On May 6, 2021 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported financial results for the first quarter ended March 31, 2021 and discussed recent corporate updates (Press release, Bicycle Therapeutics, MAY 6, 2021, View Source [SID1234579374]).

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"We’ve had a great start to 2021, as we advance multiple Bicycle Toxin Conjugates (BTCs) in the clinic, prepare for BT7480, our lead tumor-targeted immune cell agonist, to enter the clinic later this year and continue to expand the use of our platform outside of oncology, while also significantly strengthening our balance sheet," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "We plan to build on this momentum during the year, and our presentation of preclinical data at AACR (Free AACR Whitepaper) serves to highlight the potential therapeutic benefits that Bicycles may offer toward improving the treatment paradigms for people living with cancer and other serious diseases."

First Quarter 2021 and Recent Highlights

Presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021. In April 2021, Bicycle presented new preclinical data describing the discovery of BT7480, a novel Nectin-4/CD137 Bicycle tumor-targeted immune cell agonistTM (Bicycle TICA) during a "New Drugs on the Horizon" session. The Company expects BT7480 to enter the clinic in the second half of 2021. Additionally, the Company presented five posters and one presentation highlighting preclinical data across multiple programs in Bicycle’s oncology pipeline. The posters and presentations are available on the Publications section of bicycletherapeutics.com.

Provided Pipeline Progress Update Across Multiple Therapeutic Programs Beyond Oncology. In March 2021, Bicycle announced progress updates for its Bicycle programs outside of oncology:

Achieved first milestone in the collaboration with Dementia Discovery Fund (DDF) and the University of Oxford’s Alzheimer’s Research UK Oxford Drug Discovery Institute (ODDI): The Company identified and optimized nM affinity Bicycles to transferrin receptor 1 (TfR1), a molecular shuttle. The three parties are collaborating to identify and characterize Bicycles that bind to and activate TREM2, a genetically validated dementia target.

Advanced the platform in multiple anti-infective areas, including antimicrobials and antivirals: Innovate UK’s Biomedical Catalyst (BMC) awarded the Company funding to advance a Bicycle inhibitor for a key cell wall biosynthesis target in Enterobacterales, Penicillin Binding Protein 3 (PBP3). Bicycle, working with investigators at the University of Warwick, intends to progress these PbP3 inhibitors, potentially the first novel class of antibiotics identified in decades, to candidate and initial toxicology testing. Additionally, under a specific Innovate UK program targeting key technologies to rapidly respond to the challenge of the COVID-19 pandemic, Bicycle received funding to support its efforts to discover new healthcare solutions to SARS-CoV-2.

Made significant progress through partnerships: Bicycle successfully discovered and advanced targets outside of oncology through its ongoing collaboration with AstraZeneca, a global biopharmaceutical company, to discover novel agents for the treatment of respiratory and cardiometabolic diseases. Two assets were transitioned to AstraZeneca’s pipeline for further development. Bicycle also identified targets in its collaboration with Bioverativ (acquired by Sanofi) for the treatment of rare hematological diseases. The collaborations successfully identified nM multi-valent inhibitors to P-Selectin, which inhibited neutrophil binding and rolling, with potential applications in sickle cell disease and other inflammatory diseases. The Bioverativ collaboration also identified the first small molecule Factor VIII mimetic for the potential treatment of Hemophilia A. Upon termination of the collaboration in 2019, these "lead stage" assets have been returned to Bicycle.

Appointed Jose-Carlos Gutierrez-Ramos, Ph.D., to its Board of Directors: In March 2021, Bicycle announced the appointment of industry veteran Dr. Gutierrez-Ramos to its Board of Directors. Dr. Gutierrez-Ramos previously served as Chair of Bicycle’s Scientific Advisory Board and has extensive experience in leading biopharmaceutical companies and in academia.

Continued to Strengthen the Balance Sheet in 2021. Since January 2021, Bicycle has completed the sale of $75.0 million through its at-the-market (ATM) offering program. Gross proceeds during the first quarter of 2021 totaled $60.6 million, with an additional $14.4 million in gross proceeds recognized in April 2021. Also during the second quarter of 2021, the Company received $2.0 million from Genentech for achieving specified criteria under the collaboration research plan. Cash as of March 31, 2021 does not include the April 2021 ATM proceeds or Genentech proceeds. In addition, in March 2021, the Company drew an additional $15.0 million available under its debt facility with Hercules Capital, Inc. and amended the loan and security agreement to extend the interest-only payment period until the second half of 2023, with the potential to further extend it into 2024, contingent on the satisfaction of performance milestones.
Financial Results

Cash was $195.9 million as of March 31, 2021, compared to $136.0 million as of December 31, 2020. The increase in cash was primarily due to net proceeds of $58.8 million from the ATM offering and net proceeds of $15.0 million from the debt facility with Hercules Capital Inc., offset by cash used in operating activities. Cash at March 31, 2021 does not include net proceeds from the ATM offering received in April 2021. Cash of $195.9 million at March 31, 2021 is expected to provide financial runway through multiple clinical milestones and into 2024.
Research and development expenses were $9.7 million for the three months ended March 31, 2021, compared to $7.8 million for the three months ended March 31, 2020. The increase in expense of $1.9 million for the three months ended March 31, 2021 as compared to the same period in the prior year was primarily due to increased clinical program expenses for BT8009, a second-generation Bicycle Toxin Conjugate (BTC) targeting Nectin-4, and increased other unallocated discovery and platform related expenses due to the timing of development activities, and increased personnel-related expenses, including $0.5 million of incremental non-cash share-based compensation expense.
General and administrative expenses were $8.1 million for the three months ended March 31, 2021, compared to $5.0 million for the three months ended March 31, 2020. The increase of $3.1 million for the three months ended March 31, 2021 as compared to the same period in the prior year was primarily due to an unfavorable effect of foreign exchange rates and an increase in personnel-related costs, including $1.2 million of incremental non-cash share-based compensation expense for the three months ended March 31, 2021.
Net loss was $16.2 million, or $(0.73) basic and diluted net loss per share, for the three months ended March 31, 2021, compared to net loss of $11.3 million, or $(0.63) basic and diluted net loss per share for three months ended March 31, 2020.

On May 6, 2021 Epizyme (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company developing and delivering novel epigenetic therapies, reported first quarter 2021 financial results (Press release, Epizyme, MAY 6, 2021, View Source [SID1234579373]).

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"Adoption of TAZVERIK has steadily increased as we continue to navigate the unique launch environment presented by COVID-19. We saw month-over-month commercial demand growth, with March 2021 representing our most successful month since launch and we look to build on this momentum as the pandemic-associated challenges begin to ease," said Robert Bazemore, President and Chief Executive Officer of Epizyme. "TAZVERIK net revenues in the first quarter of 2021 increased by 37% from the fourth quarter of 2020, driven primarily by increased adoption in follicular lymphoma. The environment we operated in during the first quarter was not substantially different from the end of last year, however we are beginning to see some encouraging signs that things are slowly beginning to return to normal as vaccine adoption progresses.

"In early March, we hosted a strategic vision call to outline the pipeline-in-a-drug potential we see in TAZVERIK and plans to expand our portfolio starting with the anticipated IND submission for our novel SETD2 inhibitor in mid-2021. We plan to share additional pre-clinical data supporting the advancement of our SETD2 program at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress 2021. During the Vision Call we also shared encouraging preliminary safety and activity data from ongoing combination trials in follicular lymphoma and prostate cancer and look forward to providing a steady stream of data updates from these and our many other planned and ongoing trials over the next few years."

Recent Progress

Commercial Execution: TAZVERIK generated net product revenue in Epithelioid Sarcoma (ES) and Follicular Lymphoma (FL) of $6.2 million in the first quarter of 2021, with March 2021 representing our highest level of commercial demand since launch. Commercial bottle demand growth was 31% in the first quarter compared to the fourth quarter of 2020, while total revenue grew by 37%. New prescribing accounts increased 38% in the first quarter of 2021 compared to the fourth quarter of 2020, including broader adoption among community practice. This is despite the continued negative impact COVID-19 had on patient visits to physicians and new patient starts across all lines of treatment as well as the ability of our field-based teams to fully access physicians treating ES and FL patients.
EZH-302 Phase 1b/3 Confirmatory Study of TAZVERIK in Follicular Lymphoma: The combination of TAZVERIK with R2 (Lenalidomide and Rituximab) is being evaluated in a Phase 1b/3 confirmatory study in relapsed / refractory FL patients. Preliminary safety and activity data of 13 patients from the 400 mg, 600 mg and 800 mg cohorts of the Phase 1b safety run-in were presented during Epizyme’s Vision Call in March showing encouraging initial treatment responses in each dose group, and adverse events that were in line with expectations based on the respective safety profiles of the individual agents. Epizyme plans to submit an update to this safety run-in for presentation at the 2021 ASH (Free ASH Whitepaper) Annual Meeting later this year.

Based on recent discussions with the U.S. Food and Drug Administration (FDA), Epizyme has aligned on an important change to the Phase 3 protocol whereby the second interim analysis will include an efficacy evaluation once 65% of progression free survival (PFS) events have occurred. This allows access to efficacy data earlier than previously expected and may provide an opportunity to stop the study early should the predefined treatment effect be realized. Based on these discussions with FDA, Epizyme has also expanded the Phase 1b portion of the study to include a minimum of 15 patients in the cohorts of 600 mg BID and 800 mg BID to help inform selection of the Phase 3 dose. Enrollment is nearly complete in these two cohorts and patients are being evaluated for follow-up of three months before initiating the Phase 3 randomization portion of the trial.
Additional Ongoing Clinical Trials of Tazemetostat in Follicular Lymphoma: EZH-1401, the Company’s Phase 2 trial evaluating TAZVERIK plus Rituxan in relapsed / refractory FL continues to move forward as planned and is actively enrolling. Patient enrollment also continues in the Lymphoma Study Association (LYSA) trial in front-line FL and Diffuse Large B-cell Lymphoma (DLBCL), as well as other investigator sponsored trials.
EZH-1101 Phase 1b/2 Study of Tazemetostat in Prostate Cancer: The combination of tazemetostat with standard-of-care treatments, enzalutamide or abiraterone, was evaluated in the Phase 1b safety run-in portion of the EZH-1101 trial which enrolled a total of 21 men with metastatic prostate cancer. The Phase 1b protocol allowed patients to enroll who had previously failed enzalutamide, abiraterone, first generation anti-androgen receptor therapies or short course chemotherapy. In the study, patients received either abiraterone plus tazemetostat plus prednisone or enzalutamide plus tazemetostat. Based on encouraging preliminary safety and activity data, particularly in the enzalutamide plus tazemetostat group, Epizyme has initiated enrollment in the Phase 2 efficacy portion of this study which will evaluate enzalutamide plus tazemetostat compared to enzalutamide alone. Epizyme plans to submit an update to the Phase 1b safety run-in for presentation at a medical congress later this year.
EZH-301 Confirmatory Phase 1b/3 Study of TAZVERIK in Epithelioid Sarcoma: The combination of TAZVERIK with doxorubicin compared with doxorubicin plus placebo is being evaluated in a Phase 1b/3 confirmatory study as a front-line treatment for ES patients. We have completed the planned enrollment in the Phase 1b safety run-in portion of the trial and the Phase 3 efficacy expansion portion of the trial remains on track for initiation. Preliminary data from the Phase 1b portion of this study has been accepted as a poster presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting in June.
Tazemetostat Basket Trials in Additional Hematologic Malignancies and Solid Tumors: Epizyme plans to initiate two signal finding basket studies to evaluate tazemetostat safety and efficacy across multiple new types of hematologic malignancies and solid tumors. With this approach, the Company plans to study multiple combinations with standard-of-care therapies and novel mechanisms of action to expand the potential of tazemetostat. Epizyme plans to initiate both basket studies in the second half of 2021.
Planned IND Submission for Epizyme’s Novel SETD2 Inhibitor: Based on the potential of SETD2 inhibition in multiple settings, including high risk t(4;14) multiple myeloma and in other B-cell malignancies such as large-cell lymphoma, as monotherapy and in combination with existing and emerging therapies including tazemetostat, Epizyme is planning to submit an Investigational New Drug (IND) application with the FDA in mid-2021 and expects to initiate a first-in-human clinical trial this year.
First Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $298.9 million as of March 31, 2021, as compared to $373.6 million as of December 31, 2020.
Revenue: Total revenue for the first quarter of 2021 was $7.6 million, compared to $1.4 million for the first quarter of 2020. Total revenue for the first quarter of 2021 comprised of $6.2 million in net sales of TAZVERIK in the U.S. and $1.4 million in collaboration and other revenue.
Operating Expenses: Total GAAP operating expenses were $72.0 million for the first quarter of 2021 compared to $52.7 million for the first quarter of 2020. Total non-GAAP adjusted operating expenses were $63.7 million for the first quarter of 2021 compared to $45.7 million for the first quarter of 2020.
Cost of revenue: GAAP cost of revenue, which reflects the costs of TAZVERIK units sold, amortization of intangible assets, third-party royalties on net product revenue and costs of tazemetostat API and drug product sold to the Company’s licensees or collaborators, was $2.9 million for the first quarter of 2021 compared to $0.6 million in the first quarter of 2020. Non-GAAP adjusted cost of revenue was $1.8 million for the first quarter of 2021 compared to $0.3 million for the first quarter of 2020.
R&D expenses: GAAP R&D expenses were $32.7 million for the first quarter of 2021 compared to $25.2 million for the first quarter of 2020. Non-GAAP adjusted R&D expenses were $30.3 million for the first quarter of 2021 compared to $22.9 million for the first quarter of 2020.
SG&A expenses: GAAP SG&A expenses were $36.4 million for the first quarter of 2021 compared to $27.0 million for the first quarter of 2020. Non-GAAP adjusted SG&A expenses were $31.5 million for the first quarter of 2021 compared to $22.5 million for the first quarter of 2020.
Net Loss (GAAP): Net loss attributable to common stockholders was $70.3 million, or $0.69 per share, for the first quarter of 2021, compared to $50.9 million, or $0.51 per share, for the first quarter of 2020.
2021 Financial Guidance

Based on its current operating plans, Epizyme expects its current cash runway to extend into 2023. Additionally, the Company expects its non-GAAP adjusted operating expenses for 2021 to be between $235 and $255 million.
A reconciliation of non-GAAP adjusted financial measures directly comparable to GAAP financial measures is presented in the table attached to this press release.
Conference Call Information

Epizyme will host a conference call today, May 6, at 7:30 a.m. ET. To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 4139845. A webcast, as well as supplemental slides to support the webcast, will be available in the investor section of the Company’s website at www.epizyme.com, and will be archived for 60 days following the call.

About Non-GAAP Financial Measures

In addition to financial information prepared in accordance with the U.S. generally accepted accounting principles (GAAP), this press release includes the following non-GAAP financial measures: total non-GAAP adjusted operating expenses on a historical and projected basis, non-GAAP adjusted R&D expenses on a historical basis and non-GAAP adjusted SG&A expenses on a historical basis. Epizyme derives these non-GAAP financial measures by excluding certain expenses and other items from the respective GAAP financial measure, that is most directly comparable to each non-GAAP financial measure. Specifically, the non-GAAP financial measures exclude stock-based compensation expense and depreciation and amortization of intangibles. The company’s management believes that these non-GAAP financial measures are useful to both management and investors in analyzing its ongoing business and operating performance. Management does not intend the presentation of these non-GAAP financial measures to be considered in isolation or as a substitute for results prepared in accordance with GAAP, but as a complement to provide greater transparency. In addition, these non-GAAP financial measures may differ from similarly named measures used by other companies. A quantitative reconciliation of projected non-GAAP adjusted operating expenses to total operating expenses is not available without unreasonable effort primarily due to the company’s inability to predict with reasonable certainty the amount of future stock-based compensation expense.

About TAZVERIK (tazemetostat)

TAZVERIK is a methyltransferase inhibitor indicated for the treatment of:

Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.
Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies.
Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.
These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

On May 6, 2021 Cardinal Health (NYSE: CAH) reported third-quarter fiscal year 2021 revenue of $39.3 billion, in-line with the third quarter of last year (Press release, Cardinal Health, MAY 6, 2021, View Source [SID1234579372]). Third-quarter GAAP operating earnings decreased 16% to $473 million, primarily due to the write-down of the net assets held for sale from the planned divestiture of the Cordis business. Third-quarter GAAP diluted earnings per share (EPS) decreased to $0.40, due to the previously-disclosed tax effect of the litigation charge in the first quarter.

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Non-GAAP operating earnings decreased 4% to $689 million in the quarter due to the negative impact from COVID-19, primarily concentrated in the Pharmaceutical segment. Non-GAAP diluted EPS decreased 6% to $1.53 in the quarter, reflecting a higher non-GAAP effective tax rate, partially offset by lower interest expense.

"We remain focused on serving our customers and their patients and continue to advance our strategic priorities," said Mike Kaufmann, CEO of Cardinal Health. "With our resilient business model and strong fundamentals, we are navigating the effects of the pandemic and finding opportunities to adapt, innovate and invest for future growth."

Third-quarter revenue for the Pharmaceutical segment was flat at $35.1 billion. This reflects sales growth from Pharmaceutical Distribution and Specialty Solutions customers in the current period compared against the unfavorable prior-year comparison of the COVID-19-related acceleration in overall pharmaceutical sales.

Pharmaceutical segment profit decreased 4% to $511 million in the third quarter, primarily due to COVID-19-related volume declines in the company’s generics program. This was partially offset by a higher contribution from brand sales mix.

Third-quarter revenue for the Medical segment increased 3% to $4.2 billion, driven by a net positive impact from COVID-19 on products and distribution. This increase was primarily due to the impact of personal protective equipment (PPE) sales and higher volumes in our Lab business, partially offset by the adverse effects of reduced elective procedures.

Medical segment profit decreased 2% to $174 million in the third quarter. Cost savings, including global manufacturing efficiencies, were offset by a decline in products and distribution. Additionally, the segment experienced a slight negative impact due to COVID-19.

Tax rate
During the third quarters of fiscal 2021 and 2020, GAAP effective tax rates were 72.8% and 26.8%, respectively. The increase was primarily due to the previously-disclosed tax effect of the litigation charge in the first quarter. Non-GAAP effective tax rates were 31.2% and 25.7%, respectively, for the third quarters of fiscal 2021 and 2020. Third-quarter fiscal 2021 effective tax rates reflect the resolution of all open issues with the IRS for fiscal years 2008 to 2010 as well as certain transfer pricing matters for fiscal years 2011 to 2014, which also impacted reserves for later years.

Fiscal year 2021 outlook1
Cardinal Health narrowed its fiscal year 2021 guidance range for non-GAAP diluted earnings per share attributable to Cardinal Health, Inc. to $5.90 to $6.05, from the prior range of $5.85 to $6.10.

The company does not provide forward-looking guidance on a GAAP basis as certain financial information, the probable significance of which cannot be determined, is not available and cannot be reasonably estimated. See "Use of Non-GAAP Measures" following the attached schedules for additional explanation.

Recent highlights

Cardinal Health Board of Directors approved a 1% increase in the company’s quarterly dividend from $0.4859 per share to $0.4908 per share, or $1.96 on an annualized basis. The dividend will be payable on July 15, 2021 to shareholders of record at the close of business on July 1, 2021.
Cardinal Health announced that it signed a definitive agreement to sell its Cordis business to Hellman & Friedman (H&F) for approximately $1 billion. The company anticipates the transaction to close in the first quarter of fiscal 2022.
Cardinal Health recently launched Outcomes, a digital ecosystem that provides personalized medication therapy management, patient engagement and telepharmacy through its Connect platform, connecting pharmacists, payers and pharmaceutical companies to improve medication adherence, drive better outcomes and lower the cost of care.
Cardinal Health recently announced a partnership with FourKites, the largest predictive supply chain visibility platform, to create a cognitive supply chain network that combines real-time visibility, machine learning and artificial intelligence to facilitate the flow of inventory throughout the supply chain.
Cardinal Health Specialty Solutions launched Cardinal Health Navista Tech Solutions (TS), an advanced suite of technology solutions to help community oncologists improve outcomes and costs associated with patient treatment as they transition to value-based care.
Cardinal Health was awarded a $57.8 million contract, including options that if exercised by the U.S. Department of Health and Human Services (HHS) could reach $91.6 million, for the storage and distribution of 80,000 pallets of personal protective equipment (PPE) to support the Strategic National Stockpile (SNS).
Upcoming webcasted investor events

Bank of America Healthcare Conference at 8:45 a.m. Eastern, May 11
Webcast
Cardinal Health will host a webcast today at 8:30 a.m. Eastern to discuss third-quarter results. To access the webcast and corresponding slide presentation, go to the Investor Relations page at ir.cardinalhealth.com. No access code is required.

Presentation slides and a webcast replay will be available until May 5, 2022.

On May 6, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the first quarter of 2021 and provided a business update (Press release, Regeneron, MAY 6, 2021, View Source [SID1234579371]).

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"Regeneron had a strong first quarter highlighting our continued evolution into a company with multiple durable product lines helping people with a range of serious diseases including COVID-19," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "We recently reported positive Phase 3 results for REGEN-COV in both the COVID-19 outpatient treatment and prevention settings and are working with national and state authorities to improve access. We expect continued growth with EYLEA in retinal diseases, as well as with Dupixent through further penetration in existing indications and a broad Phase 3 development program. In oncology, we are in the early days of launching Libtayo for advanced basal cell carcinoma and non-small cell lung cancer and recently announced positive pivotal data in cervical cancer with regulatory submissions planned for later this year."

"Our business is off to a strong start in 2021 with double-digit top- and bottom-line growth," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "Our financial strength and solid execution across the business continue to position the Company for sustainable long-term growth."

Business Highlights

Key Pipeline Progress

Regeneron has approximately 30 product candidates in clinical development, including six marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

EYLEA (aflibercept) Injection

In March 2021, JAMA Ophthalmology announced initial results from the National Institutes of Health-sponsored Protocol W trial evaluating EYLEA in patients with moderate to severe non-proliferative diabetic retinopathy (NPDR). The two-year data confirmed results from the Company-sponsored PANORAMA trial and demonstrated that EYLEA significantly reduced the risk of developing vision-threatening complications with an every-16-weeks dosing regimen. The Company plans to submit a supplemental Biologics License Application (sBLA) for an every-16-weeks dosing regimen in patients with NPDR later this year.
Dupixent (dupilumab)

The U.S. Food and Drug Administration (FDA) accepted for review, with a target action date of October 21, 2021, the sBLA for Dupixent for children aged 6 to 11 years with moderate-to-severe asthma. A regulatory application for Dupixent for children aged 6 to 11 years with severe asthma was also submitted in the European Union (EU).
REGEN-COVTM (casirivimab with imdevimab), a dual antibody cocktail to SARS-CoV-2 virus

In March 2021, the Company announced positive top-line results from the Phase 3 treatment trial in high-risk COVID-19 outpatients. The trial met its primary endpoint, showing that REGEN-COV significantly reduced the risk of hospitalization or death by approximately 70% with both REGEN-COV doses (1,200 mg and 2,400 mg) compared to placebo. The trial also met key secondary endpoints, including the ability to reduce symptom duration. Based on these results, the Company submitted a request to the FDA to update the Emergency Use Authorization (EUA) to the lower 1,200 mg dose.
In April 2021, the National Institutes of Health (NIH) COVID-19 Treatment Guidelines were updated to strongly recommended that REGEN-COV be used in non-hospitalized COVID-19 patients at high risk of clinical progression.
In April 2021, the Company announced positive results from the Phase 3 COVID-19 prevention trial in uninfected household contacts of SARS-CoV-2 infected individuals. The trial met its primary and key secondary endpoints, showing that REGEN-COV 1,200 mg administered subcutaneously reduced the risk of symptomatic infections by 81%. The Company has shared this data with the FDA and requested that the EUA be expanded to include COVID-19 prevention for appropriate populations.
In April 2021, the Company also announced positive data from a Phase 3 treatment trial in recently infected asymptomatic COVID-19 patients. The trial met all primary and key secondary endpoints, and demonstrated that the 1,200 mg subcutaneous injection of REGEN-COV reduced the risk of progressing to symptomatic COVID-19 by 31%, and by 76% after the third day.
In January 2021, the Company announced a second agreement with the U.S. government to manufacture and deliver REGEN-COV. The U.S. government has agreed to acquire up to 1.25 million additional doses at the lowest treatment dose authorized or approved by the FDA for the indication authorized under the EUA, resulting in payments to the Company of up to $2.625 billion in the aggregate. The Company anticipates being able to provide at least 1 million doses by June 30, 2021 if the EUA is updated to the lower 1,200 mg dose. The U.S. government is obligated to purchase all filled and finished doses of drug product delivered by June 30, 2021, and may accept additional doses through September 30, 2021 at its discretion. A number of factors may impact the quantity of filled and finished product supplied by June 30, 2021, including manufacturing considerations and authorized dose levels.
Libtayo (cemiplimab)

In February 2021, the FDA approved Libtayo for the first-line treatment of patients with advanced NSCLC.
In February 2021, the FDA also approved Libtayo for the treatment of metastatic or locally advanced BCC.
In March 2021, the Company and Sanofi announced positive results from the Phase 3 trial in cervical cancer, which was stopped early based on a recommendation by the Independent Data Monitoring Committee (IDMC). The results demonstrated an overall survival benefit compared to chemotherapy. Regulatory submissions are planned for later this year.
Evkeeza, an antibody to ANGPTL3

In February 2021, the FDA approved Evkeeza for the treatment of adults and adolescents with HoFH.
Bispecific Antibodies

The Company retained the exclusive rights to develop and commercialize two bispecific antibodies targeting BCMAxCD3 (REGN5458 and REGN5459) and a bispecific antibody targeting MUC16xCD3 (REGN4018) as Sanofi did not exercise its options to license rights to these product candidates under the companies’ immuno-oncology collaboration. REGN5458 and REGN5459 are in clinical development for multiple myeloma, and REGN4018 is being studied in ovarian cancer.
REGN1908-1909, a multi-antibody therapy to Fel d 1

In February 2021, the Company announced that the Phase 2 study in cat allergic patients with mild asthma met its primary and key secondary endpoints. The Company plans to initiate a Phase 3 study in cat allergic asthmatics later this year.
First Quarter 2021 Financial Results

Revenues

Total revenues increased by 38% to $2.529 billion in the first quarter of 2021, compared to $1.828 billion in the first quarter of 2020. Total revenues excluding REGEN-COV increased by 20% to $2.200 billion in the first quarter of 2021, compared to the first quarter of 2020.

Net product sales recorded by the Company consist of the following:

Total revenues also include collaboration revenues(2) of $754 million in the first quarter of 2021, compared to $528 million in the first quarter of 2020. Sanofi collaboration revenue increased primarily due to the Company’s share of profits from commercialization of antibodies, which were $261 million in the first quarter of 2021, compared to $171 million in the first quarter of 2020. The change in the Company’s share of profits from commercialization of antibodies was primarily driven by higher Dupixent profits. In the first quarter of 2021, the Company also recorded Roche collaboration revenue of $67 million in connection with the Company’s share of gross profits from sales of the casirivimab with imdevimab antibody cocktail (known as REGEN-COV in the United States).

Refer to Table 4 for a summary of collaboration revenue.

The higher GAAP and non-GAAP R&D expenses in the first quarter of 2021 were primarily due to costs incurred in connection with development activities related to REGEN-COV.
The increase in GAAP and non-GAAP SG&A expenses in the first quarter of 2021 was primarily due to an increase in product launch-related costs and higher headcount-related costs.
The increase in COGS in the first quarter of 2021 was primarily due to the recognition of manufacturing costs in connection with product sales of REGEN-COV in the United States, as well as Praluent in the United States (which were recorded by Sanofi prior to April 1, 2020).
Other operating (income) expense, net, includes recognition of a portion of amounts previously deferred in connection with up-front and development milestone payments, as applicable, received in connection with the Company’s collaborative arrangements.
Other Financial Information

GAAP other income (expense), net, includes the recognition of net gains on equity securities of $144 million in the first quarter of 2021, compared to net losses of $57 million in the first quarter of 2020.

In the first quarter of 2021, the Company’s GAAP effective tax rate was 11.0%, compared to 6.6% in the first quarter of 2020. The GAAP effective tax rate for the first quarter 2021 was positively impacted, compared to the U.S. federal statutory rate, primarily by the reversal of liabilities related to uncertain tax positions, stock-based compensation, income earned in foreign jurisdictions with tax rates lower than the U.S. federal statutory rate, and federal tax credits for research activities. In the first quarter of 2021, the non-GAAP effective tax rate was 10.5%, compared to 9.5% in the first quarter of 2020.

GAAP net income per diluted share was $10.09 in the first quarter of 2021, compared to GAAP net income per diluted share of $5.43 in the first quarter of 2020. Non-GAAP net income per diluted share was $9.89 in the first quarter of 2021, compared to non-GAAP net income per diluted share of $6.60 in the first quarter of 2020. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

In January 2021, the Company’s board of directors authorized a new share repurchase program to repurchase up to $1.5 billion of the Company’s common stock. Repurchases may be made from time to time at management’s discretion through a variety of methods. The program has no time limit and can be discontinued at any time. During the first quarter of 2021, the Company repurchased shares of common stock under the program, and recorded the cost of the shares received, or $323 million, as Treasury Stock. As of March 31, 2021, $1.177 billion remained available for share repurchases under the program.

Net cash provided by operating activities in the first quarter of 2021 was $669 million, compared to $698 million in the first quarter of 2020, resulting in $553 million in free cash flow for the first quarter of 2021, compared to $528 million for the first quarter of 2020.

2021 Financial Guidance(3)

The Company’s full year 2021 financial guidance consists of the following components:

Conference Call Information

Regeneron will host a conference call and simultaneous webcast to discuss its first quarter 2021 financial and operating results on Thursday, May 6, 2021, at 8:30 AM Eastern Time. To access this call, dial (888) 660-6127 (U.S.) or (973) 890-8355 (International), conference ID 7794757. A link to the webcast may be accessed from the "Investors and Media" page of Regeneron’s website at www.regeneron.com. A replay of the conference call and webcast will be archived on the Company’s website and will be available for at least 30 days.

On May 6, 2021 Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs (the "Company" or "Regulus"), reported that it will report financial results and highlights for the quarter ended March 31, 2021 on Thursday, May 13, 2021, after the U.S. financial markets close (Press release, Regulus, MAY 6, 2021, View Source [SID1234579370]).

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The Company will host a conference call and live audio webcast on Thursday, May 13, 2021 at 5:00 pm Eastern Daylight Time to report its first quarter 2021 financial results and provide a corporate update. To access the call, please dial (877) 257-8599 (domestic) or (970) 315-0459 (international) and refer to conference ID 6947037. To access the telephone replay of the call, dial (855) 859-2056 (domestic) or (404) 537-3406 (international), passcode ID 6947037. The webcast and telephone replay will be archived on the Company’s website at www.regulusrx.com following the call.