On February 23, 2022 BioMarin reported that Fourth Quarter and Full Year 2021 Financial Results and Corporate Updates (Press release, BioMarin, FEB 23, 2022, View Source [SID1234608874]).

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(1) Net Product Revenues Marketed by BioMarin is the sum of revenues from Vimizim, Naglazyme, Kuvan, Palynziq, Brineura and Voxzogo (formerly known as vosoritide) for the three and twelve months ended December 31, 2021, each calculated in accordance with Generally Accepted Accounting Principles in the United States (U.S. GAAP). Sanofi (formally known as Sanofi Genzyme) is BioMarin’s sole customer for Aldurazyme and is responsible for marketing and selling Aldurazyme to third parties. Refer to page 10 for a table showing Net Product Revenues by product. In January 2020, BioMarin divested the Firdapse assets to a third party in a sale transaction. The sale is reflected in the Company’s consolidated financial statements for the twelve months ended December 30, 2020; as a result of the transaction BioMarin no longer recognizes Net Product Revenues from Firdapse.

(2) Not meaningful

(3) Non-GAAP Income is defined by the Company as reported GAAP Net Income/Loss, excluding net interest expense, provision for (benefit from) income taxes, depreciation expense, amortization expense, stock-based compensation expense, contingent consideration expense and, in certain periods, certain other specified items. Refer to Non-GAAP Information beginning on page 11 of this press release for a complete discussion of the Company’s Non-GAAP financial information and reconciliations to the comparable information reported under U.S. GAAP.

BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) (BioMarin or the Company) reported financial results for the fourth quarter and full-year ended December 31, 2021.

BioMarin Announces Fourth Quarter and Full-year 2021 Results
"During 2021, we established the foundation for a return to double-digit revenue growth and profitability in 2022," said Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin. "We are pleased with 2021 full-year results, which demonstrated solid performance despite the impact of the loss of exclusivity of Kuvan in the U.S. Following the 2021 global approvals of Voxzogo in the U.S., Europe and Brazil, the enthusiasm from families seeking treatment for their children with achondroplasia has been very encouraging. We are pleased that families now have an approved treatment option, and we look forward to increasing access to Voxzogo as the launch rolls out over the coming quarters."

Mr. Bienaimé continued, "With Voxzogo in launch mode in many countries across the globe, the regulatory team is focused on our next significant potential approval with valoctocogene roxaparvovec gene therapy for the treatment of severe hemophilia A. The two-year data from the 134-participant Phase 3 study, shared in January 2022, met all primary and secondary efficacy endpoints. The results are clinically meaningful, demonstrating superiority to standard of care and an 85% reduction in annualized bleeding rates compared to baseline. We anticipate resubmitting the U.S. application in the second quarter of 2022 and continue to anticipate the European opinion in the second quarter of 2022. With the potential approvals of valoctocogene roxaparvovec in Europe and US, and the continued strong launch of Voxzogo, we expect 2022 to be a transformational year for BioMarin and the patients we seek to serve."

Financial Highlights:

Total Revenues for the fourth quarter of 2021 were $449.8 million, essentially flat compared to the same period in 2020 despite continued erosion of the U.S. Kuvan market. Significant product level revenue fluctuations were as follows:
Higher Aldurazyme product revenues due to timing of product fulfillment to Sanofi. BioMarin Aldurazyme revenues are driven by the timing of when the product is released and control is transferred to Sanofi. Revenues for the fourth quarter of 2021 were comparatively higher than 2020 due to such timing.
Higher Palynziq product revenues primarily due to a combination of revenues from more patients in the U.S. achieving maintenance dosing and new patients initiating therapy. The commercial launch of Palynziq in BioMarin’s European, Middle East and African (EMEA) region continues to progress through individual country level pricing and reimbursement negotiations.
Higher Vimizim product revenues primarily driven by timing of orders in the Middle East and Latin America.
Voxzogo received approval from European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) in the third and fourth quarters of 2021 with commercial sales launching regionally in the same period as approval.
These factors were more than offset by the following:

Lower Naglazyme product revenues primarily driven by timing of orders from Latin America, the Middle East and Europe. High patient compliance rates and year-over-year patient growth reflect strong underlying demand.
Lower Kuvan product revenues primarily due to generic competition as a result of the loss of exclusivity in the U.S., which was consistent with expectations.
GAAP Net Loss increased to $57.9 million for the fourth quarter of 2021 compared to GAAP Net Income of $22.1 million for the same period in 2020 primarily due to the following:
Higher tax benefit in 2020 due to the change in the jurisdictional mix of earnings and the related tax impact from the completion of an intra-entity transfer of certain intellectual property rights to an Irish subsidiary. There was no similar transaction in 2021.
Higher selling, general and administrative (SG&A) expenses primarily due to higher commercialization activities to support the commercial launch of Voxzogo, as well as an increase in administrative costs.
Non-GAAP Income for the fourth quarter of 2021 decreased to $7.1 million compared to Non-GAAP Income of $39.5 million for the same period in 2020. The decrease in Non-GAAP Income for the quarter compared to the same period in 2020 was primarily attributable to higher SG&A and research and development (R&D) expenses.
Late-stage Regulatory Portfolio (Voxzogo and valoctocogene roxaparvovec)

In August 2021, the European Commission approved Voxzogo for the treatment of children, ages 2 years and older. Regulatory approvals were also received in Brazil and the U.S. in November 2021, for children ages five and older with open growth plates. The launch is actively underway, with market access and reimbursement progressing as anticipated. By February 15, 2022, an estimated 210 children were being treated with commercial Voxzogo globally, with an estimated additional 54 children in process in the U.S.
Marketing authorization reviews of Voxzogo are in process in Japan and Australia, with potential approvals in those countries in 2022. At the end of 2021, there were seven active markets contributing to Voxzogo sales.
Today, the Company announced an update from the Phase 2 randomized, double-blind, placebo-controlled Voxzogo study in infants and young children up to five years of age with achondroplasia. 52-week results trended in favor of Voxzogo compared to placebo on height Z-score, annualized growth velocity, with no worsening in proportionality in the overall study population. Height Z-score measures height adjusted for age and sex. The safety profile was generally consistent with older subjects from the Phase 3 Voxzogo 301 study and current label population. Serious Adverse Events (SAEs) were higher in the placebo group (18%) compared to Voxzogo treated children (7%). All SAEs, including a fatal event of SIDS in the treatment group, were deemed by the investigators to be unrelated to treatment. A small increase in events of sleep apnea were reported in the treatment group that were mild or moderate in severity and did not require treatment discontinuation. These events will be fully assessed when sleep study and MRI data are available. BioMarin intends to initiate discussions with regulatory health authorities to discuss next steps regarding efforts to expand access to Voxzogo treatment for this younger age group.
The European Medicines Agency (EMA) validated BioMarin’s Marketing Authorization Applications (MAA) for valoctocogene roxaparvovec resulting in an anticipated Committee for Medicinal Products for Human Use (CHMP) opinion in the second quarter of 2022. BioMarin has provided the EMA with two-year follow-up safety and efficacy data from the GENEr8-1 study.
Based on the favorable results from the two-year follow-up safety and efficacy data from the GENEr8-1 study, BioMarin is targeting a Biologics License Application (BLA) resubmission for valoctocogene roxaparvovec in the second quarter of 2022. If the resubmission satisfies FDA’s response to the Complete Response Letter received in August 2020, BioMarin expects resubmission will be followed by a 6-month review procedure by the FDA.
Earlier-stage Development Portfolio (BMN 307, BMN 255, BMN 331, BMN 351, BMN 349, DiNA-001)

BMN 307 gene therapy product candidate for PKU: In September 2021, the FDA placed a clinical hold on PHEarless, the Phase 1/2 study evaluating BMN 307, an investigational AAV5-phenylalanine hydroxylase (PAH) gene therapy, in adults with phenylketonuria (PKU). The hold was based on pre-clinical study findings from a model designed to understand the durability of BMN 307 activity in mice bearing two germline mutations, one rendering the mice immunodeficient. In February 2022, the FDA requested data from additional non-clinical studies to assess theoretical oncogenic risk to human study participants, which is expected to take several quarters. The Company will communicate next steps for the program when available.
BMN 255 for primary hyperoxaluria type 1, a subset of chronic renal disease: The Investigational New Drug application (IND) for BMN 255 is active and the Company is dosing subjects with dose selection for advanced studies expected in the second half of 2022. BioMarin believes the availability of a potent, orally bioavailable, small molecule like BMN 255, may be able to significantly reduce disease and treatment burden in certain people with chronic renal disease.
BMN 331 gene therapy product candidate for Hereditary Angioedema (HAE): The Company announced that its Phase 1/2 HAERMONY study to evaluate BMN 331, an investigational AAV5-mediated gene therapy for people living with hereditary angioedema (HAE), is open for enrollment. In addition, the FDA granted Orphan Disease Designation status to BMN 331.
BMN 351 for Duchenne Muscular Dystrophy (DMD): IND-enabling studies continue with BMN 351, an antisense oligonucleotide therapy for individuals with 51-skip-amenable DMD. BMN 351 was developed using familiar chemistry and superior biology, by targeting a novel, upstream, splice enhancer site demonstrating improved binding affinity and metabolic stability in preclinical models. Preclinical data suggest that restored expression of near-full-length dystrophin protein at previously achieved levels of up to 40% will convert phenotypes from rapid loss to durable preservation of strength and ambulation. BioMarin expects to file an IND for BMN 351 in the first half of 2022, and anticipates treating clinical trial participants with Duchenne muscular dystrophy in the fourth quarter of 2022.
BMN 349 for alpha-1 antitrypsin deficiency: Preclinical studies have demonstrated that BMN 349 is an orally bioavailable, small molecule that is titratable with rapid onset and high potency and efficacy. Preclinical results have strong implications for potential improvement of current management, particularly around burden of treatment, particularly for severe cases requiring rapid action. BioMarin’s goal is to file the IND in the second half of 2023.
DiNA-001 for MYBPC3 hypertrophic cardiomyopathy (HCM): Preclinical studies are underway with DiNA-001 following a collaboration announced in 2020 with DiNAQOR, a gene therapy platform company, to develop novel gene therapies to treat rare genetic cardiomyopathies. Mutations in MYBPC3 are the most common cause of inherited HCM. Early investigations suggest that gene therapy-mediated gene transfer can lead to widespread expression of the gene product, cardiac myosin-binding protein C (MyBP-C), in cardiac tissue, which can normalize relaxation kinetics and potentially ameliorate the disease phenotype in individuals suffering from cardiomyopathy. BioMarin’s goal is to file the IND in 2023.

(1) All Financial Guidance items are calculated based on U.S. GAAP with the exception of Non-GAAP Income. Refer to Non-GAAP Information beginning on page 11 of this press release for a complete discussion of the Company’s Non-GAAP financial information and reconciliations to the corresponding GAAP reported information.

BioMarin will host a conference call and webcast to discuss fourth quarter and year to date 2021 financial results today, Wednesday, February 23, 2022 at 4:30 p.m. ET. This event can be accessed on the investor section of the BioMarin website at www.biomarin.com.

On February 23, 2022 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the fourth quarter and full year ended December 31, 2021, and provided a corporate update (Press release, BioCryst Pharmaceuticals, FEB 23, 2022, View Source [SID1234608873]).

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"The successful launch of ORLADEYO, the rapid advancement of our pipeline and the additional capital we acquired last year have transformed BioCryst. With more than $500 million on our balance sheet and ORLADEYO revenue growing to no less than $250 million in 2022, and $1 billion in global peak sales, we are focused on compounding the value of the company by allocating capital to grow ORLADEYO and advancing our complement program to get our oral drugs to patients suffering from many different rare diseases," said Jon Stonehouse, president and chief executive officer of BioCryst.

Program Updates and Key Milestones

ORLADEYO (berotralstat): Oral, Once-daily Treatment for Prevention of Hereditary Angioedema (HAE) Attacks

U.S. Launch

ORLADEYO net revenue in the fourth quarter of 2021 was $46.2 million.

New patient demand for ORLADEYO remains strong and consistent, with a similar number of new patients added in Q4 2021 as in each of the previous three quarters of the year. Patients switching from other prophylactic therapies and acute-only therapy continue to drive the launch. More than half of patients new to ORLADEYO since launch had a previous prophylactic medicine prior to ORLADEYO and most of the remainder were from acute-only treatment.

Most patients are well-controlled on ORLADEYO and remain on therapy. Approximately 70 percent of patients starting ORLADEYO, including those switching from injectable prophylaxis, remain on ORLADEYO in the first year.
The ORLADEYO prescriber base continues to grow significantly as physicians gain real-world experience. In market research, 60 U.S. physicians, who treat an average of seven HAE patients each, reported that they expect to double their use of ORLADEYO, and that ORLADEYO will become their most prescribed prophylactic treatment in the next 12 months.

ORLADEYO is now covered by all major payors and pharmacy benefit managers, which will lead to more patients moving quickly to paid product.

ORLADEYO net revenue is expected to benefit from this wide coverage and continued new patient growth throughout 2022. Because of typical first quarter requirements from payors for prescription reauthorization of specialty products, like ORLADEYO, that can temporarily move patients from paid drug to free product, copayment assistance and Medicare D cost sharing dynamics, the company expects little to no ORLADEYO net revenue growth from Q4 2021 to Q1 2022. The company has accounted for this expected Q1 impact in its expectation that full year 2022 ORLADEYO global net revenues will double year over year to no less than $250 million.
"We are excited by the strong start to the ORLADEYO launch and the favorable experience most HAE patients are having controlling their HAE attacks with an oral, once-daily capsule. With a sizeable base of patients already on therapy, reimbursement in place for the full year in 2022, and more face-to-face opportunities for our commercial team to engage directly with patients and physicians, we are looking forward to more than doubling our revenue this year as we continue on our trajectory to become the market leader in HAE prophylaxis," said Charlie Gayer, chief commercial officer of BioCryst.

ORLADEYO: Global Updates

ORLADEYO has been launched in France, Germany, Japan, Norway, Sweden, the United Arab Emirates and the United Kingdom. The company expects launches in additional countries throughout the year.
Complement Oral Factor D Inhibitor Program – BCX9930

BioCryst is currently enrolling patients in two global pivotal trials, REDEEM-1 and REDEEM-2, with the company’s oral Factor D inhibitor, BCX9930 (500 mg bid), in patients with paroxysmal nocturnal hemoglobinuria (PNH). REDEEM-1 is a randomized, open-label, active, comparator-controlled comparison of the efficacy and safety of BCX9930 monotherapy in approximately 81 PNH patients with an inadequate response to a C5 inhibitor. REDEEM-2 is a randomized, placebo-controlled trial to evaluate the efficacy and safety of BCX9930 as monotherapy versus placebo in approximately 57 PNH patients not currently receiving complement inhibitor therapy. The primary endpoint for both trials is the change from baseline in hemoglobin, assessed at weeks 12 to 24 in REDEEM-1 and at week 12 in REDEEM-2.

The company also has begun patient enrollment for RENEW, a proof-of-concept (PoC) basket trial of oral BCX9930 (500 mg bid) in complement-mediated renal diseases. The trial is being conducted in patients with C3 glomerulopathy (C3G), IgA nephropathy (IgAN), and primary membranous nephropathy (PMN).
BioCryst plans to further advance and expand its Factor D program over the next two years by achieving the following by the end of 2023:

Complete and report data from REDEEM-1 and REDEEM-2
Prepare to submit regulatory approval filings in PNH
Complete the renal PoC basket trial and advance to pivotal trials in C3G, IgAN and PMN
Commence PoC trials in other complement-mediated diseases
Additional Updates

On November 22, 2021, the company announced financing transactions totaling $350 million in new funding for BioCryst from Royalty Pharma and OMERS Capital Markets.

On November 1, 2021, the company announced the appointment of Jinky Ang Rosselli as Chief Data and Insights Officer.
Fourth Quarter 2021 Financial Results

For the three months ended December 31, 2021, total revenues were $47.2 million, compared to $4.0 million in the fourth quarter of 2020. The increase was primarily due to $46.2 million in ORLADEYO net revenue in the fourth quarter of 2021.

Research and development (R&D) expenses for the fourth quarter of 2021 increased to $63.5 million from $35.4 million in the fourth quarter of 2020, primarily due to increased investment in the development of our Factor D program and other research, preclinical and development costs, offset by a slight reduction in spend on the ORLADEYO program following our commercial launch in December 2020.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2021 increased to $35.4 million, compared to $21.0 million in the fourth quarter of 2020. The increase was primarily due to increased investment to support the commercial launch of ORLADEYO and expanded international operations.

Interest expense was $18.8 million in the fourth quarter of 2021, compared to $5.6 million in the fourth quarter of 2020. The increase was due to service on the royalty and debt financings, which were completed in December 2020 and November 2021.

A one-time non-cash gain of $55.8 million related to the extinguishment of debt was recognized during the fourth quarter of 2021 to write-off the non-recourse PhaRMA Notes and related accrued interest payable.

Net loss for the fourth quarter of 2021 was $17.8 million, or $0.10 per share, compared to a net loss of $60.5 million, or $0.34 per share, for the fourth quarter of 2020. Non-GAAP net loss for the fourth quarter of 2021 was $73.6 million, or $0.40 per share when excluding the one-time non-cash gain on the extinguishment of the non-recourse PhaRMA Notes. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Cash, cash equivalents, restricted cash and investments totaled $517.8 million as of December 31, 2021, compared to $302.6 million as of December 31, 2020. Operating cash use for the fourth quarter of 2021 was $29.0 million.

Full Year 2021 Financial Results

For the full year ended December 31, 2021, total revenues were $157.2 million, compared to $17.8 million in the full year ended December 31, 2020. The increase was primarily due to $122.6 million of ORLADEYO net revenue following our commercial launch in December 2020, recognition of a $15.0 million milestone payment from Torii related to the Japanese National Health Insurance System approval of ORLADEYO in Japan, and increased RAPIVAB revenues. These increases in revenue were partially offset by a reduction in royalty revenue (excluding those associated with ORLADEYO sales) of $4.2 million, a reduction in contract revenue of $3.3 million and the recognition of $1.9 million of deferred revenue in the prior year period compared to none in the current year period.

R&D expenses in full year 2021 increased to $208.8 million from $123.0 million in full year 2020, primarily due to increased investment in our Factor D program, and an increase in other research, preclinical and development activities, partially offset by a ramp down of clinical investment related to ORLADEYO, which launched commercially in the U.S. during December 2020.

SG&A expenses in full year 2021 increased to $118.8 million, compared to $67.9 million in full year 2020. The increase was primarily due to increased investment to support the U.S. commercial launch of ORLADEYO and expanded international operations.

Interest and other income was $0.1 million in full year 2021, compared to $9.4 million in full year 2020. The decrease was primarily due to the one-time settlement of arbitration proceedings related to our Seqirus dispute in the first quarter of 2020.

Interest expense was $59.3 million in full year 2021, compared to $14.5 million in full year 2020. The increase was associated with the $125.0 million Term A Loan under the Credit Agreement and Royalty financing obligations which were completed in December 2020 and November 2021.

A one-time non-cash gain of $55.8 million on extinguishment of debt was recognized in the full year 2021 related to the write-off of the non-recourse PhaRMA notes and related accrued interest payable.

Net loss for full year 2021 was $184.1 million, or $1.03 per share, compared to a net loss of $182.8 million, or $1.09 per share, for full year 2020. Non-GAAP net loss for full year 2021 was $239.9 million, or $1.34 per share when excluding the one-time gain on the extinguishment of the non-recourse PhaRMA Notes. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Non-GAAP Pro forma Financial Measures

The information furnished in this release includes non-GAAP pro forma financial measures that differ from measures calculated in accordance with generally accepted accounting principles in the United States of America ("GAAP"), including financial measures labeled as "non-GAAP" or "adjusted."

We believe providing these non-GAAP measures, which show our pro forma results with these items adjusted, is valuable and useful since they allow the company and investors to better understand the company’s financial performance in the absence of these one-time events and will allow investors to more accurately understand our 2021 results and more easily compare them to future results. These non-GAAP pro forma measures also correspond with the way we expect Wall Street analysts to compare our results. Our non-GAAP pro forma measures should be considered only as supplements to, and not as substitutes for or in isolation from, our other measures of financial information prepared in accordance with GAAP, such as GAAP revenue, operating income, net income, and earnings per share.

Our references to our fourth quarter 2021 "non-GAAP pro forma" financial measures of adjusted net loss and adjusted earnings per share constitute non-GAAP financial measures. They refer to our GAAP results, adjusted to show the results without the one-time gain realized by the extinguishment of the debt from our PhaRMA notes.

Financial Outlook for 2022

Based on the strength of the ORLADEYO launch, and continued growth from new patient demand anticipated throughout the year, the company expects full year 2022 net ORLADEYO revenue to be no less than $250 million. Operating expenses for full year 2022, not including non-cash stock compensation, are expected to be in the range of $440 million to $480 million. The increase year over year is predominantly driven by additional investment in advancing the Factor D program across multiple indications.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 877-303-8027 for domestic callers and 760-536-5165 for international callers and using conference ID # 6365545. A live webcast of the call and any slides will be available online at the investors section of the company website at www.biocryst.com. A telephone replay of the call will be available by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference ID # 6365545.

On February 23, 2022 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health" or the "Company" or "we") reported its fourth-quarter and full-year 2021 financial results (Press release, Bausch Health, FEB 23, 2022, View Source [SID1234608872]).

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"In 2021, our reported revenues grew by five percent as several of our key products gained market share, and we delivered on our near-term R&D catalysts with four new product launches," said Joseph C. Papa, chairman and CEO, Bausch Health. "Thanks to the hard work and dedication of our employees, we achieved our goals in 2021 and have entered 2022 well positioned for continued growth."

"We have made great progress in our efforts to unlock value by creating three great companies, including publicly filing the registration statements for the proposed IPOs of Bausch + Lomb and Solta. Our planning and preparations to launch these IPOs are substantially complete, and we are prepared to move forward, subject to market conditions, stock exchange and other approvals," continued Mr. Papa.

Select Company Highlights

Increased total Company reported revenue by 5% compared to the full year of 2020
Reported revenue for XIFAXAN (rifaximin) grew by 11% during the full year of 2021 compared to the full year of 2020
Reported revenue for TRULANCE (plecanatide), which the Company acquired in 2019, exceeded $100 million during the full year of 2021
Reported revenue for the Solta business grew by 22% during the full year of 2021 compared to the full year of 2020
Repaid debt by approximately $1.3 billion for the full year of 2021 using cash on hand, cash generated from operations and in connection with the divestiture of Amoun Pharmaceutical Company S.A.E. ("Amoun")
Launched Solta Medical’s Clear + Brilliant Touch laser in the United States
Launched Bausch + Lomb’s Alaway Preservative Free (ketotifen fumarate ophthalmic solution 0.035%), antihistamine eye drops in the United States
Launched expanded parameters for Bausch + Lomb ULTRA Multifocal for Astigmatism contact lenses in the United States
Launched Biotrue Hydration Boost Lubricant Eye Drops in the United States
ClearVisc dispersive ophthalmic viscosurgical device for use in ophthalmic surgery was approved by the U.S. Food and Drug Administration ("FDA") and launched in the United States in June 2021
Divested Amoun to Abu-Dhabi-based ADQ in July 2021
Released the Company’s annual Environmental, Social and Governance Report in September 2021
Pipeline Advancements

Received FDA approval of the New Drug Application ("NDA") for XIPERE4 (triamcinolone acetonide injectable suspension), which uses the suprachoroidal space to treat patients suffering from macular edema associated with uveitis, and launched in the United States during the first quarter of 2022
Announced statistically significant topline results from two Phase 3 trials evaluating the investigational drug NOV035 (perfluorohexyloctane) as a first-in-class eye drop with a novel mechanism of action to treat the signs and symptoms of dry eye disease associated with Meibomian gland dysfunction; the Company expects to file an NDA with the FDA in the first half of 2022
Announced statistically significant topline results from the second pivotal Phase 3 trial evaluating the investigational IDP-126 gel in acne vulgaris
Entered into an agreement with Lochan LLC to develop the next generation of Bausch + Lomb’s eyeTELLIGENCE clinical decision support software
Initiated Phase 3 clinical trial of rifaximin soluble solid dispersion to study use of rifaximin in the prevention of hepatic encephalopathy
Initiated Phase 2 trial to evaluate amiselimod (S1P modulator) for the treatment of mild to moderate ulcerative colitis
Received regulatory approval for VYZULTA (latanoprostene bunod ophthalmic solution), 0.024%, in 2021 in South Korea, Brazil, Jordan, Qatar, Thailand, Turkey, Ukraine and the United Arab Emirates, and launched in Taiwan
Received regulatory approval for LUMIFY (brimonidine tartrate ophthalmic solution 0.025%) redness reliever eye drops in 2021 in Jordan and South Korea
Accelerating Strategic Alternatives
Bausch Health has continued to execute upon its plans to pursue an initial public offering ("IPO") of its Solta Medical ("Solta") business2 and to pursue an IPO2 and full separation of its Bausch + Lomb business from Bausch Pharma.3,6 The Company has publicly filed a Registration Statement on Form S-1 with the U.S. Securities and Exchange Commission ("SEC") and a preliminary base PREP prospectus with each of the securities regulatory authorities in all of the provinces and territories of Canada (other than Quebec) relating to the proposed IPO of Bausch + Lomb and also has publicly filed a Registration Statement on Form S-1 with the SEC relating to the proposed IPO of Solta Medical Corporation.

Bausch Health has completed all internal procedural steps and is fully prepared to launch both the Solta and Bausch + Lomb IPOs, subject to receipt of regulatory, stock exchange and other approvals. The Company is actively monitoring market conditions to determine the paths forward.2

Fourth-Quarter and Full-Year 2021 Revenue Performance
Total reported revenues were $2.196 billion for the fourth quarter of 2021, as compared to $2.213 billion in the fourth quarter of 2020, a decrease of $17 million, or 1%.

Total reported revenues were $8.434 billion for the full year of 2021, as compared to $8.027 billion in the full year of 2020, an increase of $407 million, or 5%. Excluding the favorable impact of foreign exchange of $95 million and the impact of divestitures and discontinuations of $132 million, primarily due to the divestiture of Amoun, revenue increased organically1,7 by 6% compared to the full year of 2020.

Bausch + Lomb Segment8
Bausch + Lomb segment revenues were $1.001 billion for the fourth quarter of 2021, as compared to $947 million for the fourth quarter of 2020, an increase of $54 million, or 6%. Excluding the unfavorable impact of foreign exchange of $11 million and the impact of divestitures and discontinuations of $2 million, the Bausch + Lomb segment increased organically1,7 by approximately 7% compared to the fourth quarter of 2020, primarily due to higher sales resulting from the positive impacts of the recovery from the COVID-19 pandemic.

Bausch + Lomb segment revenues were $3.765 billion for the full year of 2021, as compared to $3.415 billion for the full year of 2020, an increase of $350 million, or 10%. Excluding the favorable impact of foreign exchange of $58 million and the impact of divestitures and discontinuations of $10 million, the Bausch + Lomb segment increased organically1,7 by approximately 9% compared to the full year of 2020, primarily due to higher sales resulting from the positive impacts of the recovery from the COVID-19 pandemic.

Bausch Pharma (non-GAAP)1,8,10
Bausch Pharma revenues (non-GAAP)1,10 were $1.195 billion for the fourth quarter of 2021, as compared to $1.266 billion for the fourth quarter of 2020, a decrease of $71 million, or 6%. Excluding the unfavorable impact of foreign exchange of $6 million and the impact of divestitures and discontinuations of $70 million, revenue was flat organically.1,7

Bausch Pharma revenues (non-GAAP)1,10 were $4.669 billion for the full year of 2021, as compared to $4.612 billion for the full year of 2020, an increase of $57 million, or 1%. Excluding the favorable impact of foreign exchange of $37 million and the impact of divestitures and discontinuations of $122 million, revenue increased organically1,7 by 3%.

Salix Segment
Salix segment reported and organic1,7 revenues were $559 million for the fourth quarter of 2021, as compared to $527 million for the fourth quarter of 2020, an increase of $32 million, or 6%. The increase was primarily driven by higher sales resulting from the positive impacts of the recovery from the COVID-19 pandemic, including sales of XIFAXAN (rifaximin), RELISTOR (methylnaltrexone bromide) and TRULANCE (plecanatide), which grew by 9%, 21% and 21%, respectively, compared to the fourth quarter of 2020.

Salix segment reported and organic1,7 revenues were $2.074 billion for the full year of 2021, as compared to $1.904 billion for the full year of 2020, an increase of $170 million, or 9%. The increase was primarily driven by higher sales resulting from the positive impacts of the recovery from the COVID-19 pandemic, including sales of XIFAXAN (rifaximin), TRULANCE (plecanatide) and RELISTOR (methylnaltrexone bromide), which grew by 11%, 26% and 13%, respectively, compared to the full year of 2020.
International Rx Segment8
International Rx segment revenues were $276 million for the fourth quarter of 2021, as compared to $333 million for the fourth quarter of 2020, a decrease of $57 million, or 17%. Excluding the unfavorable impact of foreign exchange of $6 million and the impact of divestitures and discontinuations of $69 million, primarily due to the divestiture of Amoun, the International Rx segment increased organically1,7 by 7% compared to the fourth quarter of 2020.

International Rx segment revenues were $1.166 billion for the full year of 2021, as compared to $1.181 billion for the full year of 2020, a decrease of $15 million, or 1%. Excluding the favorable impact of foreign exchange of $28 million and the impact of divestitures and discontinuations of $113 million, primarily due to the divestiture of Amoun, the International Rx segment increased organically1,7 by 7% compared to the full year of 2020. The decrease in revenues was partially offset by higher sales resulting from the positive impacts of the recovery from the COVID-19 pandemic.
Ortho Dermatologics Segment8
Ortho Dermatologics segment reported and organic1,7 revenues were $146 million for the fourth quarter of 2021, as compared to $157 million for the fourth quarter of 2020, a decrease of $11 million, or 7%, primarily driven by a decrease in net realized pricing of our medical dermatology products.

Ortho Dermatologics segment revenues were $564 million for the full year of 2021, as compared to $548 million for the full year of 2020, an increase of $16 million, or 3%. Excluding the favorable impact of foreign exchange of $9 million, the Ortho Dermatologics segment increased organically1,7 by 1% compared to the full year of 2020, primarily driven by an increase in sales in the Thermage and Clear + Brilliant franchises and due to the positive impacts of the recovery from the COVID-19 pandemic, partially offset by a decrease in net realized pricing of our medical dermatology products.
Diversified Products Segment8
Diversified Products segment reported revenues were $214 million for the fourth quarter of 2021, as compared to reported revenues of $249 million for the fourth quarter of 2020, a decrease of $35 million, or 14%. Excluding the impact of divestitures and discontinuations of $1 million, the Diversified Products segment declined organically1,7 by 14% compared to the fourth quarter of 2020, primarily attributable to a decrease in volumes.

Diversified Products segment reported revenues were $865 million for the full year of 2021, as compared to reported revenues of $979 million for the full year of 2020, a decrease of $114 million, or 12%. Excluding the impact of divestitures and discontinuations of $9 million, the Diversified Products segment declined organically1,7 by 11% compared to the full year of 2020, primarily attributable to a decrease in volumes and net realized pricing.
Operating Results
Operating income was $367 million for the fourth quarter of 2021, as compared to a loss of $5 million for the fourth quarter of 2020, a favorable change of $372 million. The change was primarily driven by a decrease in Other expense, net, and lower loss on assets held for sale and amortization, partially offset by an increase in Selling, general and administrative (SG&A) expenses primarily due to an increase in separation, separation-related, IPO and IPO-related costs.

Operating income was $450 million for the full year of 2021, as compared to operating income of $676 million for the full year of 2020, an unfavorable change of $226 million. The change was primarily driven by a goodwill impairment charge of $469 million in our Ortho Dermatologics business, an increase in SG&A expenses due to the non-recurrence of profit protection measures taken in 2020 to manage and reduce operating expenses during the COVID-19 pandemic and an increase in separation, separation-related, IPO and IPO-related costs, partially offset by a decrease in the amortization of intangible assets and an increase in contribution due to the positive impacts of the recovery of the COVID-19 pandemic.

Net Income/Loss
Net income for the fourth quarter of 2021 was $69 million, as compared to a net loss of $153 million for the fourth quarter of 2020, a favorable change of $222 million. The change was primarily due to the favorable change in operating income as discussed above and lower interest expense, partially offset by a decrease in benefit from income taxes.

Net loss for the full year of 2021 was $948 million, as compared to a net loss of $560 million for the full year of 2020, an unfavorable change of $388 million. The change was primarily due to the unfavorable change in operating income as discussed above and a decrease in benefit from income taxes, partially offset by lower interest expense.

Adjusted net income (non-GAAP)1 for the fourth quarter of 2021 was $463 million, as compared to $478 million for the fourth quarter of 2020, a decrease of $15 million.

Adjusted net income (non-GAAP)1 for the full year of 2021 was $1.602 billion, as compared to $1.428 billion for the full year of 2020, an increase of $174 million.

Cash Generated from Operations
The Company generated $24 million of cash from operations in the fourth quarter of 2021, as compared to $394 million in the fourth quarter of 2020, a decrease of $370 million, or 94%. The decrease in cash from operations was primarily attributed to the timing of payments in the normal course of business, an increase in payments for legal settlements, an increase in separation, separation-related, IPO and IPO-related costs and a decrease in net cash provided by Amoun operating activities.

The Company generated $1.426 billion of cash from operations in 2021, as compared to $1.111 billion in 2020, an increase of $315 million, or 28%. The increase in cash from operations is primarily attributable to the timing of payments in the normal course of business and the positive impacts from the recovery from the COVID-19 pandemic, partially offset by an increase in payments for legal settlements, an increase in separation, separation-related, IPO and IPO-related costs and a decrease in net cash provided by Amoun operating activities.

Earnings Per Share
GAAP Earnings Per Share ("EPS") Diluted for the fourth quarter of 2021 was $0.19, as compared to ($0.43) for the fourth quarter of 2020. GAAP EPS Diluted for the full year of 2021 was ($2.64), as compared to ($1.58) for the full year of 2020.

Adjusted EBITDA (non-GAAP)1
Adjusted EBITDA (non-GAAP)1 was $909 million for the fourth quarter of 2021, as compared to $911 million for the fourth quarter of 2020, a decrease of $2 million. Excluding the impact of the Amoun divestiture, Adjusted EBITDA (non-GAAP)1 increased by $17 million, or 2%, compared to the fourth quarter of 2020.

Adjusted EBITDA (non-GAAP)1 was $3.472 billion for the full year of 2021, as compared to $3.294 billion for the full year of 2020, an increase of $178 million. The increase was driven by higher sales resulting from the positive impacts of the recovery from the COVID-19 pandemic, partially offset by the Adjusted EBITDA (non-GAAP)1 associated with Amoun, which was divested in July 2021.

2022 Financial Outlook
Bausch Health provided guidance for the full year of 2022 as follows:

Full-year revenue range of $8.40 – $8.60 billion
Full-year Adjusted EBITDA (non-GAAP)11 range of $3.45 – $3.60 billion
Other than with respect to GAAP Revenues, the Company only provides guidance on a non-GAAP basis. The Company does not provide a reconciliation of forward-looking Adjusted EBITDA (non-GAAP)11 to GAAP net income (loss), due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliation. In periods where significant acquisitions or divestitures are not expected, the Company believes it might have a basis for forecasting the GAAP equivalent for certain costs, such as amortization, which would otherwise be treated as non-GAAP to calculate projected GAAP net income (loss). However, because other deductions (such as restructuring, gain or loss on extinguishment of debt and litigation and other matters) used to calculate projected net income (loss) vary dramatically based on actual events, the Company is not able to forecast on a GAAP basis with reasonable certainty all deductions needed in order to provide a GAAP calculation of projected net income (loss) at this time. The amount of these deductions may be material and, therefore, could result in projected GAAP net income (loss) being materially less than projected Adjusted EBITDA (non-GAAP)11. These statements represent forward-looking information and may represent a financial outlook, and actual results may vary. Please see the risks and assumptions referred to in the Forward-looking Statements section of this news release.

Additional Highlights

Bausch Health’s cash, cash equivalents, restricted cash and other settlement deposits were $2.119 billion12 at Dec. 31, 2021
The Company’s availability under its 2023 Revolving Credit Facility was $886 million at Dec. 31, 2021
Basic weighted average shares outstanding for the fourth quarter of 2021 were 360.0 million
Diluted weighted average shares outstanding for the fourth quarter of 2021 were 364.1 million

On February 23, 2022 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare tumors and aggressive cancers, reported that it has completed patient enrollment in Part A of the Phase 2/3 RINGSIDE clinical trial evaluating AL102 in desmoid tumors (Press release, Ayala Pharmaceuticals, FEB 23, 2022, View Source [SID1234608871]). AL102 is a potent, selective, oral gamma-secretase inhibitor (GSI). The Company expects to report interim results from Part A by mid-2022.

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"Completion of enrollment in Part A of the RINGSIDE trial is an important milestone in our AL102 clinical program for desmoid tumors," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "Part A will help us determine the optimal dose for the randomized portion of the study, we will be looking for safety and signs of anti-tumor activity based on MRI. We are extremely grateful to the patients who are participating and we look forward to sharing top line data around mid-year."

A total of 36 patients have been enrolled in Part A of the RINGSIDE study which is evaluating the safety, tolerability of AL102, as well as tumor volume by MRI at 16 weeks. Three dosing regimens of AL102 are being tested to determine the optimal dose regimen to advance forward.

In Part A, the effect of food on AL102 absorption was tested in a sub-study and PK results indicate that no food restrictions are required.

Part B of the study will be double-blind, placebo-controlled, and will start immediately after dose selection from Part A, enrolling up to 156 patients age 12 and up with progressive disease, randomized between AL102 or placebo. The study’s primary endpoint will be progression-free survival (PFS) with secondary endpoints including objective response rate (ORR), duration of response (DOR,) and patient-reported Quality of Life (QOL) measures. Patients who participated in Part A are eligible to enroll into an open-label extension study at the selected dose, and long-term efficacy and safety will be monitored.

For more information on the RINGSIDE Phase 2/3 study with AL102 for the treatment of desmoid tumors, please visit ClinicalTrials.gov and reference Identifier NCT04871282.

About AL102

AL102 is a potent, selective, oral gamma secretase inhibitor (GSI). AL102 is currently being developed for the treatment of desmoid tumors, as well as in combination with Novartis’ B-cell maturation antigen (BCMA)-targeting agents for the treatment of multiple myeloma (MM).

About Desmoid Tumors

Desmoid tumors, also called aggressive fibromatosis or desmoid-type fibromatosis, are rare connective tissue tumors that typically arise in the upper and lower extremities, abdominal wall, head and neck area, mesenteric root and chest wall with the potential to arise in additional parts of the body. Desmoid tumors do not metastasize, but often aggressively infiltrate neurovascular structures and vital organs. People living with desmoid tumors are often limited in their daily life due to chronic pain, functional deficits, general decrease in their quality of life and organ dysfunction. Desmoid tumors have an annual incidence of approximately 1,700 patients in the United States and typically occur in patients between the ages of 15 and 60 years. They are most commonly diagnosed in young adults between 30-40 years of age and are more prevalent in females. Today, surgery is no longer regarded as the cornerstone treatment of desmoid tumors due to high rate of recurrence post-surgery and there are currently no FDA-approved systemic therapies for the treatment of unresectable, recurrent or progressive desmoid tumors.

On February 23, 2022 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported financial results for the fourth quarter and year ended December 31, 2021 and provided a corporate update on its six clinical-stage molecules targeting TIGIT, the adenosine axis (CD73 and dual A2a/A2b receptor), HIF-2a and PD-1 across common cancers, including lung, colon, pancreatic and prostate (Press release, Arcus Biosciences, FEB 23, 2022, View Source [SID1234608870]).

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"Arcus is starting 2022 with a strong cash position and late-stage pipeline that includes two ongoing, and soon to be four, registrational Phase 3 studies for the anti-TIGIT antibody, domvanalimab," said Terry Rosen, Ph.D., Chief Executive Officer of Arcus. "Our strategy is to efficiently investigate and advance novel combinations of our six clinical-stage molecules in areas of high unmet need. We look forward to presenting, later this year, randomized datasets from our trials in lung and pancreatic cancer, both settings with large patient populations with great need for better treatment options."

Anti-TIGIT program (domvanalimab and AB308)

Recent Updates:

First patient was dosed in PACIFIC-8, a registrational Phase 3 study being conducted in collaboration with AstraZeneca. PACIFIC-8 is the second Phase 3 study for domvanalimab and is evaluating domvanalimab plus durvalumab, an anti-PD-L1 antibody, in unresectable Stage 3 NSCLC with curative intent, where durvalumab is standard of care.
2022 Milestones:

Data from ARC-7, an ongoing randomized 150-patient three-arm study in first-line PD-L1≥50% NSCLC, including progression-free survival data for all three arms, are expected to be presented in 2H22.
Arcus and Gilead plan to initiate two new Phase 3 studies for domvanalimab and zimberelimab in lung and gastrointestinal (GI) cancers, as well as additional clinical studies of domvanalimab-based combinations, in 2022.
Presentation of initial data from the Phase 1/1b ARC-12 study evaluating AB308, an Fc-enabled anti-TIGIT antibody, in combination with zimberelimab in advanced malignancies.
Etrumadenant (A2a/A2b adenosine receptor antagonist)

2022 Milestones:

Data from the etrumadenant-containing arm of ARC-7 are anticipated to be presented in 2H22.
Data from the randomized cohort of ARC-6 evaluating etrumadenant plus zimberelimab and docetaxel versus docetaxel in second-line metastatic castrate-resistant prostate cancer (CRPC) are anticipated in 2H22.
Additional clinical studies for etrumadenant, including combinations with domvanalimab, are being planned with Gilead.
Quemliclustat (small molecule CD73 inhibitor)

2022 Milestones:

Results from the randomized portion of ARC-8, including data on progression-free survival, are expected to be presented in 2H22.
Full enrollment of the ARC-8 cohort in 2L pancreatic cancer, an area of high unmet need, is on track to be completed in 1H22.
Additional clinical studies for quemliclustat are being planned with Gilead.
AB521 (HIF-2a inhibitor)

Recent Updates:

Initiated a Phase 1 study (ARC-14) in healthy volunteers to confirm Arcus’s PK/PD and tolerability expectations for AB521 and support rapid advancement into cancer patients.
2022 Milestones:

Preclinical data for AB521, alone and in combination with cabozantinib, as well as initial PK/PD data from the evaluation of AB521 in healthy volunteers, will be presented at the ESMO (Free ESMO Whitepaper) Targeted Anticancer Therapies Congress on March 7, 2022.
A Phase 1/1b study to explore AB521 in clear-cell renal cell carcinoma, alone and in combination with other molecules, including those targeting the CD73-adenosine axis, is anticipated to be initiated in mid-2022.
Discovery Programs:

Recent Updates:

In January, Arcus met the first milestone under an agreement with BVF, which is focused on the discovery and development of a potentially first-in-class small molecule designed to treat a wide range of inflammatory conditions.
Arcus recently selected AB598 (CD39 antibody) as a development candidate, which is advancing into IND-enabling studies; several other oncology discovery programs continue to progress.
Financial Results for the Fourth Quarter and Full Year Ended December 31, 2021

Cash, cash equivalents and investments were $681.3 million as of December 31, 2021, compared to $735.1 million as of December 31, 2020. The decrease was primarily due to cash used in operations and purchases of property and equipment totaling $26.1 million, partially offset by gross proceeds of $220.4 million received under the Amended and Restated Stock Purchase Agreement with Gilead in February 2021. Upon the receipt of $725 million in option exercise payments from Gilead in January 2022, Arcus’s cash and cash equivalents and investments totaled approximately $1.4 billion. Arcus expects cash, cash equivalents and marketable securities on-hand to be sufficient to fund operations into 2026.
Revenues: Collaboration and license revenues were $354.5 million for the three months ended December 31, 2021, compared to $9.5 million for the same period in 2020. The increase was primarily driven by license revenue recognized upon closing of Gilead’s exercise of its options. Collaboration and license revenues were $382.9 million for the full year ended December 31, 2021, compared to $77.5 million for the same period in 2020.
R&D Expenses: Research and development expenses were $49.9 million for the three months ended December 31, 2021, compared to $48.7 million for the same period in 2020. The increase was primarily driven by costs incurred to support Arcus’s expanded clinical and development activities including increased compensation costs related to a larger employee base, increased clinical trial costs, and increased early-stage research costs. Approximately $3.2 million of the increase in compensation costs is related to non-cash stock-based compensation. Research and development expenses were $256.3 million for the full year ended December 31, 2021, compared to $159.3 million for the same period in 2020.
G&A Expenses: General and administrative expenses were $23.3 million for the three months ended December 31, 2021, compared to $12.8 million for the same period in 2020. The increase was driven by the increased complexity of supporting Arcus’s expanding clinical pipeline and collaboration obligations, as well as compliance costs associated with Arcus’s growth. Arcus’s growing employee base and 2021 stock awards drove an increase in employee compensation costs, including approximately $2.7 million of increased non-cash stock-based compensation. General and administrative expenses were $72.3 million for the full year ended December 31, 2021, compared to $42.4 million for the same period in 2020.
Net Income: Net income was $279.4 million for the three months ended December 31, 2021, compared to net loss of $51.9 million for the same period in the prior year. Net income was primarily due to license revenue recognized upon closing of Gilead’s exercise in December 2021 of its options. Net income was $52.8 million for the full year ended December 31, 2021, compared to net loss of $122.9 million for the same period in 2020.
Arcus Clinical Study Overview

Carbo/pem: carboplatin/pemetrexed; dom: domvanalimab; durva: durvalumab; etruma: etrumadenant; gem/nab-pac: gemcitabine/nab-paclitaxel; quemli: quemliclustat; R/R: relapsed/refractory; SOC: standard of care; zim: zimberelimab CRC: colorectal cancer; CRPC: castrate-resistant prostate cancer; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma