On July 22, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that its investigational BTK inhibitor zanubrutinib has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with Waldenström macroglobulinemia (WM) (Press release, BeiGene, JUL 22, 2018, View Source;p=RssLanding&cat=news&id=2359338 [SID1234527801]). Based on BeiGene’s discussions with the FDA, internal review of available data from its global Phase 1 trial of zanubrutinib in patients with WM, and supported by the Fast Track Designation, BeiGene is preparing to submit in the first half of 2019 a New Drug Application (NDA) to pursue an accelerated approval of zanubrutinib for patients with WM based on results from the global Phase 1 study. A final determination to submit the NDA will be made subsequent to the pre-NDA meeting with FDA after obtaining mature data from the study this fall.

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"We believe zanubrutinib is a differentiated BTK inhibitor based on the depth and durability of responses observed in our ongoing global Phase 1 trial of zanubrutinib in WM patients. We look forward to working closely with the FDA in the continuing development of zanubrutinib for the treatment of this disease," commented John Oyler, co-founder, CEO and Chairman of BeiGene. "We are hopeful that zanubrutinib, if approved, may represent a valuable and important treatment option for patients with WM."

The FDA’s Fast Track program is intended to expedite or facilitate the process for reviewing new drugs that are intended to treat a serious or life-threatening disease or condition for which there is no effective treatment and demonstrate the potential to address unmet medical needs for the condition. A drug candidate with a Fast Track Designation may be eligible for more frequent communications with the FDA, for Accelerated Approval and Priority Review (if relevant criteria are met), and rolling review of the NDA.

In addition to the global Phase 1 trial of zanubrutinib, which enrolled 76 WM patients to date, zanubrutinib is also being tested in a global Phase 3 clinical trial in patients with WM comparing zanubrutinib to ibrutinib, a currently approved BTK inhibitor. BeiGene announced today that this global Phase 3 study has completed patient enrollment. In addition, zanubrutinib is being tested in a global Phase 3 clinical trial as a first-line treatment for patients with chronic lymphocytic leukemia (CLL) and a Phase 2 clinical trial in patients with relapsed or refractory follicular lymphoma in combination with GAZYVA (obinutuzumab). In China, BeiGene has completed enrollment in three pivotal Phase 2 clinical trials of zanubrutinib in patients with mantle cell lymphoma (MCL), CLL and WM, and expects to file an NDA in China for MCL this year. BeiGene is also planning a Phase 3 trial for a head-to-head comparison of zanubrutinib versus ibrutinib in patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL). As of May 7, 2018, more than 1,200 patients have been enrolled in the zanubrutinib development program.

About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) that is currently being evaluated in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various B cell malignancies.

On July 20, 2018 PureTech Health plc (LSE: PRTC) ("PureTech Health"), a clinical-stage biopharmaceutical company developing novel medicines focused on the Brain-Immune-Gut (BIG) Axis, reported that it has entered into a multiyear collaboration with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc., to advance PureTech’s milk-derived exosome platform technology for the oral administration of Roche’s antisense oligonucleotide platform (Press release, PureTech Health, JUL 20, 2018, View Source [SID1234536199]). Under the terms of the agreement, PureTech Health will receive up to $36 million, including upfront payments, research support, and early preclinical milestones. PureTech Health will be eligible to potentially receive development milestone payments of over $1 billion and additional sales milestones and royalties for an undisclosed number of products.

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PureTech’s milk exosome-based technology is uniquely designed to facilitate the oral administration of complex payloads such as nucleic acids, peptides, and small molecules. These exosomes are believed to traffic via lymphatic circulation and could potentially enable the targeting of immune cells in novel ways.

Daphne Zohar, Co-founder and Chief Executive Officer of PureTech Health, said: "We are excited to accelerate the development of this promising technology from our internal lymphatic and immune cell trafficking programmes. The expertise and resources that Roche is bringing to the collaboration will help us to potentially address one of the biggest challenges in oligonucleotide-based therapeutic development: oral administration of nucleic acids."

PureTech Health has been advancing internal research and development projects that focus on the Brain-Immune-Gut (BIG) Axis, with an emphasis on lymphatics and immune cell trafficking to modulate immunity in a tissue-specific manner. These internal pipeline programmes are being consolidated into a separate division of PureTech Health called Ariya. PureTech’s Internal division, which includes the milk-derived exosome technology, has generated compelling pre-clinical data and secured key intellectual property for its lymphatic and immune cell trafficking programmes.

About PureTech’s Milk Exosomes Technology

Milk exosomes represent a significant opportunity to potentially resolve the long-standing challenge of oral bioavailability of macromolecules and complex small molecules. Exosomes, which contain mixtures of lipids, proteins and nucleic acids, play a critical physiologic role in intercellular communication and the transport of macromolecules between cells and tissues. Mammalian-derived exosomes have attractive potential as vehicles for the administration of a variety of drug payloads, especially nucleic acids, since their natural composition will likely provide superior tolerability over the variety of synthetic polymers currently in use. Most sources of mammalian exosomes are not suitable or viable as vehicles for oral administration of drugs due to their lack of stability under the harsh physiologic conditions associated with transit through the stomach and small intestine; however, the milk-derived exosomes that form the basis for PureTech’s internally-developed technology have evolved naturally and specifically to accomplish the task of oral transport of complex biological molecules. The technology is based on research conducted by PureTech Health and its academic collaborators, including Ramesh Gupta, PhD, Agnes Brown Duggan Chair in Oncological Research at the James Graham Brown Cancer Center, and Professor in the Department of Pharmacology and Toxicology at University of Louisville, and exclusively licensed to PureTech Health.

On July 20, 2018 TESARO, Inc. (NASDAQ:TSRO) reported that it will announce second-quarter 2018 financial results on Thursday, August 2, 2018, after the close of the U.S. financial markets (Press release, TESARO, JUL 20, 2018, View Source [SID1234527800]). TESARO’s senior management team will host a conference call and live audio webcast at 4:15 p.m. ET on August 2, 2018 to discuss the Company’s operating results for the quarter in greater detail, as well as the status of its development programs.

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This quarterly earnings call will be available via phone and webcast. The conference call dial-in information is listed below. To access the webcast, please log on to the TESARO website at www.tesarobio.com at least 15 minutes prior to the start of the call to ensure adequate time for any software downloads that may be required.

On July 20, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that TIBSOVO (ivosidenib) was granted approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (R/R AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA approved test (Press release, Agios Pharmaceuticals, JUL 20, 2018, View Source [SID1234527799]). TIBSOVO, an oral, targeted inhibitor of the IDH1 enzyme, is the first and only FDA-approved therapy for patients with R/R AML and an IDH1 mutation1.

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"The FDA approval of TIBSOVO – our first wholly owned drug and the second approved medicine from our research platform in less than a year – is an incredibly exciting milestone for our company and, importantly, for the approximately 6-10% of AML patients with an IDH1 mutation who have been waiting for new treatment options that work radically different than conventional chemotherapy," said David Schenkein, M.D., chief executive officer at Agios. "I want to thank the patients and their caregivers, nurses and physicians who participated in our clinical trials. With their support and the dedication of Agios’ employees, we are well on our way to becoming a sustainable multi-product biopharmaceutical company delivering medicines that have the potential to change how serious diseases are treated."

AML is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases estimated in the U.S. each year.3,4 The majority of patients with AML eventually relapse. Relapsed or refractory AML has a poor prognosis.5 The five-year survival rate is approximately 27%.3 For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia.2

"AML patients who relapse or are refractory to available therapies have few, if any, treatment options," said Hagop M. Kantarjian, M.D., professor and chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center. "The clinical study demonstrated that TIBSOVO has the potential to deliver strong, durable responses as a single agent and can help patients achieve and maintain transfusion independence. IDH inhibitors represent a new class of noncytotoxic, targeted therapies for AML patients with IDH mutations."

TIBSOVO Safety and Efficacy Data1

The FDA approval was based on the clinical data from an open-label, single-arm, multicenter dose-escalation and expansion trial of adult patients with R/R AML and an IDH1 mutation (Study AG120-C-001, NCT02074839). TIBSOVO was approved concurrently with the Abbott RealTime IDH1 companion diagnostic test for selection of patients with R/R AML for treatment with TIBSOVO.

The efficacy of TIBSOVO was evaluated in 174 adult patients with R/R AML with an IDH1 mutation identified or confirmed by the Abbott RealTime IDH1 assay. TIBSOVO was given orally at a starting dose of 500 mg daily until disease progression, development of unacceptable toxicity, or undergoing hematopoietic stem cell transplantation. Patients had a median age of 67 years (range of 18 to 87) and received a median of two prior anticancer therapies (ranging from one to six). More than half (63%) were refractory to previous therapy and 33% had secondary AML. The primary endpoint is the combined complete remission (CR) and complete remission with partial hematologic improvement (CRh) rate. CRh is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).

In this trial, TIBSOVO demonstrated:

CR+CRh rate of 32.8% (57 of 174 patients) (95% CI: 25.8, 40.3).
The CR rate was 24.7% (43 of 174 patients) (95% CI 18.5, 31.8) and the CRh rate was 8% (14 of 174 patients) (95% CI 4.5, 13.1).
Median duration of CR+CRh was 8.2 months (95% CI: range 5.6, 12 months).
For patients who achieved a CR or CRh, the median time to best response of CR or CRh was 2.0 months (range, 0.9 to 5.6 months).
Among the 110 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 41 (37.3%) became independent of RBC and platelet transfusions during any 56-day post-baseline period.
Of the 64 patients who were independent of both RBC and platelet transfusions at baseline, 38 (59.4%) remained transfusion independent during any 56-day post-baseline period.
Twenty-one of the 174 patients (12%) went on to stem cell transplant following TIBSOVO treatment.
The safety profile of single-agent TIBSOVO was evaluated in 179 patients with R/R AML with an IDH1 mutation treated with a dose of 500 mg daily. The median duration of exposure to TIBSOVO was 3.9 months (range 0.1 to 39.5 months). In the clinical trial, 19% (34/179) of patients treated with TIBSOVO experienced differentiation syndrome, which can be fatal if not treated. QTc interval prolongation and Guillain-Barré Syndrome occurred in patients treated with TIBSOVO. The most common adverse reactions (≥20%) of any grade were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, electrocardiogram QT prolonged, rash, pyrexia, cough and constipation. The most frequent serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%) and electrocardiogram QT prolonged (7%).

About TIBSOVO (ivosidenib)

TIBSOVO (ivosidenib) is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. For more information, visit TIBSOVO.com.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. Of the 34 patients who experienced differentiation syndrome, 27 (79%) recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. One patient developed ventricular fibrillation attributed to TIBSOVO. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré Syndrome: Guillain-Barré syndrome occurred in <1% (2/258) of patients treated with TIBSOVO in the clinical study. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) of any grade were fatigue (39%), leukocytosis (38%), arthralgia (36%), diarrhea (34%), dyspnea (33%), edema (32%), nausea (31%), mucositis (28%), electrocardiogram QT prolonged (26%), rash (26%), pyrexia (23%), cough (22%), and constipation (20%).
The most frequently reported ≥Grade 3 adverse reactions (≥5%) were electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), tumor lysis syndrome (6%), and differentiation syndrome (5%).
Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).
DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.

Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.

Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.

QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION

Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for at least 1 month after the last dose.

Please see full Prescribing Information, including Boxed WARNING.

About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults.4 Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells.4 AML incidence significantly increases with age, and the median age of diagnosis is 68.3 The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML.5 The five-year survival rate for AML is approximately 27 percent.3 IDH1 mutations are present in about 6 to 10 percent of AML cases.2

Conference Call Information
Agios will host a conference call and live webcast with slides today at 1p.m. ET to discuss the FDA approval of TIBSOVO. To participate in the conference call, please dial 1-877-377-7098 (domestic) or 1-631-291-4547 (international) and referring to conference ID 2065849. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

About myAgios Patient Support Services
myAgios Patient Support Services is an expansive program that helps patients with access, reimbursement, and financial assistance for TIBSOVO (ivosidenib). Healthcare providers and pharmacists can enroll patients at myAgios.com/enroll.

On July 20, 2018 SELLAS Life Sciences Group Inc. (Nasdaq:SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to the Company’s lead asset, galinpepimut-S (GPS), for the treatment of multiple myeloma (MM) (Press release, Sellas Life Sciences, JUL 20, 2018, View Source [SID1234527797]). GPS is licensed from Memorial Sloan Kettering Cancer Center and targets the Wilms Tumor 1 (WT1) protein, which is present in an array of tumor types.

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The Company reported final clinical and immunological data from a Phase 2 clinical trial for GPS in the treatment of high-risk multiple myeloma at the 44th Annual European Society for Blood and Marrow Transplantation (EBMT) Meeting on March 19, 2018.

The FDA’s Fast Track program facilitates the development of drugs intended to treat serious conditions that have the potential to address unmet medical needs. A product candidate with Fast Track status is afforded greater access to the FDA for the purpose of expediting the product candidate’s development, review and potential approval. For a product candidate with Fast Track designation, the FDA may consider sections of its Biologics License Application (BLA) for review on a rolling basis before the complete application is submitted if relevant criteria are met.

"The designation of Fast Track for GPS represents important recognition by the FDA of the potential of this novel immunotherapeutic to address the significant unmet need in the treatment of patients with high-risk multiple myeloma in patients with poor-risk cytogenetics at diagnosis who still harbor minimal residual disease (MRD) after autologous stem cell transplant," said Angelos Stergiou, M.D., Sc.D. h.c., President and Chief Executive Officer of SELLAS. "We are fully committed to working closely with the FDA as we continue development of our potential first-in-class novel WT1-targeting cancer vaccine for select high-risk MM patients in the post-autotransplant maintenance setting after standard first-line treatment."

About the Phase 2 GPS multiple myeloma study

The open-label Phase 2 study consisted of 19 patients with multiple myeloma who had high-risk cytogenetics at initial diagnosis and remained at least minimal residual disease (MRD)-positive after a successful autologous stem cell transplant ("ASCT"). GPS was administered to patients in the study who achieved a stable disease or better status (per International Myeloma Working Group criteria) following ASCT. GPS was evaluated as consolidation therapy to potentially stimulate a highly-specific immune response against WT1 in order to prevent or delay myeloma progression. Median progression-free survival (PFS) of 23.6 months was reported in the high-risk disease setting, compared to historically inferior outcomes while on an immunomodulatory drug (IMID) or proteasome inhibitor post-ASCT maintenance. Median overall survival has not been reached to date. GPS stimulated time-dependent and robust CD4+ T cell or CD8+ T cell immune responses (IRs) specific for all four WT1 peptides within GPS, two of which are heteroclitic (mutated, by design). In addition, GPS stimulated similar IRs against the two counterpart native peptides. The IRs were confirmed in up to 91% of patients across HLA allele types, with multivalent IRs emerging in up to 64% of patients. Multifunctional cross-epitope T cell reactivity was observed in 75% of patients to antigenic epitopes against which hosts were not specifically immunized, in a pattern akin to epitope spreading. A link of clinical activity to antigen-specific immune responses was suggested.

About Galinpepimut-S (GPS):
GPS is a heteroclitic multivalent, multi-peptide cancer immunotherapeutic agent composed of four peptides, addressing over 20 epitopes, and derived from the WT1 protein, which has been ranked by the National Cancer Institute as a top priority among cancer antigens for immunotherapy. Importantly, because the WT1 antigen is overexpressed in many malignancies, and is not found in most normal tissues, GPS has the potential to be a broad immunotherapy, effective across a multitude of diverse cancer types and patient populations.