PLUS THERAPEUTICS, Inc. Common Stock Investor update

Thank you, Drew. Good morning, and thank you for joining the call today. The goal for the call today is to provide investors in the capital markets with an update specifically around Cerenome's diagnostic division, CNSide. The team has made great progress over the last three quarters, and we have a number of updates, more than we can typically provide on a quarterly earnings call. As a note, we will have our full Q3 earnings call in Q4, but today the focus is on CNSide, and Russ Bradley and Andrew Sims are here with me to provide more detail. One note: you will be able to review our most recent corporate presentation on our website later today. First, though, before we talk about CNSide, I would like to provide some context.

On August 3rd, our new name, Cerenome, and brand became official, but that was really just a public acknowledgment of the two previous years of operating as an integrated CNS oncology company, combining diagnostics, therapeutics, with advanced data analytics, all under one roof. Simply put, the rationale behind the integrated strategy is that CNS cancers represent systems diseases, and therefore an integrated or systems approach is ultimately what is needed to make meaningful progress for these patients. In contrast, if you look back over the past five decades of companies taking traditional, narrowly focused approaches, they have yielded few commercial developments or regulatory wins in both diagnostics and therapeutics. A new approach is desperately needed. There are two multi-decade trends that define the CNS oncology problem and the opportunity. Trend one is the abysmal track record of gains in CNS cancer survivals.

Over the past four decades, the median overall survival for non-CNS cancers has improved nearly fourfold from roughly 35 months in 1980 to approximately 138 months today. In contrast, the median overall survival for patients with CNS cancers stands at about 15 months, and it has barely moved across that same period, despite dramatic advances in imaging and despite the major systemic therapy advances deployed around it. It seems that every oncology revolution of the last 50 years has stopped at the blood-brain barrier. Trend two is the epidemic in CNS cancers. As patients live longer with advanced cancers or metastatic disease, the incidence of CNS metastases is rising. By any definition, metastatic CNS cancer is both an epidemic and an underappreciated one at that. CNS cancers represent the largest underserved market in U.S. oncology. How does one define that market opportunity more specifically?

Of the 18.6 million U.S. cancer survivors across all sites and stages, it's estimated that approximately 2 million Americans are in the central nervous system cancer at-risk pool. Specifically, these are patients with metastatic CNS trophic disease or non-metastatic tumors at elevated risk. Of these, an estimated 600,000 patients per year receive a symptom-triggered or guideline-directed CNS workup. Furthermore, approximately 190,000 patients per year will be diagnosed with parenchymal brain metastases, and an estimated 345,000 patients per year have leptomeningeal metastases, or LM. This epidemiology drives the multi-billion-dollar addressable markets for both CNSide and our lead drug, REYOBIQ. For CNSide specifically, we sized the CNSide diagnostic market opportunity, or TAM, at approximately $2.7 billion for LM alone, with additional approximately $2.8 billion across the broader CNS at-risk workup and brain mets populations.

In our view, this represents a multi-billion-dollar hole in the current U.S. diagnostic market that we recognized when we acquired CNSide, and now, with three quarters of early commercial experience, our conviction around that opportunity hasn't changed. I would now like to invite Russell Bradley, President and General Manager of our CNSide diagnostic division, and Andrew Sims, our Chief Financial Officer, to join in on today's call and take you through the 2026 CNSide progress and provide a look forward for the remainder of 2026 and into 2027.

Russell? Thanks, Marc, and good morning.

This quarter, CNSide began submitting billing claims to payers. For two years, we have been building a reimbursed business in cerebrospinal fluid, or CSF, diagnostics: building clinical evidence, payer contracts, a proprietary reimbursement code, Medicare enrollment, laboratory accreditation, and the billing infrastructure. We are no longer building towards reimbursement; we are billing for it. We set five goals for 2026, and here is where we started: commercial coverage beyond 150 million lives for our TCE test, achieved ahead of schedule at approximately 158 million covered lives. Medicare and Medicaid coverage on track, with Medicare enrollment complete and a published Medicare rate expected to be effective January 1, 2027.

A run-rate of 1,250 total tests per year on track, additional tumor characterization tests on schedule with CNSide CSF Molecular Profile Test planned for October 12 launch, and the first CNSide CSF cellular biomarkers focused on breast cancer will be launched at the Society for Neuro-Oncology annual meeting in November. Fifty or more ordering physicians on track, with 39 physicians ordering today among 43 ordering providers. Let me take you through the details supporting our goal achievements year to date. First, commercial coverage, which we achieved ahead of schedule. We entered 2026 with approximately 67 million covered lives, people whose health plans have contracted to pay for the test, from UnitedHealthcare and Humana. New agreements this year, led by Elevance Health at approximately 45 million, and Service Corporation International at approximately 27 million, took us past our 150 million goal in August.

With Blue Cross Blue Shield of Michigan in September, we now have approximately 158 million covered lives under contract, and we continue to pursue agreements for additional covered lives. When Medicare preliminary pricing for our TCE test takes effect, which is anticipated January 1, 2027, we expect to add approximately 34 million beneficiaries, subject to coverage through Novitas Solutions, our local Medicare contractor in Texas. Medicare and Medicaid coverage, and we are on track. On May 7, we received our Medicare billing number. Our proprietary reimbursement code took effect July 1, and Medicare prices new laboratory test codes through an annual process. The Centers for Medicare & Medicaid Services, or CMS, reviews each new code with input from an independent advisory panel and public comment, then publishes a rate. We expect CMS to publish a preliminary rate for our proprietary reimbursement code effective January 1, 2027.

Coverage for traditional Medicare is a separate decision by Novitas Solutions, our local Medicare contractor in Texas, and that work is underway. Third, testing volume. We are on track to achieve a run-rate of 1,250 total tests per year in 2026. That is approximately 100 tests per month. The first half was access-led by design, limited early access through March, then broader availability from April 1. Our laboratory performed 232 CNSide tests in the first half of 2026. The second quarter volume was up 64% over the first quarter. We expect to close the third quarter at approximately 203 CNSide tests, up about 41% over the second quarter. The fourth quarter is supported by the coverage access now in place, onboarding waitlists, widening ordering breadth, and the offering of additional tumor characterization tests. Our fourth goal is adding tests to the platform, and we are on schedule.

On October 12, we plan to launch the CNSide CSF molecular profile, our DNA and RNA sequencing tests. Today, a spinal fluid specimen arrives at the lab, and we run one test. From that launch, the same specimen can also be sequenced across more than 300 DNA genes and more than 1,600 RNA transcripts to help guide therapy. More high-value clinical tests from the same specimen mean more value to our physician partners for the patients they serve and for CNSide. As the testing menu grows, one specimen can support several tests. For illustration only, the full plan menu, once launched, would carry a combined list price of up to approximately $15,000 per specimen. Of course, list price is not what we expect to be paid. Reimbursement will depend on payer contracts, coverage, and which tests our physician partners order.