Two months after laying out plans for bringing a second drug to market by 2025 and building a pipeline of oncology and hematology therapies, MorphoSys says it remains committed to those goals while changing how it plans to accomplish them—by focusing on later-stage clinical programs and consolidating in Europe its research operations, which expanded Stateside last year when the company acquired Constellation Pharmaceuticals.
Last week, Morphosys said it would concentrate its research activities on its most advanced programs for its four top drugs. The four include Monjuvi® (tafasitamab-cxix), a CD19-targeting monoclonal antibody marketed as a therapy for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in combination with lenalidomide; and Pelabresib (CPI-0610), a late-stage bromodomain and extra-terminal (BET) protein inhibitor being studied as a first-line treatment for myelofibrosis.
“[Last week’s] announcement does not change our plans to focus on hematology/oncology or to bring two medicines to market by 2025,” MorphoSys spokesman Eamonn Nolan told GEN Edge.
Monjuvi is in three Phase III trials. One trial is designed to evaluate the drug plus lenalidomide and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) versus R-CHOP alone in previously untreated, high-intermediate, and high-risk patients with newly-diagnosed DLBCL (frontMIND; NCT04824092).
“That’s a study that has more than 800 patients, and could move the needle significantly for patients who are diagnosed for the first time with diffuse large B cell lymphoma,” Malte Peters, MD, MorphoSys’ chief research and development officer, told GEN Edge, speaking of frontMIND. “You can imagine how much work it is to get this study off the ground, so we are doing really well.”
Primary analysis data from the pivotal frontMIND trial is expected to be released in the second half of 2025, MorphoSys has said.
The other two trials are designed to evaluate Monjuvi in relapsed or refractory follicular or marginal zone lymphoma (inMIND; NCT04680052), and relapsed or refractory DLBCL comparing the drug plus bendamustine to Genentech (Roche)/Biogen’s Rituxan® (rituximab) plus Bendamustine (B-MIND; NCT02763319). Incyte is overseeing inMIND, with MorphoSys carrying out the other Monjuvi studies.
MorphoSys says it expects to release primary analysis data from the pivotal inMIND trial in the second half of 2023.
B-MIND is less of a priority for MorphoSys, Peters said, because of the broad label received for Monjuvi in the United States, where MorphoSys co-markets the drug with Incyte under an accelerated approval granted in 2020; and Europe, where Incyte markets the drug alone as Minjuvi under conditional marketing authorization granted last year.
Last year at the 2021 American Society of Clinical Oncology (ASCO) annual meeting, MorphoSys published and presented positive three-year follow-up data from the Phase II L-MIND trial (NCT02399085) showing an objective response rate of 46 of 80 patients (57.5%), including a complete response in 32 of 80 (40%) and a partial response in 14 of 80 (17.5%). The median duration of response was 43.9 months, the median overall survival was 33.5 months, and the median progression-free survival was 11.6 months.
MorphoSys has also presented long-term overall survival (OS) benefit for second-line Monjuvi starting at 87% of patients one year following treatment, declining to 68% after two years, 60% after three, and 49% after four years. Median OS stood at 45.7 months in second-line patients and 15.5 months in patients undergoing third- and later-line treatment with Monjuvi.
While MorphoSys cautioned that the long-term data was exploratory—“no formal conclusion can be drawn”—Peters said the data proved positive enough to warrant further long-term study.
“I would say the data is so strong and so reassuring, indicating that four years after the initiation of therapy in our L-MIND study, roughly half of the patients who are second-line are still alive,” Peters said. “We are getting now in a range of where you could actually think about potentially curing people with this disease, which was previously always a death sentence for pretty much everybody.”
During the company’s presentation at the virtual J.P. Morgan 40th Healthcare Conference in January, CEO Jean-Paul Kress, MD, committed MorphoSys to bringing Pelabresib through clinical studies toward a commercial launch by 2025, giving the company two marketed drugs. Pelabresib, which the company acquired with Constellation, is under study in the Phase III MANIFEST-2 pivotal trial (NCT04603495), comparing the drug plus Incyte’s Jakafi® (ruxolitinib) to Opzelura alone; and the Phase II, open-label MANIFEST study (NCT02158858), evaluating the drug with and without Jakafi.
Primary analysis data from MANIFEST-2 is expected in the first half of 2024. The study’s primary endpoint is splenic response, defined as a ≥35% reduction from baseline in spleen volume (SVR35), as measured by magnetic resonance imaging (MRI) or computerized tomography (CT), at Week 24. The trial’s key secondary endpoint of the study is Total Symptom Score response (TSS50), defined as a ≥50% decrease from baseline in Total Symptom Score as measured by the Myelofibrosis Symptom Assessment Form v4.0, at Week 24.
“Our clear focus is to get the MANIFEST-2 study for Pelabresib completed and to file in front-line myelofibrosis, and to also get the front-line DLBCL study completed to file in front-line DLBCL,” Peters said.
At last December’s 63rd American Society of Hematology Annual Meeting and Exposition (ASH 2021), MorphoSys trumpeted positive Phase II data showing 57 patients (68%) treated with Pelabresib and Jakafi achieved SVR35 from baseline at week 24, while 47 patients (60%) maintained SVR35 at week 48. Most patients also saw their symptoms reduced, with 46 patients (56%) achieving TSS50 from baseline at week 24.
Pelabresib is designed to suppress cytokine production, promote red blood cell differentiation, and normalize megakaryocyte differentiation.
MorphoSys has also committed to advancing two pipeline drugs—CPI-0209, an enhancer of zeste homolog 2 (EZH2) Inhibitor in Phase II studies to treat advanced solid tumors and hematologic malignancies; and felzartamab, a CD38-targeting antibody in Phase II studies to treat Immunoglobulin A nephropathy and anti-PLA2R-positive membranous nephropathy. CPI-0209 came from Constellation, while felzartamab is derived from MorphoSys’ human combinatorial antibody library (HuCAL).
“We will have clinical data in the second half of this year for both compounds, and then we will decide how we move forward with them: Can we continue on our own, do we need a partner? Do we need some help bringing these products over the finish line? It will depend a little bit on how strong the data is,” Peters said.
MorphoSys is also partnering with a pair of pharma giants on two Phase III pipeline candidates:
- Gantenerumab, a Roche-developed anti-amyloid beta antibody under study for treating and preventing Alzheimer’s disease. Roche said on March 2 that data from the Phase III GRADUATE 1 (NCT03444870) and GRADUATE 2 (NCT03443973) trials will be released in the fourth quarter of this year.
- Otilimab (GSK3196165), a GlaxoSmithKline (GSK)-developed human monoclonal antibody directed against GM-CSF (granulocyte-macrophage colony-stimulating factor), under development for the treatment of rheumatoid arthritis. The companies are expected later this year to announce data from the Phase III ContRAst trial (NCT04134728).
MorphoSys said it will consolidate its research operations into a single hub near Munich in Planegg, Germany, where the company is headquartered. “Consequently, all U.S.-based activities relating to discovery biology and drug discovery departments were discontinued,” MorphoSys said in a statement.
Those activities were assumed by MorphoSys when it shelled out $1.7 billion to acquire Constellation, in a deal intended to expand the buyer’s presence in blood cancer treatments and expand it into solid tumors.
Constellation had 180 staffers when it was acquired by MorphoSys, of which “38 positions were eliminated as part of this consolidation,” Nolan said. The consolidation will bring MorphoSys’ headcount to 732 employees globally.
Morphosys will continue to operate in the United States, where it plans to still run operations out of Boston. There, Nolan said, the company will be “continuing to build a leading team across many different disciplines, with a focus on product development and commercialization.”
As a result of the research consolidation, MorphoSys said, it will incur a €231 million ($253 million) non-cash “goodwill” impairment charge that will add to operating expenses for the fourth quarter of 2021, as Constellation’s early-phase pipeline was deemed part of the goodwill resulting from MorphoSys’ acquisition of the company.
In January, MorphoSys reported $79.1 million in preliminary 2021 U.S. net product sales for Monjuvi, of which $23.6 million was generated during the fourth quarter. MorphoSys records 100% of U.S. product sales, but splits the resulting profit or loss 50-50 with Incyte, its partner in the development of Monjuvi. At the time, MonphoSys offered guidance to investors that projected U.S. net product sales in 2022 would range between $110 million and $135 million.
The company is scheduled to report Q4 and full-year 2021 results on Wednesday.