On November 3, 2016 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported recent progress of the Company’s clinical-stage programs and reported financial results for the third quarter of 2016 (Press release, Epizyme, NOV 3, 2016, View Source [SID1234516187]).

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"Throughout 2016, we have made substantial progress toward achieving our vision, which includes advancing the clinical development of tazemetostat and expanding its therapeutic benefit into new indications and treatment settings," said Robert Bazemore, President and Chief Executive Officer, Epizyme. "We are executing on a broad clinical program for tazemetostat based on its early clinical activity and safety profile, and guided by strong scientific rationale. We expect 2017 to be an important year for Epizyme, led by data from the Phase 2 studies in non-Hodgkin lymphoma and genetically defined solid tumors in the first half of the year, and determination of our potential registration pathways beginning mid-year."

Execution of Clinical Programs

Enrollment in Phase 2 Programs in NHL and Solid Tumors Progressing: The Company’s Phase 2 studies of tazemetostat in non-Hodgkin lymphoma (NHL) and genetically defined solid tumors are progressing and continue to enroll patients. Epizyme plans to report efficacy, safety and biomarker data from both studies in the first half of 2017. The Company is also preparing for intended regulatory engagement, beginning first with the United States Food and Drug Administration (FDA) in mid-2017 to determine potential registration paths for its genetically defined solid tumor program in adult patients. In addition, Epizyme is preparing for FDA engagement on its NHL program, also in 2017, to determine potential registration paths in various subtypes of NHL.
Immuno-oncology Combination Study Initiated: The Phase 1b study is evaluating tazemetostat in combination with Tecentriq (atezolizumab), in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Tecentriq is the first and only anti-PD-L1 cancer immunotherapy approved by FDA. This study is being conducted by Genentech, a member of the Roche Group, under Epizyme’s collaboration agreement with Roche.
Front-line Combination Study Initiated: The first study of tazemetostat in the front-line treatment setting has been initiated. The Phase 1b/2 study is evaluating tazemetostat in combination with R-CHOP, a chemotherapy regimen, as a first-line treatment for newly diagnosed elderly, high-risk patients with DLBCL. This study is being conducted under the Company’s collaboration with the Lymphoma Study Association.
Mesothelioma Study Initiated: Patient enrollment is underway in Epizyme’s global Phase 2 study evaluating tazemetostat for the treatment of adults with mesothelioma characterized by BAP1 loss-of-function. This study marks the expansion of tazemetostat development as a monotherapy into a new cancer indication.
CRADAs Established with NCI on Tazemetostat and Pinometostat: Epizyme recently entered into separate Cooperative Research and Development Agreements (CRADAs) with the National Cancer Institute (NCI) to evaluate tazemetostat in clinical trials in multiple cancer indications and to evaluate Epizyme’s novel DOT1L inhibitor, pinometostat, in multiple combination regimens. These CRADAs further expand the clinical evaluation of tazemetostat in both adults and children, while also exploring the potential for pinometostat as a combination therapy for certain kinds of acute leukemia.
Collaboration Established with Foundation Medicine: Epizyme entered into a collaboration agreement with Foundation Medicine, Inc. to support patient identification and enrollment for Epizyme’s ongoing Phase 2 clinical trial of tazemetostat in patients with NHL. Foundation Medicine’s SmartTrials Precision Enrollment Program and FoundationOne Heme panel will assist in identifying a population of individuals with NHL who harbor EZH2 mutations, which constitute specific cohorts in the Epizyme trial.
Strengthening of Epizyme Team

The Company made two, recent key hires to prepare for the intended regulatory engagement and determination of potential registration pathways in 2017. Pamela Strode was appointed to the position of Vice President of Regulatory Affairs and Quality Assurance, and Ray Mankoski, M.D., Ph.D. was appointed as Vice President of Medical Affairs.
Third Quarter 2016 Financial Results and Guidance

Cash Position: Cash, cash equivalents and marketable securities were $263.3 million as of September 30, 2016, as compared to $208.3 million as of December 31, 2015.
Revenue: Collaboration revenue was $6.6 million and $7.5 million for the three and nine months ended September 30, 2016, respectively, compared to $0.4 million and $2.0 million for the three and nine months ended September 30, 2015, respectively. The increase was driven predominantly by the recognition of the $6.0 million milestone earned upon GlaxoSmithKline’s (GSK) initiation of patient dosing in a Phase 1 clinical trial of GSK3326595, a PRMT5 inhibitor invented by Epizyme and licensed to GSK. GSK holds worldwide rights to the compound, and Epizyme may receive significant additional payments from GSK if future milestones are met for the program, plus up to double digit royalties on worldwide net sales should this product candidate progress through the clinic to commercialization.
R&D Expenses: Research and development (R&D) expenses were $23.9 million and $63.1 million for the three and nine months ended September 30, 2016, respectively, compared to $16.8 million and $94.4 million for the three and nine months ended September 30, 2015, respectively. The increase in R&D expenses for the three months ended September 30, 2016, is primarily due to the expansion of the tazemetostat clinical development program, increased spending on tazemetostat preclinical activities, and increased discovery and spending on high-priority, earlier-stage programs. The period-over-period decrease from the nine months ended September 30, 2015 was driven by the inclusion of the $40.0 million payment to Eisai for the reacquisition of the tazemetostat worldwide rights, excluding Japan, in R&D expenses in the first quarter of 2015. The Company expects that research and development expenses will continue to increase in the fourth quarter of 2016.
G&A Expenses: General and administrative (G&A) expenses were $7.5 million and $20.8 million for the three and nine months ended September 30, 2016, respectively, as compared to $6.7 million and $17.9 million for the three and nine months ended September 30, 2015, respectively. The increase is primarily due to the staffing of key leadership roles in the first half of 2016. G&A expenses were flat compared to the second quarter of 2016, and we expect G&A expenses to remain relatively constant through the fourth quarter of 2016.
Net Loss: Net loss was $24.3 million and $75.2 million for the three and nine months ended September 30, 2016, respectively, compared to a net loss of $23.1 million and $110.2 million for the three and nine months ended September 30, 2015, respectively.
Financial Guidance: Epizyme reiterates its belief that its cash, cash equivalents and marketable securities of $263.3 million as of September 30, 2016 will be sufficient to fund the Company’s planned operations into at least the second quarter of 2018.

On November 3, 2016 AMAG Pharmaceuticals, Inc. (NASDAQ: AMAG) reported unaudited consolidated financial results for the third quarter ended September 30, 2016. Total revenue for the third quarter of 2016 increased approximately 50% to $143.8 million (Filing, Q3, AMAG Pharmaceuticals, 2016, NOV 3, 2016, View Source [SID1234516181]). This increase was driven by record sales of Makena and the recognition of a full quarter of revenue from Cord Blood Registry (CBR), which was acquired by AMAG on August 17, 2015. The company reported third quarter 2016 operating income of $38.8 million and net income of $16.2 million. Non-GAAP adjusted EBITDA for the third quarter of 2016 increased to $76.2 million1, or 44%, versus the same period in 2015. Non-GAAP net income for the third quarter of 2016 increased to $61.8 million1, or 46%, versus the same period in 2015.

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"We executed well against our key priorities in the third quarter, delivering strong financial results and hitting key milestones in our next-generation development programs," stated William Heiden, AMAG’s chief executive officer. "Our Makena subcutaneous auto-injector program is on-track for an sNDA filing in the second quarter of next year and the Feraheme sNDA submission seeking approval of a broader label has been accelerated to mid-year 2017."

"We have updated the company’s financial guidance based on our fourth quarter expectations of continued strong top and bottom line performance, building on our successes achieved in the third quarter," Mr. Heiden continued.

Third Quarter 2016 and Recent Business Highlights
• Delivered total revenue of $143.8 million in the third quarter of 2016, compared with $96.2 million in the same period last year. This increase of approximately 50% was driven by record sales of Makena and the recognition of a full quarter of revenue from CBR.
• Achieved Makena sales of $93.4 million in the third quarter of 2016, compared with $65.2 million in the same period last year. Makena’s robust sales growth of 43% was driven exclusively by an increase in volume. This growth resulted in Makena market share of 41%, four percentage points over the second quarter of 2016 and an 11 percentage point gain year-to-date.
• Generated 1.8% growth to $29.9 million1 in non-GAAP revenue from CBR over the second quarter of 2016 due to improved net revenue per new customer. In addition, enrollments were higher versus the second quarter of 2016.
• Reported $22.3 million in Feraheme sales, maintaining market share in the intravenous iron market, which experienced a slight decline in the third quarter of 2016.

See summaries of GAAP to non-GAAP adjustments at the conclusion of this press release.

• Achieved key milestones in the Makena subcutaneous auto-injector development program. The company dosed first subjects in both the definitive pharmacokinetic study and comparative pain study. Data from each of these studies is intended to support the supplemental new drug application (sNDA) that the company plans to file with the Food and Drug Administration (FDA) in the second quarter of 2017.
• Continued to enroll patients more rapidly than expected in the company’s head-to-head, Phase 3 clinical trial evaluating Feraheme in adults with iron deficiency anemia (IDA). The company is seeking to broaden Feraheme’s current label beyond its chronic kidney disease (CKD) indication to include all adult IDA patients who have failed or cannot tolerate oral iron treatment. The timeline to anticipated approval has been shortened by approximately six months as a result of the trial’s rapid enrollment, which has accelerated the company’s expected sNDA submission date to mid-2017.
• Generated an increase of $147.7 million in cash and investments in the first nine months of 2016 to $614.1 million, net of $20.0 million utilized to repurchase the company’s common stock and $13.1 million to repay debt.

Third Quarter Ended September 30, 2016 (unaudited)
Financial Results (GAAP Basis)
Total revenues for the third quarter of 2016 were $143.8 million, compared with $96.2 million in the third quarter of 2015. This increase is related to record sales of Makena and the recognition of a full quarter of revenue from CBR, which was acquired by AMAG on August 17, 2015. Net product sales of Makena increased to $93.4 million in the third quarter of 2016, compared with $65.2 million in the same period last year. This 43% growth in Makena sales was primarily driven by the successful launch of the single-dose, preservative-free formulation and strong growth in the company’s Makena @Home program. Sales of Feraheme and MuGard totaled $22.4 million in the third quarter of 2016, compared with $23.8 million in the third quarter of 2015. Service revenue from CBR totaled $28.0 million in the third quarter of 2016, as compared to $7.2 million in the third quarter of 2015.

Total costs and expenses, including costs of product sales and services, totaled $105.0 million for the third quarter of 2016, compared with $97.5 million for the same period in 2015. The increase in operating expenses in 2016 was related to: (i) higher research and development expenses for the company’s next generation development programs, (ii) higher selling, general and administrative expenses due to the recognition of a full quarter of CBR-related expenses, and (iii) higher non-cash amortization of the Makena intangible asset. These increases were partially offset by expenses in the third quarter of 2015 that did not recur in 2016 related to an upfront payment for AMAG’s exclusive option to acquire rights to a development stage asset to treat severe preeclampsia (Velo) and CBR-related acquisition costs.

Third quarter 2016 operating income totaled $38.8 million, compared with a $1.4 million loss in the third quarter of last year. The company reported net income of $16.2 million, or $0.47 per basic share and $0.43 per diluted share, for the third quarter of 2016, compared with a net loss of $20.6 million, or $0.62 per basic and diluted share, for the same period in 2015.

Balance Sheet Highlights
The company’s cash, cash equivalents and investments increased by $147.7 million in the first nine months of 2016 to approximately $614.1 million, net of $20.0 million utilized to repurchase the company’s common stock and $13.1 million to repay debt. Total debt (principal amount outstanding), including $200 million of convertible debt, was approximately $1.03 billion as of September 30, 2016. For the 12 months ended September 30, 2016, sales of Makena exceeded $300 million, triggering a $100 million milestone that will be paid to former Lumara Health shareholders in the fourth quarter of 2016.

"In the third quarter, we once again generated strong cash flow as a result of our solid commercial execution and operating discipline," stated Ted Myles, chief financial officer of AMAG. "We are now in an even better position to capitalize on acquisition or licensing opportunities that would diversify and expand our product portfolio."
Financial Results (Non-GAAP Basis)1,2
Non-GAAP revenues totaled $145.8 million in the third quarter of 2016, up from $103.5 million in the third quarter of 2015. Non-GAAP CBR revenue totaled $29.9 million in the third quarter of 2016, compared with $14.5 million in the same period in 2015. CBR’s financial results for the third quarter of 2015 include only a portion of the quarter, as AMAG purchased CBR on August 17, 2015. The difference between GAAP and non-GAAP revenue for the quarter represents purchase accounting adjustments related to CBR deferred revenue.

Total non-GAAP costs and expenses, including costs of product sales and services, totaled $69.6 million in the third quarter of 2016, compared with total non-GAAP costs and expenses of $50.6 million in the same period in 2015. Non-GAAP adjusted EBITDA for the third quarter of 2016 was $76.2 million, compared with $52.8 million for the same period in 2015.

The company generated third quarter 2016 non-GAAP net income of $61.8 million, or $1.81 per non-GAAP basic share and $1.78 per non-GAAP diluted share. In the third quarter of 2015, non-GAAP net income totaled $42.3 million, or $1.27 per non-GAAP basic share and $1.02 per non-GAAP diluted share. Non-GAAP diluted shares for the third quarter of 2016 do not include 7.4 million of potentially dilutive shares from the convertible notes, as the stock price was below the convertible notes’ exercise price.

Updated 2016 Financial Guidance Range3

2016 GAAP Guidance

2016 Non-GAAP Guidance
$ in millions

Previous
Updated

Previous
Updated
Makena sales

$310 – $340
$330 – $340

$310 – $340
$330 – $340
Feraheme and MuGard sales

$95 – $105
$95 – $105

$95 – $105
$95 – $105
CBR revenue

$98 – $108
$98 – $108

$115 – $125
$115 – $125
Total revenue

$503 – $553
$523 – $553

$520 – $570
$540 – $570

Net income

$0 – $30
$3 – $23

$195 – $225
$200 – $220
Operating income

$93 – $123
$98 – $118

N/A
N/A
Adjusted EBITDA

N/A
N/A

$255 – $285
$260 – $280

On November 3, 2016 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported business highlights and financial results for the third quarter ended September 30, 2016 (Filing, Q3, Agios Pharmaceuticals, 2016, NOV 3, 2016, View Source [SID1234516180]).

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"We have made significant progress during 2016, establishing proof of concept with our lead pyruvate kinase-R (PKR) activator, executing late-stage clinical development for both of our lead isocitrate dehydrogenase (IDH) mutant inhibitors in hematologic malignancies and strengthening our balance sheet through our recent financing," said David Schenkein, M.D., chief executive officer at Agios. "As we head into year end, we are focused on supporting the enasidenib NDA submission with our partner Celgene and planning for our next steps in clinical development for our PKR and IDH portfolios based on data we will present at a number of upcoming medical meetings this quarter."

THIRD QUARTER 2016 HIGHLIGHTS & UPDATES
IDH Mutant Inhibitors in Hematologic Malignancies:
In September, Agios and Celgene announced plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration for enasidenib (AG-221) in relapsed and/or refractory (R/R) acute myeloid leukemia (AML) with an IDH2 mutation by year-end. The NDA will be based on data from an ongoing Phase 1/2 trial in patients with relapsed and/or refractory AML and other advanced hematologic malignancies with an IDH2 mutation.

Agios plans to explore a similar regulatory path for AG-120, its wholly owned, first-in-class, oral, potent inhibitor of mutant IDH1, which could lead to a NDA submission in 2017 in the U.S.

Corporate:
In September, Agios completed an underwritten public offering of common stock for 3,876,403 shares at the offering price of $44.50 per share, resulting in gross proceeds of approximately $173 million.

Agios recently announced the appointment of Andrew Hirsch to chief financial officer. Mr. Hirsch has more than 20 years of experience in a range of strategic and operating roles. He most recently served as president and chief executive officer of BIND Therapeutics. Prior to joining BIND, he was chief financial officer at Avila Therapeutics until its acquisition by Celgene and held roles of increasing responsibility during his nearly 10-year tenure at Biogen.

UPCOMING MEDICAL MEETING PRESENTATIONS

• First data from the expansion phase of the ongoing Phase 1 study of AG-120 in advanced IDH1 mutant positive chondrosarcoma at the Connective Tissue Oncology Society (CTOS) Annual Meeting on November 10, 2016 in Lisbon, Portugal.

• Preliminary data from the expansion phase of the ongoing Phase 1 study of AG-120 in advanced IDH1 mutant positive low-grade glioma at the Society for NeuroOncology (SNO) Annual Meeting on November 18, 2016 in Scottsdale, AZ.

• Updated data from the AG-348 Phase 2 DRIVE-PK study, the AG-519 Phase 1 healthy volunteer study, the Natural History Study of pyruvate kinase deficiency (PKD), and new AG-348 metabolic data in PKD patients at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 3-6, 2016 in San Diego, CA.

• Updated follow-up and molecular data from the completed dose escalation portion of the AG-120 Phase 1 study in R/R AML at ASH (Free ASH Whitepaper).

ADDITIONAL 2016 EXPECTED MILESTONES
IDH Mutant Inhibitors in Hematologic Malignancies:

• Complete enrollment of the 125-patient expansion cohort for the Phase 1 study of AG-120 in patients with R/R AML
IDH Mutant Inhibitors in Solid Tumors:

• Initiate a randomized study of AG-120 in IDH1 mutant positive cholangiocarcinoma

Cancer Metabolism Research:

• Initiate preclinical development activities for the first molecule in a program focused on MTAP (methylthioadenosine phosphorylase) deleted cancers
Rare Genetic Metabolic Disorders:

• Provide a development strategy update for our PKR activator program, including molecule selection

• Outline the clinical development plans for our PKR activators in beta-thalassemia

THIRD QUARTER 2016 FINANCIAL RESULTS
Cash, cash equivalents and marketable securities as of September 30, 2016 were $622.6 million, compared to $375.9 million as of December 31, 2015. The increase in cash was driven by cash received from Celgene totaling $251.5 million, which includes a $200 million upfront payment from the May 2016 collaboration agreement, $25 million related to initiation of the enasidenib Phase 3 IDHENTIFY study and $26.5 million of program funding related to our collaboration agreements, and net proceeds of $162.1 million received from the company’s September 2016 public offering. These items were offset by a decrease in cash related to expenditures to fund operating activities of $161.7 million and purchases of fixed assets, net of reimbursements, of $4.3 million during the nine months ended September 30, 2016.

Collaboration revenue was $9.0 million for the quarter ended September 30, 2016, compared to $5.5 million for the comparable period in 2015.

Research and development (R&D) expense was $60.6 million, including $7.9 million of stock-based compensation expense, for the quarter ended September 30, 2016, compared to $36.0 million, including $4.9 million in stock-based compensation expense, for the quarter ended September 30, 2015. The increase in R&D expense was primarily due to increased costs to support advancement of the company’s lead investigational medicines toward later-stage development. Celgene is responsible for all development costs for enasidenib and certain development costs for AG-881 and reimburses the company for development costs incurred for these investigational medicines.

General and administrative (G&A) expense was $11.9 million, including $4.2 million of stock-based compensation expense, for the quarter ended September 30, 2016, compared to $9.9 million, including $4.5 million of stock-based compensation expense, for the quarter ended September 30, 2015. The increase in G&A expense was largely due to increased headcount and other professional expenses to support growing operations.

Net loss for the quarter ended September 30, 2016 was $62.8 million, compared to a net loss of $40.3 million for the comparable period in 2015.

UPDATED FINANCIAL GUIDANCE FOR THE FULL YEAR 2016
As a result of the recent financing, Agios now expects to end 2016 with more than $550 million of cash, cash equivalents and marketable securities. The anticipated year-end 2016 cash position does not include any additional program-specific milestone payments from Celgene. Based on its current operating plans, the company expects that its existing cash, cash equivalents and marketable securities as of September 30, 2016, together with anticipated interest income, and anticipated expense reimbursements under our collaboration agreements with Celgene, but excluding any additional program-specific milestone payments from Celgene, will enable the company to fund its anticipated operating expenses and capital expenditure requirements through at least the end of 2018.