On May 4, 2017 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX) reported financial results and provided a business update for the first quarter of 2017 (Press release, Progenics Pharmaceuticals, MAY 4, 2017, View Source [SID1234518857]).

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"This first quarter of 2017 was marked by major developments within our clinical pipeline, particularly the announcement of positive topline data from our registrational Phase 2b study of AZEDRA for the treatment of pheochromocytoma and paraganglioma," said Mark Baker, Chief Executive Officer of Progenics. "The study not only achieved its primary endpoint by a significant margin, but also showed that treatment with AZEDRA resulted in favorable anti-tumor activity, a key secondary endpoint. We are now working diligently to complete our New Drug Application for this important new therapy, which we remain on track to submit by the middle of this year."

Mr. Baker continued, "With our portfolio of PSMA-targeted therapeutics and imaging agents, we continue to leverage our Find Fight and Follow strategy that provides us with multiple opportunities to improve the lives of patients who have or are at risk of developing prostate cancer. During the quarter, we continued to advance clinical trials of our three prostate cancer theranostic candidates, 1404, PyL, and 1095, reported positive data regarding our Automated Bone Scan Index (aBSI), and look forward to providing further updates on our progress throughout the year."

First Quarter and Recent Key Business Highlights

AZEDRA, Ultra-orphan radiotherapeutic candidate

Positive Topline Results for AZEDRA Announced in the First Quarter 2017. In March 2017, Progenics reported positive topline data from its Phase 2b registrational trial of AZEDRA for the treatment of rare and difficult-to-treat neuroendocrine tumors, pheochromocytoma and paraganglioma. The primary endpoint evaluated a proportion of patients who achieved a 50% or greater reduction in all antihypertensive medication for at least six months. Under the study protocol agreed to with the U.S. Food and Drug Administration (FDA), the primary endpoint was to be achieved if the lower limit of the two-sided 95% confidence interval was above 10%. In order to achieve this primary endpoint, a minimum of 12 of the total 68 evaluable patients must have a 50% or greater reduction of all antihypertensive medication for at least 6 months.

The trial met the primary endpoint with 17 of the 68 evaluable patients experiencing at least a 50% reduction in all antihypertensive medication for at least six months, with a 95% confidence interval lower limit of 16.15%. In addition, favorable data was reported for a key secondary endpoint, the proportion of patients with overall tumor response as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Of the 64 RECIST evaluable patients, 92.2% of patients showed a best response of partial response or stable disease.

AZEDRA was generally well tolerated. The most common treatment emergent adverse events were nausea, thrombocytopenia, anemia, fatigue, leukopenia, and neutropenia. These events are consistent with those observed in prior AZEDRA studies.

Based on these data, the Company has already submitted non-clinical sections of the New Drug Application to the FDA and expects to complete the submission by mid-2017.
PSMA-Targeted Prostate Cancer Pipeline

Data Presentations Highlighting Utility of Automated Bone Scan Index (aBSI). In February 2017, data was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO GU) Meeting demonstrating the utility of Progenics’ aBSI to quantitatively assess total tumor burden during the course of disease progression as called for by the Prostate Cancer Working Group (PCWG). The data will also be presented at the upcoming ASCO (Free ASCO Whitepaper) 2017 meeting. Also at ASCO (Free ASCO Whitepaper), a prognostic analysis of aBSI in men with metastatic castration-resistant prostate cancer (mCRPC) using data from a Phase 3 trial of a prostate cancer therapeutic will be discussed in an oral presentation.

Phase 3 Study of 1404 Remains On-Track; Phase 2 Data Published in the Journal of Nuclear Medicine. Progenics continues to enroll patients in a Phase 3 study of 1404. The trial is designed to evaluate the specificity of the imaging agent in identifying patients without clinically significant prostate cancer as well as its sensitivity to identify patients with clinically significant disease, and will include approximately 450 patients. Progenics still expects to complete enrollment by the end of 2017.

In March 2017, data from a Phase 2 study of 1404 were published in the online edition of the Journal of Nuclear Medicine. The data reviewed previously reported results demonstrating the sensitivity of 1404 to detect prostate cancer, potentially enabling better assessment of the stage and extent of a patient’s prostate cancer versus biopsy.
Advancing Phase 2/3 Study of PyL. Progenics’ study evaluating the diagnostic accuracy of PyL PET/CT imaging in patients with metastatic prostate cancer continues to enroll patients. The Phase 2/3 study will enroll approximately 300 patients with recurrent and/or metastatic prostate cancer in the United States and Canada.

Initiated Phase 1 Trial of 1095. Dosing has commenced in the Phase 1 open-label dose escalation study of 1095. The study, which is being conducted at Memorial Sloan Kettering, is expected to enroll approximately 30 patients with mCRPC who have demonstrated tumor avidity to 1095. The study’s primary objectives are to determine the maximum tolerated dose, safety and tolerability, biodistribution, and efficacy.
RELISTOR, treatment for opioid-induced constipation (partnered with Valeant Pharmaceuticals International, Inc.)

First Quarter 2017 RELISTOR Net Sales of $14.1 Million. The first quarter 2017 sales, as reported to Progenics by its partner Valeant, translated to $2.1 million in royalty revenue for Progenics for the quarter.
First Quarter 2017 Financial Results

First quarter revenue totaled $2.3 million, down from $2.5 million in the first quarter of 2016, reflecting RELISTOR royalty income of $2.1 million compared to $2.2 million in the corresponding period of 2016.

First quarter research and development expenses increased by $0.9 million compared to the corresponding prior year period, resulting primarily from higher clinical trial and contract manufacturing expenses for PyL, partially offset by lower compensation expenses. First quarter general and administrative expenses decreased by $0.1 million compared to the corresponding prior year period, primarily attributable to lower depreciation and compensation expenses, partially offset by higher costs associated with pre-launch activities for AZEDRA. Progenics also recorded a non-cash charge of $1.9 million in the first quarter related to an increase in the fair value estimate of the contingent consideration liability primarily resulting from an increase in the probability of success of AZEDRA used to calculate the potential milestone payments to former Molecular Insight Pharmaceuticals, Inc. stockholders. For the three months ended March 31, 2017, Progenics recognized interest expense, including amortization of the debt discount, related to the RELISTOR royalty-backed loan, of $1.3 million.

Net loss attributable to Progenics for the quarter was $16.4 million or $0.23 per diluted share, compared to a net loss of $12.7 million or $0.18 per diluted share in the corresponding 2016 period. Progenics ended the quarter with cash and cash equivalents of $126.3 million, a decrease of $12.6 million compared to cash and cash equivalents as of December 31, 2016.

MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported financial results for its third quarter ended March 31, 2017 (Press release, MEI Pharma, MAY 4, 2017, View Source [SID1234518852]). The Company also outlined a number of key upcoming milestones.

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"I am proud of the progress we have made over the past quarter, with a steadfast focus on clinical study planning and execution, while maintaining a healthy cash position," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "We have been working diligently with our partners at Helsinn on the design and implementation of a large, international Phase 3 study of Pracinostat in acute myeloid leukemia (AML) and a Phase 2 dose-optimization study in myelodysplastic syndrome (MDS), and expect to enroll the first patients next month. We also look forward to presenting new genetic analysis data from our Phase 2 study in AML at ASCO (Free ASCO Whitepaper), which increases our understanding of the study’s patient demographics.

"Finally," Dr. Gold continued, "we look forward to initial safety and efficacy data from our clinical study of ME-401 in relapsed/refractory chronic lymphocytic leukemia (CLL) and follicular lymphoma next month. ME-401 is a differentiated oral PI3K delta inhibitor that is predicted to have a wide therapeutic window which may lead to safer treatment options for patients with lymphomas. We are very encouraged by the early results from our ongoing study and look forward to presenting them in more detail. While much of our recent progress has occurred behind the scenes, the stage is now set for what should be an exciting remainder of the year."

Upcoming Milestones

Initiation of global Phase 3 study of Pracinostat in AML. In August 2016, the Company entered into an exclusive license, development and commercialization agreement with Helsinn Healthcare SA, a Swiss pharmaceutical company, for the investigational drug candidate Pracinostat in AML and other potential indications (Helsinn License Agreement). Under the terms of the agreement, Helsinn is granted a worldwide exclusive license to develop, manufacture and commercialize Pracinostat, and is primarily responsible for funding its global development and commercialization. Site recruitment for the Phase 3 study of Pracinostat and azacitidine in newly diagnosed AML patients who are ≥75 years of age or unfit for intensive induction chemotherapy is ongoing.
First patient in Phase 2 dose-optimization study of Pracinostat in MDS. As part of the Helsinn License Agreement, the Company will work with Helsinn to determine an optimal dosing regimen of Pracinostat in combination with azacitidine for the treatment of high and very high risk MDS. The cost of this study will be shared by Helsinn and the Company, and enrollment is anticipated to commence in June 2017.
Gene mutation data from Phase 2 study of Pracinostat in AML at ASCO (Free ASCO Whitepaper). Data from a post hoc analysis of a Phase 2 clinical study of Pracinostat and azacitidine in elderly patients with AML who were not eligible for induction chemotherapy were accepted for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on Monday, June 5, 2017. The abstract, entitled "Correlation between Mutation Clearance and Clinical Response in Elderly Patients with Acute Myeloid Leukemia (AML) Treated with Azacitidine and Pracinostat," will be released on abstracts.asco.org at 5:00 pm EDT on May 17, 2017.
Interim data from Phase 1b study of ME-401 in CLL and follicular lymphoma. Interim safety and efficacy data from the first cohort in a Phase 1b clinical study of ME-401 in patients with relapsed/refractory CLL or follicular lymphoma are expected in June. ME-401 is a highly differentiated oral PI3K delta inhibitor that has a distinct chemical structure from other drugs in its class, including idelalisib (marketed as Zydelig). Results from a first-in-human study of ME-401 showed levels of drug exposure that support the potential for an improved therapeutic window compared to idelalisib, with a half-life that supports once-daily dosing.
Financial Highlights

In March 2017, the Company received a $5 million payment from Helsinn in accordance with the Helsinn License Agreement. The Company is also eligible to receive up to $444 million in potential regulatory and sales-based milestones, along with royalty payments on the net sales of Pracinostat.
As of March 31, 2017, the Company had $56.8 million in cash, cash equivalents and short-term investments, compared to $55.2 million as of December 31, 2016, with no outstanding debt. The Company believes its cash position will be sufficient to fund operations through at least the end of calendar year 2018.
Research and development expenses were $1.9 million for the three months ended March 31, 2017, and $5.2 million for the nine months ended March 31, 2017. This compares with research and development expenses of $3.4 million for the three months ended March 31, 2016, and $9.4 million for the nine months ended March 31, 2016. The decrease was primarily due to a reduction in expenses related to Pracinostat pursuant to the Helsinn License Agreement.
General and administrative expenses were $2.2 million for the three months ended March 31, 2017, and $6.8 million for the nine months ended March 31, 2017, compared to $2.0 million and $5.8 million, respectively, for the same periods in 2016. The increase was primarily due to professional service costs.
Revenues were $4.5 million during the three months ended March 31, 2017, and $22.8 million during the nine months ended March 31, 2017, related to the Helsinn License Agreement. During the three and nine months ended March 31, 2017, the cost of research and development revenue was $1.1 million and $4.0 million, respectively. Cost of research and development revenue is comprised primarily of reimbursable third-party pass-through costs.
Net loss was $0.6 million, or $0.02 per share, for the three months ended March 31, 2017, compared to $5.4 million, or $0.16 per share, for the quarter ended March 31, 2016. Net income was $7.0 million, or $0.19 per share, for the nine months ended March 31, 2017, compared to a net loss of $15.1 million, or $0.44 per share for the same period in 2016.

On May 4, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported financial results for the first quarter 2017 and commented on recent accomplishments and clinical development plans for its lead, novel, oral Selective Inhibitor of Nuclear Export (SINE) compound selinexor (KPT-330), and other pipeline assets verdinexor (KPT-335), and KPT-9274, its oral, dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT) (Press release, Karyopharm, MAY 4, 2017, View Source [SID1234518847]).

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"It’s been a highly active early 2017 for Karyopharm, marked most notably by establishment of a planned approval path for selinexor in relapsed or refractory diffuse large B-cell lymphoma (DLBCL), our second lead indication after multiple myeloma (MM), following the presentation of robust interim data from the Phase 2b SADAL study at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2017 Annual Meeting," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "After the observation of a 28.6% overall response rate (ORR) with over 7 months median duration of response (DOR), we consulted with the U.S. Food and Drug Administration (FDA) and obtained their agreement to amend the SADAL study to focus solely on the 60mg twice weekly treatment cohort, in which we plan to enroll up to 90 more patients. Assuming we continue to see the response rate and durability observed to date, we plan to use the data from the SADAL study to support a request for accelerated approval in DLBCL. Looking ahead, we remain focused on the initiation of the pivotal Phase 3 BOSTON study where we will evaluate selinexor in combination with Velcade (bortezomib) and dexamethasone in patients with myeloma previously treated with one to three regimens, moving selinexor into much earlier lines of treatment."

Dr. Kauffman continued, "Importantly, during April 2017, we strengthened our balance sheet by raising net proceeds of approximately $52.2 million in equity financings, including approximately $37.8 million in an underwritten public offering and $14.5 million through our at-the-market (ATM) offering program. We plan to use these funds to support the continued clinical development of selinexor in our lead indications, including in multiple myeloma, DLBCL and other oncology indications, with a focus on filing for accelerated approvals for both myeloma and DLBCL during 2018. In addition, we expect this capital will fund our operations into 2019, while we are preparing to establish a commercial infrastructure for the potential launch of selinexor in North America and Western Europe."

First Quarter 2017 and Recent Events, Highlights and Milestones:

Selinexor in Multiple Myeloma (MM)

Upcoming Initiation of Pivotal Phase 3 BOSTON Study. Based on the strong combination data recently reported from the Phase 1b STOMP study, Karyopharm plans to initiate a pivotal randomized Phase 3 study, known as the BOSTON (Bortezomib, Selinexor and dexamethasone) study, which will evaluate selinexor in combination with Velcade and dexamethasone (SVd), compared to Velcade and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy. The BOSTON study is expected to enroll approximately 360 patients and commence in May 2017.
Ongoing Phase 2b STORM Study Expansion in Patients with Penta-refractory MM. The Company has expanded the Phase 2b STORM study, which is expected to include 122 additional patients with penta-refractory MM, a growing unmet medical need in which there are no approved therapies available. Karyopharm expects to report top-line data from the expanded cohort in early 2018, and, assuming a positive outcome, intends to use the expanded STORM study data to support a request for accelerated approval for selinexor in MM.
Completed Enrollment in Phase 1b/2 STOMP Arm Evaluating Selinexor in Combination with Velcade. In February 2017, Karyopharm completed enrollment in the Phase 1b/2 STOMP arm designed to evaluate selinexor in combination with the proteasome inhibitor Velcade and low-dose dexamethasone (SVd) in heavily pretreated patients with MM. The SVd arm of the STOMP study enrolled 42 patients and the Company expects to report updated data toward the end of 2017.
Upcoming Initiation of New Phase 1b/2 STOMP Expansion Arm Evaluating Selinexor in Combination with Darzalex (daratumumab). Karyopharm expects to dose the first patient in a new Phase 1b/2 STOMP expansion arm designed to evaluate selinexor in combination with the anti-CD38 monoclonal antibody Darzalex and low-dose dexamethasone (SDd) in heavily pretreated patients with MM. The SDd arm of the STOMP study is expected to enroll approximately 44 patients and the Company expects to report top-line data in late 2017 or early 2018.
Presented an Overview of Clinical Data Demonstrating Selinexor Activity in Combination with Proteasome Inhibitors and Immunomodulatory Agents. In an oral presentation at the International Myeloma Workshop 2017 annual meeting held March 1-4, 2017 in New Delhi, India, Karyopharm researchers presented an overview of clinical data demonstrating selinexor’s activity in combination with proteasome inhibitors and immunomodulatory drugs for the treatment of relapsed or refractory MM.
Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)

Top-line Data from Phase 2b SADAL Study in DLBCL Presented in a Late-Breaking Poster at AACR (Free AACR Whitepaper) 2017. At the April AACR (Free AACR Whitepaper) 2017 Annual Meeting, a late-breaking poster was presented that highlighted top-line data from the Company’s ongoing Phase 2b SADAL study evaluating 60mg and 100mg doses of single-agent selinexor in patients with relapsed or refractory DLBCL. The data demonstrated that selinexor achieved an ORR of 28.6% in the first 63 patients, as adjudicated by an independent central radiological committee, and a disease control rate (DCR) of 42.9%. The median overall survival (OS) was 8 months for all patients, consistent with published data in this population. As of the data cutoff date, median survival for the responders had not been reached and is over 9 months. The median DOR across all patients was greater than 7 months with most responses occurring at the first response evaluation (~2 months). As of the data cutoff date, 9 patients who responded remained on treatment, including 6 patients with a complete response (CR). Selinexor showed similar activity against GCB and non-GCB subtypes of DLBCL: Of the 32 patients with DLBCL of the GCB-subtype, selinexor achieved an ORR of 25.0% and DCR of 43.8%. Of the 31 patients with DLBCL of the non-GCB-subtype (ABC), selinexor achieved an ORR of 32.3% and DCR of 41.9%. Among the 72 patients evaluated for safety, the most common adverse events (AEs) across both dosing groups were fatigue (65%), thrombocytopenia (54%), nausea (51%), anorexia (49%), vomiting (35%) and anemia (32%), and were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care. As expected, the most common grade 3 and 4 AEs in the 60mg arm were thrombocytopenia (32%), neutropenia (16%), anemia (14%), and fatigue (11%) and were manageable with dose modifications and/or standard supportive care.
As a result of these findings, and in consultation with the FDA, Karyopharm is amending the SADAL study protocol to become a single-arm study focusing solely on single-agent selinexor dosed at 60mg twice weekly, eliminating the 100mg arm. The study is also being amended to reduce the 14-week treatment-free period to 8 weeks in patients who achieved at least a partial response (PR) on their most recent therapy. Patients whose disease was refractory or did not achieve at least a PR on their prior therapy will continue with the 14-week treatment-free period. The FDA agreed that the modification to a single-arm study was reasonable and that the proposed trial design and indication appear appropriate for accelerated approval, though eligibility for accelerated approval will depend on the complete trial results and available therapies at the time of regulatory action. The Company plans to enroll up to an additional 90 patients to the 60mg single-arm cohort and expects to report top-line results from the SADAL study in mid-2018.

Selinexor in Other Hematologic Malignancies

Announced Outcome of Phase 2 SOPRA Interim Analysis; Updated AML Development Strategy. In March 2017, Karyopharm announced the results of the planned interim analysis of the Phase 2 SOPRA study evaluating single-agent selinexor in relapsed or refractory acute myeloid leukemia (AML). In concert with the study’s independent Data Safety Monitoring Board (DSMB), the Company determined that the SOPRA study would not reach statistical significance for showing superiority of OS on selinexor versus OS on physician’s choice (PC), the study’s primary endpoint. However, the 13% of selinexor-treated patients who achieved a complete response with or without full hematologic recovery (CR/CRi) showed a substantial OS benefit as compared to PC. As a result, patients were permitted to continue on both the selinexor arm or the PC arm, as applicable, following discussion with their treating physician. Selinexor demonstrated a safety profile consistent with previous studies with similar rates of sepsis and lower rates of febrile neutropenia in the selinexor arm versus the PC arm. Karyopharm plans to continue to explore the use of selinexor in combination with novel and standard agents through investigator-sponsored AML studies.
Selinexor in Solid Tumors

Completed Enrollment in Phase 2 Portion of the Phase 2/3 SEAL Study. In March 2017, Karyopharm completed enrollment in the Phase 2 portion of the randomized Phase 2/3 SEAL study evaluating single-agent selinexor versus placebo in patients with advanced liposarcoma. Top-line data from the Phase 2 portion of this study are expected in mid-2017. The primary endpoint of the SEAL study is progression free survival (PFS) and both the trial design and endpoints have been agreed to by the FDA and the European Medicines Agency (EMA) as acceptable for approval.
Oral Presentation Highlighting Efficacy, Safety and Intratumoral Pharmacokinetic Data for Selinexor in Glioblastoma at the 2017 World Federation of Neuro-Oncology Societies (WFNOS). Clinical data from a Phase 2 study evaluating selinexor in patients with recurrent glioblastoma will be highlighted in an oral presentation on May 6, 2017 at WFNOS 2017 by Andrew Lassman, MD, Columbia University Medical Center. These data demonstrate that oral selinexor achieved responses and sufficient intratumoral penetration, with a manageable tolerability profile when accompanied by standard supportive care. Importantly, disease control rates using selinexor dosed at 80mg once weekly were as high or higher than those observed with more intensive dosing, and tolerability was improved. Accrual in this Phase 2 study utilizing once weekly dosing continues.
Verdinexor

Signed Global License Agreement with Anivive Lifesciences for Verdinexor for Animal Health Applications. Earlier this week, Karyopharm and Anivive, a privately-held biotech company, announced their entry into a licensing agreement whereby Anivive licensed from Karyopharm exclusive worldwide rights to research, develop and commercialize verdinexor for the treatment of cancer in companion animals. Under the terms of the agreement, Anivive will make a one-time upfront payment of $1 million to Karyopharm. Anivive agreed to pay up to an additional $43.5 million in certain regulatory, clinical and commercial milestones, assuming approval in both the United States (US) and the European Union (EU). In addition, Anivive agreed to pay Karyopharm a low double-digit royalty on future net sales.
KPT-9274

Preclinical Efficacy Highlighting KPT-9274’s Anti-Cancer Activity in Dogs with Spontaneous Lymphomas Presented as a Late-Breaking Poster at AACR (Free AACR Whitepaper) 2017 Annual Meeting. At the April AACR (Free AACR Whitepaper) 2017 Annual Meeting, Karyopharm collaborator Cheryl London of Tufts University presented a late-breaking poster highlighting preclinical data demonstrating the activity and synergy of KPT-9274, the Company’s oral dual inhibitor of PAK4/NAMPT, with doxorubicin to treat dogs with lymphoma. KPT-9274 is currently being evaluated in a Phase 1 safety and tolerability study in patients with advanced solid malignancies (including sarcoma, colon and lung cancer) or non-Hodgkin’s lymphoma (NHL) whose disease has relapsed after standard therapy(s). Top-line data from this clinical study are expected in mid-2017.
Other Corporate and Clinical Developments

Generated $52.2 Million in Equity Financings. In April 2017, the Company completed the sale of approximately 3.9 million shares of common stock in an underwritten public offering at a price to the public of $10.25 per share, resulting in net proceeds to the Company of approximately $37.8 million after deducting underwriting discounts and commissions and other estimated offering expenses, and the sale of approximately 1.3 million shares under the ATM offering facility for net proceeds of approximately $14.5 million.

Partial Clinical Holds Lifted by U.S. FDA. During late March and early April 2017, the FDA’s Divisions of Hematology Products, Oncology Products 1 and Oncology Products 2 lifted their respective partial clinical holds placed on the Company’s selinexor clinical trials, re-opening enrollment and dosing of new patients in all of the Company’s clinical trials across both hematological and solid tumor malignancies. There were no material impacts on development timelines for any of the ongoing selinexor studies.

Management Change. In April 2017, Justin Renz resigned as the Company’s Executive Vice President, Chief Financial Officer and Treasurer to pursue other opportunities. Mr. Renz continues to serve the Company in an advisory capacity in order to ensure a smooth transition. Karyopharm has begun a search process for the selection and appointment of a new Chief Financial Officer. In the interim, Michael Todisco, who serves as the Company’s Vice President, Finance, leads the Company’s internal finance function.
First Quarter 2017 Financial Results

Cash, cash equivalents and investments as of March 31, 2017, including restricted cash, totaled $150.6 million, compared to $175.5 million as of December 31, 2016.

On April 28, 2017, Karyopharm completed an underwritten public offering of 3,902,439 shares of its common stock at a price to the public of $10.25 per share. The net proceeds to Karyopharm from the offering, after deducting the underwriting discounts and commissions and estimated offering expenses, were approximately $37.8 million. In addition, during April 2017, the Company completed the sale of approximately 1.3 million shares under the ATM offering facility for net proceeds of approximately $14.5 million.

For the quarter ended March 31, 2017, research and development expense was $24.1 million compared to $21.8 million for the quarter ended March 31, 2016. For the quarter ended March 31, 2017, general and administrative expense was $6.3 million compared to $5.6 million for the quarter ended March 31, 2016.

Karyopharm reported a net loss of $29.9 million, or $0.71 per share, for the quarter ended March 31, 2017, compared to a net loss of $27.1 million, or $0.75 per share, for the quarter ended March 31, 2016. Net loss includes stock-based compensation expense of $5.9 million and $5.2 million for the quarters ended March 31, 2017 and March 31, 2016, respectively.

Financial Outlook

Karyopharm expects its operating cash burn, including research and development and general and administrative expenses, for the year ending December 31, 2017 to be in the range of $85 to 90 million. Based on current operating plans, Karyopharm expects that its existing cash and cash equivalents, along with the $52.2 million of net proceeds raised in April 2017, will be sufficient to fund its research and development programs and operations into 2019, including the continued clinical development of selinexor in our lead indications with a focus on filing for accelerated approvals for both MM and DLBCL during 2018, and preparing a commercial infrastructure for the potential launch of selinexor in North America and Western Europe.

On May 4, 2017 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the first quarter of 2017 and provided a business update (Press release, Regeneron, MAY 4, 2017, View Source [SID1234518845]).

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Financial Highlights

($ in millions, except per share data)

Three Months Ended
March 31,


2017

2016*

% Change



EYLEA U.S. net product sales

$
854


$
781


9
%



Total revenues

$
1,319


$
1,201


10
%



GAAP net income

$
249


$
181


38
%



GAAP net income per share – diluted

$
2.16


$
1.59


36
%



Non-GAAP net income(2)

$
337


$
273


23
%



Non-GAAP net income per share – diluted(2)

$
2.92


$
2.40


22
%












* See note (6) below and Table 3 for an explanation of revisions made to certain amounts
previously reported for the three months ended March 31, 2016.



"In the first quarter, we were thrilled to receive U.S. FDA approval for Dupixent, our breakthrough therapy for moderate-to-severe atopic dermatitis, and are working to support access for appropriate patients who suffer from this serious disease," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "We are also pleased to have positive Phase 2 results with dupilumab in moderate-to-severe eosinophilic esophagitis, which marks the fourth allergic disease in which dupilumab has shown proof of concept. These data further validate the hypothesis that the IL-4/IL-13 pathway is a major driver in multiple allergic diseases. Additionally, we have received a new FDA action date for Kevzara, our therapy for rheumatoid arthritis, and are looking forward to a potential U.S. approval and launch in late May 2017."

Business Highlights

Marketed Product Update

EYLEA (aflibercept) Injection for Intravitreal Injection

In the first quarter of 2017, net sales of EYLEA in the United States increased 9% to $854 million from $781 million in the first quarter of 2016. Overall distributor inventory levels remained within the Company’s one- to two-week targeted range.
Bayer commercializes EYLEA outside the United States. In the first quarter of 2017, net sales of EYLEA outside of the United States(1) were $484 million, compared to $419 million in the first quarter of 2016. In the first quarter of 2017, Regeneron recognized $175 million from its share of net profit from EYLEA sales outside the United States, compared to $146 million in the first quarter of 2016.
Dupixent (dupilumab) Injection

Dupilumab, an antibody that blocks signaling of IL-4 and IL-13, is currently being studied in asthma, children with atopic dermatitis, nasal polyps, and eosinophilic esophagitis.
The launch of Dupixent commenced following the March 28, 2017 U.S. Food and Drug Administration (FDA) approval for the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
In the first quarter of 2017, a Phase 3 study of Dupixent in adolescent patients (12-17 years of age) with moderate-to-severe atopic dermatitis was initiated.
In March 2017, the Company and Sanofi presented additional detailed results from the Phase 3 LIBERTY AD CHRONOS study. The study met its primary and secondary endpoints, with patients receiving Dupixent with topical corticosteroids (TCS) achieving significantly improved measures of overall disease severity at 16 and 52 weeks, compared to TCS alone in adults with uncontrolled moderate-to-severe atopic dermatitis.
In the second quarter of 2017, a Phase 3 study of dupilumab in pediatric patients (6-11 years of age) with uncontrolled persistent asthma was initiated.
The Company recently completed a positive primary analysis from a Phase 2 proof-of-concept study of dupilumab in patients with active, moderate-to-severe eosinophilic esophagitis, which can be a manifestation of food allergy. Detailed data from this study will be presented at an upcoming medical conference. The Company and Sanofi plan to meet with the FDA and other regulators to determine next steps for development of dupilumab in this indication.
Praluent (alirocumab) Injection for the Treatment of Elevated Low-Density Lipoprotein (LDL) Cholesterol

In the first quarter of 2017, global net sales of Praluent were $36 million, compared to $13 million in the first quarter of 2016. Product sales for Praluent are recorded by Sanofi, and the Company shares in any profits or losses from the commercialization of Praluent.
On January 5, 2017, the United States District Court for the District of Delaware issued a permanent injunction prohibiting the Company and Sanofi from marketing, selling, or commercially manufacturing Praluent in the United States. On February 8, 2017, the United States Court of Appeals for the Federal Circuit stayed (suspended) the injunction pending appeal. This ruling means that Regeneron and Sanofi will continue to market, sell, and commercially manufacture Praluent in the United States during the appeal process. Oral argument on the appeal is currently scheduled for June 6, 2017.
In April 2017, the FDA approved the supplemental Biologics License Application (sBLA) for a once-monthly (every four weeks), 300 mg dose of Praluent.
The ODYSSEY OUTCOMES trial remains ongoing, and is assessing the potential of Praluent to demonstrate cardiovascular benefit.
Kevzara (sarilumab) Injection

In January 2017, Health Canada approved Kevzara for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have an inadequate response to or intolerance to one or more biologic or non-biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). This was the first approval of Kevzara worldwide.
In March 2017, the Company and Sanofi resubmitted the BLA for Kevzara, which the FDA has accepted for review with a target action date of May 22, 2017.
In April 2017, the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the marketing authorization of Kevzara, recommending its approval for use in adult patients with moderately to severely active rheumatoid arthritis.
Pipeline Progress

Regeneron has sixteen product candidates in clinical development. These consist of EYLEA and fifteen fully human monoclonal antibodies generated using the Company’s VelocImmune technology, including six in collaboration with Sanofi. In addition to EYLEA, Dupixent (dupilumab), Praluent, and Kevzara, updates from the clinical pipeline include:

REGN2810, an antibody to programmed cell death protein 1 (PD-1), is being studied in patients with cancer. A Phase 2 potentially pivotal study for the treatment of advanced cutaneous squamous cell carcinoma (CSCC), as well as various Phase 1 studies (both alone and in combination with other antibodies and treatments), continue to enroll patients. Data from a cohort of patients with CSCC from our Phase 1 trial will be presented at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) conference in June 2017.

Suptavumab, an antibody to the Respiratory Syncytial Virus-F (RSV-F), finished enrolling patients in a Phase 3 study in the first quarter of 2017 subsequent to the completion of the Northern Hemisphere RSV season. Final enrollment in this study was approximately 1,200 patients.

Nesvacumab, an antibody to Ang2 co-formulated with aflibercept for intravitreal injection, is currently being studied in patients with neovascular age-related macular degeneration (wet AMD) and diabetic macular edema (DME). The Phase 2 ONYX study of nesvacumab/aflibercept for the treatment of wet AMD completed enrollment during the first quarter of 2017, and the Phase 2 RUBY study of nesvacumab/aflibercept for the treatment of DME completed enrollment during 2016.

REGN2477, an antibody to Activin A, received orphan drug designation from the FDA for the treatment of Fibrodysplasia Ossificans Progressiva (FOP) in the first quarter of 2017.

Evinacumab, an antibody to Angptl-3, received Breakthrough Therapy designation from the FDA in the first quarter of 2017 for the treatment of hypercholesterolemia in patients with homozygous familial hypercholesterolemia (HoFH).

REGN3500, an antibody to interleukin-33 receptor (IL-33), entered Phase 1 clinical development for the treatment of asthma in the first quarter of 2017.

Select Upcoming 2017 Milestones



Programs
Milestones


Dupixent (dupilumab)
Submission for additional regulatory approvals and
regulatory agency decisions on applications outside of
the United States
Report results from Phase 3 asthma study
Submit sBLA for asthma in adults
Initiate Phase 3 study in pediatric patients in atopic
dermatitis
Initiate Phase 2 study in food allergies



Kevzara
FDA target action date of May 22, 2017
Submission for additional regulatory approvals and
regulatory agency decisions on applications outside of
the United States



Praluent
Complete ODYSSEY OUTCOMES study



Suptavumab (REGN2222;
RSV-F Antibody)
Report results from Phase 3 study



Fasinumab (NGF Antibody)
Initiate additional Phase 3 study in osteoarthritis pain
Initiate Phase 3 study in chronic low back pain



REGN2810 (PD-1 Antibody)
Initiate Phase 3 study in first-line non-small cell lung
cancer
Initiate Phase 2 study in basal cell carcinoma



Nesvacumab/aflibercept
(Ang2 Antibody co-formulated
with aflibercept)
Report data from Phase 2 studies in DME (RUBY) and
wet AMD (ONYX)


First Quarter 2017 Financial Results

Product Revenues: Net product sales were $858 million in the first quarter of 2017, compared to $784 million in the first quarter of 2016. EYLEA net product sales in the United States were $854 million in the first quarter of 2017, compared to $781 million in the first quarter of 2016.

Total Revenues: Total revenues, which include product revenues described above, increased by 10% to $1.319 billion in the first quarter of 2017, compared to $1.201 billion in the first quarter of 2016. Total revenues also include Sanofi and Bayer collaboration revenues of $404 million in the first quarter of 2017, compared to $399 million in the first quarter of 2016.

Research and Development (R&D) Expenses: GAAP R&D expenses were $507 million in the first quarter of 2017, compared to $470 million in the first quarter of 2016. The higher R&D expenses in the first quarter of 2017 were principally due to higher development costs, including an increase in fasinumab and REGN2810 clinical trial costs (partly offset by a decrease in clinical trial costs for dupilumab), manufacturing drug supplies, and higher headcount to support the Company’s increased R&D activities. In addition, in the first quarter of 2017, R&D-related non-cash share-based compensation expense was $74 million, compared to $78 million in the first quarter of 2016.

Selling, General, and Administrative (SG&A) Expenses: GAAP SG&A expenses were $297 million in the first quarter of 2017, compared to $290 million in the first quarter of 2016. The increase in SG&A expenses was primarily due to higher headcount and commercialization-related expenses in connection with preparing to launch Kevzara and Dupixent. In addition, in the first quarter of 2017, SG&A-related non-cash share-based compensation expense was $54 million, compared to $60 million in the first quarter of 2016.

Cost of Goods Sold (COGS): GAAP COGS was $61 million in the first quarter of 2017, compared to $79 million in the first quarter of 2016. COGS decreased principally due to a decrease in royalties since the Company’s obligation to pay Genentech based on U.S. sales of EYLEA ended in May 2016, partly offset by an increase in various start-up costs in connection with the Company’s Limerick, Ireland commercial manufacturing facility.

Cost of Collaboration and Contract Manufacturing (COCM): GAAP COCM was $23 million in the first quarter of 2017, compared to $33 million in the first quarter of 2016. COCM decreased primarily due to lower royalties since the Company’s obligation to pay Genentech based on sales of EYLEA outside the United States also ended in May 2016.

Income Tax Expense: In the first quarter of 2017, GAAP income tax expense was $183 million and the effective tax rate was 42.4%, compared to $149 million and 45.1% in the first quarter of 2016. The effective tax rate for the first quarter of 2017 was negatively impacted, compared to the U.S. federal statutory rate, by losses incurred in foreign jurisdictions with rates lower than the federal statutory rate and the non-tax deductible Branded Prescription Drug Fee, partly offset by the tax benefit associated with stock-based compensation, the domestic manufacturing deduction, and the federal tax credit for research activities.

GAAP and Non-GAAP Net Income(2): The Company reported GAAP net income of $249 million, or $2.36 per basic share and $2.16 per diluted share, in the first quarter of 2017, compared to GAAP net income of $181 million, or $1.74 per basic share and $1.59 per diluted share, in the first quarter of 2016.

The Company reported non-GAAP net income of $337 million, or $3.19 per basic share and $2.92 per diluted share, in the first quarter of 2017, compared to non-GAAP net income of $273 million, or $2.62 per basic share and $2.40 per diluted share, in the first quarter of 2016.

A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

Tarrytown, New York Facilities Update: On March 3, 2017, the Company completed a new lease financing for its Tarrytown, New York facilities (the Facility). As a result of this transaction, the Company leased the Facility from Banc of America Leasing & Capital, LLC (BAL) for a term of five years. At the end of the lease term, the Company has an option to extend the term of the lease, purchase the Facility at a predetermined amount, or sell the Facility to a third party on behalf of BAL. The rent payments under this lease are expected to be lower than those under the Company’s previous leases for its corporate headquarters.

2017 Financial Guidance(3)

The Company’s updated full year 2017 financial guidance consists of the following components:




EYLEA U.S. net product sales
Single digit percentage growth over 2016 (reaffirmed)
Sanofi reimbursement of Regeneron
commercialization-related expenses
$385 million – $425 million
(previously $400 million – $450 million)
Non-GAAP unreimbursed R&D(2)(4)
$950 million – $1.025 billion (reaffirmed)
Non-GAAP SG&A(2)(4)
$1.140 billion – $1.200 billion
(previously $1.175 billion – $1.250 billion)
Effective tax rate
32% – 38% (reaffirmed)
Capital expenditures
$300 million – $350 million
(previously $375 million – $450 million)


(1)
Regeneron records net product sales of EYLEA in the United States. Outside the United States, EYLEA net product sales comprise sales by Bayer in countries other than Japan and sales by Santen Pharmaceutical Co., Ltd. in Japan under a co-promotion agreement with an affiliate of Bayer. The Company recognizes its share of the profits (including a percentage on sales in Japan) from EYLEA sales outside the United States within "Bayer collaboration revenue" in its Statements of Operations.


(2)
This press release uses non-GAAP net income, non-GAAP net income per share, non-GAAP unreimbursed R&D, and non-GAAP SG&A, which are financial measures that are not calculated in accordance with U.S. Generally Accepted Accounting Principles ("GAAP"). These non-GAAP financial measures are computed by excluding certain non-cash and other items from the related GAAP financial measure. Non-GAAP adjustments also include the income tax effect of reconciling items.

The Company makes such adjustments for items the Company does not view as useful in evaluating its operating performance. For example, adjustments may be made for items that fluctuate from period to period based on factors that are not within the Company’s control, such as the Company’s stock price on the dates share-based grants are issued. Management uses these non-GAAP measures for planning, budgeting, forecasting, assessing historical performance, and making financial and operational decisions, and also provides forecasts to investors on this basis. Additionally, such non-GAAP measures provide investors with an enhanced understanding of the financial performance of the Company’s core business operations. However, there are limitations in the use of these and other non-GAAP financial measures as they exclude certain expenses that are recurring in nature. Furthermore, the Company’s non-GAAP financial measures may not be comparable with non-GAAP information provided by other companies. Any non-GAAP financial measure presented by Regeneron should be considered supplemental to, and not a substitute for, measures of financial performance prepared in accordance with GAAP. A reconciliation of the Company’s historical GAAP to non-GAAP results is included in Table 3 of this press release.


(3)
The Company’s 2017 financial guidance does not assume the completion of any significant business development transactions not completed as of the date of this press release and assumes that Praluent will remain on the market throughout 2017.


(4)
A reconciliation of full year 2017 non-GAAP to GAAP financial guidance is included below:






Projected Range


(In millions)

Low

High


GAAP unreimbursed R&D (5)

$
1,245


$
1,340



R&D: Non-cash share-based compensation expense

(295)


(315)



Non-GAAP unreimbursed R&D

$
950


$
1,025










GAAP SG&A

$
1,345


$
1,435



SG&A: Non-cash share-based compensation expense

(205)


(235)



Non-GAAP SG&A

$
1,140


$
1,200



(5)
Unreimbursed R&D represents R&D expenses reduced by R&D expense reimbursements from the Company’s collaborators and/or customers.


(6)
Applicable GAAP amounts previously reported for the three months ended March 31, 2016 have been revised due to the adoption of Accounting Standards Update 2016-09 ("ASU 2016-09"), Compensation – Stock Compensation, Improvements to Employee Share-Based Payment Accounting, during the second quarter of 2016. The Company revised its GAAP net income from the amounts originally reported for the quarterly period ended March 31, 2016 to include a $15.6 million income tax benefit, which was originally recorded as additional paid-in capital. In addition, refer to Table 3 for a description of revisions to non-GAAP measures previously reported for the three months ended March 31, 2016.