On June 5, 2017 Cornerstone Pharmaceuticals, Inc., a clinical-stage, oncology-focused pharmaceutical company, reported that it is changing its corporate name to Rafael Pharmaceuticals, Inc., effective immediately (Press release, Rafael Pharmaceuticals, JUN 5, 2017, View Source [SID1234521069]). The name change signifies a new era in the company’s evolution during which the company aims to usher in a new paradigm in anticancer treatment with its breakthrough metabolic cancer drugs. The new name is derived from Raphael, the biblical angel of healing.

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"Over the past few months we’ve gained a lot of momentum across several facets and this is an ideal moment to effectuate our name change," said Howard Jonas, Executive Chairman of Rafael Pharmaceuticals. "We’ve strengthened our company’s foundation by making key hires, by adding renowned scientists and clinicians to our advisory boards, and by adding leaders in the pharmaceutical and scientific research communities to our Board of Directors. Moreover, we’ve made substantial progress towards commercializing our proprietary Altered Energy Metabolism Directed (AEMD) drug platform. Most notably, we recently completed successful End-of-Phase I Type B Meetings with the FDA, and now have approval from the FDA to initiate pivotal trials for CPI-613 in acute myeloid leukemia (AML) and pancreatic cancer."

On June 5, 2017 Laminar Pharma, a pioneering clinical stage biopharmaceutical company developing a new generation of products modulating metabolism of membrane lipids based on the groundbreaking MLT platform, reported that the final results of the of MIN-001-1203 clinical study with 2OHOA in patients with advanced solid tumours, including malignant glioma, have been presented at a poster session within the Developmental Therapeutics and Translational Research track at the 2017 ASCO (Free ASCO Whitepaper) meeting in Chicago (Press release, Laminar Pharma, JUN 5, 2017, View Source [SID1234562097]). 5 leading clinical investigational sites in Spain and in the UK have participated in this study.

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2OHOA, administered as an oral suspension two (BID) or three (TID) times daily, has been generally well tolerated in monotherapy up to 12 g/day, while patients have had difficulties to handle the large volume of liquid intake required for 16g/day (8 g BID), experiencing frequent gastrointestinal effects. Overall 54 patients have received 2OHOA at different doses. One Dose Limiting Toxicity (DLT) was reported at the dose of 12g/day and 3 DLT at 16g/day. 12G/day (4g TID) was confirmed as the maximum Tolerated Dose (MTD) since there were no DLTs reported in the second part of the study conducted with this dose (expansion phase)

No drug-related serious adverse events or other relevant toxicity effects associated to the investigational product have been reported in any of the 54 patients treated, other than the tolerability issues experienced at the highest dose levels (gastrointestinal effects). Study drug related AE (≥10%) at any grade were diarrhoea (53 [26%]), vomiting (29[14%]), nausea (26 [13%]). No G3/G4 whether regardless of study drug relationship or suspected as being study drug related occurred over 10% of patients.

Pharmacokinetic (PK) profile was determined. 2OHOA was quantifiable in all dose levels and maximum concentration (Cmax) was reached at 1 hour after administration in the fasted state. When administered under fed conditions, 2OHOA had bioavailability comparable to that found in the fasted state, although food caused a non-clinically significant delay in the time needed to reach the CMax. Therefore, 2OHOA could be taken without regard to food. The half-life was between 1.4 and 4.6 hours up to 8g/day, increasing to more than 7h at the higher doses. Systemic exposure of 2OHOA increased in proportion to dose following single and repeat BID administration. After repeat BID dosing, systemic exposure of 2OHOA, increased between 1- and 1.7-fold from first dose on Day 1 to last dose on Day 21. PK data supports the planned twice-a-day oral administration of 2OHOA

Very encouraging anti-cancer activity of 2OHOA as single agent has been confirmed in several recurrent, heavily pre-treated patients, including 5 recurrent High Grade Glioma (rHGG) and 3 with other advanced solid tumours (AST). One recurrent glioblastoma (rGBM) pt had sustained partial response for more than 2.5 years (93% shrinkage of target lesion) and 4 rHGG patients (3 GBM) achieved stable disease (SD), by RANO, for at least 6 months. Other 3 AST patients had clinical benefit by RECIST: 1 with mesothelioma (SD for 10 months), 1 with colorectal cancer (SD for 3 months) and 1 with lung metastasis of biliary duct carcinoma (SD for 5 months)

Preliminary analysis of available biomarkers data confirms biological activity by 2OHOA in cancer patients. On the one hand, a reduction of GFAP levels in plasma from rHGG patients after 8 days of treatment was observed in more than 80% of patients analyzed. Average reduction in GFAP levels in the whole set of patients was 20% (n=15). On the other hand, initial analysis of plasma miRNA expression profiles in a subset of 22 patients, shows that at least 3 miRNA were differentially expressed in response to 2OHOA treatment. Target gene analysis of these miRNA is ongoing. These, and other potential plasmatic biomarkers currently being analyzed, are expected to be developed and eventually validated in future clinical studies with 2OHOA, providing valuable support for patient selection strategies and for clinical study design.

Further clinical studies with 2OHOA are currently under preparation, including a Phase IIb study to evaluate the potential clinical benefit of adding 2OHOA to the current Standard of Care (SoC) in patients with newly-diagnosed glioblastoma, given that "the preliminary antitumor activity including a sustained PR in heavy pretreated rHGG pt warrants further investigation in a Ph2 study", as concluded in the poster presented by Dr. A. Azaro, Principal investigator at Vall d’Hebron Institute of Oncology (VHIO), one of the 5 sites participating in this study, and the first author of the poster presented at ASCO (Free ASCO Whitepaper).

Laminar Pharma is also preparing a PI trial in children with malignant glioma and other advanced cancers is being prepared in the USA, with the collaboration of top clinical investigational institutions in New Jersey and Boston.

On June 4, 2017 F-star, a biopharmaceutical company developing novel bispecific antibodies, reported a new partnership with Merck, a leading science and technology company, for the development and commercialisation of five bispecific immuno-oncology antibodies (mAb2) (Press release, f-star, JUN 4, 2017, View Source [SID1234526902]).

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Under the agreement and upon delivery of pre-defined data packages, Merck has the option to acquire five of F-star’s bispecific programmes. This option includes exclusive development and commercialisation rights to F-star’s preclinical lead asset FS118, which is designed to block LAG-3 (Lymphocyte-Activation Gene 3) and PD-L1 (Programmed Death-Ligand 1), two pathways commonly used by cancer cells to evade the immune system. In a preclinical model, F-star has demonstrated that FS118 could improve efficacy compared to monotherapy combinations, which supports the potential to initiate a clinical development programme (1).

Upon option exercise, in addition to FS118, F-star grants Merck exclusive development and commercial rights to four novel bispecific antibodies targeting specific pathways to augment the anti-tumour immune response. In return, Merck will pay up to €115m in upfront, R&D funding and milestone payments in the first two years, and make further payments upon exercising its option and based on milestones.

John Haurum, CEO of F-star, said: "This immuno-oncology collaboration expands our strong relationship with Merck and is a further validation of the potential of F-star’s bispecific antibody platform. Our vision is to transform the treatment of cancer. This is the objective of partnering our lead asset FS118 and other next-generation immuno-oncology compounds with Merck.
This deal also underscores the attractiveness of our asset-centric business model, which provides a flexible deal-making framework whilst at the same time maximising the value of F-star’s bispecific programmes and technology platform. This approach also provides us with additional non-dilutive cash to support our investment in the development of our own pipeline of bispecific antibodies, with a strong focus on immuno-oncology."

This collaboration with Merck is held within F-star’s fourth asset centric vehicle, F-star Delta. Upon the delivery of a pre-defined data package, Merck has an option to acquire the bispecific programmes through the acquisition of F-star Delta and will make further payments upon option exercise as well as milestones with the potential total deal value reaching over €1 billion.

Luciano Rossetti, Executive Vice President, Global Head of Research & Development at the biopharma business of Merck, commented: "Our collaboration with F-star will help us to rapidly enhance our pipeline and grow our portfolio of bispecific immunotherapies. This deal complements our internal capabilities in immuno-oncology and positions us as a potential leader in this important area of research."

On June 4, 2017 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported positive preliminary results with investigational REGN2810, a checkpoint inhibitor targeting PD-1 (programmed death 1), in patients with advanced cutaneous squamous cell carcinoma (CSCC) (Press release, Regeneron, JUN 4, 2017, View Source [SID1234519442]). The data, pooled from two expansion cohorts of the REGN2810 Phase 1 trial, will be presented today at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago during an oral presentation (Abstract #9503). REGN2810 is also being investigated in EMPOWER-CSCC 1, an ongoing Phase 2 potentially pivotal, single-arm, open label clinical trial that is currently enrolling advanced CSCC patients.

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Treatment with REGN2810 led to an investigator-assessed overall response rate (ORR) of 46.2 percent (12 of 26 patients, including 2 complete responses, 9 partial responses and 1 unconfirmed partial response) and a disease control rate (DCR) of 69.2 percent (18 of 26 patients, including 12 ORR and 6 stable disease). The median progression free survival and overall survival were not reached at the data cutoff date with a median follow up of 6.9 months (range: 1.1 to 13.8 months; ongoing). One patient experienced progressive disease during treatment with REGN2810 after the initial response, and two patients were not evaluable due to death, which was considered unrelated to REGN2810. Ten patients remain in response as of the data cutoff date (range: 8 to 40 weeks duration of response).

The most common treatment-related adverse event of any grade was fatigue (23.1 percent). All grade 3 or higher adverse events occurred once and included arthralgia (3.8 percent), maculopapular rash (3.8 percent), asthenia (3.8 percent), aspartate aminotransferase (AST) elevation (3.8 percent) and alanine aminotransferase (ALT) elevation (3.8 percent).

"Cutaneous squamous cell carcinoma or CSCC is the second deadliest skin cancer after melanoma, according to the most recent data available," said Kyriakos P. Papadopoulos, M.D., Senior Clinical Investigator at South Texas Accelerated Research Therapeutics (START) and the study presenter. "There are limited treatments and no established standards of care for advanced stages of this disease. CSCC has one of the highest mutation rates reported for any cancers, likely contributing to the study findings, which represent a high responder rate to a PD-1 antibody in a solid tumor cancer. These results are promising and suggest the PD-1 pathway is an important therapeutic target in these patients."

No apparent association between the objective response and level of PD-L1 (programmed death ligand 1) expression was found. PD-L1 expression by immunohistochemistry (22C3 clone, Dako) was performed in tumor cells for 21 expansion cohort patients, with 81 percent of patients (17 of 21) having greater than or equal to 1 percent positive PD-L1 expression. Additional correlative studies are in process.

This Phase 1 study was designed with an initial dose-escalation portion followed by multiple expansion cohorts that were opened to investigate safety and antitumor activity in specific patient populations. These results are from 10 patients with distantly metastatic CSCC who were enrolled in one expansion cohort (Cohort 7) and 16 patients with inoperable (unresectable) locally or regionally advanced CSCC who were enrolled in a second expansion cohort (Cohort 8). All expansion cohort patients were treated with 3 mg/kg doses of REGN2810 by intravenous infusion over 30 minutes every two weeks for up to 48 weeks.

REGN2810 is a human, monoclonal antibody targeting the checkpoint inhibitor PD-1 and is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. REGN2810 is currently being explored as a monotherapy for multiple cancers – including cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC) and non-small cell lung cancer (NSCLC) – as well as in combination with REGN3767, another investigational immunotherapy targeting the checkpoint inhibitor LAG-3 (lymphocyte-activation gene 3).

REGN2810 and REGN3767 are currently under clinical development, and their safety and efficacy have not been fully evaluated by any regulatory authority.

About CSCC
CSCC is the second most common type of skin cancer in the United States. Although CSCC has a good prognosis when caught early and removed with surgery, it can prove especially aggressive when it progresses to advanced stages. Patients at this stage can be disfigured due to multiple surgeries to remove skin-surface tumors on the head, neck and other parts of the body. CSCC is responsible for the most deaths among non-melanoma skin cancer patients.

On June 4, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that its BRACAnalysis CDx companion diagnostic test successfully identified BRCA-mutated patients with HER2- metastatic breast cancer in the OlympiAD trial (NCT02000622) who responded better to treatment with olaparib than standard chemotherapy (Press release, Myriad Genetics, JUN 4, 2017, View Source [SID1234519454]).

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OlympiAD compared olaparib (300mg twice daily) to physician’s choice of a standard chemotherapy (capecitabine, vinorelbine or eribulin) in the treatment of 302 patients with HER2-negative metastatic breast cancer harboring germline BRCA1/2 mutations as determined by Myriad’s BRACAnalysis CDx companion diagnostic test. The results showed that BRCA-positive patients treated with olaparib had a statistically-significant and clinically-meaningful PFS benefit of compared to the control group.

"In this study, patients with BRCA mutations experienced significantly prolonged PFS when treated with olaparib versus standard of care chemotherapy," said Johnathan Lancaster, M.D., Ph.D., chief medical officer, Myriad Genetic Laboratories. "Based on these findings, all patients with metastatic breast cancer should know their BRCA status as it will be a critical factor in guiding therapy selection for patients with metastatic breast cancer."

It is estimated there are approximately 60,000 patients per year in the United States who are newly diagnosed with or progress to HER2- metastatic breast cancer. Of these patients, two-thirds are not eligible for BRCA testing based upon current testing criteria. If approved by the FDA as a new indication this would potentially triple the number of patients with metastatic breast cancer who are candidates for BRCA testing.

"We believe the results from the OlympiAD study will expand the population who can benefit from the BRACAnalysis CDx test, and the results will help doctors improve care for their patients with metastatic breast cancer," said Lancaster. "This study further supports the use of advanced biomarkers, like BRACAnalysis CDx, to enable precision medicine, which benefits both patients and the healthcare ecosystem."

The collaboration between Myriad and AstraZeneca to develop a novel companion diagnostic test for olaparib began in 2007. OlympiAD is the first Phase 3 trial to demonstrate the clinical utility of the BRACAnalysis CDx test outside of ovarian cancer for which the test was approved by the U.S. Food and Drug Administration (FDA) in Dec. 2014. Based on the robustness of the OlympiaAD results, Myriad plans to submit a supplementary premarket approval (sPMA) application under its existing PMA for BRACAnalysis CDx to include the HER2- metastatic breast cancer indication.

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). This assay is for professional use only and is to be performed only at 320 Wakara Way, Salt Lake City, UT 84108.

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. Lynparza is currently approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It is also approved in the US as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Lynparza is currently being investigated in another separate non-metastatic breast cancer Phase III study called OLYMPIA. This study is still open and recruiting patients internationally.