UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 10-K
(Mark One)
For the fiscal year ended December 31, 2024
OR
For the transition period from _____ to _____
Commission File Number: 001-40901
LUCID DIAGNOSTICS INC.
(Exact Name of Registrant as Specified in Its Charter)
(State or Other Jurisdiction of (IRS Employer
Incorporation or Organization) Identification No.)
360 Madison Avenue
(Address of Principal Executive Offices) (Zip Code)
(917)813-1828
(Registrant’s Telephone Number, Including Area
Code)
Securities registered pursuant
to Section 12(b) of the Exchange Act:
Title of each Class Trading Symbol(s) Name of each Exchange on which Registered
Common Stock, $0.001 par value per share LUCD The NASDAQ Stock Market LLC
Securities registered under Section
12(g) of the Exchange Act:
None.
Indicate
by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No
☒
Indicate by check
mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Exchange Act. Yes ☐
No ☒
Indicate
by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange
Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2)
has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐
Indicate
by check mark whether the registrant has submitted electronically Interactive Data File required to be submitted pursuant to Rule 405
of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was
required to submit such files). Yes ☒ No ☐
Indicate
by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting
company, or an emerging growth company. See the definitions of “large accelerated filer”, “accelerated filer”
, “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large Accelerated filer ☐ Accelerated filed ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☒
If
an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying
with any new or revised financial accounting standards provided pursuant to section 13(c) of the Exchange Act ☐
Indicate
by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness
of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C.7262(b)) by the registered
public accounting firm that prepared or issued its audit report. ☐
If
securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant
included in the filing reflect the correction of an error to previously issued financial statements. ☐
Indicate
by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation
received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate
by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
As
of June 30, 2024, the last business day of the registrant’s most recently completed second fiscal quarter, the aggregate market
value of the registrant’s voting stock held by non-affiliates was approximately $14.6 million, based on 17,823,181 shares of
common stock held by non-affiliates and a last reported sales price per share of the registrant’s common stock of $0.82 on
such date.
As
of December 31, 2024 and March 20, 2025 there were 66,969,390 and 90,753,851, respectively, shares of the registrant’s
Common Stock, par value $0.001 per share, issued and outstanding (with such number of shares inclusive of shares of common stock underlying
unvested restricted stock awards granted under the Lucid Diagnostics Inc. 2018 Long-Term Incentive Equity Plan as of such date).
DOCUMENTS
INCORPORATED BY REFERENCE
Portions
of the registrant’s definitive proxy statement for its 2025 annual meeting of stockholders are incorporated by reference into Part
III of this Form 10-K where indicated. Such definitive proxy statement will be filed with the U.S. Securities and Exchange Commission
within 120 days after the year ended December 31, 2024.
TABLE OF CONTENTS
PART I
Item 1. Business 1
Item 1A. Risk Factors 17
Item 1B. Unresolved Staff Comments 47
Item 1C. Cybersecurity 47
Item 2. Property 48
Item 3. Legal Proceedings 48
Item 4. Mine Safety Disclosures 48
PART II
Item 6. [Reserved] 49
Item 7A. Quantitative and Qualitative Disclosure About Market Risk 61
Item 8. Financial Statements and Supplementary Data 61
Item 9A. Controls and Procedures 62
Item 9B. Other Information 62
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 62
PART III
Item 10. Directors, Executive Officers, and Corporate Governance 63
Item 11. Executive Compensation 63
Item 14. Principal Accountant Fees and Services 63
PART IV
Item 15. Exhibits and Financial Statement Schedules 64
i
FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K
(this “Form 10-K”), including the discussion and analysis of our consolidated financial condition and results of operations
set forth under Item 7 of this Form 10-K, contains forward-looking statements that involve substantial risks and uncertainties. All statements,
other than statements of historical facts, contained in this Form 10-K, including statements regarding our future results of operations
and financial position, business strategy and plans and objectives of management for future operations, are forward-looking statements.
The words “may,” “will,” “should,” “expects,” “plans,” “anticipates,”
“could,” “intends,” “target,” “projects,” “contemplates,” “believes,”
“estimates,” “predicts,” “potential” or “continue” or the negative of these terms or
other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these
identifying words. Forward-looking statements are not guarantees of future performance and the Company’s actual results may differ
significantly from those expressed or implied in the forward-looking statements. Factors that might cause such differences include, but
are not limited to, those discussed in Item 1A of Part I of the Form 10-K under the heading “Risk Factors.”
Important factors that may affect our actual results
include:
● our limited operating history;
● our financial performance, including our ability to generate revenue;
● the ability of our products to achieve market acceptance;
● our potential ability to obtain additional financing when and if needed;
● our ability to protect our intellectual property;
● our ability to complete strategic acquisitions;
● our ability to manage growth and integrate acquired operations;
● the potential liquidity and trading of our securities;
● our regulatory and operational risks;
● cybersecurity risks;
● risks related to the COVID-19 pandemic and other health-related emergencies;
● risks related to our relationship with PAVmed; and
In addition, our forward-looking
statements do not reflect the potential impact of any future financings, acquisitions, mergers, dispositions, joint ventures or investments
we may make.
We may not actually achieve the
results, plans and/or objectives disclosed in our forward-looking statements, and the intended or expected developments and/or other
events disclosed in our forward-looking statements may not actually occur, and accordingly you should not place undue reliance on our
forward-looking statements. You should read this Annual Report on Form 10-K and the documents we have filed as exhibits to this Form
10-K completely and with the understanding our actual future results may be materially different from what we expect. We do not assume
any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as
required by applicable law.
ii
Part I
Item 1. Business
Unless
the context otherwise requires, “we”, “us”, and “our”, the “Company”, “Lucid”
and “Lucid Diagnostics” refer to Lucid Diagnostics Inc. and its subsidiaries LucidDx Labs Inc. (“LucidDx Labs”)
and CapNostics, LLC (“CapNostics”).
Background and Overview
Lucid Diagnostics is a commercial-stage medical diagnostics technology company focused on the millions of patients with gastroesophageal reflux disease
(“GERD”), also known as chronic heartburn, acid reflux or simply reflux, who are at risk of developing esophageal precancer
and cancer, specifically highly lethal esophageal adenocarcinoma (“EAC”).
We believe that our flagship
product, the EsoGuard Esophageal DNA Test, performed on samples collected with the EsoCheck Esophageal Cell Collection Device, constitutes
the first and only commercially available diagnostic test capable of serving as a widespread testing tool with the goal of preventing
EAC deaths, through early detection of esophageal precancer in at-risk GERD patients.
EsoGuard is a bisulfite-converted
targeted next-generation sequencing (NGS) DNA assay performed on surface esophageal cells collected with EsoCheck. It quantifies methylation
at 31 sites on two genes, Vimentin (VIM) and Cyclin A1 (CCNA1). Analytical validation tests of EsoGuard demonstrated approximately 97%
analytical sensitivity, 95% analytical specificity, approximately 98% analytical accuracy, and 100% inter-assay and intra-assay precision.
Two independent clinical validation case control studies funded by the National Institute of Health utilized were performed using upper
endoscopy with biopsies as the diagnostic comparator and confirmed EsoGuard accurately identifies BE. A pooled analysis of both studies
demonstrated 84% sensitivity (95% confidence interval (“CI”) 76-90%), for detection of BE, and 86% specificity (95% CI 81-91%). Positive
predictive value (PPV) and negative predictive value (NPV) were calculated using a BE prevalence of 10.6% published in a meta-analysis
of U.S patients with GERD. This resulted in a PPV of approximately 42% and NPV of around 98%.
EsoCheck is an FDA 510(k) and
CE Mark cleared noninvasive swallowable balloon capsule catheter device capable of sampling surface esophageal cells in a less than five-minute
office procedure. It consists of a vitamin pill-sized rigid plastic capsule tethered to a thin silicone catheter from which a soft silicone
balloon with textured ridges emerges to gently swab surface esophageal cells. When vacuum suction is applied, the balloon and sampled
cells are pulled into the capsule, protecting them from contamination and dilution by cells outside of the targeted region during device
withdrawal. We believe this proprietary Collect+ProtectTM technology makes EsoCheck the only noninvasive esophageal cell collection
device capable of such anatomically targeted and protected sampling.
EsoGuard and EsoCheck are based
on patented technology licensed by Lucid from Case Western Reserve University (“CWRU”). EsoGuard and EsoCheck have been developed
to provide accurate, non-invasive, patient-friendly testing for the early detection of EAC and Barrett’s Esophagus (“BE”),
including dysplastic BE and related pre-cursors to EAC in patients with chronic GERD.
Market Opportunity
In 2024, approximately 22,000
U.S. GERD patients were diagnosed with EAC and approximately 16,000 will die from it. Over 80% of EAC patients will die within five years
of diagnosis, making it the second most lethal cancer in the U.S. The U.S. incidence of EAC has increased 500% over the past four decades,
while the incidences of other common cancers have declined or remained flat. In nearly all cases, EAC silently progresses until it manifests
itself with new symptoms of advanced disease. EAC is nearly always invasive at diagnosis, and, unlike other common cancers, mortality
rates are high even in its earlier stages.
As discussed below under the
heading “Clinical Guidelines for At-Risk Population”, in July 2022, the American Gastroenterology Association (“AGA”)
significantly expanded the target population for esophageal precancer screening, recommending screening in at-risk patients without symptoms
of GERD. Based on this revision, we believe the cohort recommended for screening consists of an estimated 30 million U.S. individuals
with at least 3 established risk factors for BE. Accordingly, we believe EsoGuard’s total addressable U.S. market opportunity approximates
$60 billion based on an effective Medicare payment of $1,938 and the estimated 30 million U.S. patients recommended for screening by
clinical practice guidelines. (In December 2019, we secured “gapfill” determination for EsoGuard’s PLA code 0114U through
the CMS CLFS process. This allowed us to engage directly with Medicare contractor Palmetto GBA and its MolDx Program on CMS payment and
coverage. As discussed below under the heading “Reimbursement and Market Access”, in October 2020, CMS granted EsoGuard final
Medicare payment determination of $1,938.01, effective January 1, 2021.)
Unfortunately, for a variety
of reasons, less than 10% of at-risk patients who are recommended for screening undergo traditional invasive upper gastrointestinal endoscopy
(EGD). We believe that the profound tragedy of an EAC diagnosis is that likely death could have been prevented if the at-risk patient
had been screened and then undergone surveillance and curative endoscopic esophageal ablation of dysplastic BE.
Since mortality rates are high
even in early stage EAC, preventing EAC deaths requires detection and intervention at the precancer stage. Most of the necessary elements
for such an early detection program are already well established—an at-risk population (at-risk GERD patients), a precancer (BE),
and an intervention which can halt progression to EAC (endoscopic esophageal ablation). Until recently, the only missing element for
such an early detection program is a widespread screening tool that can detect BE prior to EAC.
We believe EsoGuard, used with
EsoCheck, constitutes that missing element—the first and only commercially available diagnostic test capable of serving as a widespread
testing tool with the goal of preventing EAC deaths through early detection of esophageal precancer and cancer in patients with 3 or
more risk factors.
Clinical Guidelines for At-Risk Population
The subgroup of long-standing
or severe GERD patients at-risk for BE and progression to EAC is well defined in clinical practice guidelines, including the American
College of Gastroenterology (“ACG”) BE Guidelines. In its Recommendation 5, the ACG suggests a single screening endoscopy
in patients with chronic GERD symptoms and 3 or more additional risk factors for BE, including male sex, age greater than 50 years, White
race, tobacco smoking, obesity, and family history of BE or EAC in a first-degree relative.
An ACG clinical guideline entitled
“Diagnosis and Management of Barrett’s Esophagus: An Updated ACG Guideline,” the first such update since 2016,
was published online in April 2022 in the American Journal of Gastroenterology. The clinical guideline reiterates the ACG’s long-standing
recommendation for esophageal precancer screening in at-risk patients with GERD. For the first time, however, the clinical guideline
also endorses non-endoscopic biomarker screening as an acceptable alternative to costly and invasive endoscopy stating that “a
swallowable non-endoscopic capsule device combined with a biomarker is an acceptable alternative to endoscopy for BE.” The clinical
guideline specifically mentions EsoCheck as such a swallowable, non-endoscopic esophageal cell collection device, as well as methylated
DNA biomarkers such as EsoGuard. The summary of evidence for this recommendation includes a reference to the seminal NIH-funded, multicenter,
case-control study published in 2018 in Science Translational Medicine, which demonstrated that EsoGuard is highly accurate at
detecting esophageal precancer and cancer, including on samples collected with EsoCheck.
In July 2022, the American Gastroenterology
Association (“AGA”) published in their “Clinical Practice Update on New Technology and Innovation for Surveillance
and Screening in Barrett’s Esophagus” updated clinical guidance that mirrors the same furnished by the ACG as described above,
endorsing the use of non-endoscopic cell collection tools to screen for BE like our EsoCheck Cell Collection Device, which is cited in
the update, as an acceptable alternative to endoscopy to directly address the need for noninvasive screening tools that are easy to administer,
patient friendly, and cost-effective for the detection of BE. The clinical practice update by the AGA also significantly expands the
target population for esophageal precancer screening, including for EsoGuard and EsoCheck, by recommending, for the first time, screening
in at-risk patients without symptoms of GERD. The AGA does so by adding a history of chronic GERD as merely an additional, seventh risk
factor to the six risk factors for BE and EAC that have traditionally identified at-risk symptomatic patients recommended for screening.
In
March 2025, we announced that a recent update to the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) focused on Esophageal and Esophagogastric Junction Cancers (Version 1.2025) has added a new section on
BE screening. The NCCN Guidelines® now reference professional society guidelines on BE screening, including the most recent ACG clinical
guideline discussed above, which recommends non-endoscopic biomarker testing, such as EsoGuard performed on samples collected with EsoCheck,
as an acceptable alternative to invasive upper endoscopy to detect esophageal precancer.
Commercialization
Our EsoGuard commercialization
efforts span multiple channels including targeting primary care and GI physicians, who have generally embraced our message that EsoGuard
has the potential to expand the funnel of BE-EAC patients who will need long term EGD surveillance and, potentially, treatment with endoscopic
esophageal ablation.
To assure sufficient testing
capacity and geographic coverage, we have undertaken multiple ways for patients have access to our test. Initially, we built a limited
network of our own physical Lucid Test Centers, staffed by Lucid-employed clinical personnel, where patients can undergo the EsoCheck
procedure and have the sample sent for EsoGuard testing at our CLIA-certified laboratory. Our current test center network currently includes
locations in metropolitan areas in Arizona, California, Colorado, Florida, Georgia, Idaho, Michigan, Nevada, Texas and Utah.
In addition to our own test center
locations, we have broadened patient access to our test by establishing a satellite test center program, whereby we are making our personnel
available to perform cell collection services inside physician offices or in certain geographies, closely nearby physician offices by
way of our Lucid Mobile Testing Unit.
Also, in January 2023, we completed
our first #CheckYourFoodTube Precancer Testing Event, with the San Antonio Fire Department (the “SAFD”) during Firefighter
Cancer Awareness Month as designated by the International Association of Fire Fighters (IAFF). A total of 391 members who were deemed
to be at-risk for esophageal precancer, underwent a brief, on-site, noninvasive cell collection procedure, performed by our clinical
personnel using EsoCheck. Since then, additional testing events have been hosted with the SAFD, and similar events have been held with
fire departments throughout the country. These events are ongoing and are an extension of Lucid’s satellite test center program,
which brings our precancer testing directly to patients—at their physician’s office and now at testing day events.
In March 2023, we launched a
direct contracting strategic initiative to engage directly with large Administrative Services Only (“ASO”) self-insured employers,
unions and other entities, seeking to replicate the successes of other cancer screening diagnostic companies that have deployed similar
strategies.
In January 2025, we expanded
on our direct contracting initiative by launching a cash-pay program targeting concierge medicine, as an important component of our
strategic efforts to expand our contractually-guaranteed revenue. We have already contracted with concierge medicine
practices across the country under this initiative.
We have also established an EsoGuard
Telemedicine Program, in partnership with UpScript, LLC, an independent third-party telemedicine provider, that accommodates EsoGuard
self-referrals from direct-to-consumer marketing.
Reimbursement and Market Access
As noted above, in December 2019,
we secured “gapfill” determination for EsoGuard’s PLA code 0114U through the CMS CLFS process. This allowed us to engage
directly with Medicare contractor Palmetto GBA and its MolDx Program on CMS payment and coverage. In October 2020, CMS granted EsoGuard
final Medicare payment determination of $1,938.01, effective January 1, 2021.
A final Local Coverage Determination
(“LCD”) L39256, entitled “Molecular Testing for Detection of Upper Gastrointestinal Metaplasia, Dysplasia, and Neoplasia”
became effective in May 2023 on the Center for Medicare and Medicaid Services (“CMS”) website by MAC Palmetto GBA. (A substantially
identical LCD was published by Noridian Healthcare Solutions, the MAC whose geographic jurisdiction covers our CLIA laboratory in Lake
Forest, CA.) The LCD outlines criteria for future coverage that MolDX expects upper gastrointestinal precancer and cancer molecular diagnostic
tests to meet. These criteria include active GERD with at least three risk factors, as well as evidence of analytic validity, clinical
validity, and clinical utility. Although the LCD indicated that it found that no currently existing test has fulfilled all these criteria,
it indicated that it will “monitor the evidence and may revise this determination based on the pertinent literature and society
recommendations.” In November 2024, we submitted to MolDx our complete clinical evidence package in support of a request for reconsideration
of the non-coverage language in the LCD to secure Medicare coverage for EsoGuard.
In parallel with our request
for reconsideration of the LCD, we are aggressively pursuing EsoGuard commercial insurer coverage and payment. Although the claim adjudication
cycle can be prolonged during the early commercialization of a new test, we have received and are continuing to receive out-of-network
commercial insurance payments for the EsoGuard test, which accounts for the vast majority of our revenue to date.
Additionally, the legislatures
in a number of states have passed laws mandating coverage of comprehensive biomarker testing over the past several years. We are reviewing
how to leverage legislation in those states to expand access to and reimbursement of EsoGuard.
Clinical Utility and Clinical Trials
Demonstrating EsoGuard’s
clinical utility, which requires providing evidence that the test has a meaningful impact on clinical practice, is very important for
a variety of purposes, including, importantly, for Medicare and private payor payment and coverage. It has been established that one
of the most important factors to private payors in deciding whether to grant payment and coverage will be demonstration that the EsoGuard
test, when ordered by physicians, provides information that can be used to identify or exclude patients who would benefit from additional
management and/or treatment. Clinical utility studies are also important for general EsoGuard commercialization by facilitating physician
understanding of test indications and potential benefit to the patients.
We continue to expand the EsoGuard
and EsoCheck evidence portfolio with additional clinical utility and clinical validity data from a range of ongoing studies and those
that will be completed in the upcoming year. These efforts include completion of the ESOGUARD-BE2 study, a large multi-center case control
study recruiting patients from large academic institutions in the Netherlands and across the U.S., in the first half of the year and
submission for peer review of a publication of the results in the second half of 2025. This data will further supplement what has previously
been published from the four earlier clinical validation studies from Moinova et. al. (2018), Moinova et. al. (2024), Greer et. al.,
(2024), and Shaheen et. al. (2024). A large, nearly 12,000 patient real-world experience of EsoCheck and EsoGuard from 18 months of commercial
data is expected to be submitted for peer review publication in the first half of the year. Finally, data accrual from the PREVENT and
PREVENT-FF registries remains ongoing. Both registries capture information on the diagnostic and/or therapeutic journey of subjects following
EsoGuard testing, and in addition to provider decision impact, will contribute differing levels of clinical outcomes data to the Lucid
evidence portfolio.
Manufacturing
EsoCheck is currently manufactured
for us by our partners Coastline International (“Coastline”), a high-volume device manufacturer, and Sage Product Development.
Our current line at Coastline can produce up to 25,000 units per year. With Coastline’s improvement and expansion, there is capacity
to scale exponentially. Our EsoGuard Specimen Kits are currently manufactured for us by our partner Path-Tec. Path-Tec also manages warehousing,
logistics, fulfillment and customer support of our products.
License Agreement
Under the terms of our license
agreement with CWRU (as amended to date, the “Amended CWRU License Agreement”), we acquired an exclusive worldwide right
to use the intellectual property rights to the EsoGuard and EsoCheck technology for the detection of changes in the esophagus and on
sample preservation. We are required to pay CWRU royalties on net sales of licensed products as follows: 5% of net sales of less than
$100 million per year; and 8% of net sales greater than $100 million per year. We are also required to pay CWRU minimum annual royalty
payments as follows: $50,000 per year, beginning January 1 following the first anniversary of a commercial sale of a licensed product;
$150,000 per year, if net sales of a licensed product exceed $25 million in a year; $300,000 per year, if net sales of a licensed product
exceed $50 million in a year; and $600,000 per year, if net sales of a licensed product exceed $100 million in a year. Minimum yearly
royalty amounts are subject to increase based on the percentage change in the CPI-W Consumer Price Index and are credited against the
royalties otherwise due. The license agreement was subject to four regulatory and commercialization milestones, of which one remains
unachieved and unpaid. The remaining milestone is the FDA PMA submission of a licensed product, upon the achievement of which we will
pay CWRU a milestone payment of $200,000. The license agreement terminates upon the expiration of the last-to-expire licensed patent,
or on May 12, 2038, in countries where no such patents exist, or upon expiration of any exclusive marketing rights for a licensed product
that have been granted by FDA or other U.S. government agency, whichever comes later.
Regulatory
In June 2019, we received FDA
510(k) clearance to market EsoCheck in the U.S. as a device indicated for use in the collection and retrieval of surface cells of the
esophagus in adults followed by FDA 510(k) clearance in 2022, expanding the use of EsoCheck in adults and pediatric populations in the
U.S. In December 2019, our CLIA-certified then-laboratory partner, completed documentation of EsoGuard analytical validity allowing us
to commercialize it as a LDT.
In February 2020, we received
FDA “Breakthrough Device Designation” for EsoGuard as an in-vitro diagnostic (“IVD”) medical device. The FDA
Breakthrough Device Program was created to offer patients more timely access to breakthrough technologies which provide for more effective
treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions by expediting their development,
assessment and review through enhanced communications and more efficient and flexible clinical study design, including more favorable
pre/post market data collection balance.
In May 2021, we received CE Mark
certification for EsoCheck (under the Medical Devices Directive 93/42/EEC), and in June 2021, we completed CE Mark self-certification
for EsoGuard (under the European In-Vitro Diagnostic Devices Directive (IVDD 98/79/EC)), indicating both may be marketed in CE Mark European
countries.
In October 2023, FDA proposed
a policy under which FDA intends to phase out its general enforcement discretion approach for LDTs so that IVDs manufactured by a laboratory
would generally fall under the same enforcement approach as other IVDs. On May 6, 2024, the FDA issued a final rule aimed at helping
to ensure the safety and effectiveness of LDTs. The rule amends the FDA’s regulations to make explicit that IVDs are devices under the
Federal Food, Drug, and Cosmetic Act (FD&C Act) including when the manufacturer of the IVD is a laboratory. Along with this amendment,
the FDA is finalizing a policy under which the FDA will provide greater oversight of IVDs offered as LDTs through a phaseout of its general
enforcement discretion approach for LDTs over the course of four years, as well as targeted enforcement discretion policies for certain
categories of IVDs manufactured by laboratories.
The phaseout policy contains
the following five stages:
The FDA also intends to exercise enforcement discretion
and generally not enforce some or all applicable requirements for certain categories of IVDs manufactured by a laboratory. The categories
of enforcement discretion that are applicable to EsoGuard are summarized in the table below.
Category of IVD Stage 1 Stage 2 Stage 3 Stages 4 & 5 (Premarket Review)
As EsoGuard was marketed
prior to rule publication and is also NYS CLEP approved, hence, enforcement discretion is applicable for compliance with Stages 4
and 5. We will be implementing compliance with MDR requirements, correction and removal reporting requirements, and quality system
(QS) requirements regarding complaint files by March 31, 2025, well before the deadline of May 6, 2025. Gap analysis has been
completed and we are expecting our compliance activities to be completed for Stages 2 and 3 before the FDA’s expected timeframes in 2026 and 2027, respectively. We are confident that the proposed
final rule will not have a commercial impact as the Company already has a robust QS management platform for medical devices and
EsoGuard will be able to easily transition to the platform to fulfill the QS requirements, as required by the FDA.
Our longer-term strategy is to
secure a specific indication, based on published guidelines, for BE testing in certain at-risk populations using EsoGuard on samples
collected with EsoCheck. This use of EsoGuard together with EsoCheck as a testing system must be cleared or approved by the FDA as an
IVD device.
Laboratory Operations
On February 25, 2022, our new,
wholly owned subsidiary, LucidDx Labs Inc. (“LucidDx Labs”), acquired from ResearchDX Inc. (“RDx”), certain licenses
and other related assets necessary for LucidDx Labs to operate its own new CLIA-certified, CAP-accredited clinical laboratory located
in Lake Forest, CA. Since March 2022, we have conducted EsoGuard testing at our own laboratory with, until February 10, 2023, the assistance
of RDx, which had continued to provide certain testing and related services for the laboratory in accordance with the terms of a management
services agreement (“MSA RDx”). Our subsidiary LucidDx Labs and RDx agreed to terminate the MSA RDx effective as of February
10, 2023, such that LucidDx Labs from and after such date has operated the laboratory itself, which the Company believes has improved
the efficiency of the performance of the EsoGuard assay.
In November 2023, LucidDx Labs
launched EsoGuard 2.0, which uses multiplexing thereby allowing both genes to be interrogated on a single DNA sample. The next-generation
assay underwent rigorous analytical and clinical validation studies, including head-to-head comparisons of multiplexed triplicate consensus
versus singleplex techniques, consistent with CLIA standards. Clinical validation analysis demonstrated improved sensitivity and specificity
for the detection of esophageal precancer, having demonstrated enhanced assay performance and lower costs in extensive validation studies.
Competition
The U.S. market for esophageal
cancer (i.e., EAC) and pre-cancer (i.e., BE, with or without dysplasia) testing is large, consisting of more than 30 million at-risk
individuals over the age of 50. Given the large market for pre-cancer testing, we likely will face numerous competitors, some of which
possess significantly greater financial and other resources and development capabilities than us. Our EsoGuard test faces competition
from procedure-based detection technologies such as upper endoscopy, and other testing technologies such as multi-cancer early detection
products. Our EsoCheck device faces competition from other manufacturers with devices designed to collect cell samples from targeted
regions of the esophagus. For example, EndoSign, commercialized by Cyted, and much like Cytosponge, is a small mesh sponge within a soluble
gelatin capsule that needs to reside in the stomach for some time until it fully dissolves and then is pulled thru the targeted region
brushing the lining of the esophagus and then later retrieved, although, unlike EsoCheck, it is unprotected from sample contamination
as the brush later passes regions of the upper esophagus and mouth. Our competitors may also be developing additional methods of detecting
esophageal cancer and pre-cancer that have not yet been announced.
We will also compete in the marketplace
to recruit and retain qualified scientific, management and sales personnel, as well as in acquiring technologies and licenses complementary
to our products or advantageous to our business. We are aware of several companies that compete or are developing technologies in our
current and future products areas. In order to compete effectively, our products will have to achieve market acceptance, receive adequate
insurance coverage and reimbursement, be cost effective and be simultaneously safe and effective.
EsoCure
The EsoCure Esophageal Ablation
Device is a novel technology that allows a clinician to treat dysplastic BE before it can progress to EAC, a highly lethal esophageal
cancer, and to do so without the need for complex and expensive capital equipment.
In connection with our efforts
to expand our presence in the EAC diagnostic market, in March 2022, PAVmed and Lucid entered into an intercompany license agreement whereby
Lucid was granted the rights to commercialize EsoCure for the treating dysplastic BE. Under the intercompany license, Lucid will pay
PAVmed a 5% royalty on all EsoCure sales up to $100 million per calendar year, and 8% above that threshold.
PAVmed has successfully completed
a pre-clinical feasibility animal study of EsoCure demonstrating excellent, controlled circumferential ablation of the esophageal mucosal
lining. An acute and survival animal study of EsoCure Esophageal Ablation Device has also been completed, demonstrating successful direct
thermal balloon catheter ablation of esophageal lining through the working channel of a standard endoscope. When resources permit, PAVmed
may conduct additional development work and animal testing of EsoCure to support a future FDA 510(k) submission.
Our Relationship with PAVmed
We are currently a subsidiary of PAVmed. On September 10, 2024, following preferred equity transactions completed by the Company earlier
in 2024 and the termination of voting proxies entered into between PAVmed and certain shareholders of the Company, PAVmed’s
voting interest in the Company was reduced to less than 50.0%, resulting in the loss of a controlling financial interest. (Prior to
the completion of such transactions on such date, we were a majority-owned subsidiary of PAVmed.) However, PAVmed remains our
largest shareholder based on voting power, and therefore retains the ability to exercise significant influence over Lucid. Moreover,
we continue to depend on PAVmed to provide us various management, technical, research and development, legal, accounting, and
administrative services.
PAVmed owns approximately 46%
as of December 31, 2024 and 34% as of March 20, 2025 of the combined voting power of our outstanding common stock (with
such percentage inclusive of shares of our common stock underlying granted but unvested restricted stock awards), but excluding the voting
power of any convertible securities. Presently, PAVmed controls less than 50% of the combined voting power of our common stock and our
convertible securities. In addition, PAVmed’s percentage of the combined voting power may decrease when dividends are paid on our
convertible securities and to the extent our convertible securities are converted into shares of our common stock. PAVmed’s ownership interests may also decrease if the holder of its convertible debt exercises its right to
exchange some or all of such debt for shares of our common stock held by PAVmed. Even though PAVmed’s
ownership has fallen below 50%, it remains our largest shareholder based on voting power, and accordingly PAVmed retains substantial
influence on the election of all the members of our board of directors and any other matters submitted to a vote of our stockholders.
PAVmed’s substantial voting interest may discourage a change of control that other holders of our common stock may favor.
We are party to a management
services agreement with PAVmed (the “MSA”), as well as a payroll benefits and expense reimbursement agreement (the “PBERA”).
Under the MSA, PAVmed provides management, technical and administrative services to us, including without limitation services related
to research and development, regulatory clearance, manufacture, and commercialization of our products, as well as services related to
corporate financial, accounting and legal matters. The terms of this agreement are intended to be consistent with the terms that we could
have negotiated with unaffiliated third parties; however, they may actually be more or less favorable. Under the PBERA, PAVmed has agreed
to pay certain payroll and benefit-related expenses in respect of our personnel on our behalf, and we reimburse PAVmed for the same.
PAVmed may elect that our obligations under each of the MSA and the PBERA are settled by the issuance of our stock (instead of cash),
subject to applicable restrictions under securities laws (and, in the case of the PBERA, subject also to approval by our board), although
under the terms of PAVmed’s convertible debt, PAVmed is required to elect that these payments be made in cash. The MSA does not
have a termination date, but may be terminated by our board of directors at any time. The PBERA likewise does not have a termination
date, but may be terminated by PAVmed or Lucid at any time.
Recent Events
Medicare Coverage
In November 2024, we submitted
to MolDx our complete clinical evidence package in support of a request for reconsideration of the non-coverage language in the LCD to
secure Medicare coverage for EsoGuard. The EsoGuard clinical evidence package included six new peer-reviewed publications: three clinical
validation studies (two in the intended use population, one case control), two clinical utility studies, and one analytical validation
study. The current LCD provides clear coverage criteria consistent with the ACG guidelines for
esophageal precancer testing. The package was submitted as part of a request for reconsideration of the non-coverage language in the
LCD to secure Medicare coverage for EsoGuard.
NCCN Clinical Practice Guidelines Update
In
March 2025, we announced that a recent update to the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) focused on Esophageal and Esophagogastric Junction Cancers (Version 1.2025) has added a new section on
BE screening. The NCCN Guidelines® now reference professional society guidelines on BE screening, including the most recent ACG clinical
guideline discussed above, which recommends non-endoscopic biomarker testing, such as EsoGuard performed on samples collected with EsoCheck,
as an acceptable alternative to invasive upper endoscopy to detect esophageal precancer.
Clinical Study Publications
On
March 18, 2025, the Company announced that its ENVET-BE clinical utility study has been accepted for publication in Gastroenterology
& Hepatology—the fifth peer-reviewed publication of clinical utility data for Lucid’s EsoGuard® Esophageal DNA Test, and
the second to present findings from a real-world screening population. The manuscript, entitled “Enhancing the Diagnostic Yield
of EGD for Diagnosis of Barrett’s Esophagus Through Methylated DNA Biomarker Triage,” demonstrates that confirmatory upper endoscopy
(EGD) performed in EsoGuard-positive patients had a substantially higher diagnostic yield for detecting esophageal precancer (Barrett’s
Esophagus or BE) than the expected yield of screening EGD alone in at-risk patients. The ENVET-BE study reviewed real-world data from
a cohort of 199 EsoGuard-positive patients who completed confirmatory EGD. The overall positive diagnostic yield for BE was 2.4-fold
higher than the expected yield of screening EGD alone, based on disease prevalence within an at-risk population. The yield was nearly
three-fold higher in patients meeting ACG screening criteria.
On
November 7, 2024, the Company announced that its manuscript for its multi-center ESOGUARD BE-1 study has been accepted for publication
in The American Journal of Gastroenterology, the official journal of the ACG. This is the fourth publication presenting clinical validation
data for the Company’s EsoGuard® Esophageal DNA Test, and the second to demonstrate its performance in an intended-use screening
population. Consistent with previous studies, EsoGuard showed high sensitivity and negative predictive value in detecting esophageal
precancer (Barrett’s Esophagus or BE). The prospective, multi-center study presented data from a cohort of patients who met ACG guideline
criteria for esophageal precancer screening and underwent non-endoscopic EsoGuard testing followed by traditional upper endoscopy. EsoGuard
sensitivity and negative predictive value for detecting BE were approximately 88% and 99%, respectively. Specificity and positive predictive
value were approximately 81% and 30%, respectively. No serious adverse events were reported.
Highmark Reimbursement Approval
On March 13, 2025, the Company announced that Highmark Blue Cross Blue Shield, an independent licensee of the Blue
Cross and Blue Shield Association, has issued a positive coverage policy for non-invasive screening of esophageal precancer and cancer
in New York state. The new policy will cover EsoGuard in patients who meet established criteria for esophageal precancer testing consistent
with professional society guidelines.
CWRU NIH Grant Related to EsoGuard and EsoCheck
On February 27, 2025, the
Company announced that principal investigators from CWRU and University Hospitals (“UH”), were awarded an $8 million
National Institutes of Health (NIH) R01 grant to conduct a five-year clinical study designed to evaluate esophageal precancer
detection using EsoCheck and EsoGuard among at-risk individuals without symptoms of chronic gastroesophageal reflux disease (GERD).
The study, “A Clinical Trial of Cancer Prevention by Biomarker Based Detections of Barrett’s Esophagus and Its
Progression,” aims to evaluate the effectiveness of EsoCheck and EsoGuard in detecting esophageal precancer (Barrett’s
Esophagus or BE) to prevent esophageal cancer (EAC) within a non-GERD at-risk population. To accomplish this aim, 800 patients
without GERD symptoms who meet the AGA’s risk criteria for screening will be
recruited across five participating research centers: University Hospitals, University of Colorado, Johns Hopkins University,
University of North Carolina, and Cleveland Clinic.
IP Matters
On October 15, 2024, the Company
announced that it received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for a patent application covering
its proprietary method of using methylation of the cyclin-A1 (CCNA1) gene to help detect esophageal precancer and cancer, a key component
of its EsoGuard® Esophageal DNA Test.
EsoGuard utilizes next-generation
sequencing (NGS) to assess DNA methylation at 31 sites on two genes, vimentin (VIM) and cyclin-A1 (CCNA1). Such methylation has been shown
to be strongly associated with conditions along the spectrum from early esophageal precancer (non-dysplastic Barrett’s Esophagus or BE),
to late precancer (dysplastic BE), to cancer (esophageal adenocarcinoma). Although VIM methylation had been previously associated with
gastrointestinal neoplasias, the association of CCNA1 methylation with esophageal neoplasia is novel and appears to be more specific.
Intercompany Agreements with PAVmed
On August 6, 2024, PAVmed and
the Company entered into a ninth amendment to the management services agreement between PAVmed and Lucid (“MSA”) to increase
the monthly fee thereunder from $0.83 million per month to $1.05 million per month, effective as of July 1, 2024. In addition, under
the terms of PAVmed’s convertible debt, PAVmed is required to elect that these payments be made in cash.
Appointment
of Dennis Matheis to Board of Directors
On
May 6, 2024, the board of directors of the Company appointed Dennis Matheis as a Class C director of the Company (and he was subsequently
re-elected to the board, together with the incumbent Class C directors of the Company, at the Company’s annual shareholders meeting
held on July 23, 2024).
Financing
Registered Direct Offering
On March 5, 2025, the Company closed
on the sale of 13,939,331 shares of its common stock at a price of $1.10 per share (the “Offering”).
The
net proceeds of the Offering, after deducting the estimated placement agent’s fees and other expenses of the Offering, was approximately
$14.5 million. The Company intends to use the net proceeds from the Offering for working capital and other general corporate purposes.
Termination of ATM Prospectus Supplement
In November 2022, the Company
entered into a Controlled Equity OfferingSM Sales Agreement (the “Sales Agreement”) with Cantor Fitzgerald & Co.
(“Cantor”). Pursuant to the Sales Agreement, from time to time, the Company may offer and sell shares of its common stock
to or through Cantor, acting as sales agent or principal. Sales of the Company’s common stock by Cantor, if any, under the Sales
Agreement may be made by any method permitted by law and deemed to be an “at the market offering” as defined in Rule 415(a)(4)
promulgated under the Securities Act (the “ATM Offering”). The Company filed a prospectus supplement dated December 6, 2022
(the “ATM Prospectus Supplement”), for the offer and sale of shares of its common stock having an aggregate offering price
of up to $6,500,000 in the ATM Offering.
Effective as of March 4, 2025, the Company terminated
the ATM Prospectus Supplement. The Company will not make any sales of common stock in the ATM Offering unless and until a new prospectus
or prospectus supplement is filed.
Other than the termination of the Prospectus Supplement,
the Sales Agreement remains in full force and effect.
Debt Refinancing
On November 22, 2024, the Company
closed on the sale of $21.975 million in principal amount of 12.0% Senior Secured Convertible Notes due 2029 (collectively, the “2024
Convertible Notes”), in a private placement, to certain accredited investors (the “2024 Note Investors”). The sale
of the 2024 Convertible Notes were completed pursuant to the terms of that certain Securities Purchase Agreement, dated as of November
12, 2024 (the “2024 SPA”), between the Company and the 2024 Note Investors. The Company realized gross proceeds of $21.975
million and, after giving effect to the repayment in full of the March 2023 Senior Convertible Note, net proceeds of $18.3 million from
the sale of the 2024 Convertible Notes.
The Company used a portion of
the proceeds from the sale of the 2024 Convertible Notes to redeem the March 2023 Senior Convertible Note, by paying the contractual
redemption price of approximately $3.6 million.
NASDAQ Compliance
On February 24, 2025, the Company received a notice from the Listing Qualifications Department of The Nasdaq Stock
Market (“Nasdaq”) stating that the closing bid price of the Company’s common stock had been above the minimum of $1 per share
for continued listing on the Nasdaq Capital Market under Nasdaq
Listing Rule 5550(a)(2) for ten consecutive trading days (through February 21, 2025) and accordingly, the Company had regained compliance
with this listing requirement.
On
June 21, 2024, the Company received a notice from the Listing Qualifications Department of Nasdaq stating that, for the prior 30 consecutive
business days (through June 20, 2024), the closing bid price of the Company’s common stock had been below the minimum of $1 per
share required for continued listing. The notification letter stated that the Company would be afforded 180 calendar days (until December
18, 2024) to regain compliance, which grace period was extended by an additional 180 calendar days (until June 16, 2025).
Intellectual Property
Our business will depend on proprietary
medical device and diagnostic technologies, including the EsoCheck and EsoGuard technology licensed by us. We intend to vigorously protect
our proprietary technologies’ intellectual property rights in patents, trademarks and copyrights, as available through registration
in the United States and internationally. Patent protection and other proprietary rights are thus essential to our business. We currently
have applied for, license or own 20 domestic and foreign patents covering the EsoGuard and EsoCheck products and related technology.
Each of the technologies noted below is protected by multiple families. The date the patents protecting certain of our owned and licensed
technology will first begin to expire is as set forth in the table below (although currently pending patent applications, both foreign
and domestic, provide protection beyond such date in each instance). For EsoGuard, additional patents have been issued that offer protection
until at least 2037.
Technology Year
The EsoCheck and EsoGuard technology
is protected by patents in the United States and internationally, and our policy is to continue to aggressively file patent applications,
both independently and in collaboration with CWRU, as appropriate, to protect this technology and other of our proprietary technologies
relating to our business, including inventions and improvements to inventions. Under the CWRU License Agreement, CWRU has agreed to apply
for patent coverage, at our expense, in any country requested by us, to the extent such protection is reasonably attainable. We seek
patent protection, as appropriate, on:
● the product itself including all embodiments with future commercial potential;
● the methods of using the product; and
● the methods of manufacturing the product.
In addition to filing and prosecuting
patent applications in the United States, we intend to file counterpart patent applications in other countries where there is a value
in doing so. Foreign filings can be cumbersome and expensive, and we will pursue such filings when we believe they are warranted as we
try to balance our international commercialization plans with our desire to protect the global value of the technology.
The term of individual patents
depends upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, the patent
term is 20 years from the earliest date of filing a non-provisional patent application. In the United States, a patent’s term may
be shortened if a patent is terminally disclaimed over another patent or as a result of delays in patent prosecution by the patentee,
and a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the
U.S. Patent and Trademark Office (“USPTO”) in granting a patent, or patent term extension, which restores time lost due to
regulatory delays.
We intend to continuously reassess
and fine-tune our intellectual property strategy in order to fortify the position of our business in the United States and internationally.
Prior to acquiring or licensing a technology from a third party, we will evaluate the existing proprietary rights, our ability to adequately
obtain and protect these rights and the likelihood or possibility of infringement upon competing rights of others.
We also rely upon trade
secrets, know-how, and continuing technological innovation, and may rely upon licensing opportunities, to develop and maintain our
competitive position. We protect our proprietary rights through a variety of methods, including confidentiality agreements and/or
proprietary information agreements with suppliers, employees, consultants, independent contractors and other entities who may have
access to proprietary information. We will generally require employees to assign patents and other intellectual property to us as a
condition of employment with us. All of our consulting agreements assign to us all new and improved intellectual property that arise
during the term of the agreement.
Lucid also has proprietary rights