On February 27, 2019 NewLink Genetics Corporation (NASDAQ:NLNK) reported consolidated financial results for the fourth quarter and year ended 2018, as well as progress in its clinical development programs (Press release, NewLink Genetics, FEB 27, 2019, View Source [SID1234533736]). The Company also outlined key 2019 priorities related to its clinical pipeline.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In 2018, we published further clinical results on indoximod that suggest it has significant activity in combination therapy for a variety of cancer indications," said Charles J. Link, Jr, MD, Chairman and Chief Executive Officer. "As we enter 2019 with a strong cash position, our intention is to focus on developing the best potential registration strategy for bringing indoximod forward and further developing our pipeline assets, especially NLG207. We would like to thank the investigators and patients who support our clinical trials year after year, and we remain committed to your care."

Anticipated 2019 Outlook

Updated results on the cohort of patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG), from the efficacy portion of a Phase 1b study of indoximod for the treatment of pediatric patients with recurrent malignant brain tumors, are anticipated in 2019

Results from a Phase 2 study of NLG207 (formerly CRLX101), a nanoparticle formulation of the topoisomerase 1 inhibitor, camptothecin, conducted by the Gynecological Oncology Group (GOG) for patients with recurrent ovarian cancer, has been accepted for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, at the Georgia World Conference Center, in Atlanta, March 29 – April 3, 2019

Updated results from a Phase 1 study of NLG802, a prodrug of indoximod with enhanced pharmacokinetic properties, are anticipated in 2019

Updated results from a Phase 1b study of indoximod for pediatric patients with recurrent malignant brain tumors are anticipated in 2019

Completion by Merck of the rolling Biologics License Application (BLA) filing for V920 (rVSV∆G-ZEBOV-GP), our partnered Ebola vaccine candidate, is expected in 2019
2018 Highlights

Presented Phase 1 results of indoximod plus front-line radiation and maintenance chemotherapy for the treatment of pediatric patients with newly diagnosed DIPG at the American Association of Clinical Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 2018, and updated Phase 1 results at the International Symposium of Pediatric Neuro-Oncology (ISPNO) Annual Meeting, July 2018, showing symptomatic improvement and marked radiographic improvement in DIPG patients.

Presented updated Phase 1 results for indoximod plus standard of care chemotherapy for younger, healthy patients with newly diagnosed acute myeloid leukemia (AML) in an oral session at the 60thAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, December 2018

Presented final results from two Phase 2 studies of indoximod at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting with results for indoximod plus checkpoint inhibition in advanced melanoma which we believe showed encouraging overall and complete response rates which compared favorably to historical PD-1 monotherapy results and results for indoximod plus gemcitabine / nab-paclitaxel in metastatic pancreatic cancer demonstrating potentially promising activity that correlated with a measurable immune response

At the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2018 Annual Meeting, we presented correlative immunologic assay results from biopsies obtained during both the advanced melanoma and the metastatic pancreatic cancer trials previously presented at ASCO (Free ASCO Whitepaper) 2018, illustrating indoximod’s impact on the tumor microenvironment as well as first-in-human results showing significantly enhanced pharmacokinetic properties of our indoximod prodrug, NLG802

November 13, 2018, our partner, Merck, announced that it had begun the rolling submission of licensure application for Ebola vaccine, V920 (rVSV∆G-ZEBOV-GP), to the FDA
Financial Results

Cash Position: NewLink Genetics ended the year on December 31, 2018, with cash and cash equivalents totaling $120.7 million compared to $158.7 million for the year ending December 31, 2017. The Company projects its cash position is sufficient to fund planned operations through the end of 2021.

R&D Expenses: Research and development expenses were $5.7 million and $45.7 million in the fourth quarter and year ended December 31, 2018 compared to $17.5 million and $69.9 million during the comparable periods in 2017. The decrease year-over-year was due primarily to a $15.2 million reduction in contract research and manufacturing expense, $3.0 million in personnel-related expense, $3.3 million in supplies and equipment, $1.8 million in clinical trial costs, $1.3 million in technology and licensing, and reduction in restructuring expenses of $100,000, offset by a $500,000 increase in consulting and other costs.

G&A Expenses: General and administrative expenses in the fourth quarter and year ended December 31, 2018 were $5.4 million and $29.2 million compared to $6.7 million and $31.7 million during the comparable periods in 2017. The year-over-year decrease of $2.5 million was due to a reduction of $2.5 million in personnel-related spending, $550,000 reduction in consulting and other costs, reduction in restructuring expenses of $300,000, offset by an $850,000 increase in supplies and other expenses.

Net Loss: NewLink Genetics reported a net loss of $10.6 million or a loss of $0.28 per diluted share for the fourth quarter of 2018 and a net loss of $53.6 million or a loss of $1.44 per diluted share for the year ended December 31, 2018, compared to a net loss of $13.7 million or $0.37 per diluted share for the fourth quarter of 2017 and a net loss of $72.0 million or $2.30 per diluted share for the year ended December 31, 2017.

NewLink Genetics ended 2018 with 37,251,220 shares outstanding.

Conference Call and Webcast Details

The Company has scheduled a conference call and webcast for 4:30 p.m. ET today to discuss the results and to give an update on clinical and business development activities. NewLink Genetics’ senior management team will host the call, which will be open to all listeners. There will also be a question and answer session following the prepared remarks.

Access to the live conference call is available by dialing (855) 469-0612 (U.S.) or (484) 756-4268 (international) five minutes prior to the start of the call. The conference call will be webcast live and a link to the webcast can be accessed through the NewLink Genetics website at www.NewLinkGenetics.com in the "Investors & Media" section under "Events and Presentations," or through this link View Source To ensure a timely connection, it is recommended that users register at least 15 minutes prior to the scheduled webcast. A replay of the call will be available approximately two hours after the completion of the call and can be accessed by dialing (855) 859-2056 (U.S.) or (404) 537-3406 (international) and using the passcode 1279102. The replay will be available for two weeks from the date of the call.

About Indoximod

Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is a key immuno-oncology target, suppressing immune response and allowing for immune escape by degrading tryptophan with the resultant production of kynurenine. Indoximod reverses the immunosuppressive effects of low tryptophan and high kynurenine through mechanisms that include modulation of the AhR-driven transcription of genes that control immune function. This results in increased proliferation of effector T cells, increased differentiation into helper T cells rather than regulatory T cells, and downregulation of IDO expression in dendritic cells. Indoximod is being evaluated in combination with treatment regimens including chemotherapy, radiation, checkpoint blockade and cancer vaccines across multiple indications including recurrent pediatric brain tumors, DIPG, and AML.

About NLG207

NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone conjugated to camptothecin, a topoisomerase-1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. Topoisomerase 1 inhibitors are a class of drugs that modify DNA damage responses in cancer cells. NewLink Genetics is evaluating NLG207 in a series of clinical trials in advanced refractory ovarian cancer patients.

On February 27, 2019 NewLink Genetics Corporation (NASDAQ:NLNK) reported that a late-breaking abstract reporting results from a Phase 2 study of NLG207, a nanoparticle formulation of the topoisomerase 1 inhibitor, camptothecin, has been accepted for poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held at the Georgia World Congress Center, March 29 – April 3, in Atlanta, Georgia (Press release, NewLink Genetics, FEB 27, 2019, View Source [SID1234533735]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Abstract 7933 (Poster 17) entitled, A phase II study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer, Duska, L., et al, will be presented during the poster session entitled, "Phase II-III Clinical Trials: Part 1," in Exhibit Hall B, Poster Section 16 on Tuesday, April 2, 2019 from 8:00 a.m. – 12:00 p.m. ET.

The complete text of this abstract will be posted to the AACR (Free AACR Whitepaper) website on Friday, March 29, at 3:00 p.m. ET.

About NLG207

NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone conjugated to camptothecin, a topoisomerase-1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. Topoisomerase 1 inhibitors are a class of drugs that modify DNA damage responses in cancer cells. NewLink Genetics is evaluating NLG207 in a series of clinical trials in advanced refractory ovarian cancer patients.

On February 27, 2019 United Therapeutics Corporation (Nasdaq: UTHR) reported its financial results for the fourth quarter and year ended December 31, 2018 (Press release, United Therapeutics, FEB 27, 2019, View Source [SID1234533733]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"2018 was a truly transformative year for United Therapeutics. We signed four major agreements to acquire new product candidates, including an in-licensing agreement for ralinepag, representing our largest deal to date," said Martine Rothblatt, Ph.D., Chairman and Chief Executive Officer of United Therapeutics. "At the same time, we continued to execute against our existing commercial and clinical goals, including the successful readout of our FREEDOM-EV clinical trial, significant progress toward near-term phase III readouts for our BEAT and DISTINCT studies, and an increase to a record number of patients being treated with our treprostinil therapies."

Recent Highlights

· Closed license agreement with MannKind for Treprostinil Technosphere

· Appointed Nilda Mesa to the Board of Directors

· Health Canada approved Unituxin (dinutuximab) for high-risk neuroblastoma

· Submitted efficacy supplement to FDA to include FREEDOM-EV data in the Orenitram label

· In-licensed global rights to ralinepag, a phase III PAH drug candidate

·Presented survival data from FREEDOM-EV study of Orenitram at the Pulmonary Vascular Research Institute Annual World Congress

Financial Results for the Quarter and Year Ended December 31, 2018 compared to the same periods in 2017

Key financial highlights include (in millions, except per share data):

(1) See definition of non-GAAP earnings, a non-GAAP financial measure, and a reconciliation of net income to non-GAAP earnings below.

Revenues for the quarter and year ended December 31, 2018 decreased by $83.3 million and $97.5 million, respectively, as compared to the same periods in 2017.

Remodulin net product sales for the quarter and year ended December 31, 2018 decreased by $21.0 million and $71.9 million, respectively, as compared to the same periods in 2017. For the quarter and year ended December 31, 2018, international Remodulin net sales decreased by $30.7 million and $90.0 million, respectively, compared to the same periods in 2017, primarily due to the transfer of additional regulatory and commercial responsibilities to an international distributor in the third quarter of 2017. As a result of this transfer, we recognized $23.7 million and $47.4 million of net product sales in the quarter and year ended December 31, 2017, respectively, related to the one-time purchase of Remodulin inventory by that distributor and we reduced the price at which we sell Remodulin to that distributor. The remaining decrease was primarily due to a reduction in quantities shipped to that distributor. For the quarter and year ended December 31, 2018, U.S. Remodulin net sales increased by $9.7 million and $18.1 million, respectively, compared to the same periods in 2017, primarily due to a price increase that was implemented in April 2018, which was the first price increase for Remodulin since 2010, and an increase in the number of patients being treated with Remodulin. For the year ended December 31, 2018, these increases were partially offset by the one-time $4.5 million impact of a change in contractual minimum inventory levels with a U.S. distributor, as discussed below.

Tyvaso net product sales for the quarter and year ended December 31, 2018 increased by $14.5 million and $42.3 million, respectively, as compared to the same periods in 2017. These increases were primarily due to price increases that were implemented in April 2017 and January 2018 and the reversal in the fourth quarter of 2018 of an estimated $15.4 million liability for Medicaid rebates, of which $13.6 million was initially recorded in 2017. In addition, Tyvaso net product sales increased due to an increase in the number of patients being treated with Tyvaso. These increases were offset by (1) the impact of replacing $6.2 million of commercial Tyvaso product that our specialty pharmaceutical distributor previously used in connection with a clinical trial; and (2) the one-time $3.5 million impact of a change in contractual minimum inventory levels with a U.S. distributor, as discussed below.

Adcirca net product sales for the quarter and year ended December 31, 2018 decreased by $77.6 million and $96.0 million, respectively, as compared to the same periods in 2017. These decreases were primarily due to the launch of a generic version of Adcirca in August 2018, partially offset by price increases that were implemented by Eli Lilly and Company in May 2017 and January 2018. In addition, we increased our allowance for product returns for Adcirca by $16.4 million in the third quarter of 2018 based on our estimates of inventory held by distributors and other downstream customers that would expire unsold as a result of the increased use of a generic version of Adcirca.

Orenitram net product sales for the quarter and year ended December 31, 2018 increased by $1.6 million and $19.3 million, respectively, as compared to the same periods in 2017. These increases were primarily due to an increase in the number of patients being treated with Orenitram, a price increase that was implemented in January 2018 and, for the year ended December 31, 2018, the one-time $3.7 million impact of a change in contractual minimum inventory levels with a U.S. distributor, as discussed below.

Unituxin net product sales decreased by $0.8 million for the quarter ended December 31, 2018 and increased by $8.8 million for the year ended December 31, 2018, as compared to the same periods in 2017. For the year ended December 31, 2018, Unituxin net product sales increased due to an increase in the number of vials sold and price increases that were implemented in April and December 2017.

During the fourth quarter of 2017, we amended our agreements with one of our U.S. specialty pharmacy distributors, in part to make the monthly minimum inventory requirement consistent across Remodulin, Tyvaso and Orenitram. This change resulted in a one-time decrease in total net product sales of $4.3 million as the distributor adjusted to the new contractual inventory requirement levels in the first quarter of 2018. On an individual product basis, net product sales of Remodulin decreased by $4.5 million, net product sales of Tyvaso decreased by $3.5 million, and net product sales of Orenitram increased by $3.7 million.

(1)Refer to Share-based compensation below for discussion.

Cost of product sales, excluding share-based compensation. The decrease in cost of product sales of $14.5 million for the quarter ended December 31, 2018, as compared to the same period in 2017, was primarily attributable to a decrease in Adcirca sales.

The increase in cost of product sales of $98.8 million for the year ended December 31, 2018, as compared to the same period in 2017, was primarily attributable to a $96.9 million increase in royalty expense for Adcirca. As a result of an amendment to our license agreement with Lilly, effective December 1, 2017, our royalty rate on net product sales of Adcirca increased from five percent to an effective rate of approximately 42.5 percent.

Research and development expense. The table below summarizes research and development expense by major category (dollars in millions):

(1) Refer to Share-based compensation below for discussion.

Research and development expense, excluding share-based compensation. We continued to invest in our product pipeline during 2018, which includes products in multiple phase III clinical trials in cardiopulmonary diseases and oncology as well as programs in regenerative medicine and organ manufacturing. The increase in research and development expense of $48.4 million for the quarter ended December 31, 2018, as compared to the same period in 2017, was primarily due to an up-front payment of $45.0 million under our license agreement with MannKind.

The increase in research and development expense of $113.6 million for the year ended December 31, 2018, as compared to the same period in 2017, was driven by an increase of $95.9 million in research and development expense for the treatment of cardiopulmonary diseases, primarily due to up-front payments of $55.0 million under our license and research agreements with MannKind and $10.0 million under our license agreement with Samumed, increased spending of $22.9 million on the development of drug delivery devices, including the Implantable System for Remodulin and RemUnity, and increased spending on several clinical and non-clinical studies. Research and development expense for cancer-related projects increased by $13.9 million due to an increase in spending on the DISTINCT study. Research and development expense for organ manufacturing projects increased by $3.9 million due to increased preclinical work on technologies designed to increase the supply and distribution of transplantable organs and tissues.

Selling, general and administrative expense. The table below summarizes selling, general and administrative expense by major category (dollars in millions):

(1) Refer to Share-based compensation below for discussion.

General and administrative, excluding share-based compensation. The increase in general and administrative expenses of $6.7 million for the quarter ended December 31, 2018, as compared to the same period in 2017, primarily resulted from a $5.0 million increase in consulting fees.

The increase in general and administrative expenses of $14.7 million for the year ended December 31, 2018, as compared to the same period in 2017, primarily resulted from: (1) a $10.3 million increase in consulting expenses; (2) a $4.7 million increase in compensation due to an increase in staffing; and (3) a $4.4 million increase in acquisition and integration costs related to the SteadyMed acquisition. The increase was partially offset by a $7.1 million decrease in legal fees incurred in connection with intellectual property litigation and a Department of Justice (DOJ) investigation.

Sales and marketing, excluding share-based compensation. Sales and marketing expenses for the quarter ended December 31, 2018, remained relatively consistent as compared to the same period in 2017.

The decrease in sales and marketing expenses of $5.2 million for the year ended December 31, 2018, as compared to the same period in 2017, primarily resulted from a decrease in marketing consulting fees.

Share-based compensation. The table below summarizes share-based compensation expense (benefit) by major category (dollars in millions):

Share-based compensation. The decreases in share-based compensation of $115.7 million and $99.9 million, respectively, for the quarter and year ended December 31, 2018, were primarily due to decreases in STAP expense of $117.9 million and $120.5 million, respectively, primarily driven by a decrease in our stock price for the quarter and year ended December 31, 2018, as compared to the same periods in 2017. The decrease in STAP expense for the year-ended December 31, 2018 was partially offset by an increase of $15.5 million in stock option expense due to additional awards granted and outstanding in 2018 and a $5.1 million increase in restricted stock unit expense due to additional awards granted and outstanding in 2018.

Settlement of Loss Contingency

In December 2017, we entered into a civil Settlement Agreement with the U.S. Government to resolve a DOJ investigation. During the second quarter of 2017, we recorded a $210.0 million accrual relating to this matter, and ultimately paid this amount, plus interest, to the U.S. Government upon settlement.

Impairments of Investments in Privately-Held Companies

During the years ended December 31, 2018 and 2017, we recorded impairment charges of $53.5 million and $49.6 million, respectively, related to our investments in privately-held companies.

Income Taxes

The provision for income taxes was $169.7 million for the year ended December 31, 2018, compared to $351.6 million for the same period in 2017. The change in the provision for income taxes was primarily due to the impacts of The Tax Cuts and Jobs Act (Tax Reform) and the nondeductible portion of an accrual in 2017 in connection with a civil settlement with the DOJ. For the years ended December 31, 2018 and 2017, the effective tax rates were approximately 22 percent and 46 percent, respectively.

Non-GAAP Earnings

Non-GAAP earnings is defined as net income, adjusted for: (1) share-based compensation expense (including expenses relating to stock options, restricted stock units, share tracking awards, and our employee stock purchase plan); (2) loss contingency; (3) impairments of investments in privately-held companies; (4) license fees; (5) impact of Tax Reform; and (6) tax impact on non-GAAP earnings adjustments.

(1)We calculated the total tax impact of non-discrete quarterly non-GAAP earnings adjustments based on our annual effective tax rates, before considering discrete items, of approximately 21 percent and approximately 32 percent for each of the quarters and years ended December 31, 2018 and 2017, respectively.

(2) The tax benefit for the year ended December 31, 2017 includes $57.0 million of benefit for the estimated loss contingency recognized during the second quarter of 2017 relating to a DOJ investigation.

(3)This non-GAAP earnings adjustment is currently not considered tax deductible.

(4) The impact of Tax Reform is a significant and unusual component of tax expense, therefore in the calculation of non-GAAP earnings, it is presented separately from the tax benefit that is derived from the other non-GAAP adjustments.

Conference Call

We will host a one-hour teleconference on Wednesday, February 27, 2019, at 9:00 a.m. Eastern Time. The teleconference is accessible by dialing 1-877-351-5881, with international callers dialing 1-970-315-0533. A rebroadcast of the teleconference will be available for one week by dialing 1-855-859-2056, with international callers dialing 1-404-537-3406 and using access code 1595239.

This teleconference is also being webcast and can be accessed via our website at View Source

On February 27, 2019 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reported its fourth quarter and full year 2018 financial results and highlights (Press release, Synta Pharmaceuticals, FEB 27, 2019, View Source [SID1234533732]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Madrigal made significant progress in 2018 in advancing the development of MGL-3196. We successfully completed Phase 2 studies in both NASH and dyslipidemia and expanded the Madrigal team to meet the demands of our clinical programs," stated Paul Friedman, M.D., Chief Executive Officer of Madrigal. "In June, we also raised approximately $312 million of net proceeds from a public offering of our common stock, 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 had a positive end of phase 2 meeting with FDA for our NASH program, and we expect to initiate our Phase 3 clinical trial before the end of the first quarter of 2019. We continue to believe MGL-3196 has the potential to resolve NASH while decreasing cardiovascular risk, through reduction of levels of multiple atherogenic lipids as well as reduction of fat in the liver. Based on this potential cardiovascular risk reducing profile, we also intend to move ahead with our Phase 3 dyslipidemia clinical program later this year."

Financial Results for the Three Months and Twelve Months Ended December 31, 2018

As of December 31, 2018, Madrigal had cash, cash equivalents and marketable securities of $483.7 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 $25.5 million.

Operating expenses were $14.5 million and $40.7 million, respectively, for the three month and twelve month periods ended December 31, 2018, compared to $8.9 million and $32.1 million in the comparable prior year periods.

Research and development expenses for the three month and twelve month periods ended December 31, 2018 were $8.9 million and $25.4 million, respectively, compared to $6.5 million and $24.4 million in the comparable prior year periods. The increases are primarily attributable to increases in non-cash stock compensation, personnel and

consulting costs, the effects of which were partially offset by lower clinical costs due to completion of treatment in our Phase 2 clinical studies in 2018.

General and administrative expenses for the three month and twelve month periods ended December 31, 2018 were $5.6 million and $15.3 million, respectively, compared to $2.4 million and $7.7 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 twelve month periods ended December 31, 2018 was $3.0 million and $7.7 million, respectively, as compared to $216 thousand and $558 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.

Dyslipidemia

Patients with NASH, and its more prevalent precursor, Non-Alcoholic Fatty Liver Disease (NAFLD), are at heightened cardiovascular risk. In fact, patients suffering from these conditions die more frequently from cardiovascular events than from their liver

disease. Multiple factors may contribute to this risk, including elevated levels of LDL-C and excess liver fat. Patients with NASH and NAFLD, however, may not undergo a biopsy to confirm a NASH diagnosis until they reach the more advanced stages of fibrosis (F2 — F4). A significant segment of this large group of patients may also suffer from diabetes and metabolic syndrome, and have lipid levels that are above target despite treatment with established therapies. These patients may benefit from therapy to lower their lipid levels, including excess liver fat.

We believe Madrigal’s studies to date in patients with NASH and patients with heterozygous familial hypercholesterolemia (HeFH), have demonstrated the pleiotropic activity of MGL-3196 and the potential of the drug to reduce an array of atherogenic lipids, including liver fat, LDL-C, ApoB, triglycerides, ApoCIII, and Lp(a), as well as hs-CRP. As a result, Madrigal intends to focus its development of MGL-3196 for the treatment of patients across the entire NASH and NAFLD spectrum.

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, and a Phase 3 clinical program is dyslipidemia

On February 27, 2019 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported the Company’s VP of Business Development, Sari Fishman will participate in the Bio Asia International Conference in Tokyo, Japan on March 5th and 6th, 2019.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The BIO Asia International Conference brings together the global biotechnology and pharmaceutical industry to explore licensing collaborations and investor engagement in the current Asia-Pacific business and policy environments.

Dr. Fishman is scheduled to conduct more than 20 one-on-one meetings with business development officers from leading pharmaceutical companies interested in learning more about Can-Fite’s advanced stage drug candidates.

Can-Fite’s current pharma partnerships in Asia include distribution and development agreements with Kwang Dong in Korea for Piclidenoson, Chong Kun Dang in Korea for Namodenoson, and CMS in China for Piclidenoson and Namodenoson. The Company sees substantial additional partnership opportunities in Asia.