News
Company News: Merus starts Phase I/II clinical trial for MCLA-128, an ADCC-enhanced bispecific antibody for solid tumors
– First patient dosed in trial with potent bispecific antibody overcoming resistance to HER2-targeted therapies –
Merus B.V., a leader in developing best-in-class bispecific antibody therapeutics to treat cancer patients, today announced the initiation of a phase I/II clinical study of MCLA-128 for the treatment of solid tumors. MCLA-128 is an ADCC-enhanced, full-length IgG bispecific antibody that simultaneously targets the growth factor receptors HER2 and HER3.
The trial is an open-label, European multi-center dose escalation study to assess the safety, tolerability and anti-tumor activity of MCLA-128. The first part of the study is designed as a dose escalation study, followed by a second part to further characterize the safety, tolerability and clinical efficacy of MCLA-128. Initially, the study will enroll 52 patients with advanced epithelial tumors. Primary endpoint is safety; secondary endpoints include, among others, the immunogenicity of MCLA-128 as well as anti-tumor response and clinical benefit.
Company News: InDex Pharmaceuticals to present results from the COLLECT trial at the 10th Congress of the European Crohn’s and Colitis Organisation
InDex Pharmaceuticals today announced that results from COLLECT, a clinical study of the toll-like receptor 9 (TLR9) agonist Kappaproct as an add-on therapy for patients with moderate to severe, chronic active Ulcerative Colitis, will be subject to an oral presentation at the 10th Congress of the European Crohn’s and Colitis Organisation (ECCO). The congress is to be held in Barcelona, Spain on February 18-21, 2015.
In the COLLECT study, 131 patients with moderate to severe Ulcerative Colitis and inadequate response to conventional therapy received either Kappaproct or placebo as an add-on to conventional treatment. The study was conducted at 40 sites in seven European countries.
Despite not meeting the primary endpoint of inducing clinical remission measured at week 12, defined by a clinical activity index (CAI) score of ≤4, Kappaproct showed statistically significant improvement on important secondary endpoints at week 4 and 8, including symptomatic remission (blood in stool, number of stools) and registration remission (clinical remission with concurrent endoscopic remission) as well as rate of colectomy at week 22. Kappaproct was well tolerated and no safety signals compared to the standard of care treatment group were evident. The data strongly support continued development of Kappaproct as a promising and well-tolerated novel therapeutic option for refractory ulcerative colitis patients. The next phase III study is planned to start this year.
The presentation (Oral presentation #15) titled “Multicentre clinical trial with topical administration of the Toll-Like receptor 9 agonist DIMS0150 shows evidence for efficacy in moderate to severe Ulcerative Colitis” will be held by Professor Raja Atreya from the University of Erlangen-Nürnberg on Friday, February 20th, 2015, at 14.20pm CET.
Company News: ISA Pharmaceuticals – New Study Explains Synergy between Cancer Vaccine ISA101 and Chemotherapy
– Tumor necrosis factor alpha (TNFα) produced by T cells following vaccination sensitizes tumor cells for eradication by certain chemotherapeutics
– Data published in Clinical Cancer Research support ongoing clinical development of ISA101
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, has announced new findings on the synergy between its synthetic long peptide (SLP®) cancer vaccine and chemotherapeutics. Data published in Clinical Cancer Research* demonstrate that combined chemo-immunotherapy leads to superior T cell-mediated tumor eradication in the absence of T cell immunosuppression.
In a preclinical model of cancer induced by human papillomavirus type 16 (HPV16), ISA’s lead SLP® candidate ISA101 was combined with seven clinically relevant chemotherapeutics to treat established tumors. The researchers tested either ISA101 or chemotherapeutics alone as well as combinations of both. Topotecan, gemcitabine, carboplatin and cisplatin showed synergies with ISA101. The most effective combination was cisplatin plus ISA101, resulting in tumor regression and the durable survival of 75% of the mice, and a lasting immune response. Most importantly, synergy occurred to the same extent at only 40% of the maximum tolerated dose (MTD) of cisplatin, allowing for a reduction of chemotherapy-associated side effects as seen at MTD. There was no synergy between ISA101 and oxaliplatin, doxorubicin or paclitaxel.
While synergy was not related to overt changes in systemic T cell immunity or increased sensitivity of cisplatin-treated TC-1 tumor cells towards CTL-mediated killing, there was a strongly enhanced leukocyte infiltration of the tumor. Vaccine-specific polyfunctional CD8 T cells were a major component of this infiltration. The cisplatin allowed these cells to migrate earlier into the tumor beds, enabling them to eliminate tumor cells at an earlier stage of disease. Once inside the tumor, the T cells further enhanced tumor cell death by producing pro-inflammatory cytokines such as IFNγ and TNFα. In particular, TNFα produced by intratumoral T cells sensitized the tumor cells for cisplatin, allowing for synergistic cell death.
Another study presented at AACR in 2014, showed that cis-/carboplatin/paclitaxel depletes myeloid derived suppressor cells in patients, and thereby strongly increases an ISA101-mediated immune response.
This finding supports the ongoing clinical development program in which ISA101 is tested in a Phase I/II study (CervISA) in combination with cisplatin/carboplatin and paclitaxel in women with advanced or recurrent cervical cancer.
* van der Sluis TC et al.: Vaccine-induced Tumor Necrosis Factor producing T-cells synergize with cisplatin to promote tumor cell death. Clin Cancer Res. 2014 Dec. 12 pii: clincanres.2142.2014; Epub 2014 Dec. 12,; doi: 10.1158/1078-0432.CCR-14-2142
Company News: After U.S. court ruling, Merus reaffirms freedom to operate for its MeMo® transgenic mouse for therapeutic human antibodies
– Regeneron’s ‘018 patent’ is considered invalid and Merus not infringing –
Merus B.V., a leader in developing best-in-class antibody therapeutics to treat cancer patients, today announced a series of pivotal events in its litigation with Regeneron Pharmaceuticals Inc. Previously, Regeneron sued Merus accusing it of infringing U.S. Patent No. 8,502,018 (‘018 patent’) directed to a particular method of making a genetically modified mouse, which Regeneron asserted was useful to produce therapeutic antibodies.
Merus argued that Regeneron had interpreted its patent in an overbroad manner, and that the patent claims were indefinite and invalid. On November 21, 2014, in a fifty-nine page decision, the United States District Court for the Southern District of New York agreed with Merus on virtually every issue, stating: “[t]his Court generally agrees with the constructions Merus proposes, limiting the Patent to a far narrower scope than asserted by Regeneron.” The court also ruled that Merus has demonstrated “clear and convincing evidence that [a key claim term] lacks reasonable certainty and is therefore indefinite.” On December 19, 2014, Regeneron filed papers with the court conceding that under these rulings, Merus does not infringe any asserted claim of the ‘018 patent, and that these claims are invalid. With this ruling and Regeneron’ s concessions, there are no outstanding claims against Merus. The only remaining issues include Merus’ claim against Regeneron that it unlawfully procured its patent from the U.S. Patent Office and Merus’ request that Regeneron pay the legal fees incurred by Merus.