On December 12, 2017 GlycoMimetics, Inc. (NASDAQ: GLYC) reported updated data from the Phase 1/2 trial evaluating the safety, tolerability and efficacy of GMI-1271 in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and in older adults with newly diagnosed AML, including the following conclusions (Press release, GlycoMimetics, DEC 12, 2017, View Source [SID1234522581]):

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For patients with R/R AML treated at the Phase 2 dose (n = 54) and for whom median follow up was 6.6 months:

Clinical remission (CR+CRi) was 43%.
Median overall survival was 9.4 months (95% CI: 5.7 – 15.1 months; calculated by Kaplan Meier method). This compares favorably to a median overall survival of up to 5.4 months reported for historical, matched controls treated with mitoxantrone, etoposide and cytarabine (MEC) alone. 1,2
Median duration of remission was 11.1 months (95% CI: 5.8-NA; calculated by Kaplan Meier method).
For older patients with newly diagnosed disease (n=25) and for whom median follow up was 10.5 months:

Clinical remission rate was 68%.
Median overall survival was 15.8 months (95% CI: 10.3 – NA; calculated by Kaplan Meier method). This compares favorably to a historical median overall survival of approximately 12 months in matched controls treated with 7+3 chemotherapy alone. 3,4
Median duration of remission was 14.8 months (95% CI: 8.3 – NA; calculated by Kaplan Meier method).
Median event free survival was 11.3 months.
The data were presented yesterday during an oral scientific session at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Expo in Atlanta.

Across both populations, GMI-1271 was well tolerated with no obvious incremental toxicity observed and lower than expected rates of severe, debilitating, grade 3-4 mucositis reported (e.g., 3% incidence reported vs. historical 20-25% incidence with MEC alone).

"These new data from our Phase 1/2 clinical trial demonstrate that encouraging clinical outcomes are possible for both duration of remission and survival endpoints when GMI-1271 is added to chemotherapy in two distinct AML patient populations," noted Helen Thackray, M.D., FAAP, GlycoMimetics Senior Vice-President, Clinical Development and Chief Medical Officer. "Beyond the high response rates previously reported with GMI-1271, we can now point to additional long-term endpoints that further support our plan to move the drug candidate into a Phase 3 clinical trial scheduled to begin in mid-2018. Importantly, with respect to safety, the low mucositis rate in relapsed and refractory patients receiving MEC induction chemotherapy — where you would expect around 25% severe mucositis — is quite striking. This was predicted and explained by preclinical models in which GMI-1271 blocked inflammatory macrophages trafficking to the gut and thus prevented mucosal injury."

"These results continue to show that AML patients treated with GMI-1271 consistently perform better than expected," said Daniel J. DeAngelo, M.D., Ph.D., the trial’s lead investigator and Director of Clinical and Translational Research, Adult Leukemia Program, at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, who presented the data at the ASH (Free ASH Whitepaper) Annual Meeting. "Our Phase 2 population consists of very high-risk patients based on age, disease status, and cytogenetic risk factors. The updated data continue to support the concept that disrupting the relationship between leukemic cells and the protective bone marrow microenvironment, when combined with chemotherapy, could improve the outlook and prognosis for these patients."

The second oral presentation at the ASH (Free ASH Whitepaper) meeting highlighted a preclinical study in murine models of AML in which E-selectin was shown to be upregulated, and AML cells binding to E-selectin increased chemo-resistance by activating specific tumor cell survival signaling pathways. This effect within the bone marrow microenvironment is unique to E-selectin as compared to other vascular adhesion molecules and can be blocked by GMI-1271. This translational research provides important evidence that elucidates how treatment with GMI-1271 appears to be improving sensitivity to chemotherapy.

"Given response rates we’ve observed to date that suggest clinical benefit in combination with chemotherapy in two AML populations, this preclinical work provides important further support for the mechanism of action of GMI-1271," noted Dr. Thackray. "Together, the clinical and preclinical data we have shared at the ASH (Free ASH Whitepaper) Annual Meeting demonstrate that GMI-1271 could represent a novel and truly differentiated approach to treatment of AML," Dr. Thackray concluded.

Meeting abstracts are available on ASH (Free ASH Whitepaper)’s website.

GlycoMimetics to Hold Post-ASH Meeting Briefing in Boston on December 19

GlycoMimetics will hold a briefing for investors/analysts, which will also be available via webcast, to review the GMI-1271 program with a focus on the AML clinical data presented at the ASH (Free ASH Whitepaper) Annual Meeting, at the Langham Hotel in Boston, December 19, at 7:30 a.m. EST. Dr. DeAngelo will present the clinical data from the ASH (Free ASH Whitepaper) oral presentation and respond to questions from on-site participants.

On December 12, 2017 CEL-SCI Corporation (NYSE American: CVM) reported that no further patient enrollment is required in the pivotal Phase 3 head and neck cancer study of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection). The accrual and treatment phases of this Phase 3 study are complete (Press release, Cel-Sci, DEC 12, 2017, View Source [SID1234522593]). All of the 928 enrolled patients in the study are being followed-up as required by the study protocol.

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CEL-SCI recently announced that the study’s Independent Data Monitoring Committee (IDMC) completed its most recent review of the data from all 928 patients enrolled in the study, and recommended continuing the study as there was no evidence of any significant safety questions.

The primary endpoint of the study, a 10% improvement in overall survival of the Multikine treatment regimen plus Standard of Care (SOC) vs. Standard of Care alone, will be determined after a total of 298 deaths have occurred in these two main comparator arms of the study and have been recorded in the study database. The last patient was enrolled in the study in September 2016. Approximately 135 patients were enrolled in the study from 2011 to 2013, about 195 were enrolled in 2014, about 340 in 2015, and about 260 in 2016. The study protocol assumed an overall survival rate of about 55% at 3 years for the SOC treatment group alone.

IDMCs are committees commonly used by sponsors of clinical trials to protect the interests of the patients and the integrity of the study data in ongoing trials, especially when the trials involve patients with life threatening diseases, and when, as in cancer clinical trials, they extend over long periods of time.

On December 12, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that data from the EMBRACA trial showed Myriad’s BRACAnalysis CDx test successfully identified patients with metastatic breast cancer (MBC) who responded to Pfizer’s investigational PARP inhibitor, talazoparib (Press release, Myriad Genetics, DEC 12, 2017, View Source [SID1234522582]).

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The EMBRACA trial (NCT01945775) data were presented last week at the 2017 San Antonio Breast Cancer Symposium (SABCS). The study included approximately 400 patients, all of whom tested positive for germline BRCA mutations as determined by Myriad’s FDA-approved BRACAnalysis CDx test. As presented at SABCS, the results demonstrated that patients with gBRCA+ locally advanced and/or MBC demonstrated superior progression-free survival (PFS) in patients treated with talazoparib, compared to patients who received physician’s choice standard-of-care chemotherapy. Additionally, the PFS benefit was consistent across metastatic BRCA-positive patients, including those with hormone receptor-positive and triple negative disease.

"BRACAnalysis CDx is the only germline companion diagnostic test approved by the FDA to identify patients with BRCA1/2 mutations, and we are excited to support Pfizer’s clinical development program and help identify patients who are most likely to benefit from talazoparib," said Mark C. Capone, president and CEO, Myriad Genetics. "As the pioneers in companion diagnostics for PARP inhibitors, we are excited that more patients may benefit from these novel drugs in the future."

It is estimated there are approximately 60,000 patients with metastatic breast cancer, two thirds of whom are not currently eligible for BRCA testing based upon family and personal history alone or current testing criteria.

Myriad first announced its collaboration to develop a novel companion diagnostic test for talazoparib on Oct. 1, 2013. Under that agreement (originally with BioMarin; now Pfizer), Myriad plans to submit a supplementary premarket approval (sPMA) application to the U.S. Food and Drug Administration (FDA) under its existing PMA for BRACAnalysis CDx to include talazoparib.

About BRACAnalysis CDx
BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. Results of the test are used as an aid in identifying ovarian cancer patients with deleterious or suspected deleterious germline BRCA variants, who are or may become eligible for treatment with Lynparza (olaparib). Detection of deleterious or suspected deleterious germline BRCA variants by the BRACAnalysis CDx test in ovarian cancer patients is also associated with enhanced progression-free survival (PFS) from Zejula (niraparib)maintenance therapy. This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108. Learn more at: View Source

On December 12, 2017 Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) reported financial results for its fiscal 2017 fourth quarter and year ended September 30, 2017 (Press release, Arrowhead Research Corporation, DEC 12, 2017, View Source [SID1234522592]). The company is hosting a conference call at 4:30 p.m. EST to discuss results.

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Conference Call and Webcast Details

Investors may access a live audio webcast on the Company’s website at View Source For analysts that wish to participate in the conference call, please dial 855-215-6159 or 315-625-6887 and provide Conference ID 6977547.

A replay of the webcast will be available on the company’s website approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 3 days. To access the audio replay, dial 855-859-2056 or 404-537-3406 and provide Conference ID 6977547.

Selected Fiscal 2017 and Recent Events

Hosted an Analyst R&D Day in September 2017 to highlight the following:
The Targeted RNAi Molecule platform, or TRiM, which utilizes ligand-mediated delivery and is designed to enable tissue-specific targeting, while being structurally simple
The TRiM platform offers several potential competitive advantages including:
Simplified manufacturing at reduced cost
Multiple routes of administration (subcutaneous, intravenous, and inhaled)
Faster time to clinical candidates
Wide safety margins
Promise of taking RNAi to tissues beyond the liver
ARO-AAT, Arrowhead’s second generation subcutaneously administered clinical candidate for the treatment of alpha-1 antitrypsin deficiency liver disease with a planned Clinical Trial Application (CTA) filing in Q1 2018
ARO-HBV, Arrowhead’s third generation subcutaneously administered clinical candidate for the treatment of chronic hepatitis B virus infection with a planned CTA filing in Q2 2018
Arrowhead’s expanded cardiometabolic pipeline, which now includes ARO-APOC3, targeting apolipoprotein C-III, and ARO-ANG3, targeting angiopoietin-like protein 3 (ANGPTL3) with CTA filings planned around the end of 2018
The TRiM platform’s ability to target extra-hepatic tissues, including the lung and tumors, represented by the following programs:
ARO-Lung1, the first candidate against an undisclosed gene target in the lung, which achieved almost 90% target knockdown following inhaled administration in rodents
ARO-HIF2, Arrowhead’s candidate targeting renal cell carcinoma, which achieved 85% target gene knockdown in a rodent tumor model
CTA filings are planned in Q4 2018 and in 2019 for ARO-Lung1 and ARO-HIF2, respectively
Presented new clinical data at HEP DART 2017 demonstrating up to 5.0 log10 reduction in HBV s-antigen and a Sustained Host Response in 50% of hepatitis B patients following RNAi therapy, ARC-520, in the 2001 open label extension study
Made continued progress on our two-product cardiovascular collaboration with Amgen, in which one that was previously called ARO-LPA against the target lipoprotein(a) has been formally nominated as a clinical candidate and which is now referred to as AMG-890 by Amgen

On December 12, 2017 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Puma Biotechnology, Inc. (Nasdaq: PBYI) reported a preclinical research collaboration with Memorial Sloan Kettering Cancer Center (MSK) to explore the combination of Daiichi Sankyo’s investigational antibody drug conjugate DS-8201 and Puma Biotechnology’s irreversible pan-HER tyrosine kinase inhibitor neratinib (NERLYNX) in HER2-mutated or HER2-positive solid tumors (Press release, Daiichi Sankyo, DEC 12, 2017, View Source [SID1234522606]).

A team of scientists led by Maurizio Scaltriti, PhD, and in collaboration with a team of clinical investigators led by Bob Li, MD, will use isogenic models and established patient-derived xenograft models to assess the susceptibility of HER2-mutated or HER2-positive cancers to DS-8201, neratinib and other HER2-targeting therapies, elucidate mechanisms of action and resistance of these various tumor types, and evaluate the potential for synergistic combinations. Daiichi Sankyo and Puma Biotechnology will co-sponsor the research.

"Since early clinical data suggest that DS-8201 may have activity beyond breast and gastric cancers, the archetype HER2-driven tumors, we are interested in studying this asset on a molecular level as well as in combination with other HER2-targeting agents," said Tom Held, Vice President, Global Head, Antibody Drug Conjugate Task Force, Daiichi Sankyo. "In this collaboration, we are examining whether combining DS-8201 and neratinib, with its specific covalent binding to the HER2 receptor and associated increased internalization, is a rational combination therapy strategy to pursue. We are excited to join forces with Memorial Sloan Kettering and Puma to advance the understanding of combining HER2-targeted therapies to potentially treat various forms of HER2-mutated cancer."

"We are pleased to enter into this research collaboration with Memorial Sloan Kettering and Daiichi Sankyo to explore the combination of neratinib and DS-8201," said Alan Auerbach, Puma’s Chief Executive Officer and President. "Combination therapy with agents that address different and complementary pathways, with neratinib targeting the HER2 kinase and DS-8201 providing an innovative targeted delivery of a potent cytotoxic, represents an intriguing approach to the treatment of HER2 mutated tumors and helps to maximize the potential for both agents in treating cancers with a HER2 mutation."

About DS-8201

DS-8201 is the lead product in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in phase 2 clinical development for HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01), phase 2 development for HER2-positive advanced gastric resistent or refractory to trastuzumab (DESTINY-Gastric01) and phase 1 development for other HER2-expressing advanced/unresectable or metastatic solid tumors.

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About NERLYNX (neratinib)

Neratinib was approved by the FDA in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets.

Important Safety Information (ISI)
NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2 overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.

Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.

Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.

ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at
1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors (PPI) and H2-receptor antagonists. Separate NERLYNX by 3 hours after antacid dosing.
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.

USE IN SPECIFIC POPULATIONS:

Lactation: Advise women not to breastfeed.

Please see Full Prescribing Information for additional safety information.

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

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