On November 6, 2018 RedHill Biopharma Ltd. (Nasdaq: RDHL) (Tel-Aviv Stock Exchange: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on proprietary drugs for gastrointestinal diseases, reported that it will report its third quarter 2018 financial results on Tuesday, November 13, 2018 (Press release, RedHill Biopharma, NOV 6, 2018, View Source [SID1234530864]).

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The Company will host a conference call on Tuesday, November 13, 2018 at 8:30 a.m. EST to review the financial results and business highlights.

To participate in the conference call, please dial one of the following numbers 15 minutes prior to the start of the call: United States: +1-866-575-6539; International: +1-929-477-0402; and Israel: +972-3-376-1315. The access code for the call is: 2166581.

The conference call will be broadcast live and will be available for replay for 30 days on the Company’s website, View Source Please access the Company’s website at least 15 minutes ahead of the conference call to register.

On November 6, 2018 Oncolytics Biotech Inc. (Nasdaq: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported that it will host a conference call and live webcast for Analysts and Institutional Investors at 8:30 a.m. ET on Monday, November 12, 2018 following release of its third quarter 2018 financial results (Press release, Oncolytics Biotech, NOV 6, 2018, View Source [SID1234530862]).

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The live call may be accessed by dialing (888) 231-8191 for callers in North America. Overseas callers should contact investor relations for the toll-free dial information for their country. A replay of this call will be available approximately two hours after the call is ended at 855-859-2056, using the replay code 6463668 and will be available for six months.

A live webcast of the call will be accessible on the Investor Relations page of Oncolytics’ website at www.oncolyticsbiotech.com and will be archived for six months

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.