On August 4, 2022 AstraZeneca and MSD reported it’s Lynparza (olaparib) has been approved in the European Union (EU) as monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2 mutations (gBRCAm), who have human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy (Press release, AstraZeneca, AUG 4, 2022, View Source [SID1234617441]).

This approval by the European Commission was based on results from the OlympiA Phase III trial published in The New England Journal of Medicine in June 2021 and follows the recommendation for approval in the EU by the Committee for Medicinal Products for Human Use of Lynparza in this setting.1 In the trial, Lynparza demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS), reducing the risk of invasive breast cancer recurrences, new cancers, or death by 42% versus placebo (based on a hazard ratio [HR] of 0.58; 99.5% confidence interval [CI] 0.41-0.82; p<0.0001).

Lynparza also demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), reducing the risk of death by 32% versus placebo (based on a HR of 0.68; 98.5% CI 0.47-0.97; p=0.009). The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials.

Breast cancer is the most diagnosed cancer worldwide with an estimated 2.3 million patients diagnosed in 2020.2 Approximately 90% of all breast cancer patients worldwide are diagnosed with early breast cancer and BRCA mutations are found in approximately 10% of HER2-negative patients in Europe.3-5

Professor Andrew Tutt, Global Chair of the OlympiA Phase III trial and Professor of Oncology at The Institute of Cancer Research, London and King’s College London, said: "Today’s approval marks a new era of care in Europe for patients with an inherited form of breast cancer. For patients with high-risk early-stage breast cancer, including those with germline BRCA mutations, recurrence rates remain unacceptably high, with more than one in four of these patients seeing their cancer return following surgery and systemic treatment. Olaparib is the first PARP inhibitor to demonstrate improved overall survival for high-risk early-stage breast cancer patients with germline BRCA mutations and I am hopeful it will become a new standard of care."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said:
"With this approval, Lynparza is now the first and only PARP inhibitor available for patients with germline BRCA-mutated HER2-negative early breast cancer in Europe. We can now bring the benefits of Lynparza to this earlier setting to help reduce the risk of life-threatening recurrence."

Dr Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, said: "Today’s approval offers patients with germline BRCA-mutated HER2-negative early-stage breast cancer a new, much-needed treatment option. Lynparza as adjuvant treatment can significantly reduce the risk of disease recurrence and death, reinforcing the importance of conducting germline BRCA testing as soon as possible after diagnosis."

In March 2022, Lynparza was approved in the US for the treatment of gBRCAm, HER2-negative high-risk early breast cancer. Lynparza is also approved in the US, EU, Japan, and many other countries for the treatment of patients with gBRCAm, HER2-negative, metastatic breast cancer previously treated with chemotherapy based on results from the OlympiAD Phase III trial. In the EU, this indication also includes patients with locally advanced breast cancer.

Notes

Financial considerations
Following this approval for Lynparza in the EU, AstraZeneca will receive a regulatory milestone payment from MSD of $75m, anticipated to be booked as Collaboration Revenue during the third quarter of 2022.

Early breast cancer
Early breast cancer is defined as cancer confined to the breast with or without regional lymph node involvement, and the absence of distant metastatic disease.6,7 In the EU, breast cancer alone accounts for approximately 29% of all cancers in women with 1 in 7 women developing the disease in their lifetime. In 2020, breast cancer accounted for an estimated 350,000 new cases and over 90,000 deaths.8 Despite advancements in the treatment of early breast cancer, up to 30% of patients with high-risk clinical and/or pathologic features recur within the first few years and patients with gBRCA mutations are more likely to be diagnosed at a younger age than those without these mutations.5,9

Breast cancer is one of the most biologically diverse tumour types with various factors fuelling its development and progression.10 The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease.11

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!

OlympiA
OlympiA is a Phase III, double-blind, parallel group, placebo-controlled, multicentre trial testing the efficacy and safety of Lynparza tablets versus placebo as adjuvant treatment in patients with gBRCAm high-risk HER2-negative early breast cancer, who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.12

The primary endpoint of the trial was iDFS defined as time from randomisation to date of first locoregional or distant recurrence or new cancer or death from any cause.1

The OlympiA Phase III trial is led by the Breast International Group in partnership with the Frontier Science & Technology Research Foundation, NRG Oncology, the US National Cancer Institute, AstraZeneca and MSD. The trial is sponsored by NRG Oncology in the US and by AstraZeneca outside the US.

BRCA
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells.9 When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional alterations that can lead to cancer. Cancers with BRCA mutations are more likely to be sensitive to PARP inhibitors including Lynparza.13-16

Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents – NHAs).

Inhibition of PARP proteins with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.

Lynparza is currently approved in a number of countries across PARP-dependent tumour types with defects and dependencies in the DDR pathway including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for gBRCAm, HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in the EU and US); for gBRCAm metastatic pancreatic cancer; and HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm only in the EU and Japan).

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

The AstraZeneca and MSD strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types.

Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. The companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines independently.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge and redefine the current clinical paradigm for how breast cancer is classified and treated, to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex and Zoladex and the next-generation oral selective oestrogen receptor degrader (SERD) and potential new medicine camizestrant.

The PARP inhibitor, Lynparza, is an approved targeted treatment option for early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD continue to research Lynparza in breast cancer patients with an inherited BRCA mutation.

Building on the initial approvals of Enhertu, a HER2-directed antibody drug conjugate (ADC), in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On August 4, 2022 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, reported financial results for the second quarter ended June 30, 2022 and provided program updates (Press release, Aeglea BioTherapeutics, AUG 4, 2022, View Source [SID1234617440]).

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 continue to make progress with our Homocystinuria program and are encouraged by the physician and patient interest in advancing our Phase 1/2 trial. There remains a great need for better treatment options for Homocystinuria patients and we look forward to sharing data from this trial later this year," said Anthony Quinn, M.B., Ch.B., Ph. D., president and chief executive officer of Aeglea.

"Given the current state of the financial markets and the implications for Aeglea and the biotechnology industry broadly, we are taking measures to reduce our cash burn and strengthen our financial position," said Jonathan Alspaugh, chief financial officer of Aeglea. "This includes reevaluating the allocation of resources to the pegzilarginase program as all patients have now transitioned to open label studies from which we’ve collected significant data. While we work with the FDA to identify a viable path forward, we will ensure that patients currently on pegzilarginase continue to receive treatment. We have also made the decision to postpone certain activities in our preclinical Cystinuria program due to strategic realignment and manufacturing constraints."

Dr. Quinn continued, "We continue to believe in the power of enzyme engineering to address unmet needs in rare metabolic diseases and that with our platform we have the potential to develop life-changing enzyme therapies for these patients. We remain dedicated to advancing our programs, supporting the patient communities we serve, and building a successful company."

Program and Corporate Updates

AGLE-177 in Homocystinuria

Completed dosing of patients in cohort 2 in Phase 1/2 clinical trial; cohort 3 currently being enrolled.
Opened first U.S. site to support enrollment of clinical trial.
Expect to announce Phase 1/2 clinical data in the fourth quarter of 2022.
Pegzilarginase in Arginase 1 Deficiency

Actively engaged with U.S. Food and Drug Administration (FDA) to discuss items cited in the Refusal to File letter and to identify a viable regulatory approach and path to the resubmission of the Biologics License Application (BLA) for pegzilarginase for the treatment of Arginase 1 Deficiency.
Cystinuria

Continuing certain Investigational New Drug (IND)-enabling activities but have postponed some manufacturing and other activities due to strategic prioritization and limited availability of raw materials.
Corporate

Strengthened the company’s financial position with a registered direct offering resulting in gross proceeds of $45.0 million, which extends the company’s cash runway through the second quarter of 2023.
Second Quarter 2022 Financial Results

As of June 30, 2022, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $90.4 million, including the $45.0 million in gross proceeds from the company’s registered direct offering in May 2022. The company expects its cash, cash equivalents and marketable securities will enable it to fund its operating expenses and capital expenditure requirements through the second quarter of 2023.

Aeglea recognized development fee revenues of $0.6 million in the second quarter of 2022 as a result of its license and supply agreement with Immedica for the commercial rights to pegzilarginase in certain territories outside the U.S. The revenue was related to the PEACE Phase 3 trial and BLA package. In the second quarter of 2021, Aeglea recognized $13.7 million of license and development revenue in connection with the Immedica license and supply agreement.

Research and development expenses totaled $15.4 million for the second quarter of 2022 and $13.6 million for the second quarter of 2021. The increase was primarily associated with expenses related to IND-enabling activities for AGLE-325 for the treatment of Cystinuria and pegzilarginase manufacturing to support ex-U.S. supply. The increase was partially offset by a decrease in expenses related to the PEACE Phase 3 trial of pegzilarginase and reductions in preclinical lab work.

General and administrative expenses totaled $7.7 million for the second quarter of 2022 and $6.8 million for the second quarter of 2021. This increase was primarily due to increased compensation and other personnel expenses as well as commercial capabilities and infrastructure expenses.

Net loss totaled $22.3 million and $6.8 million for the second quarter of 2022 and 2021, respectively, with non-cash stock compensation expense of $2.0 million and $2.1 million for the second quarter of 2022 and 2021, respectively.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is a novel recombinant human enzyme engineered to degrade the amino acid arginine and has been shown to rapidly and sustainably lower levels of the amino acid arginine in plasma. Aeglea is developing pegzilarginase for the treatment of people with Arginase 1 Deficiency (ARG1-D), a rare debilitating and progressive disease characterized by the accumulation of arginine. ARG1-D presents in early childhood and patients experience spasticity, seizures, developmental delay, intellectual disability and early mortality.

The PEACE Phase 3 clinical trial met its primary endpoint with a 76.7% reduction in mean plasma arginine compared to placebo. Additionally, 90.5% of pegzilarginase treated patients achieved normal plasma arginine levels. The arginine lowering was accompanied by a positive trend in Gross Motor Function Measure Part E, a measure of patient mobility. Aeglea’s Phase 1/2 and Phase 2 Open-Label Extension (OLE) data for pegzilarginase in patients with ARG1-D demonstrated clinical improvements and sustained lowering of plasma arginine. Pegzilarginase has received multiple regulatory designations, including Rare Pediatric Disease, Breakthrough Therapy, Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration as well as Orphan Drug Designation from the European Medicines Agency.

About AGLE-177 in Homocystinuria

AGLE-177 is a novel recombinant human enzyme, which is engineered to degrade the amino acid homocysteine and its dimer. AGLE-177 is currently being studied in a Phase 1/2 clinical trial for the treatment of patients with Classical Homocystinuria, a rare inherited disorder of methionine metabolism that results in elevated levels of total homocysteine. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including thromboembolic vascular events, skeletal abnormalities (including severe osteoporosis), developmental delay, intellectual disability, lens dislocation and severe near sightedness. Preclinical data demonstrated that AGLE-177 improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. AGLE-177 has received both U.S. and EU Orphan Drug Designation as well as U.S. Rare Pediatric Disease Designation.

On August 3, 2022 Advanced Proteome Therapeutics Corporation (TSXV: APC) (FSE: 0E81) ("APC" or the "Company") reported that the United States Patent and Trademark Office has issued a patent to its US subsidiary, Advanced Proteome Therapeutics Inc. ("APTI") (Press release, Advanced Proteome Therapeutics, AUG 3, 2022, View Source [SID1234622591]).

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!

On August 2, 2022, APTI was issued U.S. Patent No. 11,400,165 titled ‘Composition and method for modifying polypeptides’. The patent covers highly site-selective antibody conjugate compositions produced with APTI’s two-step conjugation technology including the half-product of the first step and final antibody-drug conjugate (ADC) product of the second step. The claims broadly cover antibodies as a class and different classes of payloads including toxins, drugs and chelators. The patent term, including patent term adjustment, is expected to extend into November 2039. This is the first patent issued under US patent application 16/180,960. APTI is continuing to pursue expanded claims and additional patents within the initial application in order to create additional layers of intellectual property protection.

Dr. Benjamin Krantz, President and CEO of APTI commented, "The issuance of this patent is a critical milestone for APTI. The patent provides market exclusivity to highly site-selective ADC compositions that are created with our two-step antibody conjugation approach. This protection greatly enhances our ability to monetize our invention and increases our attractiveness to potential collaborators. This is another step forward in our 2022 plan and I look forward to other successes in the near future."

On August 3, 2022 Moderna Therapeutics reported financial results and provided business updates for the second quarter of fiscal year 2022 (Press release, Moderna Therapeutics, AUG 3, 2022, View Source/news/news-details/2022/Moderna-Reports-Second-Quarter-2022-Financial-Results-and-Provides-Business-Updates/default.aspx" target="_blank" title="View Source/news/news-details/2022/Moderna-Reports-Second-Quarter-2022-Financial-Results-and-Provides-Business-Updates/default.aspx" rel="nofollow">View Source [SID1234618963]).

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!

"Today’s earnings represent a strong second quarter performance, with $10.8 billion in revenue for the first half of the year. We continue to have advance purchase agreements for expected delivery in 2022 of around $21 billion of sales. Given our strong financial position and commercial momentum, we are announcing today that the Board of Directors has approved a new share repurchase program for $3 billion," said Stéphane Bancel, Chief Executive Officer of Moderna. "Despite the slowing economy and challenges in the biotech industry, Moderna is in a unique position: a platform to drive scale and speed in research of new medicines, a strong balance sheet with $18 billion of cash and an agile, mission-driven team of over 3,400 people and growing. We will continue to invest and grow as we have never been as optimistic about Moderna’s future. Right now, we have four infectious disease vaccines in Phase 3 trials, and later this year, we expect important data from proof-of-concept studies in rare diseases and immuno-oncology. Our teams are actively working to prepare these new product launches to help patients and drive growth. This is an exciting time for Moderna as we continue to see significant scientific and business momentum."

Recent progress includes:

Respiratory Vaccines

Received U.S. FDA authorization for dose-dependent, two-dose primary series of mRNA-1273 inchildren and adolescents 6 months to 17 years of age; similar approvals or authorizations have been received from international regulatory authorities in more than 40 countries for children and adolescents 6 years to 17 years of age, and in the United States, Canada, Australia and other jurisdictions for children 6 months to 5 years of age
Positive data on booster dose of bivalent candidate based on the wild-type and Omicron subvariant BA.1 (mRNA-1273.214)
Began rapid development of mRNA-1273.222 , which contains the BA.4/5 Omicron strain and is being developed in accordance with recent FDA recommendations
Moderna continues to progress respiratory vaccine pipeline with ongoing Phase 2 data on next-generation, refrigerator-stable COVID vaccine candidate (mRNA-1283)
Phase 3 safety and immunogenicity trial started in June in the Southern Hemisphere for seasonal flu vaccine candidate (mRNA-1010) to support potential accelerated approval. Company is preparing for Phase 3 efficacy study in fall 2022 (if needed); Flu (mRNA-1020/-30) Phase 1/2 trial fully enrolled
Combination COVID + flu (mRNA-1073) Phase 1/2 fully enrolled; combination COVID + flu + RSV (mRNA-1230) in preclinical studies, expected to start Phase 1 trial later this year; endemic human coronavirus (mRNA-1287) in preclinical
Pediatric hMPV + PIV3 (mRNA-1653) Phase 1b fully enrolled; pediatric RSV + hMPV (mRNA-1365) in preclinical
Older adults RSV Phase 3 (mRNA-1345) , known as ConquerRSV, is ongoing; pediatric RSV in Phase 1
Latent Vaccines

CMV vaccine (mRNA-1647) pivotal Phase 3 study, known as CMVictory, is ongoing
EBV vaccine (to prevent infectious mononucleosis) (mRNA-1189) Phase 1 is ongoing; EBV vaccine (to prevent EBV sequelae) (mRNA-1195) in preclinical studies
HIV vaccines (mRNA-1644 and mRNA-1574) Phase 1 trials are ongoing
HSV vaccine (mRNA-1608) and VZV vaccine (mRNA-1468) in preclinical studies
Public Health Vaccines

Zika vaccine (mRNA-1893) ongoing in a Phase 2 study
Nipah vaccine (mRNA-1215) Phase 1 study, led by the National Institutes of Health (NIH), is ongoing (first participant dosed in July)
mRNA therapeutics

The first and second cohorts of the Phase 1/2 Paramount study of propionic acidemia (PA) candidate (mRNA-3927) are fully enrolled. Moderna is enrolling patients into additional cohorts.
The first cohort of the Phase 1/2 Landmark study of methylmalonic acidemia (MMA) candidate (mRNA-3705) is fully enrolled. Moderna is enrolling patients into additional cohorts.
GSD1a (mRNA-3745) Phase 1 trial first patient dosed
PKU (mRNA-3283), CN-1 (mRNA-3351) and cystic fibrosis in preclinical studies (with Vertex) (VXc-522)
PCV (mRNA-4157) Phase 1 ongoing; Phase 2 fully enrolled, data expected in 4Q 2022
Checkpoint vaccine (mRNA-4359) has received safe to proceed and has an open Investigational New Drug (IND) designation from the U.S. FDA
AZD8601 , a mRNA encoding VEGF therapeutic, has been returned to Moderna from AstraZeneca. We are evaluating next steps for the program
Moderna now has 46 programs in development across 43 development candidates 1 , of which 31 are currently in active clinical trials. The Company’s updated pipeline can be found at www.modernatx.com/pipeline. Moderna and collaborators have published more than 120 peer reviewed manuscripts.

Second Quarter 2022 Financial Results

Revenue: Total revenue was $4.7 billion and $10.8 billion for the three and six months ended June 30, 2022, respectively, compared to $4.4 billion and $6.3 billion for the same periods in 2021. The revenue increase in 2022 was primarily due to increased product sales from sales of the Company’s COVID-19 vaccine. Product sales for the second quarter of 2022 were $4.5 billion, increased by $334 million, or 8%, compared to the same period in 2021, primarily driven by a higher average selling price due to customer mix. Product sales for the six months ended June 30, 2022 were $10.5 billion, increased by $4.5 billion, or 76%, compared to the same period in 2021, driven by increased sales of the Company’s COVID-19 vaccine.
Cost of Sales: Cost of sales was $1.4 billion, or 30% of product sales, for the second quarter of 2022, including third-party royalties of $157 million. Cost of sales as a percentage of product sales for the second quarter of 2022 increased by 12 percentage points, from 18% in the same period in 2021. This includes a charge of $499 million for inventory write-downs related to COVID-19 products that have exceeded or are expected to exceed their approved shelf-lives prior to being used, as well as a loss on firm purchase commitments of $184 million and an expense for unutilized external manufacturing capacity of $131 million. These charges are driven by a substantial reduction of our expected deliveries to COVAX and deferral of deliveries to other customers, particularly to the European Union.
Research and Development Expenses: Research and development expenses were $710 million and $1.3 billion for the three and six months ended June 30, 2022, respectively, compared to $421 million and $822 million for the same periods in 2021. The growth in spending in 2022 was mainly due to increases in clinical trial expenses, personnel-related costs, and consulting and outside services.
Selling, General and Administrative Expenses: Selling, general and administrative expenses were $211 million and $479 million for the three and six months ended June 30, 2022, respectively, compared to $121 million and $198 million for the same periods in 2021. The growth in spending in 2022 was mainly due to increases in distributor fees and marketing expenses, ongoing digital investments, personnel-related costs, and a $50 million endowment given to the Moderna Charitable Foundation in the first quarter of 2022.
Provision for Income Taxes: The effective tax rate was 11% and 13% for the three and six months ended June 30, 2022, respectively, compared to 9% and 7% for the same periods in 2021. The increase in 2022 was primarily due to the benefit recorded in 2021 related to the release of the valuation allowance on the majority of our deferred tax assets. Income taxes were $277 million for the second quarter of 2022, decreased by $6 million compared to the same period in 2021, primarily due to a decrease in pre-tax income, partially offset by a higher effective tax rate.Income taxes were $849 million for the six months ended June 30, 2022, increased by $527 million compared to the same period in 2021, mainly due to an increase in pre-tax income and a higher effective tax rate.
Net Income: Net income was $2.2 billion and $5.9 billion for the three and six months ended June 30, 2022, respectively, compared to $2.8 billion and $4.0 billion for the same periods in 2021.
Earnings Per Share: Diluted EPS was $5.24 and $13.85 for the three and six months ended June 30, 2022, respectively, compared to $6.46 and $9.30 for the same periods in 2021.
Cash Position: Cash, cash equivalents and investments as of June 30, 2022 and December 31, 2021 were $18.1 billion and $17.6 billion, respectively.
Net Cash Provided By Operating Activities: Net cash provided by operating activities was $3.1 billion for the six months ended June 30, 2022, compared to $7.0 billion for the same period in 2021. Net cash provided by operating activities decreased in 2022, primarily attributable to revenue recognized from deferred revenue in excess of customer deposits received and increased income tax payments, partially offset by increased product sales and higher collection of receivables.
Cash Used for Purchases of Property and Equipment: Cash used for purchases of property and equipment was $219 million for the six months ended June 30, 2022, compared to $65 million for the same period in 2021. The increase was primarily driven by the Company’s business expansion.
Cash Used for Repurchases of Common Stock: Cash used for repurchases of common stock was $1.9 billion for the six months ended June 30, 2022. Moderna did not conduct share repurchases prior to the fourth quarter of 2021. From the end of the third quarter of 2021 to the end of the second quarter of 2022, the Company repurchased 16 million shares, reducing the number of common shares outstanding from 405 million to 392 million, more than offsetting 3 million shares of common stock issued in connection with equity compensation over this period.
2022 Financial Framework

Advance Purchase Agreements (APAs): Moderna’s APAs for product sales for which we expect to make delivery in 2022 are approximately $21 billion. This includes the recently announced agreement with the U.S. government for 70 million doses (option for 4 million pediatric doses has been exercised) and an adjustment for doses that remain unallocated by COVAX due to lack of demand. Moderna anticipates that for sales in the second half, sales will be greater in the fourth quarter than the third quarter, driven by the timing for approval of our updated COVID-19 vaccines and the related manufacturing ramp-up of new products.
Cost of Sales: Cost of sales as percentage of product sales are expected to be in the mid- 20s percentage range, with possible cost of sales in the high-20s in the event of further charges due to product updates.
Research & Development (R&D) and Selling, General & Administrative (SG&A) Expenses : Full year expenses are expected to be approximately $4 billion.
Tax Rate: The Company expects an effective tax rate for the full year in the low- to mid-teen percentage range
Capital Expenditures: Expect capital investments for 2022 in the range of $0.6-$0.8 billion.
Share Repurchase Program: The Board of Directors has authorized an additional share repurchase program for $3 billion in August 2022 to return excess capital to shareholders. The previous program of $1 billion announced in August 2021 was fully utilized as of the end of January 2022 and the $3 billion repurchase program announced in February 2022 is continuing and currently has approximately $1 billion outstanding.
Corporate Updates

Continued Growth: Moderna had approximately 3,400 employees as of June 30, 2022, compared to approximately 1,800 employees as of June 30, 2021
ESG Report: Moderna released its first annual ESG report, highlighting the company’s efforts and commitment to the environment, sustainability and governance
Company Recognition: Moderna made its Fortune 500 debut and was listed in the Financial Times list of the Americas’ Fastest Growing Companies of 2022
Science & Technology Day: Moderna hosted its 5 th Science and Technology Day, highlighting advances from its commitment to basic and applied sciences
Strategic Partnership with Government of the United Kingdom: Moderna and the United Kingdom government announced an agreement in principle to establish an mRNA Innovation and Technology Center in the UK
Strategic Partnership with Government of Canada: Moderna announced its plan to build a state-of-the-art mRNA vaccine manufacturing facility in Quebec that will support a long-term strategic partnership with the Government of Canada to enhance pandemic preparedness
Japan Marketing Authorization: Moderna has become the marketing authorization holder for Spikevax in Japan, following a transition from Takeda. Moderna continues to grow its footprint in Japan
Moderna & IAVI Partner on Global Health: Moderna and nonprofit scientific research organization IAVI announced a new collaboration to employ mRNA technology to meet the challenge of a range of global health threats; Moderna and IAVI subsequently launched a first-in-Africa clinical trial of mRNA HIV vaccine development program (mRNA-1644)
Key 2022 Investor and Analyst Event Dates

R&D Day: September 8
ESG Day: November 10
Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on Wednesday, August 3, 2022.

To access the live conference call via telephone, please register at the link below. Once registered, dial-in numbers and a unique pin number will be provided. A live webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website.

Telephone: https://register.vevent.com/register/BI56aa5dacc77e41ebbba622851ac67f30
Webcast: View Source
The archived webcast will be available on Moderna’s website approximately two hours after the conference call and will be available for one year following the call.

About Moderna

In over 10 years since its inception, Moderna has transformed from a research-stage company advancing programs in the field of messenger RNA (mRNA), to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across seven modalities, a broad intellectual property portfolio in areas including mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for rapid clinical and commercial production at scale. Moderna maintains alliances with a broad range of domestic and overseas government and commercial collaborators, which has allowed for the pursuit of both groundbreaking science and rapid scaling of manufacturing. Most recently, Moderna’s capabilities have come together to allow the authorized use and approval of one of the earliest and most effective vaccines against the COVID pandemic.

Moderna’s mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. Moderna has been named a top biopharmaceutical employer by Science for the past seven years. To learn more, visit www.modernatx.com .

MODERNA, INC.
CONDENSED CONSOLIDATED STATEMENTS OF INCOME
(Unaudited, in millions, except per share data)

Three Months Ended June 30, Six Months Ended June 30,

2022 2021 2022 2021
Revenue:

Product sales
$ 4,531 $ 4,197 $ 10,456 $ 5,930
Grant revenue
183 139 309 333
Collaboration revenue
35 18 50 28
Total revenue
4,749 4,354 10,815 6,291
Operating expenses:
Cost of sales
1,381 750 2,398 943
Research and development
710 421 1,264 822
Selling, general and administrative
211 121 479 198
Total operating expenses
2,302 1,292 4,141 1,963
Income from operations
2,447 3,062 6,674 4,328
Interest income
40 3 55 7
Other expense, net
(13 ) (2 ) (26 ) (12 )
Income before income taxes
2,474 3,063 6,703 4,323
Provision for income taxes
277 283 849 322
Net income
$ 2,197 $ 2,780 $ 5,854 $ 4,001

Earnings per share:
Basic
$ 5.55 $ 6.93 $ 14.66 $ 9.98
Diluted
$ 5.24 $ 6.46 $ 13.85 $ 9.30

Weighted average common shares used in calculation of earnings per share:
Basic
396 402 399 401
Diluted
419 431 423 430
MODERNA, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(Unaudited, in millions, except per share data)

June 30, December 31,

2022 2021
Assets

Current assets:

Cash and cash equivalents
$ 2,873 $ 6,848
Investments
5,024 3,879
Accounts receivable
2,691 3,175
Inventory
1,921 1,441
Prepaid expenses and other current assets
1,054 728
Total current assets
13,563 16,071
Investments, non-current
10,162 6,843
Property and equipment, net
1,324 1,241
Right-of-use assets, operating leases
122 142
Restricted cash, non-current
12 12
Deferred tax assets
785 326
Other non-current assets
75 34
Total assets
$ 26,043 $ 24,669
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable
$ 181 $ 302
Accrued liabilities
1,780 1,472
Deferred revenue
4,093 6,253
Income taxes payable
349 876
Other current liabilities
409 225
Total current liabilities
6,812 9,128
Deferred revenue, non-current
405 615
Operating lease liabilities, non-current
87 106
Financing lease liabilities, non-current
641 599
Other non-current liabilities
113 76
Total liabilities
8,058 10,524
Stockholders’ equity:
Additional paid-in capital
2,413 4,211
Accumulated other comprehensive loss
(240 ) (24 )
Retained earnings
15,812 9,958
Total stockholders’ equity
17,985 14,145
Total liabilities and stockholders’ equity
$ 26,043 $ 24,669
MODERNA, INC.
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(Unaudited, in millions)

Six Months Ended June 30,

2022 2021
Operating activities

Net income
$ 5,854 $ 4,001
Adjustments to reconcile net income to net cash provided by operating activities:
Stock-based compensation
94 65
Depreciation and amortization
155 84
Amortization/accretion of investments
29 13
Deferred income taxes
(376 ) (72 )
Other non-cash items
15 -
Changes in assets and liabilities:
Accounts receivable
484 (629 )
Prepaid expenses and other assets
(324 ) (110 )
Inventory
(480 ) (596 )
Right-of-use assets, operating leases
20 (14 )
Accounts payable
(56 ) 44
Accrued liabilities
305 367
Deferred revenue
(2,370 ) 3,433
Income taxes payable
(527 ) 377
Operating lease liabilities
(19 ) 8
Other liabilities
263 63
Net cash provided by operating activities
3,067 7,034
Investing activities
Purchases of marketable securities
(8,734 ) (6,559 )
Proceeds from maturities of marketable securities
1,409 860
Proceeds from sales of marketable securities
2,506 1,706
Purchases of property and equipment
(219 ) (65 )
Investment in convertible notes
(35 ) -
Net cash used in investing activities
(5,073 ) (4,058 )
Financing activities
Proceeds from issuance of common stock through equity plans
29 64
Repurchase of common stock
(1,921 ) -
Changes in financing lease liabilities
(77 ) (62 )
Net cash (used in) provided by financing activities
(1,969 ) 2
Net (decrease) increase in cash, cash equivalents and restricted cash
(3,975 ) 2,978
Cash, cash equivalents and restricted cash, beginning of year
6,860 2,636
Cash, cash equivalents and restricted cash, end of period
$ 2,885 $ 5,614
Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: anticipated sales, including the timing of sales, under advance purchase agreements in 2022 and the associated dollar amounts to be received, which should not be construed as expected 2022 revenue; the timing of data from proof-of-concept studies in rare diseases and immuno-oncology; the repurchase by Moderna of shares of its common stock under its repurchase programs; potential accelerated approval of mRNA-1010 (flu); the timing of the Company’s Phase 1 trial of its combination COVID + flu + RSV vaccine candidate; COVID market dynamics; Moderna’s 2022 financial framework; Moderna’s plans to construct mRNA manufacturing facilities in the United Kingdom and Canada; and the potential of mRNA technology to address a range of global health threats. In some cases, forward-looking statements can be identified by terminology such as "will," "may," "should," "could," "expects," "intends," "plans," "aims," "anticipates," "believes," "estimates," "predicts," "potential," "continue," or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading "Risk Factors" in Moderna’s Annual Report on Form 10-K for the fiscal year ended December 31, 2021 and Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2022, each filed with the U.S. Securities and Exchange Commission (SEC), and in subsequent filings made by Moderna with the SEC, which are available on the SEC’s website at www.sec.gov . Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna’s current expectations and speak only as of the date of this press release.

Jazz Pharmaceuticals has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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!