On November 6, 2018 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL), reported financial results for the third quarter ended September 30, 2018, and also provided an update on the commercial launch of TAVALISSE for treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment and its clinical development pipeline (Press release, Rigel, NOV 6, 2018, View Source [SID1234530861]).

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Recent Highlights

·Net product sales of $4.9 million for TAVALISSE during the third quarter

·On October 29, entered into an exclusive license and supply agreement with Kissei Pharmaceutical Co., Ltd. (Kissei) for development and marketing rights to fostamatinib in Asia; Rigel to receive upfront cash payment of $33 million, with the potential for up to an additional $147 million in milestone payments and product transfer price payments based on tiered net sales

· On October 4, the European Medicines Agency (EMA) validated the company’s Marketing Authorization Application (MAA) for fostamatinib1 in adult chronic ITP, initiating the review process

· Phase 3 trial design for fostamatinib1 investigational candidate in autoimmune hemolytic anemia (AIHA) to be submitted to U.S. Food and Drug Administration (FDA) in early November

"We continue to advance our corporate strategy with solid execution across all business areas. The success of our TAVALISSE commercial launch in the United States, our collaboration with Kissei in Asia, and our MAA validation highlight the expanding capabilities of our organization," said Raul Rodriguez, president and CEO of Rigel. "In parallel, our clinical development plans continue to increase the potential of our pipeline. For our investigational agents, we plan to initiate our Phase 3 study for fostamatinib in autoimmune hemolytic anemia in the first half of 2019 and we continue to explore potential drug development opportunities including for our IRAK1/4 inhibitor, R835."

Financial Update

For the third quarter of 2018, Rigel reported a net loss of $23.8 million, or $0.14 per share, compared to a net loss of $17.7 million, or $0.14 per share, in the same period of 2017.

For the third quarter of 2018, Rigel reported net product sales from TAVALISSE of $4.9 million. Rigel recognizes revenue using the sell-in methodology when products are delivered to its distributors. There were no product sales in the third quarter of 2017.

There were no contract revenues from collaborations in the third quarter of 2018. Contract revenues from collaborations of $900,000 in the third quarter of 2017 were related to a payment received from a license agreement with a third party.

Rigel reported total costs and expenses of $29.2 million in the third quarter of 2018, compared to $18.8 million for the same period in 2017. The increase in costs and expenses was primarily due to the increases in personnel costs as Rigel expanded its customer-facing team, third party costs to support Rigel’s ongoing commercial efforts for TAVALISSE in chronic ITP, as well as stock-based compensation expense related to certain performance-based stock options.

For the nine months ended September 30, 2018, Rigel reported net product sales from TAVALISSE of $6.7 million. There were no product sales for the nine months ended September 30, 2017. For the nine months ended September 30, 2018, Rigel reported a net loss of $73.7 million, or $0.47 per share, compared to a net loss of $52.1 million, or $0.43 per share, for the same period of 2017.

As of September 30, 2018, Rigel had cash, cash equivalents and short-term investments of $115.6 million, compared to $115.8 million as of December 31, 2017. With the $33.0 million upfront payment Rigel will receive under its collaboration agreement with Kissei, as discussed below, Rigel expects that its cash, cash equivalents and short-term investments will be sufficient to support its current and projected funding requirements, including the on-going commercial launch of TAVALISSE for chronic ITP in the U.S., into the first quarter of 2020.

Business Update

Since commercial launch in May 2018, demand for TAVALISSE in adult patients with previous treatment failure in cITP continues to grow, with broad usage seen in steroid refractory patients. TAVALISSE has been utilized by a broad base of prescribers and community physicians, and the payor response has been positive with an approval rate of 85-90%.

Outside of the U.S., the company continues to further its global commercialization strategy. Rigel has entered an exclusive license and supply agreement with Kissei for the development and commercialization of fostamatinib in all indications in Japan. The agreement also provides Kissei with rights to fostamatinib in China, Taiwan, and the Republic of Korea. In exchange, Rigel will receive an upfront cash payment of $33 million with the potential for up to an additional $147 million in development and commercial milestone payments. The company will also receive product transfer price payments in the mid to upper twenty percent range based on tiered net sales for exclusive supply of fostamatinib.

In the EU, which is the second largest market for adult chronic ITP, the EMA validated the MAA for fostamatinib1 in the indication. The review process was initiated in October and the company anticipates an opinion from the Committee on Human Medicinal Products (CHMP) of the EMA by the fourth quarter of 2019.

Rigel continues to progress with its expansion plans for fostamatinib in other indications1 and will submit its Phase 3 trial design for the treatment of warm AIHA (wAIHA) to the FDA in early November. The trial, designed in consultation with the FDA, is a placebo-controlled study of approximately 80 patients with primary or secondary wAIHA who have failed at least one prior treatment. The primary endpoint will be a durable hemoglobin response by week 24, defined as Hgb > 10 g/dL and > 2 g/dL

greater than baseline and durability of response, with the response not being attributed to rescue therapy. Enrollment is expected to begin in the first half of 2019.

About ITP
In patients with ITP, the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPOs) and splenectomy. However, not all patients are adequately treated with existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About AIHA
AIHA is a rare, serious blood disorder in which the immune system produces antibodies that result in the destruction of the body’s own red blood cells. AIHA affects approximately 40,000 adult patients in the U.S. and can be a severe, debilitating disease. To date, there are no disease-targeted therapies approved for AIHA, despite the unmet medical need that exists for these patients.

About R8351

The investigational candidate, R835, is an orally available, potent and selective inhibitor of IRAK1 and IRAK4 that has been shown preclinically to block inflammatory cytokine production in response to toll-like receptor (TLR) and the interleukin-1 (IL-1R) family receptor signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to a variety of inflammatory conditions. R835 is active in multiple rodent models of inflammatory disease including psoriasis, arthritis, lupus, multiple sclerosis and gout.

Conference Call and Webcast with Slides Today at 5:00PM Eastern Time
Rigel will hold a live conference call and webcast today at 5:00pm Eastern Time (2:00pm Pacific Time).

Participants can access the live conference call by dialing 855-892-1489 (domestic) or 720-634-2939 (international) and using the Conference ID number 1398326. The webcast, with slide presentation, can be accessed from Rigel’s website at www.rigel.com. The webcast will be archived and available for replay after the call via the Rigel website.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

· Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.

· Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.

· Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (>Grade 3), interrupt, reduce dose or discontinue TAVALISSE.

· Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.

· TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.

Drug Interactions

· Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.

· It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.

· Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.

· Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.

Adverse Reactions

· Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).

· Common adverse reactions (>5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.

Please see www.TAVALISSE.com for full Prescribing Information.
t side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

TAVALISSE and RIGEL ONECARE are trademarks of Rigel Pharmaceuticals, Inc.

On November 6, 2018 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the third quarter of 2018 and provided a business update (Press release, Regeneron, NOV 6, 2018, View Source [SID1234530860]).

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"Regeneron continues to grow and diversify our business, while continuing to deliver very strong financial results. In addition to EYLEA reaching over $1 billion in quarterly U.S. net sales, we also made significant progress with Dupixent, a key driver of future growth, and launched Libtayo, our first immuno-oncology therapy," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "Dupixent is now approved in the U.S. for both atopic dermatitis and asthma and under regulatory review for the treatment of adolescents with atopic dermatitis – with another submission planned in chronic rhinosinusitis with nasal polyps. We also recently reported positive Phase 3 results for EYLEA in diabetic retinopathy, and expect an FDA action on our supplemental application for this indication in the first half of 2019."

Third Quarter 2018 Business Highlights

Key Pipeline Progress
Regeneron has twenty product candidates in clinical development, which consist of EYLEA and fully human antibodies generated using the Company’s VelocImmune technology, including eight in collaboration with Sanofi. Updates from the clinical pipeline include:
EYLEA (aflibercept) Injection
•
The FDA approved EYLEA for an every 12-week dosing regimen option after one year of effective therapy in patients with wet AMD.
•
The FDA accepted for review the supplemental Biologics License Application (sBLA) of EYLEA for the treatment of diabetic retinopathy, with a target action date of May 13, 2019.
•
The Company announced that the Phase 3 PANORAMA trial evaluating EYLEA in patients with moderately severe and severe non-proliferative diabetic retinopathy met its one-year primary endpoint and key secondary endpoints, including both the improvement of diabetic retinopathy and a reduction in the rate of vision-threatening complications.
•
The FDA issued a Complete Response Letter regarding the Chemistry, Manufacturing, and Controls Prior-Approval Supplement (PAS) for the EYLEA pre-filled syringe. The Company expects to compile all the requested information and resubmit the PAS in the first half of 2019.

Dupixent (dupilumab) Injection
•
In October 2018, the FDA approved Dupixent as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.
•
The Company and Sanofi submitted an sBLA and a Marketing Authorization Application (MAA) for an expanded atopic dermatitis indication in adolescent patients (12–17 years of age). In November 2018, the FDA accepted for priority review the sBLA for atopic dermatitis in adolescent patients, with a target action date of March 11, 2019.
•
The Company and Sanofi announced positive top-line results from both pivotal Phase 3 placebo-controlled trials evaluating Dupixent in adults with inadequately-controlled CRSwNP.
•
A Phase 2/3 study in eosinophilic esophagitis and a Phase 2 study in peanut allergy were initiated.

Praluent (alirocumab) Injection
•
The FDA approved Praluent for the treatment of patients with heterozygous familial hypercholesterolemia (HeFH) undergoing apheresis.
•
An sBLA for Praluent as a potential treatment to reduce major adverse cardiovascular events was accepted for review by the FDA, with a target action date of April 28, 2019.
•
The FDA also accepted for review an sBLA for Praluent for first-line treatment of hyperlipidemia, with a target action date of April 29, 2019.
•
A Phase 3 study in pediatric patients with homozygous familial hypercholesterolemia (HoFH) was initiated.

Kevzara (sarilumab) Injection
•
A Phase 3 study in polymyalgia rheumatica was initiated.

2

Libtayo (cemiplimab-rwlc) Injection
•
On September 28, 2018, the FDA approved Libtayo (cemiplimab-rwlc) for the treatment of patients with metastatic or locally advanced CSCC who are not candidates for curative surgery or curative radiation.

Fasinumab is an antibody targeting Nerve Growth Factor (NGF).
•
The Company and Teva announced positive top-line results from a Phase 3 study of fasinumab in patients with chronic pain from osteoarthritis of the knee or hip.

REGN3500 is an antibody to IL-33.
•
A Phase 2 study in chronic obstructive pulmonary disease (COPD) was initiated.

Business Development Update
•
In the third quarter of 2018, the Company entered into a collaboration agreement with bluebird bio, Inc. to research, develop, and commercialize novel immune cell therapies for cancer.

Financial Results

Product Revenues: Net product sales were $1.025 billion in the third quarter of 2018, compared to $957 million in the third quarter of 2017. EYLEA net product sales in the United States were $1.022 billion in the third quarter of 2018, compared to $953 million in the third quarter of 2017. Overall distributor inventory levels for EYLEA in the United States remained within the Company’s one-to-two-week targeted range.

Total Revenues: Total revenues, which include product revenues described above, increased by 11% to $1.663 billion in the third quarter of 2018, compared to $1.501 billion in the third quarter of 2017. Total revenues include Sanofi and Bayer collaboration revenues of $521 million in the third quarter of 2018, compared to $482 million in the third quarter of 2017. The increase in Sanofi collaboration revenue in the third quarter of 2018 was primarily due to the Company’s share of higher net sales of Dupixent and Praluent, partly offset by the ceasing of funding by Sanofi in connection with the Company’s Discovery and Preclinical Development Agreement, which ended on December 31, 2017, and an increase in the collaboration’s Dupixent commercialization expenses. Bayer collaboration revenue increased in the third quarter of 2018 primarily due to an increase in net profits in connection with higher sales of EYLEA outside the United States. The increase in other revenue in the third quarter of 2018 was partially due to the recognition of a portion of $80 million in development milestones achieved in the third quarter of 2018 in connection with the Company’s fasinumab collaboration with Teva and Mitsubishi Tanabe Pharma.

The Company adopted Accounting Standard Codification (ASC) 606, Revenue from Contracts with Customers, as of January 1, 2018. The Company adopted the standard using the modified retrospective method, and therefore prior period amounts have not been adjusted. A more complete description of the impact of adopting ASC 606 can be found in the Company’s Form 10-Q for the quarterly period ended September 30, 2018.

Refer to Table 4 for a summary of collaboration and other revenue.

Research and Development (R&D) Expenses: GAAP R&D expenses were $557 million in the third quarter of 2018, compared to $530 million in the third quarter of 2017. The higher R&D expenses in the third quarter of 2018 were principally due to an increase in Libtayo development expenses and higher R&D headcount and facilities-related costs, partly offset by a decrease in Dupixent development expenses. In the third quarter of 2018, R&D-related non-cash share-based compensation expense was $60 million, compared to $70 million in the third quarter of 2017.

Selling, General, and Administrative (SG&A) Expenses: GAAP SG&A expenses were $369 million in the third quarter of 2018, compared to $307 million in the third quarter of 2017. The higher SG&A expenses in the third quarter of 2018 were primarily due to higher headcount and headcount-related costs and higher contributions to independent not-for-profit patient assistance organizations. In the third quarter of 2018, SG&A-related non-cash share-based compensation expense decreased to $43 million, compared to $48 million in the third quarter of 2017.

Income Tax Expense: In the third quarter of 2018, GAAP income tax expense was $41 million and the effective tax rate was 6.5%, compared to $177 million and 31.3% in the third quarter of 2017. The Company’s effective tax rate for the third quarter of 2018 was significantly impacted by the law known as the Tax Cuts and Jobs Act (the "U.S. Tax Reform Act"), which reduced the U.S. federal corporate income tax rate from 35% to 21% effective January 1, 2018. The effective tax rate for the third quarter of 2018 was positively impacted, compared to the U.S. federal statutory rate, primarily by the tax benefit associated with tax planning in connection with the U.S. Tax Reform Act, the federal tax credit for research activities, and, to a lesser extent, stock-based compensation and income earned in foreign jurisdictions with tax rates lower than the U.S. federal statutory rate. During the third quarter of 2018, the Company recorded an income tax benefit of $11.9 million as an adjustment to the provisional amount recorded as of December 31, 2017 for the U.S. Tax Reform Act, which was related to the re-measurement of the Company’s U.S. net deferred tax assets.

GAAP and Non-GAAP Net Income(2): GAAP net income was $595 million, or $5.50 per basic share and $5.17 per diluted share, in the third quarter of 2018, compared to GAAP net income of $388 million, or $3.64 per basic share and $3.32 per diluted share, in the third quarter of 2017.

Non-GAAP net income was $675 million, or $6.25 per basic share and $5.87 per diluted share, in the third quarter of 2018, compared to non-GAAP net income of $470 million, or $4.41 per basic share and $3.99 per diluted share, in the third quarter of 2017.

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.

Conference Call Information

Regeneron will host a conference call and simultaneous webcast to discuss its third quarter 2018 financial and operating results on Tuesday, November 6, 2018, at 8:30 AM. To access this call, dial (800) 708-4539 (U.S.) or (847) 619-6396 (International). A link to the webcast may be accessed from the "Investors and Media" page of Regeneron’s website at www.regeneron.com. A replay of the conference call and webcast will be archived on the Company’s website and will be available for 30 days.

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 estimated 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 or changes in the fair value of the Company’s equity investments) or items that are not associated with normal, recurring operations (such as changes in applicable laws and regulations). 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.

The Company’s 2018 financial guidance does not assume the completion of any significant business development transactions not completed as of the date of this press release.

On November 6, 2018 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reported its third quarter 2018 financial results and described upcoming clinical events (Press release, Synta Pharmaceuticals, NOV 6, 2018, View Source [SID1234530859]):

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"Madrigal made important progress thus far in 2018 to advance the development of MGL-3196, through successful completion of Phase 2 studies in NASH and dyslipidemia. We expect to begin a Phase 3 study in NASH in late 2018 or early 2019, subject to regulatory approval. We are evaluating the trial design and objectives of a Phase 3 study in dyslipidemia which could begin in 2019," stated Paul Friedman, M.D., Chief Executive Officer of Madrigal. "We are adding appropriate personnel resources as necessary to handle these development activities, and we believe we have significant financial resources to fund our currently planned Phase 3 programs.

Becky Taub, M.D., CMO and Executive VP, Research & Development of Madrigal added, "We are looking forward to presenting our Phase 2 NASH clinical data in a presidential plenary session on November 12, 2018, at The Liver Meeting 2018 at AASLD. We continue to believe in the potential of MGL-3196 to resolve NASH and improve multiple atherogenic lipids, and we are eager to move ahead with our Phase 3 clinical programs.

Financial Results for the Three Months and Nine Months Ended September 30, 2018

As of September 30, 2018, Madrigal had cash, cash equivalents and marketable securities of $488.5 million, compared to $191.5 million at December 31, 2017. The increase in cash and marketable securities resulted primarily from the net proceeds of $311.8 million from Madrigal’s public offering of common stock in June 2018, partially offset by cash used in operations of $19.2 million.

Operating expenses were $11.3 million and $26.2 million, respectively, for the three month and nine month periods ended September 30, 2018, compared to $8.6 million and $23.2 million in the comparable prior year periods.

Research and development expenses for the three month and nine month periods ended September 30, 2018 were $6.2 million and $16.5 million, respectively, compared to $6.7 million and $17.9 million in the comparable prior year periods. The decreases are primarily attributable to completion of treatment in our Phase 2 clinical studies in 2018.

General and administrative expenses for the three month and nine month periods ended September 30, 2018 were $5.1 million and $9.7 million, respectively, compared to $2.0 million and $5.3 million in the comparable prior year periods. The increases are due primarily to higher non-cash stock compensation expense from stock option awards.

Interest income for the three month and nine month periods ended September 30, 2018 was $2.8 million and $4.7 million, respectively, as compared to $174 thousand and $342 thousand in the comparable prior year periods. The change in interest income was due primarily to a higher average principal balance in our investment account in 2018, and increased interest rates.

Clinical Program Summaries for MGL-3196

NASH

Non-alcoholic Steatohepatitis (NASH) is a common liver disease in the United States and worldwide, unrelated to alcohol use, that is characterized by a build-up of fat in the liver, inflammation, damage (ballooning) of hepatocytes and increasing fibrosis. Although people with NASH may feel well and often do not know they have the disease, NASH can lead to permanent damage, including cirrhosis and impaired liver function in a high percentage of patients.

In October 2016, the first patient was treated in the ongoing Phase 2 trial of MGL-3196 for the treatment of NASH. The randomized, double-blind, placebo-controlled, multi-center Phase 2 study enrolled 125 patients 18 years of age and older with liver biopsy-confirmed NASH and included approximately 25 clinical sites in the United States. Patients were randomized to receive either MGL-3196 or placebo in a 2:1 ratio.

The primary endpoint of the study was the reduction of liver fat at 12 weeks compared with baseline (relative change), assessed by MRI-PDFF. Key secondary endpoints at 36 weeks included: reduction in liver fat compared with baseline (relative change), also assessed by MRI-PDFF; a two-point reduction in NAS (NALFD activity score) on biopsy; resolution of NASH on biopsy; and, safety and tolerability based on adverse events and changes in laboratory values.

The primary endpoint of the study at 12 weeks was achieved. Liver fat was reduced by 36.3% in all MGL-3196 treated patients (78) and 42.0% in a pre-specified group of high exposure MGL-3196 treated patients (44/78), as compared with 9.6% median reduction in liver fat in 38 placebo treated patients. These results were statistically significant (p<0.0001) for both MGL-3196 treatment groups. Further, 75% of the high-exposure MGL-3196 treated patients showed liver fat reductions of >30%.

At 36 weeks, MGL-3196 achieved multiple key secondary endpoints including a sustained highly significant (p<0.001) reduction in liver fat compared to placebo as

measured by MRI-PDFF; mean relative fat reduction for MGL-3196 was 37% versus 8.9% for placebo. MGL-3196 was associated with a greater percentage of subjects with a 2-point improvement in NAS (56% of 73 patients vs 32% of 34 placebo subjects, p=0.02). NASH resolution (NR) was seen in 27% of MGL-3196 compared with 6% of placebo subjects, p=0.02. MGL-3196 patients with > 30% fat reduction on Week 12 MRI-PDFF demonstrated a higher percentage of 2-point improvement in NAS (70%, p=0.001) and NR (39%, p=0.001) compared with placebo, demonstrating a strong relationship between early reduction in liver fat as demonstrated by week 12 MRI-PDFF and NASH improvement on liver biopsy at Week 36. In patients with NASH Resolution, 35% of the MGL-3196 treated patients and no placebo patients had more advanced NASH (baseline NAS >5).

At Week 36, MGL-3196 treated patients showed sustained reduction of fibrosis biomarkers. In MGL-3196 patients with NASH resolution, fibrosis also resolved in 50% of patients and was decreased statistically significantly relative to all placebo patients.

There were statistically significant reductions in liver enzymes in MGL-3196 treated patients compared to placebo treated patients; reductions of greater magnitude were achieved with longer duration of MGL-3196 treatment. Statistically significantly more MGL-3196 treated patients than placebo treated patients had normalization of ALT (alanine transaminase).

Similar to week 12, at week 36 there were sustained, statistically significant reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, ApoB and lipoprotein(a).

MGL-3196 was well tolerated in this trial with mostly mild and a few moderate AEs which were balanced between drug treated and placebo patients. There was an increase in incidence of mild transient diarrhea in MGL-3196-treated, often a single episode, at the start of treatment. Diarrhea incidence was not increased later in the study.

Based on liver enzyme inclusion criteria, some patients are receiving extended treatment beyond 36 weeks for up to 36 additional weeks. All patients in this extension study will receive MGL-3196 and only non-invasive assessments will be made, including serial MRI-PDFF, safety labs, and circulating biomarkers.

Additional information about the study [NCT02912260] can be obtained at www.ClinicalTrials.gov.

HeFH

Heterozygous familial hypercholesterolemia (HeFH), and a much rarer form called homozygous familial hypercholesterolemia (HoFH), are severe genetic dyslipidemias typically caused by inactivating mutations in the LDL receptor. Both forms of FH lead to early onset cardiovascular disease. HeFH, the most common dominantly inherited disease, is present in up to 1 in 200 people; the disease is found in higher frequencies

in certain more genetically homogenous populations. Treatments exist for both HeFH and HoFH but many patients (as many as 40 percent of HeFH patients) are not able to reach their cholesterol (LDL-C) reduction goals on these therapies, reflecting the lifetime burden of cholesterol buildup in their bodies. Based on evidence of impressive LDL cholesterol lowering in Phase 1, and data suggesting that MGL-3196 has a mechanism of action that is different from and complementary to statins, Madrigal initiated a Phase 2 proof-of-concept trial in HeFH in February 2017 and enrolled 116 patients.

In this Phase 2 HeFH trial, patients who were not at their LDL-C goal were randomized in a 2:1 ratio to receive either MGL-3196 or placebo, in addition to their current cholesterol lowering regimen, which included approximately 75% taking high intensity statins (20/40 mg rosuvastatin or 80 mg atorvastatin), and about 2/3 of patients also taking ezetimibe. MGL-3196 treated patients (placebo corrected) achieved highly significant (p< 0.0001) LDL-C lowering of 18.8%, and 21% LDL-C lowering in those on an optimal dose of MGL-3196. LDL-C lowering was 28.5% in MGL-3196 treated compared to placebo in a prespecified group of patients who did not tolerate high intensity statin doses. Highly significant reductions (p<0.0001) relative to placebo were also observed with ApoB, triglycerides (TG) (25-31%), apolipoprotein CIII (Apo CIII) and Lp(a) (25-40%) in all MGL-3196 treated patients and prespecified subgroups, irrespective of statin treatment.

MGL-3196 was well-tolerated with primarily mild and some moderate AEs, the numbers of which were balanced between placebo and drug-treatment groups.

About MGL-3196

Among its many functions in the human body, thyroid hormone, through activation of its beta receptor, plays a central role in controlling lipid metabolism, impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Attempts to exploit this pathway for therapeutic purposes in cardio-metabolic and liver diseases have been hampered by the lack of selectivity of older compounds for the thyroid hormone receptor (THR)-β, chemically-related toxicities and undesirable distribution in the body.

Madrigal recognized that greater selectivity for thyroid hormone receptor (THR)-β and liver targeting might overcome these challenges and deliver the full therapeutic potential of THR-β agonism. Madrigal believes that MGL-3196 is the first orally administered, small-molecule, liver- directed, truly β-selective THR agonist. MGL- 3196 has now demonstrated in two Phase 2 double-blind, placebo-controlled trials in NASH and HeFH the potential for a broad array of therapeutically beneficial effects, improving components of both metabolic syndrome, such as insulin resistance and dyslipidemia, and fatty liver disease, including lipotoxicity and inflammation. Based on evidence of these pleiotropic actions, coupled with an excellent safety profile, Madrigal plans to initiate a Phase 3 clinical program in NASH.

On November 6, 2018 EyePoint Pharmaceuticals, Inc. (NASDAQ: EYPT), a specialty biopharmaceutical company committed to developing and commercializing innovative ophthalmic products, reported operating and financial results for its fiscal 2019 first quarter ended September 30, 2018 and highlighted recent clinical and operational developments (Press release, pSivida, NOV 6, 2018, View Source [SID1234530856]).

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"The approval of YUTIQ by the U.S. FDA in October marked a significant achievement for EyePoint and validates the Company’s innovation and ability to develop an effective treatment to decrease recurrence of uveitic flares from non-infectious posterior segment uveitis that can result in blindness," said Nancy Lurker, President and Chief Executive Officer of EyePoint Pharmaceuticals. "Following the positive reception by retina and uveitis specialists of the clinical data presented for YUTIQ at the American Academy of Ophthalmology 2018 Annual Meeting, we believe that we are well-positioned for a successful product launch planned in the first quarter of calendar 2019. In addition, we are scaling up our manufacturing of DEXYCU ahead of an anticipated launch in the first half of calendar 2019."

Recent Clinical & Operational Highlights

In October 2018, the U.S. Food and Drug Administration (FDA) approved YUTIQ (fluocinolone acetonide intravitreal implant) 0.18 mg, a three-year micro-insert for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye. YUTIQ utilizes the Company’s Durasert drug delivery technology and is an intravitreal micro-insert designed to deliver drug consistently over 36 months. The approval occurred 24 days in advance of the PDUFA date of November 5th.

At the American Academy of Ophthalmology (AAO) 2018 Annual Meeting in Chicago, IL, 24-month efficacy and safety data supporting YUTIQ was presented during the Retina Subspecialty day at a breakthrough presentation entitled, "24-month Evaluation of Fluocinolone Acetonide Intravitreal Insert Treatment for Non-Infectious Posterior Uveitis". These data demonstrated that the recurrence rate in randomized eyes treated with YUTIQ was significantly lower than in sham eyes (59.8% vs. 97.6%, respectively; p<0.001) at 24-months of the three-year trial. Safety and side effects were consistent with those reported for previous analyses of earlier timepoints.

In August, safety and efficacy data from the Phase 3 clinical trial of DEXYCU compared to prednisolone acetate 1.0% ophthalmic drops for the treatment of inflammation post-cataract surgery were published in the Journal of Cataract & Refractive Surgery. Results demonstrated similar efficacy and safety between both products in treating inflammation post cataract surgery with a preference of DEXYCU compared to drops.

EyePoint granted Ocumension Therapeutics, a China-based ophthalmology company, an exclusive license to develop and commercialize EyePoint’s three-year micro insert product using the Durasert technology for chronic, non-infectious uveitis affecting the posterior segment of the eye in the greater China territory, which is comprised of China, Hong Kong, Macau and Taiwan. EyePoint will receive a one-time upfront payment of $1.75 million and is eligible to receive up to an additional $10.0 million if certain future prespecified development, regulatory and commercial sales milestones are achieved by Ocumension. Ocumension will be responsible for funding the clinical development of EyePoint’s three-year micro-insert product using the Durasert technology for chronic, non-infectious posterior segment uveitis in Greater China. EyePoint will supply product for the clinical trials.

John Landis, Ph.D., M.S., was appointed to the EyePoint Board of Directors in October 2018. Dr. Landis brings more than 30 years of pharmaceutical research and development experience from senior level roles held at Schering-Plough Corporation, Pharmacia Corporation and The Upjohn Company.

EyePoint’s Board of Directors approved a change of the Company’s fiscal year-end to December 31 from the current fiscal year-end of June 30. The Company believes this change will align its financial reporting periods to that of its peer group in the industry and better facilitate assessment of the Company’s financial performance. The Company will file transitional audited financial statements on Form 10-KT for the six-month period ending December 31, 2018.

Fiscal First Quarter 2019 Results

Revenue for the three months ended September 30, 2018 totaled $486,000 compared to $385,000 for the prior year quarter. Revenues in both periods were primarily derived from royalty income under existing collaboration agreements.

Operating expenses for the quarter ended September 30, 2018 increased to $14.0 million from $6.4 million a year earlier, due primarily to initial investments in sales and marketing infrastructure and program costs, amortization of the DEXYCU intangible asset, professional services and stock-based compensation. Non-operating expense, net in the quarter ended September 30, 2018 totaled $19.6 million and consisted primarily of a non-cash change in fair value of derivative liability and interest expense on our term loan. Net loss for the quarter ended September 30, 2018 was $33.1 million, or $0.44 per share, compared to a net loss of $6.0 million, or $0.15 per share, for the prior year quarter.

Cash and cash equivalents at September 30, 2018 totaled $55.8 million compared to $38.8 million at June 30, 2018. The cash balance of September 30, 2018 reflects proceeds of $28.9 million from the exercise of warrants in the quarter.

Conference Call Information

EyePoint will host a conference call today, Tuesday, November 6, 2018, at 8:00 AM ET, to discuss the fiscal first quarter 2019 financial results and recent clinical and operational developments. To access the conference call, please dial (877) 312-7507 (local) or (631) 813-4828 (international) at least 10 minutes prior to the start time and refer to conference ID 3098959. A live webcast will be available on the Investor Relations section of the corporate website at View Source A replay of the webcast will also be available on the corporate website.

On November 6, 2018 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today reported financial results for the third quarter of 2018 and highlighted its recent business and pipeline successes.

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"We enter the fourth quarter in a position of financial strength, driven by strong worldwide SPINRAZA sales. In addition, we achieved numerous successes during the quarter that advanced our pipeline, technology and business and contributed to our financial strength. In 2019 and beyond, we are positioned for continued growth bolstered by the addition of TEGSEDI commercial revenue," said Stanley T. Crooke, M.D., Ph.D., chairman of the board and chief executive officer of Ionis. "Beyond our commercial-stage drugs, we have a broad and growing pipeline of innovative programs we are advancing toward the market. We continue to advance our antisense technology, expanding its application to more diseases, both rare and common. An example of this is our LICA technology, which was further validated by the results from the Phase 2 study of AKCEA-APO(a)-LRx – our largest and longest study to date with a LICA drug – which demonstrated significant reductions in Lp(a) and an attractive safety profile. We also continue to expand our Ionis-owned pipeline and our existing relationships with partners. The successes we are achieving with our commercial-stage drugs and in advancing our pipeline have increased our financial strength and our ability to deliver innovative new drugs to patients in need."

Third Quarter 2018 Financial Highlights

·
Revenues increased year-to-date by more than 15 percent compared to 2017

o
Total revenue was $145 million and $408 million for the third quarter and year-to-date 2018, respectively, compared to $118 million and $346 million for the same periods in 2017

o
Commercial revenue from SPINRAZA for year-to-date 2018 was $168 million, a nearly three-fold increase over year-to-date 2017

o
Commercial revenue was 45 percent of Ionis’ total revenue in the first nine months of 2018 compared to less than 20 percent for the same period in 2017, reflecting Ionis’ transition to a commercial-stage company

·
On track for third consecutive year of pro forma operating profitability while investing in the launches of two drugs

o
GAAP operating results were a loss of $19 million and $72 million for the third quarter and year-to-date 2018, respectively, compared to operating income of $11 million and $37 million for the same periods in 2017

o
Pro forma operating income was $16 million and $25 million for the third quarter and year-to-date 2018, respectively, compared to $33 million and $101 million for the same periods in 2017

o
Operating expenses increased primarily due to higher SG&A expenses related to preparing to launch TEGSEDI and WAYLIVRA

·
Substantial cash position of $2 billion enabling investment in commercial products and pipeline

o
The increase in Ionis’ cash position was primarily due to the $1 billion Ionis received from Biogen for the 2018 strategic neurology collaboration

"Our strong third quarter financial results put us on track for our third consecutive year of pro forma operating income. In the fourth quarter, we are excited to add TEGSEDI commercial sales to our growing SPINRAZA revenue and substantial base of R&D revenue, positioning us for significant revenue growth going forward," said Elizabeth L. Hougen, chief financial officer of Ionis. "Importantly, we are in a strong financial position with sustainable profitability and $2 billion in cash even as we support the launch of TEGSEDI in multiple markets and prepare for the launch of WAYLIVRA. Further, our financial strength coupled with our business strategy provides us with the flexibility to maximize the value of our robust antisense technology platform and innovative pipeline of drugs."

All pro forma amounts referred to in this press release exclude non-cash compensation expense related to equity awards. Please refer to the reconciliation of pro forma and GAAP measures, which is provided later in this release. Additionally, Ionis has labeled its prior period financial statements "as revised" to reflect the new revenue recognition accounting standard the Company adopted on January 1, 2018.

Business Highlights

·
SPINRAZA – the first and only approved treatment for people with spinal muscular atrophy

o
SPINRAZA sales continued to grow in the third quarter, both in the U.S. and ex-U.S., with global sales of more than $1 billion for year-to-date 2018, as reported by Biogen.

o
Nearly 6,000 SMA patients were on SPINRAZA as of the third quarter.

o
In the U.S., the number of adult patients on therapy grew by over 20 percent compared to the second quarter. Adult SMA patients, which represent the largest and most undertreated patient segment, accounted for more than 50 percent of start forms in the third quarter.

o
Access outside the U.S. expanded with formal reimbursement in 28 markets and continued revenue growth in the EU, Asia Pacific and Latin America.

·
TEGSEDI (inotersen) – launched in multiple markets for the treatment of polyneuropathy of hereditary transthyretin amyloidosis (hATTR) in adult patients

o
TEGSEDI approved in the U.S., EU and Canada

o
Commercial patients in Germany on TEGSEDI

o
TEGSEDI prescriptions received in the U.S.

·
WAYLIVRA (volanesorsen) – under regulatory review for the treatment of people living with FCS

o
Preparing for launch in the EU following approval

o
Planning to confirm a path forward in the U.S. and Canada

Pipeline and Business Progress

·
Ionis and Akcea reported positive top-line data from a Phase 2 study of AKCEA-APO(a)-LRx in people with high levels of Lp(a) and established cardiovascular disease demonstrating robust target reductions and a favorable safety and tolerability profile
·
Ionis and Roche entered a new collaboration to develop IONIS-FB-LRx for the treatment of people with complement-mediated diseases. Ionis received a $75 million upfront payment and will be eligible for development, regulatory and sales milestone payments and license fees of up to $684 million plus royalties of up to 20 percent on commercial sales
·
Positive Phase 1b/2 data for danvatirsen (IONIS-STAT3-2.5Rx) in combination with durvalumab were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, demonstrating a response rate approximately double that of durvalumab alone, based on previous studies in patients with refractory head and neck cancer. Ionis earned a $17.5 million milestone payment because AstraZeneca is advancing the program
·
Ionis completed enrollment in a Phase 2b study of IONIS-FXIRx in patients with end-stage renal disease on dialysis, with data planned for mid-2019
·
Ionis or its partners initiated clinical studies with IONIS-GHR-LRx (Phase 2), IONIS-C9Rx (Phase 1/2), IONIS-FXI-LRx and IONIS-AZ4-2.5-LRx (Phase 1)
·
Ionis earned a $10 million milestone payment from AstraZeneca for advancing an undisclosed oncology program into development
·
Ionis appointed Dr. Michael Hayden and Mr. Peter N. Reikes to its Board of Directors

Key Upcoming Events

·
Potential approval and launch of WAYLIVRA in the EU

·
Pivotal program initiation for IONIS-HTTRx in patients with Huntington’s disease

·
Results from up to three Phase 2 studies and four Phase 1 studies

·
Initiations of up to three Phase 2 studies and two Phase 1 studies
The increase in revenue in the first nine months of 2018 compared to the same period in 2017 was primarily due to increasing commercial revenue from SPINRAZA royalties, which increased over 175 percent. Our R&D revenue for the first nine months of 2018 was significant and demonstrates our ability to generate sustainable revenue from our numerous partnerships.

R&D revenue from the amortization of upfront payments increased by $22 million in the first nine months of 2018, compared to the same period in 2017 primarily due to Ionis’ 2018 strategic neurology collaboration with Biogen, which started in the second quarter of 2018. In the fourth quarter of 2018, Ionis will add amortization revenue from its new collaboration with Roche to develop IONIS-FB-LRx.

Ionis’ 2018 R&D revenue from milestone payments was bolstered by two $10 million milestone payments in the third quarter, one from Biogen and one from AstraZeneca, as Ionis’ partnered programs advanced. In the same period of 2017, R&D revenue from milestone payments included $90 million of milestone payments from Biogen for SPINRAZA approval in the EU and Japan. Already in the fourth quarter, Ionis has earned nearly $30 million in milestone payments from AstraZeneca.

Operating Expenses

Operating expenses for the three and nine months ended September 30, 2018 on a GAAP basis were $164 million and $480 million, respectively, and on a pro forma basis were $129 million and $383 million, respectively. These amounts compare to GAAP operating expenses for the three and nine months ended September 30, 2017 of $107 million and $309 million, respectively, and pro forma operating expenses of $86 million and $246 million, respectively. The increases in operating expenses were principally due to higher SG&A expenses as Akcea, Ionis’ affiliate, prepared to commercialize TEGSEDI and WAYLIVRA. The Company’s SG&A expenses also increased due to an increase in fees the Company owed under its in-licensing agreements related to SPINRAZA, as a result of increased SPINRAZA product sales.

Net Income (Loss) Attributable to Ionis Common Stockholders

Ionis reported a net loss attributable to Ionis’ common stockholders of $5 million and $46 million for the three and nine months ended September 30, 2018, respectively, compared to a net loss of $3 million and net income of $3 million for the same periods in 2017, all on a GAAP basis. On a pro forma basis, Ionis reported net income attributable to Ionis’ common stockholders of $30 million and $51 million for the three and nine months ended September 30, 2018, respectively, compared $19 million and $67 million for the same periods in 2017.

At September 30, 2018, Ionis owned approximately 75 percent of Akcea. The shares of Akcea third parties own represent an interest in Akcea’s equity that Ionis does not control. However, because Ionis continues to maintain overall control of Akcea through its voting interest, Ionis reflects the assets, liabilities and results of operations of Akcea in Ionis’ consolidated financial statements. Ionis reflects the noncontrolling interest attributable to other owners of Akcea’s common stock in a separate line called "Net loss attributable to noncontrolling interest in Akcea" on Ionis’ statement of operations. Ionis’ net loss attributable to noncontrolling interest in Akcea for the three and nine months ended September 30, 2018, was $16 million and $41 million, respectively. Ionis’ net loss attributable to noncontrolling interest in Akcea for the three and nine months ended September 30, 2017, was $5 million.

For the three months ended September 30, 2018 and 2017, basic and diluted net loss per share were $0.03 and $0.02, respectively. For the nine months ended September 30, 2018, basic and diluted net loss per share were each $0.33. For the nine months ended September 30, 2017, basic and diluted net income per share were each $0.13. All amounts are on a GAAP basis.

Balance Sheet

As of September 30, 2018, Ionis had cash, cash equivalents and short-term investments of $2 billion compared to $1 billion at December 31, 2017. The increase in Ionis’ cash, cash equivalents and short-term investments was primarily due to the $1 billion Ionis received from Biogen for the 2018 strategic neurology collaboration.

Webcast and Conference Call

Today, at 11:30 a.m. Eastern Time, Ionis will conduct a live webcast conference call to discuss this earnings release and related activities. Interested parties may listen to the call by dialing 877-443-5662 or access the webcast at www.ionispharma.com. A webcast replay will be available for a limited time.