Pipeline
Our DARPin platform has vast applicability across a range of diseases. Explore our pipeline:

MP0317 / FAP x CD40: Solid Tumors
MP0317 / FAP x CD40 is the second therapeutic candidate in our immuno-oncology pipeline. It is designed to activate immune cells specifically in the tumor and not in the rest of the body, potentially delivering greater efficacy with fewer side effects.
Mechanism of Action
Need
While checkpoint antibodies have delivered strong clinical results, immune agonistic antibodies have been either too toxic or not efficacious, with no good therapeutic window. This is especially true for high-energy and multi-functional agonist targets like CD40.
Rationale
An immunotherapy that would solely activate immune cells in the tumor would allow super-activation while avoiding systemic side effects.
Solution
MP0317 includes DARPin domains that bind to localizer (FAP) and stimulator (CD40) molecules. FAP is found in the tumor stroma in high density and FAP binding will create a local super-cluster. If CD40 on immune cells is engaged at the same time, clustering occurs and we achieve local activation of immune cells. As activation only occurs when both targets are simultaneously engaged, there is only tumor local activity and no systemic side effects.

MP0533 / CD3 x CD33+CD70+CD123: AML
Molecular Partners’ T-cell engager (TCE) programs leverage the cell surface protein CD3 as a powerful immune activator, complemented by novel control mechanisms designed to help direct CD3-mediated cytotoxicity with heightened precision. Molecular Partners first TCE candidate is being developed as a unique multi-specific treatment for acute myeloid leukemia (AML). It is designed to deliver a deeper attack on a broader range of highly variable tumor cells while lowering the risk to healthy cells. This may allow Molecular Partners to significantly shift the therapeutic window for TCE use in AML, and avoid the trade-off between effective dosage and safety that other therapeutic developers have had to make.

Need
AML represents a highly resistant type of cancer with urgent need for effective therapies. Each year about 20,000 people in the U.S. are diagnosed with AML. Nearly half of these patients will die within two years of diagnosis due to the inability of current treatments to completely eradicate AML cells, particularly the population that initiate and sustain leukemia: leukemic stem cells (LSCs). CD3 represents a powerful tool in the fight against AML but development of CD3-based TCEs has consistently failed to deliver on its promise due to toxicities resulting from CRS, damage to healthy cells or an inability to overcome specific tumor defenses.
Rationale
The ability of DARPins to integrate several capabilities has allowed Molecular Partners to deliver a finely controlled mechanism for CD3-based immune activation in AML. Through highly individualized binding specificity of each DARPin, we can elicit a specific, and conditional immune activation. Our platform allows us to limit the ability of the CD3-engaging DARPin to ‘activate’ until a minimum of two of the target proteins, CD70, CD123 and CD33, are bound. Because of this, our candidate can better target all of the sick cells, , and avoid healthy ones..
CD70 has been identified as a prominent target that is more strongly expressed on LSCs. CD123 and CD33 are mainly expressed on the cells that make up the ‘bulk’ of the cancer cell population. Their presence on healthy cell types has led to dose-limiting toxicities in other types of therapies, but in combination with a DARPin that binds to CD70, the primary intended effect of binding CD33 and CD123 is to further focus candidate binding on tumor cells and reduce damage to healthy cells.
Solution
Our candidate incorporates this three-target combination. Preclinical studies have strongly supported the intended mode of action, including an avidity ‘ramp up’ effect, whereby the overall binding to a target cell is much stronger when more than two target proteins are present. This further reduces the risk to healthy cells, which very rarely have even two of the antigens in question.

Radio DARPin Therapies: DLL3 and more
Molecular Partners has developed an in-house Radio DARPin Therapy (RDT) Platform that represents a unique and innovative delivery system for radioactive payloads to solid tumors. Radioligand therapies have proven potential but with technological limitations that DARPins may address. Molecular Partners’s first disclosed target for its in-house RDT programs is Delta-like ligand 3 (DLL3). Expression of DLL3 is low in healthy tissue but significantly increased in certain tumor types, providing an opportunity for selective targeting through the high-affinity and specificity offered by DARPins. Molecular Partners is exploring additional targets amenable to Radio DARPin Therapies internally and in its collaboration with Novartis and potentially others.
Need
Radiation therapies are a well-validated approach to treating cancer. However, the treatment often also affects healthy cells, resulting in harmful side effects. This limits the amount of radiation patients can receive, which can leave hard-to-reach tumor lesions untreated. This encourages relapse and ultimately limits therapeutic potential.
Rationale
The unique nature of DARPins as an engineered protein drug class may allow Molecular Partners to overcome the limitations of other radioligand therapies. DARPins have great potential to enable robust, tumor-specific delivery of therapeutic radionuclides owing to their small size – allowing for great tumor penetration – high specificity and long tumor residence time. The DARPin scaffold is highly customizable allowing a range of additional features tuned to an indication. Ultimately this may enable more effective treatment of small or hard-to-reach tumors.
Solution
Preclinical data shows that Molecular Partners’ proprietary Radio DARPin Therapy Platform can deliver high amount of radioactivity to tumors without accumulating in other tissues. Further data shows that Molecular Partners has been able to engineer the surface of RDT candidates to dramatically reduce accumulation in the kidney which is a historical challenge for small protein-based delivery vectors. In preclinical models, this surface engineering did not affect tumor uptake or uptake in other healthy organs and combination with another kidney reduction strategy provided a cumulative benefit.

Radio DARPin Therapy Platform: Solid Tumors
Molecular Partners has developed an in-house Radio DARPin Therapy (RDT) Platform with a unique and innovative delivery system for radioactive payloads to solid tumors. In 2021, the Company established a collaboration with Novartis in the form of a license agreement to develop, manufacture and commercialize Radio DARPin Therapies for cancer.
Need
Radiation therapies are a well-validated approach to treating cancer. However, the treatment often also affects healthy cells, resulting in harmful side effects. This limits the amount of radiation patients can receive, which can leave hard-to-reach tumor lesions untreated. This encourages relapse and ultimately limits therapeutic potential.
Rationale
The unique nature of DARPins as an engineered protein drug class may allow Molecular Partners to overcome the limitations of other radioligand therapies. Radio DARPin Therapies are extremely targeted, specifically damaging tumor cells over healthy cells. The DARPin scaffold is highly customizable allowing a range of additional features tuned to an indication. Ultimately this may enable more effective treatment of small or hard-to-reach tumors.
Solution
Preclinical data shows that Molecular Partners’ proprietary Radio DARPin Therapy Platform can deliver high amount of radioactivity to tumors without accumulating in other tissues. Further data shows that Molecular Partners has been able to engineer the surface of RDT candidates to dramatically reduce accumulation in the kidney which is a historical challenge for small protein-based delivery vectors. In preclinical models, this surface engineering did not affect tumor uptake or uptake in other healthy organs and combination with another kidney reduction strategy provided a cumulative benefit.

Abicipar / VEGF: Wet AMD
Abicipar is a long-acting anti-VEGF therapeutic candidate, which was invented by Molecular Partners and initially licensed to Allergan in 2011. The program has been through two positive Phase 3 studies, CEDAR and SEQUOIA, which supported the non-inferior efficacy of the abicipar quarterly dosing regimen to maintain vision gains with more than 50 percent fewer injections versus ranibizumab (13 vs. 6) dosed monthly in the first year.
In June 2020, a Complete Response Letter was issued for the Biologics License Application for abicipar pegol, indicating that the rate of intraocular inflammation observed following administration of abicipar pegol resulted in an unfavorable benefit-risk ratio in the treatment of nAMD (AMD), and that additional work would be required to demonstrate a lower rate of ocular inflammation than what was previously seen in the Phase 3 studies. In 2021, Molecular Partners is to regain global rights to abicipar from AbbVie and is determining appropriate next steps for the program.
Need
Current anti-VEGF treatments are injected on a monthly, bi-monthly and — only in a subset of patents — on a quarterly basis. Less frequent injections are a key advantage for patients.
Rationale
An anti-VEGF with high potency and long ocular half-life would allow less frequent injections compared to standard therapies.
Solution
Abicipar has been engineered for a long half-life in the eye and highest potency. Phase 3 results have demonstrated that quarterly injections are equivalent to monthly injections of Lucentis®.

Ensovibep / Sars-Cov-2: COVID
Ensovibep is a COVID-19 antiviral therapeutic candidate designed specifically to inactivate SARS-CoV-2 – the virus that causes COVID-19 – with extremely high potency that is preserved against novel variants. In January 2022, we announced positive topline results from our Phase 2 global clinical study of ensovibep in acute COVID-19 ambulatory patients showing approximately 80 percent reduction of the of combined risk of hospitalization, emergency room visits, or death compared to placebo, regardless of vaccination status. It was shown to be safe and well-tolerated. Comprehensive in vitro studies of ensovibep demonstrate its high inhibitory potency against all COVID-19 variants of concern, including Omicron, as of December 2021. Novartis has informed Molecular Partners of its intent to in-license ensovibep and is expected to lead late-stage development and commercialization.
Ensovibep offers a differentiated approach to treating COVID-19 through a single molecule that can target up to three parts of the SARS-CoV-2 virus simultaneously to neutralize the virus through cooperative binding. This offers potentially broader efficacy and reduced potential for the development of viral drug resistance. All DARPins are produced through a rapid, high-yield microbial fermentation process.
MP0420

Need
COVID-19 represents the biggest disease burden in the world today through its impact on healthcare, society and economies. A multi-solution strategy is needed to combat the pandemic and the need for antiviral treatments to complement global vaccination efforts has never been greater. As disease transmission continues through pockets of unvaccinated populations, in patients with compromised immune systems and co-morbidities, and as variants continue to emerge, millions of patients around the world are in need of differentiated therapies that are specifically designed to combat COVID-19 in all its forms.
Rationale
The DARPin platform is designed to be used to rapidly generate diverse, multifunctional drug candidates, capable of binding to multiple targets at once. As a tri-specific candidate with cooperative binding, ensovibep’s unique pan-variant design has allowed it to retain full potency against all known variants of concern including the Omicron variant in comprehensive preclinical studies conducted to-date.
Solution
Ensovibep is a unique tri-specific candidate designed to preserve potency against viral variance. It exhibits among the most potent viral inhibition against all variants of concern reported to date. In the EMPATHY Phase 2 global clinical trial, ensovibep demonstrated approximately an 80 percent reduction of combined risk of hospitalization, emergency room visits or death in non-hospitalized patients compared to placebo regardless of vaccination status. It was shown to be safe and well-tolerated. If approved or authorized, ensovibep will be the first multi-specific antiviral molecule for the treatment of COVID-19.
- The Company continues to evaluate potential business opportunities for abicipar, outside of Molecular Partners.
- Molecular Partners was informed by Novartis that the Emergency Use Authorization (EUA) application from the U.S. Food and Drug Administration (FDA) for ensovibep was withdrawn effective January 25th, 2023. As previously disclosed, ensovibep is not presently in clinical development. However, Molecular Partners is pursuing several other research programs within virology.