The Body Becomes the Factory
Lilly is using GLP-1 cash flow to buy four different answers to genetic medicine’s hardest problem: delivery.
One of the biggest ideas in genetic medicine is to stop manufacturing therapies in clean rooms and start manufacturing them inside the patient.
Autologous CAR-T therapies start with a patient’s own immune cells. Those cells are collected by leukapheresis, shipped or transferred into a specialized manufacturing process, activated, genetically modified, expanded outside the body, tested, cryopreserved, shipped back, and infused after lymphodepleting chemotherapy.
Recent reviews describe commercial CAR-T vein-to-vein times ranging from roughly two weeks to nearly two months, and reported trial or real-world non-infusion rates as high as 31% in some cohorts, caused by manufacturing failures or, more often, disease progression while patients wait. Current CAR-T list prices are generally in the hundreds of thousands of dollars per infusion, before hospitalization, toxicity management, and follow-up costs are counted. [1, 2, 3]
That is why the field keeps returning to one question:
How do you get rid of the clean room?
The answer drawing capital now is deceptively simple. Do not manufacture the therapy and put it into the patient. Put the instructions into the patient and let the body manufacture the therapy.
Move the factory inside.
One company is now assembling that future more aggressively than almost any other large pharma company: Eli Lilly. The reason it can do that is not a gene-editing product already on the market.
It is tirzepatide.
Lilly is treating it not as a side project, but as a platform thesis.
Why in vivo is the whole game
The reason in vivo matters is that it attacks the cost structure, timeline, and access problem at the same time.
Every limitation that makes autologous cell therapy expensive and rationed traces back to doing the engineering outside the body: harvesting, bespoke per-patient production, release testing, cryologistics, treatment-center coordination, and pre-infusion lymphodepletion.
The prize is not merely convenience. It is scale:
A therapy that can be stocked, shipped, and dosed like a biologic has a radically different addressable market than one that must be custom-built for each patient.
That is why the contested ground in genetic medicine has shifted from the therapeutic idea to delivery: getting the payload to the right cell, in the right amount, with acceptable safety, and ideally with the option to dose again.
Whoever solves delivery owns the infrastructure layer.
Everyone else rents it.
What Lilly actually assembled
Read in isolation, Lilly’s recent genetic-medicine deals look like a shopping spree.
Read together, they look more like a map of the in vivo delivery problem.
Verve Therapeutics: in vivo gene editing. In June 2025, Lilly agreed to acquire Verve for roughly $1.0 billion upfront plus a contingent value right worth up to $300 million, for total potential consideration of about $1.3 billion.
Verve’s lead program, VERVE-102, is designed to permanently turn off PCSK9 in the liver using in vivo gene editing, initially for heterozygous familial hypercholesterolemia and ultimately for broader atherosclerotic cardiovascular disease populations.
The power is durability.
The limit is scope: gene editing changes genes that are already there; it does not simply install an arbitrary new therapeutic program. [4]
Orna Therapeutics: in vivo CAR via circular RNA. In February 2026, Lilly agreed to acquire Orna for up to $2.4 billion.
Orna pairs engineered circular RNA with lipid nanoparticles, with a lead program, ORN-252, described by Lilly as a clinical-trial-ready CD19-targeted in vivo CAR-T therapy for B-cell-driven autoimmune disease.
The appeal is a non-viral, potentially redosable format.
The caveat is that RNA expression, even if circular RNA improves durability relative to conventional mRNA, still has to prove in humans that it can generate the depth and persistence of effect required for each disease setting. [5]
Kelonia Therapeutics: in vivo CAR via lentiviral gene placement. In April 2026, Lilly agreed to acquire Kelonia for up to $7.0 billion, including $3.25 billion upfront and additional clinical, regulatory, and commercial milestones.
Kelonia’s iGPS platform uses engineered lentiviral-based particles designed to enter T cells inside the body. Its lead program, KLN-1010, is a one-time intravenous anti-BCMA in vivo CAR-T candidate in Phase 1 for relapsed or refractory multiple myeloma.
The appeal is durable integration.
The risk is the familiar trade-off: viral delivery can be powerful, but it can bring immunogenicity, manufacturing complexity, and harder repeat dosing. [6]
Engage Biologics: non-viral DNA delivery. In May 2026, Engage announced that Lilly had acquired it for up to $202 million in cash, including an upfront payment and development milestones.
Engage’s Tethosome platform combines engineered DNA payloads with lipid nanoparticle delivery and an mRNA-encoded technology intended to improve nuclear localization, expression, tolerability, and redosability.
In plain English, Engage is trying to solve the two problems that have held back non-viral DNA delivery: getting DNA to the nucleus and avoiding innate immune sensing. [7, 8]
Lay those deals on a grid and the architecture appears.
RNA payloads may be controllable and redosable but must prove durability.
Viral delivery may be durable but is harder to redose.
Base editing can be permanent but is best suited to switching or correcting endogenous genes.
Non-viral DNA delivery aims for the missing square: durable, programmable, redosable genetic medicine without a virus.
Lilly did not just buy four companies.
It bought four different answers to the delivery problem.
The engine: how a weight-loss drug pays for the future
Here is what turns an interesting strategy into a structural advantage: Lilly can fund this while its core business is accelerating.
In 2025, Lilly reported $65.179 billion in revenue, up 45% from 2024. The engine was tirzepatide.
Mounjaro generated $22.965 billion, and Zepbound generated $13.542 billion. Together, those two products produced about $36.5 billion, or roughly 56% of Lilly’s total 2025 revenue.
Lilly also reported fourth-quarter 2025 gross margin of 82.5% on a GAAP basis and 83.2% on a non-GAAP basis. [9]
That cash flow changes the risk budget. Most companies cannot buy a portfolio of early genetic-medicine platforms and wait years for clinical proof.
Lilly can.
A BioSpace tally in late April 2026 counted six Lilly acquisitions in 2026 totaling nearly $21 billion in announced potential consideration, and Engage then added another $202 million deal in May.
That broader tally is not a pure in vivo-delivery tally. Lilly’s recent M&A also includes deals outside this thesis — Ventyx in inflammation, Adverum in ophthalmic AAV gene therapy, CrossBridge Bio in ADCs, and other pipeline-building moves — which I am setting aside here to focus on the in vivo genetic-medicine question. [10, 11, 12, 13]
Lilly has enough GLP-1-driven financial capacity to buy options across the in vivo stack while competitors are forced to be more selective.
Why the rest of pharma is moving slower
It would be too easy to call the rest of the industry slow or unimaginative.
The better explanation is capital-allocation pressure.
Evaluate data cited by PharmaVoice put the approaching patent cliff at about $300 billion of industry revenue at risk by 2030.
That cliff falls hardest on companies that need near-term replacement revenue.
Merck’s KEYTRUDA/KEYTRUDA QLEX franchise generated $31.680 billion in 2025, against total Merck sales of $65.011 billion, or about 49% of company revenue.
Merck’s 2025 Form 10-K lists Keytruda patent expiry dates of 2028 in the United States, 2031 in the European Union, 2032–2033 in Japan, and 2028 in China. [14, 15, 16, 17]
Bristol Myers Squibb has a different but similarly visible concentration problem.
In 2025, BMS reported $48.194 billion in total revenue. Eliquis generated $14.443 billion and Opdivo generated $10.049 billion, together equal to roughly $24.5 billion, or about 51% of BMS revenue.
Industry analyses have described BMS as having one of the largest patent-cliff growth gaps among major pharma companies, around $38 billion, driven substantially by Eliquis and Opdivo exposure. [18, 19, 14]
When a quarter-to-half of revenue is exposed over a narrow window, M&A becomes defensive.
You buy later-stage, de-risked, or already commercial assets that can replace revenue soon.
You do not have the same freedom to buy a preclinical delivery platform that might matter in 2035.
Lilly is the rare major pharma company with no comparable near-term cliff and a still-accelerating cash engine.
That lets it play offense: buy early platforms, structure some consideration with milestones, and spread scientific risk across modalities.
To be clear, Lilly is not alone in seeing the in vivo future.
AstraZeneca agreed in March 2025 to acquire EsoBiotec for up to $1.0 billion, including $425 million upfront and up to $575 million in development and regulatory milestones. EsoBiotec’s ENaBL platform uses targeted lentiviruses to deliver genetic instructions to immune cells in vivo.
AbbVie agreed in June 2025 to acquire Capstan Therapeutics for about $2.1 billion upfront, including CPTX2309, a Phase 1 targeted lipid-nanoparticle anti-CD19 in vivo CAR-T candidate for B-cell-mediated autoimmune diseases. [20, 21]
The difference is breadth.
Lilly is assembling RNA, viral, editing, and non-viral DNA delivery options at the same time.
Why this matters for operators, CDMOs, and investors
For founders, this is the signal: delivery is no longer enabling technology buried inside the platform story.
It is the platform story.
For CDMOs, it raises a harder question: if advanced therapy manufacturing shifts from bespoke ex vivo workflows toward injectable in vivo products, where does manufacturing margin migrate?
For investors, the implication is equally blunt: the highest-value companies may not be the ones with the most dramatic therapeutic concept, but the ones controlling the delivery layer that lets many therapeutic concepts scale.
This is the strategic reason delivery companies are becoming acquisition targets.
They are not just asset companies, but infrastructure companies.
The bear case, stated honestly
None of this proves Lilly is right.
It proves the bet is large.
These are mostly bets, not revenue.
Engage is preclinical.
Orna’s lead in vivo CAR-T program was described as clinical-trial-ready, not commercially validated.
Kelonia’s KLN-1010 is in Phase 1.
Verve is clinical-stage and must still prove that in vivo editing can deliver an acceptable long-term risk-benefit profile for broad cardiovascular populations.
In vivo CAR-T as a category has not yet shown, at commercial scale, that it can match or beat the efficacy of ex vivo CAR-T while meaningfully reducing toxicity, logistics, and cost. [4, 5, 6, 7]
There is also concentration risk on the funding side.
The same GLP-1 cash flow that gives Lilly this optionality is exposed to competition, pricing pressure, supply constraints, payer pushback, and the eventual arrival of oral and follow-on rivals.
Lilly itself lists intense competition, pricing and reimbursement pressure, supply risk, and dependence on relatively few products or product classes among the risks that could affect results. [22]
The honest framing is this:
Lilly is using a historic, possibly temporary cash advantage to buy a large, early, diversified position in what it believes is the next era of medicine.
If in vivo works, Lilly may have bought infrastructure before it was obvious.
If in vivo stumbles, Lilly will have spent billions learning that lesson faster than almost anyone else.
That asymmetry is the actual strategy: expensive options that Lilly can uniquely afford, spread across the delivery stack.
What to watch from here
Three signals matter.
First, clinical proof that in vivo can compete with ex vivo.
For Kelonia, that means durable responses from KLN-1010 with a safety and logistics profile that genuinely changes the CAR-T equation.
For Orna, it means showing that circular RNA plus LNP can generate enough in vivo CAR expression to reset disease biology in humans.
Second, the delivery layer.
If Lilly or a peer keeps buying targeted LNP, non-viral DNA, tissue-tropic viral, or immune-evasive delivery companies, it confirms that delivery is where the durable value sits.
Third, the patent-cliff defenders.
Watch whether Merck, BMS, Pfizer, Johnson & Johnson, or other cliff-exposed majors pivot from defensive, revenue-replacement M&A toward earlier platform bets.
The day a cliff-exposed major starts buying preclinical in vivo delivery platforms at Lilly’s pace is the day this stops being Lilly’s differentiated wager and becomes industry consensus.
The pattern underneath all of it is simple: durable value in advanced therapies rarely sits only in the dramatic single asset. It sits in the infrastructure — delivery systems, manufacturing-collapsing modalities, and platform know-how — that quietly makes everything above it work.
Lilly is using the most profitable drug franchise of its generation to buy that infrastructure while it is still early.
Whether that is visionary or premature, we will know over the next decade.
But it is one of the boldest capital-allocation bets in pharma right now.
And it is being financed by a weight-loss drug.
Disclosure
I work with Phacilitate and SaxoCell. This analysis is based only on public sources and does not use confidential information, employer-owned information, or private relationship capital. Phacilitate’s convening role and my SaxoCell work did not direct this analysis. As of publication, I hold no direct public equity positions in Eli Lilly, Merck, Bristol Myers Squibb, AbbVie, or AstraZeneca. This article is not investment advice.
Reference links
[1] Johnson, P. C. et al. “CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review.” PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC11808657/
[2] Dias, J. et al. “CAR-T cell manufacturing landscape — Lessons from the past decade and considerations for early clinical development.” Molecular Therapy Methods & Clinical Development. https://pmc.ncbi.nlm.nih.gov/articles/PMC11088187/
[3] National Academies / NCBI Bookshelf. “The Value of CAR-T-cell Immunotherapy in Cancer.” https://www.ncbi.nlm.nih.gov/books/NBK584170/
[4] Eli Lilly and Company. “Lilly to acquire Verve Therapeutics to advance one-time treatments for people with high cardiovascular risk.” June 17, 2025. https://investor.lilly.com/news-releases/news-release-details/lilly-acquire-verve-therapeutics-advance-one-time-treatments
[5] Eli Lilly and Company. “Lilly to acquire Orna Therapeutics to advance cell therapies.” February 9, 2026. https://investor.lilly.com/news-releases/news-release-details/lilly-acquire-orna-therapeutics-advance-cell-therapies
[6] Eli Lilly and Company. “Lilly to acquire Kelonia Therapeutics to advance in vivo CAR-T cell therapies.” April 20, 2026. https://investor.lilly.com/news-releases/news-release-details/lilly-acquire-kelonia-therapeutics-advance-vivo-car-t-cell
[7] Engage Biologics. “Engage Bio Acquired by Lilly to Accelerate Development of Non-Viral Genetic Medicines.” Business Wire. May 20, 2026. https://www.businesswire.com/news/home/20260520932076/en/Engage-Bio-Acquired-by-Lilly-to-Accelerate-Development-of-Non-Viral-Genetic-Medicines
[8] Engage Bio. “Tethosome platform.” Accessed May 24, 2026. https://www.engagebio.com/
[9] Eli Lilly and Company. “Lilly reports fourth-quarter 2025 financial results and provides 2026 guidance.” February 4, 2026. https://investor.lilly.com/news-releases/news-release-details/lilly-reports-fourth-quarter-2025-financial-results-and-provides
[10] BioSpace. “Lilly can’t stop the dealing, with nearly $21B spent on M&A this year — so far.” 2026. https://www.biospace.com/business/lilly-cant-stop-the-dealing-with-nearly-21b-spent-on-m-a-this-year-so-far
[11] Eli Lilly and Company. “Lilly to acquire Ventyx Biosciences to advance oral therapies targeting inflammatory-mediated diseases.” January 7, 2026. https://investor.lilly.com/news-releases/news-release-details/lilly-acquire-ventyx-biosciences-advance-oral-therapies
[12] Eli Lilly and Company. “Lilly to Acquire Adverum Biotechnologies.” October 24, 2025. https://investor.lilly.com/news-releases/news-release-details/lilly-acquire-adverum-biotechnologies
[13] CrossBridge Bio. “CrossBridge Bio Enters an Agreement to be Acquired by Eli Lilly to Advance Next-Generation Dual-Payload Antibody-Drug Conjugates.” Business Wire. April 14, 2026. https://www.businesswire.com/news/home/20260414133394/en/CrossBridge-Bio-Enters-an-Agreement-to-be-Acquired-by-Eli-Lilly-to-Advance-Next-Generation-Dual-Payload-Antibody-Drug-Conjugates
[14] PharmaVoice. “How Big Pharma is navigating a $300 billion patent cliff.” January 30, 2026. https://www.pharmavoice.com/news/big-pharma-navigating-patent-cliff-300-billion-jnj-merck-abbvie/810915/
[15] Merck & Co. “Merck Announces Fourth-Quarter and Full-Year 2025 Financial Results.” February 2026. https://www.merck.com/wp-content/uploads/sites/124/2026/02/4Q25-Merck-Earnings-Announcement.pdf
[16] Merck & Co. 2025 Form 10-K. https://www.merck.com/wp-content/uploads/sites/124/2026/02/MRK-12.31.2025-10K-FINAL.pdf
[17] FDA. “FDA approves pembrolizumab and berahyaluronidase alfa-pmph subcutaneous injection.” September 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-and-berahyaluronidase-alfa-pmph-subcutaneous-injection
[18] Bristol Myers Squibb. “Key facts.” Updated May 2026. https://www.bms.com/media/media-library/key-facts.html
[19] Bristol Myers Squibb. “Bristol Myers Squibb Reports Fourth Quarter and Full-Year Financial Results for 2025.” https://www.bms.com/assets/bms/us/en-us/pdf/investor-info/doc_financials/quarterly_reports/2025/BMY-Q4-2025-Earnings-Press-Release.pdf
[20] EsoBiotec. “EsoBiotec to Be Acquired by AstraZeneca to Advance Cell Therapy Ambition.” March 17, 2025. https://www.esobiotec.com/esobiotec-to-be-acquired-by-astrazeneca-to-advance-cell-therapy-ambition/
[21] AbbVie. 2025 Form 10-Q disclosure on proposed Capstan Therapeutics acquisition. https://investors.abbvie.com/static-files/c36e2bd6-b4b6-4073-a742-d2bb7e3769c5
[22] Eli Lilly and Company. 2025 Annual Report on Form 10-K. https://investor.lilly.com/static-files/0d64699c-0cc7-490e-9152-b2ba1de08634