AbbVie Near Deal for Revolution Medicines

“AbbVie is in advanced talks to buy cancer-drug biotech Revolution Medicines, according to people familiar with the matter, in what would be one of the year's first megadeals.

 

A deal could come together soon, granted the talks don't hit any last-minute snags, the people said.

 

After The Wall Street Journal reported on the deal talks, AbbVie said it "is not in discussions" with Revolution.

 

A person familiar with the matter said a deal hasn't been finalized and another suitor may prevail.

 

Revolution Medicines had a market value of around $16 billion before the Journal reported on the talks Wednesday afternoon. Its shares closed up around 30%, giving it a market value of around $20 billion.

 

Revolution had drawn interest from other suitors, some of the people said. It couldn't be learned how much AbbVie is offering.

 

AbbVie, which has a market value of above $400 billion, generates about half of its yearly revenue from sales of drugs for immune conditions such as psoriatic arthritis and Crohn's disease.

 

In a sign that suggests AbbVie's shareholders like the deal, the drugmaker's shares also rose following the Journal's report.

 

Adding Revolution Medicines would bolster AbbVie's efforts to build its presence in the more than $250 billion worldwide market for cancer drugs.

 

The biotech is developing drugs targeting a molecular driver of many cancers known as RAS.

 

The biotech's experimental drugs seek to block RAS, halting lung cancer, pancreatic cancer and other tumors in their tracks. The molecules are still in development, and some still haven't entered human testing, according to the biotech's website. AbbVie is making a pricey bet that they will prove to work safely -- no sure thing.

 

Yet if the drugs pan out, they would offer much-needed options for patients and provide a huge payoff to AbbVie. Drug researchers have been seeking ways to inhibit RAS for decades because of its important role in many cancers.

 

AbbVie, based outside Chicago, has said it is more interested in acquiring mechanisms and technologies that can furnish drugs powering the company's growth over the next decade and further, rather than proven assets.

 

Like many big drugmakers, AbbVie has sought to build a beachhead in cancer drugs, which are among the industry's biggest sellers.

 

In one of its biggest deals, the company bought Pharmacyclics and its share of a lucrative blood-cancer treatment for $21 billion in 2015. AbbVie has been doing other deals since, including a $10 billion purchase in 2024 of ImmunoGen and its ovarian-cancer treatment.

 

Revolution Medicines's RAS-drug research stems from the work of a Harvard University scientist and entrepreneur Gregory Verdine, who helped establish a company, called Warp Drive Bio, that found molecules that attacked the target by sequencing the genomes of bacteria.” [1]

 

Warp Drive Bio was a biotech company known for its innovative genome mining platform that sequenced bacterial DNA to find new drug molecules, especially targeting previously "undruggable" cancer proteins like KRAS and developing novel antibiotics by exploring natural compounds from soil microbes, leading to its acquisition by Revolution Medicines in 2018. Their key technology, SMART™ allowed them to re-engineer natural products to engage difficult protein surfaces, creating powerful new therapies.

 

The SMART™ Platform (Specific Molecular Architecture for Recognition and Therapy) is

a drug design method, that creates molecules to bind to previously "undruggable" protein surfaces, especially relevant in cancer by engaging flat, featureless protein areas traditional small molecules miss, often using natural product scaffolds like macrocycles to achieve novel binding and therapeutic effects, like targeting activated KRAS. It focuses on exploiting unique molecular contacts and complex structures, offering a new way to tackle challenging disease targets beyond conventional binding pockets, with applications in oncology, CNS, and age-related diseases.

 

Key Concepts & Mechanism:

 

    Targeting "Undruggable" Proteins: Traditional drugs need deep pockets, but SMART™ technology targets large, flat, or transient protein surfaces (protein-protein interaction sites) that are hard to hit.

 

    Molecular Architecture: It uses the inherent structures of natural products (like macrocycles) as starting points to build molecules that fit these complex surfaces, exploiting unique contact points.

 

Macrocycles are large ring-shaped molecules with at least 12 atoms in their ring, bridging the gap between traditional small molecules and large biologics, offering unique drug properties like improved target binding (especially for challenging protein interfaces) and potential oral bioavailability, despite historical design challenges, making them promising for new therapies.

 

In Chemistry & Drug Discovery

 

    Definition: Organic molecules with rings of 12 or more atoms, found in nature (e.g., cyclosporine, erythromycin) or synthesized.

 

    Advantages: Their preorganized, semi-rigid structures can bind with high affinity and selectivity, accessing complex protein sites (like protein-protein interactions) often missed by smaller drugs, while potentially remaining orally bioavailable.

 

    Challenges: Complex shapes (conformational flexibility) and achieving good absorption/distribution (ADME properties) have historically been hurdles, though advances are overcoming these.

 

    Examples: Used in immunosuppressants (cyclosporine), antibiotics (vancomycin), and antivirals, with new designs targeting various diseases.

 

 

 

    Novel Modality: Creates differentiated inhibitors with unique mechanisms of action, allowing for targeting activated states of oncogenes (like GTP-bound KRAS) or disrupting protein-protein interactions (PPIs).

    Versatility: Applicable to various diseases, including cancer (targeting KRAS, MYC), Alzheimer's, Parkinson's, and Age-Related Macular Degeneration.

 

How it Works (Example with Warp Drive Bio):

 

    Identify Target: Focus on disease-causing proteins with difficult-to-bind surfaces, such as the activated form of KRAS.

    Leverage Natural Products: Utilize natural product scaffolds (e.g., FKBP-binding molecules) as frameworks. FKBP-binding molecules are compounds, often drugs or natural products like rapamycin and FK506 (tacrolimus), that bind to FK506-binding proteins (FKBPs), a family of cellular chaperones involved in protein folding and signaling. These drug-protein complexes then target specific intracellular proteins (like calcineurin or mTOR), leading to powerful immunosuppressive or anti-cancer effects, with FKBPs acting as crucial molecular switches for various biological processes.

 

    Engineer Variable Domain: Modify the "variable domain" of the scaffold to create high-affinity, specific binding to the target protein's unique surface.

 

    Achieve Therapeutic Effect: The resulting molecule (SMART™ molecule) then inhibits the protein's function, leading to anti-cancer effects.

 

Significance in Cancer:

 

    Opens new avenues for targeting historically "undruggable" oncogenic drivers (e.g., KRAS, MYC).

    Enables new therapeutic strategies beyond traditional small molecule inhibition.

 

 

Key Technologies & Focus:

 

    Genome Mining: Sifting through vast bacterial DNA to discover new, unanalyzed natural compounds with therapeutic potential, bypassing traditional synthetic chemistry limits.

    SMART™ Platform: A method to design and optimize molecules that bind to "undruggable" surfaces on disease-causing proteins, particularly in cancer.

    Targets: Focused on oncology (like KRAS-G12C inhibitors) and novel antibiotics to combat drug-resistant bacteria.

 

Key Developments:

 

    Founded in 2012: Launched with backing from Third Rock Ventures and Sanofi.

    Acquired by Revolution Medicines (2018): This acquisition integrated Warp Drive's platform with Revolution Medicines' precision oncology pipeline, creating a strong oncology-focused company.

    Antibiotic Collaborations: Partnered with Roche and GSK to find new antibiotics for multi-drug resistant infections.

 

In essence, Warp Drive Bio used nature's own genetic blueprint (bacterial genomes) to find powerful, unique molecules, which they could then engineer to fight tough diseases like cancer and infections, a method later absorbed by Revolution Medicines.

 

1. AbbVie Near Deal for Revolution Medicines. Rockoff, Jonathan D; Thomas, Lauren; Lombardo, Cara.  Wall Street Journal, Eastern edition; New York, N.Y.. 08 Jan 2026: B1