Pharma BD Deal Intelligence

Bayer AG / Mammoth Biosciences Inc.

2022 · Co-Development · $1.0B · Complete

A $40M-upfront option bet still alive four years later: Bayer's Mammoth Biosciences gene-editing collaboration hasn't closed or terminated, and Mammoth has since nominated its first candidate, MB-111 — though Bayer's own $1B+ milestone payout remains entirely unrealized.

Outcome grade pending — assessed 5 years post-close.

Full analysis, sources & comparables →

The coverage arc

Jan 10, 2022 BioPharma Dive Bullish

Bayer is paying Mammoth Biosciences $40 million upfront and up to $1 billion in milestones to develop in vivo gene therapies using the biotech's ultra-compact…

Jan 10, 2022 STAT News Bullish

Bayer is partnering with Mammoth Biosciences, the CRISPR startup co-founded by Jennifer Doudna, to develop in vivo gene-editing therapies using miniature Cas…

Oct 01, 2025 Business Wire (Mammoth Biosciences) Bullish

Mammoth's first development candidate MB-111 leverages CasPhi, a proprietary ultracompact CRISPR nuclease, delivered by LNP to disrupt APOC3 in the liver as a…

Source summaries from our enrichment pipeline; follow links for originals.

All 11 sources with sentiment breakdown →

Bayer and Mammoth Biosciences entered a strategic collaboration and option agreement leveraging Mammoth's ultra-small Cas enzymes (Cas14, Cas-phi) for in vivo gene-editing therapies across five preselected indications. Mammoth received $40M upfront and is eligible for option exercise fees plus over $1B in milestones. Review (June 2026): no primary source indicates the collaboration has closed or terminated; as of 2025 Mammoth still listed Bayer among its active partnerships (alongside Vertex and Regeneron). The underlying ultracompact platform has advanced materially since signing — Mammoth reported new NanoCas extrahepatic-editor results (Jan 2025) and nominated its first development candidate, MB-111, a CasPhi-based, LNP-delivered in vivo liver editor targeting APOC3 for persistent chylomicronemia, with preclinical data at ESGCT (Oct 2025) and a planned clinic entry in 2026 — reinforcing the deal's ultra-compact / liver-targeted thesis. (MB-111 is not attributed by Mammoth to the Bayer collaboration specifically.)

Key facts

Disease & market context

Liver-Targeted Genetic Diseases (In Vivo CRISPR Editing)

1.5M US cases/yr · $3.5B Global gene editing therapeutics addressable market (modeled, 2030) · $0 FDA-approved in vivo CRISPR therapies (Casgevy is ex vivo only)

Disease Overview

In vivo gene editing in the liver is the highest-validated tissue target for systemic CRISPR delivery, anchored by Alnylam-pioneered LNP-GalNAc hepatocyte tropism and Intellia's NTLA-2001 (now nex-z) Phase 3 program in transthyretin amyloidosis demonstrating durable serum TTR knockdown after a single infusion. The therapeutic universe spans transthyretin amyloidosis (ATTR, ~50,000 U.S. patients), hereditary angioedema (HAE, ~6,000-7,000 U.S. patients), familial hypercholesterolemia (HeFH ~1.3M and HoFH ~1,300 U.S. patients), alpha-1 antitrypsin deficiency (~100,000 U.S. patients with PiZZ), and a broader set of inborn errors of metabolism. The competitive question is delivery vehicle and editor architecture: LNPs delivering Cas9 mRNA + sgRNA dominate; AAV delivery faces immunogenicity and capsid pre-existing immunity headwinds; base editors (Verve, Beam) and prime editors (Prime Medicine) offer mechanistic precision but lag in clinical readouts. Mammoth's value proposition with ultra-small Cas14 and Cas-phi enzymes is packaging flexibility — fitting into single AAV cassettes, enabling tissue beyond liver, and reducing immunogenicity risk versus full-size SpCas9 — but tradeoffs in editing efficiency must be addressed.

Competitive Landscape

The in vivo gene editing competitive arena is layered by editor architecture and delivery vehicle, with each combination addressing different therapeutic constraints. Liver-targeted LNP-Cas9 nuclease editors are led by Intellia Therapeutics (NTLA-2001/nex-z in Phase 3 MAGNITUDE for ATTR-CM, NTLA-2002 for HAE in Phase 3), validating systemic in vivo editing as a viable therapeutic modality. Base editors include Beam Therapeutics (BEAM-302 for AATD, BEAM-301 for GSDIa) and Verve Therapeutics' VERVE-102 for HeFH and broader cardiovascular indications. Prime editors are led by Prime Medicine (PM359 for chronic granulomatous disease, currently ex vivo-led with in vivo programs in development). Liver-targeted AAV gene addition is pursued by uniQure (etranacogene dezaparvovec/Hemgenix approved 2022 for hemophilia B) and Sangamo Therapeutics. Smaller-Cas systems — Mammoth's Cas14 and Cas-phi, Arbor Biotechnologies' Cas12 derivatives, and Caribou Biosciences' chRDNA — bet that ultra-compact editors will unlock tissue beyond liver via single-AAV packaging and enable in vivo editing of cell types where LNP delivery fails or where re-dosing is required. Bayer's strategic options under the Mammoth deal cover five undisclosed liver-first indications, with explicit optionality on subsequent expansion to extra-hepatic programs as packaging-size advantages translate to clinical readouts. Casgevy (exa-cel, CRISPR Therapeutics/Vertex) sets ex vivo CRISPR commercial benchmarks but does not directly address Bayer/Mammoth's in vivo strategic frame.

Deal timeline

Related deals — scored

DealYearValueOutcome
Bayer AG / Mammoth Biosciences Inc. (this deal)2022$1.0B
Bayer AG / Schering AG2006$21.5B79
Bayer AG / BlueRock Therapeutics2002$600M79
Bayer AG / Merck & Co., Inc.2014$14.2B71
Bayer AG / Schering AG (residual squeeze-out)2007$985M69
Bayer AG / Arvinas, Inc.2019$1.0B59
Bayer AG / Merck & Co. Inc.2014$14.2B56

Compare all 7 side-by-side →

See the full interactive analysis, sources & comparables →