On August 7, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with a focus on Myelodysplastic Syndromes (MDS), reported that the Company will release its second quarter financial results on August 14, 2019, before the market opens (Press release, Onconova, AUG 7, 2019, View Source [SID1234538327]). The Company will host a conference call on August 14, 2019, at 9 a.m. Eastern Time to discuss these results. Interested parties may access the call by dialing toll-free (855) 428-5741 from the U.S. or (210) 229-8823 internationally and using conference ID 9150777. The call will also be webcast live. Please click here to access the webcast on the Investor Relations page of the Company’s website. A replay will be available for 90 days.

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About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are conditions that can occur when the blood-forming cells in the bone marrow become dysfunctional and thus produce an inadequate number of circulating blood cells. It is frequently associated with the presence of blasts or leukemic cells in the marrow. This leads to low numbers of one or more types of circulating blood cells, and to the need for blood transfusions. In MDS, some of the cells in the bone marrow are abnormal (dysplastic) and may have genetic abnormalities associated with them. Different cell types can be affected, although the most common finding in MDS is a shortage of red blood cells (anemia). Patients with higher-risk MDS may progress to the development of acute leukemia.

On August 7, 2019 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company committed to giving patients back their innate ability to fight cancer, reported financial and operating results for the second quarter ended June 30, 2019 (Press release, Affimed, AUG 7, 2019, View Source [SID1234538324]).

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"After reaching agreement with the U.S. Food and Drug Administration on the study protocol design, we are now in the process of preparing to initiate the AFM13 registration-directed Phase 2 study," said Dr. Adi Hoess, Affimed’s CEO. "The recent positive final and interim results from two clinical studies of AFM13 add to the growing body of evidence supporting AFM13’s activity in CD30-positive lymphoma patients, and give us increased confidence in the potential of AFM13 to demonstrate clinical benefit in CD30-positive peripheral T cell lymphoma. To execute the Phase 2 study and to further advance our internal and partnered CD16A-targeting innate cell engager pipeline, we have significantly strengthened our organization through the addition of multiple key hires in the U.S. and Germany of individuals who have substantial drug development experience."

Corporate Updates

Affimed strengthened its drug development team with the addition of experienced personnel in several key areas, including Regulatory Affairs, Clinical Development and Operations, Drug Safety, Chemistry, Manufacturing and Control (CMC), Drug Safety & Pharmacovigilance, Biostatistics and Commercial Strategy. The new hires previously held positions at Novartis, Pfizer Inc., Abbott, Eli Lilly and Company and other large pharmaceutical or biotechnology companies.
In April, Affimed received a payment from Genentech triggered by the achievement of a preclinical milestone under its research collaboration to develop and commercialize novel natural killer (NK) cell engager-based immunotherapeutics based on Affimed’s ROCK platform to treat multiple cancers.
Affimed was added to the Russell 2000, Russell 3000, and Russell Microcap Indexes, effective after the U.S. markets closed on Friday, June 28, 2019 as part of Russell’s annual index rebalance process. Russell U.S. Indexes are widely used by investment managers and institutional investors as the basis for index funds and as benchmarks for active investment strategies.
In June 2019, Affimed’s subsidiary AbCheck entered into a five-year licensing agreement with Icosagen granting AbCheck access to Icosagen’s QMCF protein production technology. Under the terms of the agreement, AbCheck acquires the rights to utilize Icosagen’s QMCF technology platform for its commercial activities in antibody discovery.
Pipeline Updates

CD16A innate cell engager programs

AFM13 (CD30/CD16A)

Affimed reached agreement with the U.S. Food and Drug Administration regarding the design of its planned Phase 2 registration-directed study of AFM13 as monotherapy in relapsed or refractory patients with CD30-positive peripheral T cell lymphoma (PTCL). The results, if positive, could form the basis for a Biologics License Application (BLA) submission and support an accelerated approval given the unmet medical need for safe and effective new treatments in this hard-to-treat patient population. The study will also enroll a cohort of patients with transformed mycosis fungoides, an aggressive subtype of cutaneous T cell lymphoma. Study start-up activities are under way, with study commencement anticipated in the second half of 2019.
Updated data from an investigator-sponsored translational Phase 1b/2a study of AFM13 in patients with relapsed or refractory CD30-positive lymphoma with cutaneous manifestation led by Columbia University was presented at the International Conference on Malignant Lymphomas (ICML) in Lugano in June 2019. The data confirmed single-agent activity of AFM13 in CD30-positive lymphoma patients, with an objective response rate (ORR) of 50% (5 out of 10 patients). Tumor biopsies showed increased infiltration of NK cells in responders compared to non-responders, and evidence of NK cell-mediated killing.
Affimed reported the final results from the Phase 1b dose escalation study of AFM13 plus pembrolizumab that showed encouraging efficacy in the intent-to-treat (ITT) patient population (n=30) with an ORR of 83%, including complete responses (CR) in 40% and partial responses (PR) in 43% of patients with hard-to-treat Hodgkin lymphoma. At the highest treated dose (n=24), patients showed an ORR of 88% (CR of 46% and PR of 42%) as determined by independent assessment. Overall, the combination of AFM13 and pembrolizumab showed a favorable safety profile in patients, including some patients who did not respond to first-line chemotherapy and a subgroup of patients who were primary refractory to brentuximab vedotin. Importantly, a deepening of responses was reported over time in multiple patients. In addition, patients previously transplant-ineligible transitioned to transplant after achieving an objective response with the combination of AFM13 and pembrolizumab, thus increasing the chance for a cure. These positive results, taken together with data demonstrating single-agent activity of AFM13 in CD30-positive T cell lymphoma patients, form the basis for Affimed to initiate a registration-directed study of AFM13 as monotherapy in patients with PTCL.
The combination of AFM13 with allogeneic NK cells represents a novel approach in order to further improve response rates and durability of responses in patients with relapsed/refractory CD30-positive lymphoma. In a preclinical collaboration with the University of Texas MD Anderson Cancer Center (MDACC), AFM13 has been shown to bind to CD16A with much higher affinity than other CD16A binding moieties such as monoclonal antibodies, thus enabling the formation of a stable complex of AFM13 pre-mixed with cord blood-derived allogeneic NK cells. This stable complex showed strong efficacy in in vitro and in vivo experiments, forming the basis for an investigator-sponsored Phase 1 study by MDACC. In the study, MDACC intends to administer this stable complex in different doses (numbers of pre-loaded NK cells) into patients with relapsed/refractory CD30-positive malignancies.
AFM24 (EGFR/CD16A)

AFM24 is a tetravalent, bispecific EGFR- and CD16A-binding innate cell engager from Affimed’s ROCK platform. It is designed to target EGFR-expressing solid tumors by a new mechanism of action that activates innate immunity. This is a differentiated approach from cetuximab and other EGFR targeting approaches that inhibit tumor growth by EGFR-mediated signal transduction. Affimed presented data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2019 Annual Meeting that demonstrated AFM24’s ability to bridge NK cells and macrophages to EGFR expressing tumor cell lines and induce lysis through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), respectively. Due to AFM24’s different mode of action these effects were independent of RAS mutational status. Importantly, AFM24 enhanced tumor infiltration of NK cells and elicited dose-dependent anti-tumor efficacy in in vivo tumor models. AFM24 showed reduced inhibition of EGFR phosphorylation relative to the monoclonal antibody cetuximab. Treatment of cynomolgus monkeys with AFM24 resulted in a favorable safety profile, even when treated at high dose levels, demonstrating AFM24’s potential to have significantly lower toxicities in humans compared to standard of care. Affimed currently anticipates submitting the investigational new drug (IND) application for AFM24 around the end of the third quarter 2019.
Technology Updates

Data describing Affimed’s ROCK antibody platform was published in the mAbs journal, titled, "Redirected optimized cell killing (ROCK): A highly versatile multispecific fit-for-purpose antibody platform for engaging innate immunity." The paper discusses aspects of the modular platform, including the advantages of innate immune cell engagement over monoclonal antibodies and other engager concepts. The article also describes the potential of the ROCK platform to engineer a fit-for-purpose innate immune cell engager format that can be equipped with unique CD16A domains, modules that influence pharmacokinetic properties and molecular architectures that influence the activation of immune effectors, as well as tumor targeting. The article is available at: View Source
Financial Highlights

(Figures for the second quarter and six months ended June 30, 2019 and 2018 are unaudited.)

Cash, cash equivalents and current financial assets totaled €87.7 million as of June 30, 2019, compared to €108.8 million as of December 31, 2018. Based on its current operating and budget assumptions, Affimed anticipates that its cash, cash equivalents and current financial assets as of June 30, 2019 will enable the Company to fund its planned clinical development and early development activities into 2021.

Net cash used in operating activities was €18.9 million for the six months ended June 30, 2019, compared to net cash used in operating activities of €15.2 million for the six months ended June 30, 2018. The increase is primarily due to higher cash expenditure for research and development efforts.

Total revenue was €4.0 million for the three months ended June 30, 2019 compared to €0.2 million for the three months ended June 30, 2018. The increase in revenue is attributable to the recognition of €3.7 million as revenue from the Genentech collaboration in the second quarter of 2019.

Research and development (R&D) expenses for the second quarter of 2019 were €11.5 million, including accrued termination costs of €1.4 million associated with the wind-down activities for the two Phase 1 studies of AFM11. R&D expenses for the second quarter of 2018 were €7.1 million. The increase was primarily related to higher expenses related to manufacturing activities for clinical study material for AFM13, startup activities for the AFM13 registration study in PTCL, early stage development and discovery activities, and the termination costs for the two AFM11 clinical studies.

General and administrative (G&A) expenses for the second quarter of 2019 were nearly unchanged at €2.3 million compared to €2.2 million for the second quarter of 2018.

Net loss was €10.3 million, or €0.17 per common share, for the second quarter of 2019, compared to a net loss of €8.0 million, or €0.13 per common share, for the second quarter of 2018.

Note on IFRS Reporting Standards
Affimed prepares and reports the consolidated financial statements and financial information in accordance with International Financial Reporting Standards (IFRS) as issued by the International Accounting Standards Board (IASB). None of the financial statements were prepared in accordance with Generally Accepted Accounting Principles (GAAP) in the United States. Affimed maintains its books and records in Euro.

Conference Call and Webcast Information

Affimed will host a conference call and webcast today, Wednesday, August 7, 2019 at 8:30 a.m. Eastern time to discuss the company’s financial results and recent corporate developments. To access the call, please dial +1 (917) 720-0178 for U.S. callers, or +44 (0) 203 0095710 for international callers, and reference conference ID 9396039 approximately 15 minutes prior to the call. An audio webcast of the conference call can be accessed in the "Webcasts" section on the "Investors" page of the Affimed website at View Source A replay of the webcast will be available on Affimed’s website shortly after the conclusion of the call and will be archived for 30 days following the call.

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 Moderna, Inc. (Nasdaq: MRNA), a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported financial results for the second quarter of 2019 and provided business updates (Press release, Moderna Therapeutics, AUG 7, 2019, View Source [SID1234538322]).

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New updates announced today include:

Infectious Diseases

Enrollment complete for Phase 1 CMV vaccine (mRNA-1647) study
Second planned interim analysis of Phase 1 hMPV and PIV3 vaccine (mRNA-1653) study showed antibody titers remained above baseline at all dose levels at seven months
First subject dosed in Phase 1 RSV vaccine (mRNA-1172 or Merck V172) study
First subject dosed in Phase 1 Zika vaccine (mRNA-1893) study
Immuno-Oncology

First patient consented in Phase 2 PCV (mRNA-4157) study in patients with resected melanoma
First patient dosed in Phase 1 KRAS cancer vaccine (mRNA-5671 or Merck V941) study
First patient dosed in Phase 1 study of mRNA encoding IL12 (MEDI1191) injected intratumorally
Rare Diseases

Six of eight subjects dosed in the third cohort (0.6 mg/kg) of the Phase 1 antibody against chikungunya virus (mRNA-1944) study; the lipid nanoparticle (LNP) formulation used for mRNA-1944 is also utilized in Moderna’s MMA program
Three clinical sites actively recruiting for Phase 1/2 MMA (mRNA-3704) study
Research

Vertex Pharmaceuticals extended the companies’ research collaboration in cystic fibrosis (CF)
"Since our last quarterly update, our personalized cancer vaccine program with Merck has advanced into Phase 2, the cytomegalovirus vaccine Phase 1 study has completed enrollment and four new Phase 1 trials in immuno-oncology and infectious diseases have begun," said Stéphane Bancel, Moderna’s chief executive officer. "We are pleased by the advancement of our programs and look forward to sharing new clinical data in the near term. Additionally, we are excited that Vertex extended our research collaboration based on the teams’ progress to date. Our balance sheet remains strong, and we continue to deploy our capital toward the advancement and expansion of our development pipeline and the creation of potential new modalities."

Moderna currently has 21 mRNA development candidates in its portfolio with 13 in clinical studies. Across Moderna’s pipeline, more than 1,000 subjects have been enrolled in clinical studies. The Company’s updated pipeline can be found at View Source Moderna and collaborators have published more than 35 peer-reviewed papers, including 23 over the last 12 months.

Summary of Recent Highlights by Modality

Prophylactic vaccines: Moderna is developing vaccines against viral diseases where there is unmet medical need – including complex vaccines with multiple antigens for common diseases, as well as vaccines against epidemic and pandemic threats to global public health.

Respiratory syncytial virus (RSV) vaccine (mRNA-1172 or V172): The first subject has been dosed in the Phase 1 study of mRNA-1172 led by Merck. mRNA-1172 has shown enhanced potency in preclinical studies compared with the companies’ first RSV candidate (mRNA-1777).
Cytomegalovirus (CMV) vaccine (mRNA-1647): The Phase 1 study of mRNA-1647 has been fully enrolled, at a top dose of 300µg. This randomized, observer-blind and placebo-controlled study is designed to evaluate the safety and immunogenicity of mRNA-1647, a vaccine encoding the gB and pentamer complexes of CMV. CMV is a common human pathogen and a leading cause of birth defects.
Human metapneumovirus (hMPV) and parainfluenza type 3 (PIV3) vaccine (mRNA-1653): Topline data from a second planned interim analysis of an ongoing Phase 1 randomized, observer-blind, placebo-controlled and dose-ranging study in healthy adults showed that hMPV and PIV3 serum neutralizing antibody titers remained above baseline through seven months and the vaccine was generally well-tolerated. Topline data from the study’s first interim analysis, announced in February 2019, showed that mRNA-1653 boosted antibody titers one month after vaccination at all dose levels and was generally well-tolerated. Data from the study will be presented at IDWeek on October 2 – 6, 2019 in Washington, D.C. In a recent type C meeting with the U.S. Food and Drug Administration (FDA), the Company discussed a potential path forward to evaluate protection against both hMPV and PIV3 in a single Phase 3 study. Consistent with this development path, Moderna is planning to initiate a Phase 1b study of mRNA-1653 in seropositive toddler subjects as the next step.
Zika virus vaccine (mRNA-1893): The first subject has been dosed in the Phase 1 study of mRNA-1893. This development candidate is being developed in collaboration with the U.S. Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services.
Publications of note: In May, Moderna published its clinical data in Vaccine from two Phase 1 studies showing that mRNA vaccines against H10N8 and H7N9 influenza viruses were well-tolerated and elicited robust immune responses. In July, Moderna published preclinical data in the Journal of Infectious Diseases demonstrating the ability of mRNA vaccines to protect against congenital Zika virus infection in mice.
Cancer Vaccines: These programs focus on stimulating a patient’s immune system with antigens derived from tumor-specific mutations to enable the immune system to elicit a more effective anti-tumor response.

Personalized cancer vaccines (PCVs) (mRNA-4157, NCI-4650): The first patient has been consented for the randomized Phase 2 study investigating Merck’s pembrolizumab (KEYTRUDA) in combination with a 1 mg dose of mRNA-4157, compared to pembrolizumab alone, for the adjuvant treatment of high-risk resectable melanoma. Additionally, the protocol for the ongoing Phase 1 trial has been amended to include a cohort of 17 patients who are refractory to PD-1 inhibitors.
KRAS vaccine (mRNA-5671 or V941): The first patient was dosed in the Phase 1 open-label, multi-center study to evaluate the safety and tolerability of mRNA-5671 both as a monotherapy and in combination with pembrolizumab. The study, led by Merck, will enroll patients with KRAS mutant advanced or metastatic non-small cell lung cancer, colorectal cancer or pancreatic adenocarcinoma, and centrally confirmed Human Leukocyte Antigen (HLA) HLA-A*1101 and/or HLA-C*0802 allele expression. mRNA-5671 is designed to generate and present the four most prevalent KRAS mutations as neoantigens to the immune system. These four mutations comprise an estimated 80-90 percent of KRAS mutations in the study indications.
Presentations of note: Moderna presented interim data from its ongoing Phase 1 study of PCV candidate mRNA-4157, demonstrating safety, tolerability and immunogenicity of mRNA-4157 alone and in combination with pembrolizumab, at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Additionally, the National Cancer Institute (NCI) also presented data at ASCO (Free ASCO Whitepaper) from its Phase 1 study of PCV mRNA-4650 as a monotherapy for patients with advanced metastatic cancers. The NCI program uses Moderna’s mRNA technology but uses a different neoantigen selection process and study design than Moderna’s Phase 1 mRNA-4157 study.
Intratumoral Immuno-Oncology: These programs aim to drive anti-cancer T cell responses by injecting mRNA therapies directly into tumors.

OX40L (mRNA-2416): Dosing is ongoing at the highest levels (8 mg) in the Phase 1/2 open-label, multi-center, dose escalation and efficacy study of intratumoral injections of mRNA-2416 in patients with advanced malignancies. A Phase 2 expansion cohort in patients with advanced ovarian carcinoma is preparing to start enrollment; this will include the combination of intratumoral mRNA-2416 with durvalumab (IMFINZI).
OX40L + IL23 + IL36γ (Triplet) (mRNA-2752): The first patient was dosed in the combination arm of the Phase 1 trial of mRNA-2752. This study is evaluating mRNA-2752 as a single agent and in combination with durvalumab in patients with accessible solid tumors and lymphomas. mRNA-2752 is an investigational mRNA immuno-oncology therapy that encodes a novel combination of three immunomodulators.
IL12 (MEDI1191): The first patient was dosed with MEDI1191 monotherapy in the Phase 1 open-label, multi-center study of intratumoral injections of MEDI1191 alone and in combination with a checkpoint inhibitor in patients with advanced solid tumors, being led by AstraZeneca. MEDI1191 is an mRNA encoding for IL12, a potent immunomodulatory cytokine.
Systemic Secreted Therapeutics: In this modality, mRNA is delivered systemically to create proteins that are secreted outside the cell with the aim of producing pharmaceutically active proteins with therapeutic effects across the human body.

Antibody against the chikungunya virus (mRNA-1944): Six of eight subjects have been dosed in the third cohort (0.6 mg/kg) of the Phase 1 antibody against chikungunya virus (mRNA-1944) study. This study is evaluating the safety and tolerability of escalating doses of mRNA-1944 via intravenous infusion in healthy adults. mRNA-1944 is the first monoclonal antibody encoded by mRNA to be dosed in a human and the first development candidate from Moderna’s systemic secreted therapeutics modality to start clinical testing. The lipid nanoparticle (LNP) formulation used for mRNA-1944 is also utilized in Moderna’s MMA program.
Publication of note: In May, Moderna published preclinical data in Science Immunology showing mRNA encoding an antibody against the chikungunya virus (mRNA-1944) was well-tolerated, resulted in linear dose-dependent protein expression and provided complete protection in preclinical species.
Systemic Intracellular Therapeutics: These programs aim to deliver mRNA into cells within target organs as a therapeutic approach for diseases caused by a missing or defective protein.

Methylmalonic acidemia (MMA) (mRNA-3704): Three clinical trial sites are open and actively recruiting patients for the Phase 1/2 open-label, dose escalation study evaluating mRNA-3704 for the treatment of MMA. The objectives of the study are to evaluate safety and tolerability, assess the pharmacodynamic response and characterize the pharmacokinetic profile of mRNA-3704. Moderna recently updated the study protocol to widen the age bracket of the first cohort for this trial to allow for the enrollment of pediatric patients (now includes patients 8 years and older, a modification from adolescents aged 12-18.) This is Moderna’s first rare disease program to advance into clinical testing.
MMA and propionic acidemia (PA) Natural History Study (MaP): As of July 15, 2019, a total of 71 patients have been enrolled in the study (35 MMA, 36 PA). This is a global, multi-center, non-interventional study for patients with confirmed diagnosis of MMA due to methylmalonyl-CoA mutase (MUT) deficiency or PA and is designed to identify and correlate clinical and biomarker endpoints for these disorders.
Publication of note: In July, Moderna published preclinical data in EBioMedicine, a Lancet publication, showing mRNA therapy demonstrated long-term efficacy and safety, with dose-dependent and reproducible biomarker responses, in mouse models of MMA.
Information about each development candidate in Moderna’s pipeline, including those discussed in this press release, can be found on the investor relations page of its website: View Source

Research Update

Vertex CF research collaboration: In July 2016, Moderna and Vertex announced an exclusive research collaboration and licensing agreement aimed at the discovery and development of mRNA therapeutics for the treatment of CF. Based on preclinical work to date, Vertex has extended this collaboration through the first quarter of 2020 with options to extend further based on future progress. Pulmonary mRNA delivery represents a potential new route of administration for Moderna.
Annual R&D Day

Moderna will host its annual R&D Day in New York City on September 12, 2019.
Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on Wednesday, August 7, 2019. To access the live conference call, please dial 866-922-5184 (domestic) or 409-937-8950 (international), and refer to conference ID 4799277. A webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website at View Source The archived webcast will be available on Moderna’s website approximately two hours after the conference call and will be available for 30 days following the call.

Second Quarter 2019 Financial Results

Cash Position: Cash, cash equivalents and investments as of June 30, 2019 and December 31, 2018 were $1.44 billion and $1.69 billion, respectively.
Net Cash Used in Operating Activities: Net cash used in operating activities was $256.1 million for the six months ended June 30, 2019 compared to $159.6 million for the six months ended June 30, 2018. Net cash used in operating activities includes $22.0 million and $25.0 million for the six months ended June 30, 2019 and 2018, respectively, of in-licensing payments to Cellscript, LLC and its affiliate, mRNA RiboTherapeutics, Inc., to sublicense certain patent rights. After the first quarter of 2019, we have no further in-licensing payment obligations to Cellscript and its affiliate.
Cash Used for Purchases of Property and Equipment: Cash used for purchases of property and equipment was $18.2 million for the six months ended June 30, 2019 compared to $66.0 million for the six months ended June 30, 2018.
Revenue: Total revenue was $13.1 million for the three months ended June 30, 2019 compared to $28.9 million for the three months ended June 30, 2018. Total revenue was $29.1 million for the six months ended June 30, 2019 compared to $57.9 million for the six months ended June 30, 2018. On January 1, 2019, we adopted Accounting Standards Codification (ASC) Topic 606, Revenue from Contracts with Customers (ASC 606), using the modified retrospective transition method applied to those contracts which were not completed as of January 1, 2019. The total revenue decreases in 2019 were due to decreases in collaboration revenue across all our strategic alliances, particularly AstraZeneca and Merck, largely driven by our adoption of ASC 606. Total revenue under the previous revenue recognition standard would have been $16.9 million and $55.5 million for the three months and six months ended June 30, 2019, respectively.
Research and Development Expenses: Research and development expenses were $128.5 million for the three months ended June 30, 2019 compared to $104.5 million for the three months ended June 30, 2018. The increase was primarily attributable to an increase in personnel related costs including stock-based compensation, an increase in lab supplies and materials, and an increase in clinical trial and manufacturing costs. Research and development expenses were $259.1 million for the six months ended June 30, 2019 compared to $194.6 million for the six months ended June 30, 2018. The increase was primarily attributable to an increase in personnel related costs including stock-based compensation, an increase in clinical trial and manufacturing costs, an increase in lab supplies and materials, and an increase in consulting and outside services.
General and Administrative Expenses: General and administrative expenses were $28.5 million for the three months ended June 30, 2019 compared to $21.4 million for the three months ended June 30, 2018. The increase was mainly due to an increase in personnel related costs including stock-based compensation, and an increase in consulting and outside services. General and administrative expenses were $55.8 million for the six months ended June 30, 2019 compared to $37.7 million for the six months ended June 30, 2018. These increases were mainly due to the additional costs of operating as a publicly traded company, including an increase in personnel related costs and stock-based compensation, an increase in consulting and outside services, and an increase in information technology, facility and insurance related costs.
Net Loss: Net loss was $135.1 million for the three months ended June 30, 2019 compared to $90.6 million for the three months ended June 30, 2018. Net loss was $267.7 million for the six months ended June 30, 2019 compared to $163.0 million for the six months ended June 30, 2018.
2019 Expected Cash Position

Moderna reiterated its expectation for cash, cash equivalents and investments at December 31, 2019 to be in the range of $1.15 billion to $1.20 billion.

On August 7, 2019 Orion Corporation reported that sales of Nubeqa (darolutamide), jointly developed by Orion Corporation and Bayer for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC), has started in the USA. In connection with the successful commercialization of darolutamide in the USA, Orion receives from Bayer a EUR 45 million milestone (Press release, Orion , AUG 7, 2019, View Source [SID1234538321]). Orion will book the milestone in its third quarter 2019 result. The booking has no impact on Orion’s outlook for 2019 as the EUR 45 million milestone has been included in the financial guidance provided by the company.

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