On November 6, 2019 FORMA Therapeutics, Inc., a clinical stage biopharmaceutical company focused on rare hematological diseases and cancers, reported that three abstracts have been accepted for presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in Orlando, Florida from December 7-10, 2019 (Press release, Forma Therapeutics, NOV 6, 2019, View Source [SID1234550463]).

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Three oral presentations on lead assets will feature data: olutasidenib, a next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1m) in development for the treatment of patients with relapsed/refractory acute myeloid leukemia (RR/AML) or myelodysplastic syndrome (MDS), and patients with glioma and other solid tumors with an IDH1 mutation; and FT-4202, a novel selective red blood cell (RBC) pyruvate kinase (PKR) activator in development as a potentially disease-modifying therapy for the treatment of sickle cell disease (SCD). A poster presentation will feature data for a FORMA-discovered asset licensed to Celgene Corporation, FT-1101, an oral, structurally distinct and potent pan-inhibitor of the Bromodomain and Extra-Terminal (BET) epigenetic protein family.

The accepted abstracts are available online through the ASH (Free ASH Whitepaper) conference website, View Source, and include:

Oral Presentations

Title: Olutasidenib (FT-2102), an IDH1m Inhibitor As a Single Agent or in Combination with Azacitidine, Induces Deep Clinical Responses with Mutation Clearance in Patients with Acute Myeloid Leukemia Treated in a Phase 1 Dose Escalation and Expansion Study

Date/Time: Saturday, December 7, 2019 at 2:30 p.m. ET
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel Targets and Combinations
Abstract: 231
Location: Orange County Convention Center, Chapin Theater (W320)
Presenter: Justin Watts, MD. Assistant Professor University of Miami, Sylvester Comprehensive Cancer Center

Title: Olutasidenib (FT-2102), Induces Rapid Remissions in Patients with IDH1-Mutant Myelodysplastic Syndrome: Results of Phase 1/2 Single Agent Treatment and Combination with Azacitidine

Date/Time: Monday, December 9, 2019 at 10:45 a.m. ET
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Targeting Gene Mutations in MDS
Abstract: 674
Location: Orange County Convention Center, W311ABCD
Presenter: Jorge E. Cortes, MD. Professor, Augusta University, Director of the Georgia Cancer Center

Title: Phase 1 Single (SAD) and Multiple Ascending Dose (MAD) Studies of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of FT-4202, an Allosteric Activator of Pyruvate Kinase-R, in Healthy and Sickle Cell Disease Subjects

The presentation will report the effects of FT-4202 on healthy subjects in this ongoing study.

Date/Time: Monday, December 9, 2019 at 11:15 a.m. ET
Session: 114. Hemoglobinopathies, Excluding Thalassemia—Clinical: Emerging Therapies: Reports from Recent Clinical Trials
Abstract: 616
Location: Orange County Convention Center, W304ABCD
Presenter: Theodosia Kalfa, MD, PhD. Associate Professor, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center

Poster Presentation

Title: Phase 1 Dose Escalation and Expansion Study to Determine Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the BET Inhibitor FT-1101 As a Single Agent in Patients with Relapsed or Refractory Hematologic Malignancies

Date/Time: Monday, December 9, 2019 from 6:00 – 8:00 p.m. ET
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
Abstract: 3907
Location: Orange County Convention Center, Hall B
Presenter: Manish Patel, MD. Director of Drug Development, Florida Cancer Specialists. Associate Director of Drug Development, Sarah Cannon Research Institute

About Olutasidenib (FT-2102)

FORMA’s most advanced clinical asset, olutasidenib, is a potent and selective next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1) being investigated to treat patients with relapsed/refractory acute myeloid leukemia (RR/AML) or myelodysplastic syndrome (MDS), and patients with glioma and other solid tumors with an IDH1 mutation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. Mutations of IDH1 can produce excessive amounts of the oncometabolite 2-hydroxyglutarate (2-HG), which impairs cell differentiation and promotes blood malignancies and solid tumors. IDH1 mutations are present in 7-14% of patients with AML and 3-4% of patients with MDS.

About FT-4202

FT-4202 is a novel selective red blood cell (RBC) pyruvate kinase (PKR) activator designed to be a disease-modifying therapy for the treatment of sickle cell disease (SCD), with a multimodal approach. FT-4202 works upstream by activating the RBCs’ natural PKR activity to decrease 2,3-DPG levels, which leads hemoglobin to hold on to oxygen molecules longer to reduce RBC sickling. The downstream activity of FT-4202 increases ATP levels, the fuel that provides energy to cells, to improve RBC health and survival. Together, these effects are anticipated to increase hemoglobin levels and decrease painful vaso-occlusive crises. SCD is the most common disorder caused by a single gene mutation and affects approximately 100,000 people in the U.S., and millions globally.

About FT-1101 (also known as CC-95775)

FT-1101 (also known as CC-95775) is an oral, structurally distinct and potent pan-inhibitor of the Bromodomain and Extra-Terminal (BET) epigenetic protein family, which was discovered by FORMA and licensed to Celgene Corporation.

On November 6, 2019 MannKind Corporation (NASDAQ:MNKD) reported preliminary financial results for the quarter and nine months ended September 30, 2019 (Press release, Mannkind, NOV 6, 2019, View Source [SID1234550479]).

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"I am excited to see MannKind continue its transformation, with another quarter of double-digit growth in Afrezza revenue, year over year, and aggregate net revenue of $14.6 million," said Michael Castagna, Chief Executive Officer of MannKind Corporation. "In the third quarter, we completed our recapitalization and achieved several key milestones, such as booking our first international sale of Afrezza to Brazil, seeing the first PAH patient dosed with TreT and progressing two pipeline compounds into nonclinical testing."

Third Quarter 2019 Results

Net revenues were $14.6 million for the third quarter of 2019, reflecting Afrezza net revenue of $6.4 million and collaborations and services revenue of $8.2 million. Afrezza net revenue increased 46% compared to $4.4 million in the third quarter of 2018, primarily driven by higher product demand (including the first shipment to Brazil), a more favorable mix of Afrezza cartridges and price.

Collaborations and services revenue increased $8.1 million compared to the third quarter of 2018, primarily driven by the license agreement with United Therapeutics, which began in the fourth quarter of 2018.

On a GAAP basis, Afrezza gross loss was $0.7 million for the third quarter of 2019 compared to a gross loss of $0.9 million in the same period in 2018. Afrezza cost of goods sold for the third quarter of 2019 included a one-time fee of $2.75 million recorded in connection with the amendment of the Company’s insulin supply agreement with Amphastar in August 2019. As a result, on a non-GAAP basis, gross profit was $2.1 million or 33% for the third quarter of 2019.

Research and development (R&D) expenses for the third quarter of 2019 were $1.6 million compared to $2.0 million for the third quarter of 2018. This 23% decrease was primarily attributable to a $0.4 million decrease in clinical trial spending.

Selling, general and administrative (SG&A) expenses for the third quarter of 2019 were $16.7 million compared to $19.4 million for the third quarter of 2018. This decrease of $2.7 million, or 14%, was primarily attributable to a $0.8 million decrease in personnel-related costs and a $1.9 million decrease in Afrezza marketing costs.

Interest expense on notes for the third quarter of 2019 was $4.1 million compared to $1.0 million for the third quarter of 2018. This $3.1 million increase or 316% was primarily attributable to a $3.4 million charge realized as a result of achieving of a sales milestone in the third quarter of 2019 under the Company’s milestone agreement with Deerfield.

The net loss for the third quarter of 2019 was $10.4 million, or $0.05 per share compared to a $24.2 million net loss in the third quarter of 2018 or $0.16 per share. The decrease was primarily the result of increased total revenues from higher Afrezza commercial demand and from the licensing and research agreements with United Therapeutics.

Nine Months Ended September 30, 2019

Net revenues were $47.0 million for the nine months ended September 30, 2019, reflecting Afrezza net revenue of $17.5 million and collaborations and services revenue of $29.5 million. Afrezza net revenue increased 52% compared to $11.5 million for the nine months ended September 30, 2018, primarily due to higher product demand (including the first shipment to Brazil), a more favorable mix of Afrezza cartridges and price. Collaborations and services revenue increased $29.3 million compared to the nine months ended September 30, 2018, which was primarily attributed to the licensing agreement ($23.3 million) and research agreement ($5.9 million) with United Therapeutics, both of which began in the fourth quarter of 2018.

On a GAAP basis, Afrezza gross profit was $2.1 million for the nine months ended September 30, 2019, an improvement of $5.0 million or 173% compared to a gross loss of $2.9 million in the same period in 2018, primarily due to an increase of $6.0 million in net revenue, a $1.8 million decrease in inventory write-offs, partially offset by increased costs due to higher sales and the Amphastar one-time amendment fee of $2.75 million in the third quarter of 2019. As a result, on a non-GAAP basis, gross profit was $4.9 million or 28% for the nine months ended September 30, 2019.

R&D expenses for the nine months ended September 30, 2019 were $4.9 million compared to $7.7 million for the nine months ended September 30, 2018. This $2.8 million or 36% decrease was primarily attributable to a $1.0 million decrease in personnel-related costs and a $1.1 million decrease in clinical trial spending.

SG&A expenses for the nine months ended September 30, 2019 were $58.9 million compared to $61.7 million for the nine months ended September 30, 2018. This decrease of $2.7 million or 5% was primarily attributable to a $6.1 million decrease in personnel related costs, $1.9 million decrease in professional fees, a $1.0 million decrease in stock-based compensation costs offset by a $6.8 million increase in costs for a television campaign for Afrezza.

Interest income increased by $0.5 million or 160% for the nine months ended September 30, 2019 primarily attributable to a higher balance on money market funds and other short-term investments.

Interest expense on notes for the nine months ended September 30, 2019 was $5.3 million compared to $4.5 million for the nine months ended September 30, 2018. This $0.8 million increase was primarily attributable to a $3.4 million charge realized as a result of achieving of a sales milestone in the third quarter of 2019 under the Company’s milestone agreement with Deerfield, partially offset by a reduction in debt principal balances.

The net loss for the nine months ended September 30, 2019 was $37.6 million, or $0.20 per share compared to a $77.2 million net loss for the nine months ended September 30, 2018 or $0.56 per share. The lower net loss was mainly attributable to a $35.2 million increase in total revenues.

Cash, Cash Equivalents, Restricted Cash and Short Term Investments

Cash, cash equivalents, restricted cash, and short-term investments at September 30, 2019 was $50.4 million compared to $71.7 million at December 31, 2018.

Non-GAAP Measures

Certain financial information contained in this press release is presented on both a reported basis (GAAP) and a non-GAAP basis. Reported results were prepared in accordance with GAAP whereas non-GAAP measures exclude items described in the reconciliation tables below. Non-GAAP financial information is intended to portray the results of our baseline performance, supplement or enhance management, analysts and investors overall understanding of our underlying financial performance and facilitate comparisons among current and past periods. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP.

Conference Call

MannKind will host a conference call and presentation webcast to discuss these results today at 9:00 a.m. Eastern Time. To participate in the live call by telephone, please dial (866) 548-4713 or (323) 794-2093 and use the participant passcode: 8987532. Those interested in listening to the conference call live via the Internet may do so by visiting the Company’s website at View Source under News & Events.

A telephone replay of the call will be accessible for approximately 14 days following completion of the call by dialing (844) 512-2921 or (412) 317-6671 and use the participant passcode: 8987532. A replay will also be available on MannKind’s website for 14 days.

On November 6, 2019 Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) reported financial and operational results for the third quarter ended September 30, 2019 (Press release, Vanda Pharmaceuticals, NOV 6, 2019, View Source [SID1234550521]).

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"These results affirm Vanda’s corporate strategy, and continue to demonstrate our ability to grow our commercial assets and expand our pipeline of products," said Mihael H. Polymeropoulos, M.D., Vanda’s President and CEO. "I am proud of the progress we have made in our research and development programs, with several new filings expected to be submitted within the next two years. Furthermore, Vanda has put in place a proactive regulatory strategy to better support our patients and products."

Key Financial Highlights:

Total net product sales from HETLIOZ and Fanapt were $59.5 million in the third quarter of 2019, a 21% increase compared to $49.1 million in the third quarter of 2018.
HETLIOZ net product sales were $37.6 million in the third quarter of 2019, a 26% increase compared to $29.9 million in the third quarter of 2018.
Fanapt net product sales were $21.9 million in the third quarter of 2019, a 14% increase compared to $19.2 million in the third quarter of 2018.
Cash, cash equivalents and marketable securities (Cash) were $299.6 million as of September 30, 2019, representing an increase to Cash of $59.0 million compared to September 30, 2018.
Key Research and Development Highlights:

Tradipitant

Enrollment in EPIONE, the Phase III clinical study of tradipitant in atopic dermatitis, is complete. Results from EPIONE are expected in the first quarter of 2020.
In October 2019, EPIONE II, a second Phase III clinical study of tradipitant in atopic dermatitis, began enrolling patients.
Enrollment in the Phase III study of tradipitant in gastroparesis is ongoing as Vanda continues to engage with the U.S. Food and Drug Administration (FDA) on tradipitant’s regulatory path.
Vanda plans to initiate the Phase III program of tradipitant in motion sickness in the fourth quarter of 2019. Vanda expects to file a New Drug Application with the FDA for tradipitant for the treatment of motion sickness in 2020.
HETLIOZ (tasimelteon)

Vanda received a complete response letter (CRL) on August 16, 2019 from the FDA related to the supplemental New Drug Application (sNDA) of HETLIOZ for the treatment of Jet Lag Disorder (JLD). Vanda met with the FDA to discuss the CRL in a Post Action meeting and is determining its next steps.
Vanda plans to meet with the FDA in the fourth quarter of 2019 to discuss the HETLIOZ Smith-Magenis Syndrome clinical study results and expects to submit an sNDA by year-end 2019.
An observational study of delayed sleep phase disorder (DSPD) is ongoing. Vanda plans to initiate a Phase III clinical study of HETLIOZ in DSPD patients by year-end 2019.
Fanapt (iloperidone)

A pharmacokinetic study for the once-a-month long acting injectable (LAI) formulation of Fanapt is ongoing.
A study of Fanapt in bipolar disorder is planned to begin by year-end 2019.
VTR-297 (histone deactetylase (HDAC) inhibitor)

Enrollment in the Phase I clinical study (1101) of VTR-297 in hematologic malignancies is ongoing.
Corporate Highlights:

Vanda announced the appointment of Anne Sempowski Ward to its Board of Directors, effective October 28, 2019, increasing the total number of members on the Board to six.
Vanda announced the hiring of Scott L. Howell as its Chief People Officer, Aranthan "AJ" Jones II as its Chief Corporate Affairs and Communications Officer and Joakim "Kim" Wijkstrom as its Chief Marketing Officer, further bolstering the executive leadership team.
GAAP Financial Results

Net income was $100.4 million for the third quarter of 2019, or $1.88 per share, compared to net income of $7.2 million, or $0.14 per share, for the third quarter of 2018.

The income tax benefit of $88.1 million reflected in the financial results for the third quarter of 2019 includes the favorable impact of the release of Vanda’s deferred tax asset valuation allowance.

Income before income taxes was $12.3 million in the third quarter of 2019, a 69% increase compared to $7.3 million in the third quarter of 2018.

2019 Financial Guidance

Vanda reiterates its 2019 net product sales guidance and expects results in the upper half of the range. In addition, Vanda provides an update to Year-end 2019 Cash and expects to achieve the following financial objectives in 2019:

Conference Call

Vanda has scheduled a conference call for today, Wednesday, November 6, 2019, at 4:30 PM ET. During the call, Vanda’s management will discuss the third quarter 2019 financial results and other corporate activities. Investors can call 1-866-688-9426 (domestic) or 1-409-216-0816 (international) and use passcode 5377942. A replay of the call will be available on Wednesday, November 6, 2019, beginning at 7:30 PM ET and will be accessible until Wednesday, November 13, 2019, at 7:30 PM ET. The replay call-in number is 1-855-859-2056 for domestic callers and 1-404-537-3406 for international callers. The passcode number is 5377942.

The conference call will be broadcast simultaneously on Vanda’s website, www.vandapharma.com. Investors should click on the Investors tab and are advised to go to the website at least 15 minutes early to register, download, and install any necessary software or presentations. The call will also be archived on Vanda’s website for a period of 30 days.

On November 6, 2019 Kite, a Gilead Company (Nasdaq: GILD), reported the acceptance of eight abstracts, including five oral presentations, for Yescarta (axicabtagene ciloleucel) and other ongoing research from the company’s chimeric antigen receptor (CAR) T cell therapy development program, at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, in Orlando from December 7–10, 2019 (Press release, Kite Pharma, NOV 6, 2019, View Source [SID1234550535]).

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Data from Kite’s CAR T cell therapy development program to be presented at the meeting include survival data at three years from the pivotal ZUMA-1 trial of Yescarta in patients with refractory large B-cell lymphoma to be highlighted in the ZUMA-1 mechanism of relapse presentation below (Abstract #203), as well as primary results from a cohort investigating the effect of earlier steroid use with Yescarta on the rates of cytokine release syndrome and neurologic events (Abstract #243). Real-world data on Yescarta, including an analysis of post-marketing outcomes for Yescarta in large B-cell lymphoma (Abstract #764), as well as the primary analysis for the ZUMA-2 study evaluating investigational KTE-X19 in relapsed or refractory mantle cell lymphoma (Abstract #754), will also be presented.

"As we continue to lead the field in cell therapy, this year’s ASH (Free ASH Whitepaper) Annual Meeting will be a seminal one for Kite," said Christi Shaw, Chief Executive Officer of Kite. "We are excited to share three-year survival data, insights into potential adverse event management and findings from other studies that help further the understanding of Yescarta and cell therapy as we aim to bring this potentially life-saving treatment approach to as many appropriate people with blood cancers as possible."

Yescarta was the first CAR T cell therapy to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, and high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of cytokine release syndrome and neurologic toxicities; see below for Important Safety Information.

Dates and times for presentations are as follows:

Area of Focus, Presentation Number and Date/Time (ET)

Abstract Title

Presentations

Large B-cell Lymphoma
Abstract #203 (Oral)
Saturday, Dec 7 (1:00 pm)

CD19-Loss with Preservation of Other B-Cell Lineage Features with Large B-Cell Lymphoma Who Relapsed Post-Axi-Cel

Large B-cell Lymphoma
Abstract #243 (Oral)
Saturday, Dec 7 (2:30 pm)

Earlier Steroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Large B-Cell Lymphoma

Large B-cell Lymphoma
Abstract #793 (Oral)
Monday, Dec 9 (2:45 pm)

Medicare Patients Receiving Chimeric Antigen Receptor T Cell Therapy for Non-Hodgkin Lymphoma: A First Real-world Look at Patient Characteristics, Healthcare Utilization and Costs

Large B-cell Lymphoma
Abstract #764 (Oral)
Monday, Dec 9 (3:00 pm)

Outcomes of Post-marketing Use of an Anti-CD19 CAR T Cell Therapy, Axicabtagene Ciloleucel (Axi-Cel), for the Treatment of Large B-Cell Lymphoma in the United States

Mantle Cell Lymphoma
Abstract #754 (Oral)
Monday, Dec 9 (3:30 pm)

KTE-X19, an Anti-CD19 CAR T Cell Therapy, in Patients with Relapsed/Refractory Mantle Cell Lymphoma: Results of the Phase 2 ZUMA-2 Study

Large B-cell Lymphoma
Abstract #4095 (Poster)
Monday, Dec 9 (6:00-8:00 pm)

A Comparison of Two-year Outcomes in ZUMA-1 (Axicabtagene Ciloleucel) and SCHOLAR-1 in Patients with Refractory Large B-Cell Lymphoma

Trials-In-Progress

Large B-cell Lymphoma
Abstract #4084 (Poster)
Monday, Dec 9 (6:00-8:00 pm)

ZUMA-11: A Phase 1/2 Multicenter Study of Axicabtagene Ciloleucel (Axi-Cel) + Utomilumab in Patients with Refractory Large B-Cell Lymphoma

Large B-cell Lymphoma
Abstract #4093 (Poster)
Monday, Dec 9 (6:00-8:00 pm)

A Phase 2, Open-label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination with Either Rituximab or Lenalidomide in Patients with Refractory Large B-Cell Lymphoma (ZUMA-14)

For more information, including a complete list of abstract titles at the meeting, please visit: View Source

The use of Yescarta with utomilumab, rituximab, or lenalidomide is investigational and not approved globally. Efficacy and safety of these potential combinations have not been established. KTE-X19 is investigational and not approved anywhere globally. Its efficacy and safety have not been established. More information about clinical trials with KTE-X19 is available at www.clinicaltrials.gov.

About KTE-X19

KTE-X19 is an investigational, autologous, anti-CD19 CAR T cell therapy. KTE-X19 uses the XLP manufacturing process that includes T-cell selection and lymphocyte enrichment. Lymphocyte enrichment is a necessary step in certain B-cell malignancies with evidence of circulating lymphoblasts. KTE-X19 is currently in Phase 1/2 trials in acute lymphoblastic leukemia (ALL), mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS.
CYTOKINE RELEASE SYNDROME (CRS): CRS occurred in 94% of patients, including 13% with ≥ Grade 3. Among patients who died after receiving Yescarta, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to infusion of Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES: Neurologic toxicities occurred in 87% of patients. Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks, with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade 3 or higher occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures occurred with Yescarta. Fatal and serious cases of cerebral edema have occurred in patients treated with Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities. Monitor patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion and treat promptly.

YESCARTA REMS: Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS. The required components of the Yescarta REMS are: Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer Yescarta are trained about the management of CRS and neurologic toxicities. Further information is available at www.YESCARTAREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS: Allergic reactions may occur. Serious hypersensitivity reactions including anaphylaxis may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in Yescarta.

SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients, and in 23% with ≥ Grade 3. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Yescarta infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. Grade 3 or higher cytopenias not resolved by Day 30 following Yescarta infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after Yescarta infusion.

HYPOGAMMAGLOBULINEMIA: B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS: The most common adverse reactions (incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

On November 6, 2019 Supernus Pharmaceuticals, Inc. (NASDAQ: SUPN), a pharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, reported financial results for the third quarter of 2019, results from the Phase III P301 trial for SPN-810 and associated Company developments (Press release, Supernus, NOV 6, 2019, View Source;19.htm [SID1234550551]).

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Commercial Update

Third quarter 2019 product prescriptions for Trokendi XR and Oxtellar XR, as reported by IQVIA, totaled 215,033, a 6.4% increase over the third quarter of 2018.

"For the quarter and year to date periods, the beneficial impact of volume growth and price increases has been offset by continued pressure on gross-to-net sales deductions," said Jack Khattar, President and CEO of Supernus. "Going forward, we believe that competitive dynamics and pressure on gross-to-net deductions are not likely to abate; consequently, we believe that net product sales growth will essentially be flat, even with moderate growth in prescriptions."

Progress of Product Pipeline
SPN-812 – Novel non-stimulant for the treatment of ADHD

The Company expects to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for SPN-812 for the treatment of ADHD in November 2019.

A Phase III program in adult patients was initiated during the third quarter of 2019.

SPN-810 – Novel treatment of Impulsive Aggression (IA) in patients with ADHD

Phase III P301 trial in patients 6 to 11 years old did not meet its primary endpoint. The study was a randomized, double-blind, placebo controlled, multicenter, parallel group clinical trial in patients diagnosed with ADHD. Patients receiving SPN-810 36mg showed a median percent reduction of 58.6% in the average weekly frequency of impulsive aggression episodes from baseline that was not statistically significant (p= 0.092) compared to placebo. These results are based on the combined analysis of data from stages 1 and 2 in the study. In stage 1 (interim analysis stage), the median percent reduction was 60%, which was statistically significant (p= 0.029) compared to placebo. However, in stage 2 of the study, post the interim analysis, the increase in variability in the 36mg treatment arm seems to have adversely impacted the results in the combined analysis.

Percent Change from Baseline (CFB) in the Frequency of IA Behaviors
Treatment Period – Primary Analysis (ITT Population)

The median percent reduction in frequency of IA behavior in this Phase III study is consistent with the range of percent improvement in the retrospective modified aggression scale (58% – 62%) we saw in the two positive treatment arms in the Phase IIb study. The Company will continue its analysis of the results to better understand the reasons behind the increased variability in the 36mg treatment arm in the P301 study.

Overall, the trial exhibited favorable tolerability and safety profiles with low incidence of adverse events (AEs) across all doses. AEs were mild leading to low discontinuation rates of 0%, 7% and 5% for the 18mg, 36mg and combined treatment arms, respectively.

Enrollment in the Phase III P302 trial in patients 6 to 11 years old is at 98% of the target. The Company will cease enrollment in the P302 trial and analyze the data, which are expected to be available by the end of 2019. In the meantime, enrollment in the P503 Phase III trial (adolescents) is on hold until data from the P302 study are available and a final decision is reached regarding the SPN-810 program in IA. Mr. Khattar added, "We are obviously disappointed with the efficacy results from our Phase III P301 trial with SPN-810. I thank all our employees for working diligently to complete the studies and believing in what we do for our patients. I also thank all our patients, their families, and our investigators for participating in our studies."

SPN-604 – Novel treatment of bipolar disorder
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The Company initiated a pivotal Phase III monotherapy trial for the treatment of bipolar disorder in the fourth quarter of 2019.

Operating Expenses
Research and development (R&D) expenses in the third quarter of 2019 were $16.9 million, lower than the $20.4 million in the same quarter last year. This decrease is due to the completion of the four Phase III clinical trials for SPN-812, three of which were completed in December 2018 and one of which was completed in March 2019. These reductions were partially offset by SPN-812 manufacturing costs in support of the Company’s NDA submission.
Selling, general and administrative (SG&A) expenses in the third quarter of 2019 were $40.6 million, essentially unchanged from $40.9 million in the same quarter last year.
Operating Earnings and Earnings Per Share
Operating earnings in the third quarter of 2019 were $39.7 million, a 5.9% increase from $37.5 million in the same quarter last year. The increase in operating earnings was primarily due to lower R&D expenses in the third quarter of 2019.
Net earnings (GAAP) in the third quarter of 2019 were $28.9 million, or $0.54 per diluted share, compared to $28.0 million, or $0.52 per diluted share, in the same period last year. Growth in operating earnings was offset by a modestly higher effective tax rate in the third quarter of 2019 compared to the year earlier period (27.1% compared to 23.0%), resulting in net earnings in the third quarter of 2019 that were comparable to net earnings in third quarter 2018.

Weighted-average diluted common shares outstanding were approximately 53.8 million in the third quarter of 2019, as compared to approximately 54.2 million in the prior year period.

Balance Sheet Highlights
As of September 30, 2019, the Company had $893.1 million in cash, cash equivalents, marketable securities and long term marketable securities, compared to $774.8 million at December 31, 2018. This increase primarily reflects cash generated from operations in the first nine months of 2019.

Financial Guidance
The Company is revising its full year 2019 guidance for net product sales, R&D expenses and operating earnings, and reaffirming expectations for the effective tax rate as set forth below:

Net product sales in the range of $390 million to $395 million, compared to the previously expected range of $400 million to $410 million.

R&D expenses of approximately $70 million, compared to the previously expected range of $70 million to $80 million.

Operating earnings in the range of $150 million to $155 million, compared to the previously expected range of $150 million to $160 million.

Effective tax rate of approximately 23% to 25%.

Looking forward to 2020, the Company expects that the combined impact of product unit volume growth and price increases will be offset by continued pressure on gross-to-net sales deductions. In addition, the Company expects to launch SPN-812 in the second half of 2020. As such, the Company expects SG&A expenses to exceed $200 million for 2020, driven by pre-launch and launch marketing expenses, as well as the impact of fielding the psychiatry sales force in the second half of the year. Finally, R&D expenses are expected to be comparable to 2019.
Conference Call Details
The Company will hold a conference call hosted by Jack Khattar, President and Chief Executive Officer, and Greg Patrick, Senior Vice President and Chief Financial Officer, to discuss these results at 9:00 a.m. Eastern Time, on Wednesday, November 6, 2019.
Please refer to the information below for conference call dial-in information and webcast registration. Callers should dial in approximately 10 minutes prior to the start of the call.
Conference dial-in:
(877) 288-1043
International dial-in:
(970) 315-0267
Conference ID:
8278897
Conference Call Name:
Supernus Pharmaceuticals Third Quarter 2019 Earnings Conference Call

Following the live call, a replay will be available on the Company’s website, www.supernus.com, under "Investor Relations".