On February 24, 2022 Genmab A/S (Nasdaq: GMAB) and Seagen Inc. (Nasdaq: SGEN) reported that it will present preliminary data from the innovaTV 207 global, open-label, multicenter phase 2 trial of tisotumab vedotin (TIVDAK) as a monotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN) who experienced disease progression on or after a first-line platinum-containing regimen and a checkpoint inhibitor (Press release, Genmab, FEB 24, 2022, View Source [SID1234608965]). Early results showed tisotumab vedotin demonstrated a manageable safety profile and promising preliminary antitumor activity in this patient population with the primary endpoint of confirmed objective response rate (ORR) per investigator, achieved by 16 percent of patients (95% CI: 5.5 to 33.7). Findings will be presented as part of a plenary session at the American Society for Radiation Oncology (ASTRO) 2022 Multidisciplinary Head and Neck Cancers Symposium on February 25.

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"There is a significant unmet need for additional treatment options for patients diagnosed with squamous cell carcinoma of the head and neck that has progressed despite the use of chemotherapy," said David S. Hong, M.D., deputy chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and lead investigator of the innovaTV 207 clinical trial. "These preliminary data provide important insight into the safety of tisotumab vedotin in this tumor type and demonstrate the value of exploring this potential use further in the innovaTV 207 trial."

The SCCHN cohort of the innovaTV 207 trial enrolled 31 patients with a median age of 65 (range 47 to 78) years whose disease progressed on or after systemic therapy. Patients received 2 milligrams (mg)/kilogram (kg) tisotumab vedotin (maximum dose: 200 mg per infusion) intravenously on day one of each 21-day cycle. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS) per investigator and overall survival (OS). DCR per investigator was 58.1 percent (95% CI: 39.1 to 75.5), median PFS was 4.2 months (95% CI: 2.7 to 4.8), median follow-up was 10.0 months (95% CI: 8.5 to 13.1) and median OS was 9.4 months (95% CI: 8.1 to 11.8). Adverse events were consistent with the known safety profile of tisotumab vedotin: twenty-one (67.7%) patients developed Grade ≥3 treatment-emergent adverse events (TEAEs); most commonly (≥10% of patients) anemia (16.1%), pneumonia (12.9%), and dyspnea (12.9%). Incidence of treatment-emergent serious adverse events (SAEs) was 51.6%, and incidence of treatment-related SAEs was 6.5% (grade 3 hemoptysis [n=1] and grade 3 post-procedural hemorrhage [n=1]).

See TIVDAK U.S. Important Safety Information, including Boxed Warning, below.

"We recognize the high medical need for additional treatment options for patients with head and neck cancers," said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. "These initial data results are encouraging and underscore the importance of our ongoing clinical trial program that will assess the potential utility of tisotumab vedotin in various cancers."

For more information about the ongoing phase 2 innovaTV 207 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov (Identifier: NCT03485209).

"The presentation of these preliminary data represents another step forward in our work to advance the tisotumab vedotin development program," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "In partnership with Genmab, we will continue to recruit additional patients for trials to further investigate tisotumab vedotin in patients with squamous cell carcinoma of the head and neck, including its potential use as a combination therapy."

About the innovaTV 207 Trial
The phase 2 innovaTV 207 clinical trial evaluates the activity, safety, and tolerability of tisotumab vedotin in selected solid tumors with high tissue factor (TF) expression. The trial is a global, multicenter, open label basket trial which will enroll an estimated 532 adult patients with relapsed, locally-advanced or metastatic disease in separate tumor-specific cohorts. The primary endpoint of the trial is confirmed ORR per investigator, defined as the proportion of patients who achieve a confirmed complete or partial response. Key secondary endpoints include confirmed and unconfirmed ORR, DCR, duration of response, PFS, OS, safety and tolerability. For more information about the phase 2 innovaTV 207 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov (Identifier: NCT03485209).

About Tisotumab Vedotin
Tisotumab vedotin-tftv (TIVDAK) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

In September 2021, the U.S. Food and Drug Administration granted accelerated approval for tisotumab vedotin (TIVDAK) in patients with previously treated recurrent or metastatic cervical cancer. TIVDAK is the first and only approved ADC for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Indication
TIVDAK is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

BOXED WARNING: OCULAR TOXICITY
TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during, and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

Warnings and Precautions
Ocular Adverse Reactions occurred in 60% of patients with cervical cancer treated with TIVDAK across clinical trials. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8 % of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose. In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

Peripheral Neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barre syndrome. Monitor patients for signs and symptoms of neuropathy. For new or worsening PN, withhold, dose reduce, or permanently discontinue TIVDAK based on the severity of PN.

Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients. Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

Pneumonitis: Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

Monitor patients for pulmonary symptoms of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

Embryo-Fetal Toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

Adverse Reactions
In the innovaTV 204 clinical trial (n=101), serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

Drug interactions

Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

Use in Specific Populations

Moderate or Severe Hepatic Impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

On February 24, 2022 Galapagos NV (Euronext & NASDAQ: GLPG) reported that financial results 2021, reviews key events for the company, and provides outlook for 2022 (Press release, Galapagos, FEB 24, 2022, View Source [SID1234608964]).

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"2021 was a year of reflection, resulting in refocused R&D activities and resized spend, as well as commercial roll-out, with a major effort to launch Jyseleca throughout Europe," said Onno van de Stolpe, CEO of Galapagos. "We made excellent progress with Jyseleca and successfully completed the process of becoming Marketing Authorization Holder (MAH) in Europe for our first medicine. Improving patients’ lives is at the core of what we do, and completing our transition to a fully integrated, independent European biopharma is a major achievement to make that mission a reality for patients suffering from chronic debilitating conditions.

We received approval by the European Commission (EC), and most recently by the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain, for a second indication for Jyseleca for patients suffering from UC, and we continue to roll out Jyseleca in RA and UC throughout Europe. Furthermore, following the completion of patient enrollment in the DIVERSITY Phase 3 program with filgotinib in CD, we anticipate topline results in the first half of 2023.

Also for filgotinib, we were pleased to report on the primary endpoint with the MANTA and MANTA-RAy studies investigating the effect on semen parameters, indicating that 8.3% patients on placebo and 6.7% patients on filgotinib had a 50% or more decline in sperm concentration at week 13.

In 2021, we also made important progress across our broader inflammation pipeline, most notably with our TYK2 and SIKi programs. We observed clinical activity with our TYK2 inhibitor GLPG3667 in a Phase 1b study in Pso, and we are currently finalizing a Phase 1 dose escalation study in healthy volunteers. We reported results from the first patient studies of our SIKi program with SIK2/3 inhibitor GLPG3970. The biological activity observed in the studies in Pso and UC highlights the pioneering role we are playing to unravel the role of SIKi in inflammation, and support further development of our SIKi portfolio. We are currently working on a set of follow-up SIKi compounds with improved pharmacology and selectivity profiles, and plan to select a preclinical candidate to move into a healthy volunteer study this year.

Beyond inflammation, we discontinued further development of ziritaxestat (GLPG1690) in IPF due to the unfavorable risk/benefit profile observed by an Independent Data Monitoring Committee (IDMC) in the Phase 3 trials. This not only was a major setback for Galapagos but most importantly for patients suffering from this debilitating disease for which current treatment options remain limited.

Finally, we completed the patient recruitment in our MANGROVE Phase 2 trial with our novel CFTR2 inhibitor GLPG2737 in patients with ADPKD3, with results expected in the first half of 2023.

I am very proud of our committed teams for working tirelessly to bring novel mode of action medicines to patients, and now that my tenure at the helm of this company is drawing to an end, I could not be more honored to hand over the baton to Paul. As a co-founder and board member in the early years, Paul has a keen understanding of our roots as well as who we are today. I strongly believe that Paul’s strategic and inspirational leadership, along with his deep knowledge of both the industry and Galapagos, make him the right next CEO to deliver tremendous value to all stakeholders."

Bart Filius, President, COO and CFO of Galapagos, added: "We ended 2021 with a very strong balance sheet, providing us with the foundations for future growth. One year after receiving approval for Jyseleca in RA in Europe and Great Britain, we secured reimbursement in 14 countries, covering the major markets of Germany, France, Spain, Italy, and Great Britain. We reported €14.8 million of Jyseleca sales in Europe out of a total in-market performance of €25.7 million.

Following a strategic operational review in March 2021, we implemented a cost savings program of €150 million on a full year basis, which will take full effect in the course of 2022. Our operational cash burni in 2021 was €564.8 million, within our reduced guidance. For 2022 we anticipate a further significant reduction of our cash burn and expect to land between €450 and €490 million. This includes sales for Jyseleca that we anticipate between €65 and €75 million."

Details of the financial results
After the sale of our fee-for-service business (Fidelta) to Selvita on 4 January 2021, we only have one remaining reporting segment. The results of Fidelta, including the impact of the 2021 sale, are presented as "Net profit from discontinued operations" in our consolidated income statements for the years 2021 and 2020.

Revenues from continuing operations
Our net revenues from continuing operations in 2021 amounted to €484.8 million compared to €478.1 million in 2020.

We reported net sales of Jyseleca in 2021 amounting to €14.8 million, which reflects the sales booked by Galapagos after the country-by-country transition from Gilead.

Collaboration revenues amounted to €470.1 million in 2021, compared to €478.1 million last year. The revenue recognition linked to the upfront consideration and milestone payments in the scope of the collaboration with Gilead for filgotinib, amounted to €235.7 million in 2021 (€228.1 million in 2020). The revenue recognition related to the exclusive access rights for Gilead to our drug discovery platform amounted to €230.6 million in 2021 (€229.6 million last year). Additionally we have recognized royalty income from Gilead for Jyseleca for €3.8 million in 2021 (compared to €16.2 million in 2020, which was mainly from income related to upfront payments from a distribution agreement for the commercial launch of filgotinib in Japan).

Our deferred income balance at 31 December 2021 includes €1.8 billion allocated to our drug discovery platform that is recognized linearly over 10 years, and €0.6 billion allocated to the filgotinib development that is recognized over time until the end of the development period.

Results from continuing operations

We realized a net loss from continuing operations of €125.4 million in 2021, compared to a net loss of €311.0 million in 2020.

We reported an operating loss amounting to €165.6 million in 2021, compared to an operating loss of €178.6 million in 2020.

Cost of sales related to Jyseleca net sales in 2021 amounted to €1.6 million.

Our R&D expenditure in 2021 amounted to €491.7 million, compared to €523.7 million in 2020. This decrease was primarily due to the winding down of the programs with ziritaxestat (IPF), MOR106 (atopic dermatitis), and GLPG1972 (OA), and reduced spend on our other programs. This was partly offset by cost increases for our filgotinib and Toledo (SIKi) programs, on a yearly comparison basis.

Our S&M and G&A expenses were respectively €70.0 million and €140.9 million in 2021, compared to respectively €66.5 million and €118.8 million in 2020. This increase was primarily due to an increase in personnel costs resulting from an increase in headcount and other operating expenses mainly driven by the commercial launch of filgotinib in Europe. This increase was partly offset by higher cost recharges from us to Gilead in the scope of our commercial cost sharing for filgotinib in Europe.

Other operating income (€53.7 million in 2021 vs €52.2 million last year) slightly increased, mainly driven by higher grant income.

We reported a non-cash fair value gain from the re-measurement of initial warrant B issued to Gilead, amounting to €3.0 million in 2021 (€3.0 million in 2020), mainly due to the decreased implied volatility of the Galapagos share price and its evolution between 31 December 2020 and 31 December 2021.

Net other financial income in 2021 amounted to €39.6 million, compared to net other financial loss of €134.2 million in 2020. Net other financial income in 2021 was primarily attributable to €57.2 million of currency exchange gains on our cash and cash equivalents in U.S. dollars, and to €8.8 million of net interest expenses. The other financial expenses also contained the effect of discounting our long term deferred income of €9.3 million.

Results from discontinued operations
The net profit from discontinued operations in 2021 consisted of the gain on the sale of Fidelta, our fee-for-services business, for €22.2 million.

Group net results
We reported a group net loss in 2021 of €103.2 million, compared to a group net loss of €305.4 million in 2020.

Cash position
Current financial investments and cash and cash equivalents totaled €4,703.2 million on 31 December 2021, as compared to €5,169.3 million on 31 December 2020 (including the cash and cash equivalents included in the assets as classified as held for sale).

Total net decrease in cash and cash equivalents and current financial investments amounted to €466.1 million in 2021, compared to a net decrease of €611.5 million in 2020. This net decrease was composed of (i) €564.8 million of operational cash burn, offset by (ii) €6.8 million positive changes in (fair) value of current financial investments and €59.9 million of mainly positive exchange rate differences, (iii) €3.3 million of cash proceeds from capital and share premium increase from exercise of subscription rights in 2021, and (iv) €28.7 million cash in from disposal of subsidiaries.

Our balance sheet on 31 December 2021 included R&D incentives receivables from the French government (Crédit d’Impôt Rechercheiv) and from the Belgian government, for a total of €144.0 million.

Outlook 2022

Early in 2022, we announced the appointment of Dr. Paul Stoffels as successor to our co-founder and current CEO Onno van de Stolpe, effective 1 April 2022. Paul is widely recognized as an inspirational industry leader with exceptional R&D and global executive experience, with an outstanding track record of accelerated product development in biotech and pharma through insightful acquisitions and strategic partnerships.

In 2022, we expect reimbursement decisions in most key European markets for Jyseleca in UC. In Japan, collaboration partner Gilead expects a decision on the potential approval for Jyseleca in UC in the first half of 2022, which potentially could add a second indication for Jyseleca in this market.

Early this year, the EMA announced that its Pharmacovigilance Risk Assessment Committee (PRAC) started an Article 20 specific pharmacovigilance procedure to investigate the safety data for all JAK inhibitors following recent results from the ORAL Surveillance study with tofacitinib4 as well as the data from an observational study with baricitinib5. Following initiation of this procedure, all JAKi MAHs will be invited to submit evidence and we will continue to work with the EMA. The European Commission has asked the EMA to give its opinion by 30 September 2022.

Within our broader inflammation portfolio, we expect the read out from a Phase 1b trial with JAK1 inhibitor GLPG0555 in osteoarthritis and from multiple Phase 1 trials in healthy volunteers. We aim to progress our TYK2 inhibitor GLPG3667 into a Phase 2 program, following the dose escalation Phase 1 study currently being finalized, also taking into account the current regulatory and competitive landscape for TYK2 as a class. We aim to advance selected compounds with optimized pharmacology and selectivity from our SIKi portfolio into the clinic. Within our fibrosis portfolio, we anticipate starting a Phase 2 trial with chitinase inhibitor GLPG4716 in IPF.

For 2022 we anticipate a further significant reduction of our cash burn and expect to land between €450 and €490 million. This includes sales for Jyseleca that we anticipate between €65 and €75 million.

We believe our strong cash balance affords us the opportunity to develop our pipeline through internal as well as externally sourced assets. We expect our scientific expertise, strong leadership, and growing commercial Jyseleca franchise to propel us forward as we rebuild a differentiated pipeline of novel mode of action drug candidates to help patients in need of new treatment options.

Annual report 2021

Galapagos is currently finalizing its financial statements for the year ended 31 December 2021. Our independent auditor has confirmed that its audit procedures, which are substantially completed, have not revealed any material corrections required to be made to the financial information included in this press release. Should any material changes arise during the audit finalization, an additional press release will be issued. Galapagos expects to be able to publish its fully audited annual report for the full year 2021 on or around 24 March 2022.

Conference call and webcast presentation

Galapagos will conduct a conference call open to the public tomorrow, 25 February 2022, at 14:00 CET / 8 AM ET, which will also be webcasted. To participate in the conference call, please call one of the following numbers ten minutes prior to commencement:

CODE: 5438549

A question and answer session will follow the presentation of the results. Go to www.glpg.com to access the live audio webcast. The archived webcast will also be available for replay shortly after the close of the call.

Financial calendar

24 March 2022 Publication Annual Report 2021 and 20-F 2021
26 April 2022 Annual Shareholders’ meeting
5 May 2022 First quarter 2022 results (webcast 6 May 2022)
4 August 2022 Half Year 2022 results (webcast 5 August 2022)
3 November 2022 Third quarter 2022 results (webcast 4 November 2022)
23 February 2023 Full year 2022 results (webcast 24 February 2023)

On February 24, 2022 MilliporeSigma, the U.S. and Canada Life Science business sector of Merck KGaA, Darmstadt, Germany, a leading science and technology company, reported the closing of the transaction to acquire Exelead, following regulatory clearances and the fulfillment of other customary closing conditions, for approximately USD 780 million in cash (Press release, MilliporeSigma, FEB 24, 2022, View Source [SID1234608963]). The business combination is expected to enable the Life Science business to provide its customers with comprehensive end-to-end contract development and manufacturing organization (CDMO) services across the mRNA value chain. The Life Science business plans to further invest over € 500 million to scale up Exelead’s technology over the next ten years.

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MilliporeSigma Announces Close of Exelead Acquisition

"With the addition of Exelead’s leading capabilities and highly experienced team, our Life Science business achieves an important milestone in becoming one of the leading CDMO players in mRNA vaccines and therapeutics, offering an integrated CDMO across the mRNA value chain from pre-clinical to commercial," said Matthias Heinzel, Member of the Executive Board of Merck KGaA, Darmstadt, Germany, and CEO Life Science. "mRNA holds much promise as a treatment well beyond Covid-19 and we will further invest in this technology to help realize its potential."

Exelead, a biopharmaceutical CDMO, specializes in PEGylated products and complex injectable formulations, including Lipid Nanoparticle (LNP) based drug delivery technology, which is key in mRNA vaccines and therapeutics for use in Covid-19 and many other indications. The company has experience in all development phases from pre-clinical development to commercial contract manufacturing for LNP formulations, including fill and finish. Exelead will complement the Life Science business sector’s more than 20 years’ experience in producing lipids as well as its mRNA manufacturing capabilities acquired through AmpTec in 2020. This integrated offering will accelerate the Life Science business sector’s ability to bring life-enhancing vaccines and treatments to patients faster by simplifying supply chain complexity and enhancing speed to market through its end-to-end portfolio.

Over the past two years, the Life Science business sector has made significant investments to advance traditional and novel modalities (mAb, ADC, HP-API, viral vector, and mRNA) through acquisitions and expansions. The acquisition of Exelead is another milestone to accelerate innovation in the company’s Process Solutions and Life Science Services businesses, one of the company’s three growth engines ("Big 3"), through targeted smaller to medium-sized acquisitions with high impact.

Follow MilliporeSigma on Twitter @MilliporeSigma, on Facebook @MilliporeSigma and on LinkedIn.

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On February 24, 2022 Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, reported financial results and provided business updates for the fourth quarter of fiscal year 2021 (Press release, Moderna Therapeutics, FEB 24, 2022, View Source [SID1234608962]).

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"Spikevax is now approved in more than 70 countries around the world protecting hundreds of millions of people and real-world evidence from multiple independent studies has confirmed its strong effectiveness," said Stéphane Bancel, Chief Executive Officer of Moderna. "In 2021, we delivered 807 million doses with approximately 25% of those doses going to low- and middle-income countries, and we will continue to scale in 2022 to help end the COVID-19 pandemic. Moderna has experienced exponential growth and we have more than doubled the size of our team over the last year with a global team of 3,000. We also have announced plans to scale to 21 commercial subsidiaries across the world, including four new locations in Asia and six new locations in Europe. We continue to expand and advance our industry-leading mRNA pipeline with 44 programs in development. We look forward to clinical readouts from our therapeutics development candidates later in 2022 in rare genetic diseases and oncology. We are entering 2022 with a remarkable team and strategic priorities to continue advancing mRNA vaccines and therapeutics to impact human health."

Updates and recent progress include:

COVID-19 Vaccine Development

Therapeutic Goods Administration (TGA) in Australia has granted provisional registration for the use of Spikevax in a 50 µg dose, two-dose series, for active immunization to prevent COVID-19 caused by SARS-CoV-2 in children aged 6-11 years
U.S. Food and Drug Administration (U.S. FDA) approved the Biologics License Application (BLA) for Spikevax (COVID-19 Vaccine, mRNA-1273) to prevent COVID-19 in individuals in the U.S. 18 years of age and older; Spikevax approved or authorized in more than 70 countries
Pivotal studies are underway for Omicron-specific booster candidate (mRNA-1273.529)
Moderna announces bivalent booster candidate (mRNA-1273.214) combining mRNA-1273.529 and the Moderna COVID-19 vaccine (mRNA-1273)
Respiratory Vaccines

Pivotal Phase 3 study of respiratory syncytial virus (RSV) vaccine candidate (mRNA-1345) has begun
Seasonal flu vaccine candidate (mRNA-1010) successfully boosted hemagglutination inhibition (HAI) assay geometric mean titers against all strains 29 days after vaccination at all doses tested in younger and older adults in Phase 1 study and no significant safety concerns were observed through day 29; Phase 2 study of mRNA-1010 is fully enrolled; preparation for the Phase 3 study is underway
Latent Vaccines

Announcing new Herpes simplex virus (HSV) therapeutic vaccine candidate (mRNA-1608), a vaccine candidate to prevent incidence of herpes lesions due to HSV-2
Announcing a new Varicella-zoster virus (VZV) vaccine candidate (mRNA-1468)designed to reduce the rate of herpes zoster (shingles)
Enrollment in Phase 1 study of Epstein-Barr virus (EBV) vaccine candidate (mRNA-1189) is ongoing
Enrollment in Phase 3 pivotal registration study of cytomegalovirus (CMV) vaccine candidate (mRNA-1647) is ongoing
Cancer Vaccines

Announcing new checkpoint cancer vaccine (mRNA-4359) to expand naturally occurring T cells that counteract the impact of immune checkpoints Indoleamine 2,3 -dioxygenase (IDO) and programmed death-ligand 1 (PD-L1)
Moderna has regained all rights to mutant KRAS vaccine (mRNA-5671) from Merck; Moderna is evaluating next steps for the program
Therapeutics

Enrollment of the first cohort in Phase 1/2 Paramount study of Propionic Acidemia candidate (mRNA-3927) is complete; enrollment in additional dose level cohorts is continuing
Enrollment of the first cohort in Phase 1/2 Landmark study of Methylmalonic Acidemia candidate (mRNA-3705) is complete; enrollment for additional cohorts expected to begin soon
Moderna now has 44 programs in development across 41 development candidates 1, of which 25 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 100 peer reviewed manuscripts.

Summary of Program Highlights by Modality 2

Core Modalities

Prophylactic Vaccines: Moderna is developing vaccines against viral diseases where there is an unmet medical need, including vaccines against respiratory infections and vaccines against latent viruses.

Vaccines against acute respiratory infections

COVID-19 vaccine development

Moderna COVID-19 Vaccine (mRNA-1273 3 , Spikevax ): The U.S. Food and Drug Administration (FDA) has approved the Biologics License Application (BLA) for SPIKEVAX (COVID-19 Vaccine, mRNA) to prevent COVID-19 in individuals 18 years of age and older. 807 million doses of Moderna’s COVID-19 vaccine shipped globally in 2021; approximately 25% of those doses shipped to low- and middle-income countries.
Booster Dose of mRNA-1273: The U.S. FDA, European Medicines Agency (EMA), Swissmedic and other health agencies around the world have authorized a booster dose of the Moderna COVID-19 vaccine at the 50 µg dose level for adults ages 18 years and older.
Omicron-specific booster candidate (mRNA-1273.529): Moderna’s Omicron-specific booster candidate is being studied to evaluate the immunogenicity, safety, and reactogenicity of mRNA-1273.529 as a single booster dose in adults aged 18 years and older in two cohorts: individuals who previously received the two-dose primary series of mRNA-1273 with the second dose being at least six months ago (cohort 1), or who have received the two-dose primary series and a 50 µg booster dose of mRNA-1273 with the booster dose being at least three months ago (cohort 2). Participants in both cohorts will receive a single booster dose of mRNA-1273.529.
Bivalent booster candidate (mRNA-1273.214): Today, Moderna is announcing a new bivalent candidate that combines Moderna’s Omicron-specific candidate and mRNA-1273.
Moderna COVID-19 Vaccine for adolescents and children: Moderna has received regulatory authorizations for the use of the 100 µg Moderna COVID-19 vaccine primary series for adolescents 12 to 17 years of age in the European Union, UK, Australia, Canada, Switzerland and other countries. At this point, the U.S. FDA has not concluded on the benefit-risk profile of the 100 µg primary series for adolescents 12 to 17 years of age. Moderna made the decision to evaluate the potential of a 50 µg two-dose primary series to meet regulatory guidance for immunogenicity in adolescents and children ages 6 to 11 years. The Company is also evaluating a heterologous booster dose in adolescents after a two-dose primary series of 50 µg, 100 µg, or BNT162b2 and is preparing to submit data to regulators. The Company received authorization for a two-dose 50 µg primary series of the Moderna COVID-19 vaccine in children ages 6 to 11 in Australia and has submitted additional applications for the 6 to 11 age group. In the U.S., Moderna is also studying a two-dose 25 µg primary series for the 6 to 11 age group. In the 6 months to 5 years age group, Moderna is studying a two-dose 25 µg primary series, and expects data in the first quarter of 2022. The Company plans to submit these data to regulators. Additionally, the Company is evaluating lower doses in the U.S. for this age group.
Next-generation vaccine candidate against COVID-19 (mRNA-1283): The Phase 1 study of mRNA-1283 is fully enrolled and ongoing. The Phase 2 study of a booster dose of mRNA-1283 is ongoing.mRNA-1283 is a next-generation vaccine candidate against COVID-19 that encodes for the portions of the SARS-CoV-2 spike protein critical for neutralization, specifically the Receptor Binding Domain (RBD) and N-terminal Domain (NTD). The encoded mRNA-1283 antigen is shorter than mRNA-1273 and is being developed as a potential refrigerator-stable mRNA vaccine that will facilitate easier distribution and administration by healthcare providers.
Additional vaccines against respiratory infections

Seasonal influenza vaccine (mRNA-1010): On December 10, 2021, Moderna announced positive interim data from the Phase 1 study of mRNA-1010. mRNA-1010 successfully boosted hemagglutination inhibition (HAI) assay geometric mean titers against all strains 29 days after vaccination at all doses tested in both younger and older adults and no significant safety concerns were observed through day 29. The Phase 2 study of mRNA-1010 is fully enrolled and preparation for the Phase 3 study is underway. mRNA-1010 encodes for hemagglutinin (HA) glycoproteins of four flu strains and targets lineages recommended by the World Health Organization (WHO) for the prevention of influenza, including seasonal influenza A H1N1, H3N2 and influenza B Yamagata and Victoria.
Seasonal Influenza vaccines with expanded coverage (mRNA-1011 and mRNA-1012) and broader immunologic coverage (mRNA-1020 and mRNA-1030): On December 10, 2021, Moderna announced two development candidates which the Company believes may expand coverage against seasonal influenza strains. mRNA-1011 will have one additional hemagglutinin (HA) antigen and mRNA-1012 will have two additional HA antigens. Moderna is also developing two next-generation flu candidates that incorporate neuraminidase antigens to potentially improve immunity by increasing immunologic breadth targeting more conserved antigens (mRNA-1020, mRNA-1030).
COVID-19 and flu combination vaccine (mRNA-1073): mRNA-1073 encodes for the COVID-19 spike protein and the Flu HA glycoproteins.
Respiratory syncytial virus (RSV) vaccine (mRNA-1345): The pivotal Phase 3 study of RSV in older adults (ages older than 60 years) is ongoing. This is a global study conducted in locations influenced by the epidemiology of RSV and the Company expects to enroll approximately 34,000 participants. The FDA has granted Fast Track designation for mRNA-1345 in adults older than 60 years of age. RSV is the leading cause of severe respiratory illness in young children and older adults (65+). The Phase 1 study of mRNA-1345 to evaluate the tolerability and reactogenicity of mRNA-1345 in younger adults, women of child-bearing potential, older adults and seropositive toddlers is ongoing. All four cohorts of younger adults (ages 18-49 years) and all four cohorts of older adults (ages 65-79 years) are fully enrolled.
Human metapneumovirus (hMPV) and parainfluenza type 3 (PIV3) vaccine (mRNA-1653): The Phase 1 study of mRNA-1653 in children 12-59 months of age is fully enrolled.
Pediatric RSV and hMPV combination vaccine (mRNA-1365): mRNA-1365 encodes for the RSV prefusion F glycoprotein and the hMPV F protein.
Vaccines against latent viruses

Cytomegalovirus (CMV) vaccine (mRNA-1647): The Phase 3 pivotal registration study of mRNA-1647, known as CMVictory, is ongoing. The study is evaluating the safety and efficacy of mRNA-1647 against primary CMV infection in women ages 16-40 years. The Company will seek to enroll up to 6,900 women of child-bearing age, at approximately 150 sites globally, beginning in the U.S. Moderna has set a goal of enrolling a diverse group of U.S. participants into the study, including approximately 42% of participants who are Persons of Color. The ClinicalTrials.gov identifier is NCT05085366. To learn more about eligibility, visit www.CMVictory.com.
Epstein-Barr virus (EBV) vaccine (mRNA-1189): The Phase 1 study of mRNA-1189 ongoing. EBV is spread through bodily fluids (e.g., saliva) and contracted primarily by young children and adolescents. It is a major cause of infectious mononucleosis (IM), and associated risks to other long-term medical conditions, including an increased risk of developing multiple sclerosis, certain lymphoproliferative disorders and cancers, and autoimmune diseases 4,5 . Similar to Moderna’s CMV vaccine (mRNA-1647), mRNA-1189 contains four mRNAs that encode EBV envelope glycoproteins (gH, gL, gp42, gp220). There is currently no approved vaccine for EBV or IM.
Epstein-Barr virus (EBV) therapeutic vaccine candidate (mRNA-1195): mRNA-1195 is being developed to prevent longer term sequelae of EBV infection, which are associated with loss of immune control of EBV latent infection, creating longer-term complications. mRNA-1195 is in pre-clinical development and encodes for additional antigens than mRNA-1189. The Company expects to initially test the vaccine in post-transplant lymphoproliferative disorder (PTLD) because 60-80% of PTLD cases are associated with EBV infection. The Company expects to also pursue other longer-term potential indications for this vaccine, including multiple sclerosis.
HIV vaccine (mRNA-1644 & mRNA-1574): The first participant has been dosed in the ongoing Phase 1 study of mRNA-1644, which is using iterative human testing to validate the approach and antigens and multiple novel antigens will be used for germline-targeting and immuno-focusing. mRNA-1644, a collaboration with the International AIDS Vaccine Initiative (IAVI) and the Bill & Melinda Gates Foundation, is a novel approach to HIV vaccine strategy in humans designed to elicit broadly neutralizing HIV-1 antibodies (bNAbs). A second approach, mRNA-1574, is being evaluated in collaboration with the National Institutes of Health (NIH) and includes multiple native-like trimer antigens.
Herpes simplex virus (HSV) therapeutic vaccine candidate (mRNA-1608): Moderna recently announced a new development candidate, mRNA-1608, a vaccine candidate against herpes. In the U.S., approximately 18.6 million adults ages 18 to 49 years are living with HSV-2. Moderna is developing mRNA-1608 to reduce the burden of HSV lesions.
Varicella-zoster virus (VZV) vaccine candidate (mRNA-1468): Moderna recently announced a new mRNA vaccine candidate (mRNA-1468) designed to express varicella-zoster virus (VZV) glycoprotein E (gE) to reduce the rate of herpes zoster (shingles). Herpes zoster occurs in one of three adults in their lifetime and incidence dramatically increases at approximately 50 years of age. Declining immunity in older adults decreases cell-mediated immunity against VZV, allowing reactivation of the virus from latently infected neurons, causing painful and itchy lesions. Serious herpes zoster complications include postherpetic neuralgia (10-13% of herpes zoster cases), bacterial coinfections, and cranial and peripheral palsies; 1-4% of herpes zoster cases are hospitalized for complications.
Public health vaccines

Zika virus vaccine (mRNA-1893): The Phase 2 study of mRNA-1893 is ongoing in the U.S. and Puerto Rico. mRNA-1893 is being developed in collaboration with BARDA.
Nipah virus (NiV) Vaccine (mRNA-1215): NiV is a zoonotic virus transmitted to humans from animals, contaminated food, or through direct human-to-human transmission and causes a range of illnesses including fatal encephalitis. Severe respiratory and neurologic complications of NiV have no treatment other than intensive supportive care. NiV has been identified as the cause of isolated outbreaks in India, Bangladesh, Malaysia, and Singapore since 2000 and is included on the WHO R&D Blueprint list of epidemic threats needing urgent R&D action. mRNA-1215 was co-developed by Moderna and the NIH’s Vaccine Research Center (VRC).
Systemic Secreted & Cell Surface Therapeutics: In this modality, mRNA is delivered systemically to create proteins that are either secreted or expressed on the cell surface.

IL-2 (mRNA-6231): mRNA-6231 is an mRNA encoding for a long-acting tolerizing IL-2. This autoimmune development candidate is designed to preferentially activate and expand the regulatory T cell population. The Phase 1 study of mRNA-6231 in healthy adult participants (between 18 and 50 years of age) is ongoing.
PD-L1 (mRNA-6981): mRNA-6981 is an mRNA encoding for PD-L1. This autoimmune development candidate is designed to augment cell surface expression of PD-L1 on myeloid cells to provide co-inhibitory signals to self-reactive lymphocytes.
Relaxin (mRNA-0184): mRNA-0184 encodes for the relaxin protein which has been engineered to increase expression and prolong half-life. Moderna is planning for a Phase 1 study in participants with chronic heart failure. The Company expects that mRNA-0184 will be administered after heart failure decompensation to bridge patients through the vulnerable period.
Exploratory Modalities

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 vaccine (PCV) (mRNA-4157): The randomized, placebo-controlled Phase 2 study investigating a 1 mg dose of mRNA-4157 in combination with Merck’s pembrolizumab (KEYTRUDA), compared to pembrolizumab alone, for the adjuvant treatment of high-risk resected melanoma is fully enrolled (n=150). The Company expects the Phase 2 data readout to occur in the fourth quarter of 2022. The primary endpoint of the Phase 2 study is recurrence-free survival at 12 months. The Phase 1 in multiple cohorts is ongoing including in the expanded head and neck cohort. Moderna shares worldwide commercial rights to mRNA-4157 with Merck.
Mutant KRAS vaccine (mRNA-5671 or V941): Moderna has regained all rights to mutant KRAS vaccine (mRNA-5671) from Merck and Moderna is evaluating next steps for the program.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, led by Merck, is ongoing.
Checkpoint cancer vaccine (mRNA-4359): Moderna recently announced a new checkpoint cancer vaccine (mRNA-4359) expresses Indoleamine 2,3 -dioxygenase (IDO) and programmed death-ligand 1 (PD-L1) antigens. Moderna designed mRNA-4359 with the goal of stimulating effector T-cells that target and kill suppressive immune and tumor cells that express these checkpoints. Moderna is planning to explore initial indications for advanced or metastatic cutaneous melanoma and non-small cell lung carcinoma (NSCLC).
Intratumoral Immuno-Oncology : These programs aim to drive anti-cancer T cell responses by injecting mRNA therapies directly into tumors.

OX40L/IL-23/IL-36γ (Triplet) (mRNA-2752): The Phase 1 trial evaluating mRNA-2752 as a single agent and in combination with durvalumab in patients with advanced solid tumor malignancies and lymphoma is fully enrolled. Enrollment in additional cohorts is ongoing.
IL-12 (MEDI1191): The Phase 1 open-label, multi-center study of intratumoral injections of MEDI1191 alone and in combination with durvalumab in patients with advanced solid tumors, led by AstraZeneca, is ongoing. MEDI1191 is an mRNA encoding for IL-12, a potent immunomodulatory cytokine. Moderna shares worldwide commercial rights to MEDI1191 with AstraZeneca.
Localized Regenerative Therapeutics: Localized production of proteins has the potential to be used as a regenerative medicine for damaged tissues.

VEGF-A (AZD8601): Positive data from the AstraZeneca-led Phase 2 (EPICCURE) study evaluating the use of VEGF-A (AZD8601) in patients undergoing coronary artery bypass grafting (CABG) were presented at the American Heart Association’s Scientific Sessions 2021 annual meeting. The Phase 2 study met the primary endpoint of safety and tolerability of AZD8601. In the study of 11 patients, seven were treated with AZD8601 VEGF-A mRNA and four received placebo injections. Numerical trends were observed in endpoints in the heart failure efficacy domains compared with placebo, including increase in left ventricular ejection fraction (LVEF) and patient reported outcomes. In addition, all seven patients treated with AZD8601 had NT-proBNP levels below heart failure (HF) limit at 6 months follow-up compared to one of four patients treated with placebo. These results support further investigation of AZD8601 for efficacy and safety in future studies.
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.

Propionic acidemia (PA) (mRNA-3927): The Phase 1/2 Paramount study of mRNA-3927 is ongoing and the first cohort is fully enrolled. Moderna is enrolling participants into additional cohorts.
Methylmalonic acidemia (MMA) (mRNA-3705): The Phase 1/2 Landmark study to evaluate the safety and pharmacology of mRNA-3705 in patients 1 year of age and older with MMA is ongoing. Moderna received rare pediatric designation for mRNA-3705.
Glycogen storage disease type 1a (GSD1a) (mRNA-3745): The U.S. FDA has granted mRNA-3745 Orphan Drug Designation and completed its review of the IND application allowing it to proceed to clinic. Individuals with GSD1a have a deficiency in glucose-6-phosphatase resulting in pathological blood glucose imbalance. mRNA-3745 is an IV-administered mRNA encoding human G6Pase enzyme, designed to restore the deficient or defective intracellular enzyme activity in patients with GSD1a.
Phenylketonuria (PKU) (mRNA-3283): Individuals with PKU have a deficiency in phenylalanine hydroxylase (PAH) resulting in a reduced or complete inability to metabolize the essential amino acid phenylalanine into tyrosine. mRNA-3283 encodes human PAH to restore the deficient or defective intracellular enzyme activity in patients with PKU. mRNA-3283 is in preclinical development.
Crigler-Najjar Syndrome Type 1 (CN-1) (mRNA-3351): mRNA-3351 encodes for the human UGT1A1 and is designed to restore the missing or dysfunctional proteins that causes Crigler-Najjar Syndrome Type 1. mRNA-3351 has been granted Rare Pediatric Disease designation by the U.S. FDA. Moderna will provide investigational mRNA-3351 to the nonprofit Institute for Life Changing Medicines (ILCM) free of charge. ILCM will be responsible for the clinical development of mRNA-3351 and plans to initiate clinical studies of mRNA-3351.
Inhaled Pulmonary Therapeutics

Cystic Fibrosis (CF) (VXc-522): VXc-522 is an mRNA therapeutic being designed in collaboration with Vertex Pharmaceuticals. It is designed to treat the underlying cause of CF by enabling cells in the lungs to produce functional cystic fibrosis transmembrane conductance regulator (CFTR) protein for the treatment of the 10% of patients who do not produce any CFTR protein. IND-enabling studies are underway, and Vertex expects to submit an IND for this program in 2022. VXc-522 is being advanced by Vertex.
Information about each development candidate in Moderna’s pipeline can be found at investors.modernatx.com .

Fourth Quarter and Full Year 2021 Financial Results

Fourth Quarter 2021

Revenue: Total revenue was $7.2 billion for the fourth quarter of 2021, compared to $571 million for the same period in 2020. The increase in 2021 was driven by increased product sales. Product sales for the fourth quarter of 2021 were $6.9 billion from sales of 297 million doses of the Company’s COVID-19 vaccine, compared to $200 million in the fourth quarter of 2020 from sales of 13 million doses of the Company’s COVID-19 vaccine. The Company began to record product sales for the Company’s COVID-19 vaccine subsequent to its authorization for emergency use by the FDA and Health Canada in December 2020.
Cost of Sales: Cost of sales was $952 million, or 14% of the product sales for the fourth quarter of 2021, including third-party royalties of $241 million. Cost of sales was $8 million, or 4% of product sales, for the fourth quarter of 2020, comprised of third-party royalties and shipping and handling costs only as the associated inventory costs were expensed previously as pre-launch inventory.
Research and Development Expenses: Research and development expenses were $648 million for the fourth quarter of 2021, compared to $759 million for the same period in 2020. The decrease in spending in 2021 was mainly due to a decrease in pre-launch inventory costs, partially offset by an increase in clinical trial expenses.
Selling, General and Administrative Expenses: Selling, general and administrative expenses were $201 million for the fourth quarter of 2021, compared to $79 million for the same period in 2020. The growth in spending was driven by the commercialization of our COVID-19 vaccine globally with continued investments in personnel and outside services in support of the accelerated company buildout.
Provision for Income Taxes: The effective tax rate was 10.0% for the fourth quarter of 2021, which included tax benefits from the utilization of the cumulative net operating loss carry-forward of $2.3 billion, the foreign-derived intangible income deduction and stock-based compensation. Income taxes were $542 million for the fourth quarter of 2021, compared to $1 million for the same period in 2020. The increase was due to pre-tax income recognized in 2021, compared to a loss in 2020.
Net Income (Loss): Net income was $4.9 billion for the fourth quarter of 2021, compared to a net loss of $(272) million for the same period in 2020.
Earnings (Loss) Per Share: Diluted EPS was $11.29 for the fourth quarter of 2021, compared to $(0.69) for the same period in 2020.
Full Year 2021

Revenue: Total revenue was $18.5 billion for the full year 2021, compared to $803 million in 2020. Total revenue increased in 2021, primarily due to commercial sales of the Company’s COVID-19 vaccine. Product sales for the full year 2021 were $17.7 billion from sales of 807 million doses of the Company’s COVID-19 vaccine.
Cost of Sales: Cost of sales was $2.6 billion, or 15% of the product sales for full year 2021, including third-party royalties of $641 million. A portion of the inventory costs associated with the Company’s product sales for the full year 2021 was expensed as pre-launch inventory costs in 2020. The Company’s pre-launch inventory was fully utilized in the first half of 2021. If inventory sold for the full year 2021 was valued at cost, the Company’s cost of sales for the period would have been $2.8 billion, or 16% of product sales.
Research and Development Expenses: Research and development expenses were $2.0 billion for the full year 2021, compared to $1.4 billion in 2020. The growth in spending in 2021 was mainly due to increases in clinical trial expenses, personnel-related costs, and consulting and outside services, largely driven by increased mRNA-1273 clinical development and headcount.
Selling, General and Administrative Expenses: Selling, general and administrative expenses were $567 million for the full year 2021, compared to $188 million in 2020. The growth in spending in 2021 was mainly due to increases in consulting and outside services, personnel-related costs, marketing expense and distributor fees, primarily attributable to the Company’s COVID-19 vaccine commercialization-related activities and increased headcount.
Provision for Income Taxes: The effective tax rate was 8.1% for the full year 2021 which included tax benefits from the utilization of the cumulative net operating loss carry-forward of $2.3 billion, the foreign-derived intangible income deduction and stock-based compensation. Income taxes were $1.1 billion for the full year 2021, compared to $3 million in 2020. The increase was due to pre-tax income recognized in 2021, compared to a loss in 2020.
Net Income (Loss): Net income was $12.2 billion for the full year 2021, compared to a net loss of $(747) million in 2020.
Earnings (Loss) Per Share: Diluted EPS was $28.29 for the full year 2021, compared to $(1.96) in 2020.
Cash Position: Cash, cash equivalents and investments as of December 31, 2021 and December 31, 2020 were $17.6 billion and $5.2 billion, respectively.
Net Cash Provided by Operating Activities: Net cash provided by operating activities was $13.6 billion for the full year 2021, compared to $2.0 billion in 2020. Net cash provided by operating activities increased significantly in 2021, mainly due to net income of $12.2 billion and additional customer deposits received during the period for the Company’s future COVID-19 vaccine supply.
Cash Used for Purchases of Property and Equipment: Cash used for purchases of property and equipment was $284 million for the full year 2021, compared to $68 million in 2020. The increase was primarily driven by the Company’s business expansion.
2022 Financial Framework

Advanced Purchase Agreements (APAs): Moderna has signed 2022 APAs for product sales of approximately $19 billion and approximately $3 billion in options (probabilized) including for any potential updated COVID-19 vaccine booster candidates. The Company is currently in active discussions for additional orders in 2022. Moderna believes that the SARS-CoV-2 virus will evolve to an endemic phase in 2022 and as a result, the Company expects sales to be larger in the second half of 2022 than in the first half.
Cost of Sales: Cost of sales as percentage of product sales are expected to be in the low-to-mid 20s percentage range.
Research & Development (R&D) and Selling, General & Administrative (SG&A) Expenses: Full year expenses expected to be approximately $4 billion.
Tax Rate: The Company expects an Effective Tax Rate for the full year in the 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 a new share repurchase program for $3 billion to return excess capital to shareholders. The previous program of $1 billion announced in August 2021 has been fully utilized as of the end of January 2022.
Commercial Outlook in 2023 & Beyond

Spikevax 2023 commercial outlook: Moderna has received firm orders for delivery in 2023 from the United Kingdom, Canada, Taiwan, and Kuwait. The Company is currently in active discussions for additional orders in 2023.
Supply agreements with strategic countries: Moderna is committed to expanding its partnerships with governments to equip countries with access to innovative vaccines against respiratory viruses, and domestic access to rapid pandemic response capabilities. To date, Moderna has announced in principle agreements with Australia and Canada and the Company is in discussions with additional countries for similar partnerships.
Moderna’s Capital Allocation Priorities

Reinvest in the base business and accelerating investments in R&D, manufacturing infrastructure, digital, automation, and our global commercial operations.
Seek attractive external investment and collaboration opportunities (licenses and/or M&A) to further expand the reach of Moderna’s technology and capabilities.
After evaluating internal and external investment opportunities, return excess capital to shareholders through share repurchases.
2021 Commercial Network

Moderna is building a global commercial network to enable Moderna’s entire portfolio, which will facilitate the commercialization of its pipeline without a large pharmaceutical partner. The Company now has active commercial subsidiaries in the following geographies – in the Americas: Canada, the United States; Europe: France, Germany, Italy, Spain, Switzerland, and the United Kingdom; Asia Pacific: Australia, Japan, and South Korea. In addition, Moderna works with distributors or partners in other geographies.

2022 New Commercial Networks

In 2022, the Company plans to further expand its commercial network to enable Moderna’s entire portfolio by establishing or activating commercial subsidiaries in the following geographies – in Asia: Hong Kong, Malaysia, Singapore and, Taiwan; and in Europe: Belgium, Denmark, Netherlands, Norway, Poland, and Sweden. In addition, Moderna will continue to work with distributors or partners in other geographies.

Corporate Social Responsibility

Global Access: Approximately 807 million doses of the Moderna COVID-19 vaccine were shipped around the world during 2021 6 ; approximately 25% of all doses delivered in 2021 went to low- and middle-income countries through direct sales by Moderna and facilitated donations from high-income countries. The more than 200 million doses delivered to low- and middle-income countries in 2021 are more than Moderna delivered to any other country or multinational group last year, other than the United States. Gavi has exercised its option to purchase 293 million doses for delivery in 2022 under the agreement to purchase up to 650 million doses across 2021 and 2022, in addition to the 34 million doses delivered in 2021.
mRNA Facility in Africa: Moderna announced that it will build a state-of-the-art mRNA facility in Africa, in part to ensure future access to mRNA vaccines in future pandemics, and is in the final stages of country selection with assistance from the United States government.
Sustainability: Moderna announced a pledge to achieve net-zero carbon emissions globally by 2030.
Moderna Charitable Foundation: Moderna announced it is establishing a new charitable foundation to promote public health, healthcare and educational opportunities, particularly in underserved populations.
Corporate Updates

Continued Growth: Moderna now has approximately 3,000 full time employees. Moderna ended 2020 with approximately 1,300 full time employees.
Expanding Manufacturing Partnerships: Moderna announced an expanded long-term collaboration with Rovi for the manufacture of mRNA medicines over the next ten years in Madrid, Spain. Moderna announced an expanded long-term collaboration with Thermo Fisher for the manufacture of mRNA vaccines over the next 15 years in the U.S.
AI Academy: In December 2020, Moderna launched its Artificial Intelligence (AI) Academy, an innovative initiative that will bring to life an immersive learning experience for Moderna employees, in partnership with Carnegie Mellon University (CMU).
Shareholder Letter: Moderna CEO Stéphane Bancel published a letter to shareholders on January 4, 2022.
Company Recognition: Moderna was named a top employer by Science and Science Careers for the seventh consecutive year and was ranked the number one employer in BioSpace’s 2022 Best Places to Work in Biopharma report.
Juan Andres Elected to the National Academy of Engineering: Juan Andres, Chief Technical Operations and Quality Officer has been elected to the National Academy of Engineering. Moderna’s Co-founder and Chairman, Noubar Afeyan, was also elected to the Academy.
Annual Meeting of Shareholders: The Moderna Annual Meeting of Shareholders will be held on Thursday, April 28, 2022 at 8:00 a.m. ET. The meeting will be held virtually at www.virtualshareholdermeeting.com/MRNA2022 . The record date for voting or attendance as a stockholder is 4:00 p.m. ET on March 1, 2022.
Key 2022 Investor and Analyst Event Dates

Vaccines Day: March 24
Science Day: May 17
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 Thursday, February 24, 2022. To access the live conference call, please dial 866-922-5184 (domestic) or 409-937-8950 (international) and refer to conference ID 5682797. A webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website at investors.modernatx.com. 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.

On February 24, 2022 Emergent BioSolutions Inc. (NYSE: EBS) reported financial results for the fourth quarter and year ended December 31, 2021 (Press release, Emergent BioSolutions, FEB 24, 2022, View Source [SID1234608961]).

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FINANCIAL HIGHLIGHTS (1)

SELECT Q4 2021 AND OTHER RECENT BUSINESS UPDATES

Announced a supply agreement with Sandoz for them to distribute an authorized generic of NARCAN (naloxone HCl) Nasal Spray 4 mg, which is available in the U.S. via retail pharmacies and institutions, including hospitals
Initiated the rolling submission to the U.S. Food and Drug Administration (FDA) of the Biologics License Application (BLA) for AV7909 (Anthrax Vaccine Adsorbed, Adjuvanted), the Company’s investigational anthrax vaccine candidate
Initiated a pivotal Phase 3 safety and immunogenicity study to evaluate CHIKV VLP, the Company’s single-dose chikungunya virus virus-like particle (VLP) vaccine candidate
Initiated a Phase 1 safety, tolerability, and immunogenicity study to evaluate UniFlu, the Company’s universal influenza vaccine candidate comprised of multiple components intended to induce broad and supra-seasonal immunity against influenza A viruses
Announced the Company’s Board of Directors authorization to management to repurchase up to $250 million of the Company’s common stock through November 11, 2022; as of December 31, 2021, the Company repurchased approximately 2.6 million shares for $112.6 million, an average price per share of $42.67
Announced the retirement of the Company’s founder and executive chairman, Fuad El-Hibri, effective April 1, 2022
Q4 2021 FINANCIAL PERFORMANCE (1)

Product Sales, net
Anthrax vaccines
For Q4 2021, revenues from anthrax vaccines increased $22.0 million as compared to Q4 2020. The increase is largely driven by an increase in deliveries of AV7909 to the U.S. government (USG), specifically the Strategic National Stockpile (SNS). The Company received an AV7909 contract modification in September 2021 and began delivering additional doses of AV7909 under that modification, which covers a period of 18 months and is valued at approximately $399 million.

ACAM2000
For Q4 2021, revenues from ACAM2000 (Smallpox (Vaccinia) Vaccine, Live) decreased $3.5 million as compared to Q4 2020. The decrease is largely driven by the timing of deliveries to the USG. The revenues recognized in Q4 2021 reflect delivery of doses into the SNS resulting from the July 2021 exercise by the USG of the second of nine annual contract term extension options pursuant to the Company’s 10-year supply agreement with the USG. This latest option is valued at approximately $182 million.

Nasal naloxone products
For Q4 2021, revenues from nasal naloxone products increased $43.2 million as compared to Q4 2020. The increase is driven by continued demand for NARCAN (naloxone HCI) Nasal Spray across customer channels in the U.S. and Canada. The increase also reflects the impact of revenues related to the authorized generic of NARCAN (naloxone HCI) Nasal Spray 4mg, a product licensed to Sandoz and launched in late 2021 and one in which the Company retains a financial interest.

Other (4)
For Q4 2021, revenues from other product sales increased $31.7 million as compared to Q4 2020. The increase is largely due to sales of VIGIV [Vaccinia Immune Globulin Intravenous (Human)], driven by timing of deliveries to the USG and based on the June 2021 exercise by the USG of the second of nine annual contract term extension options pursuant to the Company’s 10-year supply agreement with the USG. This latest option is valued at approximately $56 million.

Contract Development and Manufacturing (CDMO)
CDMO Services
For Q4 2021, revenue from contract development and manufacturing services decreased $12.8 million as compared to Q4 2020. This decrease is largely due to the discontinuation of manufacturing activities related to the Company’s arrangement with AstraZeneca as was previously announced in the second quarter of 2021. Additionally, there was less activity as compared to Q4 2020 due to routine maintenance in the Company’s manufacturing network.

CDMO Leases
For Q4 2021, revenue from contract development and manufacturing leases increased $32.0 million as compared to Q4 2020. This increase is largely due to the timing of $155.7 million in final cash collections associated with the Center for Innovation in Advanced Development and Manufacturing (CIADM) public-private partnership with the Biomedical Advanced Research and Development Authority (BARDA), an arrangement that was mutually terminated by both parties in the fourth quarter. The Company anticipates ongoing CDMO lease revenues in subsequent periods related primarily to its existing CDMO manufacturing agreement with Johnson & Johnson, a portion of which is considered a lease.

Contracts and Grants
For Q4 2021, revenues from contracts and grants increased $27.6 million as compared to Q4 2020. The increase is a result of $59.7 million being recognized in Q4 2021, primarily deferred revenue, as a result of the CIADM base contract termination offset by a decrease in third party development activities.

Cost of Product Sales
For Q4 2021, cost of product sales increased $40.6 million as compared to Q4 2020. The increase is primarily due to a higher volume of product sales, specifically nasal naloxone products, AV7909 and VIGIV.

Cost of CDMO
For Q4 2021, cost of CDMO increased $4.0 million as compared to Q4 2020. The increase is primarily due to additional costs at the Company’s Bayview facility to further support enhancements to quality systems and capabilities at the site.

Research and Development
For Q4 2021, research and development expenses increased $23.5 million as compared to Q4 2020. The increase is primarily due to the non-cash write-off of $38.0 million associated with a contract asset balance resulting from the CIADM contract termination.

Selling, General and Administrative
For Q4 2021, selling, general and administrative expenses increased $12.1 million as compared to Q4 2020. The increase is primarily due to professional services costs.

Goodwill Impairment
During Q4 2021, the Company performed its annual impairment testing reflecting its revised reporting unit structure. Pursuant to this analysis, the Company recognized a $41.7 million non-cash impairment of goodwill in the Commercial reporting unit.

ADDITIONAL FINANCIAL INFORMATION

For Q4 2021, product gross margin increased $52.8 million as compared to Q4 2020. The increase is primarily due to the increase in product sales. Product gross margin percent decreased primarily due to changes in product mix.

For Q4 2021, CDMO gross margin decreased $16.8 million as compared to Q4 2020. Adjusted CDMO gross margin decreased $17.7 million as compared to Q4 2020. The decline in CDMO gross margin and adjusted CDMO gross margin is primarily due to routine maintenance activity that occurred in the Company’s manufacturing network in Q4 2021 that did not occur in Q4 2020 as well as increased costs to support remediation efforts for the Company’s manufacturing activities at its Bayview facility.

For Q4 2021, the Company has revised the metrics it provides related to specific aspects of the CDMO business. The Company will continue to provide the CDMO New Business Secured and Backlog metrics. The Company is introducing CDMO Customers as a new metric, and is discontinuing reporting of the CDMO Opportunity Funnel. The Company believes this set of supplemental information provides more valuable and relevant context on the performance and stability of the CDMO business.

For Q4 2021, capital expenditures increased largely due to the Company’s continued investments in expanded capacity and capabilities at the Company’s Rockville manufacturing facility. The increase in gross capital expenditures was offset by the timing of reimbursements of $60.5 million related to arrangements funded by the USG. The capital expenditures related to this reimbursement were incurred in a prior period.

Full Year 2022

For full year 2022, the Company provides the following update to its forecast of key financial metrics, which were originally announced on January 9, 2022.

The Company’s 2022 financial forecast includes the following considerations:

Revised Considerations

The revision to total revenues, CDMO services revenue, Adjusted EBITDA and adjusted net income reflect the impact of the Company’s decision to take the opportunity to initiate a maintenance period that it would normally plan for the Bayview facility earlier than anticipated and also extend it in order to make additional improvements and modifications that will better position Bayview for future non-pandemic work.

Unchanged Considerations

2022 Product/Service Level Revenues – Select Assumptions

Anthrax vaccines revenues are expected to continue at similar levels to 2021 under the terms of the Company’s existing contract with BARDA.
ACAM2000 (Smallpox (Vaccinia) Vaccine, Live) vaccine deliveries are expected to continue under the terms of the Company’s existing contract with the U.S. Department of Health and Human Services (HHS) at unit volume levels consistent with 2021 deliveries.
Nasal naloxone products revenues reflect the formation of a generic market and comprise revenues from a combination of NARCAN(naloxone HCl) Nasal Spray and the authorized generic of NARCAN Nasal Spray, a product licensed to Sandoz and launched in late 2021 and one in which the Company retains a financial interest.
Other Products + Contracts and Grants revenues: 1) other products revenues reflect continued procurement of other products not highlighted on a standalone basis from various government customers under existing multi-year contracts; 2) contracts and grants revenues reflect continued funding of select development programs from various government and other non-dilutive sources.
Other 2022 Assumptions

Gross margin primarily reflects the influence of the mix of product and services revenues.
Pipeline progress is expected across the R&D portfolio with the ongoing advancement of the CHIKV VLP Phase 3 clinical trial, the completion of the BLA filing for AV7909, and anticipated advancements of a number of early-stage programs.
Capital expenditures, net of reimbursement, are expected to be approximately 10% of total revenues at the midpoint, reflecting ongoing investments in capacity and capability expansions related to the CDMO business and the Company’s R&D programs, and aligned with the average over the previous five-year period.
Q1 2022

For Q1 2022, the Company expects total revenues of $280 million to $310 million.

FOOTNOTES

(1) All financial information incorporated within this release is unaudited.
(2) See "Reconciliation of Net Income to Adjusted Net Income," "Reconciliation of Net Income to Adjusted EBITDA," "Reconciliation of Product Gross Margin and Adjusted Product Gross Margin," "Reconciliation of CDMO Gross Margin and Adjusted CDMO Gross Margin" and "Adjusted Revenues" for a definition of terms and the reconciliation tables.
(3) Product sales, net are reported net of variable consideration including returns, rebates, wholesaler fees and prompt pay discounts.
(4) Other can include a combination of sales of any of the following products: BAT, VIGIV, Anthrasil, raxibacumab, RSDL, Trobigard, Vivotif, and Vaxchora.
(5) CDMO New Business Secured is defined as initial value of contracts secured as well as incremental value of existing contracts modified within the indicated period and is incorporated into Backlog.
(6) CDMO Backlog is defined as estimated remaining contract value as of the indicated period pursuant to signed contracts, the majority of which is expected to be recognized over the next 24 months. This excludes any value associated with an extension of the commercial supply agreement (CSA) with Johnson & Johnson.
(7) CDMO Customers is defined as a client (commercial, government, NGO) for whom the Company has performed CDMO services where there is evidence of meeting all of the following criteria: i) completion of any invoiceable project milestones in the preceding 24-month period, indicating ongoing work; ii) secured project work planned in the future, which has not yet been invoiced, capturing future work not yet indicated in the invoice record; and, iii) neither the Company nor the client having yet to formally terminate the last remaining project, thereby removing any client for whom work has fully concluded.

CONFERENCE CALL, PRESENTATION SUPPLEMENT AND WEBCAST INFORMATION

Company management will host a conference call at 5:00 pm (Eastern Time) today, February 24, 2022, to discuss these financial results. The conference call and presentation supplement can be accessed from the Company’s website or through the following: