On June 18, 2018 NeuroVive Pharmaceutical AB and BridgeBio Pharma reported that BridgeBio has entered into an exclusive licensing agreement for a subset of succinate prodrug chemistry under NeuroVive’s NVP015 program (Press release, BridgeBio, JUN 18, 2018, View Source [SID1234576278]). BridgeBio also announced that it has launched a subsidiary company Fortify Therapeutics to further develop this chemistry for local treatment of Leber’s Hereditary Optic Neuropathy (LHON), with an initial financial commitment of $20 million USD. NeuroVive’s NVP015 program for other mitochondrial disorders will continue without any changes in focus or timelines.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

LHON is caused by mitochondrial DNA mutations in subunits of NADH dehydrogenase (complex I), leading to reduced oxidative phosphorylation and energy production in retinal cells. The disease predominantly affects young adults, and results in sudden onset of progressive and severe vision loss. The licensed succinate prodrugs have the potential to overcome the disease by bypassing the dysfunctional metabolic pathway, providing an alternate source of energy to the retinal cells.

"As a targeted treatment for a genetic disease, the LHON program is a clear fit with the BridgeBio model," said Neil Kumar, Ph.D., CEO of BridgeBio. "We have been impressed with the ability of these compounds to rescue specific genetic mitochondrial deficiencies, and we have assembled a team of international experts to further develop a subset of the NVP015 chemistry to address this devastating disease."

Fortify Therapeutics will develop selected lead compounds derived from NeuroVive’s novel NVP015 succinate prodrug program into drug candidates for the localized treatment of LHON. These compounds have been selected because they have properties that make them suitable for delivery to the eye.

The licensing agreement for this particular subset of the NVP015 program has a total deal value of approximately $60 million USD, which includes limited initial funding for research, and later milestone payments and a single digit royalty stream, that are dependent on successful development and market approval.

"The agreement with BridgeBio is important to both NeuroVive and our innovative NVP015 program, as it validates the quality of the program, our business development model and potential in a variety of mitochondrial disorders," commented NeuroVive CEO Erik Kinnman, M.D., Ph.D. "We will work closely with BridgeBio to further develop this chemistry subset and make the LHON program successful. It is important to note that our intentions for the NVP015 program are unchanged, and we are progressing towards experimental proof-of-principle during 2018."

This information is information that NeuroVive Pharmaceutical AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out below, at 08:30 a.m. CET on 18 June 2018.

About LHON
Leber’s Hereditary Optic Neuropathy (LHON) is a disease caused by mitochondrial DNA mutations in subunits of NADH dehydrogenase (complex I), a component of the electron transport chain. This results in dysfunctional oxidative phosphorylation and ATP production, leading to degeneration of the retinal ganglion cells and loss of central vision. LHON most commonly affects males in their second or third decade of life. The prevalence of LHON in Europe is between 1:30,000-1:50,000.

About NVP015
One of the most common causes of mitochondrial diseases relates to Complex I dysfunction, i.e. when energy conversion in the first of the five protein complexes in the mitochondrion that are essential for effective energy conversion does not function normally. This is apparent in disorders including Leigh’s Syndrome and MELAS, both of which are very serious diseases with symptoms such as muscle weakness, epileptic fits and other severe neurological manifestations. The NVP015 project is based on a NeuroVive innovation in which the body’s own energy substrate, succinate, is made available in the cell via a prodrug technology. A prodrug is an inactive drug that is activated first when it enters the body by the transformation of its chemical structure. Results from the NVP015 project were published in the prestigious Nature Communications journal in August 2016.

On June 18, 2018 Array BioPharma Inc. (Nasdaq: ARRY) reported that it will present updated safety and efficacy results, including overall survival (OS) data, from the safety lead-in of the Phase 3 BEACON CRC trial evaluating the triplet combination of encorafenib, a BRAF inhibitor, binimetinib, a MEK inhibitor and cetuximab, an anti-EGFR antibody, in patients with BRAF-mutant colorectal cancer (CRC) (Press release, Array BioPharma, JUN 18, 2018, View Source [SID1234527431]). These data will be featured in an oral presentation on Saturday, June 23, at the ESMO (Free ESMO Whitepaper) 20thWorld Congress on Gastrointestinal Cancer in Barcelona, Spain.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Oral Presentation BEACON CRC Safety Lead-In

Title:

BEACON CRC Study Safety Lead-in: Assessment of the BRAF Inhibitor Encorafenib + MEK Inhibitor Binimetinib + Anti–Epidermal Growth Factor Receptor Antibody Cetuximab for BRAFV600E Metastatic Colorectal Cancer

Presenter:

Eric Van Cutsem, M.D., Professor, Internal Medicine, Head, Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven

Abstract:

O-027

Session:

Session XX

Date:

Saturday, June 23

Session Time:

11:40 a.m. – 12:20 p.m. CET (5:40 – 6:20 a.m. ET)

Location:

Auditorium A

Following the presentation, the slides will be available as a PDF on Array’s website at www.arraybiopharma.com.

Array will host an encore webcast presentation of the BEACON CRC safety lead-in trial data.

Encore Investor Webcast:

Presenter:

Axel Grothey, M.D., Division of Hematology/Oncology, Mayo Clinic

Date:

Saturday, June 23

Time:

4:30 pm CET (10:30 am ET)

Toll-Free:

(844) 464-3927

Toll:

(765) 507-2598

Pass Code:

8588348

Webcast, including replay and conference call slides:View Source

About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer. [1] In the U.S. alone, an estimated 140,250 patients will be diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease. [2] In the U.S., BRAF mutations are estimated to occur in 10% to 15% of patients with colorectal cancer and represent a poor prognosis for these patients. [3, 4, 5, 6] The risk of mortality in CRC patients with the BRAFV600E mutation is more than two times higher than for those with wild-type BRAF. [7] Several approved standard of care benchmarks for this population range between 4% to 8% ORR, 1.8 and 2.5 months mPFS and 4 and 6 months mOS. [8, 9, 10, 11, 12, 13, 14] Based on recent prospective historical data, the prevalence of MSI-H in tumors from patients with metastatic BRAF-mutant CRC ranged from 14% in a recent Phase 1b/2 trial (NCT01719380) (Array, data on file) to 18% in a recent Southwestern Oncology Group (SWOG) randomized phase 2 trial. [8]

About BEACON CRC
BEACON CRC is a randomized, open-label, global trial evaluating the efficacy and safety of encorafenib, binimetinib and cetuximab in patients with BRAF-mutant metastatic CRC whose disease has progressed after one or two prior regimens. BEACON CRC is the first and only Phase 3 trial designed to test a BRAF/MEK combo targeted therapy in BRAF-mutant advanced CRC. Thirty patients were treated in the safety lead-in and received the triplet combination (encorafenib 300 mg daily, binimetinib 45 mg twice daily and cetuximab per label). Of the 30 patients, 29 had a BRAFV600E mutation. Microsatellite instability-high (MSI-H), resulting from defective DNA mismatch repair, was detected in only 1 patient. As previously announced, the triplet combination demonstrated good tolerability, supporting initiation of the randomized portion of the trial.

The randomized portion of the BEACON CRC trial is designed to assess the efficacy of encorafenib in combination with cetuximab with or without binimetinib compared to cetuximab and irinotecan-based therapy. Approximately 615 patients are expected to be randomized 1:1:1 to receive triplet combination, doublet combination (encorafenib and cetuximab) or the control arm (irinotecan-based therapy and cetuximab). The primary endpoint of the trial is overall survival of the triplet combination compared to the control arm. Secondary endpoints address efficacy of the doublet combination compared to the control arm, and the triplet combination compared to the doublet therapy. Other secondary endpoints include PFS, ORR, duration of response, safety and tolerability. Health related quality of life data will also be assessed. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. Patient enrollment is expected to be completed in 2018.

About Encorafenib and Binimetinib
BRAF and MEK are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma and colorectal cancer. Encorafenib is a late-stage small molecule BRAF inhibitor and binimetinib is a late-stage small molecule MEK inhibitor, both of which target key enzymes in this pathway. Encorafenib and binimetinib are being studied in clinical trials in advanced cancer patients, including the Phase 3 BEACON CRC trial and the Phase 3 COLUMBUS trial.

The U.S. Food and Drug Administration (FDA) is currently reviewing the New Drug Applications (NDAs) to support use of the combination of encorafenib and binimetinib for the treatment of patients with BRAFV600E or K-mutant advanced, unresectable or metastatic melanoma. The FDA set a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2018 for both applications. The European Medicines Agency (EMA), as well as the Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA), are reviewing the Marketing Authorization Applications (MAAs) submitted by Pierre Fabre and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has accepted the Manufacturing and Marketing Approval (MMA) applications submitted by Ono Pharmaceutical Co, Ltd.

Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.

Array BioPharma has exclusive rights to encorafenib and binimetinib in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America. The BEACON CRC trial is being conducted with support from Pierre Fabre and Merck KGaA, Darmstadt, Germany (support is for sites outside of North America).

On June 18, 2018 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported that new data presented at the 23rd Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), held in Stockholm, Sweden, shows that BL-8040, combined with high dose cytarabine (HiDAC), significantly enhanced overall survival in difficult-to-treat relapsed or refractory AML (r/r AML) patients in a Phase 2a clinical trial (Press release, BioLineRx, JUN 18, 2018, View Source;p=RssLanding&cat=news&id=2354886 [SID1234527372]). In addition, an important new finding shows a statistically significant correlation between patient response and the mobilization of AML blasts. Responding patients demonstrated a clear and significant increase in the number of AML blasts in the peripheral blood following BL-8040 treatment, whereas non-responding patients were largely unaffected.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are extremely pleased to see further significant improvement in overall survival for this very difficult-to-treat patient population, as data continues to accumulate from our Phase 2a proof-of-concept study in relapsed or refractory AML," stated Philip A. Serlin, Chief Executive Officer of BioLineRx. "In addition, exciting new findings indicate a clear correlation between patient response and mobilization of AML blasts, thus identifying a potential biomarker for selecting patients likely to respond to BL-8040. These encouraging results strongly support the continued development of BL-8040 in relapsed or refractory AML, giving BioLineRx broad therapeutic coverage in the AML space, with potential activity at different stages of the disease and in different patient populations. We look forward to providing additional updates on overall survival from this study, and continue to execute on our other two important AML trials currently ongoing – a large, randomized, controlled Phase 2b study in consolidation AML, and a Phase 1b/2 study in maintenance of AML under our collaboration with Genentech," added Mr. Serlin.

The Phase 2a study consisted of 42 patients in two cohorts: (i) dose-escalation (range 0.5-2.0 mg/kg) and (ii) dose-expansion at the selected dose of 1.5 mg/kg. Patients with r/r AML were treated daily with BL-8040 monotherapy for two days followed by combined administration of BL-8040 and HiDAC for 5 days, for 1-2 cycles. Efficacy endpoints included response rate (CR/CRi), overall survival, duration of response and event-free survival.

BL-8040 in combination with HiDAC was safe and well tolerated at all BL-8040 dose levels (range 0.5-2.0 mg/kg). The response rate for all dosing levels was 29% and median overall survival was 9.1 months, compared with historical data on overall survival of 6.1 months for HiDAC alone. In patients receiving the 1.5 mg/kg dose selected for expansion (n=23), the response rate was 39% and median overall survival was 10.7 months with 1-year, 2-year and 3-year survival rates of 38.1%, 23.8% and 23.8%, respectively. Furthermore, median overall survival for responding patients at the 1.5 mg/kg dose (n=9) was 21.8 months, with 1-year, 2-year and 3-year survival rates of 66.7%, 44.4% and 44.4%, respectively. Responding patients also demonstrated a statistically significant mean 6.3-fold increase (p=0.003) in the number of AML blasts in the peripheral blood following BL-8040 monotherapy treatment, whereas in non-responding patients the mean-fold increase was minor and non-significant (1.66-fold; p=0.21).

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and stem cell mobilization. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells and immune-cells from the bone marrow, thereby sensitizing cancer cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis). In addition, BL-8040 has also demonstrated robust mobilization of other cell types, including the mobilization of hematopoietic stem and progenitor cells, T, B, NK and antigen presenting cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On June 18, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that the U.S. Food and Drug Administration (FDA) has accepted its supplementary premarket approval (sPMA) application for BRACAnalysis CDx to be used as a companion diagnostic with Pfizer’s PARP (poly ADP ribose polymerase) inhibitor, talazoparib (Press release, Myriad Genetics, JUN 18, 2018, View Source [SID1234527373]). The New Drug Application (NDA) for talazoparib has been granted priority review by the U.S. Food and Drug Administration and has a Prescription Drug User Fee Act (PDUFA) goal date of December 2018.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Myriad’s sPMA and Pfizer’s NDA submissions are based on results from the Pfizer-sponsored EMBRACA trial, which evaluated talazoparib versus chemotherapy in patients with germline (inherited) BRCA-mutated (gBRCAm), HER2-negative locally advanced or metastatic breast cancer (MBC). The primary results of the study were presented at the San Antonio Breast Cancer Symposium in December 2017.

"Myriad was the pioneer in developing companion diagnostics for PARP inhibitors and this submission is another milestone in our collaborations to expand access to this class of drugs across multiple cancers," said Mark C. Capone, president and CEO, Myriad Genetics. "We are excited to pursue a simultaneous diagnostic approval along with talazoparib, as another outstanding opportunity to advance personalized medicine for oncology patients."

Myriad estimates there are approximately 125,000 patients with metastatic breast cancer who would immediately qualify for the BRACAnalysis CDx test, followed by 60,000 new patients per year on an ongoing basis.

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 cancer patients with deleterious or suspected deleterious germline BRCA variants who may be candidates for a PARP inhibitor. 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.

On June 18, 2018 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel oncology therapeutics, reported that positive clinical data from ELZONRISTM (tagraxofusp; SL-401) trials were presented at the 23rdCongress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, Sweden (Press release, Stemline Therapeutics, JUN 18, 2018, View Source [SID1234527374]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Results from the completed pivotal trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN) were presented for the first time to a European audience. This oral presentation also included positive survival and safety updates. Updated results from ongoing clinical trials in patients with relapsed/refractory chronic myelomonocytic leukemia (CMML) or relapsed/refractory myelofibrosis (MF) were also presented and continue to indicate the potential of ELZONRIS in indications beyond BPDCN.

Copies of all three presentations are available on Stemline’s website (www.stemline.com) under the Scientific Presentations tab.

Highlights from the Pivotal Trial – BPDCN (ELZONRIS 5-day regimen, multicycle)

ELZONRIS demonstrated high response rates and high rate of stem cell transplant (SCT) in blastic plasmacytoid dendritic cell neoplasm (BPDCN)
° 90% overall response rate (ORR) in first-line (12 mg/kg; n=29); 69% ORR in relapsed/refractory (n=13)
• Majority of responses are complete responses
° 45% of patients treated with ELZONRIS in first-line (12 mg/kg) were bridged to stem cell transplant in remission (n=13)
No apparent cumulative adverse events, including in the bone marrow, over multiple cycles
Updated data: Median overall survival (OS) in first-line (12 mg/kg; n=29) not reached
Rolling BLA submission in BPDCN underway; on track for completion this quarter
Highlights from the CMML Phase 1/2 Trial (ELZONRIS 3-day regimen, multi-cycle)

ELZONRIS monotherapy demonstrated efficacy, including bone marrow complete responses and improvements in splenomegaly, with a manageable safety profile in patients with relapsed/refractory CMML, an area of high unmet medical need
° Patient enrollment and follow up continues
Manageable safety profile
° Most common treatment-related adverse events (TRAEs) included hypoalbuminemia (38%), thrombocytopenia (25%), and fatigue (25%). Most common TRAEs, grade 3+, include thrombocytopenia (25%) and nausea (6%)
2 bone marrow complete responses (BMCRs)
100% of evaluable patients had reduction in baseline splenomegaly (spleen response)
° 75% had reduction by ≥50%
° 60% with baseline spleen size ≥5cm had reduction by ≥50%
55% (6/11) evaluable patients with treatment duration 6+ months, including 8+ and 14+ months
Based on these encouraging results, registrational trial designs in patients with relapsed/refractory CMML are under evaluation
Highlights from the MF Phase 1/2 Trial (ELZONRIS 3-day regimen, multi-cycle)

ELZONRIS monotherapy demonstrated efficacy, namely improvements in splenomegaly, with a manageable safety profile, in patients with relapsed/refractory MF, an area of high unmet medical need
° Patient enrollment and follow up continues
Manageable safety profile
° Most common TRAEs include hypoalbuminemia and thrombocytopenia (each 27%), and alanine aminotransferase increased, anemia, dizziness, fatigue, headache and nausea (each 20%). Most common TRAEs, grade 3+, include anemia (20%) and thrombocytopenia and fatigue (each 7%)
50% of evaluable patients, with baseline spleen size ≥5cm, had reduction in baseline splenomegaly
° 33% had reduction by ≥33%
° 25% had reduction by ≥35%
67% (6/11) of patients with spleen response had treatment duration 8+ months, including 8+, 12+ and 14+ months (all 3 ongoing)
° 4 patients with baseline thrombocytopenia had treatment durations 8+ months, 3 ongoing
Initial Quality of Life assessments appear promising, and a full TSS (Total Symptom Score) analysis is ongoing
Based on these encouraging results, next steps for the program are being evaluated including single agent, combination, and registration-directed trials in patients with relapsed/refractory MF
Ivan Bergstein, M.D., Stemline’s CEO, commented, "We had another strong showing at a major oncology conference. Our ELZRONRIS pivotal data in BPDCN, which included positive updates around survival and safety, were showcased and very well-received at EHA (Free EHA Whitepaper). The completion of our rolling BLA submission remains on-track for this quarter, and we continue to aggressively advance our pre-launch activities." Dr. Bergstein continued, "Additionally, given the encouraging data we continue to see with ELZONRIS in patients with previously-treated CMML and previously-treated MF, we are actively evaluating registrational opportunities in these areas of unmet medical need."

About ELZONRISTM (tagraxofusp; SL-401)
ELZONRISTM (tagraxofusp; SL-401) is a novel targeted therapy directed to CD123, a cell surface receptor expressed on a range of malignancies. ELZONRIS has successfully completed a pivotal trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN), an indication for which it was granted Breakthrough Therapy Designation (BTD). A rolling Biologics License Application (BLA) submission is underway. ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).