Syros: Promising Data from Phase 2 Trial of Leukemia, MDS Combo at ASH

SY-1425 in Combination with Azacitidine Shows 63% Overall Response Rate and Rapid Onset of Clinical Responses in RARA or IRF8 Biomarker-Positive Newly Diagnosed Unfit AML Patients

Initial Data from Biomarker-Positive and -Negative Azacitidine Combination Cohorts Support Potential Predictive Value of RARA and IRF8 Biomarkers for Patient Selection

SY-1425 Induced CD38 Expression in Majority of Patients in Daratumumab Combination Cohort in Relapsed/Refractory AML and Higher-Risk MDS Patients

Both Combinations Have Been Generally Well-Tolerated to Date

Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, today announced initial clinical data from cohorts in its ongoing Phase 2 trial evaluating SY-1425, its first-in-class selective retinoic acid receptor alpha (RARα) agonist, in combination with azacitidine and with daratumumab in genomically defined patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (MDS). These data are being presented at the 60^th American Society of Hematology (ASH) Annual Meeting and Exposition.

“AML and MDS are complex diseases, and we need therapies that can be used in combination to help patients live longer and with a better quality of life,” said Rachel J. Cook, M.D., M.S., Assistant Professor of Medicine and Site Director for Acute Leukemia at the Knight Cancer Institute, Oregon Health and Science University and a clinical investigator in the Phase 2 study of SY-1425. “These data provide early clinical evidence that SY-1425 may be a meaningful treatment option for defined subsets of AML and MDS patients that is generally well-tolerated in combination with other therapies. I look forward to continuing to investigate SY-1425 to fully understand its potential to benefit patients.”

“These initial combination data from our ongoing Phase 2 trial of SY-1425 are promising,” said David A. Roth, M.D., Syros Chief Medical Officer. “SY-1425 in combination with azacitidine showed both a high response rate and rapid onset of clinical responses in AML patients selected with our RARA or IRF8 biomarkers that we have not seen to date in the biomarker-negative cohort. The combination was generally well-tolerated with no evidence of increased toxicities beyond what would be expected with each agent alone, including myelosuppression that can sometimes be seen when combining drugs to treat leukemia. These data speak to the combination potential of SY-1425 as well as to the potential of our platform to identify patients most likely to respond to gene control medicines. We look forward to further characterizing the clinical activity of SY-1425 in combination with azacitidine as we continue to enroll and follow patients in the trial.”

https://www.marketscreener.com/SYROS-PHARMACEUTICALS-INC-29688130/news/Syros-Pharmaceuticals-Announces-Promising-Clinical-Data-from-Ongoing-Phase-2-Trial-of-SY-1425-in-G-27693669/

Kite: Two-Year Data for Lymphoma Combo Presented at ASH

-- 39 Percent of Patients in Ongoing Response Two Years after a Single Infusion of Yescarta in the ZUMA-1 Study; Median Overall Survival was Not Reached --

-- Data Presented at the Annual Meeting of the American Society of Hematology (ASH) and Simultaneously Published in The Lancet Oncology --

Kite, a Gilead Company (Nasdaq: GILD), announced two-year efficacy and safety data from the pivotal ZUMA-1 trial of Yescarta® (axicabtagene ciloleucel) in patients with refractory large B-cell lymphoma. With a minimum follow-up of two years after a single infusion of Yescarta (median follow up of 27.1 months), 39 percent of patients were in an ongoing response. This updated analysis with at least 24 months of follow-up was presented at the Annual Meeting of the American Society of Hematology (ASH; Abstract #2967) and simultaneously published in The Lancet Oncology.
https://www.streetinsider.com/Press+Releases/Kite+Announces+Two-Year+Data+for+Yescarta%C2%AE+%28Axicabtagene+Ciloleucel%29+in+Patients+With+Refractory+Large+B-Cell+Lymphoma/14881651.html

Blueprint Updates Trial at ASH: Broad Clinical Activity, Symptom Reductions

Blueprint Medicines Corporation (NASDAQ: BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, today announced updated results for the Phase 1 EXPLORER clinical trial of avapritinib, a potent and highly selective inhibitor of D816V mutant KIT, the common disease driver in nearly all patients with systemic mastocytosis (SM). The updated EXPLORER trial data in patients with advanced SM showed durable clinical responses that deepened over time, regardless of disease subtype, prior therapy or starting dose. Avapritinib was generally well-tolerated, and most adverse events (AEs) reported by investigators were Grade 1 or 2. These results will be presented today in an oral presentation at the 60th American Society of Hematology Annual Meeting and Exposition in San Diego, California.

As of the data cutoff date of September 30, 2018, the updated results from the ongoing EXPLORER trial showed an overall response rate (ORR) of 83 percent. Twenty-four percent of patients had a complete response with a full or partial recovery of peripheral blood counts (CR/CRh). Responses deepened over time, with a median time to initial response of two months and a median time to CR/CRh of nine months. The median duration of response (DoR) was not reached, and the 12-month DoR rate was 76 percent.

https://www.streetinsider.com/Press+Releases/Blueprint+Medicines+Announces+Updated+Results+from+Ongoing+EXPLORER+Clinical+Trial+of+Avapritinib+Demonstrating+Broad+Clinical+Activity+and+Significant+Symptom+Reductions+in+Patients+with+Systemic+Mas/14881653.html

NewLink Presents Updated Phase 1 Leukemia Data at ASH

• Updated Phase 1 data for indoximod plus standard-of-care chemotherapy in newly diagnosed AML show post-induction minimal residual disease (MRD) negativity rate of 86% and post-consolidation MRD negativity of 100%
• Safety data from this study indicate the combination treatment regimen was well tolerated with no regimen limiting toxicities (RLTs) observed

NewLink Genetics Corporation (NASDAQ: NLNK) announced that updated Phase 1 data�evaluating indoximod plus standard-of-care chemotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) were presented today by Ashkan Emadi, MD, PhD, Professor of Medicine and Associate Director for Clinical Research, University of Maryland Greenebaum Comprehensive Cancer Center, in an oral session today at the 60th American Society of Hematology (ASH) Annual Meeting in San Diego, CA, from 9:30AM – 11:00AM PT, in Grand Hall B, Manchester Grand Hyatt.

This press release features multimedia. View the full release here:https://www.businesswire.com/news/home/20181202005047/en/

Indoximod plus Chemotherapy in Acute Myeloid Leukemia (AML) (Graphic: Business Wire)

This Phase 1 trial evaluated the initial safety and preliminary evidence of clinical activity of adding indoximod to standard 7+3 induction and high-dose cytarabine (HiDAC) consolidation chemotherapy for adult patients with newly diagnosed AML. The presentation highlighted an initial safety profile indicating that the treatment regimen was well tolerated with adverse events commensurate with chemotherapy alone. Evidence of clinical activity was observed for indoximod plus chemotherapy in newly diagnosed AML as supported by these Phase 1 data showing post-induction minimal residual disease (MRD) negativity rate of 86% and post-HiDAC1 MRD negativity of 100%.

“These data demonstrate the promising potential for indoximod in combination therapy for patients with newly diagnosed AML and the use of MRD status as a study endpoint,” said Dr.�Ashkan Emadi. “We remain encouraged and look forward to additional data as this study proceeds.”

Fifty-seven patients were screened, and 38 patients initiated induction therapy on protocol. Five patients never received indoximod resulting in an intent-to-treat (ITT) population of 33 patients. Twenty-two patients received the pre-specified 80% of indoximod dosing required to be included in the per protocol (PP) analysis, 8 received less than 80% of the scheduled indoximod dosage, and 3 patients remained on induction treatment as of the date of data cut off. Of these 22 PP patients, 16/22 (73%) achieved complete morphological response (CR) and 6 were primary refractory. Of the patients who achieved CR, 14 had results available from MRD testing post-induction. MRD negativity was defined by a flow cytometry assay at a level of < 0.02% (Hematologics, Inc., Seattle, WA). Of those tested, 12/14 (86%) were MRD-negative. Of the 14 patients, 1 patient proceeded to transplant, and 13 began HiDAC consolidation therapy. Post-HiDAC consolidation, all 13 patients were tested for MRD status with all 13/13 (100%) reported to be MRD-negative. When benchmarked against available published studies, these initial data appear encouraging. For a more precise comparison, a contemporaneous multi-institutional dataset is being aggregated to benchmark these data against data generated from patients undergoing the same chemotherapy regimen without the addition of indoximod using the same MRD assay assessed at the same reference laboratory.

Safety data from this Phase 1 trial indicate that the combination therapy regimen was well tolerated. No RLTs were observed when combining indoximod with standard-of-care chemotherapy. Grade 3 or greater adverse hematologic events included febrile neutropenia, anemia, and thrombocytopenia while non-hematologic events included hypoxia, anemia, and pneumonia. The overall adverse event profile observed in this small sample size is consistent with that of 7+3 induction chemotherapy plus HiDAC consolidation alone.

https://www.streetinsider.com/Press+Releases/NewLink+Genetics+Presents+Encouraging+Updated+Phase+1+Data+with+Indoximod+Plus+Chemotherapy+in+Frontline+AML+in+an+Oral+Session+at+2018+ASH+Annual+Meeting/14881652.html

Goldman Sachs Upgrades Abbott Labs (ABT) to Buy

Goldman Sachs analyst Issac Ro upgraded Abbott Labs (NYSE: ABT) from Neutral to Buy with a price target of $81.00 (from $78.00).

The analyst favors the company growth among peers, likes the disconnect between an underappreciated consensus expectation and his believes the company will accrue a favorable mix shift, the potential upside in the valuation, more favorable outlook for EPD/Nutritionals than consensus expects and share gains in Diagnostics following recent checks.

https://www.streetinsider.com/Analyst+Comments/Goldman+Sachs+Upgrades+Abbott+Labs+%28ABT%29+to+Buy/14877762.html

BeiGene announces results of Zanubrutinib in Mantle Cell Lymphoma

BeiGene announced the presentation of clinical data from two ongoing trials of its investigational Bruton’s tyrosine kinase inhibitor, zanubrutinib, in patients with mantle cell lymphoma. The presentations were made at the 60th Annual Meeting of the American Society of Hematology. Results from the pivotal Phase 2 trial of zanubrutinib in Chinese patients with relapsed or refractory MCL were featured in an oral presentation, while updated results from the global Phase 1 trial of zanubrutinib in patients with multiple subtypes of B-cell malignancies, including treatment naive and R/R MCL, were featured in a poster presentation. Zanubrutinib is being studied in several clinical trials as part of a broad development program and was granted Fast Track Designation by the U.S. Food and Drug Administration for the treatment of patients with Waldenstrom macroglobulinemia. BeiGene plans to submit an initial NDA to the FDA for zanubrutinib in 2019 or early 2020. The NDAs in China for R/R MCL and R/R chronic lymphocytic leukemia/small lymphocytic lymphoma have been accepted by the National Medical Products Administration and the MCL filing has been granted priority review. The single arm, open-label, multi-center, pivotal Phase 2 trial of zanubrutinib as a monotherapy in Chinese patients with R/R MCL enrolled 86 patients who had received a median of two prior lines of therapy. Patients were treated with zanubrutinib, dosed at 160 mg orally twice-daily. The primary endpoint of the trial was overall response rate assessed by independent review committee using PET-based imaging according to the Lugano Classification 2014. As of March 27, 2018, 85 patients with R/R MCL were evaluable for efficacy and 65 patients remained on study treatment. The median follow-up time for patients enrolled in the trial was 35.9 weeks. Results included: The ORR by IRC was 83.5%; the complete response rate was 58.8% and the partial response rate was 24.7%; The 24-week progression-free survival was estimated at 82%. The median PFS had not yet been reached; With 24.1 weeks median follow-up, the median duration of response had not yet been reached and 90% of responders were still in response at 24 weeks; Zanubrutinib tolerability was generally consistent with previous reports in patients with various B-cell malignancies and the majority of adverse events were grade 1 or 2 in severity. The most frequent AEs of any attribution were neutrophil count decreased, rash, upper respiratory tract infection, and platelet count decreased; The most frequently reported grade 3 or higher AEs were neutrophil count decreased and lung infection; Four patients had treatment emergent adverse events leading to death; and among events of special interest for BTK inhibitors, diarrhea was observed in nine patients, all grade 1-2. Major hemorrhage was observed in 1 patient with blastoid variant of MCL who had intra-parenchymal CNS bleeding. No cases of atrial fibrillation/flutter were reported in this trial. Meanwhile, the open-label Phase 1 trial of zanubrutinib as a monotherapy in patients with different subtypes of B-cell malignancies, including MCL, is being conducted in Australia, New Zealand, the U.S, Italy, and South Korea. As of July 24, 2018, 48 patients with TN or R/R MCL have been enrolled in the trial and the median follow-up time was 12.7 months. 45 patients including six with TN and 39 with R/R MCL, were evaluable for efficacy in this analysis, per the Lugano 2014 classification. At the time of the data cutoff, 26 patients remained on study treatment. Updated results included: The ORR by investigator was 88.9%; the CR rate was 26.7% and the PR rate was 62.2%. The majority of patients were assessed via CT-scan; PET scans were optional per trial protocol; The median DOR was 16.2 months and the median PFS for R/R patients was 18.0 months; Zanubrutinib tolerability was generally consistent with previous reports in patients with various B-cell malignancies and the majority of AEs were grade 1 or 2 in severity. Grade 3-5 AEs occurred in 56.3% of patients. Grade 3-5 AEs of any attribution reported in greater than three patients included anemia, major hemorrhage, cellulitis, myalgia, neutropenia, pneumonia; and thrombocytopenia; Discontinuation due to AEs occurred in 18.8% of patients with all but one event determined to be unrelated to study drug; and there were four deaths due to AEs, which were all determined by the investigators to be unrelated to zanubrutinib treatment.
https://thefly.com/landingPageNews.php?id=2830795

Regeneron presents positive data at for REGN1979 CD20xCD3 bispecific antibody

Regeneron Pharmaceuticals presented new data for REGN1979 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including promising clinical results in follicular lymphoma and diffuse large B-cell lymphoma which are the two most common types of NHL. In this Phase 1 proof-of-concept trial, REGN1979 demonstrated an acceptable safety and tolerability profile with no observed dose-limiting toxicities. There were no clinically-significant neurotoxicities, including no occurence of seizures or encephalopathy. REGN1979 is a wholly-owned, investigational, full-length bispecific monoclonal antibody designed to trigger tumor killing by binding CD3 on immune system T-cells and CD20 on B-cell malignancies. In the data presented at the 2018 American Society of Hematology Annual Meeting, heavily pre-treated patients with R/R FL grades 1 to 3a who received REGN1979 doses of 5 mg to 40 mg, experienced a 100% overall response rate; 90% of responders maintained a response during treatment. Based on these data, Regeneron plans to initiate in 2019 a potentially registrational Phase 2 trial investigating REGN1979 in R/R FL. REGN1979 also showed encouraging dose-dependent clinical activity in heavily pre-treated patients with R/R DLBCL. Among patients receiving doses between 5 mg and 12 mg, the ORR was 18%. At doses of 18 mg to 40 mg, the ORR increased to 60%. Regeneron plans to continue dose-escalation in DLBCL. The objectives for this ongoing Phase 1 proof-of-concept trial are to assess safety, tolerability and efficacy of REGN1979 monotherapy. The data presented at ASH included a total of 68 patients with R/R B-NHL who were treated with REGN1979. These patients had received a median of three prior therapies, including an anti-CD20 therapy. As of September 2018, 14 patients had completed treatment, 13 patients remained on treatment and 41 had discontinued treatment. The most common reason for treatment discontinuation was progressive disease. Two patients discontinued treatment due to a treatment-emergent adverse event. In the trial, the most common TEAEs occurring in at least 25% of patients were pyrexia, chills, cytokine release syndrome, fatigue, increased C-reactive protein, anemia, hypotension, infusion-related reaction and nausea. IRR and CRS events were generally mild to moderate in severity, and neither resulted in trial discontinuations. Three patients in the trial died due to adverse events. Of these, one death, in a patient with a tumor involving the gastric lining who experienced a gastric perforation, was attributed to REGN1979.
https://thefly.com/landingPageNews.php?id=2830789