Contract analysis

I. PURPOSE OF THIS REQUEST On behalf of Genome Dx Therapeutics Inc. ("GDT"), I am writing in my capacity as Co-Founder and Chief Executive Officer to respectfully request that Cascade Fiscal Intermediaries, LLC ("CFI"), in its capacity as the Medicare Administrative Contractor ("MAC") for Jurisdiction E (which includes the State of California, among other states), initiate a local coverage determination ("LCD") proce

II. COMPANY OVERVIEW — GENOME DX THERAPEUTICS INC. Genome Dx Therapeutics Inc. is a Delaware corporation headquartered in San Diego, California, with Employer Identification Number (EIN) 83-2947156. GDT was founded in 2018 by Dr. Anisha Raval and Dr. Marcus Yuen with a mission to develop and commercialize next-generation sequencing ("NGS")-based genomic tests that deliver clinically actionable, personalized informati

III. TEST DESCRIPTION — ONCOPRECISE GXP-47 A. Overview and Intended Clinical Use OncoPrecise GXP-47 is a laboratory-developed test ("LDT") performed exclusively at GDT's CLIA-certified reference laboratory in San Diego, California. The test utilizes a proprietary 47-gene RNA expression panel to analyze RNA extracted from formalin-fixed, paraffin-embedded ("FFPE") non-small-cell lung cancer ("NSCLC") tumor tissue spec

IV. CODING AND BILLING INFORMATION GDT has prepared, and intends to submit (or, as applicable, has submitted), a Proprietary Laboratory Analyses ("PLA") code application to the American Medical Association ("AMA") CPT Editorial Panel for OncoPrecise GXP-47. PLA codes are unique, test-specific codes assigned to laboratory-developed tests and are the appropriate coding mechanism for novel molecular diagnostic assays su

V. ANALYTICAL VALIDATION Analytical validation of OncoPrecise GXP-47 was completed on December 14, 2022, at GDT's CLIA-certified, CAP-accredited San Diego reference laboratory. The analytical validation study was designed and conducted in accordance with applicable CLIA regulations (42 C.F.R. Part 493), CAP accreditation standards, and the MolDx program's evidentiary requirements for analytical validity. The results

VI. CLINICAL VALIDATION A. The CLARITY-LUNG Trial The primary clinical validation evidence supporting OncoPrecise GXP-47 is derived from the CLARITY-LUNG trial, a prospective, multi-site, blinded clinical validation study registered on ClinicalTrials.gov under the identifier NCT05891247. The CLARITY-LUNG trial was designed to evaluate the clinical validity of the OncoPrecise GXP-47 TRI score as a predictor of respons

VII. CLINICAL UTILITY OncoPrecise GXP-47 provides actionable, clinically meaningful information that directly impacts treatment decisions in patients with Stage IIIB or Stage IV NSCLC. The clinical utility of the test is grounded in its ability to inform the critical treatment selection decision that oncologists and patients face at the time of first-line therapy initiation: whether to pursue ICI-based therapy or pla

VIII. HEALTH ECONOMIC ANALYSIS A comprehensive cost-effectiveness and budget impact analysis for OncoPrecise GXP-47 has been prepared by Larkfield Health Economics, LLC, under the direction of Dr. Nathan Ostroff, PhD, MS. The HEOR analysis is included in the MolDx Technical Assessment Dossier (Section 5). The HEOR analysis demonstrates that the use of OncoPrecise GXP-47 to guide immune checkpoint inhibitor therapy se

IX. REIMBURSEMENT RATE CONSIDERATIONS GDT has conducted a crosswalk analysis comparing OncoPrecise GXP-47 to comparable multi-gene, NGS-based oncology diagnostic panels in order to support appropriate Medicare reimbursement rate setting for the test. The crosswalk analysis identified the following primary comparator tests and associated Medicare reimbursement rates: Based on this crosswalk analysis, GDT respectfully

X. ACCOMPANYING MOLDX TECHNICAL ASSESSMENT DOSSIER GDT encloses the MolDx Technical Assessment Dossier for OncoPrecise GXP-47 (Version 1.0) for review by RAS under the MolDx program. The Dossier has been prepared in accordance with the MolDx program's published requirements and guidance for Technical Assessment submissions and contains comprehensive documentation supporting the analytical validity, clinical validity,

1. Test Description and Intended Use — Detailed description of OncoPrecise GXP-47, including the 47-gene panel composition, testing methodology, intended clinical use, and target patient population.

2. Analytical Validation Data — Complete analytical validation study report, including study design, methods, results, and statistical analyses, demonstrating the accuracy, precision, reproducibility, analytical sensitivity, and analytical specificity of the test.

3. Clinical Validation Data — Clinical validation evidence from the CLARITY-LUNG trial (ClinicalTrials.gov Identifier: NCT05891247), including the trial protocol, interim analysis results, and available clinical outcome data, as well as results from prior retrospective studies and sub-group analyses.

4. Clinical Utility Evidence — Evidence demonstrating that OncoPrecise GXP-47 provides actionable information that changes clinical management in a manner that benefits patients, including data on treatment decision impact and patient outcome improvements.

5. Health Economic Analysis — Cost-effectiveness and budget impact analysis prepared by Larkfield Health Economics, LLC, demonstrating net cost savings to the Medicare program associated with use of OncoPrecise GXP-47 to guide ICI therapy selection.

6. Annotated Bibliography — Annotated bibliography of forty-three (43) peer-reviewed publications supporting the scientific and clinical evidence base for OncoPrecise GXP-47. GDT respectfully requests that CFI forward the enclosed Dossier to Dr. Catherine Embry, MolDx Technical Assessment Director, at Ridgeline Administrative Services, LLC (1600 Hampton Street, Suite 700, Columbia, SC 29201), for technical assessment

XI. REGULATORY AND LABORATORY ACCREDITATION INFORMATION GDT's San Diego reference laboratory is fully certified and accredited under all applicable federal and state clinical laboratory regulatory programs. A summary of GDT's laboratory credentials is provided below: GDT's laboratory is in full compliance with all applicable federal and state clinical laboratory regulations, including the Clinical Laboratory Improvem

XII. GDT'S EXISTING MEDICARE COVERAGE HISTORY GDT has a demonstrated and successful history of engagement with the LCD and MolDx processes. GDT's existing commercial test, OncoPrecise GXP-12 — a 12-gene RNA expression panel for early-stage breast cancer prognosis — has been covered under LCD L38472 since August 15, 2021. LCD L38472 was issued by CFI following a thorough review of GDT's analytical validation, clinical

XIII. CONTACT INFORMATION AND AVAILABILITY GDT designates the following individuals as contacts for all inquiries related to this LCD request: Primary Contact — LCD and Reimbursement Inquiries: Kevin Driscoll Vice President of Market Access & Reimbursement Genome Dx Therapeutics Inc. 4720 Torrey Pines Road, Suite 300 San Diego, CA 92130 Telephone: [___] Email: [___] Regulatory and Legal Contact: Theresa Nakamura Gene

XIV. CONCLUSION AND REQUEST GDT respectfully requests that Cascade Fiscal Intermediaries, LLC take the following actions in response to this submission:

1. Accept this letter and the accompanying MolDx Technical Assessment Dossier (Version 1.0) as a formal request for the initiation of a local coverage determination proceeding for OncoPrecise GXP-47 under the MolDx program;

2. Coordinate with Ridgeline Administrative Services, LLC for the MolDx Technical Assessment review of OncoPrecise GXP-47, including by forwarding the enclosed MolDx Technical Assessment Dossier to Dr. Catherine Embry, MolDx Technical Assessment Director, at RAS, or by advising GDT to submit the Dossier directly to RAS; and

3. Issue a proposed LCD for public comment in due course, with a determination that OncoPrecise GXP-47 is medically reasonable and necessary for use in the identified patient population — specifically, patients with newly diagnosed Stage IIIB or Stage IV NSCLC who are candidates for first-line systemic therapy — and that the test should be covered by the Medicare program under the terms and conditions to be set forth