On December 19, 2018 Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) reported its results from the pivotal Phase III trial MEDALIST in early December 2018 (Press release, Celgene, DEC 19, 2018, View Source [SID1234532160]). The study evaluated the efficacy and safety of the investigational product luspatercept for the treatment of patients suffering from anemia due to ring dermoblast-positive (RS +) myelodysplastic syndrome (MDS), transfusions with packed red blood cells (EC), and where erythropoietin therapy was unsuccessful , there was an intolerance to it or such therapy was out of the question. The results were Alan F. List during the scientific plenary session on the 60th

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!

"Severe anemia leading to red blood cell transfusion dependence is a significant burden for patients at low risk MDS. For patients who become resistant or refractory to currently available therapies, there are only limited alternatives, "said Drs. List, President and CEO of the Moffitt Cancer Center. "The results from the MEDALIST study are very promising. They support the hypothesis that luspatercept promotes the maturation of erythroid progenitor cells, allowing patients to become transfusion-independent. Luspatercept could thus improve the treatment of anemia in RS + MDS patients. "

The MEDALIST trial reached its primary endpoint: A statistically significantly greater proportion of patients achieved RBC-TI independence of ≥ 8 weeks in the first 24 weeks of treatment with luspatercept compared to placebo. In addition, all important secondary endpoints of the study were achieved. Compared to placebo, a significantly greater proportion of patients in the luspatercept arm achieved RBC-TI ≥ 12 weeks in the first 24 and 48 weeks of study, respectively, and hematologic erythropoiesis (HI-E after IWG 2006) of 8 weeks or more.

endpoints Luspatercept placebo p-value
RBC-TI ≥ 8 weeks (Week 1-24) 37.9 % (58/153) 13.2 % (10/76) <0.0001
RBC-TI ≥ 12 weeks (Week 1-24) 28.1 % (43/153) 7.9 % (6/76) 0.0002
RBC-TI ≥ 12 weeks (Week 1-48) 33.3 % (51/153) 11.8 % (9/76) 0.0003
HI-E ≥ 8 weeks (IWG 2006, weeks 1-24) 52.9 % (81/153) 11.8 % (9/76) <0.0001

Summary of safety data from the MEDALIST study

Third or fourth degree treatment-associated adverse events (TEAEs) were observed in 42.5% (65/153) of patients receiving luspatercept and 44.7% (34/76) of patients receiving placebo. Disease progression to acute myelogenous leukemia (AML) occurred in a total of four patients: three patients (2.0%) treated with luspatercept and one patient (1.3%) receiving placebo. Five patients receiving luspatercept (3.3%) and four patients receiving a placebo (5.3%) experienced one or more TEAEs that were fatal.

The most common TEAEs of any grade in more than 10% of patients in either study arm

Luspatercept
n = 153

placebo
n = 76

fatigue 26.8 % 13.2 %
diarrhea 22.2 % 9.2 %
asthenia 20.3 % 11.8 %
nausea 20.3 % 7.9 %
dizziness 19.6 % 5.3 %
back pain 19.0 % 6.6 %

"The results of the MEDALIST study illustrate the potential clinical benefits of Luspatercept to make patients with RS + low-risk MDS less dependent on red blood cell transfusion. This is an area where new therapies are needed. " med. Alise Reicin, President of Global Clinical Development at Celgene. "These findings reinforce our belief that this first-in-class erythropoietic-based drug can help these patients address the underlying cause of their disease-related chronic anemia."

"It is a great honor to present the results of the MEDALIST study as the first presentation at the ASH (Free ASH Whitepaper) plenary session," said Habib Dable, President and Chief Executive Officer of Acceleron. "The results of the MEDALIST study give us confidence that luspatercept can provide a relevant treatment option for patients with low-risk RS + MDS anywhere in the world. We look forward to continuing our clinical development program for MDS, beta-thalassemia and myelofibrosis, while investigating other applications of luspatercept in a variety of anemia-related diseases. "

Luspatercept is not approved in any region and for no indication. Acceleron and Celgene are planning to submit regulatory filings for Luspatercept in the US and Europe in the first half of 2019.

About MEDALIST

MEDALIST is a randomized, double-blind, placebo-controlled, multicentre phase III trial to evaluate the safety and efficacy of luspatercept in patients with very low, low or medium risk RS + myelodysplastic syndromes (MDS). All patients were RBC transfusion-dependent and either refractory to previous therapy with erythropoiesis-stimulating agents (ESA), did not tolerate them or were ESA naive with endogenous serum erythropoietin ≥200 U / L and had no previous treatment with disease modifying agents receive. The median age of the study participants was 71 years in the luspatercept treatment group and 72 years in the placebo group. The mean transfusion load in both study arms was 5 RBC units / 8 weeks. A total of 229 patients were randomized to receive either luspatercept 1.0 mg / kg (153 patients) or placebo (76 patients) every 21 days as a subcutaneous injection. The study was conducted at 65 sites in 11 countries.

About Luspatercept

Luspatercept, the erythrocyte-ripening substance, is the first active ingredient in a new erythroid maturation agent (EMA). It promotes erythrocyte maturation in the late stages of erythropoiesis. Acceleron and Celgene are developing Luspatercept as part of a global collaboration. Phase III clinical trials are evaluating the safety and efficacy of luspatercept in patients with MDS (MEDALIST trial) and patients with beta thalassemia (BELIEVE trial). The COMMANDS phase III study in low-risk first-line MDS patients, the BEYOND non-transfusion-dependent beta-thalassemia phase II study and a phase II study in myelofibrosis are ongoing. For more information, seewww.clinicaltrials.gov .

On December 19, 2018 Auron Therapeutics and Elucidata Corporation reported a scientific collaboration using Elucidata’s AI-based target discovery platform to identify and validate targets for differentiation9-based therapy for Acute Myeloid Leukemia (AML) and eight other oncology indications (Press release, Auron Healthcare, DEC 19, 2018, View Source [SID1234532161]). As part of this collaboration, Elucidata will use its data analytics platform PollyTM, to analyze transcriptomic, metabolomic and epigenetic data from biological samples, as well as disease and treatment response data from patients. This four-year collaboration is among the broadest efforts to date to apply the differentiation-based approach for oncology therapies and has the potential to improve outcomes for patients living with these diseases.

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!

Elucidata’s AI-based platform combines different forms of omics data using advanced computational analysis techniques to characterize healthy and diseased states at the molecular level. Auron will provide phenotypic data along with transcriptomic, metabolomic and epigenetic data from hundreds of patient samples which will be analyzed on PollyTM to identify and validate targets to develop new therapies with improved treatment efficacy and minimal side effects for a subgroup of patients. The insights generated from this collaboration will further enable stratification of subtypes of different cancers.

"I am extremely impressed by the PollyTM platform that Elucidata has built and the power it has to digest, integrate and analyze large data sets," said Kate Yen, Ph.D., Founder and CEO of Auron Therapeutics. "The unique partnership that we have allows us to work hand-in-hand with the software engineers, scientists, and program managers to rapidly develop novel hypotheses which we can test in the lab. In just a short period of time, we have made significant progress that has had a substantial impact on Auron’s growth."

"With our platform, we are seeking to develop an atlas of differentiation paths of healthy and diseased cells that will help us identify and characterize disease mechanisms," said Abhishek Jha, Co-founder and CEO of Elucidata. "This collaboration with Auron is an incredible opportunity to realize the promise of big data analytics to discover new targets that will deliver more precise medicine to patients."

On December 19, 2018 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), reported that based on a subset of data from MD Anderson’s ongoing Phase 2 study, the U.S. Food and Drug Administration (FDA) did not grant Breakthrough Therapy Designation (BTD) to poziotinib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 20 mutations (Press release, Spectrum Pharmaceuticals, DEC 19, 2018, View Source;19.htm [SID1234532181]). The company’s overall development plan and timeline for a New Drug Application (NDA) filing based on the first cohort of the ZENITH20 trial remains unchanged.

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!

Breakthrough Therapy Designation is one of several FDA programs designed to expedite the review of drugs to treat serious or life threatening conditions. Spectrum’s BTD application included data from 30 patients from the MD Anderson Phase 2 study who had failed platinum-based chemotherapy. The data demonstrated a confirmed objective response rate of 40% and median duration of response of 6.6 months. The safety profile in this subset was consistent with historical data published on poziotinib and other tyrosine kinase inhibitors. The historical objective response rates for mutation specific NSCLC patients range between 0% and 8% with tyrosine kinase inhibitors and for non-mutation specific NSCLC patients range between 0.8% and 22.9% with other treatments.

"Our enthusiasm for poziotinib, our commitment to the program, and our overall development plan remain unchanged," said Joe Turgeon, President and Chief Executive Officer of Spectrum Pharmaceuticals. "We will continue to work with the FDA to achieve the fastest route to approval of poziotinib based on our ZENITH20 study."

ZENITH20 is a Spectrum-sponsored, open-label, single-arm, multi-center, global Phase 2 study evaluating more than 300 NSCLC patients with EGFR or HER2 exon 20 insertion mutations. The study consists of four cohorts, each of which is independently powered for a pre-specified statistical hypothesis.

"Poziotinib’s overall development program is robust, and the clinical profile remains very attractive in an area of high unmet need," said Francois Lebel, M.D., F.R.C.P.C, Chief Medical Officer of Spectrum Pharmaceuticals. "Data required for the NDA filing for previously treated NSCLC patients with EGFR exon 20 insertion mutations is expected to come from an 87-patient cohort in our ZENITH20 study. We expect to complete enrollment in this cohort in the first quarter of 2019, and announce topline data in the second half of 2019."

11500 S. Eastern Ave., Ste. 240 • Henderson, Nevada 89052 • Tel: 702-835-6300 • Fax: 702-260-7405 • www.sppirx.com • NASDAQ: SPPI

poziotinibfinal121918_image1.gif

Conference Call Details:
Wednesday, December 19, 2018 at 4:30 p.m. Eastern/1:30 p.m. Pacific
Domestic: (877) 837-3910, Conference ID# 1577888
International: (973) 796-5077, Conference ID# 1577888
The conference call will also be webcast live. To access the webcast, please visit the Investor Relations page of the Spectrum Pharmaceuticals website at View Source
For interested individuals unable to join the call, a replay will be available from December 19, 2018 @ 7:30 p.m. ET/4:30 p.m. PT through December 26, 2018, until 7:30 p.m. ET/4:30 p.m. PT.
Domestic Replay Dial-In: (855) 859-2056, Conference ID# 1577888
International Replay Dial-In: (404) 537-3406, Conference ID# 1577888

About Poziotinib
Poziotinib is a novel, oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. Spectrum received exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by Spectrum and Hanmi in several mid-stage trials in multiple solid tumors.

About ZENITH20

The ZENITH20 study is Spectrum-sponsored, Phase 2, open-label, single-arm, multi-center, global study for patients with EGFR or HER2 exon 20 insertion mutations in NSCLC. It consists of four cohorts, each of which is an independent study with pre-specified statistical hypotheses and statistical power. There are two cohorts in the previously-treated setting and two in the first-line setting. The full poziotinib targeted therapy clinical program is focused on four development areas for EGFR and HER2 mutations, including previously treated NSCLC, first-line NSCLC, treatment of other solid tumors and combination therapy.

On December 19, 2018 On December 19, 2018, BeiGene, Ltd. (the "Company") reported that it received notice from Merck KGaA ("Merck KGaA") that Merck KGaA was terminating for convenience the parties’ License Agreement dated December 10, 2013, as amended, for the Company’s investigational RAF dimer inhibitor lifirafenib (BGB-283) in the People’s Republic of China ("PRC") (Filing, 8-K, BeiGene, DEC 19, 2018, View Source [SID1234532301]). As a result of such termination, Merck KGaA’s exclusive right of first negotiation to acquire exclusive commercialization rights under the lifirafenib RAF dimer program in the PRC was terminated and the Company is no longer required to pay Merck KGaA royalties on sales of lifirafenib in the PRC or entitled to receive future milestone payments from Merck KGaA for lifirafenib. The Company’s ex-PRC agreement with Merck KGaA on lifirafenib was terminated in March 2017.

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!

On December 19, 2018 Compass Therapeutics, a biotechnology company committed to the ambitious goal of comprehensively drugging the human immune system, reported the appointment of veteran biopharma leaders Yu Liu, M.D., Ph.D., MBA, as chief medical officer and Lynne Sullivan as chief financial officer (Press release, Compass Therapeutics, DEC 19, 2018, View Source [SID1234532145]).

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!

Dr. Liu, who most recently served as vice president and head of early clinical development at Pfizer, will oversee Compass’ development of a deep pipeline of immuno-oncology and autoimmune disease candidates. The company’s lead candidate, CTX-471, a fully human monoclonal antibody that induces remodeling of the tumor microenvironment and leads to immune-mediated destruction of solid tumors, is expected to enter the clinic in the first quarter of 2019. More than 15 therapeutic candidates are advancing through preclinical development and the research team continues to generate an exciting array of novel candidates through the company’s proprietary antibody development platform.

Ms. Sullivan, who most recently served as senior vice president, finance at Biogen, will lead financial planning and management at Compass at a time of significant growth for the company.

"Yu and Lynne bring essential skills and expertise to Compass as we prepare to take our lead program into the clinic in the coming months," said Thomas Schuetz, M.D., Ph.D., the company’s co-founder and chief executive officer. "Their depth of experience and the strength of their leadership will serve us well, and we’re excited to welcome them aboard."

At Pfizer, Dr. Liu oversaw early clinical development of the company’s pipeline candidates in internal medicine, rare disease and inflammation/ immunology. Prior to Pfizer, Dr. Liu led Biogen’s early clinical development effort in rare disease, with an emphasis on cell and gene therapy. Earlier, he held various leadership roles at Bristol-Myers Squibb, culminating in his position as vice president of the oncology business unit, based in Shanghai, China. Previously Dr. Liu held positions at Essentialis Therapeutics and Amgen. Dr. Liu trained in internal medicine at Massachusetts General Hospital. He received his Ph.D. in immunology from Boston University and his MBA in finance from University of Massachusetts, Boston. He also completed a residency scholarship program in clinical research at the Harvard School of Public Health.

At Biogen, Ms. Sullivan moved through positions of increasing responsibility during her more than 10-year tenure and was named senior vice president of finance in 2015. In that role, she led financial planning and analysis, corporate finance and tax functions for Biogen’s global operations. Prior to Biogen, Ms. Sullivan served as a vice president overseeing tax function for Merck KGaA’s North American operationsand was Serono’s Vice President, Tax, Americas and International for seven years. She was a Tax Partner in the Boston office of Arthur Andersen prior to joining Serono. She currently serves as director and chair of the audit committee for both resTORbio and Solid Biosciences. Ms. Sullivan earned a bachelor’s degree in accounting from Suffolk University and a master’s in taxation from Bentley University. She is also a CPA in Massachusetts.