On February 23, 2022 Poseida Therapeutics, Inc. (NASDAQ: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, reported that the Company plans to highlight its clinical and preclinical pipeline progress during a virtual R&D Day to be held today beginning at 10:00am ET / 7:00am PT (Press release, Poseida Therapeutics, FEB 23, 2022, View Source [SID1234608899]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Poseida Therapeutics hosts R&D Day focused on novel pipeline and technology innovations. #celltherapy #genetherapy $PSTX
"R&D Day is a time for us to showcase not only our progress in the clinic but our redefining work in cell and gene therapy using our proprietary genetic engineering technologies in new and innovative ways," said Eric Ostertag, M.D., Ph.D., Executive Chairman of Poseida Therapeutics. "Today we are excited to share new data demonstrating the promise of our platforms. For the first time, we will highlight our capabilities in site-specific transposon-based DNA delivery, which is a technology that could revolutionize gene therapy by allowing insertion of large therapeutic transgenes into potentially any site in nearly any cell type or tissue."

Presentations will cover updates on both platforms and product candidates and will be delivered by the Company’s executive leadership, scientists, clinical team members, and key opinion leaders including Scientific Advisory Board member Dr. Luca Gattinoni, Director of the Division of Functional Immune Cell Modulation at the Leibniz Institute for Immunotherapy, whose research focuses on T-cell-based immunotherapies with an emphasis on T-cell differentiation; and Dr. Susan Slovin, the Associate Vice Chair, Academic Administration, Department of Medicine at Memorial Sloan Kettering, an oncologist with expertise in prostate cancer, clinical immunology, and other genitourinary malignancies and a clinical investigator on Poseida’ s P-PSMA-101 clinical trial.

Key R&D Day Topics and Highlights

TSCM-based CAR-T Therapy Programs

Dr. Gattinoni is presenting on the importance of T-stem cell memory (Tscm) in cell therapy, a desirable cell type that is associated with best responses and a differentiated tolerability profile in the clinic and may be key to CAR-T success against solid tumor indications.
Dr. Slovin is providing expanded commentary on clinical findings in the P-PSMA-101 trial, the autologous CAR-T program for patients with metastatic castrate-resistant prostate cancer, following her presentation of these results at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) earlier in the month.
Devon Shedlock, Ph.D., Poseida’s Chief Scientific Officer of Cell Therapy, is presenting on the Company’s allogeneic CAR-T platform, including preclinical findings from P-BCMA-ALLO1 and P-MUC1C-ALLO1, and will discuss the benefits of taking a dual CAR approach with the Company’s P-CD19CD20-ALLO1 program as an example, enabled by utilizing Poseida’s proprietary non-viral piggyBac DNA Delivery System.
Innovative Gene Therapy Programs

P-OTC-101 is the Company’s liver-directed gene therapy program for the in vivo treatment of urea cycle disease caused by a deficiency in the ornithine transcarbamylase (OTC) enzyme, a defect that impairs the body’s ability to detoxify ammonia, a byproduct of protein metabolism. Today the Company will show animal data demonstrating use of its hybrid delivery approach to correct the disease markers and achieve durable expression at dramatically lower doses to support a potentially more effective and more tolerable profile, thereby highlighting the ability of Poseida’s technologies to address challenges that have plagued traditional adeno associated virus (AAV)-based gene delivery.
P-FVIII-101 is a liver-directed gene therapy program partnered with Takeda utilizing the Company’s piggyBac DNA Delivery System in combination with Poseida’s biodegradable nanoparticle delivery for the in vivo treatment of Hemophilia A, a bleeding disorder with high unmet medical need caused by a deficiency in Factor VIII production. Today the Company will share data showing potentially therapeutic levels of expression of Factor VIII can be achieved using a fully nanoparticle system to deliver treatment in juvenile animal models, demonstrating the potential to achieve single treatment cures even in the underserved juvenile patient population.
Emerging Technologies

Site-Specific Super PiggyBac DNA Delivery represents the next generation in gene insertion technology, with the potential to drive highly site-specific DNA integration in nearly any cell or tissue type.
Cas-CLOVER Site-Specific Gene Editing System works with high efficiency when editing in vivo and can be delivered using the Company’s proprietary biodegradable mRNA LNPs.
The Company’s TCR-T platform combines piggyBac DNA delivery and Cas-CLOVER gene editing technologies to generate effective off-the-shelf TCR-T product candidates and could be leveraged to address indications in oncology and beyond, including infectious disease and autoimmunity.
The Company’s CAR 3.0 approach uses genetically modified hematopoietic stem cells, or HSCs, to create a next-generation anti-cancer therapeutic for some indications, which could potentially combine the advantages of T cells, NK cells and other cell types that are naturally derived from HSCs in a single CAR-based treatment approach.
R&D Day Webcast Information
A live webcast of the Company’s R&D Day event will be available on the Investors & Media section of Poseida’s website, www.poseida.com. A replay of the webcast will be available for 30 days following the presentation.

On February 23, 2022 Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines reported a distribution service agreement with Adium Pharma S.A., a leading private Latin American pharmaceutical company, to support the commercialization of the Moderna COVID-19 vaccine, Spikevax across Latin America (Press release, Moderna Therapeutics, FEB 23, 2022, View Source [SID1234608897]). The agreement covers 18 countries in Latin America, including Brazil, Mexico, Colombia, and Argentina.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"Our new partnership with Adium will help ensure broad access and delivery of our Moderna COVID-19 vaccine to people across Latin America," said Stéphane Bancel, Chief Executive Officer of Moderna. "A presence in Latin America is a key part of our global commercial strategy. These partnerships and the expansion of our global commercial footprint position Moderna to play an important role in providing healthcare security against COVID-19 and future vaccine-preventable diseases."

Moderna has a commercial presence in 11 countries worldwide (Australia, Canada, France, Germany, Italy, Japan, South Korea, Spain, Switzerland, UK, U.S.) and recently announced plans to increase its commercial footprint across ten additional markets in Asia-Pacific (Hong Kong, Malaysia, Singapore, Taiwan) and Europe (Belgium, Denmark, the Netherlands, Norway, Poland, Sweden) in 2022.

The Company also has commercial agreements with distributors to supply the Company’s COVID-19 vaccine in 45 countries, with Zuellig Pharma in the Asia Pacific, Medison Pharma in Central Eastern Europe and Israel, and Adium Pharma in Latin America. In addition, Moderna announced an agreement with Gavi, the Vaccine Alliance, to supply up to 650 million doses of the Company’s COVID-19 Vaccine across 2021 and 2022, covering the 92 Gavi COVAX Advance Market Commitment (AMC) low- and middle-income countries.

Regulators have approved Moderna’s COVID-19 vaccine in more than 70 markets, including Canada, Japan, the European Union, the UK, and Israel. In 2021, 807 million doses of Moderna’s COVID-19 vaccine were shipped globally, with approximately 25% of those doses shipped to low- and middle-income markets. In Latin America, Moderna has established bilateral and supranational supply agreements in 15 countries.

On February 23, 2022 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported a corporate and financial update for the fourth quarter and full year ended December 31, 2021 (Press release, G1 Therapeutics, FEB 23, 2022, View Source [SID1234608894]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"2021 was an important foundational year for G1; but I expect 2022 to be a year of strong execution across the Company and value creation for our shareholders and the people living with cancer we seek to serve," said Jack Bailey, Chief Executive Officer of G1 Therapeutics. "I’m very excited with the quality and experience of the members of our new COSELA sales team, who are already hired and fully deployed across the U.S., leveraging our exceptional reimbursement coverage, working to convert high intention-to-use into actual usage and uptake by promoting COSELA with prescribing oncologists and fostering clinical advocacy – all with the goal of rapidly improving COSELA usage and adoption in 2022. Further, we expect to provide initial results from three clinical trials in the second half of this year, including the ADC combination, MOA, and bladder cancer Phase 2 trials, with pivotal colorectal cancer trial data expected soon thereafter, early in the first quarter of 2023. We remain confident in the potential for COSELA in its first indication and, as our pipeline evolves, look forward to delivering on our goal of improving the lives of as many people living with cancer as possible."

Fourth Quarter 2021 and Recent Highlights

Financial

Achieved Total Revenue of $5.8 Million: G1 recognized total revenues of $5.8 million in the fourth quarter of 2021, including $4.4 million in net product revenue from sales of COSELA.
Ended the Fourth Quarter 2021 with Cash and Cash Equivalents of $221.2 million: The Company’s current financial position is expected to be sufficient to fund G1’s operations and capital expenditures into 2024.
Commercial

Completed Hiring, Training, and Deployment of G1’s COSELA Sales Team: G1 and Boehringer Ingelheim terminated the co-promotion agreement for COSELA, effective March 2, 2022. G1 has hired and fully deployed its sales team, including the Vice President of Sales, four Regional Sales Directors, and a total of 34 Oncology Sales Account Managers (OSAMs). The G1 sales team is targeting all U.S. accounts to accelerate sales activities and help maximize the adoption of COSELA. (Press release here)
Received Permanent J-code for COSELA Effective October 1, 2021: The permanent J-code that was issued in July 2021 by the Centers for Medicare & Medicaid Services (CMS) is effective as of October 1, 2021, for provider billing for all sites of care. (Press release here)
Clinical

Announced that Initial Data from Pivotal Phase 3 Trial of Trilaciclib in Colorectal Cancer (CRC) (PRESERVE 1) Are Now Expected Early in the First Quarter of 2023: This Phase 3 multi-center, randomized, placebo-controlled trial is designed to confirm the benefit of trilaciclib in combination with 5-FU-based regimens. PRESERVE 1 is being conducted in approximately 300 mCRC patients being treated with first line FOLFOXIRI, a highly efficacious but highly myelosuppressive chemotherapy frequently used in this setting. The primary endpoint of this trial is myeloprotection, with survival measures including progression free survival (PFS) and overall survival (OS) also being assessed as secondary endpoints. G1 expects to announce the initial results from this Phase 3 trial including myeloprotection and objective response rate (ORR) endpoints early in the first quarter of 2023, earlier than previously stated.
Initiated New Phase 2 Trial of Trilaciclib in Combination with an Antibody-Drug Conjugate (ADC) in Triple-Negative Breast Cancer: The Company initiated a Phase 2, single arm, open-label trial of trilaciclib to study the potential synergistic effects of trilaciclib and the antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan-hziy) in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). The primary objective is to evaluate the anti-tumor efficacy of trilaciclib when administered prior to sacituzumab govitecan-hziy as measured by PFS. Data from this trial will help determine future ADC combinations. Initial results including ORR and myeloprotection endpoints are expected in the fourth quarter of 2022. (Press release here)
Initiated New Phase 2 Trial of Trilaciclib to Support its Immune-based Mechanism of Action: G1 initiated a Phase 2, single arm, open-label trial of trilaciclib in patients with early-stage TNBC designed to confirm the mechanism of action of trilaciclib in modulating the anti-tumor immune response with and without a checkpoint inhibitor. This trial is replacing I-SPY2 neoadjuvant breast trial in G1’s pipeline given the landscape shift from chemotherapy only to chemotherapy + I/O. The primary endpoint is to evaluate the immune-based mechanism of action of trilaciclib after a single-dose as measured by the change in the ratio of effector CD8+ tumor-infiltrating lymphocytes (TILs) to suppressor regulatory T cell (Tregs) in the tumor microenvironment. Data from this trial will inform design of future pivotal studies across multiple tumor types and treatment combinations. Initial results including immune endpoints (e.g., CD8+ TIL / Treg ratio) are expected in the fourth quarter of 2022. (Press release here)
Reiterated Expectation of Initial Data in the Second Half of 2023 from Pivotal Phase 3 Trial of Trilaciclib in 1L TNBC (PRESERVE 2); Changes in Market Landscape Drive Strategic Decision to Discontinue 2L Arm: The treatment landscape is shifting rapidly in 2L TNBC given the expanded indication and rapid uptake of Trodelvy (sacituzumab govitecan-hziy) in 2L/3L TNBC, creating significant barriers to enrollment in this cohort and dramatically reducing the future market opportunity in 2L. As such, the Company has made the strategic decision to discontinue the 2L arm of the trial and will continue to enroll and focus on 1L mTNBC, an area of high unmet medical need. G1 has also modified the protocol to include post-checkpoint patients in the 1L arm to develop clinical experience in this setting. The Company has confirmed that it expects initial results from this pivotal trial, including interim overall survival, in the second half of 2023.
Medical

Announced Publication of Data Showing That Proactive Use of Trilaciclib Prior To Chemotherapy in Certain Patients Significantly Reduced the Use of Reactive Supportive Care Therapies After Chemotherapy: Results from a retrospective analysis of the pooled results of three randomized trilaciclib studies were published in Cancer Medicine, demonstrating that patients with extensive-stage small-cell lung cancer (ES-SCLC) who received trilaciclib prior to each chemotherapy treatment had significantly lower use of supportive care therapies—including G-CSFs, ESAs, and RBC transfusions— for chemotherapy-induced myelosuppression than patients who received placebo. (Press release here)
Presented Data at the 36th Annual Meeting of The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Demonstrating that Trilaciclib Enhanced Patients’ T Cell Immune Function: Results from an immunologic analysis of Phase 2 study data showed that trilaciclib enhanced both CD4 and CD8 T cell function in certain patients with metastatic TNBC when administered prior to chemotherapy. Patients who received trilaciclib prior to gemcitabine/carboplatin (GCb) had fewer immune suppressing cells (myeloid derived suppressor cells; MDSCs) than patients who received GCb alone, whether they were responders or non-responders to treatment, and showed increased T cell function. (Press release here)
Published Data in the Journal of Medical Economics Showing Cost Savings Associated with Trilaciclib Use Prior To Chemotherapy in Patients with Extensive-Stage Small Cell Lung Cancer: Data show that the use of trilaciclib prior to first-line chemotherapy resulted in cost savings due to fewer myelosuppressive adverse events and their associated treatment costs in patients with ES-SCLC suggesting that trilaciclib could provide both clinical and economic benefits for the treatment of these patients.
Fourth Quarter and Full Year 2021 Financial Results

As of December 31, 2021, cash and cash equivalents totaled $221.2 million, compared to $207.3 million as of December 31, 2020. On November 1, 2021, G1 and Hercules Capital amended Hercules’ loan terms to provide total commitments of $150.0 million, of which $100.0 million was fully available as of amendment closing. To date, G1 has drawn $75.0 million on this facility. An additional $25.0 million of debt facility is currently available but not yet drawn.

Total revenues for the fourth quarter of 2021 were $5.8 million, including $4.4 million in net product sales of COSELA and license revenue of $1.4 million. This license revenue is primarily related to clinical trial reimbursements from EQRx and Simcere. Total revenues for the full-year 2021 were $31.5 million, consisting of license revenue of $20.4 million and net product revenue of $11.1 million from sales of COSELA.

Operating expenses for the fourth quarter of 2021 were $43.4 million, compared to $40.6 million for the fourth quarter of 2020. GAAP operating expenses include stock-based compensation expense of $5.2 million for the fourth quarter of 2021, compared to $4.8 million for the fourth quarter of 2020. Operating expenses for the full-year 2021 were $173.9 million, compared to $141.8 million for the prior year. Stock-based compensation expense for the full-year 2021 was $22.3 million, compared to $18.8 million for the prior year.

Cost of goods sold expense for the fourth quarter of 2021 were $0.4 million compared to $0 for the fourth quarter of 2020. The increase is related to the Company’s period costs for the sales of COSELA, including third-party logistics costs for the sales of COSELA, inventory overhead costs, and personnel costs. Cost of goods sold expense for the full-year 2021 were $2.0 million.

Research and development (R&D) expenses for the fourth quarter of 2021 were $19.8 million, compared to $16.4 million for the fourth quarter of 2020. The increase in R&D expenses was primarily due to an increase in clinical trial spend, which is partially offset by a decrease in costs associated with the manufacturing of active pharmaceutical ingredients and drug product to support clinical trials. R&D expenses for the full-year 2021 were $76.2 million, compared to $73.3 million for the prior year.

Selling, general, and administrative (SG&A) expenses for the fourth quarter of 2021 were $23.2 million, compared to $24.3 million for the fourth quarter of 2020. The decrease in SG&A expenses was largely due to a decrease in spend on commercialization activities and medical affairs, partially offset by an increase in personnel costs due to increases in headcount. SG&A expenses for the full-year 2021 were $95.7 million, compared to $68.5 million for the prior year.

The net loss for the fourth quarter of 2021 was $40.0 million, compared to $25.3 million for the fourth quarter of 2020. Net loss for the full-year 2021 was $148.4 million, compared to a net loss of $99.3 million for the prior year. The basic and diluted net loss per share for the fourth quarter of 2021 was $(0.94) compared to $(0.67) for the fourth quarter of 2020. The basic and diluted net loss per share for the full-year 2021 was $(3.54) compared to $(2.62) for the full-year 2020.

Financial Guidance

G1 also expects its current financial position to be sufficient to fund its operations and capital expenditures into 2024.

Webcast and Conference Call

G1 will host a webcast and conference call at 8:30 a.m. ET today to provide a corporate and financial update for the fourth quarter and full year 2021 ended December 31, 2021. The live call may be accessed by dialing (866) 763-6020 (domestic) or (409) 216-0626 (international) and entering the conference code: 5256086. A live and archived webcast will be available on the Events & Presentations page of the company’s website: www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

About COSELA (trilaciclib) for Injection

COSELA (trilaciclib) was approved by the U.S. Food and Drug Administration on February 12, 2021.

Indication
COSELA (trilaciclib) is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.

Important Safety Information
COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.

Warnings and precautions include injection-site reactions (including phlebitis and thrombophlebitis), acute drug hypersensitivity reactions, interstitial lung disease (pneumonitis), and embryo-fetal toxicity.

The most common adverse reactions (>10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.

This information is not comprehensive. Please click here for full Prescribing Information. View Source

To report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or call FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.

On February 23, 2022 Integra LifeSciences Holdings Corporation (NASDAQ: IART) reported financial results for the fourth quarter and full year ended December 31, 2021, consistent with its preliminary revenue results announced on January 11, 2022 (Press release, Integra LifeSciences, FEB 23, 2022, View Source [SID1234608893]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Fourth Quarter 2021

Reported revenues were $405.5 million, representing an increase of 4.3% on a reported basis and an increase of 8.3% on an organic basis compared to the fourth quarter 2020.
GAAP earnings per diluted share were $0.53, compared to $1.09 in the fourth quarter 2020.
Adjusted earnings per diluted share were $0.84, flat compared to the fourth quarter of 2020.
Full-Year 2021

Reported revenues were $1,542.4 million representing an increase of 12.4% on a reported basis and an increase of 14.2% on an organic basis compared to full-year 2020.
GAAP earnings per diluted share were $1.98, compared to $1.57 in 2020.
Adjusted earnings per diluted share were $3.18, compared to $2.45 in 2020.
Key Accomplishments in 2021

Divested the Extremity Orthopedics business and acquired ACell to expand the regenerative tissue portfolio.
Completed the substantive manufacturing transfer of all Codman neurosurgical products.
Launched CereLink ICP Monitor​ in Europe and the U.S.
Initiated phased clinical launch for the Aurora Surgiscope for minimally invasive neurosurgery and MIRROR registry for intracerebral brain hemorrhage.
Filed SurgiMend PMA and completed panel meeting with FDA Advisory Committee and are currently working with FDA on the path forward for a specific indication for post-mastectomy breast reconstruction.
Published results of PriMatrix multicenter study in diabetic foot ulcers demonstrating statistically and clinically significant results against standard of care.
Marked the 25th anniversary of the U.S. approval of the Integra Dermal Regeneration Template (IDRT) for the treatment of life-threatening burns.
Recognized for the company’s leadership in ‘2021 Best Company for Diversity’ and ‘Top 100 Healthcare Technology Company’ lists.
Successfully executed CEO transition with the appointment of Jan De Witte.
"Our 2021 financial performance and business achievements are a testament to our broad and differentiated product portfolio, and the resilience and commitment of our team members around the world, despite the ongoing effects of the global pandemic," said Jan De Witte, president and chief executive officer. "I look forward to working with my Integra colleagues to continue to execute our growth priorities and accelerate our product pipeline and global opportunities in 2022 and the years to come."

Fourth Quarter 2021 Financial Summary

Total reported revenues for the fourth quarter were $405.5 million, an increase of 4.3% from the fourth quarter of 2020. Fourth quarter organic revenues increased 8.3% over the prior year. Total reported revenues include $16.9 million from the acquisition of ACell, which was completed on January 20, 2021. Reported revenue for the fourth quarter 2020 included Extremity Orthopedics.

The Company reported GAAP net income of $45.4 million, or $0.53 per diluted share, in the fourth quarter of 2021, compared to GAAP net income of $92.7 million, or $1.09 per diluted share, in the prior year. The decrease in GAAP net income was driven primarily by a one-time net tax benefit in the fourth quarter of 2020, attributable to an intra-entity transfer of certain intellectual property resulting in the recognition of a $59.2 million deferred tax benefit.

Adjusted EBITDA for the fourth quarter of 2021 was $105.4 million, compared to $102.7 million in the fourth quarter of the prior year. As a percentage of revenue, adjusted EBITDA was 26.0%, a decrease of 40 basis points from the prior year period.

Adjusted net income for the fourth quarter of 2021 was $72.2 million, or $0.84 per diluted share, compared to adjusted net income of $71.3 million, or $0.84 per diluted share, in the fourth quarter of 2020. The contribution of higher revenues in 2021 was offset by the gradual return of spending, which was below normal levels in the prior year in response to the global pandemic.

Cash flows from operations totaled $69.3 million in the fourth quarter and capital expenditures were $27.4 million.

Fourth Quarter 2021 Segment Performance

Codman Specialty Surgical (67% of Revenues)
Total revenues were $270.7 million, representing reported growth of 6.4% and organic growth of 9.0% compared to the fourth quarter of 2020. Sales in Instruments benefited from a strong recovery in order demand, while the strength in Neurosurgery was broad-based and included sales from our new CereLink ICP monitoring and continued recovery in sales of capital equipment.
Tissue Technologies (33% of Revenue)
Total revenues were $134.9 million, representing growth of 0.4% on a reported basis and organic growth of 6.7% compared to the fourth quarter of 2020. Organic growth in this segment was led by sales in Private Label and sales in Wound Reconstruction and Care, with strength in Integra Dermal Matrices and SurgiMend.
Full-Year 2021 Financial Summary

Total reported revenues for the full-year 2021 were $1,542.4 million, an increase of 12.4%, from the prior year. Organic sales for the full-year 2021 increased 14.2% compared to 2020. Total reported revenues include $65.4 million from the acquisition of ACell. Reported revenue for the full-year 2020 included Extremity Orthopedics.

The Company reported GAAP net income of $169.1 million, or $1.98 per diluted share, for the full-year 2021, compared to GAAP net income of $133.9 million, or $1.57 per diluted share in 2020. The increase in GAAP net income was primarily driven by increased revenues from procedure recovery from the COVID-19 impact in 2020 and the gain on sale of $41.8 million from the Extremity Orthopedics business, partially offset by a one-time net tax benefit in the fourth quarter of 2020.

Adjusted EBITDA for the full-year 2021 was $400.7 million, an increase of $66.2 million over the prior year. Full year EBITDA margins were 26.0% an increase of 160 basis points from the prior year.

Adjusted net income for the full-year 2021 was $271.7 million, or $3.18 per diluted share, compared to $208.7 million, or $2.45 per diluted share in 2020. The increase was primarily attributable to increased sales in 2021 after the COVID-19 impact of 2020.

2021 Balance Sheet, Cash Flow and Capital Allocation

The Company generated record cash flow from operations of $312.4 million for the full-year 2021. Full-year capital expenditures were $48.0 million. Net debt at the end of the year was $1.05 billion, and the consolidated total leverage ratio was 2.3x. As of year-end, the Company had total liquidity of approximately $1.78 billion, including approximately $513 million in cash and the remainder available under its revolving credit facility.

2022 Revenue and Adjusted Earnings Per Share Guidance

The Company’s guidance for 2022 revenue and adjusted earnings per share reflects the continuing uncertainty around the scope and duration of the pandemic, and its related impacts on our business in the first half of the year. For the first quarter 2022, the Company expects reported revenues in the range of $357 million to $365 million, representing reported growth of approximately -1% to 1.5% and organic growth of approximately 0% to 2.5%. Adjusted earnings per diluted share are expected to be in a range of $0.67 to $0.71.

For the full-year 2022, the Company expects revenues to be in a range of $1,580 million to $1,600 million, representing reported growth of approximately 2.5% to 3.5% and organic growth of approximately 3.5% to 5%. Adjusted earnings per diluted share are expected to be in a range of $3.27 to $3.35.

Organic sales growth excludes acquisitions and divestitures as well as the effects of foreign currency and the year-over-year change in revenue from discontinued products. Organic growth includes ACell as of January 20, 2022.

The Company is providing forward-looking guidance regarding adjusted earnings per diluted share but is not providing a reconciliation to GAAP earnings per share, because certain GAAP expense items are highly variable, and management is unable to predict them with reasonable certainty and without unreasonable effort. Specifically, the financial impact and timing of divestitures, acquisitions, integrations, structural optimization and efforts to comply with the EU Medical Device Regulation are uncertain, depend on various dynamic factors and are not reasonably ascertainable at this time. These expense items could have a material impact on GAAP results. Adjusted earnings per diluted share also excludes the impact of intangible asset amortization associated with prior business acquisitions, which we expect to be approximately $0.77 per diluted share for the full-year 2022.

2022 Share Repurchase

On January 12, 2022, the Company entered into an accelerated share repurchase agreement with Citibank, N.A. to repurchase $125 million in the aggregate of the Company’s outstanding shares of common stock, par value $0.01 per share. The repurchase transactions are expected to be completed in the first half of 2022. The impact of the share repurchase is reflected in the 2022 adjusted earnings per diluted share guidance range provided.

Conference Call and Presentation Available Online

Integra has scheduled a conference call for 8:30 a.m. ET on Wednesday, February 23, 2022, to discuss fourth quarter and full-year 2021 financial results, and forward-looking financial guidance. The conference call will be hosted by Integra’s senior management team and will be open to all listeners. Additional forward-looking information may be discussed in a question-and-answer session following the call. Integra’s management team will reference a presentation during the conference call, which can be found on the Investor section of the website at investor.integralife.com.

Access to the live call is available by dialing (888) 394-8218 and using the passcode 701830. A simultaneous webcast of the call will be available via the Company’s website at www.integralife.com. A webcast replay of the call can be accessed through the Investor Relations homepage of Integra’s website at www.integralife.com. A replay of the call will be available until March 5, 2022 by dialing (888) 203-1112 and using the passcode 701830.

On February 23, 2022 Priothera, a late-clinical stage biotechnology company pioneering the development of its S1P receptor modulator drug, mocravimod, reported that it has entered a Loan Agreement of €17.5 million with the European Investment Bank (EIB) (Press release, Priothera, FEB 23, 2022, View Source [SID1234608892]). This loan will further support a European, US and Asian registration-enabling clinical trial with mocravimod in Acute Myeloid Leukemia (AML) patients receiving hematopoietic stem cell transplant (HSCT).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

The loan facility of €17.5 million is divided into two tranches, the first of which is €10 million and unconditional. Priothera will request payment of the first tranche in 2022 to expand the clinical development of mocravimod and prepare for its commercial drug supply. The second tranche of €7.5 million is available upon achievement of specific manufacturing, clinical and regulatory milestones and will be used to finance clinical validation in CAR-T cancer indications.

Florent Gros, Co-Founder and CEO of Priothera, comments: "We are very grateful for EIB’s support, a major and high quality European financial institution, as the Company is at an inflection point of its clinical development and potential commercialization path. This financing allows Priothera to extend its financial visibility to 2024, allowing us to complete a global registration-enabling clinical trial, as well as exploring other blood cancer indications for mocravimod. This new funding tool will help reinforce Priothera’s global lead in developing S1P receptor modulators in oncology."

Christian Kettel Thomsen, Vice-President of the EIB, said: "The European Investment Bank Group supports development of innovative and pioneering treatments and medicine by leading biotech and medtech companies in Ireland and across Europe. Priothera’s new drugs offer an opportunity to revolutionise treatment of leukaemia and other cancers and the EIB is pleased to agree to €17.5 million of new financing to accelerate the clinical development and commercialization of mocravimod."

About mocravimod
Mocravimod (also known as KRP203), a propane-1,3-diol derivative, is a novel, synthetic, sphingosine 1-phosphate receptor (S1PR) agonist with long duration in the body. Phase 1 and Phase 2 trials successfully assessed mocravimod for safety and tolerability in several autoimmune indications. Promising data from a Ph1b/Ph2a clinical study with patients with haematological malignancies led Priothera to further develop mocravimod for the treatment of blood cancers.

Mocravimod will be investigated in a Phase 2b/3 study as a potential treatment for patients with Acute Myeloid Leukemia (AML) receiving HSCT. Allogenic HSCT is the only potentially curative approach for AML patients but remains having unacceptably high mortality and morbidity rates with current treatments.

Priothera leverages S1PRs unique mode of action to maintain anti-leukaemia activity while reducing tissue damage resulting from graft-versus-host disease (GVHD), a consequence of HSCT. This novel treatment approach – the only S1PR modulator treating blood cancers – tackles a high unmet medical need that intends to add quality life to patients.