Encouraging Additional Phase 3 Data Presented for Abicipar, and Start of Phase 1 Trial for MP0310, the First Immuno-oncology DARPin® with a Novel Therapeutic Design
Zurich-Schlieren, October 31, 2019. Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of drugs known as DARPin® therapies*, announced today its Interim Management Statement for the period ending September 30, 2019.
“Abicipar represents the first DARPin® therapeutic to be accepted for review by FDA (U.S.) and EMA (EU), validating the potential of the DARPin® platform to yield candidates that fulfill all dimensions of development necessary for approval. We are convinced that the expected consistent 12-week dosing interval of Abicipar can bring benefit to patients,” said Patrick Amstutz, Ph.D., Chief Executive Officer of Molecular Partners. “Additionally, we are proud that MP0310, our first candidate from our suite of novel therapeutic design immuno-oncology molecules, has successfully entered the clinic. We are recruiting patients to evaluate MP0310’s ability to localize activation of the immune system to the tumor, potentially enabling higher anti-cancer activity without dose-limiting systemic side-effects.”
Oncology: Update of MP0250 in multiple myeloma to be presented in Q4 19
MP0250 is a multi-DARPin® candidate that targets hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), two prominent tumor escape pathways, and has the potential to reverse adaptive resistance to standard of care cancer therapies.
The first phase 2 trial for MP0250 in combination with proteasome inhibitors (PIs) is evaluating MP0250 in combination with bortezomib (Velcade®) and dexamethasone in patients with multiple myeloma who have failed standard therapies. The company will provide an update on the phase 2 trial data at both the ASH conference in Orlando and at the company’s R&D Day in New York City.
Immuno-oncology: Initiation of phase 1 trial of MP0310, a novel tumor-localized immunotherapy
For MP0310, also referred to by Amgen as AMG 506, the first patient has been enrolled and dosed in the first-in-human study of MP0310 as a single agent in patients with advanced solid tumors. The trial will evaluate the optimal dose range of MP0310 in preparation for planned combination studies with Amgen’s oncology pipeline products.
MP0310 is the first product candidate in Molecular Partners’ DARPin® 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. Preclinical studies of MP0310 have demonstrated immune T cell activation restricted to solid tumor tissues, and strong CD8 T cell activation and expansion in vitro and in vivo. Additionally, preclinical data show MP0310 does not induce strong systemic activation of CD8 T cells and, therefore, has lower risk of the systemic side effects and toxicities.
The MP0310-CP101 trial intends to enroll up to 54 patients at three sites in France. The open-label, dose-escalation study will evaluate the safety, tolerability and pharmacokinetics of MP0310 in patients with locally advanced or metastatic solid tumors.
Abicipar: Additional encouraging two-year data from phase 3 studies in nAMD presented at AAO
Allergan and Molecular Partners announced the two-year data from the CEDAR and SEQUOIA clinical studies of abicipar in patients with neovascular (wet) age-related macular degeneration (nAMD) at the annual meeting of the American Academy of Ophthalmology (AAO) in San Francisco. In the second year of these studies, quarterly-dosed of abicipar resulted in the maintenance of visual gains comparable to monthly-dosed ranibizumab (Lucentis®).
Through week 104, patients received 2 mg of abicipar every 8 weeks or every 12 weeks, or 0.5 mg of ranibizumab every 4 weeks. At week 104 in the pooled phase 3 data, the proportion of patients with stable vision was 93%, 90% and 94% in 8-week abicipar, 12-week abicipar and 4-week ranibizumab treatment regimens, respectively. This continuation of stable vision in the second year further reinforces the ability of abicipar to deliver effective outcomes with consistent quarterly dosing for the majority of patients.
Mean changes in best-corrected visual acuity (BCVA) seen in year two were similar when compared to year one across all treatment arms. Central retinal thickness (CRT) continued to decrease during year two when compared to year one. CRT for patients treated with abicipar dosed quarterly and every 8 weeks were similar to ranibizumab dosed every 4 weeks through week 104. Overall incidence rates of treatment-emergent adverse events at the end of year two were comparable between treatment groups. The pooled rate of new cases of intraocular inflammation in year two for patients who received abicipar in the 8- and 12-week arms was 1.9%, which is similar to the ranibizumab arm of 1%. The data shown at AAO therefore reinforce a sustained response at two years with less frequent dosing of abicipar compared to standard of care therapy.
Abicipar: FDA accepted the BLA and EMA the MAA for patients with nAMD in Q3 2019, key milestones for the company and its DARPin® technology platform
In the third quarter 2019, the U.S. Food and Drug Administration (FDA) accepted a Biologics License Application (BLA) and the European Medicines Agency (EMA) validated a Marketing Authorisation Application (MAA) for abicipar pegol, a novel, investigational DARPin® therapy, in patients with neovascular (wet) age-related macular degeneration (nAMD). The FDA is expected to take action on the BLA mid-2020. A decision from the European Commission is expected in the second half of 2020.
The BLA and MAA filings are based on data from two phase 3 trials, 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. The FDA filing acceptance marked an important milestone for the DARPin® technology as abicipar becomes our first DARPin® candidate to receive filing acceptance by the FDA.