulmonary Focused Biopharmaceutical Company Program Pre-Clinical Phase 1 Phase 2 Phase 3 Commercial Rights Upcoming Milestone Bentracimab REVERSE-IT1 Phase 3 ongoing 2H 2020 Reversal of Ticagrelor Targeting to submit BLA in 2H222 Target for publication of Antiplatelet Activity Phase 2a trial results Pemziviptadil Phase 2b ongoing 2H 2021 Pulmonary Arterial (Enrollment was temporarily paused due to COVID-19 risk; certain sites resuming Expected to report Phase 2b Hypertension (PAH) patient screening on a limited basis) data 20213 PB6440 Pre-Clinical Plan to initiate Resistant Hypertension first-in-human clinical trial Partnering Opportunities GLP2-ELP Late Short Bowel Syndrome research CNP-ELP Late Achondroplasia research PROPRIETARY LONG ACTING INJECTABLE RECOMBINANT BIOPOLYMERS Early Programs (Elastin-like Polypeptides – ELPs) 1. REVERSE-IT: Rapid and SustainEd ReVERSal of TicagrElor – Intervention Trial 2. Targeted timeline could be impacted by the continued scope and duration of the COVID-19 pandemic. 3. Timing changed from 1H:21 to FY:21 due to COVID-19-related delays 4
Corporate
Creating Value for Stakeholders in 2020 • Following a successful 2019, PhaseBio continues a rapid pace of development and execution in 2020 Announced innovative funding and co-development collaboration for bentracimab with SFJ Pharmaceuticals Bolstered pipeline with acquisition of resistant hypertension asset, PB6440 Granted EMA PRIME designation for bentracimab Initiated pivotal REVERSE-IT Phase 3 trial for bentracimab in March 2020 Launched international expansion of REVERSE-IT Phase 3 trial, enrolling patients in Canada in October 2020 • Experienced management team • Lead program (bentracimab) funded through potential approvals in key global markets • Novel program for PAH and ARDS (pemziviptadil) being developed using ELP platform technology • Evolving focus on high-unmet need areas of cardiovascular disease with new pipeline asset 6 (PB6440)
Third-Quarter 2020 Financial Highlights • Operating expense: $20.5M ⎯ R&D: $17.4M ⎯ SG&A: $3.1M • Loss from Operations: ($20.5M) • Net Loss of ($25.1M) or ($0.86) per share ⎯ 29.2M shares used for computing Q3 2020 net loss per share • Cash and cash equivalents as of 09/30/2020: $39.4M 7
Experienced Management Team JONATHAN MOW SUSAN ARNOLD, PhD JIM BALLANCE, PhD GLEN BURKHARDT Chief Executive Officer VP of Preclinical & CMC VP Research & Scientific Affairs VP Human Resources KRIS HANSON JOHN LEE, MD, JOHN SHARP MICHAEL YORK VP Legal PhD, FACC Chief Financial Officer VP Corp Development & Chief Medical Officer Commercial Strategy Dedicated to transforming patients’ lives through science and excellence Despite the unprecedented challenges posed by the ongoing COVID-19 pandemic, 2020 has been a year of significant progress for PhaseBio. In addition to refining our mission, advancing our pipeline programs and kicking off the REVERSE-IT Phase 3 clinical trial for our lead program, bentracimab, we have evolved our corporate logo and the overall look and feel of our website, drawing inspiration for the PhaseBio brand from our prospective patients, healthcare providers and our people. The new PhaseBio logo is defined by a patient-friendly representation of the heart composed of the letters ‘P’ and ‘B’ from the PhaseBio name. This shows that cardiovascular disease is not just what PhaseBio does – it is who we are. 8
Bentracimab (PB2452) Reversal Agent for Ticagrelor
Bentracimab Bentracimab: Novel Reversal Agent for Brilinta (Ticagrelor) • Within the P2Y12 antagonist class of oral antiplatelet therapies, ticagrelor has proven superiority vs. clopidogrel, and a unique reversible binding profile ⎯ Clopidogrel and prasugrel, the other members of the oral P2Y12 antagonist class, both permanently bind to the receptor and cannot be reversed • Bentracimab is the only specific reversal agent in development for ticagrelor for both surgical and active bleed indications ⎯ Bentracimab clinical data to date have demonstrated both immediate (<5 min) and sustained (~24 hours) reversal of ticagrelor antiplatelet effects • Approval would differentiate ticagrelor on safety vs. other oral antiplatelet agents ⎯ Expect further differentiation of ticagrelor vs. other P2Y12 agents to drive increased demand Significant unmet need for antiplatelet agent reversal MAJOR BLEEDING URGENT SURGERY OR INTERVENTION • Intracranial Haemorrhage (ICH), GI, Trauma • Currently oral P2Y12 agents, including ticagrelor, require a 5-day washout prior to surgery1,2 • All oral antiplatelet agents have the potential to cause major bleeding, which can be severe or even fatal ⎯ Urgent surgery often cannot wait 5 days ⎯ Higher thrombotic risk during washout • Bentracimab designed to immediately and sustainably reverse • In Phase 1 and Phase 2a studies, bentracimab observed to the antiplatelet effects of ticagrelor immediately and sustainably reverse ticagrelor inhibition of platelet activation ⎯ Enables immediate surgery 1. Plavix/clopidogrel Prescribing Information: https://packageinserts.bms.com/pi/pi_plavix.pdf, https://www.ema.europa.eu/en/documents/product-information/plavix-epar-product- information_en.pdf 10 2. Brilinta/Brilique/ticagrelor Prescribing Information: https://www.azpicentral.com/brilinta/brilinta.pdf#page=1, https://www.ema.europa.eu/en/documents/product-information/brilique-epar- product-information_en.pdf
Bentracimab Bentracimab: Well-Characterized Mechanism of Reversal of Ticagrelor 1. ADP binds to P2Y12 3. Bentracimab binds to free 5. As free ticagrelor is eliminated, ADP can again receptor causing ticagrelor with very high affinity activate the P2Y12 receptor, restoring platelet platelet aggregation activity Bentracimab This is a reversible process with ticagrelor cycling on/off the P2Y12 receptors Bentracimab-ticagrelor binding is Ticagrelor binds to P2Y , inhibiting 12 preferential to ticagrelor-P2Y12 binding due ADP-induced platelet aggregation Bentracimab-ticagrelor is cleared from the bloodstream 2. 4. to 100x higher affinity (Ki 20 pM vs 2nM) 6. 11
Bentracimab Bentracimab: Development and Regulatory Timelines* 2019 2020 2021 2022 2023 NEJM Phase 2a Phase 2b: Older and elderly subjects N=200, 150 randomized to receive bentracimab Breakthrough FDA EMA PRIME Phase 3 interim analysis for Accelerated Approval Post-approval completion of Phase 3 Therapy EOP1 Designation N=100, ~50 major bleeding subjects, ~50 urgent surgery subjects N=100, ~50 major bleeding subjects, ~50 urgent surgery subjects Targeting BLA Submission for Accelerated Approval Targeted timelines could be impacted by the continued scope and duration of the COVID-19 pandemic *Targeted timeline could be impacted by the continued scope and duration of the COVID-19 pandemic NEJM= New England Journal of Medicine, EOP1=End-of-Phase 1 Meeting, BLA=Biologics License Application • Phase 2b initiated in October 2019 ⎯ N=200 total, evaluation of efficacy and overall safety of bentracimab in older and elderly subjects on dual antiplatelet therapy • Phase 3 initiated in March 2020 ⎯ N=200 total, evaluation of efficacy in ticagrelor-treated subjects with major bleeding events or requiring urgent surgery ⎯ Interim analysis of first ~100 patients recommended by FDA for BLA submission for Accelerated Approval 12
Bentracimab Bentracimab Phase 1 Proof-of-Concept Study in Healthy Subjects • Randomized, double-blind, placebo-controlled, single ascending dose, sequential group study (n=64) • Platelet function evaluated using three well established and commonly used assays: LTA, VerifyNow PRUTest® and VASP ⎯ Results from all three assays were highly correlated • Onset of reversal occurred within 5 minutes and was sustained for over 20 hours ORIGINAL ARTICLE • Well tolerated with no drug-related serious adverse events • Importantly, no evidence of rebound in platelet activity after drug cessation Selected as late-breaking oral presentation during featured clinical research session at the American College of Cardiology’s Annual Scientific Session – March 17, 20191 Simultaneously published in the New England Journal of Medicine2 LTA = light transmittance aggregometry, VASP = vasodilator stimulated phosphoprotein phosphorylation immunoassay 1. https://www.acc.org/latest-in-cardiology/clinical-trials/2019/03/15/21/37/ticagrelor-reversal-agent 2. Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. https://www.nejm.org/doi/full/10.1056/NEJMoa1901778 13
Bentracimab Normalized Platelet Function After Ticagrelor Reversal VerifyNow PRUTest Return to Normal Platelet Normal Platelet Function: Inhibited Platelet Function: Function: Post-Bentracimab Pre-Ticagrelor Dosing Post-Ticagrelor Dosing Dosing Normal Platelet Function Inhibited Platelet Function Platelet Reactivity Unit Reactivity Platelet PRU= Platelet Reactivity Units Nominal Time (h) Cohorts 9 and 10 achieved study objectives and are the basis for dosing regimens for subsequent clinical trials Dose-dependent response across all cohorts tested Enables rapid resumption of ticagrelor dosing post infusion Immediate reversal within 5 minutes of start of infusion Well tolerated across all cohorts Sustained duration of reversal extended to 20+ hours No drug-related SAEs reported Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. https://www.nejm.org/doi/full/10.1056/NEJMoa1901778 Presented by Dr. Deepak L. Bhatt at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA, March 17, 2019. Slides available at: https://www.acc.org/~/media/Clinical/PDF-Files/Approved- PDFs/2019/03/15/ACC19_Slides/Mar17_Sun/3pmET_Ticagrelor-Reversal-Agent-acc-2019.pdf 14
Bentracimab Positive Preliminary Bentracimab Phase 2a Results • Positive preliminary results from the bentracimab Phase 2a trial were disclosed via press release1 ⎯ First trial of bentracimab to include older and elderly subjects (ages 50-80) on dual antiplatelet therapy (DAPT) of ticagrelor and low-dose aspirin ⎯ Subjects in the trial resembled the patient population most likely to be treated with ticagrelor and potentially benefit from bentracimab, if approved • Per FDA request, the Phase 2a trial also explored reversal of supratherapeutic blood levels of ticagrelor that could result from ticagrelor overdosage or drug-drug interactions ⎯ PhaseBio believes an appropriate bentracimab regimen has been identified for these patients • Confirmed dosing regimen to be used in the Phase 2b and Phase 3 trials • Results to be published and presented at an upcoming medical congress Supratherapeutic Dose of Bentracimab Phase 2a Trial Older & Elderly Subjects on DAPT Ticagrelor Immediate and sustained reversal of the antiplatelet effects of ticagrelor ✓ ✓ Efficacy demonstrated using same three assays used in Phase 1 trial2 ✓ ✓ Results highly correlated across assays ✓ ✓ Generally well tolerated with only minor adverse events reported ✓ ✓ 1. https://investors.phasebio.com/news-releases/news-release-details/phasebio-announces-completion-phase-2a-clinical-trial-pb2452 2. Bhatt, D. L. et al. Antibody-based ticagrelor reversal agent in healthy volunteers. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa1901778 15
Bentracimab REVERSE-IT: Bentracimab Pivotal Phase 3 Trial Overview • REVERSE-IT: Rapid and SustainEd ReVERSal of TicagrElor – Intervention Trial • Phase 3 trial is a key element of development plan that has garnered FDA Breakthrough Therapy and EMA PRIME designations • Open-label, single-arm study of reversal of the antiplatelet effects of ticagrelor with bentracimab in patients who present with uncontrolled major or life-threatening bleeding or who require urgent surgery or invasive procedure • Total of 200 patients targeted for enrollment ⎯ ~100 patients from major bleeding population, ~100 patients from urgent surgery population ⎯ First ~50 patients from each of the respective target populations (total of ~100) will form the basis of accelerated BLA filing in US and MAA in EU • Accelerated BLA endpoint is restoration of platelet function based on VerifyNow® PRUTest® platelet function assay ⎯ VerifyNow has been used in the Phase 1, Phase 2a and ongoing Phase 2b trials of bentracimab with consistent results across studies completed to date • Additional clinical endpoints related to hemostasis will be captured as part of the primary outcome analysis • Trial posted online at ClinicalTrials.gov and initiated in March 2020 16
Bentracimab Bentracimab Regulatory Updates Development plan for bentracimab designed with objective to broadly support global regulatory filings Separate written guidance from FDA and EMA indicates that REVERSE-IT, a single, non-randomized, open-label Phase 3 trial of bentracimab in both surgical and major bleeding populations has the potential to support regulatory filings in the United States and the European Union EMA: FDA: • Received written Scientific Advice: February 2020 • Received meeting minutes from bentracimab End-of- Phase 1 meeting: August 2019 ⎯ Written guidance from the CHMP of the EMA generally agrees with PhaseBio’s proposed development plan for ⎯ FDA alignment on development plan and Accelerated bentracimab Approval regulatory path • Granted PRIME designation: February 2020 • Bentracimab granted Breakthrough Therapy designation: April 2019 ⎯ PRIME designation is granted by the EMA to support medicines that demonstrate the potential to address ⎯ Breakthrough Therapy designation is designed to 1 substantial unmet medical need expedite the development and review of promising new drugs2 ⎯ Potentially expedites the review and approval process 1. The European Medicines Agency. “PRIME: Priority Medicines” Available at: https://www.ema.europa.eu/en/human-regulatory/research-development/prime-priority-medicines#. Accessed February 2020 2. The U.S. Food and Drug Administration. “Expedited Programs for Serious Conditions – Drugs and Biologics.” Available at: https://www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf. Accessed 17 February 2020
Bentracimab SFJ Pharmaceuticals Funding and Co-Development Collaboration • Innovative collaboration between SFJ and PhaseBio to support the global development of bentracimab • SFJ will fund up to $120 million to support the clinical development of bentracimab ⎯ SFJ has extensive experience in the global clinical development and regulatory approval of numerous pharmaceutical products across multiple indications and therapeutic areas • SFJ will assume a central role in global development and regulatory activities for bentracimab outside the United States ⎯ SFJ will lead development and regulatory activities in China and Japan ⎯ PhaseBio and SFJ will work closely on clinical program in EU ⎯ PhaseBio is conducting REVERSE-IT Phase 3 trial in North America • PhaseBio retains exclusive worldwide commercial rights to bentracimab 18
Bentracimab Expect Continued Long-Term Rx Growth of Ticagrelor Bentracimab approval has the potential to drive continued positive momentum • Brilinta/Brilique sales in 2019 were $1.58B and growing (+20% Y/Y) ⎯ Patient growth drives Y/Y revenue growth in key regions: strong growth in the United States and Emerging Markets • In February 2019, Brilinta Phase 3 THEMIS1 trial met primary endpoint in patients with established coronary artery disease and type-2 diabetes; in May 2020, FDA approved a label update2 for BRILINTA in the US to include the reduction of the risk of a first heart attack or stroke in high-risk patients with coronary artery disease • In January 2020, Brilinta Phase III THALES3 trial met primary endpoint in patients with acute ischemic stroke or patients with high-risk transient ischemic attack Ticagrelor Differentiation Now Post Bentracimab Launch Post LOE of ticagrelor vs. clopidogrel Efficacy ✓ ✓ ✓ Safety ≈ (no reversal agent) ✓ ✓ Price (branded✕vs. generic) (branded✕ vs. generic) ✓ 1. https://www.astrazeneca.com/media-centre/press-releases/2019/brilintas-phase-iii-themis-trial-met-primary-endpoint-in-patients-with-established-coronary-artery-disease-and-type-2-diabetes-25022019.html 2. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/brilinta-approved-in-the-us-to-reduce-the-risk-of-a-first-heart-attack-or-stroke-in-high-risk-patients-with-coronary-artery-disease.html 19 3. https://www.astrazeneca.com/media-centre/press-releases/2020/brilinta-met-primary-endpoint-in-phase-iii-thales-trial-in-stroke-27012020.html
Pemziviptadil (PB1046) Once Weekly Vasoactive Intestinal Peptide (VIP) Analog
Pemziviptadil Pemziviptadil: Harnessing VIP to Create a Stable, Long-Acting Drug VIP as a THERAPEUTIC AGENT PRECLINICAL STUDIES Endogenous VIP Pemziviptadil Support Clinical Development for: • Pulmonary Arterial Hypertension • DMD Cardiomyopathy • Heart Failure (Chemotherapy-Induced HF or HFpEF) • Cystic Fibrosis Pemziviptadil MECHANISM OF ACTION VIA VPAC2 RECEPTOR • Potent vasodilator and immunomodulator • Anti-inflammatory and anti-fibrotic • Cardiac support through increased inotropy and lusitropy 21
Pemziviptadil Proprietary Elastin-Like Polypeptide (ELP) Technology Key to optimizing the profile of an injectable VIP product candidate PROLONGED CIRCULATING HALF-LIFE COACERVATION DELIVERS SLOW RELEASE “Biopolymer” Repeating Sequence of Human Elastin Peptides Outside Body Inside Body Active Moiety ↑ Temperature VPGXG n Peptide/Protein Highly Soluble ELP Non-Soluble ELP (VIP, GLP1, etc.) = UP TO 200x INCREASE IN ½ LIFE = WEEKLY OR MONTHLY DOSING IMPROVING • Pharmacokinetics • Slower rate of bioavailability • Ease of Administration • Patient Compliance 22
Pemziviptadil High Unmet Need in an Orphan Disease Primary Pulmonary Arterial Hypertension (PAH, WHO Group 1 PH) • High unmet need for novel disease-modifying PAH therapies for greater efficacy ⎯ All 3 approved drug classes in PAH are vasodilators: prostacyclin, endothelin, and nitric oxide pathways ⎯ Patients inevitably continue to decline and die on current standard of care • VIP addresses PAH vasoconstriction, progressive vascular remodeling, and right heart failure 23
Pemziviptadil Pemziviptadil Clinical Development Activities to Date Have Supported Advancement into Phase 2 Efficacy Studies PHASE 1 Studies Completed PHASE 2 PAH Studies SAD study in Open-Label Phase 2a CardioMEMS Phase 2b PAH Efficacy hypertensive patients 4-week MAD study in in PAH study: Safety and HFrEF patients on SOC 16-Wk Randomized, Controlled washed off meds Hemodynamics Study • Well tolerated for a week • Well tolerated across dose CardioMEMS Open-Label PAH Study Phase 2b PAH 16 wk randomized, controlled study over broad range of range; no drug-related SAEs exposure; no drug-related reported • N = 3 patients, dosed weekly for 8 wks, followed by • N = ~60 NYHA class II/III PAH patients, dosed SAEs reported extension weekly x 16 weeks • Replicated PK/PD from SAD • Prolonged PK/PD profile over over 4 weekly SC injections – No longer enrolling patients – Individual dose titration to MTD 1 week • VIP activity reproduced in • Real-time PA pressure and other hemodynamic • Efficacy endpoints PVR via RHC, 6MWD • VIP activity confirmed HFrEF patients on SOC monitoring (Systolic and Diastolic BP lowering) • Extension study to follow • Initial data show improved hemodynamics • One drug-related SAE reported in extension portion of open-label pilot study COMPLETED COMPLETED COMPLETED Phase 2b ongoing 24
PB6440 Aldosterone Synthase Inhibitor for Resistant Hypertension
PB6440 PB6440 for Resistant Hypertension • Upwards of 10 million patients in the United States have resistant hypertension and are at risk for serious, costly medical consequences (stroke, heart attack, kidney failure, etc.)1 • Physicians currently prescribe numerous combinations of antihypertensives to lower blood pressure and diminish risk • Blocking aldosterone has been shown to be an effective mechanism for treating resistant hypertension ⎯ Currently available aldosterone blockers suffer from poor potency and pharmacokinetics (eplerenone) or poor tolerability (spironolactone) and thus are rarely used • Recent draft guidance from the FDA outlines a streamlined regulatory path for novel drugs to treat resistant hypertension without the need for large outcomes studies2 • Market research indicates that payors aware of high medical costs associated with resistant hypertension Large, growing patient population, coupled with a high unmet need, creates an attractive opportunity for a novel therapy to help patients and care-providers better manage blood pressure 1. Carey RM, Sakhuja S, Calhoun DA, Whelton PK, Muntner P. Prevalence of apparent treatment‐resistant hypertension in the United States: comparison of the 2008 and 2018 American heart association scientific statements on resistant hypertension. Hypertension. 2019; 73: 424‐ 431. Available at: https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.118.12191?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed. Accessed February 2020 2. U. S. Food and Drug Administration. Center for Drug Evaluation and Research. (2018) Hypertension: Conducting Studies of Drugs to Treat Patients on a Background of Multiple Antihypertensive Drugs Guidance for Industry. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/hypertension-conducting-studies-drugs-treat-patients-background-multiple-antihypertensive-drugs. Accessed February 2020 26
PB6440 PB6440 Is Highly Selective for Aldosterone Synthase (CYP11B2) Selectivity and Potency Demonstrated in Primate Chronic Oral Dosing Model CYP11B Potency and Selectivity (IC50, µM) Human Monkey CYP11B2 CYP11B1# Selectivity CYP11B2 CYP11B1 Selectivity PB6440 0.024 4.859 202 0.016 5.802 363 LCI699* 0.0007 0.013 19 0.016 0.059 3.7 # Steroid 11 -hydroxylase *Discontinued Novartis compound; active in Phase 2 studies, but blocked cortisol production, likely due to inadequate selectivity β In a primate model, oral PB6440 demonstrated a sustainable reduction in aldosterone without a significant increase in steroids upstream of CYP11B1, suggesting no significant inhibition of CYP11B1 in vivo 27
