On June 1, 2017 Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) reported that they have completed target enrollment in the MEDALIST and BELIEVE Phase 3 studies of luspatercept in patients with myelodysplastic syndromes (MDS) and beta-thalassemia (Press release, Acceleron Pharma, JUN 2, 2017, View Source [SID1234519354]). The Companies expect to report top-line results from the clinical trials in the middle of 2018. Luspatercept is being developed to treat a range of hematologic diseases including MDS, beta-thalassemia, and myelofibrosis as part of a global collaboration between Acceleron and Celgene.

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"We are excited to have completed target enrollment in our MEDALIST and BELIEVE Phase 3 studies of luspatercept, ahead of schedule, and look forward to reporting top-line results in the middle of next year," said Michael Pehl, President, Hematology and Oncology for Celgene. "Patients suffering from both diseases have limited treatment options to improve their underlying anemia. We believe that luspatercept may be a potentially paradigm-changing treatment option for patients and physicians alike."

"The rapid pace of patient recruitment in our global Phase 3 trials reflects the clear need for new MDS and beta-thalassemia therapies that can significantly reduce or eliminate dependence on red blood cell transfusions," said Habib Dable, President and Chief Executive Officer of Acceleron. "We are grateful for the support and dedication of the MEDALIST and BELIEVE study investigators, our patient advocacy partners, and most importantly the more than 500 patients and their families who are participating in our studies. I would also like to acknowledge the strong collaborative effort of the Celgene and Acceleron teams that led to this important achievement."

The MEDALIST Phase 3 trial has enrolled 210 patients with lower-risk MDS. The BELIEVE Phase 3 trial has enrolled 300 patients with transfusion dependent beta-thalassemia. Patients who are currently in screening remain eligible for randomization into both Phase 3 studies. The trials will remain blinded for both the primary and secondary endpoints until the end of the 48-week treatment period for all randomized patients.

About the MEDALIST Study

The MEDALIST Phase 3 trial is a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of luspatercept in patients with ring sideroblasts (RS+), lower-risk MDS with a baseline RBC transfusion burden of at least 2 units per 8 weeks over the 16-week period prior to treatment. The primary endpoint of the study is the proportion of patients who are red blood cell (RBC) transfusion independent over any consecutive 8-week period through week 24. Secondary endpoints include duration of RBC transfusion independence and proportion of patients achieving a modified hematologic improvement – erythroid (HI-E) per the International Working Group over any consecutive 8-week period during treatment. Patients were randomized 2:1, luspatercept to placebo treatment, administered subcutaneously every 3 weeks for 48 weeks. The MEDALIST study is being conducted at 74 investigational sites in 11 countries.

About the BELIEVE Study

The BELIEVE Phase 3 trial is a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of luspatercept in patients with transfusion dependent beta-thalassemia. The primary endpoint of the study is the proportion of patients achieving a ≥ 33% reduction in red blood cell (RBC) transfusion burden from Week 13 to Week 24 compared to the baseline 12-week period prior to treatment. Secondary endpoints include reductions in RBC transfusion burden from Week 37 to Week 48 compared to baseline. Beta-thalassemia patients in the trial had a baseline RBC transfusion burden of 6 to 20 units over the 24-week period prior to treatment. Patients were randomized 2:1, luspatercept to placebo treatment, administered subcutaneously every 3 weeks for 48 weeks. The BELIEVE study is being conducted at 73 investigational sites in 15 countries.

About Luspatercept

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the transforming growth factor-beta superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoiesis-stimulating agents (ESAs), which stimulate the proliferation of early-stage erythrocyte progenitor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Acceleron and Celgene are conducting two Phase 3 clinical trials that are designed to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the "MEDALIST" study) and in patients with beta-thalassemia (the "BELIEVE" study). For more information, please visit www.clinicaltrials.gov.

Luspatercept is an investigational compound that is not approved or use in any country.

On June 2, 2017 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported presentations of clinical data for FOLOTYN (pralatrexate injection) and MARQIBO (vinCRIStine sulfate LIPOSOME injection) to be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held in Chicago, Illinois, from June 2- 6, 2017 (Press release, Spectrum Pharmaceuticals, JUN 2, 2017, View Source [SID1234519351]).

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For more information about the ASCO (Free ASCO Whitepaper) Annual Meeting and for a complete list of abstracts, please refer to the conference website at View Source


FOLOTYN() (pralatrexate injection) related abstract:

Monday June 5, 2017, 8:00 AM-11:30 AM CDT

Abstract # Type Title First Author Location
7521
Poster Innovative approach to determine overall survival (OS) benefit for orphan diseases using case match control analyses (CMCA): The PROPEL experience of pralatrexate in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). O’Connor Hall A

MARQIBO (vinCRIStine sulfate LIPOSOME injection) related abstracts:

Saturday June 3, 2017, 3:00 PM-6:00 PM CDT

Abstract # Type Title First Author Location
7506 Oral Radiotherapy to bulky disease PET-negative after immunochemotherapy in elderly DLBCL patients: Results of a planned interim analysis of the first 187 patients with bulky disease treated in the OPTIMAL > 60 study of the DSHNHL. Pfreundschuh S100bc

Monday June 5, 2017, 8:00 AM-11:30 AM CDT

Abstract # Type Title First Author Location
7539 Poster Anti-infective prophylaxis with aciclovir and cotrimoxazole to reduce the rate of infections and therapy-associated deaths in elderly patients with DLBCL undergoing R-CHOP immunochemotherapy. Murawski Hall A

On June 2, 2017 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative medicines and imaging analytical tools for targeting and treating cancer, reported the presentation of two studies highlighting the use of an automated bone scan index (aBSI) in men with bone-metastatic castration-resistant prostate cancer (CRPC) at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 2-6 in Chicago, Illinois (Press release, Progenics Pharmaceuticals, JUN 2, 2017, View Source [SID1234519350]).

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The vast majority of men with CRPC have bone metastases and bone scans are the standard imaging modality in these patients. Bone scans indirectly assess tumor activity by measuring bone mineral turnover. The bone scan index quantifies the prostate cancer disease burden shown on a bone scan. Employing artificial intelligence, the aBSI automatically calculates the bone scan index. aBSI permits a faster quantitative assessment of tumor burden compared to manual BSI and is highly reproducible

The first study, entitled, "Phase 3 prognostic analysis of the automated bone scan index (aBSI) in men with bone-metastatic castration-resistant prostate cancer (CRPC)," will be featured during an oral presentation on June 3rd. This study is the first evaluation of aBSI in a phase 3 study as a prognostic biomarker for survival in patients with bone-metastatic CRPC. The study demonstrated that in these patients, aBSI at baseline was prognostic for overall and disease specific survival (p <0.0001), progression free survival (p =0.0024), radiographic progression-free survival (rPFS) (p =0.0061), and symptomatic skeletal related events (SSEs) (p =0.0068).

"This large scale study highlights the ability of the aBSI to provide clinically meaningful prognostic information to patients with bone-metastatic CRPC, using a quantitative software method to assess the burden of bone metastases," said Andrew Armstrong, MD ScM FACP, Associate Professor of Medicine and Surgery, Associate Director for Clinical Research in Genitourinary Oncology Duke Cancer Institute, Duke University, Durham, NC. "This is the largest study to date of this bone scan index and we demonstrate clinically important outcomes associated with increasing BSI including mortality and symptomatic progression, independent of other known factors."

The second study will be presented at ASCO (Free ASCO Whitepaper) on June 5th as a poster titled "Translating Prostate Cancer Working Group (PCWG) Criteria into a Quantitative Progression Biomarker in Metastatic Castration Resistant Prostate Cancer (mCRPC)". This study demonstrates the utility of automated bone scan indexing to quantitatively assess total tumor burden during the course of disease progression as called for by PCWG2 criteria.

"Historically, assessing treatment effects in prostate cancer has been complicated by the dominance of bone metastases relative to soft tissue disease, making it difficult to accurately assess changes in disease burden over time in patients with mCRPC," said Michael J. Morris, MD of Memorial Sloan Kettering Cancer Center. "There is a significant need for a fully quantitative biomarker to demonstrate treatment response in these patients, and the current data are encouraging that the aBSI reflects clinically relevant changes in bone, and may fulfill this unmet need."



The schedule for the presentations at ASCO (Free ASCO Whitepaper) is as follows:

Date & Time: Saturday, June 3, 2017, 1:15 PM-4:15 PM

Session Title: Genitourinary (Prostate) Cancer

Session Type: Oral Abstract Presentation

Title: Phase 3 prognostic analysis of the automated bone scan index (aBSI) in men with bone-metastatic castration-resistant prostate cancer (CRPC)

Location: Hall B1

Abstract No.: 5006



Date & Time: Monday, June 5, 2017, 1:15 PM-4:15 PM

Session Title: Genitourinary (Prostate) Cancer

Session Type: Poster Session

Title: Translating Prostate Cancer Working Group (PCWG) criteria into a quantitative progression biomarker in metastatic Castration Resistant Prostate Cancer (mCRPC)

Location: Hall A, Poster Board # 142

Abstract No.: 5068

On June 2, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported results from Study 005, a large 2,000 patient prospective study of the Myriad myRisk Hereditary Cancer test, which will be featured in three poster presentations at the 53rd annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Myriad Genetics, JUN 2, 2017, View Source [SID1234519349]).

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The data will be presented by research collaborators from University of Southern California (USC) Norris Comprehensive Cancer Center and Stanford University Cancer Institute. The key findings are that more than 50 percent of the mutations identified were in patients who would not meet current testing guidelines and 34 percent of mutations were identified in unexpected genes, confirming the clinical utility of multi-gene panel testing to improve hereditary cancer-risk assessment.

"We are very excited to present new data on our myRisk Hereditary Cancer test which shows our ongoing commitment to collaborate with leading academic centers and advance the field of hereditary cancer testing," said Johnathan Lancaster, M.D., Ph.D., chief medical officer, Myriad Genetic Laboratories. "Importantly this study demonstrates that more than half of mutations would be missed with current testing guidelines and 34 percent of mutations identified were unexpected and not predicted by personal and/or family history. This study will provide vital data to facilitate review of medical guidelines in light of advances made in next generation sequencing."

The data are highlighted below and abstracts are available at: abstracts.asco.org.

myRisk Hereditary Cancer Poster Presentations
Title: Performance of Mutation Risk Prediction Models in a Racially Diverse Multi-Gene Panel Testing Cohort.
Presenter: Gregory Idos, M.D., USC Norris Comprehensive Cancer Center.
Date: Monday, June 5, 2017, 1:15 — 4:45 p.m.
Location: Poster 181; Abstract 1523

National Comprehensive Cancer Network (NCCN) guidelines recommend germline genetic testing for patients with a mutation carrier probability (CP) score of five percent or higher. An analysis of data from Study 005 evaluated the percentage of pathogenic mutations in a population of racially diverse patients with a CP score less than five percent. In total 2,000 patients were tested using the myRisk Hereditary Cancer test and 242 were found to have pathogenic mutations. The results showed that more than 50 percent of patients with BRCA1/2 or mismatch repair (MMR) mutations had a CP score less than five percent. Four percent of patients with BRCA1/2 mutations did not meet NCCN guidelines for hereditary breast and ovarian cancer syndrome, and 13 percent of patients with MMR mutations did not meet NCCN criteria for Lynch syndrome testing. Importantly, these findings support lowering the guideline-recommended CP threshold for genetic testing to help ensure that more patients can access genetic testing.

Title: Yield of multiplex panel testing exceeds expert opinion and validated prediction models.
Presenter: Gregory Idos, M.D., USC Norris Comprehensive Cancer Center.
Date: Monday, June 5, 2017, 1:15 — 4:45 p.m.
Location: Poster 183; Abstract 1525.

Data from Study 005 were evaluated to determine the diagnostic yield and clinical utility of panel testing using the myRisk Hereditary Cancer 28-gene test in 2,000 patients undergoing hereditary cancer-risk assessment. Approximately 81 percent of patients were women and 40 percent were Hispanic. Differential diagnoses were generated after standard clinical genetics assessment and before genetic testing. Differences between the differential diagnoses and genetic testing results were evaluated to determine the added diagnostic yield of multi-gene panel testing. The results show that 12.1 percent of patients tested positive for a pathogenic mutation. The most common mutations were in BRCA1 (17 percent) and BRCA2 (15 percent), APC (8 percent), CHEK2 (7 percent) and ATM (7 percent). Importantly, however, 34 percent of the mutations were not clinically suspected before genetic testing, which demonstrates the significant added value of the myRisk Hereditary Cancer test in hereditary cancer-risk assessment.

Title: Yield of multiplex panel testing exceeds expert opinion and validated prediction models.
Presenter: Allison Kurian, M.D., Stanford University Cancer Institute.
Date: Monday, June 5, 2017, 1:15 — 4:45 p.m.
Location: Poster 234; Abstract 1576.

Study 005 also evaluated the safety of gene panel testing among patients who were undergoing cancer-risk assessment with the myRisk Hereditary Cancer test. The analysis of 2,000 patients found that 12.1 percent of patients had pathogenic mutations. Overall, self-reported preventative surgery rates were low (mastectomy 9.2 percent, hysterectomy 1.6 percent, and oophorectomy 1.8 percent). There was no difference in preventative surgery rates between patients with a variant of uncertain significance (VUS) and mutation negative patients (p=0.21). Importantly, most patients never/rarely had thoughts of cancer affecting their daily activities, did not regret genetic testing and wanted to know all the results. Patients with a pathogenic mutation reported higher distress and uncertainty scores than VUS or negative patients, whose distress (p=0.06) and uncertainty (p=0.04) scores were similar. Relatives of mutation positive patients completed genetic testing more often than VUS or negative patients. This study demonstrated that multi-gene panel testing did not result in inappropriate medical management or increased distress/uncertainty among VUS and negative patients.

"The use of multi-gene panels for the clinical assessment of hereditary cancer risk is rapidly increasing in the era of personalized medicine and it’s important that we understand the benefits and risks of genetic testing on patients," said Lancaster. "Study 005 showed that multi-gene panel testing effectively improved hereditary cancer risk assessment and the results did not lead to unwarranted treatment or adverse effects."

About Myriad myRisk Hereditary Cancer
The Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 28 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma. The myRisk Hereditary Cancer test offers physicians several distinct advantages over other commercial tests, including:

Unsurpassed lab accuracy:
85,000 base pairs with ~100 percent accuracy.
856 steps using 23 major technology platforms.
100 proprietary software applications.

Industry leading variant classification:
More than 20 years of investment in research.
>2.5 million patients tested; 50,000 variants identified.
Five proprietary methods with 99.5 percent validity.

Exceptional customer service:
More than 40,000 ordering physicians annually.
450 field educators.
Extensive reimbursement support.
Lifetime commitment to patients.

On June 2, 2017 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that it enters into an agreement with Novo Nordisk A/S granting Innate Pharma full worldwide exclusive rights to develop and commercialize a first-in-class clinical-stage anti-C5aR antibody (IPH5401) representing a novel therapeutic approach in immuno-oncology (Press release, Innate Pharma, JUN 2, 2017, View Source [SID1234519348]).

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IPH5401 is a strategic fit to Innate Pharma’s current immuno-oncology pipeline. It adds a clinical-stage proprietary product that reinforces Innate Pharma’s position in the field of antibodies targeting the tumor microenvironment beyond the Company’s activities in the adenosine pathway. Innate Pharma plans to start trials with IPH5401 in oncology in 2018.

Through C5aR triggering, C5a induces accumulation and activation of myeloid-derived suppressor cells (MDSC) and neutrophils in the tumor microenvironment. These cells are associated with a poor prognosis across numerous tumor types. They secrete pro-tumor and pro-angiogenic factors and have emerged as a major immunosuppressive mechanism, associated with resistance to checkpoint blockers. By targeting and blocking this pathway, anti-C5aR has the potential to enhance anti-tumor immunity across a range of solid and hematologic tumors.

Novo Nordisk A/S has conducted two Phase I trials with anti-C5aR in patients with rheumatoid arthritis, where a good safety profile was demonstrated.

The terms of the transaction provide for a total upfront payment of €40m, of which €37.2m will be paid in new Innate Pharma shares and €2.8m in cash. Novo Nordisk A/S will be eligible for €370m in development, regulatory and sales milestone payments. Novo Nordisk A/S will also be eligible for double digit royalties on net sales.

After the issuance of the new Innate Pharma shares, the stake of Novo Nordisk A/S in Innate Pharma will increase from 10.3% currently to between 14.6% to 15.8% (See "About the transaction section").

The closing is expected to take place on July 12, 2017 at the latest.



Mondher Mahjoubi, Chief Executive Officer of Innate Pharma, commented: "With the acquisition of the first-in-class anti-C5aR antibody, we are broadening our proprietary clinical pipeline. We believe anti-C5aR has a high potential for cancer patients in multiple indications and look forward to beginning clinical development of this promising asset in 2018. Innate Pharma has a strong track record of value creation from in-licensed assets with lirilumab and monalizumab. This acquisition strengthens our asset base further and supports Innate Pharma’s transition towards becoming a fully-integrated biopharmaceutical company."



Mads Krogsgaard Thomsen, Chief Science Officer of Novo Nordisk A/S, added: "In light of Innate’s success within the immuno-oncology field, we believe that Innate is the ideal partner for the anti-C5aR program and we are looking forward to seeing the program advance further in development."