MacroGenics Reports Interim Clinical Data for Multiple Drug Candidates

MacroGenics (NASDAQ:MGNX) reported preliminary clinical data from the Phase 1 dose escalation and expansion clinical trial of MGD013 and from the Phase 1 dose expansion study of MGC018. The former drug candidate is aimed at treating patients with unresectable or metastatic neoplasms while the latter targets patients suffering from advanced solid tumors.

MGD013 aims to work by blocking PD-1 and LAG-3 checkpoint molecules to endure or reinstate the function of exhausted T cells. This dose escalation part of the study involved 53 patients suffering from advanced tumors. The patients were administered the drug candidate intravenously in cohorts of escalating flat doses of 1-1,200 mg every two weeks. For tumor-specific expansion cohorts, a flat dose of 600 mg every two weeks was selected.

As of the cutoff date of April 25, 2020, 205 eligible patients were administered the monotherapy, out of which 152 were found evaluable. Response Evaluation Criteria in Solid Tumors (RECIST) was used for measuring anti-tumor activity. For triple negative breast cancer, Objective Response Rate of 17 percent was observed while 39 percent patients showed Disease Control Rates. The ORR and DCR for epithelial ovarian cancer was 9 percent and 52 percent respectively. It was observed that the response to MGD013 monotherapy was linked with LAG-3 expression and an IFN- gene signature at baseline.

The combination cohort showed that the majority of responders whose baseline tumors were evaluated were negative for (or expressed low levels of) LAG-3 or PD-L1. This observation was in contrast to the findings in monotherapy cohort.

The other drug candidate MGC018 is being tested for solid tumors and involves delivering a DNA alkylating duocarmycin payload to dividing and non-dividing cells that express B7-H3. This ligand is found related to poor clinical outcome. The data cutoff date for the study was May 6, 2020, and by then 23 patients suffering from advanced solid tumors were enrolled in four different cohorts. The company is currently carrying out enrollment for a fifth cohort with 4 mg/kg every three weeks dose regime.

Out of the seven patients with advanced metastatic castration-resistant prostate cancer treated, five observed reductions in PSA levels of . 50%. Patients with mCRPC had been given a median of four therapies prior to MGC018, including taxane chemotherapy. The safety profile of the drug candidate has been generally manageable to date. Some of the most commonly occurring adverse events were skin and hematologic toxicities. 22 out of 24 patients reported at least one treatment related adverse event; however, no febrile neutropenia was observed.

MacroGenics is a clinical-stage biopharmaceutical company. The main focus of the company is to develop monoclonal antibody-based therapeutics for treating cancer. The company has its own proprietary suite of next-generation antibody-based technology platforms which is used for developing product candidates for different therapeutic domains.

Bristol-Myers Squibb (NYSE:BMY) reported that the FDA has sent a Refusal to File letter with regard to its Biologics License Application pertaining idecabtagene vicleucel or ide-cel. The drug candidate is being developed for treating patients suffering from heavily pre-treated relapsed and refractory multiple myeloma. The application was submitted in March 2020. Bristol-Myers Squibb is collaborating with bluebird bio (NASDAQ:BLUE) for developing this medicine.

The company stated that the FDA required the companies to provide further details related to the Chemistry, Manufacturing and Control (CMC) module of the BLA. However, it has not requested any additional clinical or non-clinical data. Bristol-Myers Squibb said that it plans to resubmit the BLA by the end of July 2020. Bristol CEO Giovanni Caforio said, We believe we submitted a completed dossier to the FDA, so what we are really discussing here is the level of detail the FDA has requested. However, the company still believes that it may accomplish expedited approval.

Bristol-Myers Squibb had acquired ide-cel as a part of its purchase of Celgene. The acquisition had brought five key pipeline assets to Bristol-Myers Squibb's portfolio. It is also one of the three key regulatory milestones required to be met for triggering Contingent Value Rights granted to the shareholders. The other two drug candidates are liso-cel and multiple sclerosis drug Zeposia (ozanimod). As per the terms of the acquisition, the approval for the drug candidate is required to be obtained by March 2021.

Ide-cel is a B-cell maturation antigen directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy. The drug candidate was granted Breakthrough Therapy Designation (BTD) by the FDA. It also has Accelerated Assessment status and PRIority Medicines (PRIME) designation in European Union.

Enochian Biosciences (NASDAQ:ENOB) stock jumped up as the company provided updates about three of its pipeline candidates related to HIV and HBV. Two of the presentations are related to HIV while the remaining one is concerned with HBV. The HIV trials deal with genetic modification of cells for overexpressing ALDH1, an enzyme which helps them protect against low doses of chemo agent cyclophosphamide. For HBV, mouse studies have shown the potential of using caspase-9 enzyme.

Enochian has undertaken a novel approach towards treating HIV. The in-vivo study carried out by the company showed a 164 percent increase in engraftment of genetically modified cells. The study pertains to Hematopoietic stem-cell transplantation (HSCT) mechanism which has been tested for a number of diseases including HIV. Aldehyde dehydrogenase-1, or ALDH1, is a naturally occurring enzyme in human stem/progenitor cells. It is known to provide enhanced cellular resistance to cytotoxic agents such as cyclophosphamide (CY). The company is working on the hypothesis that low dosage of cyclophosphamide may help in increasing engraftment of human stem/progenitor cells.

The data demonstrated that the percentage of peripheral blood granulocytes overexpressing ALDH1 increased from week 7 through 12 for all doses but was highest at 16mg/kg (95.2%) and 19mg/kg (93.5%). Further, the data also showed that ALDH1 expression increased in absolute number of granulocytes compared to control at all dose levels. The amount was the highest at 16mg/kg dosage. The average VCN in bone marrow cell was highest at 16mg/kg CY at the end of the study.

For its HBV treatment path, the company seeks to rely upon using the virus and cellular machinery for killing the infected cells. The study examined the expression of casp-9 in AAV2-treated HepG2 and the HBV-infected HepAD39 cell lines. AAV2 particles expressing Hijack RNA test AAV or green fluorescent protein were used for treating HBV-infected and uninfected hepatoma cell lines and primary human hepatocytes. The data showed 254% increase in casp-9 levels in the treated HBV-infected cells.

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