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Date

Feb. 26, 2026

Call participants

  • Chairman and Chief Executive Officer — Phillip Frost
  • Vice Chairman and President — Elias Zerhouni
  • Chief Financial Officer — Adam E. Logal
  • Independent Director and Chief Innovation Officer, MODEX — Gary Nabel

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Takeaways

  • Cash position -- Ended the quarter with $369 million in cash, cash equivalents, and restricted cash, supported by asset sales, BARDA funding, partnership payments, and operating cash from international pharmaceuticals.
  • Share and note repurchases -- Repurchased 34,600,000 shares for $47 million and deployed a total of $109 million into common stock and convertible note buybacks; $113 million remains authorized for repurchases.
  • Diagnostics revenue -- Fiscal fourth quarter Diagnostics segment revenue was $71.1 million, down from $103.1 million, with $7 million attributed to 4Kscore (up over 16% on $6 million last year); post-divestiture retained operations produced around $300 million in annual revenue.
  • Diagnostics costs and expenses -- Total fiscal fourth quarter costs and expenses were $89.4 million, compared to $124.8 million, including $5.8 million in nonrecurring charges related to headcount reduction (about 29% workforce cut, now about 1,400 FTEs) and asset write-offs.
  • Pharmaceutical revenue -- Fiscal fourth quarter pharmaceutical segment revenue was $77.4 million, with product sales rising to $43.7 million (from $37.4 million), aided by foreign exchange and volume growth; RAYALDEE revenue was $8.8 million, reflecting an approximately 17% volume decline but offset by lower rebates.
  • Pfizer gross profit share -- Pfizer gross profit share reached $12.5 million in the fiscal fourth quarter, registering a 30% increase and marking the highest to date, driven by global NGENLA performance and advancement into higher regional profit tiers.
  • Regeneron collaboration revenue -- Recognized $7.2 million in milestone revenue from the Regeneron partnership, with the collaboration holding potential for over $1 billion in milestone payments and up to low- to double-digit royalties.
  • BARDA funding -- Received $6.9 million in fiscal fourth quarter BARDA funding; total cumulative BARDA receipts for COVID-19 and influenza programs stand at $54 million, with BARDA assuming future clinical trial costs.
  • Lilly Mazdutide royalties -- Recorded $4.3 million in royalties from Eli Lilly relating to Mazdutide commercialization in China during the second half of 2025.
  • Operating results -- Fiscal fourth quarter consolidated revenue was $148.5 million, with a consolidated operating loss of $38.3 million and net loss of $31.3 million ($0.04 per share); last year reflected net income of $14 million ($0.01 per share), bolstered by investment gains.
  • 2026 outlook -- Guidance for 2026 includes fiscal first quarter revenue of $125 million to $140 million (services: $71 million–$75 million, pharmaceutical products: $38 million–$45 million, IP/other: $15 million–$20 million), and full-year revenue of $530 million–$560 million (services: $300 million–$312 million, pharmaceuticals: $160 million–$170 million, other/partnering: $70 million–$80 million); Pfizer gross profit share expected at $34 million–$37 million.
  • 2026 cost and R&D expectations -- Projected 2026 total costs and expenses of $725 million–$750 million; full-year R&D spend of $125 million–$135 million, offset by $22 million–$26 million in partnership reimbursement; approximately $100 million in depreciation/amortization expected.
  • BioReference 4Kscore test growth -- Fiscal fourth quarter 4Kscore volume increased more than 6% year over year; label update eliminated digital rectal exam requirement, which is expected to support continued momentum and entry into the primary care market.
  • MODEX pipeline progress -- Three clinical stage programs active (Merck-partnered EBV vaccine, MDX-2001, MDX-2004), with two more set to enter the clinic in coming months; MDX-2001 dosed over 25 patients at up to 10× starting dose, with regimen refinement underway and signs of efficacy observed.
  • Additional pipeline and collaborations -- IND clearance obtained for MDX-2301 (COVID-19 antibody) and regulatory approval for MDX-2003 (B-cell malignancy tetraspecific antibody); in vivo CAR T platform progressing toward late-stage pre-IND and attracting partnering interest.
  • International pharmaceuticals -- Global pharmaceutical sales increased 17%, with continuing positive international operating contributions and initial royalty income from partnerships.

Summary

OPKO Health (OPK +0.00%) is executing a focused transformation, completing its oncology asset divestiture to support BioReference concentration on regional clinical labs and national specialty testing anchored by 4Kscore. Management confirmed robust cash reserves following strategic asset sales and highlighted capital return via significant share and note repurchases. The MODEX therapeutics pipeline delivered key clinical milestones and secured substantial external funding through BARDA, Merck, and Regeneron, with multiple programs advancing toward IND or dose expansion and partnership cash flows expected to continue. Quarterly financials reflect the strategic shift, with post-divestiture revenues and lower operating expenses, while 2026 guidance sets expectations for steady revenue, margin progress, and sustained pipeline investment.

  • The exit from oncology diagnostics allowed BioReference to streamline infrastructure, optimize cost structure, and position the segment for profitability.
  • Adam E. Logal said, "expect to accelerate our repurchases over the short term," referencing the remaining $113 million buyback authorization.
  • Elias Zerhouni emphasized that the Regeneron partnership provides potential milestones exceeding $1 billion and positions OPKO Health for growing recurring collaboration revenues.
  • FDA approval for the revised 4Kscore label is expected to increase payer coverage and expand utility into primary care, which currently remains mostly untapped.
  • R&D investment will rise, offset by reimbursed collaboration funding, maintaining focus on clinical pipeline advancement and incremental international pharmaceutical growth.
  • The Merck EBV vaccine partnership, with Phase 2 trials targeting EBV-seronegative populations, remains on track for data-driven go/no-go decisions in the coming year, with Merck controlling timing and disclosure.
  • BioReference cost structure improved significantly through workforce reductions, with profitability and positive operating cash flow expected in the diagnostics segment for 2026.
  • The global launch of NGENLA by Pfizer drove a step up in profit-sharing revenues, reflecting tier elevation in key markets and expanded share.

Industry glossary

  • 4Kscore: A proprietary blood test evaluating prostate cancer risk based on four kallikrein markers, used to inform clinical decisions on biopsy or further imaging.
  • MODEX: The therapeutics platform of OPKO Health focused on multispecific antibody design spanning oncology, immunology, and vaccines.
  • BARDA: The U.S. Biomedical Advanced Research and Development Authority, which provides non-dilutive grants and reimburses R&D for infectious disease therapeutics.
  • MDX-2001 / MDX-2003 / MDX-2004 / MDX-2301: Designations for clinical-stage antibody therapies from the MODEX pipeline targeted for indications including solid tumors, B-cell malignancies, immune rejuvenation, or infectious diseases, respectively.
  • In vivo CAR T: A platform for delivering chimeric antigen receptor constructs directly into a patient's cells using lipid nanoparticles ex vivo, potentially expanding targetable cell types beyond conventional T cells.
  • Gross-to-net: The difference between gross sales and net recognized revenue after deducting rebates, discounts, and allowances—impacting recognized pharmaceutical revenues.
  • IND: Investigational New Drug application, which, if approved by regulators, clears clinical-stage drug candidates for human trials.

Full Conference Call Transcript

Phillip Frost, Chairman and Chief Executive Officer, will provide opening remarks. Elias Zerhouni, Vice Chairman and President, will then provide an overview of BioReference Health as well as OPKO Health, Inc.'s Therapeutics segment. After that, Adam E. Logal, OPKO Health, Inc.'s CFO, will review the company's fourth quarter financial results and discuss OPKO Health, Inc.'s financial outlook. Then we will open the call to questions. I will now turn the call over to Phillip Frost.

Phillip Frost: Good afternoon and thank you for joining us today. OPKO Health, Inc. exited 2025 with tremendous momentum as we executed on the priorities we laid out earlier in the year. These included positioning our Diagnostics business for a return to profitability, advancing our MODEX pipeline leveraging non-diluting funds from strategic partnerships to offset our R&D budget, and strengthening our balance sheet. We are looking forward to the year ahead as we have multiple value-creating catalysts for 2026 and beyond. In BioReference, 2025 was transformative. With the closing of a second asset sale in September, we completed the sale of our oncology division and related testing services.

This allowed us to focus BioReference on its core clinical laboratory business in the New York and New Jersey region as well as correctional health and our 4Kscore test nationally. This divestiture streamlines our infrastructure and reduces fixed costs while freeing capital to support our broader strategic objectives. BioReference is now positioned to meet our goal of sustained profitable growth in 2026. We believe that our more focused footprint, combined with the accelerating adoption of 4Kscore, gives us a clear path to modest revenue growth and improving margins this year. On the therapeutic side, MODEX continues to be a central component of our long-term strategy.

We now have multiple clinical-stage programs: an EBV vaccine that is partnered with Merck; proprietary multispecific immuno-oncology and immunology candidates, including those intended for immune rejuvenation and for the immune impaired. In 2025, we also began an important collaboration with Regeneron that aligns our deep antibody discovery capabilities with our unique multispecific platform to pursue targets in metabolism, oncology, and immunology. The value of this collaboration potentially exceeds $1 billion in milestones alone. Regeneron is responsible for reimbursing MODEX for its work in creating antibody candidates utilizing MODEX's proprietary platform and for funding all development and commercial efforts for candidates it selects for further development.

From a financial perspective, we entered 2026 with a strong cash position that was bolstered by asset sales, BARDA funding, partnership payments, and positive operating contributions from our international pharmaceutical business. This has allowed us to invest meaningfully in our R&D portfolio while returning capital to shareholders through share repurchases. Last year, we bought back over $100 million and $9 million in common shares and convertible notes. We look forward to the year ahead as we advance the MODEX pipeline with multiple clinical and partnership catalysts and continued focus on operating efficiencies as BioReference returns to profitability. With that overview, I will turn the call over to Elias.

Elias Zerhouni: Thank you, Phil, and good afternoon, everyone. I will start with MODEX. MODEX is now firmly established as a clinical-stage platform company spanning vaccines, oncology, and immunology. We have three programs in the clinic already and two more entering the clinic over the next few months. Our EBV vaccine is partnered with Merck and includes our two antigens in combination with Merck's adjuvants. Merck enrolled over 200 subjects in the Phase 1 trial that is evaluating safety, tolerability, and immunogenicity, enabling further development by Merck. Our lead immuno-oncology candidate, MDX-2001, is a tetraspecific T cell engager directed at two tumor antigens, c-Met and Trop2, and two T cell activators, CD3 and CD28.

This candidate continues to progress through Phase 1 dose escalation in solid tumors. To date, we have dosed more than 25 patients across multiple tumor types and have reached dose levels that are approximately tenfold higher than the starting dose with acceptable safety. We are now refining the final dose and regimen to be used in Phase 1b expansion cohorts, focusing on specific tumor types. MDX-2004 is a first-in-class multispecific immune rejuvenator for advanced cancers. This trispecific molecule simultaneously engages CD3, CD28, and 4-1BB to stimulate T cell activation, proliferation, and persistence, with the goal of restoring the immune system.

By restoring and maintaining T cell activity, this immune rejuvenator may address a broad range of cancers by potentially reversing immune dysfunction associated with chemotherapy, chronic illness, infections, and aging. MDX-2004 entered Phase 1 late last year in Australia and subsequently in Israel. With MDX-2003, we are now developing a tetraspecific antibody that binds CD19 and CD20 on cancerous B cells and CD3 and CD28 on T cells. This is in line with emerging data showing the benefit of targeting both CD19 and CD20 in difficult-to-treat B cell lymphomas and leukemias.

MDX-2003 is designed to maintain efficacy even if one B cell marker is lost or greatly reduced, which is a common way for tumors to escape CD19-only treatments, and to build in CD28 costimulation so that T cells can stay active and able to kill cancer cells longer. We presented a poster at the ASH Annual Meeting in December which described our preclinical findings. We have received regulatory IND approval in Australia and will begin first-in-human trials in a few weeks for cancer. I should note that this tetraspecific antibody also has potential to treat diseases associated with autoimmunity, an indication we are separately considering for entry into the clinic.

A highlight of the fourth quarter, as Phil said, was the announcement of an agreement with Regeneron which brings together their extensive library of clinically validated monoclonal antibody binders and our multispecific engineering platform to pursue four initial programs across metabolism, oncology, and immunology, with the potential to expand beyond the initial targets. During this collaboration, Regeneron will fully fund preclinical and clinical development and commercialization for selected assets, and OPKO Health, Inc. is eligible for research, development, regulatory, and commercial milestones that could exceed $1 billion, as well as up to low- to double-digit royalties on global sales.

Our joint teams are actively working towards nominating lead candidates with the goal of achieving the first milestone as these programs move into formal development. Now turning to infectious diseases in the immune impaired, our BARDA-supported programs for multispecific COVID-19 and influenza antibodies continue to move forward. We recently received IND clearance from the FDA for MDX-2301, our COVID multispecific antibody which is aimed at high-risk immunocompromised populations, and this program is to enter the clinic in 2026. Our influenza program against both Flu A and Flu B is in the pre-IND stage. We are currently evaluating the lead clinical candidates in challenge models to prioritize them for further clinical testing with potential incremental funding from BARDA.

In 2025, we received $28.5 million in non-dilutive funding from BARDA for these two programs and a total of $54 million since inception, and BARDA will assume the cost of the clinical trials. Over the past three years, we have also been building an in vivo CAR T platform that we believe represents the next generation of cellular immunotherapies. Unlike traditional CAR T approaches, our platform uses multispecific antibodies to greatly expand potential applications by targeting a proprietary lipid nanoparticle to any desired cell type and enabling the creation of multispecific chimeric antigen receptors, showing excellent B cell depletion and safety in non-human primate experiments.

We view this flexible and differentiated, unencumbered technology as a unique asset within our portfolio, generating significant interest from potential partners as we enter the late stages of the pre-IND process, hoping to enter the clinic either late this year or in 2027. During the fourth quarter, we continued to advance OPKO-88006, an analog of natural dual GLP-1/glucagon and oxyntomodulin, towards first-in-human phases, and we are in the late stages of the pre-IND work. It is intended to study healthy and presumed metabolic dysfunction associated with steatohepatitis for short NASH participants as both a weekly injectable product and, in partnership with Entera Bio, a once-daily oral formulation, which has been selected based on encouraging oral bioavailability in non-human primates.

In addition, under the collaboration with Entera, we recently announced a program to develop a first-in-class oral long-acting PTH tablet for patients with hypoparathyroidism. This program combines OPKO Health, Inc.'s proprietary long-acting PTH variants with Entera's proprietary N-Tab technology. OPKO Health, Inc. and Entera will each hold a 50% ownership interest in this program and will each be responsible for half of the program's development costs. Given the favorable PK/PD data announced last December, we are accelerating the development timeline of this product and expect to file an IND application with the FDA mid this year. Our international pharmaceutical operations continue to be a source of steady cash flow and operating income.

In 2025, global pharmaceutical product sales grew by 17% versus the prior year quarter, and I will let Adam go through the numbers in more detail. Our partnering strategy continues to provide meaningful cash flow, and we are pleased that our partner, Lilly, has brought Mazdutide to the Chinese market, and we received our first royalty payment in the fourth quarter. Finally, turning to our diagnostic business, in mid-September, we completed the sale of BioReference's oncology assets to Labcorp, transforming BioReference into a streamlined, regionally focused clinical laboratory with a national specialty testing franchise anchored by 4Kscore. We now operate with a more efficient footprint supported by correctional health nationally and also an expanding menu of higher-margin services.

In 2025, the post-transaction remaining operations represented approximately $300 million in revenue. Fourth quarter testing volume in the BioReference business, excluding the divested oncology assets, grew slightly, and we continue to realize the benefits of our cost reduction initiatives, including a workforce reduction of roughly 29% from the previous year to approximately 1,400 FTEs and other targeted operational efficiencies. These efforts have significantly improved our margins and support our expectation that BioReference will deliver positive operating income and cash flow in 2026. Of note, our 4Kscore test remains a key growth driver.

Fourth quarter volume increased more than 6% year over year, and we expect the updated label, which does not require a digital rectal examination anymore, to support continued momentum and entry in the primary care market. In the third quarter last year, FDA approved this lab labeling change to dissociate the elevated PSA from suspicious nodules for the use of the 4Kscore. The intended use population are men ages greater than 45 with age-stratified elevated PSA or men without elevated PSA but a suspicious nodule.

Most of the PSA screenings are performed by primary care physicians, and the age-stratified elevated PSA and the precision of the 4Kscore test results would facilitate precise decisions to further assess the probability of clinically significant prostate cancer before a biopsy or MR imaging decision. We view 4Kscore as an invaluable, differentiated franchise that can generate meaningful revenue and profit as we expand payer coverage and educate both urologists and primary care providers on its clinical utility. Collectively, our diagnostic transformation, our clinical progress across the company, and high-quality partnerships have positioned us as a more focused, therapeutically driven company with multiple near- and mid-term inflection points.

With that, I will turn the call over to Adam to review our financial results and outlook. Adam?

Adam E. Logal: Thank you, Elias. Capital allocation remains our top priority as we ended the quarter with $369 million in cash, cash equivalents, and restricted cash, which is more than sufficient to fund our ongoing operations and development plans, while we also return capital to our shareholders. Our strong cash position allowed us to repurchase 9,800,000 shares during 2025, and for the full year, we repurchased 34,600,000 shares for approximately $47 million. We have approximately $113 million remaining under our buyback authorization and expect to accelerate our repurchases over the short term.

We deployed over $109 million in convertible note and common stock repurchases during 2025 and almost $230 million since the start of 2024, demonstrating our commitment to strengthening our balance sheet and returning capital to our shareholders. Let us turn to the financial performance, starting with our Diagnostics business. Q4 was our first full quarter since closing our second transaction with Labcorp, and we are encouraged by the progress the team has made. Revenue for Q4 2025 was $71.1 million, including $7 million from our 4Kscore test, which grew in revenue by a little more than 16% compared to 2024's $6 million.

Revenue in Q4 2024 was $103.1 million, with the year-over-year decline primarily due to revenue attributable to the Labcorp transaction that closed in September. Revenue from our retained business declined principally due to test mix changes as we shifted some of our unprofitable higher-priced esoteric testing to our strategic partners, which was partially offset by slight volume increases. Total costs and expenses were $89.4 million, down from $124.8 million last year, reflecting the September 2025 Labcorp transaction as well as continued efforts to rationalize our cost structure to align with our focused geographic footprint and testing offerings.

Included in operating expenses were $5.8 million of nonrecurring expenses related to reducing our headcount and asset write-offs as we transition into our new operating footprint. Our Diagnostics operating loss was $18.3 million compared to $21.7 million in Q4 2024, and depreciation and amortization came in at $4.1 million, down from $6 million in 2024. Revenue from our pharmaceutical segment was $77.4 million in Q4 2025 compared to $80.5 million in the prior year. Revenue from product sales increased to $43.7 million, up from $37.4 million, reflecting foreign exchange tailwinds in the 2025 quarter as well as higher sales volumes in our international operations.

As we continue to focus on the profitability of RAYALDEE, the gross-to-net improvements that we have realized in 2025 have resulted in meaningful positive cash flow from operations while maintaining our overall revenue levels. RAYALDEE contributed $8.8 million during Q4 2025 compared to 2024's $9.1 million, reflecting lower government rebates during the 2025 period, partially offset by an approximately 17% decline in volumes. Our Pfizer gross profit share was $12.5 million, reflecting a 30% increase to 2024's $9.6 million. The 2025 figure reflects the highest gross profit share recorded to date and reflects Pfizer's progress on the global commercialization of NGENLA.

During Q4 2025, we recorded $7.2 million of revenue from our new collaboration with Regeneron, while the 2024 period included $12.5 million of milestone payments from Merck for our EBV collaboration. In addition, BARDA funding was $6.9 million compared to 2024's $11 million, reflecting activity levels for infectious disease antibody programs that BARDA supports. The 2024 period included a higher level of CMC activities, while the 2025 period reflected activities in preparation for our upcoming Phase 1 clinical trial for 2301. Finally, 2025 included $4.3 million paid by Eli Lilly for royalties on Mazdutide, which is being commercialized by Innovent in China. This reflects royalties on sales from July to December 2025.

As a result, IP and other revenue was $33.7 million compared to 2024's $43.1 million. Costs and expenses for our pharmaceutical business were $88 million, up from $82.6 million, reflecting our investments in our R&D programs. R&D for Q4 2025 totaled $32.4 million, up from $29.8 million in the 2024 quarter due to our increasing MODEX development activities. As a result, our pharmaceutical operating loss was $10.7 million compared to last year's operating loss of $2.1 million. Depreciation and amortization was $18.3 million, which was consistent with 2024's $18.1 million. Our consolidated financial results include total revenues for Q4 2025 of $148.5 million compared to $183.6 million in 2024.

Our consolidated operating loss for Q4 2025 was $38.3 million compared to $33.1 million in the 2024 period. The 2024 period benefited from the Merck milestone payment, which was approximately $5 million more than 2025's Regeneron milestone payment. Our net loss for Q4 2025 was $31.3 million, or $0.04 per share, compared to net income of $14 million, or $0.01 per diluted share, in Q4 2024, which included the benefit from gains of certain of our underlying investments.

Looking forward to our outlook for 2026, we expect total revenue to be between $125 million and $140 million, with revenue from services of $71 million to $75 million, and this range reflects several of the weather impacts that have already occurred in January and February in the Northeast, which have already impacted our volumes by $3 million to $5 million. We expect pharmaceutical product revenue of between $38 million and $45 million. We expect IP and other revenue to be between $15 million and $20 million, including Pfizer's gross profit share of $5 million to $6 million.

The first quarter reflects the reset of the global revenue base and in prior years has been negatively impacted by gross-to-net adjustments and inventory revaluations that Pfizer records. Total costs and expenses are expected to come in between $170 million to $180 million, excluding any one-time restructuring costs, with our expanding investments in R&D to come in between $30 million to $32 million, partially offset by $7 million to $9 million in collaboration funding, and depreciation and amortization expense of approximately $24 million.

Moving to the outlook for the full year, we expect total revenue of $530 million to $560 million, with revenue from services contributing $300 million to $312 million and pharmaceutical product revenue of $160 million to $170 million, other revenue from our partnering and collaboration agreements of $70 million to $80 million, including Pfizer gross profit share of $34 million to $37 million. Total costs and expenses are expected to be in the range of $725 million to $750 million. Our full-year investment in R&D is expected to be between $125 million and $135 million, offset by $22 million to $26 million in BARDA funding and reimbursement from Regeneron under our collaboration agreements.

Finally, depreciation and amortization expense is expected to be approximately $100 million in 2026. As I mentioned earlier, we have approximately $113 million authorized to repurchase shares of our common stock. We expect to continue to accelerate our repurchase program over the next several days and weeks, continuing to focus on our investments into our R&D programs, with capital being allocated to our repurchase program. That concludes our prepared remarks. Operator, we will now open for questions.

Operator: Thank you. We will now begin the question and answer session. If you are using a speakerphone, please pick up your handset before pressing any keys. Our first question comes from Maurice Raycroft of Jefferies. Please go ahead.

James D Stamos: Hi, it is James on for Maury. Congrats on the progress in the quarter and thanks for taking our questions. I will just start with MDX-2001. Can you discuss the timing of a potential data disclosure and how you are setting expectations, the proportion of patients, the 25 that you have dosed so far, how many of those could be evaluable for efficacy? Also, can you confirm whether you still plan to advance the sixth dose level or whether you are seeing sufficient activity at the fifth dose level to begin backfilling certain dose cohorts? And should we be thinking about this data disclosure as a first half or second half event? Thanks.

Elias Zerhouni: Right. So in terms of the dose, I think we are at the dose that we will proceed. We are adjusting the regimen, how many micrograms per week or every two weeks, we are adjusting that right now. We will not go to a much higher dose level based on the information we have. We have dosed 25 patients, we do see signs of efficacy. It is too early, obviously, to report formally, but we will announce the results of our Phase 1a trial in an upcoming conference and enter Phase 1b for the tumors that show the most promising signs of efficacy. That will probably be advancing so that we will have results that we can share by 2026.

James D Stamos: Thanks. And then just another quick one on NGENLA profit share. So increased to $12.5 million this quarter, consistent with the upward trajectory in weekly prescription trends that we have been seeing. Can you provide more color on the key drivers of the profit share increase? And what are the assumptions underpinning the guidance for profit share of $34 million to $37 million in 2026? Thanks.

Adam E. Logal: Yes, James, thanks. We have seen good continued growth globally for Pfizer. Really what drove the fourth quarter increase was certain regions have moved up in the overall tiering structure. In one of the regions, they actually hit the third tier, so the overall gross profit percentage sharing has been moving up in those regions. We have also seen Pfizer continue to take market share on a global basis and increase it in markets where they have historically been behind. We are pretty pleased with where they have been able to head in the fourth quarter. It came in ahead of where we had expected based on the growth rates that they have been able to deliver.

We see the $34 million to $37 million as being achievable at current growth rates and certainly could accelerate if they have some more wins on a global basis.

James D Stamos: Thanks so much for taking my question. I will hop back in.

Operator: Our next question comes from Brian Chang of JPMorgan. Please go ahead.

Brian Chang: This afternoon, maybe just first on the BioReference side of the business. Can you give a bit more color on the growth that you are seeing, especially in the 4Kscore diagnostic test segment? Is the 6% growth that you saw here driven by particular momentum in the primary care setting, and how should we think about the stability of this growth trajectory, especially in the 4Kscore diagnostic test? And then I have a follow-up. Thank you.

Adam E. Logal: So, Brian, we have not made any meaningful effort yet into the primary care setting. While we have the label change, we are still working with payers to ensure coverage. So the volume increases have all been coming from the work within the urology field. We expect to continue to push that growth upwards and think it can accelerate as we make progress with payers. The overall revenue growth came from improved revenue cycle management and selling into the right payer mix. We have continued to see overall benefits of the 4Kscore and expect that to grow at a high-single-digit, low-double-digit pace into 2026. That could accelerate as we make progress within the primary care setting as payers come along.

Brian Chang: Got it. And just on the Merck partnership for the Epstein-Barr virus vaccine, we noticed that there are additional studies being performed. What are those specific studies that will move this program into the Phase II phase, and any sense of the timing when those studies will be completed?

Elias Zerhouni: I will defer to Gary Nabel, who is the leader of the collaboration with Merck. Gary, can you respond?

Gary Nabel: Yes. I would be happy to give you some more color on that. The studies that are ongoing at the moment are designed to give us a little bit more information on the EBV-naive patients. The initial Phase 1 took all comers and since the rates of seropositivity are so high in the U.S. and throughout the world, and the vaccine ultimately is intended for patients who have never been exposed to the virus, we would like to see a little bit more data on that seronegative population because they will be the subject of Phase 2. The other activity that is ongoing is to see if we can reduce the age of inclusion in the trial.

In the current Phase 1, it was age 18 and older. While we are getting material ready for Phase 2 and beyond, we can now take this opportunity to reduce the age of entry down to 12 years of age. So it is really positioning ourselves for more success and the most relevant formulation to succeed in the prevention studies when they begin.

Elias Zerhouni: Thank you. Did you want to talk about the timing also, Gary?

Gary Nabel: Yes. In terms of the timing, I expect by the end of the year we would have most of the data that we need to make the decisions. I think we are looking at a time frame for Phase 2 that would start next year, not in this current year.

Brian Chang: Got it. Thanks for the color. Thank you.

Operator: Our next question comes from Yale Jen of Laidlaw & Company. Please go ahead.

Yale Jen: Good afternoon and thanks for taking the question. I am just going to follow up on the EBV in terms of the first data readout with the study already completed. Do you anticipate Merck to provide that? And second, has Merck made the final go/no-go decision, and the current study is simply just to supplement, or the go/no-go decision has not yet officially been made? Then I have a follow-up.

Gary Nabel: Yes. The short answer to your question is that it is a decision for Merck to make and to announce. I do not want to get too far ahead of the curve. What I will say is that the data we have seen thus far is encouraging, and at the moment, we really want to just make sure that everything is in place so that when we start Phase 2, Phase 2 goes seamlessly and, beyond that, that we can go straight from Phase 2 to Phase 3 to the launch using the same batches and the same preparations of the vaccine.

We are encouraged, but the final decisions really should be coming from Merck, and I do not want to get ahead of ourselves in that regard.

Yale Jen: Understood. Understood. Appreciate that. Maybe just another question here. In terms of the collaboration with Entera, we noticed that there is also GLP-1/glucagon combo assets you guys seem to have not yet talked much about. Could you review some information on that one and the current status of that one as well? Thanks.

Elias Zerhouni: So the GLP-1/glucagon is what we call oxyntomodulin in our report, and that is the name that is used for that. It is pretty much at the very latest stages of IND submission. In terms of the oral formulation with Entera, we are pursuing that given the results we had in December, which are very promising. In terms of the injectable, we are getting ready to enter Phase 1 once we get the IND cleared.

Yale Jen: Okay. Great. That is very helpful, and congrats on all the progress in the MODEX side.

Operator: Our next question comes from Edward Andrew Tenthoff of Piper Sandler. Please go ahead.

Edward Andrew Tenthoff: Great. Thank you very much and really impressed with so much going on at the company these days and the improvements in the balance sheet to pay for all of these resources. I wanted to ask a little bit about the in vivo CAR T, and it really is an interesting opportunity for the MODEX technology. Can you elaborate a little bit more in terms of how you are delivering the construct so that you can express the CARs on either T cells or other specific cells? Thanks.

Elias Zerhouni: Yes, so what we have developed here is a really unique approach to in vivo CAR T characterized by a few factors. Number one, we found a way to conjugate covalently the targeting antibodies that are on the surface of the lipid nanoparticle. So we are using lipid nanoparticles, which can have a cargo of either mRNA or DNA. Our ability to target with multispecifics allows us to target T cells, B cells, NK cells, so it is a very versatile platform which is very interesting. We have advanced the program in terms of CMC as well as the non-human primate experiments that are really necessary to achieve IND progression.

The characteristics of this in vivo CAR T really are quite fascinating because the possibilities are enormous, because the CAR T receptor itself, chimeric receptor itself, can be actually multispecific as well. As you know, currently they are all monospecifics, but we have been able to achieve both monospecific CAR Ts as well as multispecific CAR T developments. We believe, and others do, and we have had a lot of incoming interest on this platform, that this asset is really something that is, in my view, a large component of the value of MODEX at this time.

Edward Andrew Tenthoff: Yes, very interesting. I appreciate that color. If I may ask one additional question also on MODEX. For 2004, the immune rejuvenator, I am thinking about this almost as like an immunostimulant foreign agent. How do you envision developing it, because it could have very broad utility?

Elias Zerhouni: You are referring to MDX-2004? Is that what you are talking about? Yes. I hear you. Yes, so MDX-2004 is pretty much a rejuvenator of the immune system. As you know, many patients have exhausted immune systems when they start cancer, and they receive multiple treatments, chemo and other immuno-oncology drugs, and what we found is that the need is to really reinforce the immune system in these situations. As you know, PD-1 is a checkpoint inhibitor, so what it does is remove the brake on the immune cells, the T cells in particular, but that does not guarantee that the T cells will be effective, because you remove the brake but the car may not advance.

What MDX-2004 does is an accelerator. It really provides energy, gas, if you will, to rejuvenate the T cells and the stem cells and the memory cells so that the immune system can rev up and continue its fight against cancer cells. In terms of development, we are going into both cancer patients who have been treated in multiple lines and testing whether or not a rejuvenation of the immune system will really reignite the positive anticancer effectiveness of the immune system. In addition, we are doing it in patients who are PD-1 naive and patients who have had PD-1s in the past but where the effects of the PD-1 have basically faded. So that is the first step.

We have a two-arm trial with PD-1 naive and PD-1 previously exposed, and then we are really testing whether or not it is a tolerable molecule that can be administered without too much safety issues and observe whether or not it can prolong or rejuvenate the response, the immune system response. So far we have dosed eight patients and things are going well.

Operator: Our next question comes from Yi Chen of H.C. Wainwright & Co. Please go ahead.

Eduardo Martinez-Montes: Hi. This is Eduardo on for Yi. I was just hoping if I could get you guys to repeat the specific clinical milestones for 2001 and 2004 in 2026, just to have some clarity there.

Elias Zerhouni: Well, so 2001 is pretty straightforward. It is completion of the dose regimen and entry into Phase 1b. That is really what it is. For 2004, we are doing the escalation, the Phase 1 escalation. We passed the first step and we are going into the second, and there are multiple steps that are planned, which is Phase 1a, which we hope to complete within this year, and determine what the optimal dose is for therapy. I will point out the fact that this therapy may be effective in more indications than just tumors, simply because you have many patients who are immunosuppressed for reasons other than or cancer. So Phase 1b for 2001 and the Phase 1b for 2004.

Eduardo Martinez-Montes: Got it. That is really helpful. And then shifting over to the BioReference margin expansion and the expense bridge, I think the guidance said $725 million to $750 million in total expense. Seems a little high following the divestiture. Just wondered if you could add some more color there in terms of the OpEx for the new BioReference.

Adam E. Logal: Sure. We would expect the overall expense base to continue to decline at BioReference as we continue to work the overall operating efficiency upwards and start to work the margin profile up. Really where the expense expansion is coming from is within the R&D efforts, and it is going to be dependent on some of the successes that we have been talking about in other programs and the timing of where they start. That is where the expense expansion is. Everything else from the operating company side we should see stable or reductions.

Eduardo Martinez-Montes: Got it. Thanks so much for the clarity and congrats on the year.

Operator: This concludes our question and answer session. I would like to turn the conference back over to Phillip Frost for any closing remarks.

Phillip Frost: Thank you all for participating and for your good questions. We look forward to meeting with you again after the first quarter to discuss those results. Thank you again and have a good evening.

Operator: This concludes today's conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.