DARPin Science

Our DARPin Therapeutics
A new class of multi-functional protein drugs
with unique advantages

DARPin therapeutics a new drug classWe have pioneered DARPin (Designed Ankyrin Repeat Protein) therapeutics, a new class of custom-built drugs based on natural binding proteins with the potential to overcome several limitations of current protein-based therapeutics.

DARPin therapeutics have been clinically validated across several therapeutic areas and developed up to the registrational stage.

Through our leadership and breakthroughs with DARPin therapeutics in the clinic, we continue to unlock the versatility of DARPin therapeutics for patients, with Radio-DARPin therapy and next-generation immune cell engagers, including Switch-DARPin.

Learn more about our:

Designing DARPin therapeutics:
Leveraging key properties of DARPins

  • High affinity and specificity

    Selective binding to targets across broad target space

    High affinity and specificity
  • Multi-specificity

    Specificity to up to 6 distinct targets in one candidate

    Multi-specificity
  • Small size

    Greater tissue penetration

    Small size
  • Tunable half-life

    Half-life engineering through albumin binding to optimize target engagement and dosing

    Tunable half-life
  • 1 DARPin = 1 function

    Rapid creation of multi-functional candidates through vast libraries

    1 DARPin = 1 function
  • Stability and simple manufacturing

    Scalable, high-yield production of stable candidates with long shelf-life

    Stability and simple manufacturing

DARPin therapeutics can be tailored to specific disease biology by leveraging key properties of DARPins, such as high affinity and specificity, small size, and flexible and stable architecture.

DARPin therapeutics can also be designed in a modular manner and linked with various cytotoxic payloads, and their half-life can be tuned to match the therapeutic need of a certain mode of action and disease indication.

Molecular Partners draws on a vast library of trillions of different DARPins to find those that bind best to different targets. DARPins can be rapidly combined in different ways and the resulting combinations are run through screening processes to ensure the best performance ‘on target’.

Manufacturing DARPins: a focus on speed and simplicity

DARPins are small proteins that do not require extensive post-translational modification. This permits relatively simple, highly scalable bacterial fermentation in a short time frame, with clinical batch production every seven to ten days.

Radio-DARPin therapeutics for effective and selective delivery of radioactive payloads to solid tumors

We develop targeted alpha radiotherapeutics leveraging our Radio-DARPins as isotope-agnostic vectors with the potential to unlock to a broad range of cancer targets and indications.

Building on the DARPins’ unique properties, we have developed our Radio-DARPin platform and therapeutics balancing precise delivery of potent radioactive payloads to tumor lesions while sparing healthy tissues, thereby addressing the key challenges of targeted radiotherapy:

  • Reduce kidney toxicity: Through surface engineering of the highly stable DARPin backbone, we successfully reduced the renal reabsorption of Radio-DARPins, leading to an increased excretion in the urine and strongly reduced accumulation of radioactivity in the kidneys.
  • Increase tumor uptake: Our expertise in DARPin half-life modulation enabled further optimization of their circulation in blood and increased uptake across different targeted tumors, while keeping blood levels low.

Radio-DARPin therapeutics for effective and selective delivery of radioactive payloads to solid tumors

We have demonstrated preclinically that we can achieve an attractive biodistribution profile with high tumor uptake and low levels in healthy tissues across several targets and models.

First patient imaging and dosimetry data on MP0712 – our lead Radio-DARPin candidate -indicate specific and robust uptake in tumor lesions as well as favorable biodistribution.

We are developing our first Radio-DARPin therapeutics in collaboration with our strategic partner Orano Med, a pioneer in the development of targeted alpha therapies with 212Pb.

We design our Radio-DARPin candidates matching disease and target biology with vector and isotope properties to address unmet medical needs. Our isotope-agnostic strategy is enabled by pre-clinical data highlighting the Radio-DARPins suitability to different isotopes, including 212Pb and 225Ac.

A non-exclusive development agreement with Eckert & Ziegler, leading specialist in isotope-related components for nuclear medicine and radiation therapy, enables the development and manufacturing of Radio-DARPin therapeutics with further therapeutic alpha-emitting isotopes, including 225Ac.

Find out more about:

  • MP0712 targeting DLL3 for the treatment of SCLC and other DLL3-expressing cancers
  • MP0726 targeting MSLN for the treatment of ovarian cancer and other MSLN-expressing cancers
  • Find out more about our isotope agnostic strategy in radio

Logic-gated “on/off” Switch-DARPins
for conditional immune cell activation

Switch-DARPins as a novel “logic-gated” approach for multi-specific DARPin therapeuticsWe have developed Switch-DARPins as a novel “logic-gated” approach for multi-specific DARPin therapeutics. Switch-DARPins enable targeted and conditional immune cell activation to maximize the impact of our next-generation immune cell engagers on the targeted tumor and minimize systemic side effects.

A Switch-DARPin can bind to two different targets in a mutually exclusive way depending on the biological context. This technology has the potential to unlock historically undruggable targets, such as tumor-associated targets also expressed in healthy tissues, and to enable use of powerful immune activators for the treatment of cancer, including T cell co-stimulators, which have so far been limited by systemic toxicity.

Logic-gated “on-off” Switch-DARPins for conditional immune cell activation

Find out more about our Switch-DARPin candidates:

  • MP0632, designed to address current limitations of T cell engagers for the treatment of solid tumors such as high systemic toxicity and limited specificity
  • MP0621, designed to improve the efficacy and safety of conditioning regimen for hematopoietic stem cell transplantation

In preclinical testing, we have demonstrated that Switch DARPins allow conditional tumor-localized immune activation only in the presence of defined targets, and the feasibility of conditional T cell activation with potent co-stimulation in solid tumors while sparing healthy tissues.