On February 27, 2019 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that it will host a conference call and webcast to report its fourth quarter and fiscal year 2018 financial results on Wednesday, March 6, 2018, at 8:30 a.m. ET (Press release, GlycoMimetics, FEB 27, 2019, View Source [SID1234533738]).

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The dial-in number for the conference call is (844) 413-7154 for domestic participants and (216) 562-0466 for international participants, with participant code 5072004. A webcast replay will be available via the "Investors" tab on the GlycoMimetics website for 30 days following the call. A dial-in phone replay will be available for 24 hours after the close of the call by dialing (855) 859-2056 for domestic participants and (404) 537-3406 for international participants, participant code 5072004.

On February 27, 2019 ImmunoGen, Inc., (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that 11 posters highlighting continued innovation in the field of ADCs will be presented at the upcoming American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held March 29 – April 3, 2019 in Atlanta, Georgia (Press release, ImmunoGen, FEB 27, 2019, View Source [SID1234533737]).

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"ImmunoGen remains at the forefront of ADC innovation and the data to be presented at AACR (Free AACR Whitepaper) further demonstrate the value of our productive research platform," said Richard Gregory, Ph.D., ImmunoGen’s chief scientific officer.

The schedule of ImmunoGen’s presentations at AACR (Free AACR Whitepaper) is as follows:

IGN Payload Innovation

Title: Antibody-drug conjugates (ADCs) of a new class of N-10 amino linked DNA alkylating indolino-benzodiazepines (IGNs) – abstract #224
Date: March 31, 2019
Time: 1:00-5:00 PM ET

In an ongoing effort to further explore the structure-activity relationship of DNA alkylating effector molecules for ADCs, a new class of IGNs has been developed that possesses a self-immolative peptide linker attached at the N-10 amine of the imine-reduced IGN monomer subunit. ADCs with this class of payload displayed potent, antigen-specific in vitro activity across a panel of folate receptor α (FRα)-expressing cell lines.
Title: Antibody-drug conjugates (ADCs) with indolinobenzodiazepine dimer (IGN) payloads: DNA-binding mechanism of IGN catabolites in target cancer cells – abstract #1886
Date: March 31, 2019
Time: 1:00-5:00 PM ET

Investigation of the mechanism of binding of IGN catabolites with DNA in target cancer cells and with model duplex DNA or hairpin oligonucleotides. Both mono-and-di-imine IGN molecules remained bound to genomic DNA even at two days, suggesting a potent interaction with cellular DNA.
Advancement in Platform Linkers and Payloads

Title: Optimizing lysosomal activation of antibody-drug conjugates (ADCs) by incorporation of novel cleavable dipeptide linkers – abstract #0231
Date: March 31, 2019
Time: 1:00-5:00 PM ET

Based on screens of a panel of dipeptide linkers for efficient lysosomal proteolysis, several novel, previously unreported peptide linker designs were identified and incorporated into ADCs bearing a DNA-alkylating IGN payload. Several dipeptide linker designs were superior in rates of lysosomal processing compared to a reference standard L-Ala-L-Ala dipeptide linker.
Title: LC-MS based catabolite identification study of an ADC with DM21-C, a novel maytansinoid linker-payload – abstract #538
Date: March 31, 2019
Time: 1:00-5:00 PM ET

ImmunoGen’s newest ADC design uses the novel maytansinoid linker-payload, DM21-C that bears a peptidase/protease-cleavable linker. The goal of this study was to identify the catabolites generated upon incubation in antigen-positive cancer cells (both cell pellet and media), in mouse plasma, as well as in in vitro catabolic systems. DM51 (the thiol- resulting from self-immolation of the cleaved linker-payload) was identified as a major catabolite of the DM21-C ADC.
Title: Preclinical evaluation of DM21, a next‐generation maytansinoid payload with a stable peptide linker – abstract #3898
Date: April 2, 2019
Time: 1:00-5:00 PM ET

To evaluate the toxicity of DM21 as an ADC, it was conjugated to the non‐targeting, chimeric anti‐soybean trypsin inhibitor antibody (chKTI), and administered to cynomolgus monkeys in two groups with separate dose levels. chKTI‐DM21 was well-tolerated at both doses.
Novel Approaches to ADC Development

Title: Generation of site-specific DARPin drug conjugates using EGFR as a model system – abstract #215
Date: March 31, 2019
Time: 1:00-5:00 PM ET

DARPin molecules are small engineered proteins, derived from natural ankyrin repeat proteins that are selected to bind to specific targets with high affinity. DARPin drug conjugates (DDCs) were developed using a model EGFR multi-specific DARPin molecule, consisting of four DARPin domains linked together. Biophysical characterization showed the DDCs to be well behaved in stability and solubility assays.
Title: Development of a Probody-Drug Conjugate (PDC) targeting EpCAM for the treatment of solid tumors- abstract #1439
Date: March 31, 2019
Time: 1:00-5:00 PM ET

EpCAM is an attractive target for ADC development due to its overexpression on a variety of tumors of epithelial origin; however, EpCAM is also expressed on a variety of normal epithelia, thus limiting its utility as an ADC target due to potential toxicity. We aim to overcome this limitation by developing an EpCAM-targeting Probody drug conjugate (PDC). EpCAM-targeting PDCs were better tolerated than the corresponding EpCAM-targeting ADC even at higher dose levels and displayed longer half-lives and greater exposure.
Title: IMGC936, a first-in-class ADAM9-targeting antibody-drug conjugate, demonstrates promising anti-tumor activity – abstract #5136
Date: April 1, 2019
Time: 8:00 AM-12:00 PM ET

Under a co-development agreement with MacroGenics, it has been shown that ADAM9 is overexpressed in multiple solid tumor indications and that anti-ADAM9 antibodies are efficiently internalized and degraded by tumor cell lines, making ADAM9 an attractive target for ADC development. IMGC936 is the first ADAM9-targeting ADC to enter preclinical development. In vitro studies have demonstrated targeted cytotoxicity of IMGC936 across a panel of ADAM9-positve tumor cell lines with activity at least 2 logs greater than a non-targeting conjugate. Consistent with the activity observed in vitro, an anti-ADAM9-DM21 conjugate displayed compelling anti-tumor activity in multiple xenograft models representing non-small cell lung, gastric and colorectal cancers.
Title: Preclinical evaluation of a new, non-agonist ADC targeting MET-amplified tumors with a peptide-linked maytansinoid – abstract #4817
Date: April 3, 2019
Time: 8:00 AM-12:00 PM ET

cMet is an attractive target for ADCs, which may address the unmet treatment need for patients with tumors harboring MET amplification. To assess potential toxicity due to normal tissue expression, binding of our antibody to normal hepatocytes from humans and cynos was measured. Very low expression and binding versus tumor cell lines were found and demonstrated that the cytotoxic activity of disulfide-cleavable maytansinoid ADCs prepared from the hinge-variant cMet antibody was equivalent to the parental form in in vivo models. These data merit further exploration of this ADC as a novel treatment option for patients with MET-amplified tumors.
Optimizing ADC Dosing

Title: The potential benefit of lower drug-antibody ratio (DAR) on antibody-maytansinoid conjugate in vivo efficacy – abstract #219
Date: March 31, 2019
Time: 1:00-5:00 PM

Describes development of a cross-reactive model system that utilizes a chimeric anti-murine FRα antibody that binds with similar affinity to mouse and human FRα. Using this cross-reactive system, where the target is also expressed in normal tissues, 2.0 DAR conjugates were more efficacious than 3.5 DAR conjugates when dosed at matched payload concentrations in multiple xenograft models, suggesting that lower DAR can be an effective strategy to compensate for target-mediated drug disposition (TMDD).
Title: Utilizing a mouse cross-reactive model system to better understand antibody-drug conjugate pharmacokinetics, biodistribution and efficacy – abstract #229
Date: March 31, 2019
Time: 1:00-5:00 PM ET

Generation of a cross-reactive model system that utilized a chimeric anti-murine FRα antibody that binds both mouse and human FRα and can be conjugated to either maytansinoid or IGN payloads. This model system was predicted to have substantial TMDD due to normal tissue expression of FRα. The results showed that TMDD significantly affected the pharmacokinetics, biodistribution, and activity of the conjugate relative to a non-cross-reactive ADC, with lower ADC doses being more severely impacted than higher doses.
Additional information and full abstracts can be found at www.aacr.org.

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.

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"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]).

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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]).

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"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