MP0250

MP0250 is a proprietary, multi pathway DARPin® drug candidates that inhibits both VEGF and HGF. MP0250 is being tested in Phase 1 clinical studies in solid tumor cancers and hematological malignancies. It simultaneously targets tumor stroma, proliferation, invasion and metastasis.

We recently announced our plans to initiate a Phase II clinical trial of MP0250 patients with multiple myeloma (MM) and expect to enroll the first patient in the second half of 2016. The trial will study MP0250 in combination with bortezomib (Velcade®) and dexamethasone in patients with multiple myeloma who have developed resistance to bortezomib and have received at least two prior regimens, including bortezomib and an immunomodulatory drug (IMiD).

VEGF and HGF are both well studied disease pathways implicated in cancer. Compared to previous approaches, we focus on situations where HGF is (together with VEGF) an important resistance pathway helping tumor-cells to escape standard of care treatment.

MP0250 is the first bi-specific biologic targeting both VEGF and HGF and may be ideal to be used in combination with standard of care therapy, such as chemotherapy or tyrosine kinase inhibitors (TKIs) or immuno-oncological treatments.

We believe that MP0250 has strong potential to become a valuable treatment option in several solid tumors and hematological malignancies, including MM, head & neck cancers and others.

On October 9, 2016, the company presented completed Phase 1 dose escalation interim results of MP0250 at the Conference of the European Society of Medical Oncology (ESMO) in Copenhagen. These data, based on the enrollment of a total of 24 patients, are an important milestone in the development of DARPin® proteins as anticancer agents and expand the results that had been published following a poster presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, Mass. on Saturday, November 7, 2015

  • MP0250, used as single agent, is the first DARPin® drug candidate to be studied in humans as systemic treatment
  • MP0250 was well tolerated at the higher dose levels (up to the maximally tolerated dose of 8 mg/kg administered every 2 weeks)
  • This is an important milestone because it proves that DARPin® proteins do not negatively impact the immune system of humans and can be engineered to have a systemic half-life of around two weeks
  • The drug is well tolerated and the side effect profile is consistent with profound inhibition of the VEGF pathway
  • MP0250 has the potential to become a new therapeutic in treating various tumor types

 

Phase 2 strategy for MP0250: Initiation for two phase 2 trials planned for 2017

The first phase 2 study will examine MP0250 in combination with bortezomib (Velcade®) and dexamethasone in patients with multiple myeloma who have failed standard therapies. The first regulatory submission for such study is planned for 4Q 2016 with first safety data expected in 2017 and efficacy data in 2018.

Based on the encouraging data from Phase 1 in solid tumors, Molecular Partners committed to run an additional phase 2 trial for a solid tumor indication. Study details will be disclosed in H1 2017.

  • In a preclinical model of MM, the combination of MP0250 and bortezomib showed substantial antitumor activity in settings where bortezomib had very little effect as a single agent. In addition to inhibiting tumor growth, the combination of MP0250 and bortezomib resulted in a significant reduction in bone destruction, one of the most important clinical hallmarks of this disease.

 

Vascularization in cancer cell

Cancer Cell

MP0274

MP0274 is a proprietary, single pathway DARPin® drug candidate. It has broad anti-HER activity and is in preclinical studies, for the treatment of HER 2+ breast cancer.

MP0274 binds to HER2 and inhibits downstream HER2 and HER3-mediated signaling. It is thought to induce tumor regression and durable anti-tumor responses in breast and other HER2-expressing cancers. There is a synergistic effect of HER2 and HER3 blockade; MP0274 blocks HER2 homo- and HER3 hetero-dimerization and induces HER2 internalization.

Preclinical animal models show strong anti-HER activity and this compound has the potential to produce a higher rate of cancer cell death than Herceptin®.

  • MP0274 is currently in preclinical development with the goal to develop a powerful alternative for HER2 positive cancer patients
  • The company plans the first regulatory submission for the envisaged Phase 1 trial of MP0274 in 1Q 2017

Researchers recently presented pre-clinical data for MP0274 at the San Antonio Breast Cancer Symposium in December 2016. Here is a link to the poster presentation. The main conclusions from the poster include:

  • HER2 positivity is an important predictive factor for treatment with anti-HER2 agents in several cancers
  • However, currently available monoclonal antibody and tyrosine kinase inhibitor drugs rarely achieve full disease control
  • We have developed a new HER2-targeting molecule with a unique proapoptotic mode of action that may provide additional benefit to patients
  • The DARPin® drug candidate, MP0274, binds to two distinct non-overlapping HER2 epitopes and also to human serum albumin for half-life extension
  • MP0274, with its unique proapoptotic mode of action, demonstrates excellent activity in HER2-expressing PDX models, fast localization to HER2-expressing tumors and a PK profile consistent with a compound binding to HER2 receptors
  • MP0274 was well tolerated in all studies
  • These results suggest that MP0274 has the potential to provide additional clinical benefit to patients with HER2-expressing tumors
  • DARPin® is a registered trademark owned by Molecular Partners AG.

Inactive conformation of Her2 after handcuffing with MP0274

single path, multi-DARPin “locked up”