Smaller large molecules? Roche invests $62m in DARPin dev deal

By Dan Stanton

- Last updated on GMT

Roche and Molecular Partners team over DARPin-drug conjugate technology
Roche and Molecular Partners team over DARPin-drug conjugate technology

Related tags Protein Antibody

Roche has teamed with Molecular Profiles to test if short protein sequences can be used to target conjugated cancer drugs when antibodies prove to large.

The Swiss Giant has been focused on ADCs with its product Kadcyla currently approved in the US and Europe​, but last week the firm looked to another form of hybrid biologic drug by entering into a research collaboration with biotech firm Molecular Partners over its DARPin-drug conjugate platform.

DARPins (designed ankyrin repeat proteins) are non-antibody based, small proteins derived from natural repeat proteins, to which a highly variable region has been engineered and, according to Roche spokesman Luke Willats, are ideal targeting agents to deliver payloads to tumors and kill cancer cells.

“The DARPin platform is truly complementary to our internal capabilities in the large molecule space,”​ he told, and “will be used on targets that are difficult to tackle with antibodies, i.e., in situations where multi-modular constructs are needed to eliminate the tumor effectively and selectively.”

The advantage of using DARPins instead of antibodies is their size. Molecular Partners’s CEO, Christian Zahnd told us they are a tenth of the size of an antibody molecule and are “very stable, highly soluble, extremely potent, highly selective and specific.”

He continued: “Yield-wise it is possible to get 10 grammes/litre in microbial manufacturing. Several different DARPins can be combined in one single molecule thus targeting multiple disease targets at once.”


DARPins were developed at the University of Zurich, Switzerland, but Molecular Partners now holds the full license on the technology.

“Repeat proteins are found in nature very abundantly, mostly involved in protein-protein interactions,” ​said Zahnd. “From our libraries of engineered repeat proteins, we can select DARPins binding to any molecular disease target.”

In most cases DARPins are manufactured in E. coli but they can also be produced in mammalian cells, he added.

Molecular Partners’ Partners

This deal will see Roche pay Molecular Partners upfront payments of up to CHF 55m ($62m) though this may reach CHF 1bn depending on development and sales milestones.

As for the workings of the partnership, Zahnd told us this deal combines the best of both firms, with “Molecular Partners providing the DARPins as the targeting technology, whilst Roche has the expertise on toxins.”

Molecular Partners also has an alliance with Janssen (Johnson & Johnson) and Allergan, in immunology and ophthalmology respectively, as well as developing its own, unpartnered, proprietary molecules mostly in oncology.

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