On March 1, 2019 AIVITA Biomedical, Inc., a biotech company specializing in innovative stem cell applications, reported that the Company will be presenting mechanism of action findings and study design details at the 2019 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium taking place February 28 to March 2 in San Francisco, CA (Press release, AIVITA Biomedical, MAR 1, 2019, View Source [SID1234533882]). Chief Science Officer Dr. Gabriel Nistor will present a poster concerning Th17 responses to an autologous immunotherapy targeting cancer stem cells. Chief Medical Officer Dr. Robert O. Dillman will present a poster concerning AIVITA’s randomized Phase 2 trial of patient-specific immunotherapy targeting cancer stem cells.

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The ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium is a three-day meeting focused on clinical and translational research in immune-oncology. Dr. Nistor’s poster presentation will take place March 1 in Poster Session B of the Melanoma/Skin Cancers track. It will highlight how an autologous cancer immunotherapy can induce a Th17 phenotype preceding a Th1 type response. The findings are important for applications in settings in which tumor infiltration with Th17+ cells correlate with survival, such as in advanced ovarian cancer.

Dr. Dillman’s poster presentation will take place March 1 in Poster Session B of the Breast and Gynecologic Cancers track. It will inform attendees of the design and methodologies of AIVITA’s active Phase 2 clinical trial for ovarian cancer. The trial was initiated in November 2017 at a single site and has thus far received 11 appropriate patient tumor samples, with all 11 having successfully been expanded into viable cell lines for use in the creation of the Company’s autologous vaccine. Additional clinical sites are being initiated.

AIVITA is currently conducting three clinical studies investigating its platform ROOT OF CANCER therapy in patients with ovarian cancer, glioblastoma and melanoma. AIVITA uses 100% of proceeds from the sale of its ROOT of SKIN skincare line to support the treatment of women with ovarian cancer.

About ROOT OF CANCER

AIVITA’s treatment is a platform technology applicable to most solid tumor types and consists of autologous dendritic cells loaded with autologous tumor antigens from purified autologous self-renewing tumor-initiating cells.

AIVITA’s ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous cancer stem cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy.

For additional information about AIVITA’s AVOVA-1 trial patients can visit: www.clinicaltrials.gov/ct2/show/NCT02033616

AIVITA’s glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the cancer stem cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70 and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC).

For additional information about AIVITA’s AV-GBM-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03400917

AIVITA’s melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with the cancer stem cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations and (5) are about to initiate anti-PD1 monotherapy.

For additional information about AIVITA’s AV-MEL-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03743298

On March 1, 2019 CARsgen Therapeutics, a clinical-stage company committed to developing Chimeric Antigen Receptor T cell therapies for cancer, reported that one of its leading drug candidates, CT053 fully human BCMA (B-Cell Maturation Antigen)-CAR-T cell for the treatment of patients suffering from relapsed/refractory multiple myeloma (rrMM), has received Investigational New Drug (IND) clearance from the National Medical Products Administration (NMPA) (Press release, Carsgen Therapeutics, MAR 1, 2019, View Source [SID1234533883]).

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"At the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in December 2018, our collaborator, Dr. Songfu Jiang presented encouraging safety and efficacy data in patients with rrMM who received CT053 BCMA-CAR-T cells. The IND clearance of BCMA-CAR-T cells by China’s NMPA is of great significance to CARsgen," said Dr. Zonghai Li, founder, CEO and CSO of CARsgen. "According to JAMA Oncology, in 2016, there were about 130,000 cases of myeloma, which means from 1990 to 2016, incident cases of myeloma increased by 126% globally[1] and despite the development of novel therapies, multiple myeloma remains incurable and new treatment options are needed. As part of the CT053 development plan, we also intend to submit an IND application for BCMA-CAR-T cells to the U.S. FDA in 2019. Our goal is to continue the development of novel, safe and effective immunotherapies. This is our long-standing commitment to cancer patients worldwide."

On March 1, 2019 Pfizer reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for LORVIQUA (lorlatinib, approved in the U.S., Canada, and Japan under the brand name LORBRENA), an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) (Press release, Pfizer, MAR 1, 2019, View Source [SID1234533868]). The CHMP has adopted a positive opinion recommending conditional marketing authorization for LORVIQUA as monotherapy for the treatment of adult patients with ALK-positive advanced non-small cell lung cancer (NSCLC) whose disease has progressed after alectinib or ceritinib as the first ALK TKI therapy, or crizotinib and at least one other ALK TKI. Conversion to normal approval will be contingent on provisions of comprehensive data confirming that the benefit-risk balance is positive. The CHMP’s opinion will now be reviewed by the European Commission (EC), with a decision expected in the coming months.

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"Addressing drug resistance and relapse remains a challenge in the treatment of ALK-positive non-small cell lung cancer," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "This CHMP opinion represents a step forward in bringing LORVIQUA to patients in Europe living with advanced ALK-positive non-small cell lung cancer who have limited treatment options."

The Marketing Authorization Application (MAA) for LORVIQUA was based on results from a non-randomized, dose-ranging and activity-estimating, multi-cohort, multi-center Phase 1/2 study, B7461001, evaluating LORVIQUA for the treatment of patients with ALK-positive advanced NSCLC, who were previously treated with one or more ALK TKIs. A total of 229 patients with ALK-positive metastatic NSCLC were enrolled across various subgroups based on prior treatment.

About LORVIQUA (lorlatinib)

LORVIQUA is a TKI that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORVIQUA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier.

LORVIQUA is approved in the U.S. under the brand name LORBRENA for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease, or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. It is also approved in Japan and Canada.

LORBRENA (lorlatinib) IMPORTANT SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Contraindications: LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity.

Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers: Severe hepatotoxicity occurred in 10 of 12 healthy subjects receiving a single dose of LORBRENA with multiple daily doses of rifampin, a strong CYP3A inducer. Grade 4 ALT or AST elevations occurred in 50% of subjects, Grade 3 in 33% of subjects, and Grade 2 in 8% of subjects. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA. Avoid concomitant use of LORBRENA with moderate CYP3A inducers. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor AST, ALT, and bilirubin 48 hours after initiating LORBRENA and at least 3 times during the first week after initiating LORBRENA. Depending upon the relative importance of each drug, discontinue LORBRENA or the CYP3A inducer for persistent Grade 2 or higher hepatotoxicity.

Central Nervous System (CNS) Effects: A broad spectrum of CNS effects can occur. These include seizures, hallucinations, and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Withhold and resume at the same or reduced dose or permanently discontinue based on severity.

Hyperlipidemia: Increases in serum cholesterol and triglycerides can occur. Grade 3 or 4 elevations in total cholesterol occurred in 17% and Grade 3 or 4 elevations in triglycerides occurred in 17% of the 332 patients who received LORBRENA. Eighty percent of patients required initiation of lipid-lowering medications, with a median time to onset of start of such medications of 21 days. Initiate or increase the dose of lipid-lowering agents in patients with hyperlipidemia. Monitor serum cholesterol and triglycerides before initiating LORBRENA, 1 and 2 months after initiating LORBRENA, and periodically thereafter. Withhold and resume at same dose for the first occurrence; resume at same or reduced dose of LORBRENA for recurrence based on severity.

Atrioventricular (AV) Block: PR interval prolongation and AV block can occur. In 295 patients who received LORBRENA at a dose of 100 mg orally once daily and who had a baseline electrocardiography (ECG), 1% experienced AV block and 0.3% experienced Grade 3 AV block and underwent pacemaker placement. Monitor ECG prior to initiating LORBRENA and periodically thereafter. Withhold and resume at reduced or same dose in patients who undergo pacemaker placement. Permanently discontinue for recurrence in patients without a pacemaker.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis can occur. ILD/pneumonitis occurred in 1.5% of patients, including Grade 3 or 4 ILD/pneumonitis in 1.2% of patients. Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis. Immediately withhold LORBRENA in patients with suspected ILD/pneumonitis. Permanently discontinue LORBRENA for treatment-related ILD/pneumonitis of any severity.

Embryo-fetal Toxicity: LORBRENA can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective non-hormonal method of contraception, since LORBRENA can render hormonal contraceptives ineffective, during treatment with LORBRENA and for at least 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with LORBRENA and for 3 months after the final dose.

Adverse Reactions: Serious adverse reactions occurred in 32% of the 295 patients; the most frequently reported serious adverse reactions were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions occurred in 2.7% of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%). The most common (≥20%) adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea; the most common (≥20%) laboratory abnormalities were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase.

Drug Interactions: LORBRENA is contraindicated in patients taking strong CYP3A inducers. Avoid concomitant use with moderate CYP3A inducers and strong CYP3A inhibitors. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor ALT, AST, and bilirubin as recommended. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the LORBRENA dose as recommended. Concomitant use of LORBRENA decreases the concentration of CYP3A substrates.

Lactation: Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with LORBRENA and for 7 days after the final dose.

Hepatic Impairment: No dose adjustment is recommended for patients with mild hepatic impairment. The recommended dose of LORBRENA has not been established for patients with moderate or severe hepatic impairment.

Renal Impairment: No dose adjustment is recommended for patients with mild or moderate renal impairment. The recommended dose of LORBRENA has not been established for patients with severe renal impairment.

Please see full prescribing information for LORBRENA in the U.S. here.

About Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the most common cancer worldwide, with more than two million new cases diagnosed globally in 2018.1 About 85 percent of all lung cancers are identified as non-small cell, and approximately 75 percent of these are metastatic, or advanced, at diagnosis.2

ALK gene rearrangement is a genetic alteration that drives the development of lung cancer in some patients.3,4 Epidemiology studies suggest that approximately three to five percent of NSCLC tumors are ALK-positive.5

About Pfizer in Lung Cancer

Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer, the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies, including biomarker-driven therapies and immuno-oncology (IO) agents and combinations. By combining leading scientific insights with a patient-centric approach, Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our growing research pipeline and collaboration efforts, we are committed to delivering renewed hope to patients living with NSCLC.

On February 28, 2019 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported that the company will present at the Barclays Global Healthcare Conference in Miami Beach, Florida on Tuesday, March 12, 2019 at 8:00 a.m. ET (Press release, BioCryst Pharmaceuticals, FEB 28, 2019, View Source [SID1234533790]).

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Links to a live audio webcast and replay of the presentation may be accessed in the Investors section of BioCryst’s website at http://www.biocryst.com.

On February 28, 2019 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that preclinical data for CG-806, its first-in-class, highly potent oral small molecule pan-FLT3/pan-BTK inhibitor, and APTO-253, its MYC inhibitor, will be presented in two separate posters at the 2019 AACR (Free AACR Whitepaper) Annual Meeting in Atlanta, GA (Press release, Aptose Biosciences, FEB 28, 2019, View Source [SID1234533805]).

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CG-806 Poster Presentation Details:

CG-806, a pan-FLT3 / pan-BTK inhibitor, demonstrates superior potency against cells from IDH-1 mutant and other non-favorable risk groups of AML patients
Date & Time: Monday, April 1, 2019, 8:00 a.m. – 12:00 p.m.
Session Category: Experimental and Molecular Therapeutics
Session Title: Tyrosine Kinase and Phosphatase Inhibitors 1
Abstract Number: 1323
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 15

APTO-253 Poster Presentation Details:

Resistance to APTO-253 caused by internal deletion and alternate promoter usage of the MYC gene in malignant B cells
Date & Time: Monday, April 1, 2019, 1:00 p.m. – 5:00 p.m.
Session Category: Experimental and Molecular Therapeutics
Session Title: Drug Resistance 3
Abstract Number: 2096
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 15

All abstracts will be available on the AACR (Free AACR Whitepaper) website, www.aacr.org, and published in the 2018 Proceedings of the AACR (Free AACR Whitepaper).

About CG-806
CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor. This small molecule, in-licensed from CrystalGenomics Inc. in Seoul S. Korea, demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), cures animals of acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL, SLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. Because CG-806 targets key kinases/pathways operative in malignancies derived from the bone marrow, it is in development for B cell cancers and AML.

About APTO-253
APTO-253 is a clinical-stage, small molecule, targeted therapeutic agent that inhibits expression of the MYC oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. The MYC oncogene is overexpressed in hematologic cancers, including acute myeloid leukemia (AML). Aptose researchers have reported the ability of APTO-253 to induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved and investigational therapies for AML or myelodysplastic syndromes (MDS). New findings reveal that APTO-253 might also serve certain solid tumor patients with BRCA1/2 mutations, but without causing toxicity to the normal bone marrow functions.