Contract analysis

From: Miriam Calloway <mcalloway@calderwoodharkness.com> To: Theresa Nakamura <tnakamura@genomedx.com> Cc: Kevin Driscoll <kdriscoll@genomedx.com> Date: Wed, 10 Apr 2024 10:47:00 -0000 Subject: Re: Board Request to Reassess LCD Filing Strategy — OncoPrecise GXP-47

Matter: Genome Dx Therapeutics Inc. — Medicare Coverage & Coding Strategy (Matter No. 1043-00002)

Thank you for the prompt follow-up after yesterday's board meeting. I appreciate the board communicating its direction so quickly, and I want to confirm that we have received and fully understand the request to reassess the LCD filing strategy for OncoPrecise GXP-47 in light of the CLARITY-LUNG interim analysis results released on March 29. As you may recall, I flagged preliminary concerns about the interim data in m

In response to the board's request, Calderwood & Harkness will prepare two deliverables:

*1. Clinical Evidence Gap Analysis Memorandum*

This memorandum will provide a detailed assessment of the impact of the CLARITY-LUNG interim results on both the LCD application and the MolDx technical assessment dossier. Specifically, we will analyze:

- The shortfall in PPV (0.68 vs. ≥0.75) and NPV (0.71 vs. ≥0.80) and how Cascade Fiscal Intermediaries ("CFI") and Ridgeline Administrative Services (through the MolDx program) are likely to evaluate these results. We have a reasonably well-developed understanding of the analytical frameworks that Dr. William Hargrove at CFI and Dr. Catherine Embry at Ridgeline apply to molecular diagnostic performance data, and this

We will also consider the current CLARITY-LUNG enrollment status — 847 of 1,200 patients, approximately 70.6% enrolled — and whether the remaining enrollment trajectory and extended follow-up timeline affect the strategic calculus.

To complete this analysis, we will need to coordinate with Dr. Priya Sundaram's team on several clinical data questions, and Sean Morrissey will be reaching out to that end. We will also coordinate with Dr. Nathan Ostroff at Larkfield Health Economics regarding any necessary revisions to the HEOR analysis that may be implicated by the interim data shortfalls.

*2. Revised LCD/MolDx Strategy Memorandum*

This memorandum will present a revised strategic recommendation on LCD filing timing, structured around multiple scenarios:

- **Option A:** Proceed with LCD filing on the original August 2024 timeline using interim CLARITY-LUNG data supplemented by retrospective and literature-based evidence. - **Option B:** Defer LCD filing until final CLARITY-LUNG data is available, noting that the revised projection for final data readout has shifted from Q4 2024 to Q2 2025. - **Option C:** Explore intermediate approaches, such as pre-submission engage

For each option, we will address the downstream timeline impacts on the following workstreams:

- *PLA Code Application:* The draft application delivered on March 22 was targeting submission to the AMA CPT Editorial Panel by the June 28, 2024 deadline for consideration at the September 2024 meeting. We will assess whether the PLA application should proceed independently of the LCD decision. While a PLA code assignment does not require clinical validation data, the reimbursement rate and commercial utility of th

I have asked Joel Strauss (copied here) to participate in the revised strategy analysis, particularly on the health technology assessment and FDA/CMS regulatory intersection dimensions. CMS's evolving approach to LDT oversight may have implications that are relevant to the timing decision, and Joel's expertise in this area will strengthen the analysis.

Kevin, I would ask that you coordinate with Janet Carraway at Carraway Regulatory Advisors regarding any impact on the PLA code application mechanics and timeline. We will provide the strategic recommendation on whether and when to proceed with the PLA submission, and Janet can advise on the AMA submission logistics and any procedural considerations on her end. As noted above, the draft PLA code application delivered

- **Clinical Evidence Gap Analysis Memorandum:** Targeted delivery by Monday, April 15, 2024 (approximately 5 business days). - **Revised LCD/MolDx Strategy Memorandum:** Targeted delivery by Monday, April 22, 2024 (approximately 8 business days following the Gap Analysis). We have sequenced these intentionally so that the Gap Analysis conclusions can inform and anchor the strategic recommendations.

Sean Morrissey will be the primary drafter on both deliverables and will be reaching out to Kevin and Dr. Sundaram's team for additional clinical data inputs as needed. Please do let us know the best points of contact and any scheduling constraints on your end.

Would the board like Calderwood & Harkness to prepare a presentation or participate in a follow-up board call to discuss the revised strategy once the memoranda are delivered? We are happy to update the board presentation materials that were prepared for the April 9 meeting and tailor them to the revised analysis. Please let me know your preference, and we will build that into our timeline.

Theresa, I want to assure you and the board that we are committed to providing a thorough and clear-eyed assessment. While the interim data are undeniably a setback, the situation is not uncommon in the molecular diagnostics coverage landscape. We have navigated analogous evidentiary challenges with other clients, and there are well-established pathways to address it — the key is making the right strategic decisions

Please do not hesitate to call me or Kevin if any questions arise in the interim. I am available on my direct line at (202) 555-4180 or on my mobile at (202) 555-7293.

Miriam Calloway Partner, Healthcare & Life Sciences Calderwood & Harkness LLP 1700 K Street NW, Suite 900 Washington, DC 20006 Phone: (202) 555-4100 Direct: (202) 555-4180 Mobile: (202) 555-7293 Email: mcalloway@calderwoodharkness.com

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