OPKO Health’s 2025 Q4 Earnings Call: MDX2001 Trial Timelines, 4Kscore Growth Drivers, and GLP-1 Roadmap Shifts Spark Contradictions

Date of Call: Feb 26, 2026

Financials Results

• Revenue: $148.5M in Q4 2025, compared to $183.6M in Q4 2024 (down approximately 19% YOY).
• EPS: Net loss of $0.04 per share in Q4 2025, compared to net income of $0.01 per diluted share in Q4 2024.
• Operating Margin: Consolidated operating loss of $38.3M in Q4 2025, compared to $33.1M loss in Q4 2024. BioReference operating loss improved from $21.7M to $18.3M YOY.

Guidance:

• Q1 2026 total revenue expected between $125M and $140M, with $71M-$75M from services and $38M-$45M from pharmaceutical products.
• Full-year 2026 total revenue expected between $530M and $560M.
• Full-year 2026 R&D investment expected between $125M and $135M, offset by $22M-$26M in BARDA funding and Regeneron collaboration reimbursements.
• Depreciation and amortization expense expected to be approximately $100M in 2026.
• Expect to accelerate share repurchases, with $113M remaining under authorization.

Business Commentary:

Diagnostics Business Restructuring and Profitability:

• BioReference's Q4 2025 revenue was $71.1 million, down from $103.1 million in Q4 2024, primarily due to the sale of oncology assets to Labcorp.
• The company achieved a reduced operating loss of $18.3 million in Q4 2025 compared to $21.7 million in Q4 2024, attributed to cost reduction initiatives and a more focused geographic footprint.

Pharmaceutical Revenue and Partnerships:

• The Pharmaceutical segment reported Q4 2025 revenue of $77.4 million, with product sales increasing to $43.7 million, up from $37.4 million.
• Revenue growth was supported by the international expansion of Rayaldee and increased gross profit share from Pfizer's NGENLA, reflecting global commercialization progress.

ModeX Pipeline and Strategic Collaborations:

• OPKO's ModeX platform advanced with multiple clinical-stage programs, including partnerships with Merck and Regeneron.
• The collaboration with Regeneron could yield milestones exceeding $1 billion, highlighting strategic moves to leverage antibody discovery capabilities for metabolism, oncology, and immunology targets.

Share Repurchase and Cash Management:

• OPKO repurchased $109 million in common shares and convertible notes in 2025, with $113 million remaining under the buyback authorization.
• The strong cash position of $369 million allowed for significant capital allocation to R&D and shareholder returns, supported by asset sales and partnership payments.

Sentiment Analysis:

Overall Tone: Positive

• Dr. Frost stated the company 'exited 2025 with tremendous momentum' and has 'multiple value-creating catalysts for 2026 and beyond.' Management highlighted 'transformative' progress at BioReference, a 'clear path to modest revenue growth and improving margins' in 2026, and 'encouraging' clinical data, expressing confidence in advancing the pipeline and returning capital to shareholders.

Q&A:

• Question from James Stamos (Jefferies): Can you discuss the timing of a potential data disclosure for MDX2001 and expectations for efficacy evaluable patients? Should we think of disclosures as first half or second half events?
  Response: Management expects to announce Phase Ia trial results at an upcoming conference, with Phase Ib expansion starting soon, and results to be shared by the end of 2026.

• Question from James Stamos (Jefferies): Can you provide more color on the key drivers of the increase in NGENLA profit share and assumptions underpinning the 2026 guidance?
  Response: The profit share increase was driven by regional tiering advancements and Pfizer gaining market share globally; the 2026 guidance assumes current growth rates, with potential for acceleration.

• Question from Lut Ming Cheng (J.P. Morgan): Can you give more color on the 6% growth in 4Kscore and the stability of this growth trajectory, especially in the primary care setting?
  Response: Growth has been driven by urology, not primary care yet; management expects high-single to low-double-digit growth into 2026, with potential acceleration as payer coverage expands in primary care.

• Question from Lut Ming Cheng (J.P. Morgan): What specific studies will move the Merck EBV vaccine into Phase II, and what is the timing?
  Response: Ongoing studies focus on EBV-naive (seronegative) patients and potentially lowering the age inclusion to 12; data expected by year-end to inform Phase II, which is targeted to start next year.

• Question from Yale Jen (Laidlaw & Co.): Do you anticipate Merck to provide the first data readout for the EBV vaccine, and has Merck made the final go/no-go decision?
  Response: Management stated it is a decision for Merck to make and announce; they are encouraged by the data but want to ensure seamless progression to Phase II.

• Question from Yale Jen (Laidlaw & Co.): Can you reveal information on the GLP-1/glucagon combo asset (oxyntomodulin) with Entera and its current status?
  Response: The asset is in late stages of IND submission; the oral formulation is being pursued based on promising December results, with injectable Phase I pending IND clearance.

• Question from Edward Tenthoff (Piper Sandler): Can you elaborate on the in vivo CAR-T technology and how the construct is delivered to express CARs on specific cells?
  Response: The platform uses lipid nanoparticles conjugated with targeting antibodies to deliver mRNA/DNA cargo, enabling versatile targeting of T, B, or NK cells, and supports both mono and multispecific CAR-T development.

• Question from Edward Tenthoff (Piper Sandler): How do you envision developing MDX2004, the immune rejuvenator, given its broad utility?
  Response: Development focuses on cancer patients with exhausted immune systems, testing in both PD-1 naive and previously exposed patients to rejuvenate immune response; Phase Ia ongoing with 8 patients dosed.

• Question from Eduardo Martinez-Montes (H.C. Wainwright & Co.): Can you repeat the specific clinical milestones for MDX2001 and MDX2004 in 2026?
  Response: MDX2001: completion of dose regimen and entry into Phase Ib. MDX2004: completion of Phase Ia to determine optimal dose within the year.

• Question from Eduardo Martinez-Montes (H.C. Wainwright & Co.): Can you add more color on the expense bridge for BioReference margins, given the total expense guidance seems high post-divestiture?
  Response: Expense expansion is driven by R&D investments; BioReference operating expenses should decline or remain stable as efficiency improvements take hold.

Contradiction Point 1

MDX2001 Clinical Trial Progression and Data Disclosure

Contradiction on trial status and data availability timeline.

James Stamos (Jefferies) - James Stamos (Jefferies)

20260227-2025 Q4: They have seen signs of efficacy in the 25 patients dosed, but formal results are pending. They plan to announce Phase Ia results at an upcoming conference and advance to Phase Ib for the most promising tumor types, with results potentially available by the end of 2026. - Elias Zerhouni(President & Vice Chairman)

Can you discuss the timing of data disclosure for MDX2001, including the proportion of evaluable patients for efficacy, plans to advance to the sixth dose level, and whether disclosures are expected in the first half or second half? - Maurice Raycroft (Jefferies)

2025Q3: No conclusive signals can be shared yet due to the small sample size; assessments will occur in the planned Phase Ib expansion cohorts. - Gary Nabel(CIO) and Phillip Frost(CEO)

Contradiction Point 2

Growth Drivers for the 4Kscore Test

Contradiction on the primary driver of recent test volume growth.

Lut Ming Cheng (J.P. Morgan) - Lut Ming Cheng (J.P. Morgan)

20260227-2025 Q4: The volume growth is currently driven entirely by the urology field, not primary care, as they are still working with payers to ensure coverage for the primary care setting. - Adam Logal(Senior VP & CFO)

Is the 6% growth in 4Kscore test volume driven by momentum in the primary care setting, and how stable is this growth trajectory? - Maurice Raycroft (Jefferies)

2025Q3: The 20% volume growth is not directly due to the new label, which was implemented in September 2025. Growth accelerated prior to the label change, driven by the existing label. - Elias Zerhouni(President & Vice Chairman) and Adam Logal(Senior VP & CFO)

Contradiction Point 3

4Kscore Test Volume Growth Driver

Contradiction on whether growth is from primary care or urology only.

Lut Ming Cheng (J.P. Morgan) - Lut Ming Cheng (J.P. Morgan)

20260227-2025 Q4: The volume growth is currently driven entirely by the urology field, not primary care... - Adam Logal(CFO)

What is driving the 6% growth in 4Kscore test volume, specifically momentum in the primary care setting, and how stable is this growth trajectory? - Edward Andrew Tenthoff (Piper Sandler)

2025Q2: The new FDA approval allows use without digital rectal exam data, opening up the market to primary care providers, representing a meaningful upside opportunity. - Adam E. Logal(CFO)

Contradiction Point 4

GLP-1/Glucagon (Oxyntomodulin) Asset Development Timeline

Timeline for Phase I trial results shifts from end of 2026 to pending IND clearance.

What are Laidlaw & Co.'s key financial highlights for the quarter? - Yale Jen (Laidlaw & Co.)

20260227-2025 Q4: The injectable formulation is preparing for Phase I trials upon IND clearance. - Elias Zerhouni(CEO)

What is the current status of the GLP-1/glucagon asset in the Entera collaboration? - Yi Chen (H.C. Wainwright)

2025Q1: Phase I results could be available by the end of 2026. - Elias Zerhouni(CEO)

Contradiction Point 5

MDX2001 (TCE) Clinical Development Plan

Plan to advance to Phase Ib changes from after optimal dose determination to potentially beginning in 2026.

James Stamos (Jefferies) - James Stamos (Jefferies)

20260227-2025 Q4: They plan to announce Phase Ia results at an upcoming conference and advance to Phase Ib for the most promising tumor types, with results potentially available by the end of 2026. - Elias Zerhouni(CEO)

Can you discuss the timing of potential data disclosure for MDX2001, the proportion of patients evaluable for efficacy, plans to advance to the sixth dose level, and whether disclosures are expected in the first or second half? - Unknown Analyst (JPMorgan, on behalf of Eric Joseph)

2025Q1: Following this, a Phase Ib basket trial across several solid tumors will begin, potentially narrowing to 1-2 cancers in later stages. - Elias Zerhouni(CEO)