Contract analysis

I. EXECUTIVE SUMMARY This memorandum presents our analysis of the March 29, 2024 interim analysis results from the CLARITY-LUNG clinical validation study (ClinicalTrials.gov ID: NCT05891247) and their implications for Genome Dx Therapeutics Inc.'s ("GDT") planned Local Coverage Determination ("LCD") application with Cascade Fiscal Intermediaries, LLC ("CFI") and concurrent MolDx Technical Assessment submission to Rid

1. The current clinical validation evidence is insufficient to support an LCD filing with a reasonable probability of favorable coverage. We assess the probability of a non-coverage determination at approximately 65–75% if the LCD is filed based on the interim data as currently available, and approximately 50–60% even with the addition of supplemental evidence strategies described herein. These risk levels are unacce

2. Supplemental evidence strategies may partially address the identified gaps but are unlikely to fully substitute for final CLARITY-LUNG data meeting or approaching the pre-specified performance endpoints. Several of the strategies discussed in this memorandum — including retrospective validation sub-studies, pre-specified sub-group analyses, publication of interim results, and external expert clinical utility asses

3. A detailed revised strategy memorandum with filing timeline recommendations will follow separately. A comprehensive Revised LCD/MolDx Strategy Memorandum is in preparation and is anticipated for delivery on or about April 22, 2024. That memorandum will present alternative filing timeline scenarios — including the option of deferring the LCD application until after the final CLARITY-LUNG data readout, now projected

II. BACKGROUND A. OncoPrecise GXP-47 Test Overview OncoPrecise GXP-47 is a laboratory-developed test ("LDT") performed exclusively at GDT's reference laboratory located at 4720 Torrey Pines Road, Suite 300, San Diego, California 92130. The laboratory holds CLIA certification (CLIA No. 05D2187432) and accreditation from the College of American Pathologists ("CAP") (CAP No. 9074821). The laboratory's National Provider

1. PLA Code Assignment. GDT is seeking a Proprietary Laboratory Analyses ("PLA") code through the American Medical Association ("AMA") CPT Editorial Panel. A draft PLA code application was delivered to Calderwood & Harkness for review on March 22, 2024. The application targets the AMA CPT Editorial Panel's September 2024 meeting, for which the submission deadline is June 28, 2024. The PLA code, once assigned, would p

2. Local Coverage Determination (LCD) and MolDx Technical Assessment. GDT planned to submit an LCD application to CFI (Jurisdiction E, covering California) with a concurrent MolDx Technical Assessment submission to RAS. The original target LCD filing date was August 2024, following PLA code assignment. An LCD from CFI would establish Medicare coverage for OncoPrecise GXP-47 in Jurisdiction E, which includes the state

3. Establishment of Medicare Reimbursement Rate. GDT's target Medicare reimbursement rate for OncoPrecise GXP-47 is $3,850 per test. This rate has been determined through a combination of cost analysis, comparable test pricing, and value-based pricing considerations. Establishment of the final reimbursement rate would follow LCD issuance and would be subject to standard CMS pricing processes applicable to tests reimb

4. National Coverage Determination (NCD). GDT's longer-term objective is to pursue a National Coverage Determination through CMS, which would establish Medicare coverage for OncoPrecise GXP-47 on a nationwide basis. An NCD application would likely not be pursued until after GDT has secured at least one favorable LCD and has accumulated a more robust body of clinical evidence, including final CLARITY-LUNG results and,

III. MOLDX PROGRAM EVIDENTIARY STANDARDS A. Overview of MolDx Technical Assessment Requirements The MolDx program is a collaborative initiative among several Medicare Administrative Contractors ("MACs") that provides standardized technical assessments for molecular diagnostic tests seeking Medicare coverage. The program is administered by Ridgeline Administrative Services, LLC ("RAS"), located at 1600 Hampton Street,

1. Analytical Validity: Does the test accurately and reliably measure the analytes (in this case, RNA expression levels of 47 genes) that it claims to measure? This domain encompasses assay performance characteristics such as accuracy, precision, reproducibility, limit of detection, and analytical specificity and sensitivity.

2. Clinical Validity: Does the test accurately identify the clinical condition or predict the clinical outcome it claims to identify or predict? For OncoPrecise GXP-47, clinical validity requires demonstration that the TRI score accurately predicts response to ICI therapy, as measured by PPV and NPV for 12-month PFS.

3. Clinical Utility: Do the test results change clinical management, and do those changes lead to improved patient outcomes? For OncoPrecise GXP-47, clinical utility requires evidence — or at least a persuasive argument supported by available data — that treatment decisions guided by the TRI score lead to better patient outcomes than standard-of-care treatment selection without the TRI score. Of these three domains,

IV. DETAILED ANALYSIS OF EVIDENCE GAPS We have identified five distinct but interrelated evidence gaps arising from the CLARITY-LUNG interim analysis results and the current state of GDT's clinical evidence program. Each gap is analyzed below in terms of its magnitude, clinical significance, regulatory significance within the MolDx/LCD framework, and its individual and cumulative impact on the probability of a favora

V. RISK ASSESSMENT: PROBABILITY OF NON-COVERAGE DETERMINATION A. Likelihood Assessment if LCD Filed Based on Current Evidence Drawing on the five evidence gaps analyzed in Section IV, our assessment of precedent from comparable MolDx/LCD proceedings, and our knowledge of the evidentiary expectations of the MolDx program and CFI, we have assessed the probability of a non-coverage determination under three alternative

VI. SUPPLEMENTAL EVIDENCE STRATEGIES We have identified five supplemental evidence strategies that GDT could pursue, individually or in combination, to partially address the evidence gaps identified in Section IV. Each strategy is analyzed below in terms of its description, potential contribution, limitations, estimated timeline and cost, and overall assessment. We emphasize at the outset that none of these strategie