Seagen Reports Second Quarter 2022 Financial Results

On July 28, 2022 Seagen Inc. (Nasdaq:SGEN) reported financial results today for the second quarter ended June 30, 2022 (Press release, Seagen, JUL 28, 2022, View Source [SID1234617088]). The Company also highlighted PADCEV (enfortumab vedotin-ejfv), TUKYSA (tucatinib), ADCETRIS (brentuximab vedotin) and TIVDAK (tisotumab vedotin-tftv) commercial and development accomplishments, as well as progress across its deep and diverse oncology pipeline.

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"Seagen once again delivered strong commercial performance with record quarterly net product sales, in addition to accomplishing a number of important clinical milestones across our pipeline," said Roger Dansey, M.D., interim CEO and Chief Medical Officer. "We are pleased to have recently reported positive clinical trial results that could potentially support additional labels for ADCETRIS, PADCEV and TUKYSA and we have obtained approval of PADCEV in the EU. At the same time, we are progressing our deep pipeline of targeted cancer therapies and we are well-positioned for the future."

APPROVED PRODUCTS HIGHLIGHTS

PADCEV

Announced Positive Topline Results for Combination of PADCEV and KEYTRUDA (pembrolizumab) as First-Line Treatment for Advanced Urothelial Cancer: In July 2022, Seagen and Astellas announced positive topline results from the phase 1b/2 EV-103 clinical trial (also known as KEYNOTE-869) Cohort K evaluating PADCEV in combination with Merck’s anti-PD-1 therapy KEYTRUDA as first-line treatment in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-based chemotherapy. In patients treated with enfortumab vedotin and pembrolizumab, results demonstrated a 64.5% confirmed objective response rate (95% CI: 52.7 to 75.1) per blinded independent central review (BICR), the primary endpoint of Cohort K. The median duration of response per BICR was not reached. The most frequently reported treatment-emergent adverse events Grade 3 or greater that occurred in more than 5% of patients were rash maculo-papular, anemia, lipase increased, urinary tract infection, hyperglycemia, fatigue, neutropenia, hematuria, diarrhea, acute kidney injury, hyponatremia, chronic kidney disease, weight decreased, syncope, hypophosphatemia, pneumonitis, sepsis, and alanine aminotransferase increased. Overall, the results are generally consistent with previously reported efficacy and safety results of the EV-103 dose-escalation cohort and expansion Cohort A. Data will be presented at a future medical conference and will be discussed with the U.S. Food and Drug Administration (FDA) with the intention of submitting a supplemental Biologics License Application later in 2022 under the FDA’s Accelerated Approval Program.
Received European Commission (EC) Approval for PADCEV in Previously Treated Metastatic Urothelial Cancer in Addition to Other Countries: In April 2022, Seagen and Astellas announced the EC approval of PADCEV as monotherapy for the treatment of adult patients la/mUC who have previously received a platinum-containing chemotherapy and a PD-1/L1 inhibitor. The approval is applicable in the European Union Member States, as well as Iceland, Norway and Liechtenstein. Additionally, in the second quarter of 2022, PADCEV was approved for la/mUC in Australia, Brazil, Great Britain and Singapore.
TUKYSA

Presented Positive Results of Pivotal Trial of TUKYSA in Combination with Trastuzumab in HER2-Positive Metastatic Colorectal Cancer: In July 2022, the Company presented positive results from the pivotal phase 2 MOUNTAINEER trial investigating TUKYSA in combination with trastuzumab in patients with previously treated HER2-positive metastatic colorectal cancer at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) World Congress Gastrointestinal Cancer. The combination of tucatinib and trastuzumab was generally well-tolerated with durable responses in patients assigned to receive the combination demonstrating a 38.1% confirmed response rate after a median duration of follow-up of 20.7 months. The most common (greater than or equal to 20%) treatment-emergent adverse events were diarrhea, fatigue, nausea and infusion-related reaction. In July 2022, a supplemental New Drug Application was submitted to the FDA under the Accelerated Approval Program.
TUKYSA Granted Breakthrough Therapy Designation (BTD) for HER2-positive Metastatic Colorectal Cancer: In July 2022, the FDA granted TUKYSA BTD for use in combination with trastuzumab for the treatment of adult patients with unresectable or metastatic HER2-positive colorectal cancer who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. The designation is based on results of the MOUNTAINEER trial.
Completed Global Enrollment in Pivotal HER2CLIMB-02 Trial: The Company completed enrollment in the phase 3 HER2CLIMB-02 clinical trial evaluating TUKYSA versus placebo, in combination with KADCYLA (ado-trastuzumab emtansine), for patients with locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases.
ADCETRIS

ADCETRIS Combination Data Published in the New England Journal of Medicine (NEJM)Demonstrating Statistically Significant Improvement in Overall Survival (OS) for Patients with Advanced Hodgkin Lymphoma: In July 2022, longer-term follow-up data from the ECHELON-1 phase 3 clinical trial were published in NEJM demonstrating that ADCETRIS in combination with chemotherapy resulted in a 41% reduction in risk of death versus standard of care in patients with advanced Hodgkin lymphoma. The safety profile of ADCETRIS was consistent with previous studies, and no new safety signals were observed. The Company expects to submit the data to the FDA in a sBLA during 2022.
Children’s Oncology Group Presented ADCETRIS Plus Chemotherapy Demonstrating Superior Event-Free Survival (EFS) versus Standard of Care Alone in Children and Young Adults with Previously Untreated High-Risk Hodgkin Lymphoma: In June 2022, the Company announced results from a phase 3 Children’s Oncology Group trial evaluating ADCETRIS in children and young adults with high-risk, previously untreated classical Hodgkin lymphoma. In the trial, ADCETRIS in combination with chemotherapy showed a clinically meaningful and statistically significant 59% reduction in the risk of disease progression or relapse, second malignancy or death and achieved superior event-free survival compared to the current standard of care. Based on these data, Seagen submitted a sBLA to the FDA for review. The sBLA was granted Priority Review with a target action date of November 16, 2022.
TIVDAK

Reported Data from TIVDAK Clinical Development Program in Cervical Cancer at ASCO (Free ASCO Whitepaper): In June 2022, the Company announced interim data from the innovaTV 205 trial, which included data evaluating TIVDAK in combination with KEYTRUDA (Cohort E) in patients with recurrent or metastatic cervical cancer who have not received prior systemic therapy. These data showed encouraging and durable anti-tumor activity. TIVDAK and KEYTRUDA in combination with other anti-cancer agents continue to be evaluated in front-line recurrent or metastatic cervical cancer.
PIPELINE PROGRAMS

For additional information on Seagen’s pipeline, visit www.seagen.com/science/pipeline.

CORPORATE HIGHLIGHTS

Patent Infringement Suit Against Daiichi Sankyo. In July 2022, the U.S. Patent and Trademark Office denied Daiichi Sankyo’s Request for a Post Grant Review of the 10,808,039 Patent (the ‘039 Patent’). The U.S. District Court for the Eastern District of Texas also denied Daiichi Sankyo’s claim that the ‘039 Patent should be unenforceable under the equitable theory of prosecution laches, entered judgment in favor of Seagen based on the jury’s verdict that Daiichi Sankyo willfully infringed the ‘039 Patent consisting of pre-trial damages in the sum of $41.8 million, and awarded Seagen pre- and post-trial interest and costs. The company intends to request a royalty on Daiichi Sankyo’s future sales of ENHERTU in the United States through November 5, 2024.
Announced Roger Dansey, M.D., Chief Medical Officer, Appointment as Interim CEO: In May 2022, the Company announced Roger Dansey, M.D., Seagen’s Chief Medical Officer since 2018, was appointed interim CEO following the resignation of Clay Siegall, Ph.D. the Company’s former President and CEO.
Received Milestone Payment Triggered by AbbVie Initiating a Phase 3 Trial of Telisotuzumab Vedotin (ABBV- 399): Seagen received a $12 million milestone payment under its antibody drug conjugate (ADC) technology licensing agreement with AbbVie following the initiation of a phase 3 study of AbbVie’s telisotuzumab vedotin for the treatment of non-small cell lung cancer.
Announced Plans to Expand Biomanufacturing Capacity to Support Growing Portfolio of Cancer Medicines: In April 2022, the Company announced plans to build a new facility in Everett, WA, to expand the Company’s biomanufacturing capacity and enable the company greater control and flexibility over the production of its medicines to treat cancer. The new facility will be in addition to Seagen’s existing manufacturing site in Bothell, WA.
SECOND QUARTER AND SIX-MONTHS 2022 FINANCIAL RESULTS

Revenues: Total revenues for the second quarter and six months ended June 30, 2022 were $497.5 million and $924.0 million, respectively, compared to $388.5 million and $720.5 million for the same periods in 2021. Revenues in the 2022 periods reflected higher net product sales across the Company’s commercial portfolio.

Net Product Sales: The increases in net product sales for the second quarter and year-to-date of 2022 compared to the same periods in 2021 were driven by growth from the Company’s marketed products. PADCEV growth was driven by continued penetration in its approved indications and, to a lesser extent, sales of drug product for use in clinical trials being conducted by another company. TUKYSA growth was driven primarily by increased sales in European markets following its approval in February 2021 and continued use in its current indication in the U.S. TIVDAK commercialization began in the U.S. following FDA approval in September 2021.
Royalty Revenues: Royalty revenues were primarily driven by sales of ADCETRIS outside the U.S. and Canada by Takeda as well as royalties from sales of Polivy (polatuzumab vedotin) by Roche and Blenrep (belantamab mafodotin) by GlaxoSmithKline, which are ADCs that use Seagen technology.
Collaboration and License Agreement Revenues: The increases in collaboration and license agreement revenues in the second quarter and year-to-date in 2022 compared to the same period in 2021 were primarily the result of a $12 million milestone payment received from AbbVie in the second quarter of 2022 related to the initiation of a phase 3 trial of telisotuzumab vedotin, an upfront license payment relating to the Company’s ADC collaboration with Sanofi in the first quarter of 2022, royalty contribution from Astellas’ PADCEV sales in its territory, as well as higher amounts of drug product supplied to a collaborator.
Cost of Sales: Cost of sales for the second quarter and year-to-date of 2022 were $106.1 million and $193.7 million, respectively, compared to $78.1 million and $142.2 million for the same periods in 2021. The increases were primarily related to the gross profit share amounts owed to collaboration partners, which were $65.5 million and $118.3 million in the second quarter and year-to-date of 2022, respectively, compared to $38.6 million and $71.1 million for the same periods in 2021. Cost of sales also reflects amortization of TUKYSA acquired in-process technology costs, third-party royalties owed for PADCEV and TUKYSA net product sales, and cost of products sold.

Research and Development (R&D) Expenses: R&D expenses for the second quarter and year-to-date of 2022 were $304.3 million and $601.9 million, respectively, compared to $234.9 million and $465.3 million for the same periods in 2021. The increases in the periods ended June 30, 2022 primarily reflected continued investment in clinical development of the Company’s approved drugs and to advance its novel programs and technologies.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses for the second quarter and year-to-date of 2022 were $220.3 million and $394.5 million, respectively, compared to $165.1 million and $325.0 million for the same periods in 2021. The increases in 2022 were driven by commercialization efforts for our approved products including investments to support ongoing European TUKYSA launches, the U.S. commercial launch of TIVDAK, and other corporate activities.

Non-cash, share-based compensation expense for the six months ended June 30, 2022 was $98.0 million, compared to $76.0 million for the same period in 2021.

Net Loss: Net loss for the second quarter of 2022 was $134.8 million, or $0.73 per diluted share, and net loss for the year-to-date in 2022 was $271.3 million, or $1.48 per diluted share.

The net loss for the second quarter of 2021 was $84.6 million, or $0.47 per diluted share, and net loss for the year-to-date in 2021 was $206.0 million, or $1.14 per diluted share.

Cash and Investments: As of June 30, 2022, Seagen had approximately $1.9 billion in cash and investments.

2022 FINANCIAL OUTLOOK

Seagen anticipates 2022 revenues, operating expenses and other costs to be in the ranges shown in the table below, which includes increased net sales expectations for ADCETRIS, as well as higher collaboration and license agreement revenues.

1. TIVDAK sales guidance not provided and excluded from product sales and total revenues guidance.

2. Non-cash costs include share-based compensation, depreciation, and amortization of intangible assets.

Conference Call Details

Seagen management will host a conference call and webcast with supporting slides to discuss its second quarter 2022 financial results and provide an update on business activities. The event will be held today at 1:30 p.m. Pacific Time (PT); 4:30 p.m. Eastern Time (ET). The live event will be simultaneously webcast and available for replay from the Seagen website at investor.seagen.com. Investors may also participate in the conference call by calling 844-763-8274 (domestic) or 412-717-9224 (international). The conference ID is 10167970. Supporting slides are available on the Seagen website at investor.seagen.com under the Investors section. A webcast replay will be archived on the Company’s website investor.seagen.com, under the Investors section.

Strong execution in Q2 drives full-year 2022 guidance upgrade and delivers rich R&D news flow in Immunology and Rare Disease

On July 28, 2022 Sanofi reported that Q2 2022 sales growth of 8.1% at CER driven by Dupixent, Rare Disease, Vaccines and CHC (Press release, Sanofi, JUL 28, 2022, View Source [SID1234617087])

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•Specialty Care grew 21.6% driven by Dupixent (€1,963 million, +43.4%), and double-digit growth in Rare Disease
•Vaccines up 8.7% due to strong rebound of Travel and Booster vaccines as well as continued PPH franchise growth
•General Medicines achieved 6.0% growth in core assets despite lower COVID-19 related demand for Lovenox
•CHC delivered 5th consecutive quarter of growth (+9.1%) driven by Cough & Cold, Allergy and Digestive Wellness
Q2 2022 business EPS(1) up 16.7% at CER driven by higher sales and improving margins
•BOI margin up 1.3 ppt to 27.2% due to margin improvement from efficiency gains and EUROAPI deconsolidation
•€2.6bn savings achieved at the end of Q2, with the majority reinvested in growth drivers and R&D
•Business EPS(1) of €1.73, up 25.4% on a reported basis and 16.7% at CER
•IFRS EPS of €0.94 (down 2.1%)
Progress on Corporate Social Responsibility strategy
•Sanofi’s Global Health Unit launches a fund for healthcare solutions in underserved regions and Impact, a new brand dedicated for non-profit distribution of 30 Sanofi products to at-risk populations in 40 lower-income countries
•Valyou program continues to improve access through lower out-of-pocket cost of insulins for uninsured patients in the U.S.
•Sanofi upgraded its scope 3 GHG emission reductions ambition to -30% by 2030, unveiling low energy intensity vaccines facility
Key milestone and regulatory achievements on R&D transformation
•Efanesoctocog alfa, the first factor VIII therapy to be granted FDA Breakthrough Therapy Designation for hemophilia A
•Dupixent approved in the U.S as first treatment for adults and children aged 12 and older with eosinophilic esophagitis and as first biologic medicine for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis
•FDA accepted Dupixent for priority review in adults with prurigo nodularis
•Nexviadyme and XenpozymeTM approved in EU
•Next-generation COVID-19 booster demonstrated strong results against variants of concern, including Omicron
Full-year 2022 business EPS guidance revised upward
•Sanofi now expects 2022 business EPS(1) to grow approximately 15%(2) at CER, barring unforeseen major adverse events. Applying average July 2022 exchange rates, the positive currency impact on 2022 business EPS is estimated between +7.5% to +8.5%
Sanofi Chief Executive Officer, Paul Hudson, commented:
"Our performance in the second quarter was again marked by higher sales across our key growth drivers and outstanding financial results leading us to upgrade our business EPS guidance for the full-year. Notably, we saw significant growth momentum from our Specialty Care business, mainly driven by Dupixent. While we continue to increase our investment in R&D, we delivered important pipeline milestones such as the approval of Dupixent in its fourth disease indication, Eosinophilic Esophagitis. Earlier this month, we had the opportunity to showcase at ISTH the transformative potential of efanesoctocog alfa, the first factor replacement therapy for hemophilia A to receive FDA Breakthrough Therapy Designation. We are also making great progress in advancing our fully integrated social impact strategy, notably in Affordable Access with the launch of Impact, a dedicated brand for non-profit distribution to enable the secure distribution of 30 Sanofi medicines in 40 lower-income countries. As we continue to deliver ahead of schedule on our Play to Win strategy, we are confident in our business outlook for the second half and as a result, we are reiterating our commitment to achieving the BOI margin target of 30% in 2022."

2022 second-quarter and first-half Sanofi sales
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Unless otherwise indicated, all percentage changes in sales in this press release are stated at CER1
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In the second quarter of 2022, Sanofi sales were €10,116 million, up 15.7% on a reported basis. Exchange rate movements had a positive effect of 7.6 percentage points, mainly due to the U.S. dollar. At CER, company sales were up 8.1%.
In the first half of 2022, Sanofi sales reached €19,790 million, up 14.2% on a reported basis. Exchange rate movements had a positive effect of 5.8 percentage points. At CER, company sales were up 8.4%.
Second-quarter 2022 operating income
Second-quarter business operating income (BOI) increased 21.5% to €2,753 million. At CER, BOI increased 13.2%. The ratio of BOI to net sales increased 1.3 percentage points to 27.2% (27.1% at CER). In the first half, BOI increased 18.7% to €5,818 million. At CER, BOI increased 12.7%. The ratio of business operating income to net sales increased 1.1 percentage points to 29.4% (29.4% at CER).
Pharmaceuticals
Second-quarter Pharmaceutical sales increased 7.9% to €7,673 million, mainly driven by the Specialty Care portfolio (up 21.6%) with continued strong performance of Dupixent while sales in General Medicines decreased 4.1%. In the first half of 2022, Pharmaceuticals sales increased 7.7% to €14,999 million reflecting the strong performance of Specialty Care and General Medicines core assets.
Specialty Care
Dupixent
In the second quarter, Dupixent (collaboration with Regeneron) sales increased 43.4% to €1,963 million. In the U.S., Dupixent sales of €1,477 million (up 37.9%) were driven by continued strong demand in atopic dermatitis (AD) in adults, adolescents, and children aged 6 to 11 years, and continued uptake in asthma for patients aged 12 years and older and children aged 6 to 11 years, and chronic rhinosinusitis with nasal polyposis (CRSwNP). Dupixent total prescriptions (TRx) increased 38% (year-over-year) and new-to-brand prescriptions (NBRx) grew 23%. In Europe, second-quarter Dupixent sales grew 56.6% to €239 million reflecting continued growth in AD, asthma and CRSwNP. In the Rest of the World region second-quarter sales reached €247 million, up 65.3%. First-half Dupixent sales reached €3,577 million, up 44.4%.
Neurology and Immunology
In the second quarter and the first half, Neurology and Immunology sales grew 1.1% (to €623 million) and 0.7% respectively, driven by strong Kevzara growth which was partially offset by lower Aubagio sales.
Aubagio sales decreased 2.2% in the second quarter to €526 million due to lower sales in the U.S. and in the Rest of the World region as a result of both competitive pressure and price, partially offset by growth in Europe.
Second-quarter Kevzara (collaboration with Regeneron) sales increased 30.4% to €77 million due to a temporary increased global demand for IL-6 receptor blockers.
Rare Disease

In the second quarter, Rare Disease sales increased 11.6% to €891 million driven by growth of the Gaucher, Fabry and Pompe franchises. Sales in the Rest of the World region benefitted from favorable purchasing patterns. First-half sales of Rare Disease increased 6.7% reflecting growth across all three geographic regions and across all core brands.
Second-quarter sales of the Pompe franchise (Myozyme/Lumizyme + Nexviazyme) increased 12.0% to €295 million primarily from new patient accruals across the three regions, favorable purchasing

patterns in the Rest of the World region and the ramp up of Nexviazyme. Myozyme/Lumizyme sales decreased 3.6% to €252 million mainly reflecting the conversion to Nexviazyme in the U.S. Sales of Nexviazyme (which was launched in the U.S. in August 2021 and in Japan in November 2021) were €43 million in the second quarter (of which €37 million in the U.S.).
Sales of the Gaucher franchise (Cerezyme + Cerdelga) increased 16.8% (to €274 million) in the second quarter. Cerezyme sales were up 18.8% to €202 million, driven by the Rest of the World region, reflecting favorable purchasing patterns. In parallel, Cerdelga sales were up 11.5% driven by switches and new patient accruals.
Second-quarter Fabrazyme sales increased 9.3% to €238 million driven mainly by growth in the three geographic regions.
XenpozymeTM (olipudase alfa) was launched in Japan in June as the first and only enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase.
Oncology

Second-quarter and first-half sales of Oncology increased 8.0% (to €263 million) and 7.4% respectively, mainly driven by Sarclisa which offset the impact of Jevtana generic competition in Europe.
Second-quarter Jevtana sales decreased 15.8% to €105 million following the entry of generic competition in some European markets (down 73.3%) at the end of March 2021. In the U.S., sales were up 8.2%, where Jevtana is currently covered by four Orange Book listed patents US 7,241,907, US 8,927,592, US 10,583,110 and US 10,716,777. Sanofi filed patent infringement suits under Hatch-Waxman against generic filers asserting the ‘110 patent, the ‘777 patent and the ‘592 patent in the US District Court for the District of Delaware. Sanofi has reached settlement agreements with some of the defendants and the suit against the remaining defendants is ongoing. A 3-day trial has been scheduled starting January 2023 and the remaining defendants have agreed not to launch any generic cabazitaxel product until the earlier of a district court decision in favor of the defendants or four months after the completion of the post-trial briefing. Jevtana also received a regulatory data exclusivity related to the CARD clinical study which expires in December 2023.
Second-quarter Sarclisa sales were €64 million, up 52.5% primarily driven by performance in the U.S. (€30 million, up 62.5%) and Japan.
Sanofi has restructured its immuno-oncology collaboration with Regeneron Pharmaceuticals by granting them the worldwide exclusive license rights of Libtayo, under an amended and restated license and collaboration agreement transferring the rights to develop, commercialize, and manufacture Libtayo. Sanofi will stop consolidating Libtayo non-U.S. sales from the third quarter of 2022.
In the second quarter, Rare Blood Disorders franchise sales increased 5.5% (€336 million), mainly reflecting Alprolix growth partially offset by lower Eloctate sales. First-half franchise sales were up 3.7% driven by Alprolix and Cablivi.
Eloctate sales were €153 million in the second quarter, down 3.5% reflecting lower sales in the U.S. due to competitive environment and in the Rest of the World region.
Second-quarter Alprolix sales were up 16.0% to €129 million driven by the U.S. as well as growth in the Rest of the World region.
Cablivi sales increased by 4.3% to €51 million in the second quarter supported by growth in the U.S. Sales in Europe were stable at €24 million.
Second-quarter sales of Enjaymo, the first approved treatment for patients with cold agglutinin disease (approved in the U.S. in February), were €3 million.
General Medicines
Second-quarter General Medicines sales decreased 4.1% to €3,597 million. Adjusted from portfolio streamlining and excluding EUROAPI2 third party sales (in the second quarter of 2022 and 2021), sales decreased 1.0% driven by sustained core assets performance. Second-quarter Industrial sales were €133 million, down 33.3% and reflected deconsolidation of EUROAPI third party sales from May 10.
First-half sales of General Medicines decreased 2.3% (and decreased 1.6% excluding portfolio streamlining). In the first half, core assets sales accounted for 43.6% of General Medicines sales compared with 40.2% for the same period of 2021.

In the second quarter, core assets3 sales increased 6.0% to €1,611 million, driven by the growth of Praluent and Thymoglobulin and the strong performance of Rezurock, partially offset by lower sales of Lovenox. In the first half, core assets sales increased 5.3% to €3,205 million sustained by double digit growth of Praluent, Thymoglobulin and Soliqua as well as the contribution of Rezurock.
Second-quarter Lovenox sales decreased 10.9% to €337 million, reflecting the high base of comparison in 2021 due to a COVID-19 related demand and increased biosimilar penetration.
Second-quarter Toujeo sales increased 2.4% to €267 million, reflecting growth in the U.S. and Europe partially offset by the anticipated implementation of the Volume Based Procurement (VBP) for insulins in China from May this year.
Sanofi participated in the VBP tender for basal insulin analogues in China in November and was among the bidding winners in Group A with Toujeo and Lantus. In 2022, Sanofi expects its glargine sales to decrease not more than 30% in China, benefiting from higher volumes at significantly lower prices. In China, second-quarter and first-half Toujeo/Lantus sales were €101 million (down 24,2%) and €294 million (down 5,3%), respectively.
Plavix sales were stable in the second quarter at €247 million, reflecting consistent volume growth in China (sales were up 19.1% to €125 million) which offset lower sales in Europe and in Japan where the product was impacted by a mandatory price cut at the beginning of April.
Praluent second-quarter sales were €128 million, up 147.9%. Praluent sales in the U.S. are related to a gross to net true-up, as U.S. sales are now consolidated by Regeneron since the restructuring of the alliance. Excluding the U.S., second-quarter Praluent sales were up 47.9% driven by performance in Europe and an accelerated ramp-up in China with the inclusion in the NDRL effective January 2022.
Multaq second-quarter sales grew 2.5% to €91 million, reflecting growth in the U.S. and in the Rest of the World region.
Second-quarter Soliqua sales increased 4.3% to €53 million driven by growth in the Rest of World region (up 33.3%) which more than offset lower sales in the U.S.
Sales of Rezurock were €43 million in the second quarter. Since launch more than 1000 patients have been treated with Rezurock (25% of current addressable patient population) with excellent persistency rates. Rezurock has a broad formulary coverage in the U.S. with around 80% of lives covered nationally.
In the second quarter, non-core assets sales decreased 8.6% to €1,853 million reflecting portfolio streamlining (-1.9 ppt), and VBP impact in China on Lantus as well as on Eloxatin and Taxotere sales. In the first half, non-core assets sales decreased 6.4% and excluding portfolio streamlining decreased 4.8% (-1.6 ppt).
Lantus sales were €600 million, down 12.1% in the second quarter. In the U.S., sales decreased 19.0%, impacted by the loss of formulary as well as by the overall erosion of the basal insulin market. In Rest of the World region, sales were down 8.2% reflecting the implementation of the insulin VBP in China starting in May this year.
Second-quarter Aprovel/Avapro sales were up 13.1% to €120 million driven by the Rest of the World region recovering from supply constraints last year.
Pharmaceuticals business operating income
In the second quarter, business operating income (BOI) of Pharmaceuticals increased 17.9% to €2,826 million (up 10.4% at CER). The ratio of BOI to net sales increased by 0.7 percentage points to 36.8% (37.0% at CER), reflecting an improvement of the gross margin ratio.
First-half business operating income of Pharmaceuticals increased 15.2% to €5,657 million (up 9.6% at CER). The ratio of BOI to net sales increased by 0.5 percentage points to 37.7% (37.9% at CER).
Second-quarter and first-half Vaccines sales increased 8.7% (to €1,178 million) and 7.8%, respectively, driven by Polio/Pertussis/Hib vaccines sales as well as progressive recovery of Travel and Booster vaccines.
In the second quarter, Polio/Pertussis/Hib (PPH) vaccines sales increased 7.9% to €589 million sustained by Europe and the Rest of the World region which benefitted from strong growth of Pentaxim in China due to market gains and some inventory building. In the U.S., PPH sales were impacted by
growing market share of Vaxelis. As a reminder, Vaxelis in-market sales are not consolidated and the profits are shared equally between Sanofi and Merck.
Second-quarter Meningitis sales decreased 24.7% to €153 million, reflecting U.S CDC inventory fluctuation and lower sales in Latin America.
Booster vaccines sales increased 32.1% in the second quarter to €152 million, driven by progressive recovery in the U.S. and Europe following the COVID-19 pandemic .
Second-quarter Travel and endemic vaccines continued to recover with sales increased 83.8% to €145 million, reflecting growth across all geographies.
Influenza vaccines sales decreased 5.9% to €115 million in the second quarter, reflecting lower sales in the southern hemisphere impacted by unfavorable phasing, partially offset by a reversal of reserve for returns in Europe related to 2021 sales.

Vaccines business operating income
In the second quarter, business operating income (BOI) increased 26.5% (up 14.6% at CER) to €286 million compared to the same period of last year, reflecting strong sales growth despite higher R&D expenses related to Translate Bio and the mRNA center of excellence. BOI to net sales ratio was 24.3% (23.3% at CER) versus 22.1% for the same period of 2021.
In the first half of 2022, BOI of Vaccines decreased 2.5% (down 9.9% at CER) to €582 million reflecting the payment from Daiichi Sankyo recorded in the first quarter of 2021. The ratio of BOI to net sales was 26.5% (25.8% at CER) versus 30.8% in the first half of 2021, 24.7% excluding the payment from Daiichi Sankyo).

In the second quarter, Consumer Healthcare (CHC) sales increased 9.1% to €1,265 million sustained by double digit growth in Europe and Latin America. This performance was due to by the strong demand for Cough & Cold products driven by a strong season, including COVID-19, as well as the growth of the Digestive Wellness, Allergy and Pain Care categories. This global performance includes a positive price effect of 3.5 percentage points (ppt). The divestments of non-core products had a negative impact of 1.4 ppt in the second quarter. First-half CHC sales increased 13.1% due to the strong cough and cold season as well as growth in the Pain care, Digestive Wellness and Allergy categories which more than offset the divestments of non-core products (-1.0 ppt impact).
In the U.S., second-quarter CHC sales increased 3.1% to €335 million driven by double-digit growth of Allergy and single-digit growth of Personal Care categories partially offset by lower sales of Digestive Wellness.
In Europe, second-quarter CHC sales increased 17.9% to €375 million mainly reflecting strong growth of the Cough & Cold, Allergy and Digestive Wellness categories.
In Rest of World, second-quarter CHC sales increased 6.8% to €555 million, supported by growth in all main categories.

CHC business operating income
In the second quarter, business operating income (BOI) of CHC increased 25.5% (up 17.5% at CER) to €423 million. The ratio of BOI to net sales increased 2.5 percentage point to 33.4% (33.3% at CER) versus the prior year reflecting the strong sales growth. In the first half, BOI of CHC increased 39.4% (up 33.9% at CER) to €1,019 million due to strong sales growth and higher capital gains related to divestments of non-strategic assets. The ratio of BOI to net sales increased 6.1 percentage points to 39.3% (39.3% at CER).

Second-quarter and first-half sales in the U.S. increased 12.7% (to €4,078 million) and 12.4%, respectively, supported by the strong performance of specialty care driven by Dupixent.
In Europe second-quarter and first-half sales increased 5.7% (to €2,375 million) and 6.2%, respectively, mainly driven by Dupixent performance as well as strong Vaccines and CHC growth.
In Rest of World second-quarter and first-half sales increased 5.3% (to €3,663 million) and 6.2% respectively, reflecting the performance of Specialty care driven by Dupixent and growth of Vaccines and CHC sales. Sales in China increased 11.2% to €798 million mainly as a result of the growth of Dupixent, Plavix and Vaccines which was partially offset by the impact of VBP. In Japan, second-quarter sales increased 6.6% to €403 million driven by Dupixent and Sarclisa which more than offset lower sales of Plavix. In Russia, after unprecedented stockpiling at pharmacy and patient level in the first quarter, second-quarter sales decreased 14.1% to 156 million. In March, Sanofi has stopped any new spending not related to the supply of its essential and life-changing medicines and vaccines in Russia. This includes all advertising and promotional spending.
R&D update at the end of the second quarter 2022

Regulatory update
•The U.S. Food and Drug Administration (FDA) has approved Dupixent (dupilumab) 300 mg weekly to treat adults and adolescents aged 12 years and older with eosinophilic esophagitis (EoE). With this approval, Dupixent becomes the first and only medicine specifically indicated to treat EoE in the U.S.
•The FDA has approved Dupixent for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
•The EC has expanded the marketing authorization for Dupixent in the European Union, for the treatment of children aged 6 to 11 years as an add-on maintenance treatment for severe asthma with type 2 inflammation characterized by raised blood eosinophils and/or raised fractional exhaled nitric oxide (FeNO), who are inadequately controlled with medium to high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment.
•The FDA has accepted for priority review the supplemental Biologics License Application (sBLA) for Dupixent to treat adults with prurigo nodularis (PN), a chronic inflammatory skin disease that causes extreme itch and skin lesions.
•The EC has approved Xenpozyme (olipudase alfa) as the first and only enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD) in pediatric and adult patients with ASMD type A/B or ASMD type B. Given the urgent unmet medical needs of the ASMD community, the European Medicines Agency (EMA) granted Xenpozyme PRIority MEdicines (PRIME) designation.
•The European Commission has granted marketing authorization for Nexviadyme (avalglucosidase alfa), an enzyme replacement therapy (ERT) for the long-term treatment of both late-onset and infantile-onset Pompe disease, a rare, progressive and debilitating muscle disorder. Nexviadyme is the first and only newly approved medicine for Pompe disease in Europe since 2006, when the European Commission authorized the marketing of alglucosidase alfa, branded Myozyme. As a reminder, in November 2021, the Committee for Medicinal Products for Human Use (CHMP) issued an opinion not to grant New Active Substance (NAS) status to avalglucosidase alfa. In April 2022, the Committee for Orphan Medicinal Product (COMP) also recommended Nexviadyme to be removed from the Community Register of Orphan Medicinal Products (OMP).

Portfolio update
Phase 3:
•The FDA has granted Breakthrough Therapy designation to efanesoctocog alfa (BIVV001) for the treatment of people with hemophilia A, a rare and life-threatening bleeding disorder, based on data from the pivotal XTEND-1 Phase 3 study. Sanofi and Sobi collaborate on the development and commercialization of efanesoctocog alfa.
•Latest results from the IKEMA clinical trial evaluating Sarclisa (isatuximab), for patients with relapsed Multiple Myeloma, in combination with carfilzomib and dexamethasone (Kd), demonstrated a median progression free survival (mPFS) of 35.7 months, compared to 19.2 months in patients treated with Kd alone, as evaluated by an Independent Review Committee.
•Two studies evaluating the effect of venglustat for the treatment of Fabry Disease and Gaucher Disease Type 3 have started and enrolled their first participants.
•Results from a prespecified pooled analysis of nirsevimab pivotal Phase 3 MELODY and Phase 2b trials demonstrated an efficacy (relative risk reduction versus placebo) of 79.5% against medically attended Lower Respiratory Tract Infections (LRTI), caused by Respiratory Syncytial Virus (RSV) in infants born at term or preterm entering their first RSV season.
•In VAT08 Stage 2 trial, positive data from the Sanofi-GSK next-generation vaccine candidate, a bivalent vaccine containing D614 and Beta (B.1.351) strains, demonstrated an efficacy of 64.7% against symptomatic COVID-19 and 72% efficacy in Omicron-confirmed symptomatic cases in an environment of high Omicron variant circulation. In previously seropositive populations, it demonstrated an overall efficacy of 75.1% against symptomatic infection, and 93.2% in Omicron-confirmed symptomatic cases.
•The VAT02 Cohort 2 study of the Sanofi-GSK next-generation COVID-19 booster candidate, a monovalent formulation containing the Beta (B.1.351) variant, induced a significant boost in
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antibody titers above baseline against multiple variants of concern (15-fold increase against D614 parent virus, 30-fold increase against Beta strain, 40-fold increase against BA.1) in adults previously primed with mRNA COVID-19 vaccines.
•In parallel, the independent COVIBOOST (VAT013) study conducted by the Assistance Publique – Hôpitaux de Paris (AP-HP) demonstrated that, following primary vaccination with two doses of Pfizer-BioNTech’s Comirnaty vaccine, the Sanofi-GSK next-generation booster candidate generated a higher immune response than Pfizer-BioNTech’s booster or the Sanofi-GSK first-generation booster. Taken together with VAT08 Stage 2 study, these data strongly indicate the potential of Sanofi-GSK’s next-generation Beta-based booster to be a relevant response to public health needs.
•In May 2022, Sanofi informed investigators participating in the Phase 3 studies of tolebrutinib in multiple sclerosis (MS) and myasthenia gravis (MG) that a limited number of cases of drug-induced liver injury (DILI) had been identified with tolebrutinib exposure in those trials. The events occurred within three months of dosing, were detected with the existing liver monitoring and the majority were determined to have concurrent complications known historically to predispose to drug-induced liver injury. Importantly, the elevations of laboratory values used for monitoring liver injury were reversible after drug discontinuation for all cases. In the same month, study protocols were revised to increase the monitoring frequency, and to exclude patients with preexisting risk factors for hepatic dysfunction from enrolment. In late June, the FDA placed a partial clinical hold on the Phase 3 studies of tolebrutinib in MS and MG. As a result, new enrollment in the U.S. was paused, and participants in the U.S. who had been in the trial for fewer than 60 days had study drug suspended. Meanwhile, more than two-thousand previously enrolled patients around the globe are continuing to receive tolebrutinib treatment. In early July, the FDA provided written notification to Sanofi requesting information pertaining to additional analyses of clinical safety data and some preclinical data. Sanofi is confident in its efforts to provide the Agency with the requested information by end of September. After submission of the response, the FDA can take up to 30 days to render their decision on whether they agree to lift the partial clinical hold, which could occur as early as Q4. In the meantime, enrollment in the clinical program continues with the revised study protocols, including enhanced safety monitoring, in most countries. Close to 190 patients were enrolled since the updated protocols came into effect in May and those patients have shown no signs of liver injury to date. Sanofi expects to finalize the recruitment of the RRMS studies, GEMINI I and GEMINI II, by the end of the year. Sanofi is working closely with the independent data monitoring committee members and investigators around the world to evaluate the effectiveness of these safety measures. Based on tolebrutinib’s strong Ph2b efficacy data and risk mitigation measures, Sanofi remains confident in the future of tolebrutinib as a potentially transformative oral treatment option for people living with MS.
Phase 2:
•The study evaluating SAR445088 for the treatment of Antibody-mediated Rejection has started and enrolled its first participants.
•The study assessing the safety and efficacy of SAR443820 for the treatment of Amyotrophic Lateral Sclerosis has started enrollment.
•Positive results from the Phase 1/2 dose-finding study evaluating the safety, pharmacokinetics and clinical activity of rilzabrutinib in adults with heavily pre-treated Immune Thrombocytopenia (ITP) were published in the New England Journal of Medicine. Results demonstrate treatment with rilzabrutinib led to a rapid and durable increase in platelet count and support an acceptable safety profile.
•The study assessing the efficacy of the investigational miRNA-21 lamidersen (also known as SAR339375), in Alport Syndrome has been discontinued for failure to meet pre-defined futility criteria.
•The development of Dupixent in Peanut Allergy has been discontinued.
Phase 1:
•The study assessing the safety and efficacy of SAR446309 (acquired with Amunix, and formerly known as AMX-818) alone and in combination with pembrolizumab in adult participants with locally advanced or metastatic HER2-expressing cancers has started enrollment.

With the war in Ukraine, Sanofi has adapted its clinical trial implementation in the region. The company decided to halt any new recruitment of patients for ongoing clinical trials in Russia and Belarus, though it will continue to treat patients already enrolled. In Ukraine, Sanofi is doing everything it can to support and supply patients currently enrolled in Sanofi-sponsored clinical trials, including transferring them within Ukraine or into neighboring countries. In anticipation of potential loss of data, Sanofi has activated new clinical sites and expanding patient enrollment in geographies not impacted by the war. This may lead to the planned primary completion dates of pivotal trials in Multiple Sclerosis and Chronic Obstructive Pulmonary Disease (COPD) to shift, previously communicated submission timelines remain unchanged.

Progress on implementation of the Corporate Social Responsibility strategy

Sanofi continues its progress to improve access to medicines
Sanofi’s Global Health Unit announces the establishment of a fund and the launch of Impact
Sanofi Global Health announces the launch of Impact, a new brand of standard of care medicines produced by Sanofi dedicated for nonprofit distribution to at-risk populations in the world’s most impoverished countries. The Impact brand, which includes insulin, glibenclamide and oxaliplatin amonst others, will enable the secure distribution of 30 Sanofi medicines in 40 lower-income countries. Considered essential by the World Health Organization, the medicines cover a wide range of therapeutic areas, including diabetes, cardiovascular disease, tuberculosis, malaria and cancer.
The company also announces the establishment of an Impact fund that will support startup companies and other innovators that can deliver scalable solutions for sustainable healthcare in underserved regions. By providing inclusive businesses financing and technical assistance, the fund will complement the GHU mission of leveraging global, regional and local investment to support the training of healthcare professionals and aiding communities in running sustainable care systems.
Sanofi expands access for underserved communities in the U.S.
Uninsured people living with diabetes in the United States will be able to obtain Sanofi insulins (Lantus, Insulin Glargine U-100, Toujeo, Admelog, and Apidra) from Sanofi’s Insulins Valyou Savings Program with a valid prescription for a fixed price of $35 for a 30-day supply. This is an enhancement to the Insulins Valyou Savings Program. Previously, the program offered a 30-day supply of Sanofi insulins for $99 up to ten boxes of SoloStar pens and/or 10 mL vials or 5 boxes of Max SoloStar pens.
The Insulins Valyou Savings Program has helped thousands of people living with diabetes save on their prescription costs since its launch in 2018. In 2021, the Insulins Valyou Savings Program was used more than 97,000 times and provided more than $37 million in savings to people living with diabetes.
This update is intended to offer more savings to individuals participating in the program.

Sanofi joins Novartis’ Beacon of Hope program to address racial inequities in clinical trials, health and education
Sanofi is proud to announce a collaboration with the Beacon of Hope program to address the root causes of disparities in health and education and to create greater diversity, equity and inclusion across R&D in the pharmaceutical industry.
Racial and ethnic minorities have historically been marginalized in clinical research. Sanofi recognizes and supports the urgency to change this situation and help correct this disparity in clinical trial participation.
Launched in July 2021 as a $33.7 million commitment from Novartis and the Novartis U.S. Foundation, Beacon of Hope began as a 10-year collaboration with Morehouse School of Medicine and 26 other Historically Black Colleges and Universities, the Thurgood Marshall College Fund, Coursera, and the National Medical Association, to work together to increase diversity among clinical trial participants and investigators; improve access to high-quality education and promising jobs; address inherent bias in the data standards used to diagnose and treat disease; and find actionable solutions to environmental and climate issues that disproportionately affect health among communities of color.

Sanofi continues its progress to limit its impact on the environment
CO2 Scope 3 emissions reduction new target
As Sanofi’s ambitious strategy to minimize its environmental impacts including climate change delivers important progress, the company has decided to upgrade its greenhouse gas (GHG) emission reduction target on scope 3, pushing it from -14% initially to -30% by 2030 as part of its carbon neutrality by 2030 ambition.
Last Q3 2021, Sanofi has pledged to achieve carbon neutrality by 2030 across all operations and its entire value chain, as well as net zero greenhouse gas emissions by 2050, bringing the company target date forward by 20 years compared with its previous pledge made in 2015 after COP21 and the Paris Agreement. As part of this ambition, GHG reduction targets vs 2019 baseline were set at -55% by 2030 for operations (Scopes 1 & 2) and at -14% for the value chain (Scope 3). These goals were validated by the Science Based Target initiative (SBTi). Last May Sanofi submitted to SBTi the Net-Zero Target and the upgraded Scope 3 reduction target for validation.

Evolutive Vaccine Facility in Singapore: low energy intensity and 100% electrified by design
Building a path towards carbon neutrality is not only about facilities revamping or optimization but also about designing new factories with the lowest environmental footprint.
Our new vaccine facility in Singapore maximized its energy efficiency including energy recovery in all processes and is 100% electrified and with gas-boiler replaced by heat-pumps and energy recovery in all processes. All available surfaces are equipped with solar panels to generate renewable electricity. The remaining electricity supply will be sourced from renewable alternatives such as long-term power purchase agreements and renewable energy certificates, with the objective to source 100% renewable electricity by 2030, in line with Sanofi RE100 commitment.

ESG dashboard
In 2020, as Sanofi renewed its CSR ambitions, the Company reviewed and updated its portfolio of initiatives. Numbers shown below highlight the ongoing progress in the implementation of Sanofi’s integrated CSR strategy.
Data in YTD unless stated otherwise
Affordable access
Sanofi Global Health, a non-profit unit formed within the company in April 2021, aims to provide 30 of Sanofi’s medicines across a wide range of therapeutic areas to patients in 40 of the lowest income countries. Beyond the products provided, Sanofi Global Health works on integrating programs that ensure optimal care management over time for patients.
Sanofi is also committed to helping 1,000 patients living with rare diseases who have no access to treatments and will donate 100,000 vials of medicine for their treatments each year. This continues Sanofi’s 30-year commitment to patients suffering from rare diseases, such as Fabry, Gaucher or Pompe diseases, for which access to treatment is often limited.
The third initiative on access is to develop a global access plan for all new products, making them available in selected relevant markets within two years of launch.

R&D for unmet needs
Sanofi continues its efforts to fight polio and sleeping sickness, two of its legacy programs that address global health issues.
Sanofi has been involved in the fight against polio from the beginning and continues to play a critical role in the delivery of polio vaccines. The Company has also committed to collaborate with WHO to eliminate sleeping sickness by 2030.

In and beyond the workplace
As a global company, Sanofi is committed to ensuring that its leaders reflect the communities and patients it serves. The Company is committed to continue fostering an organization where all employees have equal opportunities to reach positions of responsibility within the company. Sanofi’s ambition is to have 40% of women in top executive roles and 50% of women in senior leadership roles by 2025. Sanofi is continuing its social and economic engagement in the communities it operates in. Finally, Sanofi is embedding its commitment to society in its leaders’ career development paths to strengthen the social impact of their decisions.

Second-quarter and first-half 2022 financial results
Business Net Income4
In the second quarter of 2022, Sanofi generated net sales of €10,116 million, an increase of 15.7% (up 8.1% at CER). First-half net sales were €19,790 million up 14.2% (up 8.4% at CER).
Second-quarter other revenues increased 108,0% (up 85.0% at CER) to €626 million, including increased VaxServe sales of non-Sanofi products of €393 million (up 53.5 % at CER). In the first half, other revenues increased 68.6% (up 54.7% at CER) to €1,005 million, including VaxServe sales of non-Sanofi products of €679 million (up 35.0% at CER).
Second-quarter Gross Profit increased 21.1% (up 12.2% at CER) to €7,493 million. The gross margin ratio increased 3.3 percentage points to 74.1% versus the same period of 2021, reflecting strong improvement of the Pharmaceuticals gross margin ratio (which increased from 74.9% to 78.5%) driven by favorable product mix and efficiency gains. The Vaccines gross margin ratio increased to 59.3% from 56.5%. CHC gross margin ratio was 66.3%, up 0.3 percentage points. In the first half, the gross margin ratio increased 2.6 percentage point to 74.1% (73.6% at CER) driven by Pharmaceuticals combined with efficiency gains.
Research and Development (R&D) expenses were up 18.8% (up 12,8% at CER) to €1,658 million in the second quarter, reflecting increased expenses in pharmaceuticals priority assets development as well as in Vaccines. In the first half, R&D expenses increased 18.2% to €3,147 million (up 13.4% at CER).
Second-quarter selling general and administrative expenses (SG&A) increased 10.1% to €2,574 million. At CER, SG&A expenses were up 2.8%, reflecting increased commercial investments in Specialty Care growth drivers coupled with a strict control of expenses. In the second quarter, the ratio of SG&A to sales decreased 1.3 percentage points to 25.4% compared to the prior year. In the first half, SG&A expenses increased 9.3% to €4,953 million (up 3.5% at CER) and the ratio of SG&A to sales was 1.1 percentage point lower at 25.0% compared to the same period of 2021.
Second-quarter and first-half operating expenses were €4,232 million, (up 13.4% and 6.6% at CER) and €8,100 million (up 12.6% and 7.2% at CER).
Second-quarter other current operating income net of expenses was €-523 million versus €-198 million in the second quarter of 2021. Other current operating income net of expenses included an expense of €621 million (versus an expense of €307 million in the second quarter of 2021) corresponding to the share of profit to Regeneron of the monoclonal antibodies Alliance, reimbursement of development costs by Regeneron and the reimbursement of commercialization-related expenses incurred by Regeneron. In the second quarter, this line also included €24 million of net capital gains related to General Medicines portfolio streamlining compared to €47 million in the same period of 2021. In the first half of 2022, other current operating income net of expenses was €-788 million versus €-299 million in the same period of 2021 and included €256 million of net capital gains related to portfolio streamlining compared to €103 million in the same period of 2021. The first-half 2022 expense associated with the monoclonal antibodies Alliance with Regeneron was €1,098 million, which compared with €586 million in the same period of 2021 (see appendix 7 for further details).
The second-quarter and first-half share of profit from associates was €25 million and €55 million versus €17 million and €26 million in the same periods of 2021, respectively, and included the share of U.S profit related to VaxelisTM.
Second-quarter business operating income4 (BOI) increased 21.5% to €2,753 million. At CER, BOI increased 13.2%. The ratio of BOI to net sales increased 1.3 percentage points to 27.2% mainly reflecting gross margin ratio improvement. In the first half, business operating income was €5,818 million, up 18.7% (up 12.7% at CER). In the first half, €230 million of savings were generated of which €200 by Industrial Affairs and fully reinvested in key programs in R&D. In the first half, the ratio of business operating income to net sales increased 1.1 percentage points to 29.4% (29.4% at CER).
Net financial expenses were €-77 million and €-155 million in the second quarter and the first half of 2022, respectively, versus €-76 million and €-160 million in the same periods of 2021.
Second-quarter and first-half 2022 effective tax rate was 19.0% versus 21.0% in the prior year. Sanofi expects its effective tax rate to be around 19% in 2022.
Second-quarter business net income4 increased 25.4% to €2,170 million and increased 16.6% at CER. The ratio of business net income to net sales increased 1.7 percentage points to 21.5% versus the second quarter of 2021. In the first half of 2022, business net income increased 22.6% to €4,594 million and increased 16.3% at CER. The ratio of business net income to net sales increased 1.6 percentage points to 23.2% versus the same period of 2021.

In the second quarter of 2022, business earnings per share4 (EPS) was €1.73, up 25.4% on a reported basis (up 16.7% at CER). The average number of shares outstanding was 1,250.8 million versus 1,251.3 million in second quarter of 2021. In the first half of 2022, business earnings per share8 was €3.68, up 22.7% on a reported basis and up 16.3% at CER. The average number of shares outstanding was 1,250.0 million versus 1,250.3 million in the first half of 2021.

Reconciliation of IFRS net income reported to business net income (see Appendix 4)
In the first half of 2022, the IFRS net income was €3,184 million. The main items excluded from the business net income were:
•An amortization charge of €910 million related to fair value remeasurement on intangible assets of acquired companies (primarily Genzyme: €273 million, Bioverativ: €181 million, Boehringer Ingelheim CHC business: €95 million, Ablynx: €84 million and Kadmon: €77 million and to acquired intangible assets (licenses/products: €57 million). These items have no cash impact on the Company.
•An impairment of intangible assets of €87 million.
•Restructuring costs and similar items of €792 million related to streamlining initiatives.
•A €573 million tax effect arising from the items listed above, mainly comprising €218 million of deferred taxes generated by amortization and impairments of intangible assets and €199 million associated with restructuring costs and similar items (see Appendix 4).

EUROAPI spin-off impact on Sanofi IFRS accounts

The line "Other gains and losses, Litigations" includes EUROAPI pre-tax deconsolidation gain of €10 million following distribution in kind of EUROAPI shares on May 10 2022.
At that date, Sanofi lost control ceasing consolidating EUROAPI. Sanofi derecognized 100% of EUROAPI net book value assets €1 227 million including goodwill. Other impacts are:
•an equity reduction of an amount of €793 million corresponding to the fair value of the distribution in kind measured at the EUROAPI market share price observed on Euronext at that date,
•the cash-in on June 17, 2022 from the 12% of the share capital of EUROAPI acquired by the French State, through its French Tech Sovereignty fund, EPIC BPIFrance, for a amount of €150 million,
•the retained interest in EUROAPI measured at fair value for an amount of €413 million.
The "Tax income" line includes €102 million gain following EUROAPI transaction.

Capital Allocation
In the first half of 2022, free cash flow before restructuring, acquisitions and disposals decreased by 17.6% to €3,735 million, after net changes in working capital (€-710 million) and capital expenditures (€-696 million). After acquisitions5 (€-419 million), proceeds from disposals5 (€541 million) and payments related to restructuring and similar items (-€615 million), free cash flow6 decreased 3.3% to €3,242 million. After the acquisition of Amunix (-€875 million), the dividend paid by Sanofi (-€4,168 million), net debt increased from €9,983 million at December 31, 2021 to €12,190 million at June 30, 2022 (amount net of €6,899 million cash and cash equivalents).

Pieris Pharmaceuticals to Host Second Quarter 2022 Investor Call and Provide Corporate Update on August 4, 2022

On July 28, 2022 Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases, cancer and other indications, reported that it will host a second quarter 2022 investor call on Thursday, August 4, 2022 at 8:00 AM EDT to discuss financial results and provide a corporate update (Press release, Pieris Pharmaceuticals, JUL 28, 2022, View Source [SID1234617086]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

To access the call, participants may dial (800) 285-6670 (Toll Free US & Canada) or (713) 481-1320 (International) at least five minutes prior to the start of the call. Alternatively, a listen-only audio webcast of the call can be accessed here.

For those unable to participate in the conference call or listen to the webcast, a replay will be available on the Investors section of the Company’s website, www.pieris.com.

PFIZER REPORTS SECOND-QUARTER 2022 RESULTS

On July 28, 2022 Pfizer Inc. (NYSE: PFE) reported that strong financial results for second-quarter 2022 and updated certain components of 2022 financial guidance(4) (Press release, Pfizer, JUL 28, 2022, View Source [SID1234617085]). Pfizer reaffirmed its previous 2022 revenue guidance, despite unfavorable impacts from foreign exchange, while reaffirming its revenue guidance for Comirnaty(1), the Pfizer-BioNTech SE (BioNTech) COVID-19 vaccine, and for Paxlovid, its oral COVID-19 treatment.

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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The second-quarter 2022 earnings presentation and accompanying prepared remarks from management as well as the quarterly update to Pfizer’s R&D pipeline can be found at www.pfizer.com.
EXECUTIVE COMMENTARY
Dr. Albert Bourla, Chairman and Chief Executive Officer, stated: "In multiple meaningful ways, we made significant progress this quarter on our strategies to bring value to our patients and shareholders, while also making commitments to prioritize the broader needs of the world, including those of the environment and our most vulnerable populations. For example, we set an ambitious goal for ourselves to achieve the Net-Zero Standard for greenhouse gas emissions by 2040, ten years ahead of the timeline described in the standard. We also launched an initiative to help bring all of our current and future patented medicines and vaccines to the 1.2 billion people living in 45 lower-income countries around the world at not-for-profit prices, a first in the industry."
Dr. Bourla continued: "Even while launching these initiatives to support a healthier, more equitable world, we remain equally committed to strong financial execution on behalf of our shareholders. In the second quarter, we
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recorded the largest amount of quarterly sales in our history. We also presented potentially best-in-class data for etrasimod and announced the proposed strategic acquisition of Biohaven, both of which are closely tied to our purpose: Breakthroughs that change patients’ lives."
David Denton, Chief Financial Officer and Executive Vice President, stated: "I am very pleased with the performance of our business this quarter, with strong operational revenue and earnings growth driven by multiple therapeutic areas across the company, and our COVID-19 franchises continuing to serve patients in need while also propelling us to an all-time high in quarterly sales. We continue to prioritize high-value uses for our capital, with an emphasis on reinvesting in our business by funding both internally and externally developed science and innovation while also continuing to grow our dividend and buy back shares, when appropriate, to help offset dilution. I am confident that Pfizer is well-positioned to continue to deliver exceptional value for our patients and shareholders going forward."

Beginning in the first quarter of 2022, Adjusted(3) financial measures include expenses for all acquired in-process research and development (IPR&D) costs incurred in connection with upfront and milestone payments on collaboration and in-license agreements, including premiums on equity securities, as well as asset acquisitions of acquired IPR&D and are reported as a separate income statement line item. Previously, these costs were recorded within the R&D expenses line item and certain of these costs were excluded from Adjusted(3) results. The change to include all acquired IPR&D expenses within Adjusted(3) results had no impact on Adjusted(3) diluted EPS in second-quarter 2022 and negatively impacted Adjusted(3) diluted EPS by $0.03 in second-quarter 2021.
Also in the first quarter of 2022, Pfizer implemented a change in policy to exclude all amortization of intangibles from Adjusted(3) income, which favorably impacted Adjusted(3) diluted EPS by $0.02 in second-quarter 2022 and by $0.03 in second-quarter 2021.
Prior period amounts have been revised to conform to the current period presentation for both amortization of intangibles and acquired IPR&D.
Business development activities(6) completed in 2021 and 2022(5) impacted financial results in the periods presented. Some amounts in this press release may not add due to rounding. All percentages have been calculated using unrounded amounts. References to operational variances pertain to period-over-period changes that exclude the impact of foreign exchange rates(7).
2022 FINANCIAL GUIDANCE(4)
Pfizer raised its 2022 financial guidance, on an operational basis(7), for revenues and Adjusted diluted EPS(3) by approximately $2 billion and $0.24, respectively. After including the expected incremental unfavorable impacts of changes in foreign exchange rates since last quarter’s earnings report, the guidance range for revenues remains unchanged and the bottom end of the guidance range for Adjusted diluted EPS(3) was increased by $0.05.
▪Comirnaty(1) revenues of approximately $32 billion, which reflects favorable operational updates compared to prior guidance, offset by unfavorable incremental impacts from foreign exchange. This guidance includes doses expected to be delivered in fiscal 2022(5), primarily under contracts signed as of mid-July 2022.
▪Paxlovid revenues of approximately $22 billion, which reflects favorable operational updates compared to prior guidance, offset by unfavorable incremental impacts from foreign exchange. This guidance includes treatment courses expected to be delivered in fiscal 2022(5), primarily relating to supply contracts signed or committed as of mid-July 2022.
The midpoint of the guidance range for Adjusted diluted EPS(3) reflects a 65% operational increase over the 2021 Adjusted diluted EPS(3) of $4.06, which has been revised from its original presentation to exclude all amortization of intangibles and to include the impact of all acquired IPR&D expenses.
Financial guidance for Adjusted diluted EPS(3) is calculated using approximately 5.75 billion weighted average shares outstanding, and assumes no additional share repurchases in 2022. The expected increase in weighted average shares outstanding compared to 2021 of approximately 50 million shares has an unfavorable impact on 2022 Adjusted diluted EPS(3) of $0.03 at the midpoint of the guidance range.
Other components of Pfizer’s 2022 financial guidance, all of which are presented with the expected impacts from changes in foreign exchange rates included, are presented below.
Guidance for Adjusted(3) SI&A expenses was decreased by $300 million compared to the previous guidance range, primarily reflecting lower expected selling expenses for certain products and geographies, as well as a decline in deferred compensation savings plan expenses, which are tied to market performance.
The midpoint of the guidance range for Adjusted(3) R&D expenses was increased by $250 million compared to the previous guidance, primarily as a result of planned incremental investments in mRNA vaccine programs outside of COVID-19 as well as various other projects.
Guidance for the effective tax rate on Adjusted(3) income was lowered by 0.5 percentage points compared to the
previous guidance, reflecting favorability in the jurisdictional mix of earnings, settlements of global tax examinations and the expiration of local statutes of limitations, among other drivers.
CAPITAL ALLOCATION
During the first six months of 2022, Pfizer deployed its capital in a variety of ways, which primarily include the following two broad categories:
▪Reinvesting capital into initiatives intended to enhance the future growth prospects of the company, including:
▪$5.1 billion invested in internal research and development projects, and
▪More than $7 billion invested in completed business development transactions, including approximately $6.3 billion for the acquisition of Arena Pharmaceuticals, Inc.
▪Returning capital directly to shareholders through a combination of:
▪$4.5 billion of cash dividends, or $0.80 per share of common stock, and
▪$2.0 billion, which was used to repurchase 39.1 million shares on the open market in March 2022, at an average cost of $51.10 per share.
In addition to the capital investments listed above, in the first six months of 2022, Pfizer announced the acquisitions of ReViral Ltd. (ReViral), which closed in the international third quarter of 2022, and Biohaven Pharmaceutical Holding Company Ltd. (Biohaven), which, upon completion, will require upfront capital investments totaling approximately $13.3 billion.
As of July 28, 2022, Pfizer’s remaining share repurchase authorization is $3.3 billion. Current financial guidance does not anticipate any additional share repurchases in 2022.
Second-quarter 2022 diluted weighted-average shares outstanding used to calculate Reported(2) and Adjusted(3) diluted EPS was 5,712 million shares, an increase of 35 million shares, primarily due to shares issued for employee compensation programs, partially offset by the impact of shares repurchased in first-quarter 2022, which resulted in a $0.01 reduction to Reported(2) and Adjusted(3) diluted EPS compared to the prior-year quarter.
QUARTERLY FINANCIAL HIGHLIGHTS (Second-Quarter 2022 vs. Second-Quarter 2021)
Second-quarter 2022 revenues totaled $27.7 billion, an increase of $8.8 billion, or 47%, compared to the prior-year quarter, reflecting operational growth of $10.1 billion, or 53%, as well as an unfavorable impact of foreign exchange of $1.3 billion, or 7%. Excluding growth from Paxlovid and Comirnaty(1), company revenues grew $128 million, or 1%, operationally.
Second-quarter 2022 operational growth was primarily driven by:
▪Paxlovid, which contributed $8.1 billion in global sales, driven by the U.S. launch under emergency use authorization in December 2021 and international launches in late 2021 and early 2022 following regulatory approvals or emergency use authorizations;
▪Comirnaty(1) globally, up 20% operationally, driven by strong operational growth in international markets, led by increased sales of doses to serve emerging markets and increased deliveries to certain international developed markets, partially offset by a slower pace of deliveries to the U.S. and Canada;
▪Eliquis globally, up 23% operationally, driven primarily by continued oral anti-coagulant adoption and market share gains in non-valvular atrial fibrillation, particularly in the U.S. and certain markets in Europe, as well as favorable changes in channel mix in the U.S.;
▪Prevnar family (Prevnar 13 & 20) in the U.S., up 41%, driven by strong stocking and patient demand following the launch of Prevnar 20 for the adult population, partially offset by unfavorable timing of government and private purchasing of Prevnar 13 for the pediatric indication; and
▪Vyndaqel/Vyndamax globally, up 16% operationally, driven by continued strong uptake of the transthyretin amyloid cardiomyopathy indication, primarily in the U.S. and developed Europe, partially offset by a planned price decrease which recently went into effect in Japan,
partially offset primarily by lower revenues for:
▪Chantix globally, down 99% operationally, which continues to be negatively impacted by a global pause in shipments of Chantix due to the presence of N-nitroso-varenicline above an acceptable level of intake set by various global regulators, the ultimate timing for resolution of which may vary by country;
▪Xeljanz in the U.S., down 35%, driven primarily by declines in net price due to unfavorable changes in channel mix, decreased prescription volumes resulting from ongoing shifts in prescribing patterns related to Janus kinase (JAK) class label changes, and unfavorable wholesaler inventory buying patterns; and
▪Sutent globally, down 47% operationally, primarily reflecting lower volume demand in the U.S. and Europe following its loss of exclusivity in August 2021 and January 2022, respectively.
Second-quarter 2022 Cost of Sales(2) as a percentage of revenues decreased 5.8 percentage points compared with the prior-year quarter. The drivers for the decrease include, among other things:
▪favorable changes in sales mix, including significant sales of Paxlovid as well as higher alliance revenues, which have no associated cost of sales; and
▪favorable impacts resulting from changes in foreign exchange rates,
partially offset by:
▪higher sales of Comirnaty(1), which includes a charge for the 50% gross profit split with BioNTech and applicable royalty expenses; and
▪a $450 million write-off of inventory related to COVID-19 products that have exceeded or are expected to exceed their approved shelf-lives prior to being used.
SI&A Expenses(2) increased 7% operationally in second-quarter 2022 compared with the prior-year quarter, primarily reflecting higher investments for Paxlovid and Comirnaty and a higher provision for healthcare reform fees based on sales of Paxlovid and Comirnaty, partially offset by a decrease in deferred compensation savings plan expenses.
Second-quarter 2022 R&D Expenses(2) increased 27% operationally compared with the prior-year quarter, primarily driven by increased investments across multiple late-stage clinical programs, including development costs and at-risk manufacturing for programs to prevent and treat COVID-19, as well as costs to develop recently acquired assets.
Acquired IPR&D Expenses(2) decreased 100% operationally in second-quarter 2022 compared with the prior-year quarter, primarily reflecting the acquisition of Amplyx Pharmaceuticals, Inc. in second-quarter 2021, and no transactions giving rise to acquired IPR&D expenses in second-quarter 2022.
Pfizer recorded $772 million of other deductions––net(2) in second-quarter 2022 compared with $1.3 billion of other income––net(2) in second-quarter 2021. The period-over-period change was primarily driven by:
▪net losses on equity securities in second-quarter 2022 versus net gains on equity securities recognized in the prior-year quarter; and
▪net periodic benefit costs associated with pension and postretirement plans incurred in second-quarter 2022 versus net periodic benefit credits recognized in second-quarter 2021.
Pfizer’s effective tax rate on Reported income(2) for second-quarter 2022 decreased compared to the prior-year quarter primarily due to a favorable change in the jurisdictional mix of earnings.
RECENT NOTABLE DEVELOPMENTS (Since May 3, 2022)
Product Developments
▪Comirnaty (COVID-19 vaccine, mRNA)(8)
▪Clinical and Research Developments
▪In May 2022, Pfizer and BioNTech announced topline safety, immunogenicity and vaccine efficacy data from a Phase 2/3 trial evaluating a third 3-µg dose of the vaccine in children 6 months to under 5 years of age. Following a third dose in this age group, the vaccine was found to elicit a strong immune response, with a favorable safety profile similar to placebo. A formal analysis will be performed when at least 21 cases have accrued from seven days after the third dose, and will be shared once available.
▪In June 2022, Pfizer and BioNTech announced positive data evaluating the safety, tolerability and immunogenicity of two Omicron-adapted COVID-19 vaccine candidates: one monovalent and the other bivalent, a combination of the current COVID-19 vaccine and a vaccine candidate targeting the spike protein of the Omicron BA.1 variant of concern. Data from the Phase 2/3 trial found that a booster dose of both Omicron-adapted vaccine candidates elicited a substantially higher immune response against Omicron BA.1 as compared to the companies’ current COVID-19 vaccine. The robust immune response was seen across two investigational dose levels, 30-µg and 60-µg. One month after administration, a booster dose of the Omicron-adapted monovalent candidates (30-µg and 60-µg) increased neutralizing geometric mean titers (GMT) against Omicron BA.1 13.5 and 19.6-fold above pre-booster dose levels, while a booster dose of the Omicron-adapted bivalent candidates conferred a 9.1 and 10.9-fold increase in neutralizing GMTs against Omicron BA.1. Both Omicron-adapted vaccine candidates were well-tolerated in participants who received one or the other Omicron-adapted vaccine.
▪In July 2022, Pfizer and BioNTech announced the initiation of a randomized, active-controlled, observer-blind, Phase 2 study to evaluate the safety, tolerability, and immune response of an enhanced COVID-19 mRNA-based vaccine candidate at a 30-µg dose level. This next-generation bivalent COVID-19 vaccine candidate, BNT162b5, consists of RNAs encoding enhanced prefusion spike proteins for the SARS-CoV-2 ancestral strain (wild-type) and an Omicron variant. The enhanced spike protein encoded from the mRNAs in BNT162b5 have been modified with the aim of increasing the magnitude and breadth of the immune response that could better protect against COVID-19. This is the first of multiple vaccine candidates with an enhanced design which the companies plan to evaluate as part of a long-term scientific COVID-19 vaccine strategy to potentially generate more robust, longer-lasting and broader immune responses against SARS-CoV-2 infections and associated COVID-19.
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▪Regulatory Developments
▪In May 2022, Pfizer and BioNTech announced that the U.S. Food and Drug Administration (FDA) expanded the emergency use authorization (EUA) for Comirnaty to include a booster dose after completion of the primary series of the vaccine in children 5 through 11 years of age. The 10-µg booster dose is given at least five months after the second dose of the two-dose 10-µg primary series.
▪In June 2022, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted to include a SARS-CoV-2 Omicron component for COVID-19 boosters in the U.S. for the fall of 2022. Following the meeting, an official recommendation stated that the FDA has asked manufacturers, including Pfizer, to develop and begin clinical trials with a modified vaccine containing an Omicron BA.4/BA.5 component.
▪In June 2022, Pfizer and BioNTech announced that the European Medicines Agency (EMA) has initiated a rolling review for a variant-adapted version of the companies’ COVID-19 vaccine. This rolling review is initially based on chemistry, manufacturing, and controls (CMC) data shared with EMA earlier in June. As clinical data become available, including data on immunogenicity against Omicron and its subvariants, it will be added to the rolling submission.
▪In June 2022, Pfizer and BioNTech announced the FDA granted EUA of Comirnaty as a three 3-µg dose series for children 6 months through 4 years of age (also referred to as 6 months to less than 5 years of age). The 3-µg dose was carefully selected as the preferred dose for children under 5 years of age based on safety, tolerability and immunogenicity data.
▪In July 2022, Pfizer and BioNTech announced that the companies have submitted a variation to the EMA requesting to update the Conditional Marketing Authorization (CMA) in the European Union (EU) with data supporting the vaccination of children ages 6 months to less than 5 years of age with the 3-µg dose of Comirnaty as a three-dose series.
▪In July 2022, Pfizer and BioNTech announced the FDA approved the companies’ supplemental Biologics License Application (sBLA) for Comirnaty to include individuals 12 through 15 years of age. The vaccine was previously made available to this age group in the U.S. under EUA, and to date more than 9 million 12- to 15-year-old adolescents in the U.S. have completed a primary series. Pfizer and BioNTech have also filed for regulatory approval of the vaccine for this age group with the EMA and other regulatory authorities around the world.
▪Commercial Developments
▪In May 2022, Pfizer and BioNTech announced an agreement with the European Commission (EC) to amend their originally agreed contractual delivery schedules for Comirnaty. The
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amendment rephases planned deliveries to help support the EC and Member States’ ongoing immunization programs and is aligned to the companies’ commitment to working collaboratively to identify pragmatic solutions to address the evolving pandemic needs. Doses scheduled for delivery in June through August 2022 will now be delivered in September through fourth-quarter 2022. This change of delivery schedule did not impact the companies’ full-year 2022 revenue guidance or the full-year commitment of doses to be delivered to EC Member States in 2022.
▪In June 2022, Pfizer and BioNTech announced a new vaccine supply agreement with the U.S. government to provide an additional 105 million COVID-19 doses (30-µg, 10-µg and 3-µg) that may include adult Omicron-adapted COVID-19 vaccines, subject to authorization from the FDA. The doses are planned to be delivered as soon as late summer 2022 and continue into the fourth quarter of this year. The U.S. government will pay the companies $3.2 billion upon delivery of the first 105 million doses. The U.S. government also has the option to purchase up to 195 million additional doses, bringing the total number of potential doses to 300 million.
▪Ibrance (palbociclib)
▪In May 2022, Pfizer announced the presentation of real-world evidence of 2,888 patients demonstrating an associated benefit for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) patients treated with Ibrance in combination with an aromatase inhibitor (AI), as compared to AI alone, in the first-line setting. After balancing for baseline demographic and clinical characteristics, palbociclib + AI versus AI alone was associated with a 24% reduction in the risk of death (HR=0.76 [95% CI, 0.65–0.87]) and a 30% reduction in the risk of disease progression (HR=0.70 [95% CI, 0.62–0.78]) in the observational, retrospective real-world analysis. Safety data were not collected as part of this analysis.
▪In June 2022, Pfizer announced overall survival (OS) results from the Phase 3 PALOMA-2 trial, which evaluated Ibrance in combination with letrozole compared to placebo plus letrozole for the first-line treatment of postmenopausal women with estrogen receptor-positive (ER+), HER2- mBC. With a median follow-up of 90 months, patients receiving Ibrance in combination with letrozole had numerically longer OS compared to placebo plus letrozole (median (95% CI) 53.9 months (49.8–60.8) vs median 51.2 months (43.7–58.9)); the results were not statistically significant. The PALOMA-2 trial was designed for a primary endpoint of progression-free survival (PFS), which was met in 2016, with OS as one of the secondary endpoints.
▪Myfembree (relugolix 40 mg, estradiol 1.0 mg and norethindrone acetate 0.5 mg)
▪In May 2022, Myovant Sciences (Myovant) and Pfizer announced the FDA had extended the review period for the supplemental New Drug Application (sNDA) for Myfembree for the management of moderate to severe pain associated with endometriosis. The FDA requires extended time to review
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additional information it had requested from the companies regarding bone mineral density. The extended Prescription Drug User Fee Act (PDUFA) goal date is August 6, 2022.
▪In June 2022, Myovant and Pfizer announced that the FDA accepted for review a sNDA for Myfembree proposing updates to Myfembree’s U.S. Prescribing Information based on safety and efficacy data from the Phase 3 LIBERTY randomized withdrawal study in premenopausal women with heavy menstrual bleeding associated with uterine fibroids for up to two years. The PDUFA goal date for this sNDA is January 29, 2023.
▪In June 2022, Myovant and Pfizer announced that results of the Phase 3 SPIRIT 1 and SPIRIT 2 studies of investigational once-daily Myfembree in over 1,200 women with moderate to severe pain associated with endometriosis were published in The Lancet. SPIRIT 1 and 2 each met their co-primary endpoints with 75% of women in the relugolix combination therapy group in both studies achieving a clinically meaningful reduction in dysmenorrhea compared with 27% and 30% of women in the placebo groups at Week 24, respectively (both p < 0.0001). For non-menstrual pelvic pain, relugolix combination therapy achieved a clinically meaningful reduction in 59% and 66% of women, compared with 40% and 43% of women in the placebo groups (p < 0.0001). In both studies, relugolix combination therapy was associated with a generally well-tolerated safety profile, including bone mineral density loss of <1% over 24 weeks.
▪Paxlovid (nirmatrelvir [PF-07321332] tablets and ritonavir tablets)(8)
▪Clinical and Research Developments
▪In June 2022, Pfizer announced data from the Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) study evaluating the use of Paxlovid in patients who are at standard risk for developing severe COVID-19. In the EPIC-SR study, the novel primary endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days was not met, as previously reported. While not all statistically significant, data from standard-risk patients, both vaccinated and unvaccinated, are supportive of efficacy data observed in the EPIC-HR study. Due to a very low rate of hospitalization or death observed in the standard-risk patient population, Pfizer decided to cease enrollment into EPIC-SR and include available data in the New Drug Application (NDA) submission to the FDA to support the use of Paxlovid in appropriate individuals at high risk of progression to severe illness.
▪Regulatory Developments
▪In June 2022, Pfizer announced the submission of an NDA to the FDA for approval of Paxlovid for the treatment of COVID-19 in both vaccinated and unvaccinated individuals who are at high risk for progression to severe illness from COVID-19, consistent with current emergency use authorization. The submission provides the longer-term follow-up data necessary for acceptance
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and potential approval. According to the U.S. Centers for Disease Control and Prevention’s (CDC) defined risk factors, 50-60% of the U.S. population aged 12 and older is estimated to have one or more risk factors for progressing to severe COVID-19 illness.
Pipeline Developments
A comprehensive update of Pfizer’s development pipeline was published today and is now available at www.pfizer.com/science/drug-product-pipeline. It includes an overview of Pfizer’s research and a list of compounds in development with targeted indication and phase of development, as well as mechanism of action for some candidates in Phase 1 and all candidates from Phase 2 through registration.
▪Elranatamab (PF-06863135) — In June 2022, Pfizer announced new data from a planned interim analysis of the Phase 2 MagnetisMM-3 registration-enabling trial of elranatamab, an investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody, in people with relapsed/refractory multiple myeloma whose disease is refractory to at least one agent in each of three major classes of medications approved for the disease. With a median follow up of 3.71 months, initial efficacy results showed that the objective response rate for elranatamab was 60.6%. The trial is still ongoing to the primary endpoint analysis with results expected later this year, which, if positive, would form the basis of potential regulatory filings.
▪Etrasimod (Selective S1P Receptor Modulator) — In May 2022, Pfizer presented detailed results from two pivotal studies that make up the ELEVATE UC Phase 3 registrational program evaluating etrasimod, a once-daily, oral, selective sphingosine 1-phosphate (S1P) receptor modulator candidate for the treatment of moderately-to-severely active ulcerative colitis (UC). Both Phase 3, multi-center, randomized, placebo-controlled trials achieved all primary and key secondary endpoints, with etrasimod demonstrating a safety profile consistent with previous studies. In the 52-week ELEVATE UC 52 study, clinical remission was 27.0% for patients receiving etrasimod compared to 7.4% for patients receiving placebo at week 12 (19.8% differential, P=˂.001) and was 32.1% compared to 6.7% at week 52 (25.4% differential, P=˂.001). In the 12-week ELEVATE UC 12 study, clinical remission was achieved among 24.8% of patients receiving etrasimod compared to 15.2% of patients receiving placebo (9.7% differential, P=.0264). The data are expected to form the basis for planned future regulatory filings, which will be initiated later this year.
▪Ervogastat (PF-06865571)/Clesacostat (PF-05221304) Combination Therapy — In May 2022, Pfizer announced the FDA had granted Fast Track designation to its investigational combination therapy of ervogastat (a diacylglycerol O-acyltransferase 2 inhibitor, or DGAT2i) and clesacostat (an acetyl-CoA carboxylase inhibitor, or ACCi) for the treatment of non-alcoholic steatohepatitis (NASH) with liver fibrosis. Pfizer is currently studying the combination in an ongoing Phase 2 clinical trial evaluating the impact of treatment on resolution of NASH or improvement in liver fibrosis, expected to complete in 2024.
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▪TTI-622 (Signal-Regulatory Protein α-Fc Fusion Protein) — In June 2022, Pfizer, MorphoSys U.S. Inc. (MorphoSys) and Incyte announced a clinical trial collaboration and supply agreement to investigate the immunotherapeutic combination of Pfizer’s TTI-622, a novel SIRPα-Fc fusion protein, and Monjuvi(9) (tafasitamab-cxix) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT). Under the terms of the agreement, Pfizer will initiate a multicenter, international Phase 1b/2 study of TTI-622 with Monjuvi and lenalidomide for patients with relapsed or refractory DLBCL who are not eligible for ASCT. MorphoSys and Incyte will provide Monjuvi for the study, which will be sponsored and funded by Pfizer and is planned to be conducted in North America, Europe and Asia-Pacific.
Corporate Developments
▪In May 2022, Pfizer and Biohaven announced that the companies have entered into a definitive agreement under which Pfizer will acquire Biohaven and its calcitonin gene-related peptide (CGRP) programs, including rimegepant, zavegepant and a portfolio of five pre-clinical CGRP assets. Under the terms of the agreement, Pfizer will acquire all outstanding common shares of Biohaven not already owned by Pfizer for $148.50 per share in cash. Biohaven common shareholders, including Pfizer, will also receive 0.5 of a share of New Biohaven, a new publicly traded company that will retain Biohaven’s non-CGRP development stage pipeline compounds, per Biohaven common share. Pfizer will pay transaction consideration totaling approximately $11.6 billion in cash. Pfizer will also make payments at closing to settle Biohaven’s third party debt and for the redemption of all outstanding shares of Biohaven’s redeemable preferred stock. New Biohaven will also have the right to receive tiered royalties from Pfizer on any annual net sales of rimegepant and zavegepant in the U.S. in excess of $5.25 billion. The proposed transaction is expected to close by early 2023, subject to the completion of the New Biohaven spin-off transaction and other customary closing conditions. All required antitrust clearances have been received.
▪In May 2022, Pfizer launched ‘An Accord for a Healthier World’, a groundbreaking initiative that seeks to greatly reduce the health inequities that exist between many lower-income countries and the rest of the world. The initiative aims to provide all of Pfizer’s current and future patented, high-quality medicines and vaccines available in the U.S. or the EU on a not-for-profit basis to 1.2 billion people in 45 lower-income countries.
▪In June 2022, Pfizer provided an update on its ownership interest in Haleon plc (Haleon), the newly independent company which holds the joint Consumer Healthcare business of GSK plc (GSK) and Pfizer following the demerger of approximately 80% of GSK’s ownership interest in the business to GSK’s shareholders and the listing of Haleon on the London Stock Exchange, which occurred in July 2022. In addition, Haleon listed American Depositary Shares (ADSs) representing Haleon ordinary shares on the New York Stock Exchange. In keeping with Pfizer’s transformation into a more focused, global leader in science-
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based innovative medicines and vaccines, Pfizer intends to exit its 32% ownership interest in Haleon in a disciplined manner, with the objective of maximizing value for Pfizer shareholders.
▪In June 2022, which falls in Pfizer’s international(5) third quarter of 2022, Pfizer completed its acquisition of ReViral, a privately held, clinical-stage biopharmaceutical company focused on discovering, developing, and commercializing novel antiviral therapeutics that target respiratory syncytial virus (RSV). ReViral brings to Pfizer a portfolio of promising therapeutic candidates, including sisunatovir, an orally administered inhibitor designed to block fusion of the RSV virus to the host cell currently in Phase 2 clinical development for both adult and pediatric populations.
▪In June 2022, Valneva SE (Valneva) and Pfizer announced the companies have entered into an equity subscription agreement and have updated the terms of their collaboration and license agreement for Lyme disease vaccine candidate VLA15. As part of the equity subscription agreement, which closed on June 22, 2022, Pfizer invested €90.5 ($95) million in Valneva, representing 8.1% of Valneva’s share capital at a price of €9.49 per share, through a reserved capital increase. Valneva will fund 40% of the remaining shared development costs compared to 30% in the initial agreement. Pfizer will pay Valneva tiered royalties ranging from 14% to 22% of net sales of VLA15, compared to royalties starting at 19% in the initial agreement. In addition, the royalties will be complemented by up to $100 million in milestones payable to Valneva based on cumulative sales. Other development and early commercialization milestones are unchanged, of which $168 million remain, including a $25 million payment to Valneva upon Pfizer’s initiation of the Phase 3 study.
▪In June 2022, Roivant Sciences (Roivant) and Pfizer announced the unveiling of Priovant Therapeutics (Priovant), a clinical-stage biotechnology company dedicated to developing and commercializing novel therapies for autoimmune diseases with the greatest morbidity and mortality. Priovant was established in September 2021 through a transaction between Roivant and Pfizer, in which Pfizer granted an exclusive license to brepocitinib and ropsacitinib to Priovant. Pfizer holds a 25% equity ownership interest in Priovant.
▪In June 2022, Pfizer announced a commitment to further reduce Greenhouse Gas (GHG) emissions and aims to achieve the voluntary Net-Zero Standard by 2040, ten years earlier than the timeline described in the standard. As part of the commitment, Pfizer aims to decrease its GHG emissions by 95% and its value chain emissions by 90% from 2019 levels by 2040 through accelerating the transition away from fossil fuels and engaging suppliers to catalyze equivalent action. Pfizer also signed a pledge by the U.S. Department of Health & Human Services (HHS) that calls on stakeholders in the U.S. healthcare system – including hospitals, health systems, payers, suppliers and pharmaceutical companies – to reduce GHG emissions and build a more climate resilient healthcare infrastructure.

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For additional details, see the attached financial schedules, product revenue tables and disclosure notice.
(1)Comirnaty includes direct sales and alliance revenues related to sales of the Pfizer-BioNTech SE (BioNTech) COVID-19 vaccine, which are recorded within Pfizer’s Vaccines therapeutic area. It does not include revenues for certain Comirnaty-related manufacturing activities performed on behalf of BioNTech, which are included in the Pfizer CentreOne contract development and manufacturing organization. Revenues related to these manufacturing activities totaled $55 million and $101 million for second-quarter and the first six months of 2022, respectively, and $87 million for both second-quarter and the first six months of 2021.
(2)Revenues is defined as revenues in accordance with U.S. generally accepted accounting principles (GAAP). Reported net income and its components are defined as net income attributable to Pfizer Inc. and its components in accordance with U.S. GAAP. Reported diluted earnings per share (EPS) is defined as diluted EPS attributable to Pfizer Inc. common shareholders in accordance with U.S. GAAP.
(3)Adjusted income and Adjusted diluted EPS are defined as U.S. GAAP net income attributable to Pfizer Inc. common shareholders and reported EPS attributable to Pfizer Inc. common shareholders—diluted before the impact of amortization of intangible assets, certain acquisition-related items, discontinued operations and certain significant items. See the accompanying reconciliations of certain GAAP Reported to Non-GAAP Adjusted information for the second quarter and the first six months of 2022 and 2021. Adjusted income and its components and Adjusted diluted EPS measures are not, and should not be viewed as, substitutes for U.S. GAAP net income and its components and diluted EPS(2). See the Non-GAAP Financial Measure: Adjusted Income sections of Management’s Discussion and Analysis of Financial Condition and Results of Operations in Pfizer’s 2021 Annual Report on Form 10-K and Quarterly Report on Form 10-Q for the quarterly period ended April 3, 2022 and the accompanying Non-GAAP Financial Measure: Adjusted Income section of this press release for a definition of each component of Adjusted income as well as other relevant information.
(4)Pfizer does not provide guidance for GAAP Reported financial measures (other than revenues and acquired IPR&D expenses) or a reconciliation of forward-looking non-GAAP financial measures to the most directly comparable GAAP Reported financial measures on a forward-looking basis because it is unable to predict with reasonable certainty the ultimate outcome of pending litigation, unusual gains and losses, certain acquisition-related expenses, gains and losses from equity securities, actuarial gains and losses from pension and postretirement plan remeasurements and potential future asset impairments without unreasonable effort. These items are uncertain, depend on various factors, and could have a material impact on GAAP Reported results for the guidance period.
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Financial guidance for full-year 2022 reflects the following:
▪Does not assume the completion of any business development transactions not completed as of July 3, 2022, with the exception of signed transactions through mid-July 2022, which are expected to give rise to acquired in-process R&D (IPR&D) expenses during fiscal 2022.
▪Reflects an anticipated incremental negative impact of $0.11 on Adjusted diluted EPS(3) related to the inclusion of all acquired IPR&D expenses that have been incurred or are expected to be incurred for transactions signed as of mid-July 2022, which would have been excluded from Adjusted(3) results under our previous accounting policy on non-GAAP measures. This excludes any impact from the proposed acquisition of Biohaven, which is expected to close by early 2023.
▪Includes Pfizer’s pro rata share of Haleon plc’s (Haleon) anticipated earnings, which is recorded in Adjusted other (income)/deductions(3) on a one-quarter lag, and assumes no changes to Pfizer’s 32% ownership stake in Haleon in 2022.
▪Includes an estimated benefit of approximately $0.06 on Adjusted diluted EPS(3) resulting from a change in policy for intangible amortization expense in which Pfizer began excluding all amortization of intangibles from Adjusted income(3) compared to excluding only amortization of intangibles related to large mergers or acquisitions under the prior methodology. This change went into effect beginning in the first quarter of 2022 and prior period amounts have been revised to conform to the new policy.
▪Reflects an anticipated negative revenue impact of $0.6 billion due to recent and expected generic and biosimilar competition for certain products that have recently lost patent protection or that are anticipated to lose patent protection during fiscal-year 2022.
▪Exchange rates assumed are a blend of actual rates in effect through second-quarter 2022 and mid-July 2022 rates for the remainder of the year. Financial guidance reflects the anticipated unfavorable impact of approximately $5.0 billion on revenues and approximately $0.31 on Adjusted diluted EPS(3) as a result of changes in foreign exchange rates relative to the U.S. dollar compared to foreign exchange rates from 2021.
▪Guidance for Adjusted diluted EPS(3) assumes diluted weighted-average shares outstanding of approximately 5.75 billion shares, which assumes only share repurchases completed to date in 2022.
(5)Pfizer’s fiscal year-end for international subsidiaries is November 30 while Pfizer’s fiscal year-end for U.S. subsidiaries is December 31. Therefore, Pfizer’s second quarter and first six months for U.S. subsidiaries reflects the three and six months ended on July 3, 2022 and July 4, 2021, while Pfizer’s second quarter and first six months for subsidiaries operating outside the U.S. reflects the three and six months ended on May 29, 2022 and May 30, 2021.
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(6)The following business development activity, among others, impacted financial results for the current or prior fiscal year:
▪On March 11, 2022, Pfizer announced the completion of its acquisition of Arena Pharmaceuticals, Inc., a clinical-stage company developing innovative potential therapies for the treatment of several immuno-inflammatory diseases, for $100 per share, in cash. The total fair value of the consideration transferred was $6.6 billion ($6.2 billion, net of cash acquired).
▪On December 31, 2021, Pfizer completed the sale of its Meridian subsidiary, the manufacturer of EpiPen and other auto-injector products, which generated approximately $300 million in annual revenues and which previously had been managed within the Hospital therapeutic area. Beginning in the fourth quarter of 2021, the financial results of Meridian are reflected as discontinued operations for all periods presented.
▪On December 24, 2021, Pfizer entered into a multi-year research collaboration with Beam Therapeutics Inc. (Beam) to utilize Beam’s in vivo base editing programs, which use mRNA and lipid nanoparticles, for three targets for rare genetic diseases of the liver, muscle and central nervous system. Under the terms of the agreement, Pfizer paid Beam a $300 million upfront payment. If Pfizer elects to opt in to licenses for all three targets, Beam would be eligible for up to an additional $1.05 billion in development, regulatory and commercial milestone payments for a potential total deal consideration of up to $1.35 billion. Beam is also eligible to receive royalties on global net sales for each licensed program.
▪On November 17, 2021, Pfizer acquired all outstanding shares, warrants, options and deferred shares not already owned by Pfizer of Trillium Therapeutics Inc. (Trillium), a clinical-stage immuno-oncology company developing therapies targeting cancer immune evasion pathways and specific cell targeting approaches, for a price of $18.50 per share in cash, for total consideration of $2.0 billion, net of cash acquired. Pfizer accounted for the transaction as an asset acquisition since the lead asset, TTI-622, represented substantially all of the fair value of the gross assets acquired. As a result, Pfizer recorded a $2.1 billion charge in fourth-quarter 2021, representing the acquired in-process R&D asset.
▪On November 9, 2021, Pfizer and Biohaven Pharmaceutical Holding Company Ltd. (Biohaven) announced a strategic collaboration and license agreement for Pfizer to commercialize rimegepant and zavegepant for the treatment and prevention of migraines outside of the U.S., subject to regulatory approval. Upon the closing of the transaction on January 4, 2022, Pfizer paid Biohaven $500 million, including an upfront payment of $150 million and an equity investment of $350 million. Pfizer recognized $263 million for the upfront payment and premium paid on its equity
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investment in acquired IPR&D expenses. Biohaven is also eligible to receive up to $740 million in non-U.S. commercialization milestone payments, in addition to tiered double-digit royalties on net sales outside of the U.S. In addition to the milestone payments and royalties above, Pfizer will also reimburse Biohaven for the portion of certain additional milestone payments and royalties due to third parties in accordance with preexisting Biohaven agreements, which are attributed to ex-U.S. sales.
▪On July 22, 2021, Arvinas Inc. (Arvinas) and Pfizer announced a global collaboration to develop and commercialize ARV-471, an investigational oral PROTAC (PROteolysis TArgeting Chimera) estrogen receptor protein degrader. The estrogen receptor is a well-known disease driver in most breast cancers. Under the terms of the agreement, Pfizer paid Arvinas $650 million upfront and made a $350 million equity investment in Arvinas. Arvinas is also eligible to receive up to $400 million in approval milestones and up to $1 billion in commercial milestones. The companies will equally share worldwide development costs, commercialization expenses and profits.
(7)References to operational variances in this press release pertain to period-over-period changes that exclude the impact of foreign exchange rates. Although exchange rate changes are part of Pfizer’s business, they are not within Pfizer’s control and since they can mask positive or negative trends in the business, Pfizer believes presenting operational variances excluding these foreign exchange changes provides useful information to evaluate Pfizer’s results.
(8)Paxlovid and emergency uses of the Pfizer-BioNTech COVID-19 Vaccine have not been approved or licensed by the FDA. Emergency uses of Comirnaty have been authorized by the FDA, under an Emergency Use Authorization (EUA) to prevent Coronavirus Disease 2019 (COVID-19) in individuals 6 months of age and older. Comirnaty is licensed by the FDA for individuals 12 years of age and older. In addition, Comirnaty is under EUA for individuals 6 months of age and older, a third dose for certain immunocompromised individuals 5 years of age and older, a booster dose for individuals 5 years of age and older, and a second booster dose for individuals 50 years of age and older and for certain immunocompromised individuals 12 years of age and older. Paxlovid has been authorized for emergency use by the FDA under an EUA, for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg [88 lbs]) with positive results of direct SARS-CoV-2 viral testing, and who are at high-risk for progression to severe COVID-19, including hospitalization or death. The emergency uses are only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of the medical product under Section 564(b)(1) of the FD&C Act unless the declaration is terminated or authorization revoked sooner. Please see the EUA Fact Sheets at www.cvdvaccine-us.com and www.covid19oralrx.com.
(9)Monjuvi is a registered trademark of MorphoSys AG.
Adjusted income and its components and Adjusted diluted EPS are non-GAAP financial measures that have no standardized meaning prescribed by GAAP and, therefore, are limited in their usefulness to investors. Because of their non-standardized definitions, they may not be comparable to the calculation of similar measures of other companies and are presented to permit investors to more fully understand how management assesses performance. A limitation of these measures is that they provide a view of our operations without including all events during a period, and do not provide a comparable view of our performance to peers. These measures are not, and should not be viewed as, substitutes for their most directly comparable GAAP measures of Net income attributable to Pfizer Inc. common shareholders, components of Net income attributable to Pfizer Inc. common shareholders and EPS attributable to Pfizer Inc. common shareholders—diluted, respectively.
We also recognize that, as internal measures of performance, these measures have limitations, and we do not restrict our performance-management process solely to these measures. We also use other tools designed to achieve the highest levels of performance. For example, our R&D organization has productivity targets, upon which its effectiveness is measured. In addition, total shareholder return, both on an absolute basis and relative to a publicly traded pharmaceutical index, plays a significant role in determining payouts under certain of our incentive compensation plans.
Beginning in the first quarter of 2022, our reconciliation of certain GAAP reported to non-GAAP adjusted information is updated to reflect the following, and prior period information has been revised to conform to the current period presentation:
Adjusted Income and Adjusted Diluted EPS
Acquired IPR&D—Non-GAAP Adjusted financial measures include expenses for all acquired in-process research and development (IPR&D) costs incurred in connection with upfront and milestone payments on collaboration and in-license agreements, including premiums on equity securities, as well as asset acquisitions of acquired IPR&D. Previously, certain of these items were excluded from our non-GAAP adjusted results. Acquired IPR&D expenses that previously would have been excluded from non-GAAP Adjusted income but are now included in both GAAP Reported income and non-GAAP Adjusted income: (i) had no impact in the second quarter of 2022, (ii) were approximately $339 million pre-tax ($276 million, net of tax), or $0.05 per share, in the first six months of 2022 and (iii) were approximately $186 million for both pre-tax and net of tax, or $0.03 per share, in both the second quarter and first six months of 2021.
Amortization of Intangible Assets—We began excluding all amortization of intangibles from non-GAAP Adjusted income, compared to excluding only amortization of intangibles related to large mergers or acquisitions under the prior methodology, and presenting it as a separate reconciling line. Previously, the adjustment under the prior methodology was included as part of a reconciling line entitled "Purchase accounting adjustments" that we no longer separately present. The impact of this policy change resulted in a benefit of $0.02 and $0.03 on Adjusted diluted EPS in the second quarter and first six months of 2022, respectively, and $0.03 and $0.04 in the second quarter and first six months of 2021, respectively.
Acquisition-Related Items—Acquisition-related items may now include purchase accounting impacts that previously would have been included as part of a reconciling line entitled "Purchase accounting adjustments" that we no longer separately present, such as: (i) the incremental charge to cost of sales from the sale of acquired inventory that was written up to fair value, (ii) depreciation related to the increase/decrease in fair value of acquired fixed assets, (iii) amortization related to the increase in fair value of acquired debt and (iv) the fair value changes for contingent consideration.
See the reconciliations of certain GAAP Reported to Non-GAAP Adjusted information for the second quarter and first six months of 2022 and 2021 below and the Non-GAAP Financial Measure: Adjusted Income sections of Management’s Discussion and Analysis of Financial Condition and Results of Operations in Pfizer’s 2021 Annual Report on Form 10-K and Quarterly Report on Form 10-Q for the quarterly period ended April 3, 2022 for additional information.

Moleculin Concludes Phase 1b and Opens Recruitment in Phase 2 Clinical Trial of
Annamycin for the Treatment of Soft Tissue Sarcoma Lung Metastases

On July 28, 2022 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported it has completed the safety review of the fourth cohort in a dose escalation clinical trial evaluating Annamycin for the treatment of soft tissue sarcoma (STS) lung metastases, thus concluding the Phase 1b portion of its U.S. Phase 1b/2 clinical trial (Press release, Moleculin, JUL 28, 2022, View Source [SID1234617084]). Preliminary results from the study continue to document clinical activity for Annamycin in the treatment of STS. The safety review committee (SRC) has deemed the dose of 390 mg/m2 to be safe after conclusion of the fourth cohort. Notwithstanding that there was safety at this dose level, tolerability issues present at the 390 mg/m2 dose level caused delays in follow-on cycles and the reduction of subsequent doses, suggesting that a Recommended Phase 2 Dose (RP2D) below 390 mg/m2 was warranted.

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With this in mind and with the recommendation of the SRC, the Company has determined that the RP2D will be 360 mg/m2 for the first three subjects in the Phase 2 portion of the study. The SRC will then review the clinical safety data at this dose and determine whether the RP2D should be further reduced to 330 mg/m2 prior to proceeding with the additional 22 subjects. In addition to continuing to assess safety, including gathering additional information about short-term side effects and possible risks, this Phase 2 portion of the study will also explore the efficacy of Annamycin as a single agent for the treatment of subjects with STS lung metastases for whom prior chemotherapy has failed, and for whom new chemotherapy is considered appropriate.

In the Phase 1b portion of the study, 15 subjects were enrolled and treated per the protocol in four cohorts to determine the maximum tolerable dose and/or the RP2D. Each cohort had three subjects, except for the fourth cohort, which (per the protocol) was expanded to six subjects after a dose-limiting toxicity (DLT) occurred in a single subject. The Company concluded the Phase 1b portion after the fourth cohort of 390 mg/m2 was documented to be safe. Up to 28 subjects, to account for potential over enrollment, will be enrolled at the RP2D in Phase 2 to focus more on quantifying efficacy as well as providing additional safety information.

"As we end the Phase 1b portion of this trial, the preliminary data continue to be encouraging," said Moleculin Chairman and CEO Walter Klemp. "Of the fifteen subjects treated per the protocol, two continue with treatment, and eight subjects have been followed without evidence of disease progression for two months or greater, with three of the eight free of disease progression for 120 days or more. These data are early-stage, and we look forward to developing confirmatory data from future studies. However, based on the data available thus far, we believe Annamycin has the potential to bring a new and effective treatment option to patients with significant unmet needs."

Mr. Klemp added, "We’re also encouraged by the pace of recruitment to date for this trial. To have completed the Phase 1b in just over one year was faster than we expected, especially for a rare disease like STS lung metastases. This is encouraging as we open the Phase 2 portion of the study."

The summary of interim Phase 1b data, which are preliminary and subject to change, from the four cohorts of the study are as follows:

First Cohort (210 mg/m2):

Two subjects received 6 cycles of Annamycin, initially having stable disease, and were then discontinued due to progressive disease.
One subject received 1 cycle, but then discontinued from the study because of a Dosing Delay greater than the time between doses permitted by the protocol. At the End of Study scan performed 39 days post initiation of treatment, the subject had stable disease. The subject was followed and continued to exhibit disease free progression up to 61 days after treatment, at which point the subject began a different therapy.
Second Cohort (270 mg/m2):

In one subject, the end of cycle 2 scan showed a partial response (≥30% reduction in tumor size), and when scanned at the end of cycle 4 the subject showed stable disease. The subject subsequently discontinued from the study, electing to undergo surgical resection to potentially eradicate the disease. The subject is continuing to be followed and at the last follow-up no disease progression was reported at 272 days.
One subject was discontinued from the study when the end of cycle 2 scan revealed progressive disease.
One subject received 1 cycle of treatment and discontinued treatment due to a Dosing Delay. The End of Study scan revealed progressive disease.
Third Cohort (330 mg/m2):

One subject received 1 cycle and was discontinued when an interim, unscheduled scan revealed progressive disease.
One subject was discontinued from the study when the end of cycle 2 scan revealed progressive disease.
One subject was treated with 2 cycles and the end of cycle 2 scan revealed stable disease. The subjected elected to withdraw from receiving any further treatment. The subject was followed and no disease progression was reported at 146 days. The subject elected at that time to discontinue from further follow-up in the study.
Fourth Cohort (390 mg/m2):
Efficacy data for this cohort are incomplete as not all subjects have received their scans and treatment is ongoing.

One subject received 3 cycles of treatment without evidence of any DLTs, with the last 2 cycles at a reduced dose of 292 mg/m2 due to a drug tolerability issue that did not qualify as a DLT. The subject exhibited stable disease at the end of cycle 2. The subject showed progressive disease in the end of treatment scan on the 78th day.
One subject was discontinued from the study after 2 cycles with cycle 2 administered at a reduced dose of 292 mg/m2. The subject discontinued receiving cycles because of a DLT of febrile neutropenia, and the cohort was expanded per the protocol. The end of cycle 2 scan revealed stable disease. The subject initiated additional therapy unrelated to the study on the 68th day and will continue to be followed for Overall Survival.
One subject received 3 cycles of treatment without evidence of any DLTs, with the last 2 cycles administered at reduced doses, due to drug tolerability. The subject exhibited stable disease at the end of cycle 2. The subject showed progressive disease in an unscheduled scan on the 79th day.
One subject received 4 cycles without evidence of any DLTs, with the last three cycles administered at a reduced dose of 292 mg/m2, due to drug tolerability. The end of cycle 4 scans revealed stable disease. The subject is ongoing in the study.
One subject received 3 cycles without evidence of any DLTs, with the last two cycles administered at a reduced dose of 292 mg/m2, due to drug tolerability. The end of cycle 2 scans revealed stable disease. The subject is ongoing in the study.
One subject received 1 cycle without evidence of any dose-limiting toxicities and is ongoing in the study.
One subject received a markedly lower dose than the specified 390 mg/m2 in a protocol violation by the site, also without evidence of any DLTs. That subject’s safety data, but not efficacy, is deemed to be evaluable in the study.
"Consistent with our earlier and ongoing acute myeloid leukemia trials, in the subjects evaluated to date we have seen a complete absence of cardiotoxicity in our trials," Mr. Klemp said. "Again, these are early-stage data, but we’re seeing consistent results in this regard across our Annamycin studies, and we think they’re important because, even though anthracyclines are considered a cornerstone chemotherapy for many types of cancer including STS lung metastases, all currently approved anthracyclines are significantly cardiotoxic. Annamycin was designed to overcome this problem and we believe it has the potential to become the first non-cardiotoxic anthracycline approved for use. If these data continue and our product is approved, Annamycin may not only reduce the risk of many current anthracycline treatment regimens, but it could also enable longer treatment periods with reduced concern for cardiac risk."

Annamycin currently has Fast Track Status and Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of soft tissue sarcoma, in addition to Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia. For more information about the Phase 1b/2 study evaluating Annamycin for the treatment of STS lung metastases, please visit clinicaltrials.gov and reference identifier NCT04887298.

Study Design
In Phase 1b, Annamycin was administered as an intravenous (IV) infusion over 2 hours on Day 1, followed by 20 days off (1 cycle = 21 days). Subjects visit the study site every 21 days (±3 days) at which time safety monitoring – including for adverse events (AEs), as well as a physical examination, laboratory evaluations (clinical chemistry, complete blood count), vital signs, weight measurements, Eastern Cooperative Oncology Group (ECOG) performance status, and electrocardiograms (ECGs) – is performed, followed by an IV infusion of study drug. Cardiac function is followed by echocardiogram (ECHO) scans at screening, at the end of the first two cycles and then following every other cycle thereafter, at the End of Treatment visit, and if feasible, during follow up at 6 months (±1 month) and 1 year (±1 month) after study drug discontinuation. As long as the Investigator considers that the benefits of treatment with Annamycin continue to outweigh the risks, treatment will continue every 21 days until tumor progression is observed or unacceptable toxicity occurs.

Tumor response is monitored every 6 weeks (±1 week) from Cycle 1 Day 1 during treatment, at the End of Treatment visit, and then every 3 months (±1 month) until disease progression using RECIST 1.1 criteria. Those subjects who leave the study after a maximum response is achieved and who do not start another therapy will be followed every 3 months (±1 month) for progression-free survival (PFS). If a subject receives further therapy after discontinuing from the study, they will be followed only for overall survival (OS) and if feasible, follow-up ECHO scans at 6 months (±1 month) and 1 year (±1 month) will be conducted after study drug discontinuation.

About Annamycin
Annamycin is the Company’s next-generation anthracycline that has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin. Importantly, Annamycin has also demonstrated a lack of cardiotoxicity in multiple early-stage human clinical trials, including ongoing trials for the treatment of acute myeloid leukemia (AML) and STS lung metastases. For that reason, although additional data will be necessary, the Company believes Annamycin may not face the same usage limitations imposed on doxorubicin, one of the most common currently approved anthracyclines. Annamycin is currently in development for the treatment of AML and STS lung metastases and the Company believes the drug may have the potential to treat additional indications.