Pipeline
Our DARPin therapeutics offer unique solutions
to challenges not readily addressable by other modalities
Co-development*
MP0712 / 212Pb x DLL3 Radio-DARPin Therapy: SCLC and neuroendocrine tumors
MP0712 is a targeted alpha radiotherapy directed specifically against DLL3 (delta-like ligand 3), a validated target expressed in more than 85% of patients with small cell lung cancer (SCLC).
Despite recent advances in the treatment of SCLC, there is still a high unmet need for patients not responding or relapsing from bispecific T-cell engagers or antibody-drug conjugates (ADC).
MP0712 delivers the potent alpha-emitting therapeutic isotope 212Pb in a targeted manner to DLL3-expressing tumor cells, thereby killing tumor lesions and minimizing impact on healthy tissues. This powerful mode of action offers the potential to significantly improve treatment options for these patients.
MP0712 is currently being evaluated in a US multi-site Phase 1/2a study in patients with SCLC and other DLL3-expressing neuroendocrine cancers (https://clinicaltrials.gov/study/NCT07278479).
MP0712 is being co-developed by Molecular Partners and our strategic partner Orano Med, a pioneer in targeted alpha therapy.
MP0726 / 212Pb x MSLN Radio-DARPin Therapy: Ovarian cancer
MP0726 is a radiopharmaceutical delivering the potent alpha-emitting therapeutic isotope 212Pb to mesothelin (MSLN) expressing tumors. MSLN is a tumor target highly expressed in patients with ovarian cancer (>80% prevalence), and its expression is maintained in metastases. Molecular Partners has designed DARPins which selectively bind to a MSLN part proximal to the target cell membrane to avoid impact from high shedding, a potential challenge for the development of therapeutics against MSLN.
MP0726 is being co-developed by Molecular Partners and our strategic partner Orano Med, a pioneer in targeted alpha therapy.
MP0317 / FAP x CD40: Advanced Solid Tumors
MP0317 is a tumor-localized CD40 agonist designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP) which is found at high density in the tumor stroma. This tumor-localized mechanism of action aims to achieve greater activity with fewer side effects compared to systemic CD40-targeting therapies.
MP0317 is currently being evaluated in an investigator-initiated, proof-of-concept Phase 2 study in combination with standard-of-care (SoC) for the treatment of patients with advanced cholangiocarcinoma (https://clinicaltrials.gov/study/NCT07036380). The study is a randomized, multicenter study in France with the objective to assess the clinical benefit of MP0317 combined with SoC, which comprises the immunotherapy durvalumab (an anti-PD-L1 checkpoint inhibitor) plus gemcitabine-cisplatin-based chemotherapy. The tumor microenvironment (TME) is known to play a crucial role in cholangiocarcinoma development and treatment resistance. MP0317 is hypothesized to lead to immune-mediated reshaping of the TME, thereby improving the 12-month progression-free survival rate of patients compared to those treated with SoC only.
Mechanism of Action
MP0533 / CD33 x CD123 x CD70 x CD3: r/r AML and AML/MDS
MP0533 is a novel tetra-specific T cell engager designed to kill all acute myeloid leukemia (AML) cells – blasts and also leukemic stem cells known to drive relapse – while minimizing damage to healthy cells. MP0533 targets three antigens preferentially co-expressed on AML cells. The strength of binding to cells increases with the number of targets engaged, thereby strongly favoring binding to AML cells over healthy cells.
MP0533 is currently being evaluated in a Phase 1/2a study in patients with relapsed/refractory AML or myelodysplastic syndrome (MDS) (https://clinicaltrials.gov/study/NCT05673057).
Mechanism of Action
MP0632 / CD3 x CD2 x MSLN X EpCAM Switch-DARPin
MP0632 is a logic-gated Switch-DARPin T-cell engager (TCE), designed to achieve conditional tumor-localized immune activation targeting MSLN and EpCAM, which are highly co-expressed in ovarian cancer and other solid tumors. The CD3-engaging DARPin is unmasked (“Switched” on) and activates T cells only upon binding to both MSLN and EpCAM. MP0632 is half-life extended through a Fc domain, which broadens the Company’s capabilities in half-life engineering modalities.
Mechanism of Action
MP0621 / cKIT x CD16a x CD47 Switch-DARPin
MP0621 is a Switch-DARPin candidate designed to induce killing of hematopoietic stem cells (HSCs) as a next-generation conditioning regimen for HSC transplantation.
MP0621 is an immune cell engager which combines targeting of cKit with conditional blockade of CD47. cKit is a highly attractive target to eliminate HSCs as it is critical for stem cell maintenance and renewal. The CD16a DARPin enables engaging NK cells and macrophages to selectively kill HSCs. Conditional blocking of the “do-not-eat-me” signal (CD47) only on HSCs via a Switch-DARPin allows leveraging the power of CD47 inhibition without its associated toxicity.
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.
Mechanism of Action
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 co-development agreement with Orano Med includes ten programs, including MP0712 (DLL3) and MP0726 (MSLN).
