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ArQule Presents Preclinical Data for ARQ 531, a Proprietary Reversible Inhibitor of Wild Type and Mutant BTK, at the 2016 Pan Pacific Lymphoma Conference

On July 18, 2016 ArQule, Inc. (Nasdaq:ARQL) reported the first public presentation of data on its novel BTK inhibitor, ARQ 531, at the 2016 Pan Pacific Lymphoma Conference in Koloa, Hawaii (Press release, ArQule, JUL 18, 2016, View Source [SID:1234513933]). ARQ 531 is an investigational, orally bioavailable, potent and reversible Bruton’s tyrosine kinase (BTK) inhibitor.

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In preclinical testing, ARQ 531 demonstrated biochemical inhibition of both wild type and C481S-mutant BTK at sub-nanomolar levels and potent cellular inhibition in C481S-mutant BTK cells that are resistant to ibrutinib. This molecule also exhibits a distinct kinase selectivity profile with inhibitory activity against several key oncogenic drivers related to ibrutinib resistance. It is currently estimated that about 10% of patients treated with ibrutinib develop resistance with over 80% presenting the C481S mutation. This incidence rate is expected to increase.

Additionally, the compound potently suppresses cell proliferation of hematological malignancies in vitro, with B-cell receptor signaling inhibition. ARQ 531 also demonstrates strong in vivo target and pathway inhibition of phospho-BTK with potent and durable growth suppression.

"We are beginning to see increasing resistance to ibrutinib which is creating the need for a BTK inhibitor, like ARQ 531, that targets the C481S mutation," said Dr. Brian Schwartz, Head of Research and Development and Chief Medical Officer at ArQule. "The preclinical profile of ARQ 531 as a potent and reversible inhibitor of wild type and mutant BTK presents the potential for a first-in-class and best-in-class molecule. We are working toward completing GLP toxicology studies and filing an IND in early 2017."

The poster titled "ARQ 531, a Novel, Oral, Non-Covalent Inhibitor of Wild Type and C481S Mutant BTK with Potent Anti-Tumor Activity" can be viewed at View Source

About BTK and ARQ 531

ARQ 531 is an investigational, orally bioavailable, potent and reversible Bruton’s tyrosine kinase (BTK) inhibitor. Biochemical and cellular studies have shown that ARQ 531 inhibits both the wild type and C481S-mutant forms of BTK. The C481S mutation is a known emerging resistance mechanism for first generation irreversible BTK inhibitors. ARQ 531 has high oral bioavailability as well as good ADME, pharmacokinetic and metabolic properties. The company plans to file an IND for ARQ 531 in early 2017. BTK is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers.

Delcath Announces Acceptance Of Abstracts For Poster Presentation At CIRSE 2016

On July 18, 2016 Delcath Systems, Inc. (NASDAQ: DCTH), a specialty pharmaceutical and medical device company focused on oncology with an emphasis on the treatment of primary and metastatic liver cancers, reported that abstracts from two studies conducted in Germany of use of the Delcath Hepatic CHEMOSAT Delivery System to treat patients with liver metastases, have been accepted for presentation as posters at the Cardiovascular and Interventional Radiology Society of Europe (CIRSE) annual meeting (Press release, Delcath Systems, JUL 18, 2016, View Source;p=RssLanding&cat=news&id=2186055 [SID:1234513927]). The abstracts are:

Percutaneous Isolated Hepatic Perfusion (Chemosaturation) In Patients With Primary Or Secondary Liver Tumours: Experience In 20 Patients, by S. Marquardt, et al, of Hanover Medical School in Hanover, Germany.

Secondary Resectability Of Ocular Melanoma Liver Metastases Following Percutaneous Hepatic Perfusion by M. Zeile, and A. Stang, et al of the Asklepios Barmbek Clinic in Hamburg, Germany.

Ipsen announces the acceptance by the European Medicines Agency of the marketing authorization application for telotristat etiprate to treat carcinoid syndrome caused by neuroendocrine tumors, in combination with somatostatin analogues

On Ipsen (Euronext: IPN; ADR: IPSEY) reported that the European Medicines Agency (EMA), the European regulatory authority, has accepted the submission of filing for telotristat etiprate as an adjunct to somatostatin analogue therapy for the long-term treatment of carcinoid syndrome to improve symptom control in adult patients with metastatic neuroendocrine tumors (Press release, Ipsen, JUL 18, 2016, View Source [SID:1234513935]).

In addition to this European submission, Ipsen will pursue a worldwide regulatory plan for marketing authorization submissions in the territories where it operates. As such the Marketing Authorization Application was submitted to SwissMedic (the Swiss Regulatory Agency) on July 5th 2016. In October 2014, Ipsen and Lexicon announced that they had entered into an exclusive licensing agreement for Ipsen to commercialize telotristat etiprate in all territories excluding the United States and Japan, where Lexicon retains the rights. Lexicon filed a New Drug Application in the United States on 30 March 2016 and was granted priority review on 31 May 2016 by the U.S. Food and Drug Administration (FDA).

Regulatory submission is supported by the results of TELESTAR, a pivotal, placebo-controlled phase 3 clinical trial and TELECAST, the phase 3 companion study to TELESTAR. Results from TELESTAR demonstrated a statistically significant (p<0.001) reduction from baseline in the average number of daily bowel movements over the first 12-week study period in both treatment arms (250 mg tid and 500 mg tid) compared with placebo, thereby meeting the study’s primary endpoint. A statistically significant (p<0.001) reduction in urinary 5-hydroxyindoleacetic acid (the main metabolite of serotonin) was also observed at week 12 compared with placebo in both treatment arms. The most common adverse reactions associated with the use of telotristat etiprate were nausea, abdominal pain, fatigue and gamma-glutamyl transferase increased in the pooled placebo-controlled data of the two phase 3 clinical trials, TELESTAR and TELECAST.

David Meek, Chief Executive Officer of Ipsen, said: "Ipsen is a global leader in neuroendocrine tumors, and is committed to improve patient outcomes from diagnosis to each stage of the disease including symptomatic treatment of carcinoid syndrome. We look forward to working with the EMA so that as many patients as possible can benefit from telotristat etiprate".

About carcinoid syndrome
Well-differentiated neuroendocrine tumor (NET) is a relatively rare tumor type that arises from cells of the neuroendocrine system. Carcinoid syndrome (CS) occurs when well-differentiated NETs secrete large amounts of serotonin and other vasoactive products into the systemic circulation. Classically, symptoms associated with CS include cutaneous flushing, diarrhea, wheezing, abdominal pain, and in the long-term, valvular heart disease.

Somatostatin analogues (SSA) are the cornerstone of therapy for the relief of CS and tumor control. SSA inhibit the release of serotonin by NETs and have become first-line therapy for CS. However, SSA may not adequately control symptoms for all patients.

Due to the severe morbidity of CS and the lack of established treatment options, the population of patients with CS needing further control in addition to their SSA therapy is one with a high unmet medical need.

About telotristat etiprate
Telotristat etiprate is a novel, orally administered, inhibitor of the enzyme tryptophan hydroxylase (TPH). Through inhibition of TPH, the rate-limiting step in the synthesis of serotonin, the compound was designed to reduce the production of serotonin within neuroendocrine tumors. Carcinoid syndrome occurs when well differentiated neuroendocrine tumors secrete large amounts of serotonin and other vasoactive products into the systemic circulation. Telotristat etiprate has been developed as an adjunct to SSA therapy for the long term treatment of CS to improve symptom control in adult patients with metastatic NETs.

Telotristat etiprate received priority review status and orphan drug designation from the FDA in the United States, and has received orphan drug designation from the EMA.

Aeglea BioTherapeutics Provides Update on AEB1102 Clinical Program in Rare Diseases and Cancer

On July 18, 2016 Aeglea BioTherapeutics, Inc., (NASDAQ:AGLE) a biotechnology company committed to developing enzyme-based therapeutics in the field of amino acid metabolism to treat rare diseases and cancer, reported a regulatory and clinical update for its AEB1102 program (Press release, Aeglea BioTherapeutics, JUL 18, 2016, View Source [SID:1234513934]). AEB1102, the company’s lead investigational molecule, is a recombinant human enzyme designed to degrade the amino acid arginine and is being developed to treat two extremes of arginine metabolism.

"We have developed a clinical program for AEB1102 with three ongoing clinical trials. The momentum for this program continues to build with AEB1102 receiving Fast Track designation from the FDA for hyperargininaemia in May and also receiving a positive opinion for Orphan Drug Designation from the European Medicines Agency this month," said David G. Lowe, Ph.D., co-founder, president and chief executive officer at Aeglea. "We believe this molecule has great potential for patients with rare diseases and cancer, and we look forward to gathering critical data as we continue to advance our programs."

AEB1102 for the Treatment of Rare Diseases

The European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending Orphan Drug Designation for AEB1102 for the treatment of hyperargininaemia in the European Union.

The EMA’s Orphan Drug Designation provides benefits, such as protocol assistance, fee reductions and ten years of market exclusivity upon regulatory approval, to companies working to develop treatments for life-threatening or chronically debilitating conditions that affect no more than five in 10,000 people in the EU and where no satisfactory treatments are available.

Additionally, Aeglea’s Phase 1 open-label, dose escalation study of AEB1102 for the treatment of patients with Arginase I deficiency has been initiated. The single arm study will enroll up to six patients to assess the safety, tolerability and pharmacokinetics of AEB1102. Enrollment is anticipated to be completed in 2016 with topline data expected in the first half of 2017.

Hyperargininaemia, or excessively high levels of arginine, is the result of a hereditary deficiency of arginase I. Arginase I deficiency is a urea cycle disorder caused by a mutation in the arginase I gene that leads to the inability to degrade arginine, the last step of the urea cycle. AEB1102 is intended to replace the function of arginase I in patients by returning elevated blood arginine levels to the normal physiological range.

AEB1102 for the Treatment of Arginine-Dependent Tumors

A Phase 1 open-label, dose escalation study of AEB1102 in advanced solid tumors, has currently enrolled six cohorts. To date, the maximum tolerated dose (MTD) has not yet been determined. Enrollment, which was initiated in October 2015, is expected to be completed by the end of 2016. Topline data are expected in 2017.

Following the determination of the MTD, additional cohorts of approximately 25 patients each with a specific solid tumor subtype will be enrolled and treated with AEB1102 at the MTD. The solid tumor subtype expansion arms are expected to initiate in 2017.

Additionally, Aeglea has initiated a Phase 1 open-label, dose escalation study of AEB1102 in patients with relapsed refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The objectives of the trial will be to determine the MTD and recommended Phase 2 dose as well as to assess the safety profile of AEB1102. Based off of data from the Phase 1 trial of AEB1102 for the treatment of advanced solid tumors, the company has recently amended the trial protocol to increase the starting dose in patients with AML and MDS. Enrollment is expected to be completed in 2017.

Dysregulation of amino acid metabolism has been shown to be a key event in tumor growth and development. Unlike healthy cells, these tumors cells have an abnormally high appetite for certain amino acids and are unable to create their own supply, making them vulnerable to starvation through depletion of that amino acid in the blood. AEB1102 is intended to address an unmet need for these tumor types by degrading arginine in the blood, reducing its level below the normal range to starve the tumor.

"We are pleased to have initiated our Arginase I deficiency and hematological malignancies trials, advancing our programs to bring AEB1102 one step closer to patients," said Sandra Rojas-Caro, M.D., chief medical officer at Aeglea. "There remain significant unmet medical needs for both Arginase I deficiency and cancer. Fulfilling this need and bringing effective treatments to patients are at the center of what drives us at Aeglea."

About AEB1102

AEB1102 is a recombinant human arginase I enzyme designed to degrade the amino acid arginine. Aeglea is developing AEB1102 to treat two extremes of arginine metabolism, including arginine excess in patients with Arginase I deficiency, as well as some cancers which have been shown to have a metabolic dependency on arginine. In patients with Arginase I deficiency, AEB1102 is intended for use as Enzyme Replacement Therapy to restore the function of arginase I in patients and return elevated blood arginine levels to the normal physiological range. Aeglea is currently conducting a Phase 1 clinical trial in solid tumor cancer patients to evaluate the safety and tolerability of AEB1102. Data from this trial demonstrated that AEB1102 has the ability to reduce blood arginine levels, providing initial human proof of mechanism.

MabVax Therapeutics Initiates Patient Enrollment in a Phase I Trial for a New Diagnostic Imaging Product for Pancreatic Cancer

On July 18, 2016 MabVax Therapeutics Holdings, Inc. (OTCQB: MBVX), a clinical-stage oncology drug development company, reported the initiation of patient enrollment at Memorial Sloan Kettering Cancer Center (MSK) in a Phase I clinical trial evaluating its new generation diagnostic PET imaging agent, MVT-2163 for patients with locally advanced or metastatic adenocarcinoma of the pancreas (PDAC) or other CA19-9 positive malignancies (Press release, MabVax, JUL 18, 2016, View Source [SID:1234513931]). This study follows another investigational Phase I trial recently initiated at MSK utilizing the Company’s HuMab-5B1 antibody MVT-5873 as a therapeutic product for the treatment of Pancreatic cancer.

The diagnostic imaging study will administer MVT-2163 as a PET imaging agent for patients with pancreatic cancer. 89Zr-HuMab-5B1 combines a well-established PET imaging radiolabel, Zirconium [Zr-89], with the targeting specificity of the Company’s HuMab-5B1 antibody. This clinical trial will evaluate the safety, pharmacokinetics and biodistribution of MVT-2163 in patients with pancreatic cancer. The trial will also determine the ideal dose and timing for an optimal PET scan image. Preclinical xenograft animal models demonstrated high image resolution of tumors, making MVT-2163 attractive as a potential companion diagnostic agent for use with the MVT-5873 therapeutic product. Some of the preclinical data supporting the development of this new agent was funded by the National Cancer Institute contract (HHSN261201300060C) and previously published in the Journal of Nuclear Medicine, Bioconjugate Chemistry, and the Proceedings of the National Academy of Sciences. This study is under the direction of Dr. Christian Lohrmann as lead investigator who has received a grant from a non-profit foundation to help support this clinical trial.

"We are very excited to begin patient enrollment for this Phase I trial at MSK," said David Hansen, MabVax President and CEO. "We expect to see in the next few weeks the first PET images from this study establishing the level of targeting specificity of the HuMab-5B1 antibody. The results of our study are intended to provide investigators with a better understanding of the cancers afflicting these patients. If the product produces the desired images, it could help improve diagnosis and physician decision making on treatment options for pancreatic cancer and other CA19-9 positive malignancies. We look forward to announcing interim results from this trial during the third quarter of 2016."

About HuMab-5B1:

MabVax’s HuMab-5B1 antibody is fully human and was discovered from the immune response of cancer patients vaccinated with an antigen-specific vaccine during a Phase I trial at Memorial Sloan Kettering Cancer Center. In preclinical research, the 5B1 antibody has demonstrated high specificity and affinity, and has shown potent cancer cell killing capacity and efficacy in animal models of pancreatic, colon and small cell lung cancers. The antigen the antibody targets is expressed on more than 90% of pancreatic cancers making the antibody potentially broadly applicable to most patients suffering from this type of cancer. MabVax’s two lead antibody clinical programs utilize HuMab-5B1 as a naked antibody (MVT-5873) and as an immuno-PET imaging agent (MVT-2163).