On August 7, 2019 Horizon Therapeutics plc (Nasdaq: HZNP) reported its second-quarter 2019 financial results and increased its full-year 2019 net sales and adjusted EBITDA guidance (Press release, Horizon Therapeutics, AUG 7, 2019, View Source [SID1234538323]).

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"The second quarter was another quarter of outstanding execution and strategic progress," said Timothy Walbert, chairman, president and chief executive officer, Horizon. "We generated double-digit net sales growth in our orphan and rheumatology segment, driven by continued momentum from KRYSTEXXA, our medicine for uncontrolled gout and our main growth driver. In addition, we recently submitted teprotumumab for U.S. FDA approval, another milestone toward delivering the first FDA-approved treatment to people living with active thyroid eye disease."

Second-Quarter and Recent Company Highlights

Submitted BLA for Teprotumumab for Active TED: In early July, the Company submitted a BLA for its investigational medicine teprotumumab for the treatment of active TED to the U.S. Food and Drug Administration (FDA). The submission included results from the Phase 3 clinical trial, OPTIC (Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study), as well as the positive Phase 2 results.

Teprotumumab has Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA. Horizon has requested Priority Review for the application, which, if granted, could result in a six-month review process. The FDA has a 60-day filing review period to determine whether the BLA is complete and acceptable for filing. If approved, teprotumumab would be the first and only approved treatment for active TED.

In April, additional results from OPTIC were presented at the American Association of Clinical Endocrinologists (AACE) Scientific and Clinical Congress, which included measurements of improvement in proptosis, the major driver of morbidity in TED. These data showed that after the full course of treatment for 24 weeks, patients treated with teprotumumab demonstrated a mean proptosis reduction of 3.32 mm compared with 0.53 mm for patients on placebo (p<0.001).

Announced Teprotumumab Expanded Access Program (EAP): The Company recently announced the availability of an expanded access program for teprotumumab. The expanded access program will be available for people living with active TED while the FDA reviews the teprotumumab BLA.

Initiated KRYSTEXXA Immunomodulation Trial: In June,the Company initiated its registrational clinical trial MIRROR (Methotrexate to Increase Response Rates in Patients with Uncontrolled GOut Receiving KRYSTEXXA). The trial is evaluating administration of KRYSTEXXA in combination with methotrexate to determine the potential for dampening anti-drug antibody formation and increasing response rates with KRYSTEXXA, allowing more patients living with uncontrolled gout to fully benefit from treatment. The randomized placebo-controlled study is expected to enroll approximately 135 patients to receive either KRYSTEXXA and methotrexate or KRYSTEXXA and placebo. The primary endpoint will assess the proportion of serum uric acid (sUA) responders (sUA <6 mg/dL) at Month 6.

FDA Accepted New Drug Application (NDA) for PROCYSBI Oral Granules: In July, the FDA accepted the NDA for PROCYSBI Delayed-Release Oral Granules in Packets. If approved, this new dosage form would provide another administration option for patients, in addition to the currently available PROCYSBI delayed-release capsules, which are FDA-approved for children one year of age and older and adults living with nephropathic cystinosis. The submission is part of the Company’s ongoing investment in the cystinosis community.

Appointed Sue Mahony to the Board of Directors: The Company recently appointed Sue Mahony, Ph.D., MBA, to its board of directors. Dr. Mahony brings more than 30 years of diverse industry experience to the Board, including an 18-year tenure at Eli Lilly and Company, where she served in a variety of global and domestic leadership roles of increasing responsibility, including helping oversee the development of an innovative pipeline. Before Lilly, Dr. Mahony spent five years at Bristol-Myers Squibb Company.

Changed Company Name to Horizon Therapeutics plc: In May, shareholders approved the change of the Company’s name to Horizon Therapeutics Public Limited Company at the Annual General Meeting. The new name captures the Company’s long-term strategy to develop and commercialize innovative new medicines that address rare and rheumatic diseases with very few effective treatment options. The Company believes the new name also better reflects its work with patients, caregivers, physicians and communities that goes well beyond its medicines.

Improved the Company’s Capital Structure: In May,the Company repaid $250 million of its outstanding debt, reducing it to $1.443 billion as of June 30, 2019. In May, the Company also refinanced its senior secured term loans, lowering the interest rate by 25 basis points and extending the final maturity date to May 22, 2026. Additionally, in July, the Company issued $600 million of 5.5 percent Senior Notes due 2027 and is using the proceeds along with cash on hand to repay $625 million of its outstanding debt. These actions serve to reduce interest expense and extend the maturity of the debt, furthering the Company’s strategy to improve its capital structure.
Research and Development Programs

Orphan Disease Candidate and Program:

Teprotumumab: Teprotumumab is a fully human monoclonal antibody insulin-like growth factor-1 receptor (IGF-1R) inhibitor candidate for the treatment of active TED, a serious, progressive, vision-threatening autoimmune disease in which the muscles and fatty tissue behind the eye become inflamed and expand. This can lead to proptosis (eye bulging) and diplopia (double vision) and impact activities of daily living and quality of life. The development program for teprotumumab in TED includes positive Phase 2 results published in The New England Journal of Medicine, as well as positive results from the confirmatory Phase 3 OPTIC clinical trial, announced in February 2019. The OPTIC study met its primary endpoint of a ≥2 mm reduction in proptosis (p<0.001), the main cause of morbidity in TED, with 82.9 percent of patients treated with teprotumumab demonstrating a significant improvement in proptosis compared to 9.5 percent of placebo patients. In addition, all secondary endpoints were met (p≤0.001), and the safety profile was consistent with the Phase 2 study.
Rheumatology Pipeline Candidates and Programs:

KRYSTEXXA Immunomodulation Trial: The Company is evaluating the use of methotrexate to increase the response rate with KRYSTEXXA through its MIRROR study. Methotrexate is the immunomodulator most used by rheumatologists, and has been shown to reduce anti-drug antibody formation to biologic therapies when combined with these therapies. The MIRROR trial is designed to support the potential for registration and commenced in June.
KRYSTEXXA Study in Kidney Transplant Patients with Uncontrolled Gout: The Company plans to initiate a clinical trial in the second half of 2019 evaluating the effect of KRYSTEXXA on serum uric acid levels in kidney transplant patients with uncontrolled gout. Kidney transplant patients have more than a tenfold increase in the prevalence of gout when compared to the general population, and literature suggests that persistently high serum uric acid levels can be associated with organ rejection. Managing uncontrolled gout is one of the most common and significant unmet needs of kidney transplant patients.
Next-generation Biologic Programs for Uncontrolled Gout: The Company is pursuing several development programs for next-generation biologics for uncontrolled gout to support and sustain the Company’s market leadership in this area. These include HZN-003, HZN-007 and a discovery and development collaboration with HemoShear Therapeutics, LLC.
Second-Quarter Financial Results

Note: For additional detail and reconciliation of non-GAAP financial measures to the most directly comparable GAAP financial measures, please refer to the tables at the end of this release.

Net Sales: Second-quarter 2019 net sales were $320.6 million, an increase of 6 percent.

Gross Profit: Under U.S. GAAP, the second-quarter 2019 gross profit ratio was 72.2 percent compared to 69.8 percent in the second quarter of 2018. The non-GAAP gross profit ratio in the second quarter of 2019 was 90.9 percent compared to 90.2 percent in the second quarter of 2018.

Operating Expenses: Research and development (R&D) expenses were 8.8 percent of net sales and selling, general and administrative (SG&A) expenses were 52.1 percent of net sales. Non-GAAP R&D expenses were 6.9 percent of net sales, and non-GAAP SG&A expenses were 45.4 percent of net sales.

Income Tax Rate: In the second quarter of 2019, the income tax benefit rate on a GAAP basis was 48.8 percent and the income tax expense rate on a non-GAAP basis was 11.3 percent.

Net Income (Loss): On a GAAP basis in the second quarter of 2019, net loss was $5.1 million. Second-quarter 2019 non-GAAP net income was $95.6 million.

Adjusted EBITDA: Second-quarter 2019 adjusted EBITDA was $124.1 million.

Earnings (Loss) per Share: On a GAAP basis diluted loss per share in the second quarter of 2019 and 2018 was $0.03 and $0.15, respectively. Non-GAAP diluted earnings per share in the second quarter of 2019 and 2018 was $0.49 and $0.48, respectively. Weighted average shares outstanding used for calculating GAAP and non-GAAP diluted earnings per share in the second quarter of 2019 were 185.3 million and 193.2 million, respectively.
Second-Quarter Segment Results

Management uses net sales and segment operating income to evaluate the performance of the Company’s two segments. While segment operating income contains certain adjustments to the directly comparable GAAP figures in the Company’s consolidated financial results, it is considered to be prepared in accordance with GAAP for purposes of presenting the Company’s segment operating results.

Beginning in 2019, the Company no longer recognizes revenue from RAVICTI and AMMONAPS sales outside of North America and Japan, nor from sales of LODOTRA. On Dec. 28, 2018, the Company divested the rights to RAVICTI and AMMONAPS outside of North America and Japan. AMMONAPS is known as BUPHENYL in the United States. In addition, effective Jan. 1, 2019, the RAYOS and LODOTRA license and supply agreements were amended, including the transfer of LODOTRA to Vectura Group plc. LODOTRA is known as RAYOS in the United States.

Second-quarter 2019 net sales of the orphan and rheumatology segment, the Company’s strategic growth segment, were $223.5 million, an increase of 11 percent over the prior year’s quarter, driven by growth of KRYSTEXXA, RAYOS, PROCYSBI and ACTIMMUNE.
Second-quarter 2019 orphan and rheumatology segment operating income was $74.5 million, which includes the impact of investment in teprotumumab pre-launch activities.

Previously known as the primary care segment.

(2)

In June 2019, the Company divested the rights to MIGERGOT.

Second-quarter 2019 net sales of the inflammation segment were $97.1 million and segment operating income was $49.7 million.
Cash Flow Statement and Balance Sheet Highlights

On a GAAP basis in the second quarter of 2019, operating cash flow was $91.3 million. Non-GAAP operating cash flow was $95.7 million.

The Company had cash and cash equivalents of $866.0 million as of June 30, 2019.

As of June 30, 2019, the total principal amount of debt outstanding was $1.443 billion. As of June 30, 2019, net debt was $577 million and net-debt-to-last-12-months adjusted EBITDA leverage ratio was 1.1 times, compared to 3.6 times at June 30, 2018.

In May,the Company repaid $250 million of its outstanding debt, reducing it to $1.443 billion as of June 30, 2019. In May, the Company also refinanced its senior secured term loans, lowering the interest rate by 25 basis points and extending the final maturity date to May 22, 2026. In July, the Company issued $600 million of 5.5 percent Senior Notes due 2027 and is using the proceeds along with cash on hand to repay $625 million of its outstanding debt. Following the refinancing transactions, the Company expects the total principal amount of debt outstanding to be $1.418 billion, consisting of $418 million in senior secured term loans due 2026, $600 million of Senior Notes due 2027 and $400 million of Exchangeable Senior Notes due 2022.
New 2019 Guidance

The Company now expects full-year 2019 net sales to range between $1.28 billion to $1.30 billion, an increase from the previous guidance range of $1.26 billion to $1.28 billion. Full-year 2019 adjusted EBITDA is now expected to range between $460 million to $475 million, an increase from the previous guidance range of $450 million to $465 million.

Webcast

At 8 a.m. EDT / 1 p.m. IST today, the Company will host a live webcast to review its financial and operating results and provide a general business update. The live webcast and a replay may be accessed at View Source Please connect to the Company’s website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. A replay of the webcast will be available approximately two hours after the live webcast.

On August 7, 2019 Quantum Leap Healthcare Collaborative (QLHC) joins Merck in acknowledging the promising data from the KEYNOTE-522 trial (Press release, Merck & Co, AUG 7, 2019, View Source [SID1234538341]). Merck recently reported that the Phase 3 KEYNOTE-522 trial met a primary endpoint, demonstrating statistically significant improved rates of pathological complete response for KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with chemotherapy as neoadjuvant therapy for patients with triple negative breast cancer (TNBC). The positive finding serves as validation of the QLHC-sponsored I-SPY 2 trial, an adaptive phase II platform trial designed to rapidly screen agents and find the most effective drug combinations for each specific tumor subtype. In this study, patients start with chemotherapy before surgery so that response to treatment can be assessed. I-SPY 2’s evaluation of pembrolizumab formed the basis for targeting the immunotherapy to the TNBC subtype.

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I-SPY TRIALs are sponsored by Quantum Leap Healthcare Collaborative (QLHC), a 501c(3) charitable organization dedicated to facilitating and accelerating the development and transfer of high-impact solutions to advance healthcare and evidence-based medicine. (PRNewsfoto/Quantum Leap Healthcare Collabo)
I-SPY TRIALs are sponsored by Quantum Leap Healthcare Collaborative (QLHC), a 501c(3) charitable organization dedicated to facilitating and accelerating the development and transfer of high-impact solutions to advance healthcare and evidence-based medicine. (PRNewsfoto/Quantum Leap Healthcare Collabo)
As stated by Dr. Roger M. Perlmutter, president, Merck Research Laboratories, "When I have been asked over the last two years why I was prepared to see Merck initiate a Phase 3 trial in triple negative breast cancer, my response has always rested heavily on data from I-SPY 2. The KEYNOTE-522 pCR results offer promise for triple negative breast cancer patients who need better treatment options."

The I-SPY 2 trial is considered the archetype of a new approach to clinical trials. Rather than the traditional ‘one drug, one disease’ model for drug development, it is a ‘platform’ trial. I-SPY 2 evaluates up to 5 drugs (or combination of drugs) in parallel with the goal of determining which drugs work best in various types of breast cancer. I-SPY 2 is also designed for efficiency and speed, by employing an ‘adaptive’ statistical model. In this approach, the results of each patient are used to refine how the investigational drugs are assigned to new patients. In this way, I-SPY 2 can achieve similar results in a fraction of the time with fewer patients than traditional trials. The goal is to get the right drug to the right patient at the right time.

In results presented at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, I-SPY 2 investigators reported that pembrolizumab, when added to standard neoadjuvant therapy for early breast cancer, nearly tripled the response (the chance of the tumor going away before surgery) in HER2 negative breast cancer subtypes. It was observed to be particularly effective in the difficult-to-treat ‘triple negative’ subset of breast cancers, which do not express genes for estrogen or progesterone receptors, nor the HER2 oncogene. I-SPY 2’s adaptive model predicted that there was a greater than 99% chance that the treatment regimen including pembrolizumab would be successful in a Phase 3 trial in TNBC.

I-SPY 2 principal investigator, Dr. Laura Esserman of the University of California San Francisco, said the KEYNOTE-522 results validate both I-SPY 2’s pioneering approach and the vision of Merck leadership for being one of the trial’s early partners.

"The whole I-SPY team is thrilled to see that the KEYNOTE-522 results came out just as we predicted. It is an important advance for TNBC patients and a clear demonstration that the I-SPY model can not only accelerate the development of new cancer treatments, it can target treatment to the patients who will benefit most."

Importantly, the 2017 I-SPY 2 results were obtained after only 11 months and enrolling only 69 patients to the pembrolizumab arm of the study; Traditional Phase 2 trials typically require 100-200 patients and last two years or more.

About I-SPY and the I-SPY 2 TRIAL

The I-SPY (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis) TRIAL is conducted by a consortium that brings together the U.S. Food and Drug Administration (FDA), leading academic medical centers, and patient advocates, as well as Merck and other pharmaceutical and biotech companies.

The I-SPY 2 TRIAL is a collaborative effort among academic investigators from 20 major cancer research centers across the U.S. and Quantum Leap Healthcare Collaborative, the FDA, and the Foundation for the National Institutes of Health (FNIH) Cancer Biomarkers Consortium. Major supporters include The Safeway Foundation, and the Bill Bowes Foundation.

The I-SPY 2 TRIAL’s adaptive statistical design was developed by the pioneering principal investigators for the I-SPY trial, Laura J. Esserman, M.D., MBA, and Donald A. Berry, Ph.D., professor of biostatistics at The University of Texas MD Anderson Cancer Center and founder of Berry Consultants in collaboration with the FDA, industry, and many leading academic collaborators including the Agents working group chair (Doug Yee, M.D., University of Minnesota) and the Trial Operations working group chair (Angie DeMichele, M.D., University of Pennsylvania). The trial is a unique collaborative effort where over 50 clinicians are actively engaged in the conduct of the trial.

The I-SPY 2 TRIAL adaptive-trial design is based on Bayesian predictive probability that a biological regimen will be shown to be statistically superior to standard therapy in an equally randomized 300-patient confirmatory trial. Regimens that have a high Bayesian predictive probability of showing superiority in at least one of 10 predefined signatures graduate from the trial. Regimens are dropped for futility if they show a low predictive probability of showing superiority over standard therapy in all 10 signatures. A maximum total of 120 patients can be assigned to each experimental regimen. A regimen can graduate early and at any time after having 60 patients assigned to it.

Based on the confirmatory results of the Merck phase 3 trial, the I SPY 2 team is working on an improved design in an effort to get over 90% of high-risk patients to experience a complete response (disappearance of tumor) with targeted and less toxic combinations before surgery. This will accelerate the ability to personalize care for women with breast cancer.

On August 7, 2019 AMAG Pharmaceuticals, Inc. (NASDAQ: AMAG) reported unaudited consolidated financial results for the second quarter ended June 30, 2019 and provided a business update (Press release, AMAG Pharmaceuticals, AUG 7, 2019, View Source [SID1234538370]).

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"We are pleased to report both year-over-year and sequential revenue and market share growth in the quarter for each of our key commercial products – Makena subcutaneous (SC) auto-injector, Feraheme and Intrarosa. This strong, consistent execution by our commercial team positions us well for next month’s launch of Vyleesi, our fourth commercial product," said William Heiden, AMAG’s president and chief executive officer. "Despite the strong commercial success of our promoted products, we have lowered our 2019 financial guidance to reflect the impact of Makena intramuscular (IM) supply issues and our changed expectations of milestone payments due to us from a development partner related to ciraparantag."
KEY UPDATES

Makena supply: due to sustained supply disruptions, resulting in loss of market share, and increased generic competition, the company made the decision to exit the IM market and, through mutual agreement, has terminated the arrangement with Prasco, LLC, its authorized generic partner.

Makena PROLONG study: in a recent meeting with the U.S. Food and Drug Administration (FDA) regarding PROLONG, the Agency informed the company that it plans to hold an Advisory Committee meeting. This meeting is expected to occur in the fourth quarter of 2019 to facilitate transparent discussions of the PROLONG trial and allow FDA to obtain the necessary input from Advisory Committee members and important stakeholders to inform regulatory decision-making for Makena. In addition to presentations by the company and the FDA, clinical experts, medical society representatives and patients will have the opportunity to provide their perspectives on the clinical importance and medical need for Makena.

Quarterly growth across all promoted products: strong revenue and market share performance in the second quarter

Makena (hydroxyprogesterone caproate (HPC) injection) SC auto-injector achieved 63% market share of all FDA-approved HPC prescription volume in the quarter.

Feraheme (ferumoxytol injection) achieved record market share of 17.2% in the quarter.

Intrarosa (prasterone) exited the quarter at a TRx share of 4.8%, the highest share achievement since launch.

VyleesiTM (bremelanotide injection) on track for national launch in September: June 21 approval generated coverage from more than 300 news outlets across the country, which has helped drive early awareness of Vyleesi alongside the initial marketing campaign.

Development pipeline is progressing: the company expects to initiate a phase 3a study of ciraparantag in the fourth quarter of 2019. AMAG-423 Phase 2b/3a study continues to open new sites and enroll patients.

1 See summaries of GAAP to non-GAAP adjustments at the conclusion of this press release.

COMMERCIAL PRODUCTS AND DEVELOPMENT PROGRAM UPDATES
Makena
The Makena SC auto-injector was launched in March 2018 and has continued to grow and increase its market share every quarter since launch. Second quarter 2019 revenues increased to $41.0 million, or 8.5%, over the first quarter of 2019. Market share grew 9 percentage points to 63%, compared with 54% in the first quarter of 2019. With no intramuscular product shipped, the $10.0 million of negative revenue for the Makena IM product, for the three months ended June 30, 2019, was the result of changes in estimated Medicaid and commercial liability obligations from prior periods.

As previously disclosed, AMAG’s primary third-party manufacturer failed to timely deliver Makena IM drug product to AMAG, which led to supply disruptions and ultimately an out-of-stock situation. These supply issues hindered AMAG’s ability to provide Makena IM product, which caused Prasco to lose significant market share. Although AMAG received notice of approval from the FDA of an additional manufacturing site for the Makena IM product late in the second quarter, AMAG and Prasco concluded that it was no longer commercially viable to recapture sufficient market share following the out-of stock situation. As such, AMAG made the decision to exit the generic IM market and reached a mutual agreement with Prasco to terminate their distribution and supply agreement on August 6, 2019.

Accordingly, the company recorded a $77.4 million non-cash charge to fully write-off the intangible asset associated with the IM form of Makena and an inventory write-down of $4.8 million. In addition, the company revised its full-year 2019 financial guidance.

Vyleesi
As previously reported, on June 21, 2019 the FDA approved Vyleesi, a melanocortin receptor agonist, to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. The Vyleesi autoinjector is the first treatment for this patient population that can be self-administered as needed in anticipation of sexual activity. HSDD is characterized by low sexual desire that causes distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. AMAG is committed to working with payers and healthcare professionals to help ensure that women with HSDD have access to Vyleesi, as well as minimizing the cost burden to patients through a comprehensive copay assistance program. AMAG plans to launch Vyleesi nationally in September with approximately 125 sales representatives on the company’s women’s and maternal health salesforce who will be calling on an estimated 15,000 healthcare professionals.

Ciraparantag, which has been granted fast track designation by the FDA, is in development as a single-dose, ready-to-use solution for use in patients treated with novel oral anticoagulants (NOACs) or low molecular weight heparin (LMWH) when reversal of the anticoagulant effect is needed for emergency surgery or serious uncontrolled bleeding. AMAG and Perosphere Technologies (an independent company) recently met with the FDA and Perosphere Technologies is preparing to submit an investigational device exemption (IDE) to enable the use of the automated coagulometer in a Phase 3a clinical study, which AMAG expects to begin in the fourth quarter of 2019. Separately, AMAG was recently informed by a development partner for ciraparantag of its intention to terminate the existing collaboration agreement. Although AMAG does not believe that this partner has grounds for termination, it has removed expected milestone payments from its 2019 financial guidance.

UPDATED 2019 FINANCIAL GUIDANCE
"Although our commercial teams delivered strong results for our promoted products, we are lowering our 2019 financial guidance because we exited the Makena IM market and revised our expectation of ciraparantag development milestone revenue. The changes to our 2019 guidance do not alter our previously-stated preliminary view that we will achieve neutral adjusted EBITDA in 2020," said Ted Myles, AMAG’s chief financial officer. "With strong cash flows from our commercial products and our flexible cost structure, we believe we are well positioned to bring innovative therapies to patients in need and to build a new chapter of durable growth for shareholders. Our updated guidance and our preliminary view of an adjusted EBITDA-neutral 2020 reflects continued strong commercial performance from Makena SC auto-injector, Feraheme and Intrarosa, and includes a fully-funded launch of Vyleesi and our clinical development plans for AMAG-423 and ciraparantag."

2019 Financial Guidance

2 See reconciliations of 2019 GAAP to non-GAAP financial guidance at conclusion of this press release.

SECOND QUARTER ENDED JUNE 30
Revenue
Growth of the company’s key marketed products continued in the second quarter, with strong revenue and market share performance.

Makena SC auto-injector revenue grew to $41.0 million, compared with $13.5 million in the same period last year (launched March 2018).

The company did not ship any Makena IM product during the quarter, therefore the full impact of the $10.0 million change in estimated Medicaid and commercial rebate liabilities from prior period sales appears as negative revenue during the quarter.

Feraheme revenue increased to $42.1 million, an increase of 12% over the same period last year. Feraheme’s average quarterly market share increased to 17.2%, compared with 16.3% in the same period last year and 16.1% in the first quarter of 2019.

Intrarosa revenue totaled $4.9 million, compared with $3.2 million in the same period last year. TRx share increased to 4.5%, compared with 3.2% in the same period last year and 3.9% in the first quarter of 2019.

Operating Expenses

Cost of products sales (CoPS) in the second quarter of 2019 included a $4.8 million write-down of Makena IM inventory; CoPS in the second quarter of 2018 included $61.4 million in amortization expense primarily related to the Makena IM intangible asset.

Selling, general and administrative (SG&A) expenses in the second quarter of 2018 included an expense reversal of $49.8 million related to the Makena contingent consideration liability because the company no longer believed that it was probable that a sales milestone would be achieved. Excluding this expense reversal, SG&A expenses increased by $11.6 million, or 18%, in the second quarter of 2019, compared with the same period last year, primarily due to increased marketing expenses related to the upcoming launch of Vyleesi.

The intangible asset impairment charge relates to the full impairment of the Makena IM intangible asset (described above).

As of June 30, 2019, the company’s cash and investments totaled $261.0 million.

The FDA approval of Vyleesi triggered a $60.0 million payment obligation to Palatin Technologies, which was paid in July 2019.

Long-term debt totaled $320.0 million (representing the principal amounts outstanding of the 2022 convertible notes).

Operating Loss and Adjusted EBITDA

The impact of the $77.4 million non-cash impairment charge and the related $4.8 million inventory write-down in the second quarter of 2019 contributed to an operating loss of $115.8 million. The company reported negative adjusted EBITDA of $24.4 million in the second quarter of 2019.

CONFERENCE CALL AND WEBCAST ACCESS
AMAG Pharmaceuticals, Inc. will host a conference call and webcast today at 8:00 a.m. ET to discuss the company’s second quarter 2019 financial results, recent business highlights and 2019 outlook.

DIAL-IN NUMBER
U.S./Canada Dial-in Number: (877) 412-6083
International Dial-in Number: (702) 495-1202
Conference ID: 8573359

Replay Dial-in Number: (855) 859-2056
Replay International Dial-in Number: (404) 537-3406
Conference ID: 8573359

A telephone replay will be available from approximately 11:00 a.m. ET on August 7, 2019 through midnight on August 14, 2019.

The webcast with slides will be accessible through the Investors section of the company’s website at www.amagpharma.com. A replay of the webcast will be archived on the website for 30 days.

On August 7, 2019 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer and wet age-related macular degeneration through our license to Santen Pharmaceutical Co. Ltd., and utilizing our product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported financial results for the second quarter ended June 30, 2019 (Press release, Tracon Pharmaceuticals, AUG 7, 2019, View Source [SID1234538447]).

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Recent Corporate Highlights

In August, our partner Santen announced the completion of enrollment in the randomized Phase 2 AVANTE study of DE-122 in combination with Lucentis (ranibizumab) in patients with wet age-related macular degeneration (AMD).

In July, we initiated dosing of the first patient in a Phase 1 study of TJ004309 (CD73 antibody) as a single agent and in combination with Tecentriq (atezolizumab), a PD-L1 checkpoint inhibitor marketed by Roche, in patients with advanced solid tumors.

In June, data from the ongoing Phase 1/2 clinical trial of TRC253 in metastatic castrate resistant prostate cancer patients were published in the 2019 ASCO (Free ASCO Whitepaper) Proceedings. 22 patients who had progressed on prior Xtandi (enzalutamide) or Erleada (apalutamide) treatment were enrolled into one of six cohorts of escalating doses of TRC253. The single patient with a F877L androgen receptor (AR) point mutation at baseline remained on treatment for 49 weeks with a partial response by RECIST. The remaining 21 patients did not have a F877L AR point mutation at baseline, and 48% (10) remained on study for at least 6 months and one patient had a greater than 50% decrease in prostate specific antigen. TRC253 was well-tolerated and no drug-related serious adverse events were reported.
"We are excited to have initiated clinical development of TJ004309 and next look forward to collaborating on up to five bispecific antibodies with I-Mab Biopharma beginning with the first IND in 2020," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "We also continue to evaluate opportunities to establish new corporate partnerships. We are focused on ex-U.S. companies with first-in-class, best-in-class or fast follower clinical stage assets that could benefit from accessing our product development platform, which we believe offers a rapid and capital-efficient U.S. drug development and commercialization solution."

Expected Upcoming Milestones

Top-line data, including the primary endpoint of mean change in best corrected visual acuity at six months, from the randomized Phase 2 AVANTE trial of DE-122 in patients with wet AMD are expected in the first half of 2020.

Presentation of Phase 2 data from Phase 1/2 clinical trial of TRC253 in metastatic castrate resistant prostate cancer to Janssen is expected in the second half of 2020, whereupon Janssen will have an exclusive option to reacquire full rights to TRC253 for an opt-in payment of $45 million to TRACON, and obligations to pay regulatory and commercialization milestones totaling up to $137.5 million upon achievement of specified events and a low single-digit royalty on net sales.
Second Quarter 2019 Financial Results

Cash, cash equivalents and short-term investments were $26.3 million at June 30, 2019, compared to $39.1 million at December 31, 2018. We expect our current cash, cash equivalents and short-term investments to fund operations into the third quarter of 2020.

Research and development expenses for the second quarter of 2019 were $4.3 million compared to $8.1 million for the second quarter of 2018. The decrease was primarily attributable to lower manufacturing expenses due to the discontinuation of the TRC105 program.

General and administrative expenses for the second quarter of 2019 were $1.9 million compared to $1.6 million for the second quarter of 2018.

Net loss for the second quarter of 2019 was $6.3 million compared to $9.8 million for the second quarter of 2018.
Investor Conference Call

The Company will hold a conference call today at 4:30 p.m. EDT / 1:30 p.m. PDT to provide an update on corporate activities and to discuss the financial results of its second quarter 2019. The dial-in numbers are (855) 779‑9066 for domestic callers and (631) 485-4859 for international callers. Please use passcode 7498077. A live webcast of the conference call will be available online from the Investor/Events and Presentation page of the Company’s website at www.traconpharma.com.

After the live webcast, a replay will remain available on TRACON’s website for 60 days.

About DE-122 (carotuximab)

DE-122, an ophthalmic formulation of carotuximab, is active in preclinical choroidal neovascularization (CNV) models and designed to enhance the effect of approved VEGF inhibitors used to treat wet AMD. DE-122 is being investigated in the Phase 2 randomized AVANTE trial assessing the efficacy and safety of intravitreal injections in combination with Lucentis (ranibizumab) compared to Lucentis monotherapy in patients with wet AMD.

About TRC253

TRC253 is a novel, orally bioavailable small molecule drug that is a potent, high affinity competitive inhibitor of the androgen receptor (AR) and AR mutations, including the F877L mutation. The AR F877L mutation results in an alteration in the AR ligand binding domain that confers resistance to therapies for prostate cancer. Therapies targeting the AR have demonstrated clinical efficacy by extending time to disease progression, and in some cases, the survival of patients with metastatic castration-resistant prostate cancer. However, resistance to these agents is often observed and several molecular mechanisms of resistance have been identified, including gene amplification, overexpression, alternative splicing, and point mutation of the AR. TRC253 is currently being studied in a Phase 1/2 clinical trial in prostate cancer. For more information about the clinical trial, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php

About TJ004309

TJ004309 is a novel, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine, which is highly immunosuppressive. TJ004309 is currently being studied in a Phase 1 trial to assess safety and preliminary efficacy as a single agent and when combined with the PD-L1 checkpoint inhibitor Tecentriq in patients with advanced solid tumors.

On August 7, 2019 MannKind Corporation (NASDAQ:MNKD) reported financial results for the quarter and six months ended June 30, 2019 (Press release, Mannkind, AUG 7, 2019, View Source [SID1234538292]).

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"We continue to execute our commercial strategy for Afrezza, which resulted in product growth of 62% versus the second quarter of 2018," said Michael Castagna, Chief Executive Officer of MannKind Corporation. "Our partner in Brazil, Biomm, received marketing approval for Afrezza and expects to launch in the second half of this year. Meanwhile, our partnership with United Therapeutics continues to gain strength as we celebrated the completed construction of a new high-potency manufacturing suite in our Danbury facility in July."

Second Quarter 2019 Results
Total revenues were $15.0 million for the second quarter of 2019, reflecting Afrezza net revenue of $6.1 million and collaboration and services revenue of $8.9 million. Afrezza net revenue increased 62% compared to $3.8 million in the second quarter of 2018, primarily driven by higher product demand, a more favorable mix of Afrezza cartridges and price. Collaboration and services revenue increased $8.9 million compared to the second quarter of 2018, reflecting the licensing and research agreements signed with United Therapeutics in September 2018.

Afrezza gross profit was $1.7 million for the second quarter of 2019, an increase of $3.1 million, or 230%, compared to a gross loss of $1.3 million for the same period in 2018, primarily due to an increase of $2.3 million in net revenue, a $0.4 million decrease in realized currency loss associated with a foreign exchange contract and a $0.2 million decrease in inventory write-offs, partially offset by increased costs due to higher sales.

Research and development (R&D) expenses for the second quarter of 2019 were $1.6 million compared to $3.0 million for the second quarter of 2018. This 45% decrease was primarily attributable to a $0.5 million decrease in clinical trial spending and a $0.5 million decrease in personnel costs.

Selling, general and administrative (SG&A) expenses for the second quarter of 2019 were $16.6 million compared to $21.7 million for the second quarter of 2018. This decrease of $5.1 million, or 24%, was primarily attributable to a $2.3 million decrease in personnel related costs, a $1.3 million decrease in professional fees and a $1.0 million decrease in marketing spending.

Interest expense on notes (facility financing obligation and senior convertible notes) for the second quarter of 2019 was $0.6 million compared to $1.7 million for the second quarter of 2018. This $1.1 million decrease was primarily due to a reduction in debt principal balances.

The net loss for the second quarter of 2019 was $12.4 million, or $0.07 per share compared to a $22.7 million net loss in the second quarter of 2018 or $0.16 per share. The decrease was primarily the result of total revenues increasing from higher Afrezza commercial demand and from our licensing and research agreements with United Therapeutics.

Six Months Ended June 30, 2019
Total revenues were $32.5 million for the six months ended June 30, 2019, reflecting Afrezza net revenue of $11.1 million and collaboration and services revenue of $21.3 million. Afrezza net revenue increased 56% compared to $7.2 million for the six months ended June 30, 2018, primarily due to higher product demand, a more favorable mix of Afrezza cartridges and price. Collaboration and services revenue increased $21.2 million compared to the six months ended June 30, 2018, reflecting the licensing and research agreements signed with United Therapeutics in September 2018.

Afrezza gross profit was $2.8 million for the six months ended June 30, 2019, an increase of $4.7 million or 243% compared to a gross loss of $1.9 million in the same period in 2018, primarily due to an increase of $4.0 million in net revenue, a $0.8 million decrease in inventory write-offs, partially offset by increased costs due to higher sales.

R&D expenses for the six months ended June 30, 2019 were $3.3 million compared to $5.6 million for the six months ended June 30, 2018. This 41% decrease was primarily attributable to a $1.0 million decrease in personnel related costs and a $0.7 million decrease in clinical trial spending.

SG&A expenses for the six months ended June 30, 2019 and June 30, 2018 were both $42.3 million. The first half of 2019 included a $9.3 million expenditure for a television campaign for Afrezza offset by a $4.5 million decrease in personnel related costs, a $2.0 million decrease in professional fees, a $1.6 million decrease in marketing spending and a $0.4 million decrease in sponsorship expense.

Interest expense on notes (facility financing obligation and senior convertible notes) for the six months ended June 30, 2019 was $1.2 million compared to $3.5 million for the six months ended June 30, 2018. This $2.3 million decrease was primarily due to a reduction in debt principal balances.

The net loss for the six months ended June 30, 2019 was $27.3 million, or $0.15 per share compared to a $53.1 million net loss for the six months ended June 30, 2018 or $0.41 per share. The lower net loss was mainly attributable to a $25.1 million increase in total revenues.

Cash and Cash Equivalents
Cash, cash equivalents, restricted cash, and short-term investments at June 30, 2019 was $38.2 million compared to $71.7 million at December 31, 2018. The decrease was primarily due to net cash used in operating activities of $31.5 million for the six months ended June 30, 2019, including the receipt of a $12.5 million milestone payment from United Therapeutics, and a principal payment to Deerfield of $2.5 million.

Business Update
On August 6, 2019, MannKind Corporation and MannKind LLC entered into a Credit and Security Agreement with Apollo Investment Corporation, as lender, and MidCap Financial Trust, as lender and agent, which provides a secured term loan facility in an aggregate principal amount of up to $75.0 million and which matures on August 1, 2024 (the "MidCap Credit Facility"). MannKind borrowed the first advance of $40.0 million on August 6, 2019. In connection with the MidCap Credit Facility, MannKind also entered into privately negotiated exchange agreements with each of its existing creditors in order to pay off (in the case of Deerfield as a secured creditor) and restructure (in the case of Bruce & Co. and The Mann Group as unsecured creditors) MannKind’s existing debt obligations. When combined with a July 2019 exchange agreement with Deerfield, these exchanges reduced the principal amount of existing debt by $28.4 million and extended the maturity until November 2024 for $75.1 million (out of $80.3 million) of the remaining debt.

Conference Call

MannKind will host a conference call and presentation webcast to discuss these results today at 5:00 p.m. Eastern Time. To participate in the live call by telephone, please dial (866) 548-4713 or (323) 794-2093 and use the participant passcode: 8241782. Those interested in listening to the conference call live via the Internet may do so by visiting the Company’s website at View Source under News & Events.

A telephone replay of the call will be accessible for approximately 14 days following completion of the call by dialing (844) 512-2921 or (412) 317-6671 and use the participant passcode: 8241782#. A replay will also be available on MannKind’s website for 14 days.