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Lilly Doubles Down on In Vivo CAR-T with $7B Kelonia Acquisition
Eli Lilly is acquiring Kelonia Therapeutics for $3.25 billion upfront plus potential milestones totaling $7 billion, announced April 20, 2026, according to Fierce Biotech. This marks Lilly's second in vivo CAR-T acquisition this year, following the $2.4 billion Orna Therapeutics deal in February 2026. Kelonia's lead program KLN-1010, a BCMA-targeting in vivo CAR-T using its proprietary iGPS® (in vivo gene placement system) lentiviral platform, is in Phase 1 (inMMyCAR study) for relapsed/refractory multiple myeloma. At ASH 2025, KLN-1010 demonstrated 100% MRD-negative response rate in four patients maintained through 5-month follow-up, with no grade 3+ CRS or neurotoxicity and no preparative chemotherapy required. Kelonia's BCMA-targeting approach competes directly with Bristol Myers Squibb's Abecma and Johnson & Johnson's Carvykti in multiple myeloma, but promises faster treatment initiation by eliminating ex vivo manufacturing. Lilly solidifies leadership in manufacturing-free CAR-T with $9.4B committed across two deals Traditional CAR-T players face new competitive pressure from streamlined approaches
AACR 2026 Showcases Revolution Medicines KRAS Pipeline and Merck Bispecific Data
At AACR 2026, Revolution Medicines presented updated Phase 1 data for zoldonrasib, its RAS(ON) G12D-selective inhibitor, in previously treated KRAS G12D-mutated NSCLC, showing a 52% objective response rate, 93% disease control rate, and 11.1-month median PFS among 27 evaluable patients, BioPharma Dive reported. Zoldonrasib received FDA Breakthrough Therapy Designation in January 2026 and Revolution plans a registrational trial of zoldonrasib plus daraxonrasib in H2 2026, per a Revolution Medicines press release. Separately, Merck's partner LaNova Medicines (now part of Sino Biopharm) presented first-in-human data for PD-1/VEGF bispecific MK-2010, showing an unconfirmed 55% ORR (6 of 11 previously untreated PD-L1+ NSCLC patients) at 20 mg/kg, per BioPharma Dive. MK-2010 combines checkpoint inhibition with anti-angiogenic activity in a single molecule, potentially offering convenience advantages over Merck's Keytruda plus bevacizumab combinations. Revolution Medicines strengthens KRAS franchise with G12D-selective data complementing daraxonrasib KRAS G12D cancers — previously undruggable — now face multiple targeted approaches
CAR-T Therapy Shows Promise in Smoldering Multiple Myeloma Prevention Strategy
The Phase 2 CAR-PRISM trial from Dana-Farber Cancer Institute presented data at AACR 2026 showing ciltacabtagene autoleucel (Carvykti) achieved 100% MRD negativity in all 20 high-risk smoldering multiple myeloma patients within two months of treatment, maintained after a median 15.3 months of follow-up, with no disease progression or death observed, according to STAT News. This preemptive approach challenges the standard practice of waiting for active disease, given that approximately 50% of high-risk smoldering patients progress to active myeloma within two years. No high-grade side effects were reported, per an AACR press release. The results follow the November 2025 FDA approval of daratumumab (Darzalex Faspro) as the first therapeutic for high-risk SMM, which reduced progression by 51%. The CAR-PRISM approach raises questions about treating asymptomatic patients with intensive cell therapy and faces regulatory hurdles since FDA typically requires active disease for CAR-T approval. Preemptive CAR-T demonstrates unprecedented MRD clearance in smoldering myeloma Watch-and-wait approach in high-risk smoldering myeloma faces challenge from early intervention data
Pipeline Watch
BridgeBio Oncology Therapeutics (BBOT) announced on April 20, 2026, that the FDA granted Fast Track designation to BBO-11818 for adult patients with advanced KRAS-mutant pancreatic ductal adenocarcinoma, according to CancerNetwork. BBO-11818 is a selective, orally bioavailable non-covalent KRAS inhibitor targeting both ON and OFF states with activity against KRAS G12D and G12V mutations and high selectivity over HRAS and NRAS. It is being evaluated in the Phase 1 KONQUER-101 trial in patients with locally advanced unresectable or metastatic KRAS-mutant solid tumors. Preliminary data from January 2026 showed a confirmed partial response in pancreatic cancer with monotherapy and anti-tumor activity across dose levels. Updated Phase 1 data are expected in H2 2026.
New analysis examines how post-progression therapies impact overall survival interpretation for Lilly's RET inhibitor selpercatinib (Retevmo), per Journal of Clinical Oncology. The study addresses the crossover conundrum where control arm patients receive experimental therapy after progression, potentially diluting survival benefits and complicating regulatory assessment of life-extending drugs in RET-altered cancers.
A federal judge rejected Bayer's bid to block Johnson & Johnson's survival claims in prostate cancer marketing, according to Fierce Pharma. The ruling allows J&J to continue promoting survival benefits for its prostate cancer therapy, dealing a blow to Bayer in the competitive prostate cancer market where survival messaging drives treatment decisions.
The National Cancer Institute opened enrollment for EVOLVE CLL/SLL, testing early intervention in high-risk chronic lymphocytic leukemia patients before symptomatic disease, per ClinicalTrials.gov. This prevention-focused approach mirrors trends in multiple myeloma, where treating pre-malignant conditions could reshape treatment paradigms and expand addressable patient populations for leading CLL therapies.
Merck's partner Sino Biopharm (via LaNova Medicines, licensed for $588M upfront in November 2024) presented first-in-human data for PD-1/VEGF bispecific MK-2010 at AACR 2026, with an unconfirmed 55% ORR (6/11 patients) in previously untreated PD-L1+ NSCLC at the 20 mg/kg dose level, per Endpoints News. MK-2010 enters a competitive bispecific landscape where Akeso/Summit's ivonescimab and BioNTech/BMS's pumitamig are significantly further in development.
Merck and Eisai announced on April 21, 2026, that the Phase 3 LITESPARK-012 trial did not meet its dual primary endpoints of overall survival and progression-free survival, per BioSpace. The trial enrolled 1,688 patients with advanced clear cell renal cell carcinoma and tested two experimental arms — Keytruda (pembrolizumab) plus Lenvima (lenvatinib) plus Welireg (belzutifan), and a coformulation of pembrolizumab with quavonlimab (MK-1308A, an anti-CTLA-4 antibody) plus Lenvima — against the control of Keytruda plus Lenvima. Neither combination regimen improved upon the established doublet. The failure narrows Welireg's (belzutifan, an HIF-2α inhibitor) path in first-line RCC, though the separate LITESPARK-011 trial evaluating Welireg plus Lenvima in previously treated RCC has an FDA PDUFA date expected by October 2026.
Agenus announced promising Phase II results for BOT/BAL plus agenT-797 in PD-1 refractory gastroesophageal cancer patients, per OncoDaily. The investigator-initiated trial suggests potential activity in a difficult-to-treat population where current options provide limited benefit, though larger controlled studies will be needed to confirm efficacy in this competitive indication.
Competitive Landscape
Lilly's $7 billion Kelonia deal, following the $2.4 billion Orna acquisition in February 2026, brings Lilly's total in vivo CAR-T investment to $9.4B, according to Fierce Biotech. Other recent in vivo CAR-T deals include AbbVie/Capstan ($2.1B), BMS/Orbital ($1.5B), and AstraZeneca/EsoBiotec ($1B). In vivo CAR-T developers command premium valuations Traditional ex vivo CAR-T manufacturers face competitive pressure from streamlined approaches.
| Approach | Manufacturing | Timeline | Cost |
|---|---|---|---|
| In Vivo CAR-T | None Required | Days | Lower |
| Ex Vivo CAR-T | 2-4 Weeks | Weeks | Higher |
The CAR-PRISM trial's 100% MRD negativity in high-risk smoldering myeloma, presented at AACR 2026, challenges the standard watch-and-wait approach, per STAT News. Given that approximately 50% of high-risk smoldering patients progress to active myeloma within two years, preemptive treatment could create first-mover advantages for companies developing early-intervention cell therapies.
Revolution Medicines presented Phase 1 zoldonrasib data at AACR 2026 showing 52% ORR in KRAS G12D-mutated NSCLC, according to BioPharma Dive. Zoldonrasib received Breakthrough Therapy Designation in January 2026. Revolution builds a complementary KRAS franchise spanning G12D (zoldonrasib) and broader RAS(ON) mutations (daraxonrasib) Amgen's Lumakras (sotorasib), limited to KRAS G12C, faces competitive pressure from broader-spectrum approaches.
Forward Looking
- Lilly's Kelonia acquisition expected to close H2 2026; continued Phase 1 inMMyCAR data for KLN-1010 will determine whether in vivo CAR-T can match ex vivo efficacy in multiple myeloma
- CAR-PRISM trial in smoldering myeloma could set precedent for prevention-based cell therapy approvals across hematologic malignancies; regulatory pathway for treating asymptomatic patients with CAR-T remains uncharted
- Revolution Medicines plans registrational trial of zoldonrasib plus daraxonrasib in KRAS G12D NSCLC in H2 2026, per company guidance
- BBOT expects updated Phase 1 KONQUER-101 data for BBO-11818 in H2 2026
- LITESPARK-012 failure narrows Welireg's (belzutifan) path in first-line RCC; Merck and Eisai's LITESPARK-011 PDUFA date for Welireg plus Lenvima in previously treated RCC expected by October 2026