PRIVILEGED & CONFIDENTIAL ATTORNEY WORK PRODUCT
CALDERWOOD & HARKNESS LLP 1700 K Street NW, Suite 900 Washington, DC 20006
MEMORANDUM
Matter Number: 1043-00002
Date: May 14, 2024
To: Kevin Driscoll, VP of Market Access & Reimbursement, Genome Dx Therapeutics Inc. Raymond Ota, Chief Financial Officer, Genome Dx Therapeutics Inc.
From: Sean Morrissey, Senior Associate, Healthcare & Life Sciences Practice Christopher Aiken, Associate, Healthcare & Life Sciences Practice
Re: Reimbursement Rate Analysis — Crosswalk/Gapfill Pricing Strategy for OncoPrecise GXP-47
Reviewed by: Miriam Calloway, Partner, Healthcare & Life Sciences Practice
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I. Executive Summary
The purpose of this memorandum is to analyze and recommend Medicare reimbursement rate positioning for OncoPrecise GXP-47 ("GXP-47"), Genome Dx Therapeutics Inc.'s ("GDT") 47-gene RNA expression panel designed for use in patients with Stage IIIB/IV non-small-cell lung cancer ("NSCLC"). As described in greater detail below, rate determination for a new test assigned a Proprietary Laboratory Analyses ("PLA") code under the Clinical Laboratory Fee Schedule ("CLFS") is governed by two primary pricing methodologies: crosswalk and gapfill. This memorandum evaluates both methodologies and identifies the approach most favorable to GDT's commercial and financial objectives.
Primary Recommendation. We recommend that GDT pursue a crosswalk pricing strategy targeting a Medicare reimbursement rate of $3,850 per test. This recommendation is grounded in a systematic analysis of three crosswalk comparators that we have identified as the most analogous tests currently on the CLFS:
• PLA Code 0250U — Elara Genomic Sciences, "GeneSight Onco-48" ($3,742/test)
• CPT Code 81455 — NGS, solid organ neoplasm, 51 or greater genes ($2,919/test)
• PLA Code 0239U — Marlowe Asset Management Molecular Diagnostics, "TumorMap Pro" ($4,206/test)
The equally weighted average of these three comparators yields a benchmark rate of $3,622.33 per test. Our recommended target rate of $3,850 represents a 6.28% premium over this weighted average. The premium is justified by GXP-47's proprietary Therapy Response Index ("TRI") algorithm, which generates a unique composite predictive score not replicated in any existing comparator test, as well as GXP-47's narrow indication specificity and direct clinical decision impact in the context of immune checkpoint inhibitor ("ICI") therapy selection.
Alternative Gapfill Analysis. As a fallback strategy, we have prepared an alternative analysis of the gapfill methodology. Based on publicly available gapfill determinations for comparable NGS-based molecular diagnostic tests, we estimate that gapfill pricing would yield a rate in the range of $2,800–$3,400 per test — approximately $450 to $1,050 below the recommended crosswalk target. We strongly recommend that GDT pursue the crosswalk methodology as the primary approach and maintain gapfill as a contingency with prepared cost data.
Timing Note. This reimbursement rate analysis proceeds notwithstanding our current recommendation to defer the Local Coverage Determination ("LCD") filing, as set forth in the Revised LCD/MolDx Strategy Memorandum dated April 22, 2024. The deferral recommendation was premised on the CLARITY-LUNG trial interim analysis results, which did not meet pre-specified clinical validation thresholds. We have prepared this rate positioning analysis now to ensure that the work is complete and deployment-ready when final clinical data supports the LCD filing and commercial launch. The rate analysis and supporting materials should be viewed as preliminary and subject to revision upon availability of final trial data.
Revenue Projection Implications. At the target Medicare reimbursement rate of $3,850 per test, GDT's projected Year 1 Medicare revenue is approximately $20,290,500, contributing to total projected Year 1 revenue of approximately $34,502,500 when combined with estimated commercial payer revenue. These projections are material to GDT's financial planning and to the revenue covenants under the Pacific Coast National Bank revolving credit facility.
II. Background
A. OncoPrecise GXP-47 Test Overview
OncoPrecise GXP-47 is a laboratory-developed test ("LDT") performed exclusively at GDT's CLIA-certified, CAP-accredited reference laboratory located in San Diego, California. The laboratory operates under CLIA Certificate Number 05D2187432, CAP Accreditation Number 9074821, and is enrolled in the National Provider Identifier system under NPI 1902847365. As an LDT, GXP-47 is developed, validated, and performed within a single laboratory and is not currently subject to FDA premarket review under the current regulatory framework, although we note that GDT should continue to monitor developments in the FDA's proposed LDT rulemaking.
GXP-47 is a 47-gene expression panel that utilizes RNA extracted from formalin-fixed, paraffin-embedded ("FFPE") NSCLC tumor tissue specimens. The test employs next-generation sequencing ("NGS") technology to quantify the expression levels of 47 genes that have been identified through GDT's proprietary research as being associated with responsiveness or resistance to immune checkpoint inhibitor therapy in advanced NSCLC. The gene panel encompasses markers related to tumor immunogenicity, the tumor microenvironment, immune cell infiltration, and immune evasion pathways.
The central analytical output of GXP-47 is the Therapy Response Index ("TRI"), a composite score generated by a proprietary algorithm that integrates the expression data from all 47 genes into a single numerical score ranging from 0 to 100. The TRI score stratifies patients into three clinically actionable categories:
• High Likelihood of Response (TRI ≥ 70): Patients in this category are predicted to derive meaningful clinical benefit from first-line ICI therapy, supporting initiation of ICI-based treatment regimens.
• Intermediate Likelihood of Response (TRI 40–69): Patients in this category have an uncertain predicted response, and the treating oncologist should consider the TRI score alongside other clinical factors, including PD-L1 expression status and tumor mutational burden, in determining the optimal first-line treatment approach.
• Low Likelihood of Response (TRI < 40): Patients in this category are predicted to have a low probability of meaningful clinical benefit from ICI therapy, suggesting that platinum-based chemotherapy or alternative treatment strategies should be considered as first-line treatment.
The intended clinical use of GXP-47 is to guide oncologist decision-making on initiating first-line immune checkpoint inhibitor therapy — including pembrolizumab (Keytruda®), nivolumab (Opdivo®), and atezolizumab (Tecentriq®), among other approved ICIs — versus platinum-based chemotherapy in patients diagnosed with Stage IIIB or Stage IV NSCLC. GXP-47 is designed to address a significant unmet clinical need: while PD-L1 immunohistochemistry testing and tumor mutational burden assessment are currently used as biomarkers for ICI therapy selection, these markers have well-documented limitations in predictive accuracy, and a substantial proportion of NSCLC patients treated with ICIs fail to respond to therapy or experience immune-related adverse events without clinical benefit.
Validation Status. GDT completed analytical validation of GXP-47 on December 14, 2022. The analytical validation study demonstrated the test's accuracy, precision, reproducibility, and reportable range across the 47-gene panel and TRI scoring algorithm. The analytical validation results were published in a peer-reviewed article in the Journal of Molecular Oncology Diagnostics (Vol. 18, Issue 4, pp. 412–429, December 2022).
Clinical validation of GXP-47 is being conducted through the CLARITY-LUNG trial, a prospective, multi-center clinical validation study registered under ClinicalTrials.gov identifier NCT05891247. The trial is designed to assess the clinical validity and clinical utility of the TRI score in predicting response to first-line ICI therapy in Stage IIIB/IV NSCLC patients. An interim analysis of CLARITY-LUNG data was released on March 29, 2024. The interim results reported a positive predictive value ("PPV") of 0.68 and a negative predictive value ("NPV") of 0.71. Both values fall below the trial's pre-specified performance thresholds of PPV ≥ 0.75 and NPV ≥ 0.80, respectively. As discussed in detail in Section VIII.A below, these interim results are a material consideration in the overall reimbursement strategy timeline.
B. Coding Strategy Context
Pursuant to the Coding Strategy Memorandum dated March 11, 2024, our team recommended that GDT pursue a Proprietary Laboratory Analyses ("PLA") code for GXP-47, rather than billing under an existing Category I CPT code such as CPT 81455 (NGS, solid organ neoplasm, 51 or greater genes). This recommendation was based on several factors, including the proprietary nature of the TRI algorithm, the test's unique clinical application, and the strategic advantages of having a dedicated PLA code for payer contracting, claims adjudication, and reimbursement rate-setting purposes. A PLA code provides GDT with a unique billing identifier tied exclusively to GXP-47, eliminating the ambiguity and adjudication challenges that arise when a proprietary test is billed under a generic Category I CPT code.
A draft PLA code application was delivered to GDT on March 22, 2024, for review. The proposed PLA code descriptor reads as follows:
"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."
The PLA code application is targeted for submission to the American Medical Association ("AMA") CPT Editorial Panel for consideration at the September 2024 meeting. The submission deadline for the September meeting cycle is June 28, 2024. Assuming approval at the September meeting, the PLA code would become effective on the next quarterly PLA code effective date, which is anticipated to be January 1, 2025.
Reimbursement rate determination follows PLA code assignment. During the initial pricing period for a new PLA code, the CLFS rate is established using either the crosswalk or gapfill methodology, as described in detail in Section III below. The present memorandum addresses the rate-setting strategy to be deployed once the PLA code is assigned.
C. Relevance to Engagement Scope
The reimbursement rate analysis presented in this memorandum is a core deliverable under the Calderwood & Harkness engagement with GDT, as defined in the engagement letter dated February 14, 2024. The engagement encompasses comprehensive market access and reimbursement strategy advisory services for GXP-47, including coding strategy, reimbursement rate positioning, LCD/MolDx strategy, and related regulatory and payer matters.
The rate assumptions developed in this analysis have direct implications for GDT's financial planning and capital structure. Specifically:
Revenue Projections. The reimbursement rate assumptions in this memorandum directly impact GDT's revenue projections as modeled by Verdant Life Sciences Capital, LLC ("Verdant"), under the direction of Christine Lau, Managing Director. Verdant has developed GDT's financial projections incorporating assumptions provided by GDT's management team and reviewed by Calderwood & Harkness for accuracy with respect to reimbursement rate assumptions. The rate target of $3,850 per test is a key input to the Verdant financial model.
Credit Facility. The rate assumptions also factor into the financial models underlying the Pacific Coast National Bank $15M Revolving Facility (Credit Agreement Ref. PCNB-GDT-RF-2023-0922). Under the terms of the credit agreement, Medicare reimbursement revenue is a component of GDT's projected cash flows used to calculate compliance with certain financial covenants. Material deviations from the target reimbursement rate could affect GDT's ability to maintain compliance with borrowing base and revenue-based covenants under the facility.
Accordingly, the reimbursement rate strategy set forth in this memorandum should be considered in the context of GDT's broader financial and commercial planning.
III. Medicare Reimbursement Rate-Setting Framework
This section provides an overview of the statutory and regulatory framework governing Medicare reimbursement rate-setting for clinical laboratory tests, with particular emphasis on the crosswalk and gapfill methodologies applicable to new tests receiving PLA codes.
A. Clinical Laboratory Fee Schedule (CLFS) — Statutory and Regulatory Overview
Medicare reimburses clinical laboratory tests under Part B through the Clinical Laboratory Fee Schedule, administered by the Centers for Medicare & Medicaid Services ("CMS") pursuant to Section 1833(h) of the Social Security Act, 42 U.S.C. § 1395l(h). The CLFS establishes national payment amounts for laboratory tests identified by CPT and HCPCS codes, and payments are made to laboratories that perform covered tests for Medicare beneficiaries.
Historically, CLFS rates were established based on a combination of the national limitation amount (set as a percentage of the median of fee schedule amounts established by individual Medicare Administrative Contractors ("MACs")) and various statutory caps. However, the rate-setting methodology underwent significant reform with the enactment of the Protecting Access to Medicare Act of 2014 ("PAMA"), Pub. L. No. 113-93, § 216, which fundamentally restructured CLFS rate-setting for the majority of established laboratory tests.
Under PAMA, applicable laboratories — defined as laboratories that receive a majority of their Medicare revenues from the CLFS or the Physician Fee Schedule — are required to report private payer rate data to CMS. For each test, reported data includes the payer-specific rates and associated test volumes. CMS uses the reported data to calculate a weighted median private payer rate, which becomes the CLFS payment amount for the test. The PAMA-based rate-setting methodology applies to established tests — that is, tests for which private payer rate data exists and has been reported. PAMA rate reporting occurs in defined data collection periods, and rates are recalculated on a periodic basis. The most recent reporting period data was collected in 2019, with updated rates effective January 1, 2023, subject to the statutory annual reduction limits.
Critically for purposes of this memorandum, the PAMA private payer rate methodology does not apply to new tests during their initial pricing period. For new tests — including tests receiving newly assigned PLA codes — the CLFS rate is established through one of two alternative methodologies: crosswalk or gapfill. The distinction between these methodologies, and their application to GXP-47, is the central subject of this analysis.
B. Crosswalk Methodology
Under the crosswalk methodology, CMS (or the applicable MAC or the MolDx program, acting as CMS's contractor for molecular diagnostic test coverage and pricing) identifies an existing test on the CLFS that has similar resources, methodologies, and clinical applications to the new test and assigns the new test a rate that is the same as, or comparable to, the rate of the existing test.
The crosswalk methodology is applicable when the new test is sufficiently analogous to one or more existing tests on the CLFS that the existing test's rate provides a reasonable proxy for the value and resources associated with the new test. The applicant laboratory (in this case, GDT) is permitted — and encouraged — to propose specific crosswalk comparators and to submit supporting rationale explaining why each proposed comparator is analogous to the new test. The applicant may also argue for adjustments (upward or downward) from the comparator rate based on distinguishing factors between the new test and the comparator.
The crosswalk process generally proceeds as follows:
1. The applicant submits a crosswalk recommendation to CMS or the applicable MAC/MolDx program, identifying proposed comparator test(s) and providing a detailed rationale for why each comparator is analogous.
2. CMS or the MAC/MolDx program evaluates the proposed crosswalk comparators, considering the technical similarity, clinical application, resources required, and other relevant factors.
3. CMS or the MAC/MolDx program may accept the proposed crosswalk, modify it (e.g., by selecting a different comparator or adjusting the rate), or reject it in favor of the gapfill methodology.
4. A public comment period may be provided, during which interested stakeholders may submit comments on the proposed crosswalk determination.
5. The final crosswalk rate is established and becomes effective on the applicable quarterly effective date.
Advantages of the Crosswalk Methodology. The crosswalk approach offers several significant strategic advantages to GDT:
• Predictability. Because the crosswalk rate is derived from an existing, publicly available CLFS rate, the applicant can develop a reasonably accurate estimate of the expected reimbursement rate before submission.
• Speed. The crosswalk methodology typically results in a faster rate determination than the gapfill methodology, which involves a multi-year process of MAC-specific rate determinations and subsequent national rate calculation.
• Transparency. The crosswalk methodology allows the applicant to affirmatively advocate for specific comparators and rate levels, rather than relying on MACs to independently derive a rate from cost data.
• Premium Justification. The applicant can argue for a premium over the comparator rate based on distinguishing characteristics of the new test, such as proprietary algorithms, enhanced clinical utility, or additional analytical outputs.
C. Gapfill Methodology
Under the gapfill methodology, in the absence of a suitable crosswalk comparator, each MAC independently determines a rate for the new test based on an analysis of the resources required to perform the test. The gapfill rate is intended to reflect the cost of test performance, including both direct costs (such as reagents, consumables, technician labor, and equipment) and indirect costs (such as laboratory overhead, compliance costs, and general and administrative expenses).
The gapfill methodology is applicable when the new test is sufficiently novel or distinct that no existing test on the CLFS provides a meaningful basis for comparison. In practice, gapfill is the methodology of last resort — it is used when crosswalk cannot be reasonably supported.
The gapfill process proceeds in two phases:
Year 1 (Interim Rate). During the first calendar year after the test receives a code, each MAC independently sets an interim gapfill rate for the test. Because different MACs may assess the resource requirements differently, the interim rates may vary significantly across MAC jurisdictions, leading to geographic rate inconsistency during the first year.
Year 2 (National Rate). CMS calculates a national gapfill rate based on the median of the MAC-determined interim rates from Year 1. This national rate is then applied uniformly across all jurisdictions beginning in Year 2.
Disadvantages of the Gapfill Methodology. The gapfill methodology presents several significant disadvantages from GDT's perspective:
• Lower Expected Rate. Cost-based rate-setting typically yields rates below market-based or comparator-based rates, because MACs focus on the incremental cost of test performance rather than the clinical value or proprietary innovation embedded in the test.
• Unpredictability. Because each MAC independently assesses costs, there is significant variability and uncertainty in the interim gapfill rates during Year 1, and the ultimate national rate depends on the median of these variable determinations.
• Geographic Inconsistency. During Year 1, GDT could face different reimbursement rates depending on the MAC jurisdiction in which the ordering physician is located, complicating revenue forecasting and financial planning.
• Longer Timeline to Rate Certainty. The two-year gapfill process means that GDT would not have a stable national rate until the beginning of Year 2, delaying rate certainty by approximately twelve months compared to the crosswalk methodology.
• Limited Advocacy Opportunities. Unlike the crosswalk methodology, which permits the applicant to propose specific comparators and argue for premium adjustments, the gapfill methodology is primarily driven by the MAC's independent cost analysis, affording the applicant less direct influence over the outcome.
Relevance to GXP-47. Gapfill is the fallback methodology for GXP-47 in the event that CMS, the applicable MAC, or the MolDx program rejects the proposed crosswalk comparators as insufficiently analogous. As discussed in Section V below, we have prepared an alternative gapfill analysis to ensure that GDT is positioned to respond in the event that the crosswalk methodology is not accepted.
D. Proprietary Laboratory Analyses (PLA) Code Rate-Setting Specifics
Proprietary Laboratory Analyses codes are a category of CPT codes established by the AMA to identify specific clinical laboratory tests that are performed by a single ("sole-source") laboratory and that are not adequately described by existing CPT codes. PLA codes are assigned on a quarterly basis (effective dates of January 1, April 1, July 1, and October 1), in contrast to Category I CPT codes, which are assigned on an annual cycle.
Upon assignment, each PLA code receives its own CLFS rate, which is typically set via crosswalk or gapfill during the initial pricing period, consistent with the framework described above. The PLA code rate is specific to the test identified by the code and applies only to the designated laboratory.
Following the initial pricing period, the PLA code rate becomes subject to PAMA private payer rate reporting requirements. Under PAMA, GDT will be required to report its private payer rate data for GXP-47 during the applicable data collection period, and CMS will recalculate the CLFS rate based on the weighted median of reported private payer rates. This transition from crosswalk/gapfill pricing to PAMA-based pricing is a critical long-term consideration, as the PAMA-based rate may differ materially from the initial crosswalk rate depending on GDT's commercial payer contract rates at the time of data collection.
Timing. Assuming GXP-47 receives a PLA code at the September 2024 AMA CPT Editorial Panel meeting, the PLA code would become effective on the next quarterly effective date, which is anticipated to be January 1, 2025. The CLFS rate for the new PLA code would be established via crosswalk or gapfill and would become effective on the same date or shortly thereafter, depending on the processing timeline.
IV. Crosswalk Comparator Analysis
A. Comparator Selection Methodology
The selection of appropriate crosswalk comparators is a critical component of the rate-setting strategy. We applied the following criteria in identifying candidate comparators:
1. Similar Assay Technology. The comparator should employ NGS-based genomic profiling technology, consistent with GXP-47's methodology.
2. Comparable Gene Panel Size. The comparator should involve a gene panel of similar scope and complexity to GXP-47's 47-gene panel.
3. Similar Specimen Type. The comparator should use FFPE tissue specimens, consistent with GXP-47's input requirements.
4. Oncology Clinical Application. The comparator should be used in a clinical oncology context, consistent with GXP-47's intended use in NSCLC treatment decision-making.
5. Existing CLFS Rate. The comparator must have an established rate on the current CLFS to serve as a meaningful pricing reference.
We conducted a systematic review of all PLA codes and Category I CPT codes for molecular diagnostic oncology tests currently listed on the CLFS. This review encompassed approximately 85 PLA codes and 45 Category I CPT codes in the molecular diagnostics and genomic profiling categories. From this review, we identified three comparators as the most analogous to GXP-47, each capturing a different dimension of the test's value proposition. These three comparators are described in detail below.
B. Comparator 1: PLA Code 0250U — Elara Genomic Sciences, "GeneSight Onco-48"
Test Description. PLA Code 0250U identifies GeneSight Onco-48, a proprietary 48-gene NGS-based expression panel manufactured by Elara Genomic Sciences, Inc. GeneSight Onco-48 is performed on FFPE tissue specimens from solid tumors and generates a multi-gene expression score used for solid tumor profiling across multiple tumor types. The test employs RNA extraction and NGS-based expression quantification to assess a curated panel of 48 genes associated with tumor biology and treatment response.
Current Medicare CLFS Rate: $3,742 per test.
Similarities to GXP-47. GeneSight Onco-48 is the strongest single comparator to GXP-47 due to the following shared characteristics:
• Gene Panel Size. GeneSight Onco-48 utilizes a 48-gene panel, nearly identical to GXP-47's 47-gene panel. The difference of a single gene is immaterial from the standpoint of assay complexity, resource requirements, and analytical workflow.
• Specimen Type. Both tests are performed on FFPE tissue, involving the same specimen processing, RNA extraction, and quality control requirements.
• Assay Technology. Both tests employ NGS-based RNA expression profiling, utilizing comparable sequencing platforms, library preparation methodologies, and bioinformatics pipelines.
• Algorithmic Output. Both tests generate an algorithmic composite score derived from the expression data, providing a synthesized clinical output beyond raw gene expression values.
• Oncology Application. Both tests are used in clinical oncology for tumor characterization and treatment-related decision-making.
Differences from GXP-47. Despite the substantial technical similarities, GeneSight Onco-48 differs from GXP-47 in several respects:
• Clinical Indication. GeneSight Onco-48 is a pan-tumor panel applicable to multiple solid tumor types. GXP-47, by contrast, is specifically focused on Stage IIIB/IV NSCLC and the prediction of ICI therapy response.
• Predictive Specificity. GeneSight Onco-48 generates a general tumor profiling score but does not produce a therapy-specific predictive score analogous to GXP-47's TRI. The TRI score is designed to predict response to a specific class of therapy (ICI) in a specific disease setting, providing greater clinical decision specificity.
• Clinical Decision Impact. Because GeneSight Onco-48 covers multiple tumor types and does not target a specific therapeutic decision, its clinical output is informational rather than directly actionable in the same manner as the TRI.
Relevance to Crosswalk. PLA Code 0250U is the strongest available crosswalk comparator for GXP-47. The near-identical gene panel size, shared specimen type, common assay technology, and parallel algorithmic output make GeneSight Onco-48 a compelling technical analog. The $3,742 rate provides a robust floor for GXP-47 pricing, with the differences between the tests — specifically GXP-47's greater indication specificity and therapy-specific predictive output — supporting a premium above the 0250U rate.
C. Comparator 2: CPT Code 81455 — NGS, Solid Organ Neoplasm, 51 or Greater Genes
Test Description. CPT Code 81455 is a Category I CPT code describing next-generation sequencing-based genomic analysis of solid organ neoplasms, covering panels of 51 or more genes. This is a generic (non-proprietary) CPT code used by multiple laboratories to bill for comprehensive genomic profiling of solid tumors. The code encompasses both DNA and RNA analysis and is commonly used for large-panel NGS testing in oncology.
Current Medicare CLFS Rate: $2,919 per test.
Similarities to GXP-47. CPT 81455 shares the following characteristics with GXP-47:
• Assay Technology. Both utilize NGS-based genomic analysis of tumor tissue.
• Clinical Application. Both are used in clinical oncology for the genomic characterization of solid tumors to inform treatment decisions.
• Specimen Type. CPT 81455 is typically performed on FFPE solid tumor tissue specimens.
• Gene Panel Scale. While CPT 81455 covers panels of 51 or more genes, GXP-47's 47-gene panel is in a comparable size range, reflecting a similar level of analytical complexity and sequencing depth.
Differences from GXP-47. CPT 81455 differs from GXP-47 in several important respects:
• Generic vs. Proprietary. CPT 81455 is a non-proprietary stacking code used by numerous laboratories. It does not identify a specific test or laboratory and does not carry the premium associated with proprietary algorithmic outputs.
• Gene Panel Threshold. CPT 81455 covers panels of 51 or more genes. GXP-47's 47-gene panel falls slightly below this threshold, which could be raised as a technical distinction by CMS/MACs during crosswalk evaluation. However, the four-gene difference does not reflect a material difference in assay complexity or resource requirements.
• Analyte Type. CPT 81455 typically encompasses DNA sequencing for somatic mutation analysis (e.g., variant detection, copy number analysis) and may include some RNA analysis. GXP-47, by contrast, is exclusively an RNA expression profiling test, which involves different library preparation methodologies and analytical workflows.
• Algorithmic Output. CPT 81455 does not encompass proprietary algorithmic composite scoring. Tests billed under CPT 81455 typically report individual gene variants and alterations without generating a synthesized predictive score analogous to the TRI.
Relevance to Crosswalk. CPT 81455 serves as a conservative lower-bound comparator for GXP-47. The $2,919 rate reflects the commodity pricing assigned to non-proprietary NGS panels without algorithm-derived outputs. The rate differential between CPT 81455 and GXP-47 is attributable to GXP-47's proprietary TRI algorithm, indication-specific clinical utility, and PLA code status. CPT 81455 is included in the comparator set to demonstrate that GXP-47's target rate is reasonable in the context of the broader NGS oncology testing landscape and to support the argument that the TRI algorithm merits a substantial premium over generic NGS billing codes.
D. Comparator 3: PLA Code 0239U — Marlowe Asset Management Molecular Diagnostics, "TumorMap Pro"
Test Description. PLA Code 0239U identifies TumorMap Pro, a proprietary multi-gene NGS-based genomic profiling test developed by Marlowe Asset Management Molecular Diagnostics, Inc. for advanced solid tumors. TumorMap Pro is performed on FFPE tissue specimens and encompasses comprehensive genomic profiling ("CGP"), including both DNA sequencing and RNA expression analysis across a broad gene set. The test generates an algorithmic treatment pathway recommendation — a proprietary output that identifies potential therapeutic options based on the patient's genomic profile, including targeted therapy, immunotherapy, and chemotherapy options.
Current Medicare CLFS Rate: $4,206 per test.
Similarities to GXP-47. TumorMap Pro shares several characteristics with GXP-47:
• PLA Code Status. TumorMap Pro is a proprietary test with a dedicated PLA code, reflecting its unique analytical and clinical characteristics, consistent with GXP-47's anticipated PLA code status.
• Assay Technology. Both tests employ NGS-based genomic analysis, including RNA expression profiling, performed on FFPE tissue specimens.
• Oncology Application. Both tests are designed for use in clinical oncology, providing actionable information to guide treatment selection in advanced cancer patients.
• Proprietary Algorithmic Output. Both tests include a proprietary algorithmic component that generates a synthesized clinical decision-support output — TumorMap Pro produces a treatment pathway recommendation, and GXP-47 produces the TRI score. This shared characteristic is particularly significant for crosswalk purposes, as it reflects a common value proposition: the transformation of raw genomic data into an actionable clinical output through proprietary analytics.
Differences from GXP-47. TumorMap Pro differs from GXP-47 in the following respects:
• Test Scope. TumorMap Pro is a comprehensive genomic profiling test that encompasses a broader gene set than GXP-47, including both DNA variant analysis and RNA expression profiling. GXP-47 is a focused 47-gene RNA expression panel.
• Clinical Indication. TumorMap Pro is a pan-tumor test used across multiple cancer types for treatment selection. GXP-47 is narrowly focused on a single indication (Stage IIIB/IV NSCLC ICI therapy response prediction).
• Analyte Breadth. TumorMap Pro includes tumor mutational burden ("TMB") and microsatellite instability ("MSI") assessments in addition to gene-level analysis, reflecting a broader analytical scope. GXP-47 does not include TMB or MSI assessment.
• Output Type. TumorMap Pro's treatment pathway recommendation is a multi-treatment option output spanning targeted therapies, immunotherapies, and chemotherapy. GXP-47's TRI score is a binary-decision predictive tool (ICI vs. chemotherapy) with greater specificity and clinical precision for its intended indication.
Relevance to Crosswalk. PLA Code 0239U serves as the upper-bound comparator for GXP-47. The $4,206 rate reflects the premium that CMS/MACs have assigned to proprietary algorithmic output tests in the oncology molecular diagnostic category. The inclusion of TumorMap Pro in the comparator set demonstrates that CMS has accepted rates significantly above the generic CPT 81455 level for proprietary tests with algorithmic clinical decision-support outputs, supporting the argument that GXP-47's TRI algorithm justifies a rate above the generic NGS code level and within the range established by proprietary comparators.
E. Weighted Average Calculation and Target Rate Derivation
Weighted Average Calculation
We calculated the weighted average of the three comparator rates using equal weighting, as follows:
Calculation: ($3,742 + $2,919 + $4,206) ÷ 3 = $3,622.33 per test.
Equal Weighting Rationale
We employed equal weighting across the three comparators because each captures a distinct and independently relevant dimension of GXP-47's value proposition and resource profile:
• PLA 0250U (GeneSight Onco-48) captures the technical methodology and gene panel size dimension — the most technically analogous comparator in terms of assay design and analytical workflow.
• CPT 81455 captures the NGS-based oncology genomic profiling dimension — establishing the baseline rate for non-proprietary NGS panels and illustrating the commodity pricing floor.
• PLA 0239U (TumorMap Pro) captures the proprietary algorithmic output dimension — establishing the premium rate level for tests that include proprietary analytics generating actionable clinical outputs.
Each comparator is equally relevant to the overall crosswalk analysis, and no single comparator is dispositive. Equal weighting ensures that the target rate reflects a balanced synthesis of all three valuation dimensions.
Recommended Target Rate
Based on the crosswalk analysis, we recommend a target Medicare reimbursement rate of $3,850 per test for GXP-47.
Premium Calculation. The recommended target rate of $3,850 represents a premium over the weighted average of $3,622.33, calculated as follows:
($3,850 − $3,622.33) ÷ $3,622.33 = 6.28%
Premium Justification. The 6.28% premium over the weighted average is justified by four key factors that distinguish GXP-47 from the comparator tests:
(1) Proprietary TRI Algorithm. GXP-47's Therapy Response Index is a unique composite scoring system that integrates expression data from 47 genes into a single predictive score (0–100) specifically calibrated for ICI therapy response prediction in NSCLC. No comparator test replicates this specific analytical output. The TRI algorithm represents a significant research and development investment by GDT: GDT 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, gene panel composition, and associated bioinformatics methods. The proprietary nature and patent protection of the TRI algorithm represent substantial intellectual property value that is not captured in any comparator rate.
(2) Indication Specificity. GXP-47 is narrowly focused on a single clinical indication — Stage IIIB/IV NSCLC ICI therapy response prediction. This indication specificity provides greater clinical precision and relevance than pan-tumor panels such as GeneSight Onco-48 and TumorMap Pro, which cover multiple tumor types with correspondingly less specificity for any individual indication. Indication-specific tests require dedicated clinical validation studies (such as CLARITY-LUNG) and generate outputs that are directly applicable to a specific clinical decision point, adding value beyond what is provided by broader profiling tests.
(3) Clinical Decision Impact. The TRI score directly guides the specific binary treatment decision that is most consequential in Stage IIIB/IV NSCLC: whether to initiate first-line ICI therapy or platinum-based chemotherapy. This direct, actionable clinical utility distinguishes GXP-47 from comparators that provide informational genomic outputs without generating a specific predictive score tied to a discrete therapeutic decision. The clinical decision impact of the TRI score is the central value proposition of GXP-47 and supports a premium over tests that provide less targeted clinical guidance.
(4) Health Economic Value. GXP-47 has the potential to generate meaningful cost savings for the Medicare program by avoiding futile ICI therapy in patients predicted to be non-responders (TRI < 40). ICI therapy costs for NSCLC are substantial — first-line pembrolizumab monotherapy costs approximately $9,000–$12,000 per infusion cycle, with treatment continuing for up to two years in responding patients. By identifying patients unlikely to benefit from ICI therapy, GXP-47 may prevent unnecessary ICI utilization and associated cost, including the costs of managing immune-related adverse events. The health economic value proposition will be quantified in detail by Larkfield Health Economics (Dr. Nathan Ostroff) as part of the cost-effectiveness analysis to be included in the MolDx technical assessment dossier. The cost savings potential supports a premium rate that reflects the value GXP-47 provides to the Medicare program beyond the cost of test performance.
Historical Precedent for Premium Acceptance
The proposed premium of 6.28% over the weighted average of comparator rates is within the range of premiums that CMS and MACs have historically accepted for proprietary algorithmic enhancements over analogous non-algorithmic tests. As summarized in Appendix D, CMS/MAC crosswalk determinations for molecular diagnostic tests with proprietary algorithmic outputs have typically resulted in premiums of 4% to 12% over the closest non-algorithmic comparator. GXP-47's premium of 6.28% is well within this established range and is supported by the substantive justifications described above.
V. Gapfill Alternative Analysis
A. Gapfill Scenario Overview
Although we strongly recommend the crosswalk methodology as the primary pricing strategy for GXP-47, we have prepared an alternative analysis under the gapfill methodology to ensure that GDT is positioned to respond in the event that CMS, the applicable MAC, or the MolDx program determines that the proposed crosswalk comparators are insufficiently analogous to GXP-47 and rejects the crosswalk approach.
Circumstances under which the crosswalk methodology could be rejected include, without limitation:
• CMS/MAC determination that the technical or clinical differences between GXP-47 and the proposed comparators (e.g., RNA-only vs. DNA+RNA analysis, single-indication vs. pan-tumor scope) are too significant to support a crosswalk;
• CMS/MAC determination that the 47-gene panel size of GXP-47 falls outside the acceptable range for crosswalk to CPT 81455 (which covers panels of 51 or more genes);
• Policy-level preference by the MolDx program for gapfill pricing for new ICI response prediction tests, particularly in the context of evolving coverage policies for this test category.
If crosswalk is rejected, the applicable MACs — including Cascade Fiscal Intermediaries ("CFI"), which serves as the MAC for the jurisdiction encompassing GDT's San Diego laboratory — would independently determine GXP-47's rate based on a resource cost analysis during the first year following PLA code assignment.
B. Direct Cost Inputs for Gapfill Pricing
Under the gapfill methodology, MACs consider the direct costs of performing the test as a primary input to rate determination. For GXP-47, the relevant direct cost categories include:
• Reagent and Consumable Costs. Costs of all reagents and consumables required to perform a single GXP-47 test, including RNA extraction kits, library preparation reagents, NGS sequencing reagents (flow cells, cluster generation reagents), and quality control materials. Based on comparable NGS workflow cost profiles, we estimate reagent and consumable costs in the range of $450–$650 per test, although GDT should provide exact per-test cost data from its laboratory operations.
• Laboratory Technician Labor. The labor cost associated with each test, including specimen receipt and accessioning, RNA extraction from FFPE tissue, library preparation, NGS sequencer loading and operation, bioinformatics analysis, TRI algorithm processing, and pathologist review and sign-out. We estimate approximately 6–8 hours of combined technician and pathologist time per test, with blended labor costs in the range of $350–$500 per test.
• Equipment Depreciation Allocation. Per-test allocation of depreciation costs for capital equipment, including the NGS sequencer (e.g., Marlowe Group NovaSeq or comparable platform), RNA extraction instruments, computational servers and storage infrastructure, and associated laboratory equipment. Depreciation allocation depends on test volume and equipment useful life; we estimate $200–$350 per test at projected Year 1 volumes.
• Specimen Processing and Handling. Costs associated with specimen receipt, logging, FFPE block sectioning, and tissue preparation for RNA extraction, estimated at $50–$100 per test.
Total Estimated Direct Costs: $1,050–$1,600 per test.
C. Indirect Cost Inputs
In addition to direct costs, MACs consider indirect costs in gapfill rate determination:
• Laboratory Overhead. Facility costs (rent, utilities, maintenance), CLIA and CAP compliance costs (including proficiency testing, inspections, and quality management systems), and general laboratory quality assurance expenses.
• Bioinformatics Infrastructure and Algorithm Maintenance. Ongoing costs of maintaining and updating the computational infrastructure supporting the TRI algorithm, including server costs, data storage, software licensing, and algorithm validation and refinement.
• Clinical Reporting and Result Delivery Systems. Costs associated with the electronic medical record integration, result reporting portal, and clinical consultation services provided to ordering physicians.
• General and Administrative Allocation. Proportional allocation of GDT's corporate overhead, including executive management, legal and compliance, finance, and human resources functions.
Total Estimated Indirect Costs: $700–$1,100 per test (at projected Year 1 volumes; indirect cost per test is inversely related to volume).
D. Estimated Gapfill Rate Range
Based on our analysis of publicly available gapfill rate determinations for comparable NGS-based molecular diagnostic tests, and incorporating the direct and indirect cost estimates described above, we estimate that the gapfill rate for GXP-47 would fall in the range of $2,800–$3,400 per test.
This estimate reflects the following considerations:
• Recent gapfill determinations for NGS-based molecular diagnostic tests with proprietary analytical outputs have generally resulted in rates in the $2,500–$3,800 range, with variability depending on the specific MAC, the complexity of the test, and the quality of the cost data submitted by the laboratory.
• The lower end of the estimated range ($2,800) reflects a conservative scenario in which MACs apply a narrow cost-based methodology without significant allowance for the proprietary TRI algorithm or the test's clinical utility.
• The upper end of the estimated range ($3,400) reflects a scenario in which MACs recognize the additional analytical complexity and clinical value of the TRI algorithm and apply a modest value-based adjustment above strict cost recovery.
Comparison to Crosswalk Target. The estimated gapfill rate range of $2,800–$3,400 falls approximately $450 to $1,050 below the recommended crosswalk target rate of $3,850, representing a potential revenue reduction of 12%–27% relative to the crosswalk target. At the midpoint of the gapfill range ($3,100), the revenue reduction versus the crosswalk target would be approximately 19%.
Variability Risk. A significant risk of the gapfill methodology is the potential for inconsistent rates across MAC jurisdictions during Year 1. Different MACs may apply different assumptions regarding cost allocation, volume projections, and the appropriate treatment of proprietary algorithm costs, resulting in a range of interim rates that could vary by several hundred dollars per test. This variability complicates revenue forecasting and could create administrative challenges for GDT's billing and collections operations.
E. Strategic Recommendation — Crosswalk Preferred Over Gapfill
Based on the foregoing analysis, we strongly recommend that GDT pursue the crosswalk methodology as the primary pricing strategy for GXP-47. The crosswalk approach is preferred for the following reasons:
1. Higher Expected Rate. The crosswalk target of $3,850 exceeds the estimated gapfill range of $2,800–$3,400, representing materially higher per-test revenue for GDT.
2. Greater Rate Predictability. The crosswalk methodology allows GDT to predict the likely reimbursement rate with reasonable accuracy based on the comparator rates, whereas the gapfill methodology introduces significant uncertainty and variability.
3. Faster Rate Certainty. The crosswalk methodology typically yields a final rate more quickly than the two-year gapfill process, enabling GDT to achieve revenue certainty sooner after PLA code assignment.
4. Ability to Advocate. The crosswalk methodology provides GDT with the opportunity to affirmatively propose comparators, present supporting rationale, and argue for a premium — tools that are not available under the MAC-driven gapfill process.
Notwithstanding this recommendation, we advise that GDT maintain gapfill as a backup position and prepare the necessary cost data for submission in the event that crosswalk is not accepted. Specifically, we recommend that GDT's finance team, under the direction of Raymond Ota, prepare a detailed per-test cost breakdown — including all direct and indirect cost categories identified above — to be ready for submission to the applicable MACs if gapfill is the required methodology. Having this data prepared in advance will ensure that GDT can respond promptly and with strong supporting documentation if the crosswalk comparators are rejected.
VI. Revenue Projection Implications
A. Revenue Model Assumptions
The revenue projections presented in this section were developed by Verdant Life Sciences Capital, LLC ("Verdant"), under the direction of Christine Lau, Managing Director, and reviewed by Calderwood & Harkness for accuracy of the Medicare reimbursement rate assumptions. The projections are based on GDT management's assumptions regarding test volume ramp, payer mix, and commercial payer rates, and are subject to revision based on the following factors:
• Final results of the CLARITY-LUNG trial, which may affect clinical validation claims, LCD coverage probability, and commercial payer contracting;
• Actual timing of commercial launch, which is contingent on PLA code assignment, LCD coverage determination, and GDT board approval;
• Actual payer contracting outcomes, which may differ from the blended commercial rate assumption;
• Competitive dynamics and market adoption rates, which are inherently uncertain.
The projections set forth below should be treated as illustrative estimates for planning purposes and are not guarantees of future revenue.
B. Medicare Revenue Projections at Target Rate ($3,850/test)