Pharma BD Deal Intelligence

Merck & Co. Inc. / Orna Therapeutics, Inc.

2022 · Co-Development · $3.6B · Complete

Merck paid $150M upfront on up to $3.65B for Orna's circular RNA platform, plus a $100M Series B stake, but Orna's subsequent restructuring — new CEO, layoffs, and a pivot toward in vivo CAR programs — culminated in Eli Lilly agreeing to acquire Orna for up to $2.4B, though Orna said it would keep the Merck collaboration alive.

Outcome grade pending — assessed 5 years post-close.

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The coverage arc

Aug 16, 2022 BioPharma Dive Bullish

Merck on Tuesday announced a research collaboration with Orna Therapeutics worth up to $3.65 billion to develop circular RNA vaccines and therapies for…

Aug 16, 2022 Fierce Pharma Bullish

Merck is paying as much as $3.65 billion to access Orna Therapeutics' next-generation circular RNA technology, with the pharma giant agreeing to develop…

Aug 17, 2022 BioWorld Neutral

Merck & Co. Inc. and Orna Therapeutics Inc. have struck a research collaboration and license agreement to develop multiple programs spanning vaccines and…

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Merck and Orna Therapeutics announced a collaboration to discover, develop and commercialize multiple programs (vaccines and therapeutics) in infectious disease and oncology using Orna's circular RNA (oRNA) technology. Orna received $150M upfront, with up to $3.5B in development/regulatory/sales milestones plus royalties; Merck also invested $100M in Orna's $221M Series B. Since signing, Orna restructured significantly: it acquired ReNAgade Therapeutics (May 2024) for its LNP RNA-delivery platform, installed Amit Munshi as CEO, ran multiple layoff rounds (Dec 2023, Nov 2024), and refocused on in vivo CAR (panCAR) programs led by ORN-252, a CD19 in vivo CAR-T for B-cell autoimmune disease (CTA targeted end-2025, first-in-human early-2026); as of Nov 2024 Orna affirmed it would continue the Merck vaccine collaboration. On Feb 9, 2026, Eli Lilly agreed to acquire Orna for up to $2.4B in cash (upfront plus clinical-development milestones), subject to HSR clearance and customary conditions; Lilly is expected to honor Orna's pre-existing Merck and Vertex collaborations, leaving the 2022 Merck oRNA pact in effect under new ownership. No products from the Merck collaboration have been approved; the deal remains in development.

Key facts

Disease & market context

Infectious Disease Vaccines and Oncology Therapeutics (Circular RNA Platform)

30M US cases/yr · $50.0B Global mRNA/RNA therapeutics + vaccine market peak (2022) · $24.7B Combined Moderna+Pfizer/BioNTech mRNA COVID vaccine 2022 revenue

Disease Overview

The Merck-Orna collaboration is a platform deal addressing two umbrella therapeutic areas: prophylactic and therapeutic infectious disease vaccines and oncology immunotherapy candidates - both built on Orna's circular RNA (oRNA) technology. Within infectious disease, the addressable U.S. opportunity is anchored by influenza (~30M annual cases), respiratory syncytial virus (~177,000 hospitalizations annually in adults 65+), SARS-CoV-2 (endemic, ~700,000 hospitalizations 2022 season), CMV, HIV, and pandemic preparedness; the global RNA-vaccine market exceeded $50B at peak COVID and is consolidating around mRNA-LNP platforms with circular RNA as the next-generation iteration aimed at extending intracellular protein expression duration and avoiding 5' cap requirements. Within oncology, the indication scope spans cancer vaccines (personalized neoantigen and shared tumor-associated antigen) and engineered immune-cell therapies, where Merck's KEYTRUDA franchise creates pull for combination biologics that drive durable T-cell responses. Orna's wholly synthetic circular RNA differentiates from linear mRNA by lacking 5' and 3' ends, theoretically enabling longer protein expression and potentially in vivo CAR-T applications - the strategic prize that justifies Merck's $150M upfront commitment.

Competitive Landscape

The RNA therapeutics and vaccine landscape is dominated by linear mRNA-LNP platforms with multiple emerging modalities. Approved/marketed: Comirnaty (BNT162b2, Pfizer/BioNTech), Spikevax (mRNA-1273, Moderna), Onpattro (patisiran siRNA, Alnylam) and Givlaari (givosiran siRNA, Alnylam). Late-stage clinical: mRNA-1345 (RSV, Moderna, Phase 3 ConquerRSV positive), mRNA-1010 (flu, Moderna), BNT161 (flu, Pfizer/BioNTech), mRNA-4157 / V940 (Moderna/Merck personalized neoantigen, Phase 2b positive in melanoma KEYNOTE-942), and BNT122 (BioNTech/Genentech autogene cevumeran). Circular RNA peers include Laronde (oRNA-class, $440M Series B), Orbital Therapeutics (founded 2023 post-deal), VIVO Capital-backed Capstan Therapeutics (in vivo CAR-T mRNA), and Replicate Bioscience (self-amplifying RNA). Self-amplifying / saRNA from Arcturus (ARCT-154, COVID, KOSTAIVE approved Japan) and Gritstone bio (samRNA platform). Merck's existing in-house RNA strategy includes the Moderna mRNA-4157/V940 personalized cancer vaccine partnership announced 2022 - the Orna deal builds optionality on circular RNA modality next to that linear mRNA bet.

Deal timeline

Related deals — scored

DealYearValueOutcome
Merck & Co. Inc. / Orna Therapeutics, Inc. (this deal)2022$3.6B
Merck & Co. Inc. / Acceleron Pharma Inc.2021$11.5B90
Merck & Co. Inc. / Peloton Therapeutics Inc.2019$2.2B88
Merck & Co. Inc. / AstraZeneca PLC2017$8.5B87
Merck & Co. Inc. / Moderna, Inc.2022$250M86
Merck & Co. Inc. / Moderna, Inc.2016$250M84
Merck & Co. Inc. / Eisai Co., Ltd.2018$5.8B83

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