Biora Therapeutics, Inc. · OTC:BIORQ
Biora Therapeutics — Progenity — Investor Day (November 2020)
68 slides from Biora Therapeutics's investor day presentation, Nov 20, 2020
Slide 1: Preeclampsia R&D Day
Mathew Cooper, PhD, MBA Chief Scientific Officer November 20, 2020 Preeclampsia R&D Day Exhibit 99.1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of the federal securities laws, which statements are subject to substantial risks and uncertainties and are based on estimates and assumptions. All statements, other than statements of historical fa
Slide 3: Preecludia - A High Potential Rule Out Test for Preeclampsia
Preecludia™ - A high Potential Rule Out Test for Preeclampsia Established a fundamental understanding of preeclampsia and the great clinical unmet need that exists today in assessing patient risk in our channel: Ob/Gyn and MFM Showed the incremental healthcare cost burden of $9B+ associated with man
Slide 4: Agenda
Agenda Opening remarks and Introductions Closing Remarks Preecludia™: Clinical Evidence Development Program, Christina Settler, MS, CGC Preeclampsia: The Gravity of the Condition and the Unmet Need, Dr. Christopher Robinson, MD, MSCR, FACOG Preecludia™: The Development Journey from Bench to Bedside,
Slide 5: Introduction to Preeclampsia
Introduction to preeclampsia Douglas Woelkers, MD Professor Obstetrics, Gynecology, and Reproductive Science University of California, San Diego
Slide 6: What is preeclampsia?
What is preeclampsia? A disease of pregnancy Characterized by High blood pressure Multi-organ injury Fetal compromise Named for the syndrome that precedes eclampsia (seizures) Unique to humans Related to presence of placenta Resolves spontaneously after pregnancy
Slide 7: The pathophysiology of preeclampsia is complex
The pathophysiology of preeclampsia is complex STAGE II – MATERNAL Endothelial dysfunction Vasospasm Hypertension Capillary leak Edema Proteinuria STAGE I – PLACENTAL Poor implantation Defective remodeling Perfusion mismatch Hypoxia, inflammation Oxidative stress Free radicals, lipid hydroperoxides
Slide 8: Severe maternal and fetal consequences of preeclampsia
There are severe maternal and fetal consequences of preeclampsia Maternal Impact ✔ Eclamptic Seizures ✔ Intracranial hemorrhage ✔ Posterior reversible encephalopathy ✔ Heart failure ✔ Pulmonary edema ✔ Acute renal failure ✔ Subcapsular hepatic hematoma ✔ DIC, hemorrhage ✔ Death Fetal Impact ✔ Growth
Slide 9: Preeclampsia can affect any pregnancy
Preeclampsia can affect any pregnancy 3.75 million total births US, 2019 3 to 8% of all births complicated by preeclampsia 112,500 to ~300,000 cases per year Occurs in 2nd half of pregnancy After 20 weeks Mostly diagnosed near term (37 to 42 weeks) But disproportionate effect on preterm births “ it
Slide 10: Rates and incidence of preeclampsia by gestational week
Rates and incidence of preeclampsia by gestational week 2009 Natality Statistics, CDC *Lain, et al. JAMA 2002 Late Preterm % of all preeclampsia % births with PE per week 65% 10% 25% Most preterm deliveries due to PE occur between GA 28-37 weeks Gestational Age
Slide 11: Risk Factors for Preeclampsia
Risk Factors for Preeclampsia First pregnancy More than 5 pregnancies Twins Triplets Older maternal age Younger maternal age Obesity Low body mass index Short inter-pregnancy interval Long inter-pregnancy interval New partner Old partner History of subfertility IVF and surrogate pregnancy Preexistin
Slide 12: Clinical and economic burden of preeclampsia is substantial
The clinical and economic burden of preeclampsia is substantial and potentially underestimated # 1 cause iatrogenic preterm delivery 42% of indicated preterm deliveries # 1 indication for labor induction 25% of induced labors # 2 cause of maternal mortality > 15% of direct maternal deaths 50-60 deat
Slide 13: Diagnosis of preeclampsia is based on historical concepts
The diagnosis of preeclampsia is based on historical concepts 1 ACOG Practice Bulletin No. 222: Gestational Hypertension and Preeclampsia. 2020; 135:e237-60. New hypertension with proteinuria or severe features Hypertension Onset usually after 20 weeks Systolic BP ≥ 140, and/or diastolic BP ≥ 90 Sus
Slide 14: Diagnostic features poorly predict adverse outcomes
The diagnostic features of preeclampsia poorly predict adverse outcomes 1 Ukah, U, et al. Pregnancy Hypterten 11, Jan 2018;115-123. Blood pressure and other markers fail to reliably predict adverse outcomes Providers need tests they can trust Feature Adverse Outcome + LR - LR Headache Composite 0.6
Slide 15: The Status Quo: definition of preeclampsia is problematic
The Status Quo: the definition of preeclampsia is problematic Diagnostic Uncertainty Over-use of Resources Latrogenic Preterm Delivery Missed Opportunity to Intervene Medico-legal Risk Not based on pathophysiology Purely clinical diagnosis; no available biomarkers Criteria for diagnosis are unreliab
Slide 16: At UCSD, 30% of pregnancies evaluated for suspected preeclampsia
At UCSD, 30% of pregnancies were evaluated for suspected preeclampsia 2402 deliveries at UCSD (2009) 725 (30%) had lab test(s) for preeclampsia 406 (56%) tested more than once 146 (20%) ultimately diagnosed with PE 75 (46%) severe PE 654 (90%) had a urine P/C ratio 336 (51%) had repeat assays 159 (2
Slide 17: New hypertension criteria will increase suspected cases
New criteria for hypertension and increased prevalence of risk factors will increase number of preeclampsia suspected cases 2017 ACA/AHA Redefinition of Hypertension BP Category Prevalence Risk of PE Normal 71.7% 4.2% Elevated BP 14.1% 6.7% Stage 1 HTN 7.4% 10.9% Stage 2 HTN 6.8% 28.4% BP category,
Slide 18: Evaluation of suspected preeclampsia is cumbersome
The evaluation of suspected preeclampsia is cumbersome Signs or Symptoms Hypertension Proteinuria Headache Visual changes Abdominal pain Nausea Weight gain Edema Decreased fetal movement Spotting Etc… Office Exam Repeat BP Outpatient labs Urine Blood Hospital Triage Serial blood pressures Urine labs
Slide 19: Patient Case
Patient Case 27 y.o. 1st pregnancy, generally healthy Early blood pressure 127/82, overweight, family history diabetes 34 weeks blood pressure 144/85, repeat 136/82 Urine 1+ protein Reports headaches, occasional visual floaters, swelling of legs and feet, post meal abdominal pain Sent to hospital. F
Slide 20: Significant clinical unmet need in diagnosis of preeclampsia
There is a significant clinical unmet need to assist in the diagnosis of preeclampsia Biomarkers of preeclampsia High specificity and PPV Assist confirmation of clinical diagnosis Stratify risk for delivery or severe phenotype High sensitivity and NPV Assist exclusion of diagnosis Provide confidence
Slide 21: Summary
Summary Preeclampsia presents in many ways and is difficult to diagnose Overlooking mild signs may lead to missed diagnosis and adverse outcomes Overreacting to mild signs may lead to unnecessary intervention Providers (MDs and midwives) need accurate, reliable diagnostics to modernize their approac
Slide 22: Preeclampsia cost of illness study
Preeclampsia cost of illness study Maternal & infant costs Mathew Cooper, PhD, MBA Chief Scientific Officer
Slide 23: Maternal & Infant Health Care Costs Related to Preeclampsia
Maternal & Infant Health Care Costs Related to Preeclampsia Objective: Determine PE maternal + fetal cost estimates compared to uncomplicated and hypertensive pregnancies using US primary case data Data collected retrospectively from Geisinger Healthcare system Healthcare outcomes and actual billing
Slide 24: Methods Overview
Methods Overview US, maternal + fetal costs, payer perspective, from 2010-2015 Compared PE to hypertensive and uncomplicated cohorts Equivalence using maternal age, parity, BMI, comorbidities Mothers of singleton pregnancies only Costs GA 20 weeks to 6 weeks post delivery maternal Birth to 12 months
Slide 25: Cohort Normalization
Cohort Normalization focus on incremental PE costs Pulled from patient pop of uncomplicated = 4,210; hypertension = 1,005; PE = 736
Slide 26: Results: maternal and infant costs by cohort
$41,790 $24,182 $13,187 Results: maternal and infant costs by cohort $28,603 ($3,374 for mothers and $25,229 for infants) vs. normal cohort $17,608 ($1,358 for mothers and $16,250 for infants) vs. hypertension cohort Obstet Gynecol. 2019 Dec;134(6):1227-1233 Total incremental costs
Slide 27: Key Clinical Findings
Key Clinical Findings Average gestational age (wks) at delivery lowest in PE Uncomplicated (40), hypertensive (38.7), PE (36.5) Cesarean delivery (%) highest in PE Uncomplicated (29.6), hypertensive (38.3), PE (50.0) LOS (days) highest for mothers/infants highest in PE Uncomplicated (2.2/2.1), hyper
Slide 28: Preeclampsia presents a High Cost Burden in US
Preeclampsia presents a High Cost Burden in US Preeclamptic pregnancies represent an estimated total cost of $8.6-13.8B1 Based on 2019 birth rate2, PE incidence rate of 5-8%3, avg total cost per case $45,8904 Estimated incremental cost of $5.4-8.6B1 Based on 2019 birth rate2, PE incidence rate of 5-
Slide 29: Items to Note
Items to Note One healthcare system, not a national estimate Geography, race known confounders Payer perspective limits cost burden to direct medical care costs Not a comprehensive societal perspective, which would include additional cost components (direct nonmedical and indirect costs) and a longe
Slide 30: Acknowledgements and additional information
Acknowledgements and additional information Geisinger Study Team Susan R. Snyder, PhD; Principal Investigator Jing Hao, PhD, MD; Co-Investigator Jove Graham, PhD, Co-Investigator Michael Paglia, MD, PhD; Co-Investigator Dina Hassen, MPP; Economic Research Analyst Qiang Hao, MS, PhD Candidate; Intern
Slide 31: Preecludia: The development journey from bench to bedside
November 20, 2020 Preecludia™ | The development journey from bench to bedside. Pankaj Oberoi, PhD Vice President Research & Development, Progenity
Slide 32: ACOG Guidelines: equivocal findings are common
ACOG Guidelines provide clinical criteria for diagnosis of preeclampsia, but equivocal findings are common. Symptoms Headache Abdominal pain Shortness of breath Generalized swelling Complaints of “I just don’t feel right” Signs Blood pressure ≥140/90 mmHg Proteinuria ≥ 300mg/dL per 24 hrs Protein: C
Slide 33: Preecludia Targeted Population
3rd 2nd 1st Preecludia™ Targeted Population 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 37 weeks GA: Indicated delivery PE without severe features 34 weeks GA: Indicated delivery PE with severe features https://www.sciencedirect.com/topics/medicine-and-dentistry/gestational-hypertensio
Slide 34: Product development process using proteomics platform
Feasibility Optimization Reagents / Assays / Operation Analytical Verification CLIA Lab Processes Manufacture Kits Multiple Assays Automation Identify Reagent Clinical Studies (more than 3,000 subjects enrolled) Discovery Cohort Feasibility and Optimization PRO-105 Verification PRO-129 Validation PR
Slide 35: Eight biomarkers used to assess placental & maternal health
Eight biomarkers used to help assess placental & maternal health Poor invasion of trophoblasts Intrauterine growth restriction Poor metabolic health of placenta Oxidative stress of placenta Gestational diabetes Liver/kidney damage Heightened maternal immune response to developing placenta Proteinuri
Slide 36: Clinical samples identified improvement to biomarker assay
Clinical samples identified improvement to biomarker assay. Increased robustness to different patient populations Novel form of biomarker Improved test performance with combination of biomarker forms. Biologically relevant for placental health Extensive and developing Intellectual Property portfolio
Slide 37: Preecludia analytical verification achieved
UNMET NEED CLINICAL DILEMMA Preecludia analytical verification achieved Achieved acceptance criteria for CAP Validation Test Performance Specifications Complete accuracy, precision, sensitivity on multiple lots of reagents. Verified linearity, interference, specificity, stability and reference range
Slide 38: Feasibility and optimization results: PRO-105
Training (>900 Subjects) Positive subjects with a diagnosis of preeclampsia Negative subjects do not have preeclampsia Optimization Test Only subjects from intended use population Women with signs and symptoms Healthy subjects not used “Clinical evidence” to measure performance: Independent adjudica
Slide 39: Verification Study (PRO-129)
Verification Study (PRO-129) Process to ensure uniformity in the classification of patients across clinical sites 2-3 Independent Clinicians (Maternal Fetal Medicine specialists) adjudicated the clinical data based on the 2013/2019 ACOG Guidelines All central adjudicators were required to reach agre
Slide 40: Rule-Out Window
Initial Visit Sample A B Patient diagnosed with preeclampsia Delivery C 14 days Rule-Out Window Window for ruling out risk of preeclampsia Status: “At Risk” Expected “at risk” result when the diagnosis is within 14-days of the sample/initial visit. Status: Negative Expected “negative” result when th
Slide 41: Performance in Clinical Verification study (PRO-129)
Performance of our test with the Clinical Verification study (PRO-129) 4 Evaluated locked algorithm from feasibility with the same cutoffs Optimization performance replicated on independent patient cohorts Observed high sensitivity and high NPV required to assist with ruling out the risk of preeclam
Slide 42: Next phase: Clinical Validation Study (PRO-104)
Next phase: Clinical Validation Study (PRO-104) >1,700 Subjects (>3,000 samples) Blinded, prospective, multi-center study 21 Geographically diverse U.S. sites: MFM, OBGYN (L&D) Samples have been collected and ready to be tested starting Q1 2021. Adjudication of clinical diagnosis will be performed b
Slide 43: The gravity of the condition and the unmet need in assessment
November 20, 2020 Preeclampsia: The gravity of the condition and the unmet need in assessment Christopher Robinson, MD, MSCR, FACOG Partner, Charleston Maternal Fetal Medicine
Slide 44: Preeclampsia – the great obstetrical syndrome
Preeclampsia – the great obstetrical syndrome Proteinuria – Lever/Simpson 1843 “Father of Preeclampsia Investigation” Recognized the “spectrum of preeclampsia” Leon C. Chesley, Ph.D. 1908-2000
Slide 45: One of the unsolved obstetric syndromes remaining
Preeclampsia: one of the unsolved “obstetric syndromes” remaining Preeclampsia Currently treated with delivery of the baby Lacks warning signs that can be detected prior to onset of the maternal symptoms. Limits prognostication of course and severity of the disease Risk groups exist and allow for mo
Slide 46: Neonatal hospital costs versus incidence of preterm birth
Distribution of neonatal hospital costs versus incidence of preterm birth in the United States for all births, by gestational age Phibbs CS, Schmitt SK. Estimates of the cost and length of stay changes that can be attributed to one-week increases in gestational age for premature infants. Early Hum D
Slide 47: Improving gestational age at delivery improves outcomes and cost
Improving gestational age at delivery is primary to improved outcomes for pregnancy and cost Preeclampsia is associated with a lower gestational age at birth by ~2-3 weeks gestation and higher NICU costs Preeclampsia is associated with greater long-term costs to mothers and infants not captured in t
Slide 48: No advances in diagnostic assessment despite increasing rates
Despite the increasing rates of preeclampsia There have been no advances in diagnostic assessment There have been no improvements in triage of patients with suspected preeclampsia
Slide 49: ACOG diagnostic criteria
Preeclampsia: ACOG diagnostic criteria Blood Pressure 300 mg or more per 24-hour urine collection (or this amount extrapolated from a timed collection) OR Protein/creatinine ratio of 0.3 or more OR Dipstick reading of 2+ (used only if other quantitative methods not available) Proteinuria Systolic bl
Slide 50: Variability of Proteinuria in Hypertensive Complications of Pregnancy
J. Clin. Invest., 18 (1939), p. 617 The Variability of Proteinuria in the Hypertensive Complications of Pregnancy by Leon C. Chesley (From the Department of Biochemistry, Margaret Hague Maternity Hospital, Jersey City) (Received for publication July 10, 1939)
Slide 51: The obstetric triage dilemma
Common presentations often lead to preeclampsia evaluation: the obstetric triage dilemma Patient presents for triage for obstetrical problem. Often, these are false labor or pregnancy related complaints Initial nursing triage would include assessment of chief complaint, collection of urine and measu
Slide 52: Current definitions and relationship with outcomes are incomplete
Current Preeclampsia definitions and their relationship with outcomes are incomplete Detection rate of adverse pregnancy outcomes according to different definitions of preeclampsia Additional precision is needed – biomarkers of disease activity / severity
Slide 53: Preeclampsia: more than just hypertension
Preeclampsia: more than just hypertension . . .
Slide 54: Origins of preeclampsia are multifactorial
The origins of preeclampsia are multifactorial and are derived from multiple biologic pathways Sarosh Rana. Circulation Research. Preeclampsia, Volume: 124, Issue: 7, 2019, Pages: 1094-1112, DOI: (10.1161/CIRCRESAHA.118.313276) Naljayan, M.V., & Karumanchi, S. (2013). New developments in the pathoge
Slide 55: Current vs ideal triage assessment
Current Triage Assessment Blood pressure Protein assessment in urine Lab Assessments AND Biomarkers of Disease Involved in Pathophysiology Ideal Triage Assessment Blood pressure Protein assessment in urine Lab Assessments This approach misses 50% of adverse neonatal outcomes Preeclampsia: more than
Slide 56: Current vs. ideal triage of suspected preeclampsia patient
The current vs. ideal triage of the suspected preeclampsia patient Current Triage Assessment of Blood pressure and Protein Steroids (in case PE is present) Magnesium (in case PE is present) Inpatient admission (until course of disease is determined) – Possible delivery if worsens Outpatient follow-u
Slide 57: Patient Triage Typical Case Scenario
Patient Triage Typical Case Scenario Patient in triage for obstetrical complaint with blood pressure elevated at 140/92. Fetus is placed on electronic fetal monitoring and testing is reassuring. Urine is noted for trace protein. Clinician Dilemma: Admit to hospital for ongoing care or manage in outp
Slide 58: What do clinicians need in management and triage?
What do clinicians need in the management and triage of patients with symptoms suspected of preeclampsia? A test that is based in the pathophysiology of preeclampsia Rapid ability to rule out disease and thereby prevent unnecessary interventions, hospitalizations and cost. Ability to notify patient
Slide 59: Improving outcomes requires accuracy in assessment of preeclampsia risk
The incidence of preeclampsia is increasing There is no effective cure for preeclampsia – delivery always remains the treatment of choice Current diagnostic testing for preeclampsia lacks a direct relationship to the biologic pathways involved in disease leading to missed opportunities in diagnostic
Slide 60: Preecludia Clinical Evidence Development
Preecludia™ Clinical Evidence Development Christina Settler, MS, CGC Vice President of Medical Affairs, Progenity
Slide 61: Progenity Preeclampsia Clinical Program Overview
Progenity Preeclampsia Clinical Program Overview Patients in Intended Use Population are Managed by All Types of Clinicians OB-GYN MFM L&D Center Specialized Care Influence OB/GYN decision making Routine Care Refer Complex and PE cases to MFMs Delivery Manage all types of patients IRB approved obser
Slide 62: Clinical Study Portfolio
Clinical Study Portfolio Completed Studies Future Studies A total of > 3,700 patients enrolled to date to support the development of Preecludia™ Clinical Study Application Number of patients enrolled PRO-105 Biology/Feasibility >1,300 PRO-129 Verification >450 PRO-104 Validation >1,800 PRO-139 Stabi
Slide 63: Planned publications & Future PE clinical program
Planned publications & Future PE clinical program Summary Planned publications Clinical verification data Clinical validation data Meta analysis combining verification and validation data Preeclampsia disease biology and pathophysiology PRO-136: Observational Clinical Study; acquire clinical samples
Slide 64: Summary
Summary Progenity has a strong, well-established Clinical Operations Department including: Clinical Research coverage of the entire US Data-Management and biostatistics Progenity Biorepository in Ann Arbor We have a robust and diverse network of Clinical Researchers / Key Opinion Leaders necessary f
Slide 65: Q&A
Q&A
Slide 66: Closing Remarks
Closing Remarks Harry Stylli, PhD CEO, Chairman, and Co-founder, Progenity
Slide 67: Preecludia - A High Potential Rule Out Test for Preeclampsia
Preecludia™ - A high Potential Rule Out Test for Preeclampsia Established a fundamental understanding of preeclampsia and the great clinical unmet need that exists today in assessing patient risk in our channel: Ob/Gyn and MFM Showed the incremental healthcare cost burden of $9B+ associated with man
Slide 68: Thank You
THANK YOU