On August 1, 2024 GSK plc (LSE/NYSE: GSK) reported the US Food and Drug Administration (FDA) has approved Jemperli (dostarlimab) in combination with carboplatin and paclitaxel (chemotherapy) followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer (Press release, GlaxoSmithKline, AUG 1, 2024, View Source [SID1234645260]). This approval broadens the previous indication for Jemperli plus chemotherapy to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours who represent 70-75% of patients diagnosed with endometrial cancer and who have limited treatment options. The supplemental Biologics License Application (sBLA) supporting this expanded indication received Priority Review and was approved ahead of the Prescription Drug User Fee Act action date.

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Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "Jemperli plus chemotherapy is the first and only immuno-oncology regimen to show significant and meaningful improvement in overall survival for adult patients with primary advanced or recurrent endometrial cancer regardless of biomarker status. We are thrilled this option is now available for more patients in the US, including the 70-75% with MMRp/MSS tumours where treatment options have been limited."

Today’s expanded approval is based on results from dual primary endpoints of investigator-assessed progression-free survival (PFS) and overall survival (OS) from Part 1 of the RUBY phase III trial. RUBY Part 1 is the only clinical trial in this setting to show a statistically significant OS benefit in the full population of patients with primary advanced or recurrent endometrial cancer, demonstrating a 31% reduction in risk of death (HR: 0.69; 95% CI: 0.54–0.89) compared to chemotherapy alone.

At the 2.5-year landmark, 61% (95% CI: 54-67) of patients in the Jemperli plus chemotherapy group compared to 49% (95% CI: 43-55) in the chemotherapy group were alive. In addition, a 16.4-month improvement in median OS was observed with Jemperli plus chemotherapy versus chemotherapy alone (44.6 months [95% CI: 32.6–NR] vs. 28.2 months [95% CI: 22.1–35.6], respectively). The median duration of follow-up was more than three years.1 The safety and tolerability analysis from RUBY Part 1 showed a safety profile for Jemperli and carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse events (≥ 20%) in patients receiving Jemperli plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anaemia, arthralgia, constipation, diarrhoea, myalgia, rash, hypomagnesemia, decreased appetite, peripheral sensory neuropathy and vomiting.

Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial said: "The initial approval of Jemperli plus chemotherapy was practice-changing for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and today’s expanded approval will offer even more patients the opportunity for improved outcomes. This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer."

Adrienne Moore, Survivor, Founding Member and President of Endometrial Cancer Action Network for African-Americans (ECANA) said: "With this expanded approval for Jemperli plus chemotherapy, GSK is bringing a much-needed new treatment regimen to the endometrial cancer community that may help patients with primary advanced or recurrent endometrial cancer live longer, providing hope to patients and their families. Survivors and advocates should be excited by today’s news and especially delighted that this approval means that more patients in the US who are diagnosed with endometrial cancer will have a new treatment option."

About endometrial cancer
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecologic cancer in developed countries,2 with an estimated 1.6 million people living with active disease at any stage and 417,000 new cases reported each year worldwide.3 Incidence rates are expected to rise by approximately 40% between 2020 and 2040.4 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.5 Among patients with primary advanced or recurrent endometrial cancer, approximately 70-75% have MMRp/MSS tumours.6

About RUBY
RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.

In Part 1, the dual-primary endpoints are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and overall populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma.

In Part 2, the primary endpoint is investigator-assessed PFS in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organisation dedicated to transforming the standard of care in gynaecologic oncology.

About Jemperli (dostarlimab)
Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development programme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies in gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes.

In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This includes patients with MMRp/MSS and dMMR/MSI-H tumours. Jemperli is also approved as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. Additionally, Jemperli is indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli and cobolimab (GSK4069889), a TIM-3 antagonist.

Please see accompanying US Prescribing Information.

On August 1, 2024 Daiichi Sankyo (TSE: 4568) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the first patient has been dosed in the IDeate-Lung02 Phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) in patients with relapsed small cell lung cancer (SCLC) versus treatment of physician’s choice of chemotherapy (Press release, Merck & Co, AUG 1, 2024, View Source [SID1234645278]).

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Ifinatamab deruxtecan is a specifically engineered potential first-in-class B7-H3 directed DXd antibody-drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Merck.

Small cell lung cancer is the second most common type of lung cancer, accounting for about 15% of cases. SCLC is aggressive and progresses rapidly to the metastatic stage, which has a five-year survival rate of only 3%. Approximately 65% of all SCLC tumors have a moderate-to-high expression of the protein B7-H3, which is associated with disease progression and poor prognosis.

"Patients living with small cell lung cancer face poor outcomes with currently available treatments," said Mark Rutstein, MD, global head, oncology clinical development, Daiichi Sankyo. "The IDeate-Lung02 trial is an important next step as we look to better understand the role of ifinatamab deruxtecan as a potential new medicine for patients with certain types of small cell lung cancer."

"The initiation of the IDeate-Lung02 trial for ifinatamab deruxtecan marks the second pivotal study since the start of our collaboration with Daiichi Sankyo and follows the recent initiation of the REJOICE-Ovarian01 Phase 2/3 study for raludotatug deruxtecan," said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "This is a significant milestone as we work together to evaluate an innovative medicine that may have the potential to make a meaningful difference in the lives of people facing small cell lung cancer, a difficult-to-treat cancer."

The initiation of IDeate-Lung02 is based on updated results from a subgroup analysis of the IDeate-PanTumor01 Phase 1/2 trial of ifinatamab deruxtecan presented at the 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer.

About the IDeate-Lung02 trial

IDeate-Lung02 is a global, multicenter, randomized, open-label Phase 3 trial evaluating the efficacy and safety of ifinatamab deruxtecan (I-DXd) versus treatment of physician’s choice of chemotherapy (amrubicin, lurbinectedin or topotecan) in patients with relapsed SCLC following disease progression with only one prior line of platinum-based chemotherapy. Eligible patients will be randomized to receive ifinatamab deruxtecan (12 mg/kg) or physician’s choice of chemotherapy.

The dual primary endpoints are objective response rate (ORR) as assessed by blinded independent central review (BICR) and overall survival. Secondary endpoints include ORR as assessed by investigator, and progression-free survival, duration of response, disease control rate and time to response – all assessed by both BICR and investigator.

IDeate-Lung02 is expected to enroll approximately 460 patients across Asia, Europe, Oceania, North America and South America. For more information, please visit ClinicalTrials.gov.

About small cell lung cancer

More than 2.48 million lung cancer cases were diagnosed globally in 2022. Small cell lung cancer is the second most common type of lung cancer, accounting for about 15% of cases. SCLC is aggressive and progresses rapidly to the metastatic stage, which has a five-year survival rate of only 3%. While conventional first-line therapy for patients with advanced SCLC may help some patients live longer, the current second-line standard of care offers limited clinical benefit and new treatment approaches are needed.

About B7-H3

B7-H3 is a transmembrane protein that belongs to the B7 family of proteins which bind to the CD28 family of receptors that includes PD-1. B7-H3 is overexpressed in a wide range of cancer types, including small cell lung cancer, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. There are currently no B7-H3 directed medicines approved for the treatment of any cancer.

About ifinatamab deruxtecan

Ifinatamab deruxtecan (I-DXd) is an investigational, potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Ifinatamab deruxtecan is being evaluated in a global development program, which includes IDeate-Lung02, a Phase 3 trial in patients with relapsed SCLC versus investigator’s choice of chemotherapy, IDeate-Lung01, a Phase 2 monotherapy trial in patients with previously treated extensive-stage SCLC and IDeate-PanTumor01, a Phase 1/2 first-in-human trial in collaboration with Sarah Cannon Research Institute (SCRI) with study operational oversight and delivery provided through SCRI’s early phase oncology clinical research organization, SCRI Development Innovations in Nashville, TN. Ifinatamab deruxtecan was granted orphan drug designation by the U.S. Food and Drug Administration in April 2023 and by the European Commission in February 2024 for the treatment of SCLC.

On August 1, 2024 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on its Phase III clinical trial, FLAMINGO-01, which is evaluating GLSI-100, an immunotherapy to prevent breast cancer recurrences, reported the following update of the expansion of clinical sites into Spain (Press release, Greenwich LifeSciences, AUG 1, 2024, View Source [SID1234645239]).

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As previously announced, the Company has partnered with GEICAM, the largest academic breast cancer research network in Spain, where 38 hospitals have agreed to participate in FLAMINGO-01.

To date, approximately 30 out of 38 sites have conducted site initiation visits (SIVs). An SIV is followed by site activation, HLA type screening, and study treatment. To date approximately 19 sites have been activated. Multiples sites have begun screening patients for HLA type and have started treating patients. The Company has visited and trained in-person at approximately 26 out of the 38 sites to ensure optimal treatment at each site. In the coming months, GEICAM hopes to complete the remaining SIVs and the Company hopes to visit the remaining sites.

"It has been an honor to meet with the excellent study staff, investigators and GEICAM staff across Spain. Their expertise and interest in FLAMINGO-01 is encouraging for the success of the study. We look forward to seeing patient recruitment increase in Spain as other countries in the European Union become active," remarked Jaye Thompson, VP of Clinical and Regulatory Affairs.

CEO Snehal Patel commented, "The remarkable progress in Spain, in just May through July, is a testament to the commitment of GEICAM and our team to collaborate and to train the sites together, which we hope will lead to high quality treatment of patients. With just these 30 sites, we have approximately doubled the number of sites that we have opened in the US."

The Company may provide updates on the status of other countries in Europe as the clinical trial is expanded to up to 150 sites in the US, Spain, Italy, France, Germany, and Poland.

About GEICAM

Founded in 1995, GEICAM is a not-for-profit organization leading academic breast cancer research in Spain. It has conducted more than 140 studies involving more than 67,000 women and men and is comprised of more than 900 experts based in over 200 Spanish hospitals. Its mission is to promote independent clinical, epidemiological, and translational research in oncology, with a multidisciplinary approach and under quality criteria, to improve health outcomes, as well as prevention, medical education, and the dissemination of the knowledge of this disease to patients and general society. More information on GEICAM can be found at View Source

About FLAMINGO-01 and GLSI-100

FLAMINGO-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2 positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US clinical sites from university-based hospitals and cooperative networks with plans to expand into Europe and to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

For more information on FLAMINGO-01, please visit the Company’s website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: [email protected]

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 300,000 new breast cancer patients and 4 million breast cancer survivors. HER2 (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On August 1, 2024 Instil Bio, Inc. (Nasdaq: TIL, "Instil") and ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (HKEX Code: 1541.HK, "ImmuneOnco"), reported a definitive agreement pursuant to which Instil is in-licensing ex-China development and commercial rights to ImmueOnco’s proprietary PD-L1xVEGF bispecific antibody, IMM2510, as well as its next-generation anti-CTLA-4 antibody, IMM27M (Press release, Instil Bio, AUG 1, 2024, View Source [SID1234645261]).

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IMM2510 is a novel, potentially best-in-class bispecific antibody consisting of an anti-PD-L1 antibody fused to a vascular endothelial growth factor (VEGF) receptor "trap" which binds VEGF. IMM2510 is differentiated from other PD(L)1xVEGF antibodies by its ability to bind multiple VEGF receptor ligands beyond VEGF-A, a smaller molecular weight allowing for potentially better tumor penetration, and enhanced antibody-dependent cellular cytotoxicity (ADCC) designed to improve tumor killing. IMM2510 has completed a dose-escalation clinical trial for advanced solid tumors and demonstrated multiple responses including patients with squamous non-small cell lung cancer (NSCLC) who previously failed PD-1 inhibitors.

IMM27M is a next-generation anti-CTLA-4 antibody with enhanced ADCC activity, which has been designed to promote intratumoral regulatory T cell depletion to enhance the efficacy and reduce the toxicity associated with first-generation anti-CTLA-4 antibodies. IMM27M has completed a dose-escalation clinical trial demonstrating anti-tumor activity in patients with advanced solid tumors and has entered combination studies with IMM2510 in China in July 2024.

Terms of License and Collaboration Agreement
Under the terms of the agreement, a wholly owned subsidiary of Instil will receive global development and commercialization rights for IMM2510 and IMM27M outside of Greater China, while ImmuneOnco will retain development and commercialization rights in Greater China including Taiwan, Macau, and Hong Kong. ImmuneOnco will receive an upfront payment and potential near-term payments of up to $50 million as well as potential additional development, regulatory, and commercial milestones exceeding $2 billion plus single digit to low double-digit percentage royalties on global ex-China sales.

On August 1, 2024 Moderna, Inc. (NASDAQ:MRNA) reported financial results and provided business updates for the second quarter of 2024 (Press release, Moderna Therapeutics, AUG 1, 2024, View Source/news/news-details/2024/Moderna-Reports-Second-Quarter-2024-Financial-Results-and-Provides-Business-Updates/default.aspx" target="_blank" title="View Source/news/news-details/2024/Moderna-Reports-Second-Quarter-2024-Financial-Results-and-Provides-Business-Updates/default.aspx" rel="nofollow">View Source [SID1234645279]).

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"During the second quarter, we marked the approval of our second mRNA product and significantly lowered our operating costs. We remain focused on execution for the 2024-25 COVID season and the launch of our RSV vaccine in the U.S.," said Stéphane Bancel, Chief Executive Officer of Moderna. "With continued positive Phase 3 data across our respiratory portfolio, we are using our mRNA platform to address significant unmet medical needs and advance public health. Our platform is poised to reach millions globally this year and we are excited by its continued positive impact on patients."

Recent progress includes:

Commercial Updates

COVID-19: The Company reported $184 million in Spikevax (COVID-19 vaccine) sales in the second quarter of 2024, which includes $162 million of U.S. sales and $22 million of international sales.

Contracting is mostly complete in a highly competitive COVID market. Moderna is ready for the upcoming vaccination season with ample and timely supply. In the U.S., the majority of contracts are finalized and Moderna’s focus is on working with public health officials, health care providers and pharmacies to drive vaccination coverage rates to reduce the substantial burden of COVID-19. In the European Union (EU), Moderna is negotiating a tender framework agreement to provide market access; however, based on recent discussions, the Company now expects very low EU sales in 2024. In the Rest of World, the Company has multiple signed contracts in place, with some potential revenue deferrals into 2025.

RSV: Following U.S. Food and Drug Administration (FDA) approval in May and the Advisory Committee on Immunization Practices (ACIP) recommendation in June, Moderna’s RSV vaccine, mRESVIA, has launched in the U.S. and deliveries are underway as of July 2024. The Company is targeting the pharmacy segment in the U.S. and its commercial focus is on reaching vaccinators in a highly competitive market. Additionally, the European Medicines Agency (EMA) has adopted a positive opinion recommending marketing authorization in the EU for mRESVIA.

Second Quarter 2024 Financial Results

Revenue: Total revenue for the second quarter of 2024 was $241 million, compared to $344 million in the same period in 2023. This decline was primarily attributable to decreased sales of the Company’s COVID-19 vaccine. Net product sales for the second quarter of 2024 were $184 million, reflecting a 37% decrease compared to the same period in 2023. This reduction aligns with the expected shift to a seasonal COVID-19 vaccine market, with higher demand anticipated in the fall and winter. In the prior year period, product sales were largely recognized from doses delivered and deferred from 2022.

Cost of Sales: Cost of sales for the second quarter of 2024 was $115 million, which included third-party royalties of $10 million, unutilized manufacturing capacity and wind-down costs of $55 million, and inventory write-downs of $14 million. Compared to the same period in 2023, the cost of sales decreased by $616 million, or 84%. Cost of sales as a percentage of net product sales was 62% for the second quarter of 2024, down from 249% in the second quarter of 2023. The reduction in cost of sales was primarily due to a lower sales volume and decreased unutilized manufacturing capacity, inventory write-downs, and losses on firm purchase commitments and related cancellation fees. The reduction in cost of sales as a percentage of net product sales in 2024 was mainly driven by lower costs, partially offset by the reduced sales volume, reflecting a decline in product demand and increased product seasonality.

Research and Development Expenses: Research and development expenses for the second quarter of 2024 increased by 6% to $1.2 billion, compared to the second quarter in 2023. This increase was mainly due to higher personnel-related costs, driven by an increased headcount to support ongoing research and development efforts. Research and development expenses for the quarter also include the purchase of a priority review voucher. The increase was partly offset by a decrease in clinical development and manufacturing expenses, resulting from lower spending on clinical trials for the Company’s COVID-19 and seasonal flu programs, in line with its planned trial schedules.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for the second quarter of 2024 decreased by 19% to $268 million, compared to the second quarter in 2023. This decrease is a result of cost discipline and the efficiencies resulting from investments the Company made in foundational capabilities over the last year, which allowed for a significant reduction of purchased services and the use of external consultants. The Company continues to invest in digital and commercial capabilities and has intensified its focus on building and utilizing AI technologies to further streamline operations and enhance productivity.

Income Taxes: The Company did not recognize an income tax expense for the second quarter of 2024, in contrast to an income tax benefit of $369 million in the same period last year. The shift primarily resulted from the continued application of a valuation allowance on the majority of the Company’s deferred tax assets, first established in the third quarter of 2023. The Company only maintained a valuation allowance on certain state deferred tax assets prior to the third quarter of 2023.

Net Loss: Net loss was $(1.3) billion for the second quarter of 2024, compared to $(1.4) billion for the second quarter of 2023.

Net Loss Per Share: Net loss per share was $(3.33) for the second quarter of 2024, compared to $(3.62) for the second quarter of 2023.

Cash Position: Cash, cash equivalents and investments as of June 30, 2024, were $10.8 billion, compared to $12.2 billion as of March 31, 2024. The decrease in the cash position during the second quarter of 2024 was largely attributable to research and development expenses and operating activities.

2024 Financial Framework

Net Sales: The Company revises its 2024 expected net product sales to $3.0 to $3.5 billion from its respiratory franchise. For the second half of the year, it expects a sales split of 40-50% in the third quarter with the balance in the fourth quarter of 2024, subject to the timing of regulatory approvals. The update in product sales is driven by three primary factors: very low EU sales in 2024, potential revenue deferrals for certain international sales into 2025, and an increasingly competitive environment for respiratory vaccines in the U.S.

Cost of Sales: Cost of sales is expected to be in the range of 40-50% of product sales for the year.

Research and Development Expenses: Full-year 2024 research and development expenses are anticipated to be approximately $4.5 billion.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for 2024 are projected to be approximately $1.3 billion.

Income Taxes: The Company continues to expect its full-year tax expense to be negligible.

Capital Expenditures: Capital expenditures for 2024 are expected to be approximately $0.9 billion.

Cash and Investments: Year-end cash and investments for 2024 are projected to be approximately $9 billion.

Recent Progress and Upcoming Late-Stage Pipeline Milestones

Respiratory vaccines:

Respiratory syncytial virus (RSV) vaccine: After Moderna received U.S. FDA approval for its RSV vaccine (mRNA-1345), ACIP issued a recommendation for all unvaccinated people 75 years of age and older and unvaccinated people ages 60-74 who are at increased risk for RSV to receive the vaccine for the prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) and acute respiratory disease (ARD). Additionally, the EMA adopted a positive opinion recommending marketing authorization in the EU for mRESVIA. The Company is awaiting regulatory approvals in additional countries.

Seasonal flu vaccine: Moderna’s seasonal flu vaccine (mRNA-1010) demonstrated consistently acceptable safety and tolerability across three Phase 3 trials. The Company is engaging with regulators and intends to file in 2024.

Next-generation COVID-19 vaccine: A recent announcement of positive interim results from the NEXTCove Phase 3 trial showed that Moderna’s next-generation COVID-19 vaccine (mRNA-1283) has met its primary efficacy endpoint, demonstrating non-inferior vaccine efficacy against COVID-19 compared to Spikevax (mRNA-1273) in participants 12 years of age and older. Higher efficacy was also observed compared to Spikevax in adults 18 years of age and older. The Company is engaging with regulators and intends to file in 2024.

Seasonal flu + COVID vaccine: Moderna recently announced the Phase 3 trial of its combination vaccine against seasonal flu and COVID-19 (mRNA-1083) has met its primary endpoints, eliciting higher immune responses against influenza virus and SARS-CoV-2 than licensed flu and COVID vaccines in adults 50 years and older, including an enhanced influenza vaccine in adults 65 years and older. The Company is engaging with regulators on next steps.

Oncology therapeutics:

Individualized Neoantigen Therapy (INT): Moderna and Merck announced additional 3-year data for mRNA-4157 in combination with KEYTRUDA (pembrolizumab), demonstrating sustained improvement in recurrence-free survival and distant metastasis-free survival versus KEYTRUDA in patients with high-risk stage III/IV melanoma following complete resection. At a median planned follow-up of the Phase 2b study at 34.9 months, mRNA-4157 in combination with KEYTRUDA reduced the risk of recurrence or death by 49% and the risk of distant metastasis or death by 62% compared to KEYTRUDA alone in these patients. The 2.5-year recurrence-free survival rate of mRNA-4157 in combination with KEYTRUDA was 74.8% as compared to 55.6% for KEYTRUDA alone, with the benefit observed across exploratory subgroups.

Rare disease therapeutics:

Methylmalonic acidemia (MMA) therapeutic: Moderna’s investigational therapeutic for MMA (mRNA-3705) has been selected by the U.S. FDA for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program. mRNA-3705 was chosen by the Center for Biologics Evaluation and Research (CBER) as one of four investigational medicines for accelerated development to address unmet medical needs for rare diseases. The Company expects to advance its MMA program into a registrational study in 2024.

Moderna Corporate Updates

Announced that David M. Rubenstein, Co-Founder and Co-Chairman of The Carlyle Group, will join Moderna’s Board of Directors, effective August 5, 2024, when directors Robert Langer and Stephen Berenson will retire from the Board.

Entered into an agreement with Mitsubishi Tanabe Pharma Corporation to promote Moderna’s mRNA respiratory vaccine portfolio in Japan.

Received a project award of $176 million through BARDA’s Rapid Response Partnership Vehicle Consortium to accelerate the development of an mRNA-based pandemic influenza vaccine.

Published third annual ESG Report, Impacting Human Health, on June 25, 2024.

Company Accolades

Moderna was named to the Boston Business Journal’s annual list of the Most Charitable Companies in Massachusetts (second consecutive year)

Moderna was recognized as a top-scoring company on Disability:IN’s Disability Equality Index and a Best Place to Work for Disability Inclusion (third consecutive year)

Moderna was recognized as a Great Place to Work in the U.S. by Great Place To Work (second consecutive year)

Key 2024 Investor and Analyst Event Dates

R&D Day: September 12

Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on August 1, 2024. 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/BI2ef72dcc8f6e4477bf2f61ab92054abb

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.