nasdaq: pavm, pavmz corporate overvie€¦ · nasdaq: pavm, pavmz corporate overview lishan aklog,...

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PAVmed, Inc.Nasdaq: PAVM, PAVMZ

Corporate Overview

LISHAN AKLOG, MD

Chairman & CEO

DENNIS M. MCGRATH

Executive VP & CFO

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Disclaimers

This presentation contains certain forward-looking statements that involve risks and uncertainties.

▪ Actual results and events may differ significantly from results and events discussed in forward-looking statements.

▪ Factors that might cause or contribute to such differences include, but are not limited to, those discussed in “Risk Factors” in our Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission.

▪ We undertake no obligation to update publicly any forward-looking statements to reflect new information, events, or circumstances after the date they were made.

This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of securities in any jurisdictions in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.

PAVmed has not yet received clearance from the FDA or any other regulatory agency for any of the products described in this presentation.

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HIGHLY DIFFERENTIATED

MULTI-PRODUCT

MEDICAL DEVICE COMPANY

Focus on high-margin, single-use products

Interventional or acute care

Broad spectrum of clinical conditions and specialty call points

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PRODUCT

ESTIMATED

MARKET

SIZE1

REGULATORY

PATHCURRENT STATUS

POTENTIAL UPCOMING

MILESTONES

CarpX

Minimally Invasive Device to

Treat Carpal Tunnel Syndrome

>$1B 510(k)

• Preparing for pre-submission meeting for resubmission

• Completing manufacturing qualifications

• Pre-commercial activities including physician engagement

• FDA 510(k) Clearance

• First-in-Human (FIH) in New Zealand

• CE Mark Submission

EsoCheck

Non-Invasive Device & DNA

Biomarkers to Detect Esophageal Cancer Precursor

>$1B 510(k) + LDT

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• Human study documenting >90% accuracy published

• Large NIH-funded multi-center clinical trial for Barrett’s screening indication enrolling, 90 patients to date

• CLIA certification in process

• Gen 2 510(k) testing in process

• Balloon sampling device FDA 510(k) Submission

• CLIA certification for LDT

• Liquid media validation from data on 80-100 patients

PortIO

Implantable Intraosseous

Vascular Access Device

>$750M de novo

• FDA presubmission guidance received

• Pilot 7-day animal completed

• GLP 7-day animal protocol approved by FDA

• Ongoing strategic engagements

• Complete GLP 7-day animal study

• Strategic partnership

DisappEAR

Antimicrobial Resorbable Ear

Tubes

~$300M 510(k)

• Process to manufacture tubes from commercially sourced silk blocks established

• Optimizing process for drug coating vs. impregnation

• Initiate three-month animal study to confirm resorption rates

Lead Products

*PAVmed has not yet received clearance from the FDA or any other regulatory agency for any of these products.1Company estimate2Laboratory Developed Test

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Key Recent DevelopmentsProgress towards major lead product milestonesCarpX (510k)

▪ 510(k) process proceeding with pre-submission meeting to be scheduled for

resubmission following expiration of FDA review period for initial submission

▪ Plan to update investors once the FDA meeting date is scheduled

▪ Active pre-commercial engagement with physicians

PortIO (de novo)▪ Successful 7-day pilot animal study based on FDA recommendations

▪ FDA approved protocol for 7-day GLP animal study, scheduled for next month

▪ Encouraging strategic discussions with market leaders

EsoCheck (510k, PMA)

▪ 510(k) process initiated

▪ Clinical trial enrollment progressing

▪ Active pre-commercial engagement with physicians

Strengthened balance sheet▪ Raised $10.4 million gross proceeds from oversubscribed equity rights offering

▪ Adequate capital to reach major milestones in 2019

Strengthened management team▪ Hired industry veteran to serve as Chief Commercial Officer

▪ Hired full-time Director of Investor Relations

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Growth Strategy

Advance lead products to commercialization▪ CarpX – Push 510(k) clearance over finish line, complete FIH

and CE Mark

▪ EsoCheck – Target 510(k) submission in Q4-2018 and CLIA

certification in Q1-2019, accelerate clinical trial enrollment

▪ PortIO – Target completion of de novo animal study and IDE

submission in Q4-2018, complete strategic partnership

▪ DisappEAR – Complete resorption study in animals for 2019

FDA 510(k) submission

Pursue strategic initiatives to enhance

shareholder value

▪ Continue to evaluate product opportunities presented to us by

clinician innovators and academic medical centers

▪ Explore M&A and strategic partnership opportunities

synergistic with lead products and broader vision

Continue to strengthen balance sheet

▪ Retire or refinance senior secured debt

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LISHAN AKLOG, MDCHAIRMAN & CEO

DENNISMCGRATHEXECUTIVE VP & CFO

BRIANDEGUZMAN, MDCHIEF MEDICAL OFFICER

SHAUN O’NEILCHIEF COMMERCIAL

OFFICER

Management Team

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Capital Structure

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Business Model

COMMERCIAL OPPORTUNITY

ATTRACTIVE MARKET• Unmet clinical need

• Regulatory pathway

HIGH-MARGIN PRODUCT• Reimbursement

• Technologic Complexity

• Cost-of-goods

KEY BUSINESS PROCESSES

CAPITAL EFFICIENCY &SPEED TO MARKET• Outsourced best-in-class

process experts

• Light infrastructure, low fixed costs

• Shortest path to INITIAL Regulatory Clearance

MULTIPLE PATHWAYS TO COMMERCIALIZATION

MULTI-PRODUCT PIPELINE

RISK MITIGATION• Non-binary success

ECONOMIES OF SCALE

CORPORATE FLEXIBILITY• Dynamic resource

allocation and prioritization

• Streamlined channel to incorporate external innovation

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Multiple Pathways to CommercializationTailored to Maximize Value Creation

TARGETED INITIAL COMMERCIALIZATION

• Key Opinion Leaders

• Independent Distributors

CORPORATEACQUIRER

• Asset sale to strategic

• Non-dilutive financing

CORPORATEPARTNER

• Sales & distribution agreement

• Option to acquire

FULL SELF COMMERCIALIZATION

• Hybrid sales channel

• Build organically or acquire

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CarpXMinimally Invasive Device to Treat Carpal Tunnel Syndrome

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Carpal Tunnel SyndromeCLINICAL OVERVIEW

Incidence▪ Over 600,000 US procedures annually1

▪ Up to 1.5 million with symptoms who “suffer in silence” 2

Mechanism▪ Inflammation and scarring of transverse carpal ligament

▪ Entrapment of the median nerve ⇒ hand pain, numbness and

weakness

1Fajardo, et al. J Hand Surg 2012; 37(8):1599-16052Estimate based on CTS prevalence data from Dale et al. Scand J Work Environ Health. 2013 Sep 1;39(5):495-505.

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TRADITIONAL CARPAL TUNNEL SURGERY IS INVASIVE

ENDOSCOPIC SURGERYIS LESS EFFECTIVE

•Up to 2 inch incision

•Performed in an OR

•At least 3-4 month, up

to 6-9 month recovery

• Remains a surgical

procedure

• Higher recurrence and

reoperation rate

• Increased nerve injury

• Higher costs

Carpal Tunnel Syndrome

MARKET OPPORTUNITY

600,0001 current surgeries* x $1,500 minimum ASP = ~$1 billion

Additional 1.5M2 “silent sufferers” who choose to defer surgery

UNMET CLINICAL NEED – CURRENT LIMITATIONS

1Fajardo, et al. J Hand Surg 2012; 37(8):1599-16052Estimate based on CTS prevalence data from Dale et al. Scand J Work Environ Health. 2013 Sep 1;39(5):495-505.

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CarpX – Minimally Invasive CTS Device

Key Features

Single-use precision radiofrequency

(RF) energy cutting tool

▪ Connects to standard electrosurgical

generator

Balloon creates anatomic separation

▪ Protects nerve and tendons by pushing them

away from ligament

Balloon tensions ligament

▪ Facilitates cutting of ligament by stretching it

and pushing electrode into it

Active RF electrode cuts ligament

▪ Short (< 1.5 second) burst of RF energy

▪ Automatically cuts off if complete cut

detected by monitoring balloon pressure

▪ Can test for nerve proximity prior to cutting

using nerve stimulator

*PAVmed has not yet received clearance from the FDA or any other regulatory agency for any of these products.

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CarpX Procedure

Inflate balloon with contrast material

Narrowed “waist” at

point of maximal constriction

Insert device over wire and position electrodes relative to carpal bones

Wire

Wire Electrodes

Test placement of electrodes relative to nerves using nerve stimulator

Electrodes

Wire

Activate device, cutting ligament with <2 sec burst of RF energy

Constriction relieved, no

residual waist


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CarpX in Action


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CarpX in Action


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CarpX – Advantages

LESS INVASIVE MORE COST EFFECTIVE

• Option to perform the procedure

truly percutaneously

• Less pain, scarring

• Accelerate time to full recovery

Anticipate 1-2 weeks vs often >6 months

• Shift from OR to interventional lab

• Shorten procedural times

• Shorten time out of work

FEWER COMPLICATIONS EXPANDED MARKET

• Better nerve protection

• Minimal risk of infection

• Lower threshold for intervention

for patients “suffering in silence”


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CarpX – Preclinical Testing Results

In Vivo Animal Testing▪ < 1 mm maximum zone of thermal injury

▪ Limited to cut edges of ligament

completely sparing nearby tissues and

structures including nerves and blood

vessels (encircled in red)

▪ Any rise in temperature limited to 1mm

and transient (< 20 sec)

Human Cadaver Testing▪ Complete and reliable cutting of ligament

with no adverse events noted in multiple

cadavers

▪ Multiple surgeons successfully

performed multiple procedures after an

initial training session

▪ Excellent anatomic separation created by

balloon, safely displacing key nerves

away from cutting electrode far beyond

thermal zones


PATHOLOGY RESEARCH LABORATORY, INC.

Experimental Pathology Services with GLP Compliance

521 Rocca Avenue, South San Francisco, California 94080. Tel (650) 225 0666. (650) 580 1951.

2829 Depot Road, Suite #4, Hayward, California 94545. email: [email protected]

Page 9 of 25

Figure 2. Treatment site 1. Histopathology section at low magnification (contact image).

SK=skin surface, FA=fascia, M-muscle.

Figure 3. High magnification of the rectangular region highlighted in Figure 2. Blood vessels

and nerve fibers located below the severed fascia are normal and unaffected.

SK

FA

M

TUNNEL

PATHOLOGY RESEARCH LABORATORY, INC.

Experimental Pathology Services with GLP Compliance

521 Rocca Avenue, South San Francisco, California 94080. Tel (650) 225 0666. (650) 580 1951.

2829 Depot Road, Suite #4, Hayward, California 94545. email: [email protected]

Page 10 of 23

Figure 1. Treatment site #1. Red dashes represent device insertion. EN=device entrance,

EX=device exit

Figure 2. Site #1. Tunnel represents the device pathway under the skin. Blood vessels and

nerve fibers located adjacent to the severed fascia are normal and unaffected.

EN EX

Representative histologic images showing minimal thermal injury (red circles) limited to cut edges of ligament (fascia)

Representative X-ray images showing excellent anatomic separation of key nerves, protecting them from electrode

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FDA 510(k) PathwayFILED FDA 510(K) PRE-MARKET NOTIFICATION SUBMISSION

▪ Existing carpal tunnel release system as predicate

▪ Submitted robust and complete response to request for additional testing to document limited thermal spread and addressing all issues raised showing CarpXat least as safe as predicate, consistent with substantial equivalence standard

▪ Review period expired before consensus could be reached between branches

▪ In process of filing package for pre-submission meeting prior to 510(k) resubmission, per FDA recommendation

US Commercialization Strategy▪ Initial launch using independent distributors

▪ Hand Surgery/Interventional Radiology Key Opinion Leaders

▪ Hybrid Sales with regional managers overseeing distributors▪ Accelerating pre-commercial physician engagement

OUS Strategy▪ Plan First-in-Man in Q4-2018 in New Zealand

▪ Preparing for European CE Mark Submission in Q4-2018

▪ Active discussions with distributors in Europe, South America and Asia

CarpX – Current Status

*PAVmed has not yet received clearance from the FDA or any other regulatory agency for any of these products.1 Based on Company Estimates.

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EsoCheckNon-Invasive Device & DNA Biomarkers to Detect

Esophageal Cancer Precursor

mVIM + mCCNA

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Esophageal Adenocarcinoma Cancer (EAC)Fastest growing cancer in US1

Lowest survival rate2

▪ 5-year survival < 20%

▪Death toll exceeds ovarian cancer

Among highest cost of care3

Seldom detected early4

1Pohl & Welch. J Natl Cancer Inst. 2005; 97:142-146. 2Siegel, et al. CA Cancer J Clin 2016; 66:7-303Mariotto et al. J Natl Cancer Inst 2011; 103:117-128.4Dulai et al. Gastroenterology 2002; 122:26-33.

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GERD / Barrett’s Esophagus

GASTROESOPHAGEAL

REFLUX (GERD)

BARRETT’S

ESOPHAGUS (BE)

ESOPHAGEAL

ADENOCARCINOMA

• “Heartburn”, “Acid Reflux”

• 15-30% of Western populations1

• Treatment with OTC meds can mask pathology

• Lower esophageal lining transformed from exposure to acid

• Precursor to dysplasia and esophageal cancer

• Can be treated with ablation if detected early

• Nearly all EAC patients shows evidence of prior Barrett’s esophagus

• Can be prevented if Barrett’s detected and treated prior to progression to cancer

1El-Serag et al. Gut 2014; 64(6):871-880.

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Screening for Barrett’s EsophagusCurrent Standard – Upper Endoscopy▪ Invasive, costly and requires sedation

▪ Relies on pathology so cannot be automated

▪ Only recommended in high-risk symptomatic GERD and Minimal overall impact in preventing EAC ~40% of new EAC patients have GERD symptoms1

< 10% of new EAC patients have prior diagnosis of BE2

▪ Widespread BE screening with EGD not practical or cost-effective

Unmet Clinical Need▪ Non-invasive alternative to endoscopy to

detect BE and prevent progression to EAC

▪ Must be highly accurate

▪ Efforts to date (e.g., CytoSponge) depend on cytology and have other limitations

▪ Biomarkers superior for screening because can be automated, not dependent on individual pathologist

CytoSponge

1Chak et al. Cancer 2006; 107:2160-2166.2Lagergren et al. NEJM 199; 340:825-831.

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EsoCheck – Noninvasive BE Biomarker Test

BALLOON DNA SAMPLING

DEVICE

HIGHLY ACCURATE DNA

BIOMARKER ASSAY

• Vitamin pill-sized silicone-covered capsule containing small deflated balloon attached to thin catheter

• Patient swallows capsule

• Balloon inflated in the stomach

• Balloon pulled back, swabbing the lower esophagus for cells

• Balloon deflated protecting sample of cells from dilution or contamination

• Methylated DNA Assay, similar to ones already used in FDA-cleared tests

• mVIM - well established biomarker in colon cancer

• mCCNA – newly discovered biomarker

• IP protection of modified genes (composition of matter) and algorithms

• Low-cost, automatable

• Returns simple binary result

mVIM + mCCNA

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EsoCheck – In Action

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EsoCheck Clinical Results

Study Design▪ Patient referred for endoscopy

▪ 322 patients underwent endoscopic brushing sampling and EsoCheck assay (mVIM+ or mCCNA+) to set and validate assay cut-offs

▪ 86 patients underwent EsoCheck balloon sampling and EsoCheck assay

Results▪ Assay highly accurate with >90% sensitivity

and specificity

▪ Balloon sampling device well tolerated same accuracy as endoscopic brushings

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Gastroesophageal Reflux (GERD) ▪ Over 20 million weekly GERD patients

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▪ 9 million physician visits per year2

Barrett’s Esophagus (BE) ▪ 3-4M patients in US

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▪ ~ 10 % of symptomatic reflux patients undergoing EGD have BE vs <1% of patients without reflux symptoms

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Market▪ Target ASP $1000 (Cologuard $649)

▪ Target gross margin 85%

▪ Immediately addressable market 10% of GERD patients = $2 billion

▪ Total addressable market all white men over 50 years of age = $45 billion

▪ OUS market similarly sized

EsoCheck – Market Opportunity

1El-Serag et al. Gut 2014; 64(6):871-880.2Peery et al. Gastroenterology 2012; 143:1179-1197.3Runge et al. Gasterentrol Clin North Am 2015; 44(2):203-201.4Modiano et al. Ther Clin Risk Manag 2007; 3(6):1035-1145.5US Census Bureau. Annual Estimates of the Resident Population by Sex, Age, Rac...April 1, 2010 to July 1, 2016. factfinder.census.gov.

2M GERD

Patients

GERD population of 20M

~45M

White men over 50 yrs5

US Market

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Phase I: Initial Commercial Product (510k+LDT)

▪ Target launch: Q1-2019

▪ 510(k) submission of Gen2 EsoCheck balloon sampling device Q4-2018

▪ Complete CLIA certification of CWRU reference laboratory for DNA

biomarker assay in Q1-2019

▪ Market EsoCheck kit with balloon sampling device and sample sent to

reference laboratory under Laboratory Developed Test (LDT)

designation

▪ CE Mark submission: Q2-2019

Phase II: Expanded Indication (PMA)

▪ Target clearance: Q1-2021

▪ PMA submission seeking specific indication for widespread BE

screening in high risk population ACG-recommended population

consisting of 20 million white males >50 years with >5-year history of

GERD.

▪ Large NIH-funded multi-center trial of Gen 2 EsoCheck device + Assay

(Two arms: case-control assay revalidation and detection) currently

actively enrolling at 8 centers (ClinicalTrials.gov: NCT00288119)

EsoCheck – Regulatory/Commercial Strategy


EsoCheck

mVIM + mCCNA

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EsoCheck – Regulatory/Commercial Strategy

Phase IInitial Commercial Product

510(k) Balloon + LDT Assay

▪ REGULATORY• 510(k) submission of Gen2 EsoCheck

balloon sampling device (Q4-2018)• Laboratory Developed Test (LDT)

designation of EsoCheck Assay at reference lab (Q1-2019)• CE Mark submission (Q2-2019)

▪ COMMERCIAL• Target US launch late Q1-2019• EsoCheck Kit provided to clinicians,◆ Balloon sampling device◆ Cytolyte vial◆ Mailer

• Assay◆ 3-4 day turnaround◆ Binary result reported based on > 1% of DNA

for mVIM or mCCNA1◆ Lab bills payor under Proprietary Laboratory

Assay (PLA) code

Phase IIWidespread Screening Test

PMA Submission

▪ REGULATORY• PMA for widespread BE screening

indication in high risk population◆ ACG-recommended population consisting of 20

million > 5-year history of GERD with 2 risk factors

• Current NIH-funded EsoCheck trial◆ ClinicalTrials.gov: NCT00288119◆ Case-control and Detection arms◆ Enrolled ~100 patients at 8 centers

• Lucid considering parallel studies to support PMA◆ Detection study in US◆ PCP-targeted detection study in Europe

• Target milestones◆ FDA Pre-Submission (Q1-2019)◆ Target clearance (Q1-2021)

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Lucid Diagnostics

▪ PAVmed subsidiary (82%)

▪ Managed by PAVmed pursuant to a Management Services Agreement working closing with

CWRU faculty inventors/consultants

▪ Retained veteran biopharma executive with extensive clinical trial experience as

clinical/regulatory consultant

▪ Raising capital to support Phase I, strategic planning with bankers on Phase II

Phase I (510k + LDT)

▪ Target launch Q1-2019

▪ 510(k) application for Gen2 EsoCheck balloon sampling device on target for Q4-2018

submission

▪ CLIA certification of CWRU reference laboratory for DNA biomarker assay for Q1-2019

completion and Laboratory Developed Test (LDT) designation

Phase II (PMA)

▪ NIH trial has enrolled 90 patients to date

▪ Early experience indicates better tolerance and higher DNA yields, results from first 100 patients

expected to validate switch to liquid medium

▪ Finalizing regulatory strategy that leverages ongoing NIH trial but supercharges it with regard to

enrollment rate, site support and CRO control. Considering separate streamlined detection

study in US and PCP-targeted trial in Europe.

▪ Planning FDA pre-submission meeting in early 2019 to finalize study design. Estimate 600-800

patients across all studies towards PMA will suffice.

EsoCheck – Current Status


mVIM + mCCNA

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PortIOImplantable Intraosseous Vascular Access Devices

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ER INPATIENT HOME

<24 Hours <7-10 days <6 weeks <1 year

Peripheral IV Central Venous Catheter (CVC)

Tunneled Central Venous Catheter

Intraosseous Device

Peripherally Inserted Central Catheter (PICC)

Implantable Port(Port-a-Cath)

Vascular Access DevicesUsed to deliver medications, fluids, nutrition and other substances

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OCCLUSION INFECTION

• Up to 35%1

• Clot-busting medications or

a repeat procedure

• Up to 10%1

• 50% life-threatening

bloodstream infections

POOR VEINS RESOURCE UTILIZATION

• >10% of patients2

• Pacemaker/Defibrillator

Leads and catheters

• Dialysis patients

• Surgical insertion &

removal

• Maintenance with regular

flushes

Vascular Access Devices

UNMET CLINICAL NEED – CURRENT DEVICE LIMITATIONS

Limitations driven by intravascular component

1CKutar. The Oncologist 2004;9:207-2016.2Mickley. Eur J Vasc & Endovasc Surgery 2006; 32(4):439-444.

.

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Infusion directly into the Bone

Marrow Cavity

Decades of experience using

temporary needle access

▪ Trauma, esp. military

▪ Pediatric emergencies

▪ Bioequivalent to intravenous route

Intraosseous Vascular Access


Teleflex EZ-IO Device

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Key Features

▪ Implanted into bone

✓ Tip positioned in bone marrow

✓No Intravascular Component

▪ Functionally identical to

traditional implantable port

✓ Resides under the skin

✓ Patient can bathe/swim

✓ Standard Huber access needle

PortIO – Implantable Intraosseous Port


Huber Access Needle

Implantable Port

SiliconeSeptum

HollowTitanium

Bone Screw

TitaniumHub w/ Internal Conical Needle Guide

InsertionKit

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ER INPATIENT HOME

Duration Duration Duration

<24 Hours <7-10 days <6 weeks <1 year

Estimated Market Size 1 Estimated Market Size 1 Estimated Market Size 1

~$150M (Current IO pts) ~$200M (Poor vein pts) ~$500M

Advantages Advantages Advantages

• Near limitless access sites• Less prone to dislodgement

• Near limitless access sites• Simple bedside insertion• More cost effective

• Near limitless access sites• Less invasive• More cost effective• Less prone to occlusion• Fewer, less serious infections

PortIO – Market Opportunity

Separate unique opportunity in large dialysis patient population

Current IO Devices

PortIO

*PAVmed has not yet received clearance from the FDA or any other regulatory agency for any of these products.1 Based on Company Estimates

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FDA de novo PathwayFILED FDA DE NOVO PRE-SUBMISSION PACKAGE

▪ Initial indication targeting inpatient use for up to 7 days

▪ Can serve as own predicate for 510(k) submissions for expanded 6-week/outpatient and 6-month/home use indications

HELD IN-PERSON FDA PRE-SUBMISSION MEETING

▪ Requested 7-day animal study showing local healing and no marrow toxicity

▪ Expect request for small single-arm human safety trial

7-DAY ANIMAL STUDY IN PROCESS

▪ Successful pilot completed

▪ FDA approved GLP animal study protocol

▪ GLP study to begin next month

Monetization Strategy▪ Pre-clearance engagements with natural strategic partners initiated

▪ Encouraging strategic engagements with market leaders

PortIO – Current Status


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PROVEN BUSINESS

MODEL

Speed to Market

Capital Efficiency

Multiple Pathways to Commercialization

EXPANDING PRODUCT PIPELINE

Near-term Milestones

Total Addressable Market over $3B

PROVEN LEADERSHIP

TEAM

Strong Track Record of Innovation and

Value Creation

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Contact Us

PAVmed Inc.

One Grand Central Place

Suite 4600New York, NY 10165

[email protected]

mailto:[email protected]

nasdaq: pavm, pavmz corporate overvie€¦ · nasdaq: pavm, pavmz corporate overview lishan aklog,...

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