On December 11, 2017 Aileron Therapeutics, the clinical-stage leader in the field of stapled peptides developing therapeutics for cancers and other diseases, reported two oral presentations of preclinical data from collaborators on ALRN-6924 in T-cell lymphomas (TCL) and acute myeloid leukemia (AML) (Press release, Aileron Therapeutics, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322188 [SID1234522542]). ALRN-6924, a stapled peptide therapeutic, is believed to be the first product candidate undergoing clinical evaluations that has been shown to disrupt both MDMX- and MDM2-mediated inhibition of the wild type p53 tumor suppressor gene. The data were reviewed in separate oral presentations by researchers from the Dana-Farber Cancer Institute and the Albert Einstein College of Medicine during the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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"We are encouraged by these positive preclinical data from our collaborators, which demonstrate that dual inhibition by ALRN-6924 induces strong p53 activity that leads to anti-cancer effects," said Dr. Manuel C. Aivado, Chief Medical Officer. "These data support the clinical results we saw in our Phase 1 all-comers trial, and we look forward to continuing to evaluate ALRN-6924 in our ongoing PTCL and AML clinical trials."

TCL Study Highlights (Abstract #571)

In an in vitro and in vivo preclinical study, MDMX and MDM2 were evaluated as potential targets for treating wild type p53 T-cell lymphomas by using ALRN-6924 to inhibit their expression. The data showed that ALRN-6924 induced apoptotic cell death in TCL lines, and significantly reduced tumor burden compared to the vehicle in animal models. Furthermore, ALRN-6924 had a favorable safety profile and demonstrated superior efficacy across multiple TCL subtypes compared to the current standard-of-care.

Commented David Weinstock, M.D. of Dana-Farber Cancer Institute, "Given the need for new treatment approaches for T-cell lymphomas, we evaluated ALRN-6924 in animal models and found that the compound’s dual inhibition mechanism for restoring the function of p53 showed promising activity across multiple TCL subtypes, including PTCL. Animal models in our studies displayed key markers that demonstrated consistency with on-target p53 activation and apoptosis, supporting further clinical development of ALRN-6924 for PTCL." i

AML Study Highlights (Abstract #795)

The preclinical data presented showed that dual inhibition of MDMX and MDM2 by ALRN-6924 led to activation of p53-dependent pathways in AML cells. The disruption of MDMX/p53 and MDM2/p53 interactions resulted in strong anti-leukemic effects, and induced cell cycle arrest and apoptosis in cell lines and wild type p53 AML patients’ cells. The compound exhibited strong on-target activity in AML cell lines and primary cells in vitro, as well as in a patient who received ALRN-6924. The data further demonstrated that ALRN-6924 showed superiority over MDM2-only inhibition, and led to improved survival in in vivo AML models.

"These results support our understanding that in most patients with acute myeloid leukemia, a devastating disease with limited therapeutic options, p53 is circumvented by activation of its natural suppressor proteins, MDMX and MDM2," said Ulrich Steidl, Ph.D., M.D. of the Albert Einstein College of Medicine. "The ability to reactivate the p53 pathway by inhibiting both MDMX and MDM2 using a novel therapeutic modality such as stapled peptides is an exciting new chapter in p53 research. The studies presented today strengthen the rationale for the use of ALRN-6924 in acute myeloid leukemia and other wild type p53 cancers." ii

About ALRN-6924
ALRN-6924 is a first-in-class product candidate designed to reactivate wild type p53 tumor suppression by disrupting the interactions between the two primary p53 suppressor proteins, MDMX and MDM2. Aileron believes ALRN-6924 is the first and only product candidate in clinical development that can equipotently bind to and disrupt the interaction of MDMX and MDM2 with p53. Based on preclinical data and preliminary evidence of safety and anti-tumor activity in its ongoing clinical trials, there may be a significant opportunity to develop ALRN-6924 as a monotherapy or combination therapy for a wide variety of solid and liquid tumors. ALRN-6924 is currently being evaluated in multiple clinical trials for the treatment of acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS) and peripheral T-cell lymphoma (PTCL). For information about its clinical trials, please visit www.clinicaltrials.gov.

On December 11, 2017 Spark Therapeutics (NASDAQ:ONCE), a fully integrated gene therapy company dedicated to challenging the inevitability of genetic disease, and Pfizer Inc. (NYSE:PFE), reported that, with a cumulative follow-up of more than 13 patient years of observation, all 11 participants in the ongoing Phase 1/2 clinical trial of investigational SPK-9001 for the treatment of patients with hemophilia B had discontinued routine infusions of factor IX concentrates and shown sustained steady-state factor IX activity levels with no serious adverse events, thrombotic events or factor IX inhibitors observed (Press release, Pfizer, DEC 11, 2017, View Source [SID1234522561]). Based on individual participant history for the year prior to the study, the overall annualized bleeding rate (ABR) was reduced by 97 percent (calculated based on data after week four; 95 percent based on data after infusion) to a mean of 0.3 (0.5) annual bleeds, compared to a mean of 10.5 bleeds annually before SPK-9001 administration. Overall annualized infusion rate (AIR) was reduced 99 percent (calculated based on data after week four; 97 percent based on data after infusion) to a mean of 0.8 (1.7) annual infusions, compared to a mean of 62.5 infusions per year before SPK-9001 administration. Data on all 11 participants were presented today by Lindsey A. George, M.D., attending physician in the Division of Hematology at Children’s Hospital of Philadelphia and principal investigator of the trial, at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta.

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"We believe these longer-term data are meeting critical goals of our hemophilia programs," said Katherine A. High, M.D., president and head of research and development at Spark Therapeutics. "Now, with four participants followed for more than 18 months, we continue to see consistent levels of factor IX activity, no serious adverse events, as well as a sustained reduction in both the symptoms of hemophilia and the prophylactic and disease management protocols that were used prior to infusion with SPK-9001."

As of the Nov. 29, 2017 data cutoff, the mean steady-state factor IX activity level at 12 weeks post-administration for the 11 participants was 36 percent of normal (range as of the data cutoff: 15 to 78 percent). As of the data cutoff, the last participant to be infused, who received SPK-9001 manufactured using an enhanced process, was out eight months following SPK-9001 infusion, with a mean factor IX activity level of 60 percent. Spark Therapeutics will enroll up to four additional participants in the current Phase 1/2 clinical trial who will receive SPK-9001 manufactured using an enhanced process to test its comparability to the SPK-9001 received by the first 10 participants enrolled in the ongoing trial.

In this open-label, non-randomized and multicenter Phase 1/2 clinical trial, there were no serious adverse events during or following infusion with SPK-9001, and no participants experienced thrombotic events or developed factor IX inhibitors. Two participants developed an asymptomatic and transient increase in liver enzymes that resolved with a tapering dose of oral corticosteroids. One participant with severe joint disease administered factor for suspected joint bleeding, while a second participant recorded one spontaneous bleed.

About Hemophilia B
Hemophilia, a rare genetic bleeding disorder that causes the blood to take a long time to clot because of a deficiency in one of several blood clotting factors, is almost exclusively found in males. People with hemophilia are at risk for excessive and recurrent bleeding from modest injuries, which have the potential to be life threatening. People with severe hemophilia often bleed spontaneously into their muscles or joints, or rarely into other critical closed spaces such as the intracranial space, where bleeding can be fatal. The incidence of hemophilia B is one in 25,000 male births. People with hemophilia B have a deficiency in clotting factor IX, a specific protein in the blood. Hemophilia B also is called congenital factor IX deficiency or Christmas disease. The current standard of care requires recurrent intravenous infusions of either plasma-derived or recombinant factor IX to control and prevent bleeding episodes. There exists a significant need for novel therapeutics to treat people living with hemophilia.

About the SPK-FIX Program and SPK-9001
SPK-9001 is a novel investigational vector that contains a bio-engineered adeno-associated virus (AAV) capsid and a codon-optimized, high-activity human factor IX gene enabling endogenous production of factor IX.

Spark Therapeutics and Pfizer entered into a collaboration in December 2014 for the SPK-FIX program, including SPK-9001, under which Spark Therapeutics is responsible for conducting all Phase 1/2 studies for any product candidates, while Pfizer will assume responsibility for pivotal studies, any regulatory activities and potential global commercialization of any products that may result from the collaboration.

On December 11, 2017 GlaxoSmithKline plc (LSE/NYSE: GSK) reported promising new data from the dose expansion phase of the DREAMM-1 study of GSK2857916, an investigational anti-B-cell maturation antigen (BCMA) antibody-drug conjugate (Press release, GlaxoSmithKline, DEC 11, 2017, View Source [SID1234522570]). In this study of heavily pre-treated multiple myeloma patients (n=35), GSK2857916 monotherapy demonstrated a 60% response rate (95% confidence interval [CI]: 42.1% – 76.1%) and a median progression free survival of 7.9 months (95% CI: 3.1 – not estimable). Results were presented during an oral presentation at the 59th annual meeting of the American Society for Hematology (ASH) (Free ASH Whitepaper).

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Patients were enrolled in DREAMM-1 independent of BCMA expression levels. The study participants were heavily pre-treated, with 57% of the patients having at least five prior lines of treatment and 40% having prior daratumumab treatment. The most commonly reported adverse events were corneal events (63%) and thrombocytopenia (57%); no dose-limiting toxicities were reported. Infusion-related reactions (IRRs) occurred in 23% of patients (without pre-medication) on the first infusion and no IRRs occurred on subsequent infusions.

Axel Hoos, SVP Oncology R&D, GSK said "The patients participating in the DREAMM-1 trial had very limited options for further treatment, so we are encouraged by the response rate seen in this trial. GSK2857916 is the leading asset in our emerging pipeline of potentially transformative Oncology medicines and we plan to rapidly progress its development programme, initiating pivotal monotherapy studies as well as new combination studies in 2018."

Multiple myeloma is the second most common blood cancer in the United Statesi and is generally considered treatable but not curable. Multiple myeloma commonly becomes refractory to available treatments, so research into new treatments is vital. GSK2857916 was recently awarded Breakthrough Therapy designation from the US Food and Drug Administration and PRIME designation from the European Medicines Agency; these designations are intended to facilitate development of investigational medicines that have shown clinical promise for conditions where there is significant unmet need.

The DREAMM -1 study is a first-in-human, open-label study of GSK2857916 in patients with relapsed/ refractory multiple myeloma. The primary objective is safety; response rate, pharmacokinetics and immunogenicity are secondary endpoints. The study consists of two parts: a dose escalation phase in which patients received GSK2857916 at escalating doses and a dose expansion phase in which all patients received GSK2857916 at the recommended phase II dose. Results from the dose escalation phase of the study were presented at ASH (Free ASH Whitepaper) 2016ii

GSK in Oncology
GSK is focused on delivering transformational therapies for cancer patients. GSK’s pipeline is focused on immuno-oncology, cell therapy, and epigenetics. Our goal is to achieve a sustainable flow of new treatments for cancer patients based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, multi-specific molecules, adjuvants and cells, either alone or in combination.

The data presented at ASH (Free ASH Whitepaper) show important R&D progress in GSK’s Oncology pipeline. The company has also strengthened its commercial and R&D interface within Oncology through the recent appointment of Christine Roth as Oncology Franchise Head, who will be responsible for shaping the commercial and global product strategy for GSK’s innovative pipeline of Oncology assets.

In 2015 GSK divested its Oncology business for an aggregate cash consideration of $16 billion, while retaining its portfolio of early stage Oncology assets. Novartis has a right of first negotiation (ROFN) that is triggered upon a decision to seek a partner or divest certain Oncology assets or if GSK proposes to seek a marketing authorisation for such Oncology assets, on an asset by asset basis. The ROFN does not oblige GSK to sell to, or partner with, Novartis. Novartis does not have an "opt-in" or a "call" option related to GSK’s Oncology pipeline. Under the ROFN, GSK is able to continue to develop and commercialise assets on its own. GSK’s obligation is to negotiate in good faith. GSK would only enter into a transaction if GSK believes it was in the best interest of its shareholders. The ROFN extends for 12.5 years from closing; i.e. September 2027.The complete contractual terms of the ROFN are available at View Source

Conference call for investors and analysts
GSK will host a conference call for investors and analysts at 18:00 GMT/ 1:00PM EST on Tuesday, 12 December 2017.

On December 11, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported initial clinical data from its ongoing Phase 2 trial of SY-1425, its first-in-class oral, selective retinoic acid receptor alpha (RARα) agonist, in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (Press release, Syros Pharmaceuticals, DEC 11, 2017, View Source [SID1234522519]). The data are being presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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"I’m encouraged with the single-agent activity and tolerability of SY-1425 in difficult-to-treat leukemia and MDS patients who have few treatment options," said Joseph G. Jurcic, Professor of Medicine at Columbia University Medical Center and Director of the Hematologic Malignancies Section of the Division of Hematology/Oncology. "We saw improved blood counts and reduced blast counts in conjunction with differentiation of cancer cells in genomically defined patients. These data, along with the mechanistic and preclinical data supporting combinations with azacitidine and with daratumumab, suggest SY-1425 could be a meaningful combination agent with the potential to address a substantial unmet need for patients with AML and MDS."

"The biologic and clinical activity seen in patients selected by our proprietary RARA and IRF8 biomarkers provide validation of our platform’s ability to enrich for patients most likely to respond to gene control therapies," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "These data support continued development of SY-1425 in combination,

which will be our focus going forward. Our preclinical data showing the tumor-killing activity of SY-1425 in combination with azacitidine and with daratumumab support the ongoing development of SY-1425 in combination with these therapies, and we plan to present initial clinical data on these two combinations in 2018."

Data from the Ongoing Phase 2 Clinical Trial

The ongoing Phase 2 clinical trial of SY-1425 is assessing the safety and efficacy as both a single agent and a combination agent in AML and MDS patients who are positive for either the RARA or IRF8 biomarkers, or both. The data being presented at ASH (Free ASH Whitepaper) are from two of the five cohorts in the ongoing trial. As of the data cutoff at the end of October 2017, 58 patients had been treated with SY-1425 in two single-agent cohorts, consisting of 29 patients in the relapsed or refractory AML and higher-risk MDS cohort and 29 patients in the lower-risk transfusion-dependent MDS cohort.

The relapsed or refractory AML and higher-risk MDS cohort had a median age of 72 years with more than half the patients having poor risk cytogenetics and 45% having two or more prior therapies, and the lower-risk MDS cohort had a median age of 76 years. Target enrollment has been reached in both cohorts.

Initial Safety Data

· Chronic daily dosing of SY-1425 administered at 6 mg/m2 orally divided in two doses was generally well-tolerated, with a median treatment duration of 80 days, and patients treated up to eight months and remaining on study.
· The majority of adverse events (AEs) were Grade 1 or Grade 2.
· Across all grades and causality, the most commonly reported AEs included hypertriglyceridemia (36%), fatigue (31%), and dermatologic effects (28%).
· The most common Grade 3 or 4 AE was hypertriglyceridemia (16%).

Initial Clinical Activity Data

As of the data cutoff, 48 patients were evaluable for response assessment, including 23 patients in the relapsed or refractory AML and higher-risk MDS cohort and 25 patients in the lower-risk transfusion-dependent MDS cohort.

· Ten of the 23 (43%) evaluable relapsed or refractory AML and higher-risk MDS patients and two of the 25 (8%) evaluable transfusion-dependent lower-risk MDS patients had evidence of clinical activity, including:.

· Nine with improvements in hematological parameters. Of those, four achieved hematological improvement lasting at least eight weeks, as defined by Revised International Working Group (IWG) criteria.
· Five with reductions in bone marrow blasts. Of those, one relapsed or refractory higher-risk MDS patient achieved a marrow complete response as defined by IWG criteria. The patient had been on treatment 238 days and remained on treatment as of the data cutoff.

· 13 of the 23 (57%) evaluable relapsed or refractory AML and higher-risk MDS patients had stable disease.
· 11 of 13 (85%) of patients with pre- and post-treatment immunophenotyping samples showed increased expression of CD38, a marker of cell differentiation, on bone marrow blasts after one 28-day cycle of treatment.
· No patients with lower-risk MDS achieved transfusion independence.

Additionally, myeloid cell differentiation in the bone marrow, as measured by morphologic evaluation, FISH analysis and immunophenotyping, was observed, consistent with the underlying mechanism of action of SY-1425 as a differentiating agent. The induction of CD38 observed in bone marrow blasts from patients treated with SY-1425 supports the combination cohort with daratumumab recently added to the Phase 2 trial.

As presented at the European School of Haematology’s 4th International Conference on Acute Myeloid Leukemia in October 2017, approximately 40% of 201 patients screened for the clinical trial as of the end of August 2017 were biomarker-positive, including approximately one-third of relapsed or refractory AML and higher-risk MDS patients. In blood samples taken from patients upon screening and treated ex vivo with SY-1425, a positive biomarker status was significantly correlated with SY-1425 induced myeloid cell differentiation, supporting the predictive value of the biomarker test for patient selection.

Preclinical Combination Data for SY-1425

SY-1425 has shown synergistic tumor-killing activity in combination with azacitidine, a standard-of-care therapy in AML and MDS, as well as with daratumumab, an anti-CD38 antibody approved to treat multiple myeloma, in preclinical models of RARA biomarker-positive AML. In combination with azacitidine, SY-1425 demonstrated greater clearance of tumor cells in bone marrow and other tissues and greater depth and duration of tumor response, compared to either azacitidine or SY-1425 alone. In combination with daratumumab, SY-1425 triggered robust immune cell-mediated tumor death. Notably, AML cells do not normally express high levels of CD38. Syros has shown that by inducing CD38 expression, SY-1425 sensitizes biomarker-positive AML models to the tumor-killing effects of daratumumab.

Clinical Development Plans for SY-1425

Syros plans to focus its ongoing Phase 2 clinical trial on assessing the safety and efficacy of SY-1425 in combination with other therapies. Syros is continuing to enroll patients in a cohort evaluating SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy. Syros recently added a cohort in relapsed or refractory AML and higher-risk MDS patients to evaluate SY-1425 in combination with daratumumab and expects to begin enrolling patients in that cohort in early 2018. All patients enrolled or to be enrolled in the trial are prospectively selected using the Company’s RARA or IRF8 biomarkers. Syros expects to report initial clinical data from each combination cohort in 2018. Syros does not plan to pursue further development of SY-1425 as a single agent and is stopping enrollment in the single-agent cohort in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.

Additional details about the trial can be found using the identifier NCT02807558 at www.clinicaltrials.gov.

Investor Event and Webcast Information

Syros will host an investor event on Monday, December 11 beginning at 12:00 p.m. ET in Atlanta to discuss the initial SY-1425 clinical data presented at ASH (Free ASH Whitepaper). The event can be accessed by dialing 866-595-4538 (domestic) or 636-812-6496 (international) and providing the passcode 8887999. A live webcast will also be available and can be accessed under "Events & Presentations" in the Investors section of the Company’s website at View Source A replay of the webcast will be available approximately two hours after the event and will be available for 30 days following the event.

On December 11, 2017 Oscotec reported that shares of Oscotec rebounded on the company’s announcement that it has launched a clinical trial in the U.S. on SKI-G-801, a treatment for acute myeloid leukemia (AML) (Press release, Oscotec, DEC 11, 2017, View Source [SID1234573544]).

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The biotech company said in a public regulatory filing on Monday that its phase-1 clinical trial on SKI-G-801 will begin at six U.S. hospitals.

Oscotec’s shares, which had slid since Dec. 4, rebounded to 10,250 won ($9.4) as of noon on Monday, up 150 won from the previous trading day. Compared with early this year’s stock price of 7,390 won per share, it was up 38 percent.

SKI-G-801 is a treatment that selectively inhibits fms-like tyrosine receptor kinase 3 (FLT3). The company hopes that the new drug candidate will lower side effects and recurrence rate, compared to existing chemotherapies.

The U.S. study will check safety and drug tolerance, after administering SKI-G-801 to recurring or non-reacting AML patients and raising doses in a phased way. The trial will also test the drug’s appropriate doses and efficacy in AML patients with FLT3 mutations.

"Compared to the existing FLT3 inhibitors, SKI-G-801 has excellent pharmacologic activation and long-acting efficacy. Besides, we confirmed its efficacy on FLT3 mutations, which existing inhibitors had no effectiveness, as well as in the drug-resistant environment," Oscotec said.

It went on to say,"If we confirm the safety, drug tolerance, and oncolytic efficacy in the clinical trial, we expect that we will be able to transfer our technology to a multinational pharmaceutical company."

In July 2015, Oscotec transferred its investigational non-small cell lung cancer therapy YH25448 to Yuhan Corp. under an income-sharing contract.

Oscotec’s revenue reached 3.25 billion won ($2.99 million) in the first three quarters this year, with an operating loss of 992 million won.

Its flagship product is InduCera, a material for bone transplant, which takes up about 30 percent of the total sales.