On February 24, 2021 Paratek Pharmaceuticals, Inc. (Nasdaq: PRTK), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel life-saving therapies for life-threatening diseases or other public health threats for civilian, government and military use, reported financial results and provided an update on corporate activities for the quarter and year ended December 31, 2020 (Press release, Paratek Pharmaceuticals, FEB 24, 2021, View Source [SID1234575546]).

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 launch of NUZYRA continued to demonstrate consistent quarter-over-quarter growth through 2020 in a challenging environment created by the ongoing COVID-19 pandemic," said Evan Loh, M.D., Chief Executive Officer at Paratek. "The full year commercial net U.S. sales of NUZYRA, which landed at the high end of our guidance range, reflects the strong health of the underlying core commercial business. With two Biomedical Advanced Research and Development Authority (BARDA) Project BioShield procurements for the Strategic National Stockpile (SNS) now anticipated in 2021 plus the expected continued commercial growth of NUZYRA, we are anticipating a significant ramp up in total revenue for 2021. We believe prescribers recognize NUZYRA as an important life-saving antibiotic that addresses patient needs in the face of the growing global threat from antibiotic resistance."

"In our conversations with clinicians over the past several years, it is clear there is a tremendous unmet need for a well-tolerated, once daily oral broad-spectrum antibiotic that includes coverage against MRSA for skin infections. Current generic antibiotic options are universally challenged by either significant bacterial resistance or serious safety concerns that limit their clinical utility," said Adam Woodrow, Paratek’s President and Chief Commercial Officer. "NUZYRA’s product profile makes it a very attractive treatment option for community use. With access now solidly established with the payers and significant support from infectious disease specialists, we believe our primary care expansion will accelerate and strengthen our sales trajectory, especially as we enter the second half of 2021."

Key 2021 Priorities

Expansion of NUZYRA into Primary Care Setting: Paratek completed the hiring of approximately 40 U.S. sales representatives in February 2021 to enable the expansion of the NUZRYA launch into the primary care setting. The Company expects to execute this expansion within its previously communicated cash runway guidance.
NTM Rare Disease Opportunity: The Company plans to initiate a Phase 2b study, as early as mid-2021, to explore the potential utility of omadacycline as a treatment for non-tuberculous mycobacteria (NTM) infections due to Mycobacterium abscessus (M. abscessus), a rare disease with currently no approved therapies. M. abscessus and based on Company estimates represents a potential $1.0 billion addressable market opportunity in the U.S.
Continued Progress of the BARDA Project BioShield Anthrax Program: The Company expects to continue to execute and deliver on its contract with BARDA to develop NUZYRA for the treatment of pulmonary anthrax, a critical bioterrorism threat deemed important to national security by BARDA. These activities include advancing the U.S. onshoring of NUZYRA manufacturing and the continued execution of certain preclinical research activities supporting the pulmonary anthrax development program. Under Paratek’s five-year agreement with BARDA, the Company also anticipates two procurements of 2,500 treatment courses of NUZYRA each in 2021 for addition to the SNS.
Other Recent Highlights

In December 2020, Paratek entered into a $60 million non-recourse loan agreement with an affiliate of R-Bridge Healthcare Investment Advisory (the R-Bridge Loan) that will be repaid using (i) all proceeds of royalties from the Company’s License and Collaboration Agreement with Zai Lab and (ii) an initial 2.5% revenue interest from the Company’s U.S. net sales of NUZYRA (initial annual cap of $10 million).
The net proceeds of the R-Bridge Loan, together with cash on hand, was used to prepay in full all obligations outstanding under the Company’s Amended and Restated Loan and Security Agreement with Hercules Capital on December 31, 2020.
Fourth Quarter and Full Year 2020 Financial Results

Fourth quarter 2020 revenue
Total revenue was $16.0 million for the fourth quarter of 2020, an increase of 17% over the third quarter of 2020 and an increase of 78% over the fourth quarter of 2019.
NUZYRA generated $12.4 million in net U.S. sales during the fourth quarter of 2020, an increase of 14% over the third quarter of 2020 and an increase of 130% over the fourth quarter of 2019.
Government contract service and grant revenue was $2.8 million for the fourth quarter of 2020 versus $2.7 million in the third quarter of 2020. No revenue was generated from the BARDA contract in 2019 as it was executed in December of that year.
Full year 2020 total revenue
Full year 2020 total revenue was $46.9 million, an increase of 184% over full year 2019 total revenue.
NUZYRA generated $38.8 million in net U.S. sales for the full year 2020, an increase of 237% over the full year 2019.
The growth in NUZYRA sales in 2020 reflects the Company’s continued commitment to strong execution and NUZYRA’s attributes that address unmet needs in the marketplace despite the significant disruptions of patient traffic to physician offices and institutions throughout the ongoing COVID-19 pandemic.
In today’s COVID-19 environment, NUZYRA’s ability to minimize hospital stays with the oral formulation is especially relevant for many prescribers and a meaningful benefit for patients.
Government contract service and grant revenue was $6.7 million in 2020. No revenue was generated from the BARDA contract in 2019 as it was executed in December of that year.
Collaboration and royalty revenue of $1.5 million in 2020 is primarily comprised of royalties earned from SEYSARA sales in the U.S. Collaboration and royalty revenue of $5.0 million in 2019 included a $3.0 million milestone earned from Zai Lab in addition to royalties earned from SEYSARA sales in the U.S.
Research and development (R&D) expenses were $6.3 million for the fourth quarter of 2020, compared to $9.1 million for same period in the prior year. R&D expenses were $23.9 million for the full year 2020, compared to $39.6 million in the prior year. The decrease in both periods is primarily the result of lower clinical study costs associated with completion of the Phase 2 UTI program in 2019, partially offset by an increase in expenses incurred under the BARDA contract and third-party manufacturing process scale-up to meet expected future demand for NUZYRA.

Selling, general and administrative (SG&A) expenses were $24.3 million for the fourth quarter of 2020, compared to $21.3 million for the same period in the prior year.  The $3.0 million increase is primarily due to costs incurred to realign our hospital territories and our community expansion.

SG&A expenses were $89.9 million for the full year 2020, compared to $89.1 million in the prior year. The $0.8 million increase is primarily the result of costs for the Company’s contract sales organization and higher product distribution fees, partially offset by lower marketing and promotional program expenses, personnel-related costs and travel due to the COVID-19 pandemic.

Paratek reported a net loss of $25.0 million, or ($0.54) per share, for the fourth quarter of 2020, compared to a net loss of $27.4 million, or ($0.81) per share, for the same period in 2019.

Paratek reported a net loss of $96.5 million, or ($2.19) per share, for the full year 2020 compared to a net loss of $128.8 million, or ($3.93) per share, for the same period in 2019.

Financial Guidance
Paratek also announced its full year 2021 financial guidance.

Paratek estimates 2021 total revenue in the range of $166 to $177 million. This range includes the following components:
2021 NUZYRA net U.S. product sales are expected to be approximately $138 to $144 million, which includes:
U.S. net product sales between $62 to $68 million from the core commercial business
Two SNS procurements by BARDA valued at approximately $76 million
Royalty and collaboration revenue of approximately $8 million
BARDA government contract service and grant revenue between $20 to $25 million
BARDA contract service and grant revenue consists of reimbursement of NUZYRA post-marketing requirements, the anthrax development program and the U.S. onshoring of NUZYRA manufacturing
Paratek estimates 2021 R&D and SG&A expense to be approximately $150 to $155 million. This range includes the following components:
Core business R&D and SG&A expense of $130 million, an increase of 20% over 2020 but consistent with 2019 pre-pandemic levels
The expected increase in R&D and SG&A expense in 2021 when compared to 2020 will be driven by costs associated with the primary care expansion and the initiation of the phase 2b study in NTM
BARDA R&D and U.S. onshoring cost reimbursements between $20 to $25 million
Based upon the Company’s current operating plan as described above, Paratek anticipates its existing cash, cash equivalents and marketable securities of $125.2 million as of December 31, 2020, provide for a cash runway through the end of 2023 with a pathway to cash flow break even.
Company performance and unanticipated events could cause actual results to vary from this forward-looking guidance.

Call and Webcast
Paratek’s earnings conference call for the quarter and year ended December 31, 2020 will be broadcast at 4:30 p.m. EST on February 24, 2021. The live audio webcast can be accessed under "Events and Presentations" in the Investor Relations section of Paratek’s website at www.ParatekPharma.com.

Domestic investors wishing to participate in the call should dial: 877-407-0792 and international investors should dial: 201-689-8263. The conference ID is 13716761. Investors can also access the call at View Source

Website Information
Paratek routinely posts important information for investors on the Investor Relations section of its website at www.ParatekPharma.com. Paratek intends to use this website as a means of disclosing material, non-public information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investor Relations section of Paratek’s website, in addition to following its press releases, U.S. Securities and Exchange Commission (SEC) filings, public conference calls, presentations and webcasts. The information contained on, or that may be accessed through, Paratek’s website is not incorporated by reference into, and is not a part of, this document.

On February 24, 2021 Halozyme Therapeutics, Inc. (NASDAQ: HALO) ("Halozyme" or the "Company"), a leader in converting IV biologics to subcutaneous delivery, reported the pricing of $700 million aggregate principal amount of its convertible senior notes due 2027 (the "Convertible Notes") (Press release, Halozyme, FEB 24, 2021, View Source [SID1234575563]). The Convertible Notes are being offered in a private placement to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act"). The Company granted an option to the initial purchasers to purchase up to an additional $105 million aggregate principal amount of Convertible Notes.

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 Convertible Notes will be senior, unsecured, obligations of the Company, will pay interest semi-annually in arrears at an annual rate of 0.25% and under certain circumstances, will be convertible into cash and, if applicable, shares of the Company’s common stock, at the Company’s election. The Convertible Notes have an initial conversion rate of 12.9576 shares of the Company’s common stock per $1,000 principal amount of Convertible Notes (which is equivalent to an initial conversion price of approximately $77.17 per share of the Company’s common stock, representing an initial conversion premium of approximately 50% above the closing price of $51.45 per share of the Company’s common stock on February 24, 2021). The conversion rate is subject to adjustment in some events but will not be adjusted for any accrued and unpaid interest. Holders of the Convertible Notes will have the right to require the Company to repurchase all or a portion of their Convertible Notes upon the occurrence of a fundamental change (as defined in the indenture governing the Convertible Notes) at a cash repurchase price of 100% of their principal amount plus any accrued and unpaid interest. The Convertible Notes will mature on March 1, 2027, unless repurchased, redeemed or converted in accordance with their terms prior to such date. Prior to the close of business on the business day immediately preceding September 1, 2026, the Convertible Notes will be convertible only upon the satisfaction of certain conditions and during certain periods, and on and after September 1, 2026, at any time prior to the close of business on the scheduled trading day immediately preceding the maturity date regardless of these conditions. The Company expects to close the offering on March 1, 2021, subject to the satisfaction of various customary closing conditions.

The Company will receive net proceeds from the offering of approximately $681.9 million (or approximately $784.3 million if the initial purchasers exercise their option to purchase additional Convertible Notes in full). The Company expects to use a portion of the net proceeds of the offering to enter into privately negotiated agreements with certain holders of its outstanding 1.25% convertible senior notes due 2024 (the "Existing Convertible Notes") to exchange their Existing Convertible Notes for a combination of cash and shares of its common stock through privately negotiated transactions entered into concurrently with or shortly after the offering (the "Note Repurchases"). In connection with the Note Repurchases, the Company expects to pay approximately $370.2 million in cash, which includes accrued interest, and issue approximately 9.08 million shares of its common stock, to settle such exchanges. In addition, the Company plans to use up to $75.0 million of the net proceeds from the offering to repurchase shares of its common stock under its existing stock repurchase program (the "Share Repurchases").

These Note Repurchases and Share Repurchases could increase (or reduce the size of any decrease in) the market price of Halozyme common stock or the Convertible Notes. We also expect that some existing noteholders may purchase or sell shares of the Company’s common stock in the market to hedge their exposure in connection with these transactions. The Note Repurchases, Share Repurchases and any associated hedging by holders could have affected or affect the market price of the Company’s common stock prior to, concurrently with or shortly after the pricing of the Convertible Notes, and could have also resulted in a higher effective conversion price for the Convertible Notes.

The Company intends to use the remainder of the net proceeds from the offering for general corporate purposes, including other repurchases of the Company’s common stock from time to time under its existing stock repurchase program, working capital, capital expenditures, potential acquisitions and strategic transactions. If the initial purchasers exercise their option to purchase additional Convertible Notes, the Company intends to use net proceeds from the sale of additional Convertible Notes for general corporate purposes.

This press release is neither an offer to sell nor a solicitation of an offer to buy the Convertible Notes or the shares of the Company’s common stock issuable upon conversion of the Convertible Notes, if any, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction. Any offer of these securities will be made only by means of a private offering memorandum.

The offer and sale of the Convertible Notes and the shares of the Company’s common stock issuable upon conversion of the Convertible Notes, if any, have not been registered under the Securities Act, or the securities laws of any other jurisdiction, and the Convertible Notes and such shares may not be offered or sold in the United States absent registration or an applicable exemption from registration requirements.

On February 24, 2021 Cerus Corporation (Nasdaq: CERS) and Shandong Zhongbaokang Medical Implements Co. Ltd. (ZBK) reported that they are forming a joint venture (JV) with the intent to develop, obtain regulatory approval for, manufacture and commercialize the INTERCEPT Blood System for platelets and red blood cells in China (Press release, Cerus, FEB 24, 2021, View Source [SID1234575789]). The JV, which will be named "Cerus ZBK Biomedical" (CEZB), will be headquartered in Zibo, Shandong Province in eastern China.

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!

"We are honored to join forces with ZBK in China, furthering our mission to make INTERCEPT the standard of care for patients globally," said Pascal Maillard, Cerus’ vice president of commercial operations for the Asia Pacific region. "We believe that ZBK’s experience with local clinical and regulatory requirements, ISO-certified manufacturing infrastructure, and existing sales channels will facilitate accelerated and broad access to INTERCEPT across China’s transfusion medicine community."

China represents one of the largest potential blood transfusion markets globally for INTERCEPT, with red blood cell collections in excess of 23 million unit-equivalents each year, and an estimated production of 1.8 million platelet doses per year. The healthcare system in China continues to grow at a rapid pace, enabling expanded access to blood components expected to benefit from pathogen inactivation.

"We are delighted to collaborate with Cerus to work to bring INTERCEPT to China as the market for platelets continues to grow rapidly," said Mr. Xu Junfeng, chief executive officer of ZBK. "INTERCEPT-treated platelets would address an unmet clinical need in the blood transfusion market in China and would offer an important new, prospective measure of safety against known and emerging pathogens during this new era of pandemic preparedness planning."

ZBK is a subsidiary of the Taibao Group and a leading developer, manufacturer and marketer of blood transfusion, blood safety, and infusion products in China. ZBK markets and sells its products through its own sales force network to over 280 blood centers nationwide.

Under the terms of the JV agreement, Cerus and ZBK are the sole shareholders in CEZB, with Cerus owning a majority (51%) of the entity. Cerus anticipates that it will consolidate the results of CEZB in its consolidated financial statements. Additionally, Cerus will contribute an exclusive license to the INTERCEPT Blood System for platelets and red blood cells for CEZB to market across China. ZBK will contribute its significant local expertise to help perform necessary clinical studies and seek regulatory approval. Ultimately it is expected that ZBK will establish local manufacturing and leverage its commercial expertise and presence in the region.

On February 24, 2021 United Therapeutics Corporation (Nasdaq: UTHR) reported its financial results for the fourth quarter and year ended December 31, 2020 (Press release, United Therapeutics, FEB 24, 2021, View Source [SID1234575507]). Full year net revenue rose to $1,483 million, as U.S. patients being treated with the company’s treprostinil-based therapies reached an all-time high during the fourth quarter.

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!

"We’re entering 2021 better positioned than at any time in our history," said Martine Rothblatt, Ph.D., Chairman and Chief Executive Officer of United Therapeutics. "We are working toward four product launches this year, led by the recent launch of the Remunity Pump and followed by the upcoming Tyvaso label expansion into pulmonary hypertension associated with interstitial lung disease (PH-ILD), the Implantable System for Remodulin (ISR), and the innovative Tyvaso DPI device, assuming we receive the relevant FDA approvals. At the same time, our development teams continue to drive innovation in the pulmonary hypertension space as detailed in the recent New England Journal of Medicine publication of our INCREASE data in PH-ILD and our recent announcement of Tyvaso DPI clinical data, which suggest a comparable systemic treprostinil exposure to our approved Tyvaso Inhalation System."

"We are pleased that our treprostinil-based products achieved another record year of annual net revenues and total U.S. patients on therapy, trends we expect to continue, fueled by our four planned product launches this year," said Michael Benkowitz, President and Chief Operating Officer of United Therapeutics. "We are deep into commercial launch preparations for Tyvaso in PH-ILD and expect that this indication could expand the use of Tyvaso to more than double the current number of patients on therapy in the near term. Additionally, we’re focused on the ISR and the Tyvaso DPI launches targeted for later this year."

FOURTH QUARTER AND FULL YEAR 2020 FINANCIAL RESULTS

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

Net product sales of our treprostinil-based products (Remodulin, Tyvaso, and Orenitram) grew by $65.2 million for the year ended December 31, 2020, as compared to 2019. This increase was driven by growth in U.S. net product sales of our treprostinil-based products of $122.6 million in 2020, as compared to 2019, partially offset by a $57.4 million decline in net product sales of our treprostinil-based products outside the United States.

In addition, as previously disclosed, our 2019 quarterly results were impacted by a mistake by one of our U.S. distributors in its utilization data, which resulted in the distributor ordering more product than normal, primarily in the third quarter of 2019. Upon the distributor’s correction of its utilization data in the fourth quarter of 2019, the distributor reduced its purchases of our products in the fourth quarter of 2019 in order to normalize its inventory levels (collectively, the Corrected Order). We estimate that the Corrected Order reduced net product sales for Remodulin, Tyvaso, and Orenitram by approximately $18.3 million, $12.7 million, and $6.1 million, respectively, or $37.1 million in total, during the fourth quarter of 2019. Absent the Corrected Order, there would have been no change in U.S. net product sales for Remodulin and our net product sales for Tyvaso and Orenitram would have grown by 27 percent and 30 percent, respectively, in the fourth quarter of 2020, as compared to the fourth quarter of 2019. We are providing these non-GAAP financial measures to show the period-to-period revenue change for these products in the absence of the Corrected Order to improve investors’ understanding of our financial results. In addition, while this inventory fluctuation had a significant impact on our U.S. revenues during the third and fourth quarters of 2019, the effect on full-year U.S. revenues was negligible.

The year-over-year increase in quarterly revenues for Remodulin, Tyvaso, and Orenitram were all impacted by the Corrected Order, as discussed above. In addition, the increases in year-over-year quarterly revenues for Tyvaso and Orenitram resulted from: (1) an increase in quantities sold, reflecting a growing number of patients; and (2) to a lesser extent, price increases for Tyvaso.

The reduction in annual Remodulin revenues for 2020 compared to 2019 was primarily driven by: (1) a reduction in quantities sold in Europe, which we believe resulted from generic competition and the impact of COVID-19; and (2) to a lesser extent, a reduction in U.S. Remodulin revenues, which we believe resulted from the impact of COVID-19. The growth in annual Tyvaso revenues for 2020 compared to 2019 was due to an increase in quantities sold, reflecting a growing number of patients, and price increases. The growth in annual Orenitram revenues for 2020 compared to 2019 was due to an increase in quantities sold, as the number of patients being treated with Orenitram grew following the update to Orenitram’s labeling to reflect the FREEDOM-EV clinical trial results. The decrease in annual Adcirca revenues for 2020 compared to 2019 was driven by continued erosion of market share due to generic competition.

Expenses

Cost of product sales. The table below summarizes cost of product sales by major category (dollars in millions):

Cost of product sales, excluding share-based compensation. The decrease in cost of product sales for the year ended December 31, 2020, as compared to the same period in 2019, was primarily attributable to decreases in royalty expense for Adcirca, as fewer bottles were sold following the onset of generic competition for Adcirca beginning in August 2018.

Research and development expense, excluding share-based compensation. The decrease in research and development expense for the year ended December 31, 2020, as compared to the same period in 2019, was due to a one-time, $800.0 million up-front payment to Arena Pharmaceuticals, Inc. (Arena) under our license agreement related to ralinepag during the year ended December 31, 2019. The remainder of the decrease resulted primarily from: (1) the completion of the phase 3 BEAT study of esuberaprost in April 2019, the completion of the phase 3 DISTINCT study of Unituxin in February 2020, and the discontinuation of the phase 3 SOUTHPAW study of Orenitram in October 2019; (2) a decrease in spending due to terminated drug delivery device projects; and (3) an impairment charge related to the termination of a license agreement during the year ended December 31, 2019.

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

The increase in share-based compensation expense for the quarter and year ended December 31, 2020, as compared to the same periods in 2019, was primarily due to an increase in STAP expense driven by a 50 percent and a 72 percent increase in our stock price during the quarter and year ended December 31, 2020, respectively, as compared to a 10 percent increase and 19 percent decrease in our stock price for the quarter and year ended December 31, 2019, respectively. The increase in share-based compensation expense for the year ended December 31, 2020 was partially offset by a decrease in stock option expense due to fewer awards granted and outstanding in 2020 as compared to the same period in 2019.

Other income, net. The increase in other income, net for the quarter and year ended December 31, 2020, as compared to the same periods in 2019, was primarily due to net unrealized and realized gains on our investments in privately-held companies and our investments in publicly-traded equity securities.

Income taxes. Income tax expense was $124.1 million for the year ended December 31, 2020, as compared to income tax benefit of $60.5 million for the same period in 2019. For the year ended December 31, 2019, the income tax benefit resulted primarily from the $800.0 million payment under our license agreement with Arena which caused us to incur a net loss before taxes. For the years ended December 31, 2020 and 2019, our effective income tax rates (ETR) were approximately 19 percent and 37 percent, respectively. Changes to the ETR for the years ended December 31, 2020 and 2019 were primarily due to tax credits, partially offset by non-deductible compensation, which decreased our tax expense for 2020 and increased our tax benefit for 2019.

Non-GAAP Earnings

Non-GAAP earnings is defined as net income (loss), 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) unrealized gains on investments in privately-held companies; (3) impairments of investments in privately-held companies; (4) asset impairment charges; (5) license-related fees; (6) net changes in recurring fair value measurements; and (7) tax impact on non-GAAP earnings adjustments.

A reconciliation of net income (loss) to non-GAAP earnings is presented below (in millions, except per share data):

PRODUCT COMMERCIALIZATION UPDATE

In 2021, we plan to launch four new products and indications. In February 2021, we launched commercial sales of the Remunity Pump for Remodulin. In April 2021, we plan to launch a label expansion for Tyvaso, to include an indication for PH-ILD, assuming FDA approval. We also plan to launch the Implantable System for Remodulin and Tyvaso DPI, assuming the FDA grants the necessary clearances.

Remunity Pump for Remodulin. In February 2020, we announced FDA clearance of the pharmacy-filled version of the Remunity Pump for Remodulin, developed in collaboration with DEKA Research & Development Corp (DEKA). In February 2021, we announced the first commercial shipments of the Remunity Pump to specialty pharmacies. The Remunity Pump is a pre-filled, semi-disposable system for subcutaneous delivery of treprostinil, developed in collaboration with DEKA under an exclusive development and license agreement. The system consists of a small, lightweight, durable pump and controller designed to have a service life of at least three years. The pump uses disposable cartridges filled with Remodulin, which can be connected to the pump with less patient manipulation than is typically involved in filling other currently-available subcutaneous pumps.

Tyvaso Inhalation Solution in PH-ILD. In February 2020, we reported that the INCREASE study of Tyvaso in patients with PH-ILD met its primary endpoint of demonstrating improvement in six-minute walk distance (6MWD). Tyvaso also showed benefits across several key subgroups, including etiology of PH-ILD, disease severity, age, gender, baseline hemodynamics, and dose. Significant improvements were also observed in each of the study’s secondary endpoints, including reduction in the cardiac biomarker NT-proBNP, time to first clinical worsening event, change in peak 6MWD at week 12, and change in trough 6MWD at week 15. Treatment with Tyvaso of up to 12 breaths per session, four times daily, in the INCREASE study was well tolerated and the safety profile was consistent with previous Tyvaso studies and known prostacyclin-related adverse events. Comprehensive data from the INCREASE study were recently published in the New England Journal of Medicine.

In April 2020, the FDA indicated that the results of the INCREASE study appear to support our proposed indication of treatment of patients with PH-ILD to improve exercise ability and delay clinical worsening. In June 2020, we submitted an efficacy supplement (sNDA) to the Tyvaso new drug application (NDA), which we expect to result in revised labeling reflecting the outcome of the INCREASE study. In August 2020, the FDA accepted the sNDA for review, which we expect will be completed in April 2021.

Implantable System for Remodulin. Developed in collaboration with Medtronic, the premarket approval application (PMA) for the ISR was approved by the FDA in December 2017. However, our ability to launch the product is subject to Medtronic satisfying various conditions to its PMA approval. We are working with Medtronic to meet these conditions to the FDA’s satisfaction by the fourth quarter of 2021, with a goal of commencing launch activities during late 2021. Our ability to launch the ISR in 2021, or at all, depends on our ability to work with Medtronic to satisfy the FDA’s conditions and other factors, many of which are entirely outside our control.

Tyvaso DPI. We have completed two clinical studies of Tyvaso DPI. One was a study in healthy volunteers, comparing the pharmacokinetics of Tyvaso DPI to Tyvaso Inhalation Solution. We completed the study in October 2020, and announced in January 2021 that the study demonstrated comparable systemic treprostinil exposure between Tyvaso DPI and Tyvaso Inhalation Solution. In December 2020, we completed a clinical study (called BREEZE), which evaluated the safety and pharmacokinetics of switching pulmonary arterial hypertension (PAH) patients from Tyvaso Inhalation Solution to Tyvaso DPI. In January 2021, we announced that the study demonstrated safety and tolerability of Tyvaso DPI in subjects with PAH transitioning from Tyvaso Inhalation Solution. We are awaiting the final pharmacokinetics data from the BREEZE study. The FDA has indicated that these two studies will be the only additional clinical studies necessary to support FDA approval. If our pending sNDA for Tyvaso Inhalation Solution to treat PH-ILD is approved by the FDA in April 2021, we plan to submit an NDA later in April 2021 seeking an indication for Tyvaso DPI that includes both PAH and PH-ILD. In January 2021, we purchased a pediatric disease priority review voucher for $105.0 million, which we plan to redeem upon submission of the Tyvaso DPI NDA. The voucher is expected to reduce the typical 12-month timeframe for FDA to review the Tyvaso DPI NDA to eight months.

RESEARCH AND DEVELOPMENT UPDATE

Updates on selected later-stage programs are below.

Tyvaso in chronic fibrosing interstitial lung diseases — TETON. We are planning a new phase 3 program called TETON, which will be comprised of one or more phase 3 studies of Tyvaso in subjects with various forms of chronic fibrosing interstitial lung diseases, including patients with idiopathic interstitial pneumonias (IIP), chronic hypersensitivity pneumonitis (CHP), and environmental/occupational lung disease. The first TETON study is designed to enroll subjects with idiopathic pulmonary fibrosis (IPF). The primary endpoint of this study is planned to be the change in absolute forced vital capacity (FVC) from baseline to week 52.

The TETON program was prompted by data from the INCREASE study, which demonstrated improvements in certain key parameters of lung function in pulmonary hypertension patients with fibrotic lung disease. Specifically, in the INCREASE study, treatment with Tyvaso resulted in significant improvements in percent predicted FVC at weeks 8 and 16, with subjects having underlying etiologies of IIP showing greater improvement. Consistent positive effects were also observed in patients with CHP and environmental/occupational lung disease. These data points, combined with substantial preclinical evidence of antifibrotic activity of treprostinil, suggest that Tyvaso may offer a treatment option for patients with fibrotic lung disease.

In December 2020, the FDA granted orphan designation for treprostinil to treat IPF.

Tyvaso in pulmonary hypertension due to chronic obstructive pulmonary disease — PERFECT. Enrollment is ongoing for the phase 3 PERFECT study (NCT03496623) evaluating Tyvaso in patients with WHO Group 3 pulmonary hypertension associated with chronic obstructive pulmonary disease. In a 30-week crossover study, 136 subjects will be randomized between inhaled treprostinil and placebo for a 26-week treatment period. The primary endpoint of the study is the change in 6MWD from baseline to week 12.

Ralinepag phase 3 clinical studies — ADVANCE CAPACITY and ADVANCE OUTCOMES. We are enrolling two phase 3 clinical studies to support the potential approval of oral ralinepag for PAH.

Trevyent. We are developing Trevyent, a drug-device combination product that combines our two-day, single use, disposable PatchPump technology with treprostinil, for the subcutaneous treatment of PAH. We submitted a 505(b)(1) NDA for Trevyent to the FDA in June 2019. In April 2020, the FDA issued a complete response letter (CRL) related to our NDA indicating that some of the deficiencies previously raised by the FDA had not yet been addressed to its satisfaction. In January 2021, we met with the FDA to discuss certain deficiencies noted in the CRL, and our plans to address them. The FDA clarified certain matters and indicated that a small clinical study of Trevyent in PAH patients may be required to evaluate further the pharmacokinetic profile and safety as correlated to the pump performance. We are assessing the FDA’s comments and awaiting additional written feedback from the agency, but currently believe that resubmission of our NDA will likely be delayed to 2022. We anticipate a six-month review period by the FDA following our resubmission.

Unituxin in relapsed/refractory neuroblastoma — ANBL1221. We are pursuing an indication expansion for Unituxin in relapsed or refractory neuroblastoma based on the results of the Children’s Oncology Group’s ANBL1221 study (NCT01767194). We met with the FDA in April 2020 to discuss the proposed label expansion, and plan to file a supplemental BLA in the near term.

INDUCEMENT RESTRICTED STOCK UNITS

On February 19, 2021, we granted a total of 909 restricted stock units under our 2019 Inducement Stock Incentive Plan to two newly hired employees. These restricted stock units vest in three equal installments on February 28, 2022, February 28, 2023, and February 28, 2024, assuming continued employment on such dates, and are subject to the standard terms and conditions we filed with the SEC as Exhibit 10.2 to our Current Report on Form 8-K on March 1, 2019. We are providing this information in accordance with Nasdaq Listing Rule 5635(c)(4).

CONFERENCE CALL

We will host a teleconference on Wednesday, February 24, 2021, at 9:00 a.m. Eastern Time. The teleconference is accessible by dialing +1 (866) 393-4306 in the United States, with international callers dialing +1 (763) 488-9145. A rebroadcast of the teleconference will be available for one week and can be accessed by dialing +1 (855) 859-2056 in the United States, with international callers dialing +1 (404) 537-3406, and using access code: 8999095.

On February 24, 2021 Crown Bioscience (CrownBio), JSR Life Sciences and Cambridge Quantum Computing (CQC) reported a partnership agreement to explore the application of quantum technology to drive the identification of multi-gene biomarker discovery for oncology drug discovery (Press release, Crown Bioscience, FEB 24, 2021, View Source [SID1234575531]).

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 partnership will combine CrownBio’s domain expertise and vast data sets generated from 15 years of preclinical and translational research and CQC’s advanced capabilities in quantum algorithms, quantum machine learning, and quantum computing.

Utilizing quantum machine algorithms and CQC’s software development framework for execution on NISQ (Noisy Intermediate-Scale Quantum) computers, the initial approach will focus on deriving insight from the analysis of genetic data to identify cancer treatment biomarkers and drive the next generation of bioinformatics.

The objective is to identify a strategy to implement an early quantum computing application that will ultimately address and explore solutions to broad challenges in life sciences.

Armin Spura, CEO of CrownBio commented, "The agreement continues CrownBio’s commitment to innovation and the application of technology to accelerate and de-risk drug development, leading to stronger drug candidates and a more rapid transition from preclinical phases to the clinic."

llyas Khan, CEO of CQC said, "CQC was founded to develop technologies that could help address some of the most pressing societal challenges, particularly in areas such as human biology, so we are excited to enter into our latest partnership with CrownBio to determine how cutting-edge quantum machine learning methods can be applied to critical use cases."