MEETING AGENDA
OncoPrecise GXP-47 Medicare Coverage & Coding Strategy Kickoff
Calderwood & Harkness LLP Matter No.: 1043-00002
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1. Attendees and Participant Roster
The following individuals are expected to participate in the kickoff meeting. Participants joining remotely are noted below.
Genome Dx Therapeutics Inc. (GDT) — Client
Calderwood & Harkness LLP — Outside Counsel (Medicare Coverage & Coding)
Carraway Regulatory Advisors, Inc. — Coding & Billing Consultant
Larkfield Health Economics, LLC — Health Economics & Outcomes Research Consultant
Regrets / Not Attending
2. Welcome and Introductions
Scheduled Time: 10:00 – 10:15 AM PST
Welcome. Theresa Nakamura will open the meeting on behalf of Genome Dx Therapeutics Inc. and welcome all participants to the kickoff meeting for the OncoPrecise GXP-47 Medicare Coverage and Coding Strategy engagement.
Round-Table Introductions. Each participant will provide a brief introduction, including name, organization, role, and primary responsibilities for this engagement. Remote participants will be invited to introduce themselves following in-person attendees.
Overview of the Engagement. Calderwood & Harkness LLP was retained by Genome Dx Therapeutics Inc. pursuant to the engagement letter executed on February 14, 2024, to develop and execute a comprehensive Medicare coverage and coding strategy for OncoPrecise GXP-47, GDT's next-generation 47-gene RNA expression panel for non-small-cell lung cancer (NSCLC) treatment selection. The engagement encompasses all aspects of securing Medicare coverage and reimbursement for the test, from initial coding strategy through local coverage determination and preliminary assessment of a national coverage pathway.
Roles and Responsibilities of Each Team. The following summary of team responsibilities will be reviewed for confirmation and alignment:
Calderwood & Harkness LLP will serve as lead counsel on the engagement. Calderwood & Harkness's scope of responsibility includes: (i) development and submission of the Proprietary Laboratory Analyses (PLA) code application to the American Medical Association (AMA) CPT Editorial Panel; (ii) development and execution of the Local Coverage Determination (LCD) and MolDx program strategy, including preparation of the MolDx technical assessment dossier; (iii) analysis and assessment of the National Coverage Determination (NCD) pathway; and (iv) reimbursement rate analysis under crosswalk and gapfill methodologies.
Carraway Regulatory Advisors, Inc. will provide specialized consulting support on coding mechanics, including AMA CPT Editorial Panel submission formatting, code descriptor drafting guidance, and billing compliance advisory. Ms. Carraway brings extensive experience in molecular diagnostic coding and has worked on over sixty PLA code applications since the inception of the PLA code section in the CPT code set.
Larkfield Health Economics, LLC will prepare the clinical utility analysis and cost-effectiveness analysis that will form critical components of the LCD application and MolDx technical assessment dossier. Larkfield has been retained directly by GDT and its work product will be coordinated through Calderwood & Harkness to ensure consistency with the overall submission strategy and to preserve applicable privileges where appropriate.
Coordination with Existing Counsel. GDT's regular outside counsel for corporate and intellectual property matters is Whitford & Sable LLP (Harrison Whitford, Partner; Danielle Reeves, Senior Associate). Whitford & Sable will be looped in as needed on board-level matters, regulatory and corporate governance issues, and intellectual property questions that arise in connection with the PLA code application or coverage submissions. Calderwood & Harkness will coordinate with Whitford & Sable through Theresa Nakamura to avoid duplication of effort and ensure consistent advice across all workstreams.
3. Project Scope and Objectives
Scheduled Time: 10:15 – 10:35 AM PST
Review of Engagement Scope. The engagement scope, as defined in the executed engagement letter dated February 14, 2024, encompasses four principal objectives:
(a) Obtain a Unique CPT/PLA Code for OncoPrecise GXP-47. Secure a test-specific Proprietary Laboratory Analyses (PLA) code from the AMA CPT Editorial Panel that will serve as the billing identifier for OncoPrecise GXP-47 in all Medicare and commercial payer claims submissions. This will provide GDT with a unique billing identity for the test, distinct from generic genomic sequencing codes currently available under the CPT code set.
(b) Secure a Local Coverage Determination (LCD) from the Applicable Medicare Administrative Contractor. Prepare and file a comprehensive LCD application with Cascade Fiscal Intermediaries, LLC (CFI), the Medicare Administrative Contractor (MAC) for Jurisdiction E, which covers the State of California, where GDT's CLIA-certified reference laboratory is located. The LCD application will be supported by a MolDx technical assessment dossier prepared in accordance with the requirements of the MolDx program administered by Ridgeline Administrative Services, LLC. The goal is to obtain an affirmative coverage determination establishing that OncoPrecise GXP-47 is reasonable and necessary for Medicare beneficiaries within the test's intended clinical use population.
(c) Establish a Medicare Reimbursement Rate via Crosswalk/Gapfill Methodology. Develop and support a Medicare reimbursement rate for OncoPrecise GXP-47 through crosswalk analysis to comparable multi-gene, NGS-based oncology panels, with gapfill pricing methodology as a secondary or fallback approach. The target reimbursement rate and supporting rationale will be presented in a detailed Reimbursement Rate Analysis Memorandum.
(d) Navigate CMS National Coverage Pathways (NCD Feasibility Assessment). Prepare a comprehensive NCD Feasibility Assessment Memorandum evaluating the strategic considerations, evidentiary requirements, timeline, and likelihood of success for pursuing a National Coverage Determination from the Centers for Medicare & Medicaid Services (CMS), to be initiated following successful LCD coverage.
Budgeted Fee Estimate. The engagement letter provides a budgeted fee estimate of $475,000 to $575,000 for the full scope of services through LCD issuance, billed on an hourly basis in accordance with Calderwood & Harkness's standard billing rates. This estimate covers all four workstreams described above and assumes a project duration of approximately twelve to eighteen months from engagement opening to LCD final determination. The estimate does not include the fees of Carraway Regulatory Advisors or Larkfield Health Economics, each of which is separately engaged. Calderwood & Harkness will provide monthly billing statements and will notify GDT promptly if the engagement is trending materially above or below the budgeted estimate.
Success Criteria and Key Milestones. The team will discuss and confirm the criteria by which success will be measured for each workstream, including:
• Assignment of a unique PLA code by the AMA CPT Editorial Panel at the earliest available meeting cycle;
• Filing of the LCD application and MolDx technical assessment dossier with CFI within the target timeline;
• Achievement of a proposed LCD with an affirmative coverage determination;
• Establishment of a Medicare reimbursement rate at or near the target level of $3,850 per test; and
• Delivery of an NCD Feasibility Assessment Memorandum that provides GDT's leadership and board with a clear, actionable recommendation on whether and when to pursue national coverage.
Out-of-Scope Items. The following items are expressly outside the scope of this engagement and will not be addressed by Calderwood & Harkness absent a separate engagement letter or amendment to the current engagement:
• Commercial payer contracting and negotiations (to be handled by GDT's internal market access team or separate counsel);
• FDA regulatory submissions, including any premarket submissions related to OncoPrecise GXP-47 as a laboratory-developed test;
• intellectual property prosecution, maintenance, or licensing (handled by Whitford & Sable LLP);
• State-level Medicaid coverage or reimbursement strategies; and
• International market access and reimbursement matters.
4. Overview of OncoPrecise GXP-47 — Test Characteristics
Scheduled Time: 10:35 – 11:05 AM PST
4.1 Test Description
Presenters: Kevin Driscoll and Dr. Priya Sundaram
OncoPrecise GXP-47 is a laboratory-developed test (LDT) performed exclusively at Genome Dx Therapeutics Inc.'s CLIA-certified, CAP-accredited reference laboratory located at 4720 Torrey Pines Road, Suite 300, San Diego, California 92130. The laboratory's relevant credentials and identifiers are as follows:
• CLIA Certificate Number: 05D2187432
• CAP Accreditation Number: 9074821
• National Provider Identifier (NPI): 1902847365
The test is a 47-gene RNA expression panel that utilizes RNA extracted from formalin-fixed, paraffin-embedded (FFPE) non-small-cell lung cancer (NSCLC) tumor tissue specimens. The panel interrogates expression levels across 47 genes associated with immune checkpoint inhibitor (ICI) response pathways, tumor microenvironment characteristics, and resistance mechanisms.
OncoPrecise GXP-47 produces a composite Therapy Response Index (TRI) score, reported on a continuous scale from 0 to 100. The TRI score is generated by GDT's proprietary algorithm, which integrates normalized RNA expression data across the 47-gene panel into a single, clinically actionable metric. The TRI score is stratified into three categories for clinical interpretation:
• High Likelihood of Response: TRI ≥ 70 — Patients in this category are predicted to have a high probability of clinical benefit from first-line immune checkpoint inhibitor therapy.
• Intermediate: TRI 40–69 — Patients in this category have an uncertain predicted response; the test report recommends that the treating oncologist weigh additional clinical and pathological factors in making a treatment decision.
• Low Likelihood of Response: TRI < 40 — Patients in this category are predicted to have a low probability of clinical benefit from first-line ICI therapy, and the test report suggests that platinum-based chemotherapy or combination regimens may be more appropriate first-line approaches.
The intended clinical use of OncoPrecise GXP-47 is to guide oncologist decision-making on whether to initiate first-line immune checkpoint inhibitor (ICI) therapy — such as pembrolizumab, nivolumab, or atezolizumab — versus platinum-based chemotherapy in patients with newly diagnosed Stage IIIB or Stage IV NSCLC. The test is positioned as a companion decision-support tool that supplements, but does not replace, existing biomarker testing (e.g., PD-L1 immunohistochemistry, tumor mutational burden) and clinical judgment.
The proprietary TRI algorithm is GDT's principal differentiating feature relative to other RNA expression profiling tests in the oncology space. The algorithm incorporates a machine-learning model trained on a proprietary dataset of over 4,800 paired gene expression profiles and clinical outcomes, and is the subject of multiple issued and pending U.S. patents.
Kevin Driscoll and Dr. Sundaram will present a summary of the test's technical methodology, specimen requirements, turnaround time, and reporting format, including a sample test report for the team's review.
4.2 Analytical Validation Status
Analytical validation of OncoPrecise GXP-47 was completed on December 14, 2022. The validation study was conducted in accordance with applicable CLIA, CAP, and Clinical and Laboratory Standards Institute (CLSI) guidelines for laboratory-developed molecular diagnostic tests.
The analytical validation results were published in the Journal of Molecular Oncology Diagnostics, Volume 18, Issue 4, pages 412–429, in December 2022. The publication describes the test's performance characteristics across the following domains: analytical sensitivity (limit of detection), analytical specificity, precision (repeatability and reproducibility), accuracy (comparison to reference methods), reportable range, specimen stability, and interference testing.
Dr. Sundaram will present a summary of the key analytical validation metrics from the published study. The published validation data will serve as a foundational component of the MolDx technical assessment dossier and will be referenced in the PLA code application as evidence of the test's technical rigor and laboratory performance characteristics.
4.3 intellectual Property Landscape
Genome Dx Therapeutics Inc. holds fourteen (14) issued U.S. patents and seven (7) pending U.S. patent applications related to the OncoPrecise platform, including patents covering the TRI algorithm, specific gene expression signatures, and methods of treatment selection based on the TRI score. The intellectual property portfolio is managed by GDT's regular outside patent counsel at Whitford & Sable LLP (Harrison Whitford, Danielle Reeves).
The IP landscape is relevant to the PLA code application because the AMA requires that PLA code applicants demonstrate that the test is a proprietary, single-source laboratory analysis. GDT's extensive patent portfolio supports its position that OncoPrecise GXP-47 is a proprietary test that cannot be replicated or ordered from another laboratory. Calderwood & Harkness will coordinate with Whitford & Sable LLP, through Theresa Nakamura, to obtain any IP-related documentation needed for the PLA code submission.
4.4 Existing GDT Product — OncoPrecise GXP-12
Genome Dx Therapeutics Inc. currently markets and performs OncoPrecise GXP-12, a 12-gene RNA expression panel for early-stage breast cancer prognosis. GXP-12 has been commercially available since 2020 and is currently reimbursed by Medicare under an existing Local Coverage Determination, LCD L38472, which was issued by Cascade Fiscal Intermediaries, LLC and became effective on August 15, 2021.
GXP-12 generated fiscal year 2023 revenue of $6.2 million, which constitutes the entirety of GDT's current revenue base. GXP-12's coverage and reimbursement history provides valuable precedent and institutional knowledge for the GXP-47 coverage strategy, particularly with respect to GDT's established relationship with CFI, its experience navigating the MolDx technical assessment process, and the operational infrastructure already in place for Medicare billing and claims submission.
Kevin Driscoll will provide a brief overview of lessons learned from the GXP-12 LCD process that may inform the GXP-47 strategy. The team will discuss how the GXP-12 experience can be leveraged while recognizing the material differences between the two tests — including the larger gene panel, the different clinical indication (NSCLC treatment selection versus breast cancer prognosis), and the distinct evidentiary requirements for a therapy-selection test.
5. Clinical Validation: CLARITY-LUNG Trial Status
Scheduled Time: 11:05 – 11:30 AM PST
5.1 Trial Design
Presenter: Dr. Priya Sundaram
The clinical validation of OncoPrecise GXP-47 is being conducted through the CLARITY-LUNG trial, a prospective, multi-site, blinded clinical validation study designed to establish the clinical validity and clinical utility of the TRI score in predicting response to first-line ICI therapy in patients with advanced NSCLC.
The trial is registered on ClinicalTrials.gov under identifier NCT05891247 and is being conducted at fourteen (14) clinical sites across the United States. The sites include a mix of academic medical centers and community oncology practices, selected to ensure a patient population representative of the intended use population for OncoPrecise GXP-47.
Key trial design parameters include:
• Study Type: Prospective, multi-site, blinded clinical validation
• Enrollment Target: 1,200 patients with newly diagnosed Stage IIIB or Stage IV NSCLC
• Primary Endpoint: Positive predictive value (PPV) and negative predictive value (NPV) of the TRI score for twelve-month progression-free survival (PFS) on immune checkpoint inhibitor therapy
• Pre-Specified Performance Thresholds:
• PPV ≥ 0.75 (i.e., at least 75% of patients classified as "High Likelihood of Response" [TRI ≥ 70] achieve twelve-month PFS on ICI therapy)
• NPV ≥ 0.80 (i.e., at least 80% of patients classified as "Low Likelihood of Response" [TRI < 40] do not achieve twelve-month PFS on ICI therapy)
Dr. Sundaram will provide a detailed overview of the trial protocol, including inclusion and exclusion criteria, specimen collection and processing procedures, the blinding methodology (treating physicians do not receive TRI scores during the blinded phase), follow-up intervals, and secondary endpoints.
5.2 Current Enrollment Status
As of late February 2024, the CLARITY-LUNG trial is actively enrolling across all fourteen clinical sites. Dr. Sundaram will present the current enrollment numbers and trajectory toward the 1,200-patient enrollment target.
Enrollment commenced on January 18, 2023. The total trial budget is $28.5 million. Dr. Sundaram will review expenditures to date and the remaining budget, as well as any enrollment challenges or site-specific issues that could affect the projected timeline for enrollment completion.
The enrollment trajectory is a critical factor in the project timeline, as the availability of clinical validation data from the CLARITY-LUNG trial directly affects the timing and strength of the LCD application and MolDx technical assessment dossier.
5.3 Interim Analysis Plan
The CLARITY-LUNG trial protocol includes a pre-specified interim analysis at fifty percent (50%) enrollment, which corresponds to approximately n = 600 evaluable patients. The interim analysis is designed to provide an early read on the test's clinical validity and to assess whether the pre-specified performance thresholds are being met.
Dr. Sundaram will discuss the anticipated timing of the interim analysis based on current enrollment rates. The interim analysis results will be reviewed by the Data Safety Monitoring Board (DSMB) chaired by Dr. Evelyn Matsuda, MD, PhD, of the Carrington Cancer Institute in Houston, Texas. The DSMB has the authority to recommend modifications to the trial, including early stopping for overwhelming efficacy or futility, although the protocol was not powered for early stopping.
The team will discuss the extent to which interim analysis results can be used to support the LCD application and MolDx technical assessment dossier, and the strategic implications of filing with interim data versus waiting for final data readout.
5.4 Projected Final Data Readout
Based on current enrollment rates and the twelve-month follow-up requirement, the current projection for final data readout from the CLARITY-LUNG trial is Q4 2024. This projection assumes that enrollment is substantially complete by mid-2024 and that the twelve-month follow-up period for the final enrolled patients concludes by late 2024.
The team will discuss how the trial timeline aligns with the coding and coverage filing milestones described in Section 10 of this agenda, and whether any adjustments to the filing strategy may be needed depending on the pace of enrollment and the timing of the interim analysis.
5.5 Implications for Coverage Strategy
The clinical validation data from the CLARITY-LUNG trial represents the cornerstone of the LCD application and MolDx technical assessment dossier. The MolDx program's technical assessment requirements place significant emphasis on prospective clinical validation data, and the strength of the CLARITY-LUNG results will be the single most important factor in determining the outcome of the LCD review process.
The team will discuss the following strategic considerations:
• What clinical evidence is currently available for submission (analytical validation data, prior retrospective studies) versus what will be available at the time of LCD filing;
• The feasibility and strategic advisability of filing the LCD application with interim analysis data, with final data to be supplemented during the LCD review period;
• The availability and quality of prior retrospective studies that may be used as supplementary evidence to support the LCD application, even if the prospective CLARITY-LUNG data is the primary evidence;
• The risk calculus associated with filing before final data is available versus the cost of delay; and
• The implications of different clinical validation outcomes (e.g., meeting one threshold but not the other, meeting both thresholds, or failing to meet either) on the coverage strategy.
6. Coding Pathway: PLA Code vs. CPT Code Analysis
Scheduled Time: 11:30 AM – 12:00 PM PST
6.1 Overview of Coding Options
Presenters: Miriam Calloway, Christopher Aiken, and Janet Carraway
A critical threshold determination in the engagement is the selection of the appropriate coding pathway for OncoPrecise GXP-47. The coding pathway will determine how the test is identified on Medicare and commercial payer claims, and will have significant downstream implications for reimbursement rate-setting and payer recognition. The team will evaluate three options:
Option A: Proprietary Laboratory Analyses (PLA) Code. Apply for a unique PLA code specific to OncoPrecise GXP-47 as a proprietary, single-source laboratory-developed test. The PLA code section of the CPT code set was established by the AMA in 2018 specifically to accommodate tests that are performed by a single laboratory and cannot be replicated elsewhere. A PLA code would give OncoPrecise GXP-47 its own billing identity, separate from any existing generic or panel-based CPT codes.
Option B: Billing Under an Existing CPT Code. Bill OncoPrecise GXP-47 under an existing, broadly applicable CPT code, such as CPT 81455 (next-generation sequencing, solid organ neoplasm, 51 or more genes). This option would not require an application to the AMA but would result in the test being billed under a generic code used by many different laboratories and tests, without a unique identifier for OncoPrecise GXP-47.
Option C: Stacking Existing CPT Codes. Bill OncoPrecise GXP-47 using a combination of existing CPT codes that, taken together, describe the various analytical components of the test. This approach is sometimes used as an interim billing strategy but carries compliance risks and may result in claim denials or reduced reimbursement.
6.2 PLA Code Pathway — Advantages and Requirements
Based on preliminary analysis, Calderwood & Harkness and Carraway Regulatory Advisors anticipate recommending the PLA code pathway (Option A) as the preferred coding strategy for OncoPrecise GXP-47. The PLA code pathway offers several important advantages:
• A PLA code provides a test-specific billing identity that is uniquely associated with OncoPrecise GXP-47 and Genome Dx Therapeutics Inc. This test-specific identity enhances payer recognition, simplifies claims processing, supports premium reimbursement positioning, and reduces the risk of claim denials based on code mismatch or medical necessity disputes.
• A unique PLA code facilitates LCD coverage by providing a specific code that the MAC can reference in the coverage determination, rather than covering a generic code for a broad category of tests.
• The PLA code designation reinforces the proprietary nature of the test and is consistent with GDT's intellectual property position.
The AMA CPT Editorial Panel reviews PLA code applications on a quarterly basis. Submission requirements include a completed application form, test description and methodology, evidence of CLIA certification and laboratory accreditation, demonstration of the test's proprietary nature, the proposed code descriptor, and supporting documentation.
Calderwood & Harkness and Carraway Regulatory Advisors have prepared a preliminary proposed PLA code descriptor for the team's review and discussion:
"OncoPrecise GXP-47 (Genome Dx Therapeutics Inc.), genomic profiling, non-small-cell lung cancer, 47-gene RNA expression panel, formalin-fixed paraffin-embedded tissue, algorithm-derived Therapy Response Index (TRI) score"
This preliminary descriptor will be refined based on input from the GDT team and finalized prior to submission. The team will discuss whether any modifications are needed to accurately and completely describe the test's methodology and clinical application within the character and format constraints of PLA code descriptors.
AMA Meeting Cycles and Target Submission. The team's target is the September 2024 AMA CPT Editorial Panel meeting. To be considered at the September 2024 meeting, the completed PLA code application must be submitted to the AMA by June 28, 2024. The team will discuss whether the June 28, 2024 deadline is achievable given the current state of the test documentation and the anticipated workflow for application preparation and internal review.
6.3 Action Items — Coding Pathway
The following action items will be confirmed during this discussion:
1. Calderwood & Harkness (Aiken, Morrissey, with Calloway oversight) to prepare a detailed Coding Strategy Memorandum analyzing the PLA code pathway, the existing CPT code pathway, and the stacking approach, with a recommended course of action. Target delivery: March 11, 2024.
2. Carraway Regulatory Advisors (Carraway) to advise on AMA CPT Editorial Panel submission formatting requirements, coding mechanics, and any recent changes to AMA submission procedures or PLA code policies that may affect the application.
3. GDT (Driscoll) to provide Calderwood & Harkness and Carraway with complete technical test methodology documentation — including specimen requirements, analytical workflow, bioinformatics pipeline, TRI algorithm description, and sample test reports — to support code descriptor drafting and the overall PLA code application.
7. LCD / MolDx Strategy
Scheduled Time: 12:00 – 12:30 PM PST
7.1 Medicare Administrative Contractor: Cascade Fiscal Intermediaries, LLC
Presenters: Miriam Calloway and Sean Morrissey
The Medicare Administrative Contractor (MAC) with jurisdiction over GDT's CLIA-certified reference laboratory in San Diego, California is Cascade Fiscal Intermediaries, LLC (CFI), which administers Medicare Part B claims for Jurisdiction E, encompassing the states of California, Hawaii, Nevada, American Samoa, Guam, and the Northern Mariana Islands.
CFI is headquartered at 2800 SW Moody Avenue, Suite 500, Portland, Oregon 97201. The key CFI personnel with whom Calderwood & Harkness anticipates interacting in connection with the GXP-47 LCD application are:
• Dr. William Hargrove, MD, FACP — CFI Medical Director for Molecular Diagnostics Coverage. Dr. Hargrove is the senior physician reviewer responsible for evaluating the clinical evidence supporting coverage requests for molecular diagnostic tests within Jurisdiction E. He was the reviewing medical director on GDT's prior LCD for OncoPrecise GXP-12 (LCD L38472).
• Sandra Phu — CFI LCD Analyst for Genomic Diagnostics. Ms. Phu serves as the primary administrative and analytical point of contact for LCD applications involving genomic and molecular diagnostic tests.
GDT has an established working relationship with CFI from the OncoPrecise GXP-12 LCD process. The team will discuss how to leverage this existing relationship while recognizing that each LCD application is evaluated independently on its own merits. Calderwood & Harkness will review GDT's prior CFI correspondence and GXP-12 LCD file to identify any relevant precedent, lessons learned, or relationship dynamics that may inform the GXP-47 strategy.
7.2 MolDx Program: Ridgeline Administrative Services, LLC
The MolDx (Molecular Diagnostic Services) program is a multi-MAC initiative that provides a standardized framework for the coverage and payment of molecular diagnostic tests under Medicare. The MolDx program is administered by Ridgeline Administrative Services, LLC (RAS), which conducts technical assessments of molecular diagnostic tests seeking Medicare coverage and provides coverage recommendations to participating MACs, including CFI.
RAS is headquartered at 1600 Hampton Street, Suite 700, Columbia, South Carolina 29201. The key RAS personnel for the OncoPrecise GXP-47 technical assessment process is:
• Dr. Catherine Embry, PhD — MolDx Technical Assessment Director. Dr. Embry oversees the scientific and technical review of molecular diagnostic test submissions and is responsible for coordinating the technical assessment review panel.
The MolDx technical assessment dossier is the central evidentiary document submitted in support of an LCD application for a molecular diagnostic test. The dossier must comprehensively address the following six core content areas:
1. Test Description and Intended Use — A detailed description of the test methodology, specimen requirements, analytical workflow, and intended clinical application.
2. Analytical Validation Data — A summary of the test's analytical performance characteristics, including sensitivity, specificity, precision, accuracy, and reproducibility.
3. Clinical Validation Data — Evidence demonstrating that the test accurately identifies, measures, or predicts the clinical condition or outcome it is intended to assess.
4. Clinical Utility Evidence — Evidence demonstrating that the test results change clinical management decisions and lead to improved patient outcomes.
5. Health Economic Analysis — Analysis of the cost-effectiveness and budget impact of the test relative to existing standard of care.
6. Supporting Bibliography — A comprehensive bibliography of peer-reviewed publications and other relevant literature supporting the test's clinical validity and utility.
7.3 LCD Application Process and Timeline
The LCD application process involves the submission of a formal request letter to CFI, accompanied by the MolDx technical assessment dossier and all supporting documentation. The request letter will identify the test, the proposed patient population, the clinical indication, and the requested coverage determination, and will reference the PLA code (or placeholder code, if the PLA code has not yet been assigned at the time of filing).
The team's target date for filing the LCD application is August 2024, which is intended to follow the assignment of the PLA code at the September 2024 AMA CPT Editorial Panel meeting. However, the team recognizes a potential sequencing issue: the September 2024 AMA meeting may occur after the target August 2024 LCD filing date. The team will discuss the following options to address this sequencing:
• File the LCD application in August 2024 with a placeholder code (e.g., a miscellaneous or unlisted molecular pathology code), with the understanding that the PLA code will be assigned during the LCD review period and can be substituted at that time;
• Defer the LCD filing until after the PLA code is assigned in September 2024, recognizing the modest delay but ensuring that the LCD application references the final, assigned PLA code; or
• Explore whether the AMA submission timeline permits the PLA code to be assigned prior to August 2024 through an accelerated review process or an earlier meeting cycle.
The typical LCD processing timeline from filing to final determination is six to twelve months. This estimate accounts for RAS technical assessment review, CFI medical director review, a public comment period (typically 30 days), consideration of public comments, and issuance of a final LCD. The actual timeline may vary depending on the complexity of the review, the adequacy of the submitted evidence, and the volume of pending LCD applications at CFI.
The team will discuss the risk of a non-coverage determination if the clinical evidence available at the time of filing is insufficient to satisfy the evidentiary standards applied by CFI and RAS. This risk assessment will inform the decision on whether to file with interim CLARITY-LUNG data or wait for final data readout.
7.4 MolDx Technical Assessment Dossier — Content and Assignments
The preparation of the MolDx technical assessment dossier is a collaborative effort involving all members of the engagement team. The following content assignments will be confirmed:
The target for the supporting bibliography is 40 or more peer-reviewed publications encompassing the clinical evidence base for RNA expression-based treatment selection in NSCLC, the scientific rationale for the TRI algorithm, the performance characteristics of similar genomic profiling tests, and the clinical utility of molecular diagnostics in oncology treatment decision-making.
GDT (Dr. Sundaram and Driscoll) will be responsible for providing all source clinical and laboratory data, including raw and analyzed CLARITY-LUNG trial data, analytical validation study data, and internal technical documentation.
7.5 Coordination with Larkfield Health Economics
Dr. Nathan Ostroff of Larkfield Health Economics will present a brief overview of the planned scope for the HEOR analysis, including the analytical framework, data inputs required from GDT, and the anticipated format and length of the clinical utility and cost-effectiveness deliverables.
The timeline for Larkfield's HEOR deliverables must be coordinated with the overall dossier compilation schedule to ensure that the clinical utility analysis and cost-effectiveness analysis are completed and reviewed by Calderwood & Harkness in advance of the target LCD filing date.
Calderwood & Harkness will review all Larkfield work product for regulatory compliance, consistency with the overall coverage strategy, and conformance with MolDx program expectations before incorporating the HEOR materials into the technical assessment dossier. Dr. Ostroff and Sean Morrissey will establish a direct working relationship for ongoing coordination on the HEOR workstream.
8. Reimbursement Rate Strategy — Preliminary Discussion
Scheduled Time: 12:30 – 12:45 PM PST
8.1 Target Reimbursement Rate
Presenters: Sean Morrissey and Kevin Driscoll
GDT's target Medicare reimbursement rate for OncoPrecise GXP-47 is $3,850 per test. This target has been developed by GDT's market access team in consultation with its financial advisors and reflects the test's clinical value, development costs, operational costs, and competitive positioning relative to comparable multi-gene, NGS-based oncology panels currently on the Medicare Clinical Laboratory Fee Schedule (CLFS).
The methodology for establishing the Medicare reimbursement rate for a new PLA code is determined by CMS through a crosswalk or gapfill process. Under the crosswalk methodology, CMS assigns a rate to the new code based on the rate of an existing code that is deemed comparable in terms of clinical utility, test complexity, and resource utilization. Under the gapfill methodology, the MAC establishes a rate based on the laboratory's actual costs of performing the test, charges for the test, and other relevant factors.
8.2 Preliminary Crosswalk Comparators
Calderwood & Harkness has conducted a preliminary identification of potential crosswalk comparator codes for OncoPrecise GXP-47. The following codes and rates are presented for initial discussion; a detailed Reimbursement Rate Analysis Memorandum with a comprehensive crosswalk analysis will be prepared later in the engagement:
The weighted average of these three comparator rates is:
($3,742 + $2,919 + $4,206) ÷ 3 = $3,622.33
GDT's target reimbursement rate of $3,850 represents a 6.28% premium over the weighted average of the identified comparators. The justification for this premium will be developed in the Reimbursement Rate Analysis Memorandum and will focus on the proprietary nature of the TRI algorithm, the clinical differentiation of OncoPrecise GXP-47 relative to existing tests, the prospective clinical validation data from the CLARITY-LUNG trial, and the test's demonstrated clinical utility in guiding ICI therapy selection — a treatment decision with significant clinical and economic consequences.
8.3 Gapfill Alternative
If CMS declines to establish the reimbursement rate through the crosswalk methodology, the gapfill methodology serves as an alternative or fallback approach. Under gapfill pricing, the MAC would establish a rate based on factors including the laboratory's actual costs of performing the test, the laboratory's charges for the test, and the rates established by other MACs. The gapfill rate is set for one year, after which CMS establishes a national rate based on the weighted median of the gapfill rates set by individual MACs.
The gapfill methodology carries inherent uncertainty, as the resulting rate may be higher or lower than the crosswalk rate depending on the MAC's assessment of the relevant cost and pricing factors. GDT (Raymond Ota and Kevin Driscoll) will be asked to provide detailed cost data for OncoPrecise GXP-47 — including reagent costs, equipment depreciation, labor, overhead, and allocated development costs — in the event that gapfill analysis is needed.
8.4 Revenue Projection Context
The reimbursement rate is a critical input to GDT's financial model and revenue projections for OncoPrecise GXP-47. The following revenue projections have been provided by GDT and its financial advisor, Verdant Life Sciences Capital (Christine Lau, MD, Managing Director), and are presented here for context:
Year 1 Projected Revenue:
• Medicare revenue: 8,500 × 0.62 × $3,850 = $20,290,500
• Commercial revenue: 8,500 × 0.38 × $4,400 = $14,212,000
• Total Year 1 projected revenue: $34,502,500
Verdant Life Sciences Capital has modeled these projections as part of GDT's broader financial planning and investor relations activities. Calderwood & Harkness will review the reimbursement rate assumptions embedded in the financial model for accuracy and consistency with the reimbursement rate strategy developed during this engagement. Any discrepancies or risks identified will be communicated to GDT's financial team through Raymond Ota.
A detailed Reimbursement Rate Analysis Memorandum will be prepared by Calderwood & Harkness later in the engagement and will include a comprehensive crosswalk analysis, gapfill analysis, and recommendation on the reimbursement rate strategy.
9. NCD Pathway — Preliminary Overview
Scheduled Time: 12:45 – 12:55 PM PST
9.1 National Coverage Determination Considerations
Presenter: Miriam Calloway
The overall coverage strategy for OncoPrecise GXP-47 contemplates the eventual pursuit of a National Coverage Determination (NCD) from the Centers for Medicare & Medicaid Services (CMS), following successful LCD coverage at the MAC level. An NCD would provide nationwide Medicare coverage for the test, eliminating the need for separate LCD applications to each MAC jurisdiction and providing coverage certainty for ordering physicians and patients across the country.
Miriam Calloway will provide a brief overview of the two primary pathways available for obtaining an NCD:
CMS Coverage with Evidence Development (CED) Framework. Under the CED framework, CMS may issue a conditional NCD that provides Medicare coverage for the test when it is furnished in the context of an approved clinical study or registry designed to generate additional evidence of clinical utility. The CED pathway may be appropriate if the evidence base at the time of the NCD application is sufficient to demonstrate promising clinical validity but falls short of the evidentiary threshold for a full, unconditional NCD.
Traditional NCD Pathway. Under the traditional NCD pathway, CMS conducts a comprehensive evidence review and issues an unconditional national coverage determination. This pathway requires a robust evidence base demonstrating that the test is reasonable and necessary for the Medicare population, and typically involves a formal evidence review, a Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) meeting, a proposed NCD with public comment period, and a final NCD.
The estimated timeline for NCD review and issuance is 18 to 24 months from the date of the NCD request, although this timeline can vary significantly based on the complexity of the clinical question, the adequacy of the evidence, and CMS's review capacity and priorities.
Calderwood & Harkness will prepare a comprehensive NCD Feasibility Assessment Memorandum later in the engagement, evaluating the strategic considerations, evidentiary requirements, costs, and likelihood of success for each NCD pathway. The NCD Feasibility Assessment will be informed by the outcome of the LCD process and the final results of the CLARITY-LUNG trial.
For purposes of this kickoff meeting, the team's preliminary strategic recommendation is to pursue LCD coverage first, and then evaluate the NCD pathway based on the LCD outcome, the strength and completeness of the final CLARITY-LUNG data, and the broader competitive and clinical landscape at that time. This phased approach allows GDT to begin generating Medicare revenue under LCD coverage while building the evidence base and strategic positioning needed for a successful NCD application.
10. Project Timeline and Key Milestones
Scheduled Time: 12:55 – 1:10 PM PST
10.1 Master Timeline
Presenter: Sean Morrissey
The following master timeline summarizes the key milestones and target dates for the engagement:
10.2 Milestone Dependencies and Sequencing
The team will discuss the following critical dependencies and sequencing considerations: