Third, through the advancement of our early-stage pipeline with AG-236 and AG-181, we have the potential to unlock future value in hematologic and other rare diseases. And finally, we remain committed to long-term sustainability, supported by disciplined capital allocation and continued operational efficiency. Building on those priorities, the next slide maps key pipeline catalysts in 2026 across multiple high-value indication opportunities. These milestones and continued progress in our early-stage pipeline position the portfolio for growth and long-term value creation.

We exited 2025 with solid momentum across the business, commercial execution, pipeline progress, and continued focus on financial discipline, which together provide a strong foundation to deliver on our 2026 strategic priorities. Starting with commercial performance, PYRUKYND delivered $20 million in net revenue in the fourth quarter, bringing full-year 2025 revenue to $54 million, reflecting robust year-on-year growth. launch, pursue the path forward for mitapivat in sickle cell disease, and continue to advance our pipeline programs. Please move to the next slide, and I'll turn the call over to Cecilia to provide additional details on our 2025 fourth quarter and full year performance, as well as our 2026 outlook.

R&D expenses were $88.1 million, an increase of $5.3 million compared to the fourth quarter of 2024, associated with the advancement of our earlier-stage pipeline program. As a reminder, in future quarters, we will report mitapivat revenue as a whole, breaking out U.S. This guidance assumes investment to maximize launch of ACTIVASE in thalassemia in the U.S., gated investment for sickle cell disease, and operating model refinement. Fourth quarter ex-US revenue was roughly $4 million, which primarily reflects supply ahead of demand pull-through, as PK deficiency patients in Europe transition onto commercial supply.

What went well
  • Q4 worldwide PYRUKYND revenue of $20M, up 86% year-over-year and up 55% sequentially from $13M in Q3, bringing full-year 2025 revenue to $54M
  • Received FDA approval of ACTIVASE for alpha and beta thalassemia (regardless of transfusion burden) on December 23, 2025, with the U.S. launch now underway
  • 44 prescriptions written by REMS-certified physicians in the first five weeks (through January 30), with healthy breadth, strong geographic distribution, and no payer hurdles seen so far
  • Completed enrollment in the phase II sickle cell disease trial of tebapivat, with faster-than-expected enrollment reflecting community enthusiasm after RISE UP data
  • Ended the year with approximately $1.2B in cash, cash equivalents, and marketable securities, providing flexibility to fund the launch and pipeline
What went wrong
  • Revenue lags demand early in the launch because it takes an average of 10-12 weeks to convert a prescription to treatment initiation (insurance authorization plus baseline liver test)
  • Ex-U.S. revenue of $4M reflected one-time European inventory stocking ahead of demand, and a sequential decline into Q1 2026 is expected
  • R&D expense rose to $88.1M in Q4, up $5.3M year-over-year on advancement of earlier-stage pipeline programs
  • GCC (Saudi Arabia) sales remain on a named-patient, case-by-case basis with broad access still 12-18 months away
  • No approval timeline yet for mitapivat in sickle cell disease; company has only guided to a pre-sNDA meeting in Q1 2026

Guidance Changes

MetricPeriodCurrent guidance
U.S. PK deficiency revenueFY2026$45-$50 million
Operating expensesFY2026roughly flat with 2025
Ex-U.S. revenueQ1 2026sequential decline expected
Thalassemia gross-to-netFY202610%-20%, similar to PK deficiency
Prescription-to-treatment-initiation timeearly launch quartersaverage 10-12 weeks, expected to shorten as launch progresses

Performance Breakdown

MetricYoYNote
Worldwide PYRUKYND revenue +86% Continued PK deficiency demand ahead of ACTIVASE approval, an additional ordering week in Q4, and favorable gross-to-net adjustments
R&D expense +$5.3M Advancement of earlier-stage pipeline programs
SG&A expense roughly flat $51.6M in Q4, roughly flat year-over-year

Earnings Call Themes & Trends

TopicPrevious mentionCurrent periodTrend
ACTIVASE thalassemia U.S. launchPre-launch planning ahead of FDA approvalLaunch underway with 44 early prescriptions, community-physician-led prescribing, and no REMS barrier observed—
Mitapivat in sickle cell diseaseReported RISE UP phase III top-line data in Q4Pre-sNDA meeting planned for Q1 2026 to define the regulatory path, targeting full approval—
Tebapivat pipelineTwo phase II trials ongoingLower-risk MDS phase 2b top-line data expected H1 2026; sickle cell disease enrollment complete with top-line data expected H2 2026—
Path to profitabilityGoal of becoming a sustainable rare disease companyClear path to profitability through existing thalassemia and PK deficiency franchises, supported by disciplined OpEx management—
Ex-U.S. commercializationGlobal managed access program providing PYRUKYND free of chargeTransition to commercial supply via Advanz (Europe) and NewBridge (GCC); potential EC decision in coming months after Oct 2025 CHMP opinion—

Q&A Summary

Truist: How will early prescriptions translate into treatment initiation and revenue recognition in the coming quarters?
Prescriptions and demand will grow ahead of revenue because conversion takes 10-12 weeks; most Q1 prescriptions should turn into treatment initiations, and demand and revenue will track more closely as the year progresses. Filspari, another product with a liver REMS, is cited as a useful analog for the revenue curve shape.
Truist: What do you want to see from the phase II tebapivat sickle cell data to get excited?
It is a dose-finding, standalone 12-week trial reading out hemoglobin response, with VOCs as safety assessments. The company can leverage RISE UP data across the PK activation franchise to model clinical benefit, and views the faster enrollment as a sign of community enthusiasm.
Citi: What is the script cadence since approval, and what outcomes could come from the pre-sNDA meeting?
The company is holding to the disclosed 44 prescriptions; early demand is encouraging and playing out as expected across transfusion-dependent and engaged non-transfusion-dependent patients. The pre-sNDA meeting aims to gain insight into the regulatory pathway, going in with a package supporting full approval based on the strong anti-hemolytic RISE UP profile.
Bank of America: What is the main bottleneck in the 10-12 week prescription-to-initiation window, and can you see activity at the 10mg tebapivat MDS dose?
The bottleneck is insurance prior authorization (about a month on average) plus the required pre-treatment liver test; formulary placement and testing efficiencies should shorten it over time. The MDS phase 2b tests 10mg, 15mg, and 20mg doses to identify the best dose and characterize response across transfusion-burden and later-line subgroups.
TD Cowen: Where are REMS-certified physician numbers and their trajectory, and is accelerated approval still on the table for sickle cell?
Large academic centers certified first while community physicians certify almost simultaneously with their first prescription; REMS is not a barrier and certification can take one visit. On sickle cell, the package supports full approval, but the FDA's ASH comments that hemoglobin can be a surrogate endpoint keep accelerated approval as a viable path, with several confirmatory-trial options available.
Cantor: What is the breakeven revenue and timeline for profitability, and were there any GCC sales in Q4?
Profitability is expected from PKD and thalassemia regardless of the sickle cell path, but no specific breakeven level or timing was given; it also requires proactive OpEx management across pipeline catalysts. Q4 ex-U.S. revenue was mostly Europe; GCC remains a named-patient basis with broader access expected over 12-18 months.
HC Wainwright: Are early ACTIVASE prescribers new to the drug, and could sickle cell be approved in 2026?
Early prescribers are largely community hematologists the company had already engaged, with little overlap with the ultra-rare PK deficiency prescriber base. No sickle cell approval date has been guided beyond the Q1 pre-sNDA meeting, and sickle cell commercial build-out remains gated until data supports it.
Goldman Sachs: What is the transfusion-dependent vs. non-transfusion-dependent split among the 44 scripts, and will IQVIA capture scripts?
Early prescriptions are largely transfusion-dependent plus engaged symptomatic non-transfusion-dependent patients, with non-transfusion-dependent expected to drive later scale-up. Because a single specialty pharmacy distributes the product, IQVIA will not capture scripts, so the company will report prescriptions and revenue directly.
JP Morgan: What are the initial payer dynamics and payer mix, and how does SG&A change if sickle cell is approved?
Payer mix is majority commercial, similar to PK deficiency, with early access via medical exceptions until formulary placement in about 6-9 months; no payer hurdles seen and gross-to-net assumed at 10%-20%. Sickle cell would leverage the existing PKD/thalassemia infrastructure but require scaling up given the much larger patient population.
RBC: Why dose higher in lower-risk MDS than in sickle cell, and is there read-through from the thalassemia REMS to sickle cell?
MDS patients metabolize tebapivat faster than healthy volunteers, so doses were pushed to 10/15/20mg, whereas sickle cell patients metabolize like healthy volunteers. The sickle cell profile resembles PK deficiency (no REMS expected), giving optionality; if a REMS were required, the thalassemia REMS execution provides a solid commercial foundation.

More on Agios Pharmaceuticals, Inc.

Reported 2026-02-12 · figures from the Agios Pharmaceuticals, Inc. Q4 2025 earnings call.

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