Astrazeneca plc, of Cambridge, U.K., said the European Commission has approved a new indication for Faslodex (fulvestrant) in combination with a CDK4/6 inhibitor, palbociclib, for the treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer in women who have received prior endocrine therapy. The approval is based on data from the phase III PALOMA-3 trial, which showed a statistically significant increase in investigator-assessed median progression-free survival of 4.9 months (9.5 months vs 4.6 months) in patients who received fulvestrant 500 mg and palbociclib 125 mg over fulvestrant and placebo (p <0.0001).
Autolus Ltd., of London, said an article describing a targeting strategy for the treatment of patients with T-cell lymphomas has been published in Nature Medicine. The approach is based on the mutually exclusive expression of two subtypes of the T-cell receptor beta chain (TRBC1 and TRBC2). Normal T cells contain both TRBC1 and TRBC2 compartments whereas T-cell lymphoma cells express only TRBC1 or TRBC2 due to clonal origin and evolution of those cancerous cells. As proof of concept for anti-TRBC immunotherapy, anti-TRBC1 CAR T cells were developed, which recognize and kill normal and malignant TRBC1 but not TRBC2 T cells in mouse models of T-cell lymphoma. Unlike nonselective approaches targeting the entire T-cell population, that approach eradicates a portion of T cells containing the malignancy while preserving a healthy T-cell subpopulation to preserve cellular immunity. The work forms the scientific basis for AUTO-4, a CAR T-cell product developed by Autolus to target TRBC1, which is due to enter the clinic shortly.
Bioxcel Therapeutics Inc., of Branford, Conn., and Nektar Therapeutics Inc., of San Francisco, entered a research collaboration to explore the combination of Nektar's NKTR-214, a CD122-biased agonist, and BTI's BXCL-701, a small-molecule immune-modulator and DPP 8/9 and FAP inhibitor, for the treatment of multiple oncology indications. The collaborative research studies will evaluate the potential of the therapies in preclinical mouse models of pancreatic and prostate cancers. Financial terms were not disclosed.
Bristol-Myers Squibb Co., of New York, and Syngene International, an Indian CRO, said they expanded their ongoing collaboration, which will include the addition of a new facility to support future BMS R&D operations, an expansion of the team and extension of the existing agreement through 2026. The companies said the expansion will enable them to undertake a greater range of scientific research and development for pharmaceuticals across a broader range of activities. Financial terms were not disclosed. The companies have worked together since 1998.
Debiopharm International SA, of Lausanne, Switzerland, part of Debiopharm Group, said the EMA granted orphan drug designation to Debio-1347 for the treatment of biliary tract cancer. Debio-1347 is an orally available small molecule selectively targeting FGFR 1, 2, 3 signaling pathways and is currently being tested in a phase I study in patients with FGFR genomically activated advanced solid tumors, including patients with biliary tract cancer.
Endoceutics Inc., of Quebec City, said the EMA's Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of marketing authorization for Intrarosa, intended for the treatment of vulvar and vaginal atrophy in postmenopausal women. The active substance of Intrarosa is prasterone, also known as dehydroepiandrosterone, or DHEA.
Itus Corp., of San Jose, Calif., executed an exclusive worldwide license agreement with the Philadelphia-based Wistar Institute for a chimeric antigen receptor T-cell technology aimed initially at treating ovarian cancer, and eventually additional solid tumors. Itus formed a subsidiary, Certainty Therapeutics Inc., to develop and commercialize the technology initially in ovarian cancer and potentially later in prostate, pancreatic and other cancers. The engineered T cells will use the follicle stimulating hormone (FSH) to target ovarian cells that express the FSH-receptor. Financial terms of the deal were not disclosed.
Mirati Therapeutics Inc., of San Diego, said it is reprioritizing its development programs "to capitalize on encouraging data and development opportunities" in its sitravatinib and KRAS programs. The company also announced it will deprioritize further investment in glesatinib (MGCD-265) and will pursue opportunities to partner the program. The reallocation of resources will support the acceleration and expansion of the sitravatinib and KRAS programs and is expected to provide funding for operations into late 2019. In addition, the cancer-focused company said it has selected a clinical lead and backup compounds in its KRAS program that potently target KRAS G12C mutations for which it expects to file an investigational new drug application by the fourth quarter of 2018. (See BioWorld, Sept. 18, 2017.)
Oncoquest Inc., of Edmonton, Alberta, presented preclinical data from its IgE-based immunotherapy platform at the Society for Immunotherapy of Cancer meeting in National Harbor, Md., demonstrating the generation of an antigen-specific immunity that protected against pancreatic cancer in a transgenic animal tumor model using combinatory immunotherapy with that class of antibodies. Data showed NK and CD8 cells are implicated for the observed cell-mediated antitumor responses, and the IgE also induced a time-dependent increase in intratumor vascular permeability that may enhance chemotherapeutic effects.
Pfizer Canada Inc., of Kirkland, Quebec, a unit of Pfizer Inc., announced that Health Canada has expanded the indication of Xalkori (crizotinib) to include its use as a monotherapy in the treatment of patients with ROS1-positive locally advanced (not amenable to curative therapy) or metastatic non-small-cell lung cancer (NSCLC). Xalkori was previously approved by Health Canada as a monotherapy for use in patients with anaplastic lymphoma kinase-positive locally advanced or metastatic NSCLC. In Canada and the U.S., Xalkori is co-promoted by Pfizer Inc. and EMD Serono Canada, the Canadian biopharmaceutical business of Merck KGaA, of Darmstadt, Germany.
Proclara Biosciences Inc., of Cambridge, Mass., said new preclinical data demonstrates that General Amyloid Interaction Motif (GAIM)-based therapies, including its lead candidate, NPT-088, and second-generation candidate NPT-189, can reduce the accumulation and cell-to-cell transmission of multiple types of toxic protein aggregates in diseases caused by toxic protein buildup. NPT-088 is currently in a phase Ib trial for the treatment of patients with Alzheimer's disease. Proclara plans to file an investigational new drug application with the FDA for NPT-189 for the treatment of orphan peripheral amyloidoses in the first half of 2018. Data on the candidates were presented at the annual meeting of the Society for Neuroscience in Washington.
Purdue Pharma LP, of Stamford Conn., announced the completion of what it said were "significant" oncology-related investments, made as part of its ongoing efforts to diversify its scientific research. The company now has four drug candidates in development for multiple cancer types: EDO-S7.1, a topoisomerase inhibitor being tested in patients with refractory advanced biliary tract cancers; EDO-S101, an alkylating deacetylase inhibitor thought to have potential utility in both solid and hematologic tumors; and EDO-B776 and EDO-B278, two late preclinical-stage antibody-drug conjugates. EDO-B776 is being studied for its potential to target the cancer antigen 125 in ovarian cancer. EDO-B278 is an antibody-drug conjugate targeting the human tissue factor and is in development for various solid tumors.
Q Biomed Inc., of New York, said its research partner and licensor, Mannin Research Inc., of Toronto, received R&D funding from the National Research Council of Canada Industrial Research Assistance Program to initiate work on a Tie2-activating biologic for the treatment of glaucoma. Mannin will conduct a proof-of-concept study of the biologic as part of its research.
Sorrento Therapeutics Inc., of San Diego, said Scilex Pharmaceuticals Inc., its majority-owned subsidiary, filed an EMA marketing application for lead candidate Ztlido (lidocaine medicated plaster 1.8 percent) through a hybrid regulatory pathway with the U.K.'s Medicines and Healthcare products Regulatory Agency. Scilex expects a decision in the fourth quarter of 2018. An NDA is under review in the U.S. Ztlido was specifically designed to deliver lidocaine with superior adhesion compared to existing products.
Steadymed Ltd., of San Ramon, Calif., said the U.S. Court of Appeals for the Federal Circuit affirmed a March 31, 2017, ruling by the Patent Trial and Appeal Board (PTAB) of the Patent and Trademark Office, invalidating U.S. Patent No. 8,497,393 owned by United Therapeutics Corp., of Silver Spring, Md. The case was filed by United on June 1, 2017, and sought to reverse the earlier decision by PTAB, which found that all 22 claims in the '393 patent were invalid, and therefore, canceled them. The patent claimed a prostacyclin-derivative product, treprostinil, or treprostinil salts, made by a particular process. Treprostinil is the active pharmaceutical ingredient used in United's approved drug, Remodulin, and in Steadymed's lead drug candidate, Trevyent, which is in development for the treatment of pulmonary arterial hypertension.
Takeda Pharmaceutical Co. Ltd., of Osaka, Japan, said the EMA's Committee for Medicinal Products for Human Use adopted a positive opinion for the extension of the marketing authorization of CD30-targeting antibody-drug conjugate Adcetris (brentuximab vedotin) and recommended its approval for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma after at least one prior systemic therapy.
Theratechnologies Inc., of Montreal, said it was notified by partner Taimed Biologics Inc., of Taipei, Taiwan, that the FDA extended its review of the BLA for ibalizumab after Taimed submitted additional documentation for the manufacturing section of the BLA that the FDA deemed a major amendment. The BLA has a new PDUFA date of April 3, 2018.
Tusk Therapeutics Ltd., of London, said it was awarded a £2.5 million (US$3.3 million) grant from Innovate UK to support preclinical activities and conduct a phase I trial for its anti-CD38 monoclonal antibody as a cancer immunotherapy.
Xbiotech Inc., of Austin, Texas, presented findings at the American Heart Association Scientific Sessions in Anaheim, Calif., on the role of IL-1 alpha associated with neutrophil extracellular traps (NETs) in promoting endothelial activation and thrombogenicity, pointing to the role for anti-IL-1 alpha antibody MABp-1 in heart disease. Data showed that exposure of human saphenous vein endothelial cells to NETs increase expression of adhesion molecules on the surface of endothelial cells such as VCAM-1 and ICAM-1, which may participate in atherogenesis. Pre-treatment of NETs with MABp-1, but not with an anti-IL-1beta-neutralizing antibody, blocked the initiation of VCAM-1, ICAM-1 and TF expression, each of which link to coronary thrombosis.