On June 3, 2019 SpringWorks Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for PD-0325901, an investigational, oral, small molecule inhibitor of MEK1 and MEK2, for the treatment of patients ≥ 2 years of age with neurofibromatosis type 1-associated inoperable plexiform neurofibromas that are progressing or causing significant morbidity (Press release, SpringWorks Therapeutics, JUN 3, 2019, View Source [SID1234538850]).

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Neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) is a rare genetic disorder characterized by mutations in the MAPK pathway, leading to the growth of peripheral nerve sheath tumors that cause significant pain, disfigurement and morbidity. NF1-PNs are most often diagnosed in the first two decades of life and are characterized by aggressive tumor growth, which is typically more rapid during childhood.1-3 There are currently no therapies approved for the treatment of NF1-PN.

"The Fast Track designation recognizes that plexiform neurofibromas have a substantial impact on the lives of patients, and that our MEK inhibitor has the potential to address the significant needs faced by this patient community who currently do not have an FDAapproved treatment," said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics. "We look forward to continuing to work closely with the FDA on our upcoming Phase 2b study, which will enroll pediatric and adult NF1 patients with plexiform neurofibromas.

" The FDA’s Fast Track program is designed to expedite the development and review of drugs with the potential to treat serious or life-threatening conditions, and with nonclinical or clinical data that demonstrate the potential to address unmet medical needs. Fast Track designation enables a company to have frequent communication with the FDA throughout the drug development and review process.4

In November 2018, the FDA granted Orphan Drug designation for PD-0325901 for the treatment of neurofibromatosis type 1. SpringWorks expects to initiate a Phase 2b singlearm, open-label study of PD-0325901 in pediatric and adult patients with NF1-PN in the third quarter of 2019.

About Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that is caused by mutations in the NF1 gene, and that affects both children and adults. Throughout their lifetime, about 30 to 50 percent of NF1 patients progress to a more severe form of the disease that results in the development of plexiform neurofibromas (PN), which are progressive peripheral nerve sheath tumors that cause severe pain, disfigurement, debilitating loss of range of motion, and can significantly shorten lifespan.1-3 The clinical course of NF1-PN is heterogeneous with varying manifestations and severity across patients.

It is estimated that NF1 affects 1 in 3,000 individuals worldwide, and that there are approximately 100,000 patients in the United States living with this disease.5 Most patients with NF1-PN are treated with surgical removal of the tumors, sometimes requiring amputation; however, surgery has variable success rates and a high rate of recurrence has been observed because of the aggressive nature of these tumors.6 There are no therapies currently approved for the treatment of NF1-PN.

About PD-0325901

PD-0325901 is an oral small molecule inhibitor of MEK1 and MEK2. MEK proteins occupy a pivotal position in the MAPK pathway, a key signaling network that regulates cell growth and survival, and whose activity is highly relevant in multiple oncology and rare disease indications.

PD-0325901 has been evaluated in several Phase 1 and Phase 2 clinical trials, with over 200 subjects having been exposed to treatment. A Phase 2 trial conducted by the Neurofibromatosis Clinical Trial Consortium evaluated PD-0325901 in 19 adolescent and adult patients with inoperable and symptomatic or growing plexiform neurofibromas. Results demonstrated an objective response in 42 percent of patients, prospectively defined as having greater than or equal to 20 percent reduction in tumor volume as measured by volumetric MRI. In the clinical trial, PD-0325901 given at 2mg/m2 on a 3-week on 1-week off schedule was generally well-tolerated. The most commonly reported treatmentemergent grade 2 or higher AEs were acneiform rash in 53% (10/19), fatigue in 26% (5/19) and nausea in 21% (4/19) of patients.

SpringWorks is evaluating PD-0325901 as a monotherapy for the treatment of patients with NF1-PN and is also pursuing PD-0325901 in combination with other rational anti-cancer agents across a range of solid tumors.

On June 3, 2019 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported data from two Phase 1 studies evaluating TIBSOVO (ivosidenib) in adult patients with newly diagnosed acute myeloid leukemia (AML) and an isocitrate dehydrogenase-1 (IDH1) mutation who are ineligible for intensive chemotherapy (Press release, Agios Pharmaceuticals, JUN 3, 2019, View Source [SID1234536795]). The data were presented as part of the scientific program at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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"Newly diagnosed AML patients who are not eligible for intensive chemotherapy are typically older or have comorbidities that can lead to a worse prognosis and poor outcomes," said Courtney DiNardo, M.D., lead investigator and associate professor, department of leukemia at the University of Texas MD Anderson Cancer Center. "With an additional six months of follow up since the last data cutoff in the Phase 1 combination study of TIBSOVO with azacitidine, it is encouraging to see a 12-month survival rate of 82% and a continued increase in CR+CRh rate to 70% and CR rate to 61%. In addition, the majority of patients with CR also had IDH1 mutation clearance, suggesting direct impact on the biology of IDH1 mutant AML."

"As the data from these frontline Phase 1 studies of TIBSOVO mature, the durability of response has continued to improve over time and demonstrates that treating these patients with an IDH1 inhibitor early in the disease has the potential to provide deep, durable responses," said Chris Bowden, M.D., chief medical officer at Agios. "The recent sNDA approval in newly diagnosed AML patients with an IDH1 mutation who are ineligible for intensive chemotherapy was the first step in our broad program to develop TIBSOVO across the frontline setting."

Phase 1 Study of TIBSOVO in Combination with Azacitidine

The ongoing Phase 1/2 study is evaluating an investigational use of TIBSOVO or IDHIFA (enasidenib) in combination with azacitidine in patients with newly diagnosed IDH mutant AML unable to receive intensive chemotherapy. As of the February 19, 2019 data cutoff, 23 patients received 500 mg of TIBSOVO daily plus azacitidine in the TIBSOVO arm of the Phase 1b portion of the study. Enrollment in the TIBSOVO arm is complete. As of the data cutoff, 10 (43%) patients remained on study, and the median number of treatment cycles was 15 (range 1-30). The median age was 76 years old, and 52% of patients were age 75 or older. Sixty-five percent of patients had de novo AML and 35% had secondary AML.

Safety Results

The most common Grade 3/4 adverse events (AEs) regardless of cause were thrombocytopenia (61%), anemia (44%), febrile neutropenia (44%) and neutropenia (30%).
Investigator reported IDH differentiation syndrome was reported in four patients, of which three were serious AEs. All four cases resolved, among whom two achieved a complete response (CR), one stable disease and one was not evaluable for response.
Mean neutrophil and platelet counts were maintained near or above thresholds for CR with partial hematologic recovery (CRh) while on study treatment with TIBSOVO and azacitidine. CRh is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (ANC >500/microliter and platelets >50,000/microliter).
Efficacy Results

Overall, 78% (18/23) of patients had a response.
70% (16/23) of patients had a CR or CRh.
61% (14/23) of patients had a CR.
The median duration of CR (95% CI 9.3, NE) as well as CR+CRh (95% CI 12.2, NE) had not been reached.
The median time to response was 1.8 months (range 0.7-3.8 months) and the median time to CR was 3.7 months (range 0.8-15.7 months).
The 12-month survival rate was 82% (95% CI 58.8, 92.8).
The median duration of follow-up was 16.1 months (range 1.3-31.7 months).
For patients who achieved a CR, IDH1 mutation clearance was observed in 9 of 14 (64%) patients with available bone marrow mononuclear cells (BMMCs) and 11 of 14 patients (79%) with available peripheral blood mononuclear cells (PBMCs) as quantified by a digital PCR assay with lower limit of sensitivity for mutant IDH1 of 0.02-0.04% (or 10-4).
TIBSOVO is not approved in any country for the treatment of patients with newly diagnosed AML in combination with azacitidine.

Untreated AML Arm of Phase 1 Study of Single Agent TIBSOVO in IDH1 Mutant Hematologic Malignancies

As of the November 2, 2018 data cutoff, a total of 258 patients with advanced hematologic malignances and an IDH1 mutation were treated in the Phase 1 study, including 34 patients with untreated AML (nine from dose-escalation and 25 from expansion) who received 500 mg of TIBSOVO daily. Enrollment in the study is complete. The median treatment duration for the untreated AML patients was 4.3 months (0.3-40.9). The median age for these patients was 76.5 years (64-87) and 47% had received a prior hypomethylating agent. Among the untreated AML patients, 24% had de novo AML and 76% had secondary AML.

Safety Results

The most common AEs of any grade >25% regardless of causality were diarrhea (53%), fatigue (47%), nausea (38%), decreased appetite (35%), leukocytosis (26%), anemia (26%), edema peripheral (26%) and thrombocytopenia (26%).
Adverse events of interest were the following:
9% reported Grade ≥3 ECG QT prolongation. TIBSOVO was dose reduced in two patients and held in four patients (for any grade of ECG QT prolongation).
18% reported IDH differentiation syndrome of any grade, which was managed with corticosteroids and diuretics. Three patients had their dose temporarily held, and no patients required dose reductions.
3% reported Grade ≥3 leukocytosis.
No AEs of interest lead to any permanent treatment discontinuations or deaths.
Efficacy Results

Data from the 33 untreated AML patients with an IDH1 mutation confirmed by the Abbott RealTimeTM IDH1 assay demonstrated an overall response rate of 55% (18/33 patients).
42% (14/33) of patients had a CR or CRh.
30% (10/33) of patients had a CR.
The median duration of CR (95% CI 4.2, NE) as well as CR+CRh (95% CI 4.6, NE) had not been reached. The estimated 12-month durations of response were 78% for CR and 62% for CR+CRh.
Median overall survival was 12.6 months.
Among patients who were transfusion dependent at baseline, transfusion independence was observed across all response categories, where it was defined as an absence of transfusions for at least 56 consecutive days on treatment.
IDH1 mutation clearance, defined as a reduction in mIDH1 variant allele frequency to below the limit of detection of 0.02–0.04% (or 10-4), was observed in 64% (9/14) of patients who achieved CR+CRh, including 50% (5/10) of patients with CR and 100% (4/4) of patients with CRh.
About TIBSOVO (ivosidenib)
TIBSOVO is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:

Adult patients with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
Adult patients with relapsed or refractory AML.
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, 25% (7/28) of patients with newly diagnosed AML and 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 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. Of the 34 patients with relapsed or refractory AML who experienced differentiation syndrome, 27 (79%) patients 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, or 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 including laboratory abnormalities (≥20%) were hemoglobin decreased (60%), fatigue (43%), arthralgia (39%), calcium decreased (39%), sodium decreased (39%), leukocytosis (38%), diarrhea (37%), magnesium decreased (36%), edema (34%), nausea (33%), dyspnea (32%), uric acid increased (32%), potassium decreased (32%), alkaline phosphatase increased (30%), mucositis (28%), aspartate aminotransferase increased (27%), phosphatase decreased (25%), electrocardiogram QT prolonged (24%), rash (24%), creatinine increased (24%), cough (23%), decreased appetite (22%), myalgia (21%), constipation (20%), and pyrexia (20%).
In patients with newly diagnosed AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were fatigue (14%), differentiation syndrome (11%), electrocardiogram QT prolonged (11%), diarrhea (7%), nausea (7%), and leukocytosis (7%). Serious adverse reactions (≥5%) were differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES).
In patients with relapsed or refractory AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were differentiation syndrome (13%), electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), and tumor lysis syndrome (6%). 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

Because 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 Myeloid Leukemia (AML)
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. AML patients are typically older or have comorbidities that preclude the use of intensive chemotherapy. These patients typically have a worse prognosis and poor outcomes. The majority of patients with AML eventually relapse. The five-year survival rate is approximately 28%. 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. IDH1 mutations have been associated with negative prognosis in AML.

On June 3, 2019 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a clinical stage biotechnology company focused on developing targeted cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that its Chief Executive Officer, Kenneth L. Waggoner, and PharmaCyte’s consultant cellular biologist, David Judd, will be on site at Austrianova’s GMP manufacturing facility in Bangkok, Thailand, as the production of its clinical trial material for the treatment of locally advanced, non-metastatic, inoperable pancreatic cancer (LAPC) is underway (Press release, PharmaCyte Biotech, JUN 3, 2019, View Source [SID1234536811]).

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Mr. Waggoner and Mr. Judd will observe the culturing of the genetically altered HEK-293 cells both before and after they are encapsulated. Mr. Judd has a broad array of experience in development of cell culture media for many primary cells and cell lines and is particularly knowledgeable in the growth of HEK-293 cells. He has developed manufacturing processes, cell assays, biochemical analysis, cell culture processes and downstream recovery strategies. Although Mr. Judd has already offered advice to both PharmaCyte and Austrianova via telephonic communications, his actual on-site presence should prove to be invaluable. Mr. Judd will lend assistance in helping correct any unforeseen problems in the production process as the latest two staggered manufacturing "runs" are carried out and completed.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, said, "After the changes to the manufacturing process allowed us to get back on track and proceed with GMP production of the "CypCaps," our clinical trial product for the company’s planned clinical trial in LAPC, I felt it was necessary to be on-site with David, our consulting expert in the culture of HEK-293 cells, to oversee the process and ensure we are staying on the path and clinical trial development timeline that we’ve developed to submit our Investigational New Drug application (IND). His presence will be particularly important since this time two manufacturing runs will be performed in a staggered fashion rather than consecutively as has been done in the past."

While in Thailand, Mr. Waggoner, Mr. Judd, Prof. Dr. Walter H. Günzburg and Dr. Brian Salmons of Austrianova and possibly others will be interviewed on the progress of the production, the testing of the clinical trial product, factors involved in the manufacturing process that will be included in the submission of the IND and various other topics related to the company’s planned clinical trial in LAPC.

While on-site at the GMP facility in Thailand, the company expects to post pictures, videos and interviews on its social media platforms. Shareholders and others who are interested in PharmaCyte’s content, should follow the company’s social media platforms:

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On June 3, 2019 Epizyme, Inc. (Nasdaq: EPZM), a late-stage biopharmaceutical company developing novel epigenetic therapies, reported updated data on tazemetostat from the epithelioid sarcoma cohort of its ongoing Phase 2 study in patients with molecularly defined solid tumors (Press release, Epizyme, JUN 3, 2019, View Source [SID1234536832]). The data will be presented today in an oral presentation entitled "Safety and efficacy of tazemetostat, a first-in-class EZH2 inhibitor, in patients with epithelioid sarcoma" at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting by Silvia Stacchiotti, M.D., Fondazione IRCCS Istituto Nazionale Tumori, Milan, and an investigator in the Phase 2 clinical trial.

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In July 2017, Epizyme completed enrollment of 62 patients in the epithelioid sarcoma cohort of its Phase 2 trial. Updated data reported today from that cohort are as of a September 17, 2018 cutoff date. Findings include that treatment with tazemetostat resulted in a 15% objective response rate (ORR) and a 26% disease control rate (DCR). The median duration of response (DOR) has not yet been reached. Among the 62 patients, tazemetostat continues to be generally well-tolerated with favorable safety.

"Today, there are limited effective and tolerable treatment options available for patients with epithelioid sarcoma, a rare and aggressive cancer that affects people in the prime of their lives," said Dr. Shefali Agarwal, chief medical officer of Epizyme. "We are pleased that the data presented today are consistent with what we have seen throughout our development of tazemetostat for epithelioid sarcoma, demonstrating meaningful clinical activity and good tolerability. Importantly, the totality of these data formed the foundation for our first NDA submission, which we just announced last week. If we are successful, tazemetostat would be the first FDA-approved EZH2 inhibitor. We are thankful to the patients, physicians and caregivers who have participated in our study and hope that tazemetostat may positively impact patients with this devastating cancer in the future."

Efficacy Data
The epithelioid sarcoma cohort in Epizyme’s Phase 2 study represents the largest prospective study of epithelioid sarcoma with any approved or investigational anticancer treatment to date. Epithelioid sarcoma is an ultra-rare and aggressive soft tissue sarcoma, characterized by a loss of the INI1 protein. It is most commonly diagnosed in young adults (20-40 years old) and is often fatal, with a median overall survival (OS) of less than one year in patients with metastatic disease.

The fully enrolled cohort includes 24 treatment-naive patients and 38 relapsed and/or refractory patients for a total of 62 adult and pediatric epithelioid sarcoma patients (at least 16 years of age). Patients enrolled were administered 800 mg of tazemetostat orally twice daily. The primary endpoint of the study is ORR, comprised of complete and partial responses as measured by RECIST 1.1. Secondary endpoints include DOR, DCR, OS and safety.

Updated findings are summarized below, based on a September 17, 2018 data cut-off date.

Key Efficacy Endpoint

Treatment-naive
(n=24)

Relapsed and/or
Refractory

(n=38)

Total
(n=62)

Objective Response Rate, n (%) 6 (25%) 3 (8%) 9 (15%)
Median Duration of Response, weeks
41.1
(34.1, not reached)

Not reached
(40.1, not reached)

Not reached
(34.1, not reached)

Disease Control Rate*, n (%)
(95% confidence interval)

10 (42%)
(22.1, 63.4)

6 (16%)
(6.0, 31.3)
16 (26%)
(15.5, 38.5)

Median Overall Survival, weeks
(95% confidence interval)

Not reached 47.4
(29.0, 68.1)

82.4
(47.4, not reached)

*Comprised of confirmed objective responses for any duration or disease stabilization of 32 weeks or more

Tazemetostat Safety Data
Favorable safety and tolerability have been observed with tazemetostat in this Phase 2 study cohort. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2, with only 13 percent of patients experiencing grade 3 or higher treatment-related TEAEs. Reported TEAEs regardless of attribution with an incidence of 10% or greater were fatigue (39%), nausea (35%), cancer pain (32%), decreased appetite (26%), constipation (21%), vomiting (24%), cough and headache (18% each), diarrhea, weight decrease and anemia (16% each), dyspnea (13%) and plural effusion (11.% ). Two percent of patients were dose-reduced due to an adverse event and one patient discontinued treatment due to an adverse event in the Phase 2 cohort.

The safety data from the 62 epithelioid sarcoma patients in the study cohort are consistent with the overall safety observed to date in over 800 people in the tazemetostat clinical program.

Tazemetostat NDA Submission for Epithelioid Sarcoma
In May, Epizyme announced that it submitted the New Drug Application (NDA) for tazemetostat for the treatment of patients with metastatic or locally advanced epithelioid sarcoma not eligible for curative surgery to the US. Food and Drug Administration (FDA). The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing.

About Epithelioid Sarcoma
Epithelioid sarcoma is an ultra-rare soft tissue sarcoma characterized by a loss of the protein INI1. Patients are most commonly diagnosed as young adults, between 20 and 40 years of age. Median overall survival from initial diagnosis is 30 months. Epithelioid sarcoma becomes more aggressive after recurrence or metastases, with a typical survival of less than one year for patients with metastatic disease.

About the Tazemetostat Clinical Trial Program
Tazemetostat, an oral, potent, first-in-class EZH2 inhibitor, is currently being studied as a monotherapy in ongoing clinical programs in patients with certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors, and in patients with follicular lymphoma, both with and without EZH2 activating mutations. Multiple clinical studies are underway through collaborations assessing tazemetostat as a combination treatment for patients with diffuse large B-cell lymphoma. Epizyme also plans to conduct multiple additional clinical trials designed to evaluate the potential benefit of tazemetostat in earlier lines of therapy for follicular lymphoma, as well as new combinations and cancer indications.

On June 3, 2019 AIVITA Biomedical, Inc., a biotech company specializing in innovative stem cell applications, reported that Chief Medical Officer Dr. Robert O. Dillman presented clinical data on melanoma patients treated with patient-specific vaccines on June 1 at the 55th Annual Meeting of ASCO (Free ASCO Whitepaper) in Chicago, Illinois (Press release, AIVITA Biomedical, JUN 3, 2019, View Source [SID1234536849]). The data is being published concurrently in the journal Melanoma Management.

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The abstract and publication describe survival data for 72 patients pooled from two Phase 2 trials. In the first trial conducted in 54 patients, the projected median overall survival was 54% at a time when median follow up was 4.5 years (Dillman et al. Cancer Biother Radiopahrm 2009;24:311-319.). Actual 5-year survival was 50% once all patients had been followed a minimum of five years. In the second Phase 2 trial patients were randomized for treatment with either their patient-specific dendritic cell vaccine (DCV) or patient-specific tumor cell vaccine (TCV). In both treatment arms the source of antigen was autologous tumor cells that were self-renewing in cell culture. Median overall survival was better in the DCV-treated patients: median survival 40.3 vs 20.5 months, 3-year actual survival of 61% vs 25% (p=0.018), and a 70% reduction in the risk of death (p=0.0053) [Dillman et al. J Immunother Cancer 2018;6:19.] The data for DCV-treated patients was pooled in order to address questions related to survival of specific subsets of patients [Dillman et al. Melanoma Manag 2019]. All patients had been followed for five years. The data showed that for melanoma patients who had recurrent Stage III disease that was not measurable at the time DCV-treatment was initiated, the 5-year survival rate was 72%. In melanoma patients who had previous Stage IV melanoma but did not have measurable disease at the time of treatment, the 5-year survival rate was 53%. Patients with measurable Stage IV melanoma had a median survival of 18.5 months with a two-year survival rate of 46%, which compares favorably to results achieved with anti-PD-1 checkpoint inhibitors in similar patients.

AIVITA is currently conducting three clinical studies investigating its platform ROOT OF CANCER therapy in patients with ovarian cancer, glioblastoma and melanoma. AIVITA uses 100% of proceeds from the sale of its ROOT of SKIN skincare line to support the treatment of women with ovarian cancer.

About ROOT OF CANCER

AIVITA’s treatment is a platform technology applicable to most solid tumor types and consists of autologous dendritic cells loaded with autologous tumor antigens from purified autologous self-renewing tumor-initiating cells.

OVARIAN CANCER:

AIVITA’s ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous cancer stem cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy. The trial is not open to patients with recurrent ovarian cancer.

For additional information about AIVITA’s AVOVA-1 trial patients can visit: www.clinicaltrials.gov/ct2/show/NCT02033616

GLIOBLASTOMA:

AIVITA’s glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the cancer stem cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70 and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC). The trial is not open to patients with recurrent glioblastoma.

For additional information about AIVITA’s AV-GBM-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03400917

MELANOMA:

AIVITA’s melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with the cancer stem cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients. This trial is not yet open for enrollment.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations and (5) are about to initiate anti-PD1 monotherapy.

For additional information about AIVITA’s AV-MEL-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03743298