Merck held its Q1 2026 earnings conference call on April 30, 2026, during which the company's pipeline narrative was dominated by three converging signals: a downward revision to efficacy data for its newly acquired chronic myeloid leukemia (CML) asset TERN-701, a mixed set of outcomes from the Welireg (belzutifan) renal cell carcinoma (RCC) program following the failure of LITESPARK-012, and an accelerating regulatory timeline for enlicitide, its oral PCSK9 inhibitor, ahead of a potential second-half 2026 approval.
Key strategic signals
TERN-701 and the hematology bet
The acquisition of Terns Pharmaceuticals (which closed May 5, 2026) and its lead asset TERN-701, an oral allosteric inhibitor of the BCR::ABL oncogene, drew the most pointed analyst scrutiny during the earnings call. Evercore ISI analyst Umer Raffat pressed management on a discrepancy between the major molecular response (MMR) rates presented at public medical congresses and the figures underpinning Merck's acquisition rationale.
Dean Li, Executive Vice President and President of Merck Research Laboratories, acknowledged that the publicly cited 75% MMR rate required recalibration when assessed against a more conservative intent-to-treat population consistent with regulatory standards. The revised estimate, Li said, placed MMR "north of 50%", which management maintained was still within the confidence interval of publicly stated data and remained compelling for a registration-enabling program. Li also flagged deep molecular response (DMR) as a potential secondary treatment goal that could differentiate TERN-701 from existing approved therapies in CML, framing DMR achievement as a field-defining ambition rather than a secondary endpoint.
Welireg program: LITESPARK-012 failure and downstream uncertainty
The Welireg program generated a complex set of signals during the MRK earnings call transcript discussion. The LITESPARK-012 study, evaluating a triple combination of Keytruda (pembrolizumab), Lenvima (lenvatinib), and Welireg in first-line RCC, recently failed its dual primary endpoints of progression-free survival and overall survival. Management said the data provided "learnings to the broader program" but declined to characterize the failure as having direct negative implications for other ongoing LITESPARK studies.
BofA Securities analyst Jason Gerberry pressed Li on whether the LITESPARK-012 outcome introduced read-through risk to LITESPARK-022 and LITESPARK-011, both of which carry near-term PDUFA dates. Li said he was "very bullish" on those outcomes and cautioned against drawing mechanistic equivalence between a three-agent regimen and the two-agent combinations under review. The FDA has set a PDUFA date of June 19 for Welireg in combination with Keytruda in the adjuvant RCC setting based on LITESPARK-022, which demonstrated a 28% reduction in the risk of disease recurrence or death compared to Keytruda alone. A separate PDUFA date of October 4 has been set for Welireg in combination with Lenvima based on LITESPARK-011, which showed a 30% reduction in the risk of disease progression or death versus cabozantinib in certain patients with advanced RCC.
Studies LITESPARK-033 and LITESPARK-034, evaluating Welireg in combination with zanzalintinib, remain ongoing. The overall picture is one of a program with meaningful near-term regulatory upside but a three-drug combination failure that management has not fully explained and analysts have not fully accepted as mechanistically isolated.
Enlicitide: Oral PCSK9 inhibitor advancing to approval
Phase III CORALreef AddOn data for enlicitide, presented at the American College of Cardiology Congress in April, showed statistically significant and clinically meaningful greater reductions in low-density lipoprotein cholesterol at eight weeks compared to other oral add-on lipid-lowering therapies when added to background statin therapy. Enlicitide also met statistically significant reductions across key secondary endpoints including apolipoprotein B and non-high-density lipoprotein cholesterol.
Li described enlicitide as designed to function similarly to injectable PCSK9 antibody therapies but with the accessibility of a daily oral pill, framing the asset as having the potential to "democratize access" to potent lipid-lowering therapy. The compound is advancing through the Commissioner's National Priority Voucher pathway, a regulatory mechanism Li described as analogous to a rolling submission, in which formal acceptance and a PDUFA date are issued at the conclusion of the process rather than at filing. Li said discussions with the US FDA were progressing well and that a second-half 2026 approval remained the working assumption with no current obstacles identified.
TD Cowen analyst Steve Scala asked about titration changes and the specifics of administration timing currently under discussion with the FDA. Li declined to detail the label language under negotiation, noting that those conversations were "extremely active." The administration and titration parameters in the final label will have direct implications for commercial positioning against subcutaneous PCSK9 inhibitors.
Analyst pressure points
TERN-701 efficacy revision: Raffat's question on the MMR data discrepancy was the sharpest exchange of the Merck investor relations earnings call. Management's defense — that a greater than 50% ITT-adjusted MMR remained within the confidence interval of publicly stated data — did not fully resolve the concern that the asset's registration-grade profile is materially lower than initial presentations suggested, and that a pivotal trial design has not yet been disclosed.
LITESPARK-012 read-through risk: Gerberry's question on whether the triple-combination failure introduced risk to the two-agent LITESPARK studies was met with management confidence but without mechanistic data to substantiate the separation. With PDUFA dates in June and October, the market will have clarity on LITESPARK-022 and LITESPARK-011 before year-end, but the LITESPARK-012 failure has introduced a degree of uncertainty that management's verbal reassurances have not eliminated.
Sac-TMT positioning: Merck also used the Q&A to position sac-TMT and PD-1/VEGF combinations as central elements of its next oncology growth wave. Li said Kelun will present data from OptiTROP-Lung05 at ASCO, evaluating sac-TMT plus Keytruda versus Keytruda in PD-L1-positive first-line non-small cell lung cancer, and framed the China study as an important signal-generating readout for Merck’s global TroFuse program. He highlighted TroFuse-007, Merck’s global study of sac-TMT plus Keytruda versus Keytruda in patients with TPS greater than 50%, while also confirming that Merck is actively considering combinations of sac-TMT with PD-1/VEGF bispecifics. The exchange underscored Merck’s effort to build beyond Keytruda through layered oncology combinations spanning ADCs, immunotherapy, and VEGF-directed mechanisms.
Forward-looking catalysts
The most concentrated set of regulatory milestones in Merck's near-term calendar falls in the second half of 2026. The FDA PDUFA date of August 17 covers supplemental biologics license applications for Keytruda and Keytruda Qlex (pembrolizumab subcutaneous formulation) in muscle-invasive bladder cancer based on KEYNOTE-B15, which showed a 47% reduction in the risk of event-free survival events and a 35% reduction in the risk of death for cisplatin-eligible patients. Li described this as the first perioperative immunotherapy plus antibody-drug conjugate regimen to extend survival in this setting.
An October 10 PDUFA date covers ifinatamab deruxtecan (I-DXd), developed in collaboration with Daiichi Sankyo, for previously treated extensive-stage small cell lung cancer (SCLC) based on the Phase II IDeate-Lung01 trial and the Phase I/II IDeate-PanTumor01 trial. I-DXd received FDA priority review, and its approval would represent Merck's first regulatory success in SCLC.
In HIV, Phase III data from the ISLEND-1 and ISLEND-2 trials evaluating a once-weekly oral two-drug regimen of islatravir and lenacapavir, developed in collaboration with Gilead Sciences, are expected to be presented at an upcoming medical meeting. Li described islatravir as capable of anchoring a weekly regimen and framed the once-weekly oral HIV treatment concept as a potential milestone for both commercial and global public health purposes.
In immunology, data from the Phase III ATLAS-UC trial evaluating tulisokibart in ulcerative colitis and Phase II ATHENA data in systemic sclerosis-associated interstitial lung disease are expected in 2026. Li positioned tulisokibart as a potential first-in-class and best-in-class TL1A inhibitor with a profile that could support both standalone use and combination strategies across inflammatory and fibrotic indications. Davis added that Merck's immunology pipeline extends beyond TL1A, with additional undisclosed assets in earlier development expected to enter Phase II in the coming years.
Merck also initiated two pivotal Phase IIb/III trials — MALBEC and TORRONTES — for MK-8748, a bispecific Tie2 agonist and VEGF inhibitor, in neovascular age-related macular degeneration (AMD), with the decision to advance based on results from the Phase I/IIa RIOJA trial. An analyst question on MK-3000, a novel Wnt pathway agonist in Phase III evaluation for diabetic macular edema in the BRUNELLO study, drew a response from Li confirming that dosing frequency beyond every four weeks is under active consideration, though the initial label target remains a four-week interval.
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