On April 18, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported that the Company will present new preclinical data on SY-1425, its oral first-in-class selective retinoic acid receptor alpha (RARα) agonist currently in a Phase 2 clinical trial in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (Press release, Syros Pharmaceuticals, APR 19, 2017, View Source [SID1234518617]). These data were selected for oral presentation during a plenary session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Hematologic Malignancies: Translating Discoveries to Novel Therapies conference taking place from May 6-9 in Boston. Schedule your 30 min Free 1stOncology Demo! Details on the plenary talk and corresponding poster presentation are as follows:
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Presentation Title: SY-1425 (tamibarotene), a potent and selective RARα agonist, induces changes in the transcriptional regulatory circuit of AML cells leading to differentiation
Presenter: Christopher Fiore, Ph.D., Scientist, Syros Pharmaceuticals
Date & Time of Plenary Session: Sunday, May 7, from 10:30 a.m. – 1 p.m.
Plenary Session 3: Chemical Biology
Location: Westin Boston Waterfront, Harbor Ballroom 3
Date & Time of Poster Presentation: Sunday, May 7, from 1 – 3 p.m.
Location: Westin Boston Waterfront, Harbor Ballroom 1-2, Poster Board Number 06
Month: April 2017
Kura Oncology Granted U.S. Patent for Clinical-Stage ERK Inhibitor, KO-947
On April 19, 2017 Kura Oncology, Inc. (NASDAQ:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported issuance of a U.S. patent for KO-947, its drug candidate targeting extracellular-signal-regulated kinases (ERK) (Press release, Kura Oncology, APR 19, 2017, View Source [SID1234518614]). The new patent, U.S. 9,624,228, entitled "Inhibitors of ERK and Methods of Use," covers KO-947 and structurally-related compounds as well as methods of using the compounds for the treatment of diseases including cancer. Schedule your 30 min Free 1stOncology Demo! "We believe KO-947 holds much promise as a potential therapeutic, and we were pleased to have advanced it into Phase 1 clinical testing earlier this month," said Troy Wilson, Ph.D., J.D., President and CEO of Kura Oncology. "Issuance of this composition of matter patent is an important development for Kura and the program."
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About KO-947
KO-947 is a potent and selective small molecule ERK1/2 inhibitor. KO-947 exhibits potent anti-proliferative activity across a broad panel of tumor cell lines with mutations in BRAF, NRAS or KRAS and demonstrates prolonged pathway inhibition, both in vitro and in vivo. Durable tumor regression has been observed with KO-947 in preclinical cell line and patient derived xenograft models, including KRAS- and BRAF-mutant adenocarcinomas and squamous cell carcinomas lacking BRAF/RAS mutations.
CytRx Announces FDA Agreement on Regulatory Pathway to Approval for Aldoxorubicin in Soft Tissue Sarcomas
On April 19, 2017 CytRx Corporation (NASDAQ: CYTR) reported the U.S. Food and Drug Administration (FDA) has reached an agreement with CytRx on preparations for a New Drug Application (NDA) submission for aldoxorubicin in soft tissue sarcomas (STS) (Press release, CytRx, APR 19, 2017, View Source;p=RssLanding&cat=news&id=2262830 [SID1234518613]). STS remains a high unmet medical need.
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"We are very pleased to have achieved clarity from the FDA regarding CytRx’s soft tissue sarcoma program," said Daniel Levitt, MD, PhD, Chief Operating Officer and Chief Medical Officer. "The FDA agreed that CytRx could use the application pathway for its filing that has been successfully used previously by the oncology drugs Abraxane, Doxil and Onivyde. Our interaction with the FDA was part of a continued collaborative and productive relationship with the Agency. We look forward to providing the study reports and analysis that can lead to the approval of aldoxorubicin for the treatment of patients with soft tissue sarcomas."
The Company’s goal is to submit a rolling NDA under section 505(b)(2) to the FDA for soft tissue sarcomas in the last quarter of 2017. CytRx also plans to discuss with the European Medicines Agency (EMA) a path to filing a Marketing Authorization Application (MAA). The commercial launch of aldoxorubicin is still projected for 2018 in the United States. Aldoxorubicin has received Orphan Drug Designation by the FDA for the treatment of STS. Orphan designation provides several benefits including seven years of market exclusivity after approval, certain R&D related tax credits and protocol assistance by the FDA. European regulators granted aldoxorubicin Orphan Medicinal Product Designation for STS which confers ten years of market exclusivity among other benefits.
The proposed product label would include the treatment of soft tissue sarcomas. New data could allow future use of aldoxorubicin in neoadjuvant (pre-surgery) settings, as well as a replacement for doxorubicin in combinations. CytRx is also working on a market expansion strategy which could include other indications for aldoxorubicin including combinations with other chemotherapeutics and immunotherapies.
CytRx is under confidentiality agreements with a number of companies for a commercial partnership for the marketing of aldoxorubicin. The Company believes those active discussions may be further advanced by this latest news.
About a 505(b)(2) New Drug Application
A new drug application (NDA) under the Food and Drug Administration’s (FDA) section 505(b)(2) is for a new drug containing similar active ingredients as a previously approved drug. According to the publication Regulatory Focus, a drug reviewed under 505(b)(2) represents a modified version of a previously approved product that requires additional clinical and nonclinical studies, other than bioavailability/bioequivalence studies, to demonstrate safety and efficacy. Such an application differs from a typical NDA in that the sponsor can rely on, at least in part, the FDA’s findings of safety and/or effectiveness for a previously approved reference drug.
About the Phase 2b and Phase 3 Clinical Trials
The Phase 2b trial involved 123 patients at 31 sites. Patients with advanced soft tissue sarcomas were randomized 2:1 to receive either 350 mg/m2 of aldoxorubicin (83 patients) or 75 mg/m2 of doxorubicin (40 patients) every 3 weeks for up to 6 cycles. The trial was designed to compare aldoxorubicin directly with doxorubicin.
The randomized, controlled Phase 3 trial enrolled a total of 433 patients at 79 clinical sites. Patients with metastatic, locally advanced or unresectable soft tissue sarcomas who had either not responded to, or who had progressed following treatment with one or more systemic regimens of non-adjuvant chemotherapy were randomized 1:1 to be treated with aldoxorubicin or the investigator’s choice of an approved chemotherapeutic regimen, including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient), or gemcitabine plus docetaxel.
About Soft Tissue Sarcoma
Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue. It can arise anywhere in the body at any age. STS remains a high unmet medical need because of the difficulty in treating the more than 50 types of this aggressive cancer. According to the American Cancer Society, in 2016 more than 12,300 new cases were diagnosed in the U.S. and approximately 5,000 Americans died from this disease. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.
About Aldoxorubicin
Aldoxorubicin is a rationally engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of the drug well in excess of 5,000 mg/m2. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS.
Aptose Biosciences to Present CG’806 Data at AACR Hematologic Malignancies Meeting
On April 19, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported that preclinical data for its pan-FLT3/BTK inhibitor CG’806 will be presented in two separate posters at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference Hematologic Malignancies: Translating Discoveries to Novel Therapies, being held May 6-9 in Boston, MA (Press release, Aptose Biosciences, APR 19, 2017, View Source [SID1234518612]). Schedule your 30 min Free 1stOncology Demo! Aptose is developing CG’806, a first-in-class pan-FLT3/BTK inhibitor, for acute myeloid leukemia (AML) and other hematologic malignancies. CG’806 is a highly potent inhibitor of the wild type and mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and the gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. In addition, CG’806 is a reversible, non-covalent, inhibitor of the wild type and mutant forms of the BTK enzymes. The spectrum of activity against specific clusters of kinase enzymes supports the development of CG’806 for AML, certain B cell malignancies and other hematologic malignancies.
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Two separate presentations are planned for CG’806. Aptose scientists, with researchers from the Knight Cancer Institute at Oregon Health & Science University (OHSU), will present data related to the potency of CG’806 against various hematologic malignancy cell lines and patient bone marrow specimens. In a separate presentation, Aptose scientists, with researchers from the MD Anderson Cancer Center, will present data demonstrating CG’806’s potent activity against AML cells harboring specific wild type or mutant forms of FLT3.
Abstract Details
Title: "CG’806, a first-in-class FLT3/BTK inhibitor, exhibits potent activity against AML patient samples with mutant or wild-type FLT3, as well as other hematologic malignancy subtypes"
Presenter: Stephen E. Kurtz, Ph.D, Oregon Health & Science University, Portland, OR
Date/Time: May 7, 2017 / 1:00 p.m. ET – 3:00 p.m. ET
Location: Harbor 1/2, Westin Boston Waterfront, Boston, MA
Session: Poster Session
Abstract Details
Title: "CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3"
Presenter: Weiguo Zhang, M.D., Ph.D, UT MD Anderson Cancer Center, Houston, TX
Date/Time: May 7, 2017 / 1:00 p.m. ET – 3:00 p.m. ET
Location: Harbor 1/2, Westin Boston Waterfront, Boston, MA
Session: Poster Session
About CG’806
CG’806 is a once daily, oral, first-in-class pan-FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting the CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.
PRIMA BIOMED RECEIVES APPROVAL FOR THIRD COHORT OF PHASE I MELANOMA TRIAL
On April 19, 2017 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima" or the "Company") reported that approval has been granted for the third cohort of its Phase I clinical trial for IMP321 in combination with KEYTRUDA being conducted in Australia. The third cohort will recruit six patients with unresectable or metastatic melanoma (Press release, Prima Biomed, APR 19, 2017, View Source [SID1234518607]). Schedule your 30 min Free 1stOncology Demo! The positive safety profile was also confirmed in the second cohort dosed with 6 mg of IMP321. None of the 6 patients treated with KEYTRUDA plus IMP321 at this higher dose level experienced any serious adverse reaction nor dose limiting toxicity. As a result, the independent Drug Safety Monitoring Board (DSMB) has granted approval for the third cohort, at the 30mg dose level, to commence with the first patient to be dosed in due course.
Interim data results from the first patient cohort released in December 2016 indicate IMP321 at the 1mg dose level is safe and well tolerated. Out of the six patients in the first cohort (all with suboptimal response to KEYTRUDA monotherapy) two patients had a partial or complete radiological tumour response according to immune related response criteria (irRC).
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TACTI-mel (Two ACTive Immunotherapeutics in melanoma) is a multicentre, open label, Phase I study in which patients with unresectable or metastatic melanoma will be dosed with IMP321 in combination with the PD-1 checkpoint inhibitor pembrolizumab (KEYTRUDA). The study will evaluate safety as the primary endpoint and anti-tumour activity and the immune response to the combination as secondary endpoints.
About IMP321
IMP321, a first-in-class Antigen Presenting Cell (APC) activator based on the immune checkpoint LAG-3, represents one of the first proposed active immunotherapy drugs in which the patient’s own immune system is harnessed to respond to tumour antigenic debris created by chemotherapy. As an APC activator IMP321 boosts the network of dendritic cells in the body that can respond to tumour antigens for a better anti-tumour CD8 T cell response.