Our third quarter earnings call agenda is shown on the next slide. In the third quarter, we reported $12.9 million in net revenue, underscoring the strong value proposition of PYRUKYND. With continued momentum across our commercial portfolio and pipeline, our team has demonstrated strong execution and agility, keeping us firmly focused on our mission to deliver transformative medicines for patients. Please move to the next slide and I'll turn the call over to Cecilia to provide commentary on our third quarter performance and full year outlook.

Third quarter net revenue growth reflects continued commercial execution in PKD ahead of potential U.S. R&D expenses were $86.8 million, an increase of $14.3 million compared to the third quarter of 2024. This increase was primarily driven by increased clinical trial costs associated with our PK activation franchise. SG&A expenses were $41.3 million in the third quarter, an increase of $2.7 million compared to the prior year, driven by disciplined investment.

Our capital allocation strategy, backed by a strong balance sheet, enables strategic investment in future growth and delivery of our ongoing pipeline programs. First, we have built a capital-efficient global commercial model, prioritizing our investment in potential U.S. We have executed partnerships with NewBridge Pharmaceuticals in the GCC and Avanzanite Bioscience in Europe, both of which are structured as revenue-sharing arrangements that favor Agios. Over the long term, we will record our share of sales as net revenues.

What went well
  • PYRUKYND Q3 net revenue of $12.9M, up 44% year-over-year and 3% sequentially, driven by continued PKD commercial execution
  • First global thalassemia approval secured with Saudi Arabia SFDA clearance in August; launch activities underway via partner NewBridge
  • Positive CHMP opinion in Europe recommending PYRUKYND for adult thalassemia, with an EC decision expected early 2026
  • Completed enrollment in the phase II-B trial of tebapivat in lower-risk MDS, with top-line data expected early 2026
  • Strong balance sheet of ~$1.3B in cash and investments funding U.S. launches and pipeline advancement
  • 262 cumulative patients completed prescription enrollment forms and 149 patients on therapy, up 5% sequentially
What went wrong
  • FDA requested a REMS program (tied to hepatocellular injury risk), extending the thalassemia PDUFA date 3 months to December 7th
  • Revenue growth acknowledged to be off a relatively small base
  • European commercialization delayed by 12-18 month country-level pricing and reimbursement processes, so no immediate revenue impact after EC approval
  • Saudi Arabia access is a slow, burdensome case-by-case process taking months per patient and ~2 years to a national procurement agreement
  • R&D expense rose $14.3M year-over-year on increased PK activation clinical trial costs

Guidance Changes

MetricPeriodCurrent guidance
PYRUKYND thalassemia PDUFA date2025extended to December 7, 2025 following FDA REMS request
Full-year 2025 net revenueFY2025robust growth vs 2024, on a relatively small revenue base; Q4 to benefit from an additional ordering week
RISE UP phase III sickle cell top-line results2025reiterated by year end
Tebapivat phase II-B lower-risk MDS top-line dataearly 2026reiterated early 2026 following enrollment completion

Performance Breakdown

MetricYoYNote
PYRUKYND net revenue +44% ($12.9M vs $9.0M) continued commercial execution in PKD ahead of potential U.S. thalassemia approval; also +3% sequentially vs $12.5M in Q2 2025
R&D expense +$14.3M ($86.8M) primarily increased clinical trial costs associated with the PK activation franchise
SG&A expense +$2.7M ($41.3M) disciplined investment ahead of the potential PYRUKYND thalassemia commercial launch
Cost of sales $1.7M for the quarter
Cash, cash equivalents and marketable securities ended Q3 at approximately $1.3B, supporting U.S. launches and pipeline
Patients on therapy 149 patients on therapy, up 5% sequentially; 262 cumulative prescription enrollment forms with 14 added in Q3 (+6%)

Earnings Call Themes & Trends

TopicPrevious mentionCurrent periodTrend
Thalassemia launch readiness under REMSOriginal PDUFA date without a REMS requirementPDUFA extended to Dec 7; management uses added time for community engagement and asserts REMS is not viewed as a barrier to prescribing
Global commercialization modelU.S.-centric launch focuscapital-efficient ex-U.S. partnerships (NewBridge in GCC, Avanzanite in Europe) via revenue-sharing arrangements favoring Agios, preserving capital for U.S. launches
Sickle cell disease opportunityRISE UP phase III enrolling/ongoingtop-line results expected by year end; positioned as potential first-in-class oral therapy targeting hemolysis and vaso-occlusion
Pipeline diversification / business developmentOrganic pipeline focusactively and opportunistically pursuing internal and external assets, not tied to any specific catalyst or the sickle cell readout
Tebapivat in lower-risk MDSPhase II-B enrollingenrollment complete; positioned as potential first oral therapy for anemia due to ineffective erythropoiesis, data early 2026

Q&A Summary

Cantor: Any better sense of the type of REMS program the FDA wants for thalassemia, and what BD makes sense at this stage - would you wait for the sickle cell readout to transact?
Management does not comment on REMS/label details but expects it to include monitoring and some form of education given the hepatocellular injury basis. BD pursuit is not tied to any specific catalyst; focus is rare diseases with transformative/best-in-class potential, sourced internally or externally.
Bank of America: What liver monitoring is required in Saudi Arabia and potentially Europe, could it change with the U.S. label, and how does monitoring affect the commercial approach?
Saudi label aligns with the proposed once-monthly monitoring for the first 6 months; EU label finalizes only at EC decision; U.S. review ongoing. Management remains convicted in the benefit-risk profile and does not anticipate REMS being a barrier to prescribing given physician familiarity with REMS.
Analyst: How should we think about tebapivat's potential in lower-risk MDS, and the Avanzanite and NewBridge partnerships?
Large unmet need in lower-risk MDS with quality-of-life-focused goals suited to PK activators; more data early next year. Europe (Avanzanite) faces a 12-18 month pricing/reimbursement process post-approval; Saudi (NewBridge) starts with case-by-case individual patient requests, reaching a national procurement agreement in ~2 years.
TD Cowen: Have any additional liver events been observed with longer follow-up across the PKR trials, and are they consistent with the prior pattern? Any early demand in the Gulf?
No change to the safety profile; nothing observed warrants updating the hepatocellular injury risk as currently understood. Early interest in Saudi Arabia is high with physicians wanting to try it in individual patients, but the approval/budget process is burdensome and slow.
JPMorgan: Has the last patient exited RISE UP yet, and what are the steps/timing to top-line?
Management will not comment on individual patient status but reiterated it is on track to deliver top-line data by year end, describing the team as a well-oiled machine from database lock to top-line.
JPMorgan follow-up: Can you say whether top-line will be before or after the PDUFA date?
Management declined to be more specific, reiterating only that RISE UP top-line will come by year end.
Goldman Sachs: Will the REMS requirements apply across the label to PKD and sickle cell, and any physician feedback on uptake impact in sickle cell?
The REMS request is specific to thalassemia; for sickle cell the most important next step is the RISE UP phase III data, after which the benefit-risk profile will guide any requirements.

More on Agios Pharmaceuticals, Inc.

Reported 2025-10-30 · figures from the Agios Pharmaceuticals, Inc. Q3 2025 earnings call.

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