On February 23, 2023 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported its financial results for the fourth quarter and full year ended December 31, 2022 and provided an update on the Company’s operations (Press release, BridgeBio, FEB 23, 2023, View Source [SID1234627599]).

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"We are excited to enter 2023 back on the doorstep of potentially meaningful advances for the patients we serve," said Neil Kumar, Ph.D., founder and CEO of BridgeBio. "Amidst our six ongoing Phase 2 or 3 clinical trials, we anticipate important upcoming readouts from our achondroplasia Phase 2 trial in March, and our ATTR-CM Phase 3 trial mid-year."

BridgeBio’s key programs:

Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM):
The Phase 3 ATTRibute-CM study continues to have high operating fidelity.
The Company expects to announce topline registrational data for the month 30 primary endpoint, a hierarchical composite including all-cause mortality and cardiovascular-related hospitalizations, in mid-2023.

Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia:
In July 2022, we reported initial data from the fourth dosing cohort of the Phase 2 dose-escalation trial PROPEL 2, demonstrating a mean change from baseline in annualized height velocity (AHV) of +1.52 cm/year and a responder rate of 64% in children five years of age and older.
Through the fifth dosing cohort to date, infigratinib has been well-tolerated with no serious adverse events reported, no adverse events that required discontinuation reported, and with no dose-dependent phosphate elevation reported.
The Company expects to share preliminary data from the fifth dosing cohort in March 2023, and to initiate a registrational Phase 3 trial in 2023.
In Cohort 5, the Company hopes to observe a tolerability profile and efficacy at least in-line with Cohort 4. If successful, the Company believes infigratinib, if approved, has the potential to capture a significant share of the market based on blinded market research.

Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1):
In December 2022, the Company initiated the CALIBRATE Phase 3 trial, a pivotal trial comparing the effects of encaleret to standard of care on blood calcium concentration and 24-hour urine calcium excretion over a 24-week treatment period in patients with ADH1.
In a Phase 2b safety and efficacy trial of encaleret for ADH1, 69% of the participants achieved concurrent values of both blood calcium concentration and 24-hour urine calcium excretion within the reference range after 24 weeks of outpatient encaleret treatment; none of these individuals attained this dual therapeutic goal while on standard of care.
Population genetics analyses estimate approximately 25,000 carriers of gain-of-function variants of the CaSR, the underlying cause of ADH1, in the US and EU.
The Company anticipates sharing topline data from CALIBRATE in late 2023 or the first half of 2024.
If approved, encaleret could be the first therapy specifically indicated for the treatment of ADH1.

BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2i (LGMD2I):
The Company reported positive top line data from the ongoing Phase 2 clinical trial in October 2022 and anticipates initiating a global Phase 3 registrational trial of BBP-418 for LGMD2I in 2023.
To that end, the Company has engaged with regulatory authorities to align on a Phase 3 trial design.
BBP-418 has a potentially-addressable population of 7,000 LGMD2I patients in the US and EU.
There are currently no disease-modifying treatments available for LGMD2I.

BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH):
The Phase 1/2 gene therapy trial of BBP-631 for CAH continued to progress; as of February 1, 2023, BBP-631 has been generally well-tolerated in four patients treated at the first two dose levels.
The Company plans to provide an update from patients treated at the third dose level by the end of 2023.
CAH is one of the most prevalent genetic diseases potentially addressable with adeno-associated virus (AAV) gene therapy, with more than 75,000 cases estimated in the United States and European Union.

RAS cancer portfolio:
BridgeBio is continuing to progress the three main programs of its RAS franchise:
BBO-8520, an investigational, next-generation small molecule KRAS G12C dual inhibitor candidate that is designed to directly bind and inhibit KRAS G12C in both its active (GTP bound) and inactive (GDP bound) conformations, which remains on track to file an IND and enter the clinic in the second half of 2023.
A PI3Kα:RAS breaker program, investigational small molecules that are designed to block Ras-driven PI3Kα activation with a novel and potentially broad mechanism of action to target not only PI3Kα mutant tumors and RAS mutant tumors, but potentially other tumors driven by RTK activation of RAS signaling. The Company remains on track to select a development candidate in 2023, with IND filing to follow in 2024.
The Company’s pan-KRAS program, which targets multiple KRAS mutants including KRASG12D and KRASG12V, which are present in a large percentage of colorectal, pancreatic, and non-small cell lung cancer tumors. Development candidate selection for this program is planned for late 2023 or early 2024.
Corporate Updates:

Board of Directors: Appointed Frank McCormick, Ph.D., FS, DSc (Hon) to the BridgeBio Board of Directors. Dr. McCormick is a co-founder of BridgeBio and serves as the Chairman of Oncology. He is also a professor at the UCSF Helen Diller Family Comprehensive Cancer Center, where he holds the David A. Wood Chair of Tumor Biology and Cancer Research, and he has led the National Cancer Institute’s Ras Initiative since its inception in 2013. Dr. McCormick rotates in as Dr. Richard Scheller leaves the Board of Directors; Dr. Scheller will continue to serve as BridgeBio’s Chairman of Research and Development. In addition, Brent Saunders will resign from the board of directors in early March in order to focus on his recent appointment as Chief Executive Officer and Chairman of the Board of Bausch + Lomb.
Fourth Quarter and Full Year 2022 Financial Results:
Cash, Cash Equivalents, Marketable Securities and Restricted Cash (Current)

Cash, cash equivalents, marketable securities and restricted cash (current), totaled $466.2 million as of December 31, 2022, compared to $787.7 million as of December 31, 2021. The net decrease of $321.5 million in cash, cash equivalents, marketable securities and restricted cash (current) is primarily attributable to net cash used in operating activities of $419.5 million. Net cash used in operating activities during the fiscal year 2022 was partially offset by a $90.0 million upfront payment received under the License, Development and Commercialization Agreement by and among the Company, its affiliate, Navire Pharma, Inc., and Bristol-Myers Squibb Company, or BMS (the "Navire-BMS License Agreement").

During fiscal year 2022, the Company also received $110.0 million from the sale of its priority review voucher, $10.0 million upon closing of an asset purchase agreement between its affiliate, Origin Biosciences, Inc., and Sentynl Therapeutics, Inc. and $4.9 million of net proceeds from the sale of common stock through an "at-the-market" offering. The Company made a $20.5 million mandatory prepayment of a portion of its term loan obligations under its Loan and Security Agreement, as amended, in connection with the upfront payment received from BMS.

As of December 31, 2022, the Company’s restricted cash (current) balance of $37.9 million primarily represents funds in a controlled account that was established in connection with the Second Amendment of the Company’s Amended Loan and Security Agreement. The use of such non-interest-bearing cash is restricted per the terms of the underlying amended loan agreement and is to be used solely for certain research and development expenses directly attributable to the performance of obligations associated with the Navire-BMS License Agreement.

Cash, cash equivalents, marketable securities and restricted cash (current), decreased by $92.3 million when compared to the balance as of September 30, 2022 of $558.5 million. Net cash used in operating activities was $93.2 million for the three months ended December 31, 2022 which primarily contributed to the decline in the cash, cash equivalents, marketable securities and restricted cash (current) during the fourth quarter of fiscal year 2022.

Operating Costs and Expenses
Operating costs and expenses for the three months and year ended December 31, 2022 were $131.1 million and $589.9 million, respectively, as compared to $178.5 million and $646.3 million for the same periods in the prior year. The overall decrease in operating costs and expenses for the three months and year ended December 31, 2022 compared to the comparative periods was mainly due to overall decreases in research, development and other (R&D) expenses and selling, general and administrative expenses resulting from the Company’s reprioritization of its R&D programs and company-wide streamlining of costs. The effects of the Company’s restructuring initiative that began in the first quarter of fiscal year 2022 are now being realized due to reductions of operating costs and expenses. Restructuring, impairment and related charges for the three months and year ended December 31, 2022 of $7.7 million and $43.8 million, respectively, were primarily comprised of winding down costs, exit and other related costs, impairments and write-offs of long-lived assets, and severance and employee-related costs. The Company continues to evaluate its restructuring alternatives to drive operational changes in business processes, efficiencies, and cost savings.

"We head into 2023 with cash on hand providing us with runway into 2024, and as we read out our key upcoming catalysts we expect to continue to allocate our capital carefully in order to preserve that runway and our optionality," said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. "We will also continue to look for ways to extend our runway by considering potential royalty monetizations and partnerships."

The Company’s research and development and other expenses have not been significantly impacted by the global COVID-19 pandemic for the periods presented. While BridgeBio experienced some delays in certain of its clinical enrollment and trial commencement activities, it continues to adapt with alternative site, telehealth and home visits, and at-home drug delivery, as well as mitigation strategies with its contract manufacturing organizations. The longer-term impact, if any, of COVID-19 on BridgeBio’s operating costs and expenses is currently unknown.

BRIDGEBIO PHARMA, INC.
Condensed Consolidated Statements of Operations
(in thousands, except shares and per share amounts)

Three Months Ended December 31, Year Ended December 31,

2022 2021 2022 2021
(Unaudited) (Unaudited) (1)
Revenue $ 1,870 $ 12,886 $ 77,648 $ 69,716
Operating costs and expenses:
Research, development and others 91,549 123,751 402,896 454,138
Selling, general and administrative 31,862 54,749 143,189 192,210
Restructuring, impairment and related charges 7,691 — 43,765 —
Total operating costs and expenses 131,102 178,500 589,850 646,348
Loss from operations (129,232 ) (165,614 ) (512,202 ) (576,632 )
Other income (expense), net:
Interest income 4,092 182 7,542 1,133
Interest expense (19,990 ) (15,134 ) (80,438 ) (46,778 )
Gain from sale of priority review voucher, net — — 107,946 —
Other income (expense), net 4,560 28,284 (7,500 ) 35,823
Total other income (expense), net (11,338 ) 13,332 27,550 (9,822 )
Net loss (140,570 ) (152,282 ) (484,652 ) (586,454 )
Net loss attributable to redeemable convertible noncontrolling interests and noncontrolling interests 2,979 5,105 3,469 23,915
Net loss attributable to common stockholders of BridgeBio $ (137,591 ) $ (147,177 ) $ (481,183 ) $ (562,539 )
Net loss per share, basic and diluted $ (0.92 ) $ (1.01 ) $ (3.26 ) $ (3.90 )
Weighted-average shares used in computing net loss per share, basic and diluted 149,344,380 145,283,213 147,473,076 144,356,619


Three Months Ended December 31, Year Ended December 31,

Stock-based compensation 2022 2021 2022 2021
(Unaudited) (Unaudited) (1)
Research, development and others $ 8,941 $ 9,654 $ 37,987 $ 56,195
Selling, general and administrative 13,643 12,859 54,669 49,379
Restructuring, impairment and related charges — — 1,172 —
Total stock-based compensation $ 22,584 $ 22,513 93,828 $ 105,574
(1) The condensed consolidated financial statements as of and for the year ended December 31, 2021 are derived from the audited consolidated financial statements as of that date.

BRIDGEBIO PHARMA, INC.
Condensed Consolidated Balance Sheets
(In thousands)

December 31 December 31,

2022 2021
(Unaudited) (1)
Assets
Cash and cash equivalents and marketable securities $ 428,269 $ 787,515
Investment in equity securities 43,653 49,148
Receivable from licensing and collaboration agreements 17,079 19,749
Restricted cash, current 37,930 177
Prepaid expenses and other current assets 21,922 32,269
Property and equipment, net 14,569 30,066
Operating lease right-of-use assets 10,678 15,907
Intangible assets, net 28,712 44,934
Other assets 20,224 33,027
Total assets $ 623,036 $ 1,012,792
Liabilities, Redeemable Convertible Noncontrolling Interests and Stockholders’ Deficit
Accounts payable $ 11,558 $ 11,884
Accrued and other liabilities 106,195 118,247
Operating lease liabilities 15,949 22,366
2029 Notes 734,988 733,119
2027 Notes 541,634 539,934
Term loan 430,993 430,752
Other long-term liabilities 26,643 22,069
Redeemable convertible noncontrolling interests (1,589 ) 1,423
Total BridgeBio stockholders’ deficit (1,254,617 ) (870,414 )
Noncontrolling interests 11,282 3,412
Total liabilities, redeemable convertible noncontrolling interests and stockholders’ deficit $ 623,036 $ 1,012,792
(1) The condensed consolidated financial statements as of and for the year ended December 31, 2021 are derived from the audited consolidated financial statements as of that date.

BRIDGEBIO PHARMA, INC.
Consolidated Statements of Cash Flows
(In thousands)

Year Ended December 31,

2022 2021
Unaudited (1)
Operating activities
Net loss $ (484,652 ) $ (586,454 )
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation 91,559 99,505
Depreciation and amortization 6,771 5,843
Noncash lease expense 5,172 5,611
Net loss (gain) from investment in equity securities 8,222 (29,914 )
Gain from sale of priority review voucher, excluding transaction costs (110,000 ) —
Accrual of payment-in-kind interest on term loan 13,562 —
Gain from recognition of receivable from licensing and collaboration agreement (12,500 ) —
Fair value of shares issued under a license agreement 4,567 —
Accretion of debt 8,570 5,795
Fair value adjustment of warrants 1,571 1,197
Loss on sale of certain assets 6,261 —
Impairment of long-lived assets 12,720 —
LEO call option expense (income) — (5,550 )
Loss on early extinguishment of debt — 3,337
Other noncash adjustments 604 7,092
Changes in operating assets and liabilities: —
Receivable from licensing and collaboration agreements 15,169 (19,749 )
Prepaid expenses and other current assets 7,671 (4,262 )
Other assets 10,971 (9,816 )
Accounts payable (349 ) 2,833
Accrued compensation and benefits (2,362 ) 7,378
Accrued research and development liabilities (4,309 ) 11,178
Accrued professional services (4,996 ) 2,157
Operating lease liabilities (6,245 ) (6,122 )
Deferred revenue 15,262 —
Other accrued and other long-term liabilities (2,733 ) 12,007
Net cash used in operating activities (419,494 ) (497,934 )
Investing activities
Purchases of marketable securities (137,493 ) (589,892 )
Maturities of marketable securities 479,688 380,200
Sales of marketable securities — 62,691
Purchases of investment in equity securities (55,562 ) (53,383 )
Sales of investment in equity securities 52,835 34,150
Increase in cash and cash equivalents from consolidation of PellePharm — 13,654
Payment for intangible assets (1,500 ) (35,000 )
Proceeds from sale of priority review voucher, excluding transaction costs 110,000 —
Proceeds from sale of certain assets 10,000 —
Purchases of property and equipment (4,821 ) (13,246 )
Net cash provided by (used in) investing activities 453,147 (200,826 )
Financing activities
Proceeds from issuance of 2029 Notes — 747,500
Issuance costs and discounts associated with issuance of 2029 Notes — (16,064 )
Purchase of capped calls — (61,295 )
Repurchase of common stock — (200,000 )
Proceeds from issuance of noncontrolling interests — 3,500
Repurchase of Eidos noncontrolling interest, including direct transaction costs — (85,090 )
Proceeds from term loan, net of issuance costs — 456,296
Repayment of term loan (20,486 ) (124,119 )
Proceeds from common stock issuances under ESPP 2,558 3,821
Repurchase of common stock to satisfy tax withholding (1,561 ) (4,746 )
Proceeds from stock option exercises, net of repurchases 666 16,643
Proceeds from issuance of common stock through at-the-market offering, net 4,852 —
Other financing activities 837 —
Net cash (used in) provided by financing activities (13,134 ) 736,446
Net increase in cash, cash equivalents and restricted cash 20,519 37,686
Cash, cash equivalents and restricted cash at beginning of year 396,365 358,679
Cash, cash equivalents and restricted cash at end of year $ 416,884 $ 396,365

Year Ended December 31,

2022 2021
Unaudited (1)
Supplemental Disclosures of Cash Flow Information:
Cash paid for interest $ 54,443 $ 29,774
Supplemental Disclosures of Non-Cash Investing and Financing Information:
Payment-in-kind interest accrued in prior year added to principal of term loan $ 1,763 $ —
Leasehold improvements paid by landlord $ — $ 2,449
Transfers to noncontrolling interests $ (3,512 ) $ (2,124 )
Noncash contribution by a noncontrolling interest $ — $ 21,600
Unpaid property and equipment $ 47 $ 563
Recognized intangible asset recorded in other accrued and other long-term liabilities $ 11,000 $ 12,500
Unpaid debt issuance costs $ — $ 1,120
Net noncash portion of repurchase of Eidos noncontrolling interests $ — $ 38,168
Direct transaction costs in the repurchase of Eidos recorded in additional paid-in capital previously classified in prepaid expenses and other current assets $ — $ 8,749
Reconciliation of Cash, Cash Equivalents and Restricted Cash
Cash and cash equivalents $ 376,689 $ 393,772
Restricted cash (current) 37,930 177
Restricted cash – included in other assets 2,265 2,416
Total cash, cash equivalents and restricted cash at end of year $ 416,884 $ 396,365
(1) The condensed consolidated financial statements as of and for the year ended December 31, 2021 are derived from the audited consolidated financial statements as of that date.

On February 23, 2023 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health", "BHC", the "Company", or "we") reported its fourth-quarter and full-year 2022 financial results (Press release, Bausch Health, FEB 23, 2023, View Source [SID1234627598]).

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"2022 was a transformative year for Bausch Health, as we executed on our strategic priorities," said Thomas J. Appio, Chief Executive Officer, Bausch Health. "Since completing the initial public offering of Bausch + Lomb last May, we have made significant progress in de-levering our balance sheet, reducing our debt principal net of unrestricted cash by $3.2 billion. We are encouraged by our second half performance and look to build on this momentum. We will invest in sustainable growth drivers across our products and pipeline to position us for long-term success," concluded Appio.

Fourth-Quarter and Full-Year 2022 Revenue Performance
Total reported revenues were $2.2 billion for the fourth quarter of 2022, flat compared with the fourth quarter of 2021. Excluding the unfavorable impact of foreign exchange of $78 million and the impact of divestitures and discontinuations of $6 million, revenue increased by 4% organically1 compared with the fourth quarter of 2021.

Total reported revenues were $8.1 billion for the full year of 2022, compared with $8.4 billion in the full year of 2021, a decrease of $310 million, or 4%. Excluding the unfavorable impact of foreign exchange of $264 million and the impact of divestitures and discontinuations of $178 million, revenue increased organically1 by 2% compared with the full year of 2021.

Revenues by segment were as follows:

Three Months Ended December 31,
(in millions) 2022 2021 Reported Change Reported Change
Change at Constant Currency1
(non-GAAP)
Organic
Change1
(non-GAAP)
Total Bausch Health Revenues $2,193 $2,196 ($3) 0% 3% 4%
Bausch Health (Excl. B+L) $1,197 $1,195 $2 0% 2% 2%
Salix segment $581 $559 $22 4% 4% 4%
International segment2
$261 $276 ($15) (5%) 0% 2%
Solta Medical segment2
$99 $89 $10 11% 20% 20%
Diversified Products segment2
$256 $271 ($15) (6%) (6%) (6%)
Bausch + Lomb segment2
$996 $1,001 ($5) 0% 5% 5%

Twelve Months Ended December 31,
(in millions) 2022 2021 Reported Change Reported Change
Change at Constant Currency1
(non-GAAP)
Organic
Change1
(non-GAAP)
Total Bausch Health Revenues $8,124 $8,434 ($310) (4%) (1%) 2%
Bausch Health (Excl. B+L) $4,356 $4,669 ($313) (7%) (5%) (1%)
Salix segment $2,090 $2,074 $16 1% 1% 1%
International segment2
$988 $1,166 ($178) (15%) (10%) 5%
Solta Medical segment2
$300 $308 ($8) (3%) 2% 2%
Diversified Products segment2
$978 $1,121 ($143) (13%) (13%) (13%)
Bausch + Lomb segment2
$3,768 $3,765 $3 0% 5% 5%

Salix Segment
Salix segment reported and organic1 revenues were $581 million for the fourth quarter and $2,090 million for the full year of 2022, compared with $559 million for the fourth quarter and $2,074 million for the full year of 2021, an increase of $22 million, or 4% in the fourth quarter, and $16 million, or 1% for the full year. Sales growth for the quarter and full year was primarily driven by Xifaxan, Relistor, Trulance and Plenvu.

International Segment2
International segment reported revenues were $261 million for the fourth quarter and $988 million for the full year of 2022, compared with $276 million for the fourth quarter and $1,166 million for the full year of 2021, a decrease of $15 million, or 5% in the fourth quarter, and $178 million, or 15% for the full year.

Excluding the unfavorable impact of foreign exchange of $16 million for the fourth quarter and $65 million for the full year of 2022, and the impact of divestitures and discontinuations of $4 million for the fourth quarter and $167 million for the full year of 2022, segment revenues increased organically1 by 2% for the fourth quarter and 5% for the full year, compared with the fourth quarter and the full year of 2021, primarily driven by Canada and Europe.

Solta Medical Segment2
Solta Medical segment reported revenues were $99 million for the fourth quarter and $300 million for the full year of 2022, compared with $89 million for the fourth quarter and $308 million for the full year of 2021, an increase of $10 million, or 11% in the fourth quarter, and a decrease of $8 million, or 3% for the full year.

Excluding the unfavorable impact of foreign exchange of $8 million for the fourth quarter and $15 million for the full year of 2022, segment revenues increased organically1 by 20% for the fourth quarter and 2% for the full year, compared with the fourth quarter and the full year of 2021, primarily driven by strong results in Asia Pacific (excluding China).

Diversified Products Segment2
Diversified Products segment reported revenues were $256 million for the fourth quarter and $978 million for the full year of 2022, compared with $271 million for the fourth quarter and $1,121 million for the full year of 2021, a decrease of $15 million, or 6% in the fourth quarter, and a decrease of $143 million, or 13% for the full year.

Segment revenues declined organically1 by 6% for the fourth quarter and 13% for the full year, compared with the fourth quarter and the full year of 2021, primarily attributable to declines in Neurology and Generics.

Bausch + Lomb Segment2
Bausch + Lomb segment reported revenues were $996 million for the fourth quarter and $3,768 million for the full year of 2022, compared with $1,001 million for the fourth quarter and $3,765 million for the full year of 2021, a decrease of $5 million, or less than 1% in the fourth quarter, and an increase of $3 million, or less than 1% for the full year.

Excluding the unfavorable impact of foreign exchange of $54 million for the fourth quarter and $184 million for the full year of 2022, and the impact of divestitures and discontinuations of $3 million for the fourth quarter and $10 million for the full year of 2022, segment revenues increased organically1 by 5% for the fourth quarter and for the full year, compared with the fourth quarter and the full year of 2021.

Consolidated Operating (Loss) Income
Consolidated operating loss was $236 million for the fourth quarter of 2022, compared with operating income of $367 million for the fourth quarter of 2021, a decrease of $603 million, primarily driven by a goodwill impairment charge of $622 million in our Neurology business.

Consolidated operating income was $454 million for the full year of 2022, compared with operating income of $450 million for the full year of 2021, an increase of $4 million. The change reflects, among

other factors: a decrease in contribution (product sales revenue less cost of goods sold, exclusive of amortization and impairments of intangible assets) of $271 million, mainly due to the unfavorable impact of foreign currencies and impact of our divestiture of Amoun on July 26, 2021, an increase in Goodwill impairments of $355 million associated with our Neurology and Ortho Dermatologics reporting unit, a decrease in Amortization of intangible assets of $160 million, a decrease in Asset impairments, including loss on assets held for sale of $219 million, primarily attributable to adjustments to the loss on assets held for sale in connection with the Amoun sale during 2021, a favorable change in Other expense, net of $338 million, primarily attributable: (i) to higher adjustments related to the settlements of certain litigation matters during 2021 and (ii) the loss on the completion of the Amoun sale in 2021, partially offset by insurance recoveries related to certain litigation matters.

Net (Loss) Income Attributable to Bausch Health
Net loss attributable to Bausch Health for the fourth quarter of 2022 was $410 million, compared with income of $69 million for the fourth quarter of 2021, an unfavorable change of $479 million. The change was primarily due to the increase in goodwill impairments, partially offset by a gain on extinguishment of debt.

Net loss attributable to Bausch Health for the full year of 2022 was $225 million, compared with a loss of $948 million for the full year of 2021, a favorable change of $723 million. The change was primarily due the changes in operating income as discussed above and gains on extinguishment of debt in 2022 of $875 million.

Adjusted net income attributable to Bausch Health (non-GAAP)1 was $372 million for the fourth quarter and $1,113 million for the full year of 2022, compared with $463 million for the fourth quarter and $1,602 million for the full year of 2021, a decrease of $91 million in the fourth quarter and $489 million for the full year.

Earnings (Loss) Per Share Attributable to Bausch Health
GAAP Earnings Per Share attributable to Bausch Health was ($1.13) for the fourth quarter and ($0.62) for the full year of 2022, compared with $0.19 for the fourth quarter and ($2.64) for the full year of 2021.

Adjusted EBITDA attributable to Bausch Health (non-GAAP)1
Adjusted EBITDA attributable to Bausch Health (non-GAAP)1 was $823 million for the fourth quarter and $3,022 million for the full year of 2022, compared with $909 million for the fourth quarter and $3,472 million for the full year of 2021, a decrease of $86 million in the quarter and $450 million for the full year.

Cash (Used in) Provided by Operating Activities
The Company generated $475 million of cash from operations in the fourth quarter and used cash of $728 million for the full year of 2022, compared with generating $24 million in the fourth quarter and $1,426 for the full year of 2021. The decrease in cash flow from operations of $2,154 million for the full year is primarily attributable to: (i) reductions of restricted cash as certain litigation settlements became final and unappealable, (ii) changes in business performance, (iii) the impact of our divestiture of Amoun on July 26, 2021 and (iv) an increase in payments for separation costs, separation-related costs, IPO costs and IPO-related costs in 2022 as compared to 2021.

Balance Sheet Highlights as of December 31, 2022
•Cash, cash equivalents, and restricted cash were $591 million.
•Executed open market repurchases during the second and fourth quarters of this year, retiring an aggregate of $927 million in principal of bonds for $550 million of cash consideration.
•Reduced debt principal net of unrestricted cash by $3.2 billion since the IPO of B+L.
•Bausch Health (excl. B+L) had availability under its revolving credit facility of approximately $480 million and Bausch + Lomb had availability under its revolving credit facility of approximately $475 million.

2023 Financial Outlook
The Company is not providing consolidated full year guidance, as Bausch + Lomb has not provided full year guidance. Bausch Health (excl. B+L) has provided guidance for the full year of 2023 as follows:
•Full-year revenue range of $4.45 – $4.6 billion
•Full-year adjusted EBITDA (non-GAAP)1 range of $2.3 – $2.4 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)1 to GAAP net income (loss), due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliation. Because 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)1. 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. The guidance in this news release is only effective as of the date it is given, and will not be updated or affirmed unless and until the Company publicly announces updated or affirmed guidance.

Conference Call Details
Date: Thursday, Feb. 23, 2023
Time: 8:00 a.m. ET
Webcast: View Source

A replay of the conference call will be available on the investor relations website.

On February 23, 2023 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported financial results for the fourth quarter and full year ended December 31, 2022 and provided a corporate update (Press release, Arvinas, FEB 23, 2023, View Source [SID1234627597]).

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"2022 was an exciting year for Arvinas as we transitioned into a late-stage development organization and laid the foundation for an important year of data readouts and trial initiations in 2023," said John Houston, Ph.D., president and chief executive officer at Arvinas. "Notably, the initiation of our Phase 3 monotherapy trial with ARV-471 in ER+/HER2- metastatic breast cancer marks our first registrational study and if successful, will lead to our first commercial product bringing an important new treatment option to patients. We are on-track to initiate our second and third Phase 3 trials – one in the first line setting with ARV-471 and one with bavdegalutamide in metastatic castrate resistant prostate cancer – in the second half of this year, further validating our novel PROTAC discovery engine platform."

Recent Developments and 4Q Business Highlights

Gained alignment with FDA on an approach to the planned 1L Phase 3 trial with ARV-471 in combination with palbociclib to enable trial initiation in 2H 2023
The approach includes a Phase 3 lead-in to evaluate the optimal dose of palbociclib (100 mg or 75 mg) in combination with 200 mg ARV-471
The approach follows the recent analysis of data from the ongoing Phase 1b combination study of ARV-471 with palbociclib, in which an increase in palbociclib exposure was observed relative to historical palbociclib pharmacokinetic data
Initiated the VERITAC-2 Phase 3 2L+ clinical trial of ARV-471 as a monotherapy for the treatment of patients with ER+/HER2- metastatic breast cancer
Presented results from the Phase 2 cohort expansion portion (VERITAC) of a Phase 1/2 study with ARV-471 for the treatment of ER+/HER2- metastatic breast cancer
Initiated two arms of a Phase 1b umbrella trial with ARV-471; one in combination with ribociclib and another with abemaciclib (TACTIVE-U)
Initiated a Phase 2 trial with ARV-471 as a monotherapy in the neoadjuvant setting (TACTIVE-N)
Presented new preclinical neuroscience data at Society for Neuroscience’s "Neuroscience 2022" meeting demonstrating cross-species oral bioavailability and biodistribution into deep brain regions of nonhuman primates
Disclosed a BCL6 (B-cell lymphoma 6) PROTAC degrader in oncology and a LRRK2 (leucine-rich repeat kinase 2) PROTAC degrader in neuroscience as the Company’s next IND or CTA submissions
Appointed Everett Cunningham to the Company’s Board of Directors
Anticipated Upcoming Milestones and Expectations

ARV-471
With Pfizer, the companies plan to:

Initiate a Phase 3 trial with ARV-471 + palbociclib as a first-line treatment in patients with ER+/HER2- locally advanced or metastatic breast cancer (2H 2023)
Initiate additional arms of the Phase 1b combination umbrella trial (TACTIVE-U) with other targeted therapies (2023)
Provide an update with preliminary data from the Phase 1b combination trial with palbociclib (1H 2023)
Submit and present data from the Phase 1b combination trial with palbociclib at a medical congress (2H 2023)
AR Franchise (Bavdegalutamide/ARV-110, ARV-766)

Initiate a global Phase 3 trial with confirmed bavdegalutamide dose in metastatic castration-resistant prostate cancer (mCRPC) for patients with AR T878/H875 tumor mutations (2H 2023)
Complete enrollment in the Phase 1b combination study with bavdegalutamide plus abiraterone (2H 2023)
Share Phase 1 dose escalation trial data with ARV-766 in mCRPC (2Q 2023)
Initiate a Phase 1b or Phase 2 trial in patients who have not previously received novel hormonal agents (2H 2023)
Pipeline:

Submit two investigational new drug (IND)/clinical trial authorization (CTA) applications for the Company’s BCL6 (oncology) and LRRK2 (neuroscience) PROTAC protein degraders by year-end 2023
Progress at least two additional PROTAC protein degrader programs into IND- or CTA-enabling studies by year-end 2023
Financial Guidance
Based on its current operating plan, Arvinas believes its cash, cash equivalents, restricted cash and marketable securities as of December 31, 2022, is sufficient to fund planned operating expenses and capital expenditure requirements into 2026.

Full Year and Fourth Quarter Financial Results

Cash, Cash Equivalents, Restricted Cash and Marketable Securities Position: As of December 31, 2022, cash, cash equivalents, restricted cash and marketable securities were $1,210.8 million, as compared with $1,507.1 million as of December 31, 2021. The decrease in cash, cash equivalents, restricted cash and marketable securities of $296.3 million for the year was primarily related to cash used in operations of $279.2 million (net of $6.5 million received from two collaborators), unrealized loss on marketable securities of $14.6 million, loss on the sales of securities of $0.4 million and the purchase of lab equipment and leasehold improvements of $6.8 million, partially offset by proceeds from the exercise of stock options of $4.7 million.

Research and Development Expenses: Research and development expenses were $315.0 million and $98.3 million for the year and quarter ended December 31, 2022, as compared with $180.4 million and $61.8 million for the year and quarter ended December 31, 2021. The increase in research and development expenses of $134.6 million for the year was primarily due to an increase in expenses associated with our platform and exploratory programs of $77.7 million, our AR program (which includes bavdegalutamide (ARV-110) and ARV-766) of $15.7 million and our ER program of $41.2 million, which is net of the cost sharing of ARV-471 under the global Pfizer collaboration agreement to develop and commercialize ARV-471 that was initiated in July 2021 (ARV-471 Collaboration Agreement). The increase in research and development expenses of $36.5 million for the quarter was primarily due to an increase in expenses associated with our platform and exploratory programs of $24.9 million, our AR program of $5.5 million and our ER program of $6.0 million.

General and Administrative Expenses: General and administrative expenses were $79.6 million and $15.1 million for the year and quarter ended December 31, 2022, as compared with $61.6 million and $18.9 million for the year and quarter ended December 31, 2021. The increase in general and administrative expenses of $18.0 million for the year was primarily due to an increase of personnel related costs of $15.0 million and professional fees of $5.6 million. The decrease in general and administrative expenses of $3.8 million for the quarter was primarily due to a decrease in facility costs attributable to our general and administrative functions.

Revenue: Revenue was $131.4 million and $38.0 million for the year and quarter ended December 31, 2022 as compared with $53.6 million and $28.7 million for the year and quarter ended December 31, 2021. Revenue is related to the ARV-471 Collaboration Agreement with Pfizer that was initiated in July 2021, the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Bayer that was initiated in July 2019, the collaboration and license agreement with Pfizer that was initiated in January 2018, the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017 and revenue related to our Oerth Bio joint venture which was initiated in July 2019. The increase in revenues of $77.8 million and $9.3 million for the year and quarter was primarily due to revenues from the ARV-471 Collaboration Agreement with Pfizer.

Income Tax Expense: Income tax expense was $20.9 million and $10.8 million for the year and quarter ended December 31, 2022, as compared with zero for the year and quarter ended December 31, 2021 due to taxable income projected for fiscal year 2022 primarily related to revenue recognized in 2022 for tax purposes from the ARV-471 Collaboration Agreement.

Loss from Equity Method Investment: Loss from equity method investment totaled $10.6 million and $3.0 million for the year and quarter ended December 31, 2022, compared with $6.9 million and $2.3 million for the year and quarter ended December 31, 2021 due to increased operating losses incurred by Oerth Bio.

Net Loss: Net loss was $282.5 million and $82.9 million for the year and quarter ended December 31, 2022, as compared with $191.0 million and $52.9 million for the year and quarter ended December 31, 2021. The increase in net loss for the year and quarter was primarily due to increased research and development expenses, general and administrative expenses and losses from equity investment, partially offset by increased revenue.

About bavdegalutamide (ARV-110)
Bavdegalutamide (ARV-110) is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). Bavdegalutamide is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

Bavdegalutamide has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About ARV-471
ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of ARV-471; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.

About ARV-766
ARV-766 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade AR. In preclinical studies, ARV-766 degraded all resistance-driving point mutations of AR, including L702H, a mutation associated with treatment with abiraterone and other AR-pathway therapies.

ARV-766 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer, and ARV-766 may also have applicability in other AR-driven diseases both in and outside oncology. ARV-766 has demonstrated activity in preclinical models of resistance to currently available AR-targeted therapies.

On February 23, 2023 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its consolidated financial results for the fourth quarter and full year ended December 31, 2022 and reviewed recent business highlights (Press release, Alnylam, FEB 23, 2023, View Source [SID1234627596]).

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"2022 was another year of strong progress at Alnylam, including our continued commercial execution which delivered 35% full-year product revenue growth (43% with constant exchange rate*) compared to 2021. A key factor in these results was the approval and launch of AMVUTTRA, which is off to a great start in its first two full quarters on the market. Further to our leadership in TTR amyloidosis, we’re thrilled to have submitted our sNDA for ONPATTRO for the treatment of the cardiomyopathy of ATTR amyloidosis, which has now been accepted by the FDA, and look forward to potentially bringing this important therapy to patients, if approved," said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. "Looking ahead to 2023, we are excited for a number of important milestones across the pipeline, with 10 clinical readouts from proprietary and partner-led programs, including first-in-human results for an RNAi therapeutic in the CNS from our Phase 1 study of ALN-APP, as well as Phase 2 results from the KARDIA studies of zilebesiran. With the totality of this progress, we believe we are on track to achieve our Alnylam P5x25 goals and position Alnylam as a top-tier biotech company poised to deliver sustainable innovation."

Fourth Quarter 2022 and Recent Significant Corporate Highlights

Commercial Performance

Total TTR: ONPATTRO (patisiran) & AMVUTTRA (vutrisiran)

Achieved global net product revenues for ONPATTRO and AMVUTTRA for the fourth quarter of $122 million and $69 million, respectively, representing 12% total TTR quarterly growth compared to Q3 2022, and full year 2022 revenues of $558 million and $94 million, respectively, representing 37% total TTR annual growth compared to full year 2021.
Attained over 2,975 hATTR amyloidosis patients with polyneuropathy worldwide on commercial treatment with ONPATTRO or AMVUTTRA as of December 31, 2022, up from over 2,580 commercial patients as of September 30, 2022, representing 15% total TTR quarterly growth and 46% total TTR annual growth vs. 2021.
Received 760 Start Forms in the U.S. for AMVUTTRA from launch through December 31, 2022, with ~53% representing new patients and ~47% representing patients switching from ONPATTRO.
GIVLAARI (givosiran)

Achieved global net product revenues for the fourth quarter and full year 2022 of $47 million and $173 million, respectively, representing quarterly and annual growth of 3% and 35% compared to Q3 2022 and full year 2021, respectively.
Attained over 520 patients worldwide on commercial GIVLAARI treatment as of December 31, 2022, up from over 460 commercial patients as of September 30, 2022, representing 13% quarterly growth and 47% annual growth vs. 2021.
OXLUMO (lumasiran)

Achieved global net product revenues for the fourth quarter and full year 2022 of $24 million and $70 million, respectively, representing quarterly and annual growth of 45% and 17% compared to Q3 2022 and full year 2021, respectively.
Attained over 280 patients worldwide on commercial OXLUMO treatment as of December 31, 2022, up from over 230 commercial patients as of September 30, 2022, representing 22% quarterly growth and 101% annual growth vs. 2021.
Leqvio (inclisiran)

Launch is ongoing, with focus on patient on-boarding, removing access hurdles and enhancing medical education.
R&D Highlights

Patisiran (the non-proprietary name for ONPATTRO), in development for the treatment of ATTR amyloidosis.

Submitted and received acceptance of the sNDA for ONPATTRO (patisiran) for the treatment of the cardiomyopathy of ATTR amyloidosis. The FDA has set an action date of October 8, 2023 under the Prescription Drug User Fee Act (PDUFA).
In their file acceptance letter, the FDA stated that they have not identified any review issues. The Agency also noted that they are planning to hold an advisory committee meeting to discuss the application.
Vutrisiran (the non-proprietary name for AMVUTTRA), in development for the treatment of ATTR amyloidosis.

Announced topline results from the Randomized Treatment Extension (RTE) of the HELIOS-A Phase 3 study evaluating a biannual dosing regimen of vutrisiran.
Non-inferiority of 50 mg biannual (vs. 25 mg quarterly) was established, as measured by TTR lowering through nine months in the RTE, along with an acceptable safety profile.
However, the Company announces its strategic decision not to proceed with regulatory submissions for a biannual dosing regimen of vutrisiran and instead will focus on advancing ALN-TTRsc04, which has now entered the clinic and offers the potential for more durable and potent TTR silencing via annual dosing.
Received approval from the Brazilian Health Regulatory Agency (ANVISA) for AMVUTTRA for the treatment of hATTR amyloidosis in adults.
Lumasiran (the non-proprietary name for OXLUMO), for the treatment of primary hyperoxaluria type 1 (PH1).

Based on the successful outcome of the ILLUMINATE-C study in children and adults with advanced PH1, received approval from the U.S. FDA of an sNDA for OXLUMO, expanding the indication for the treatment of PH1 to lower urinary oxalate and plasma oxalate levels in pediatric and adult patients, and received approval from the European Medicines Agency (EMA) of a Type II variation to include the ILLUMINATE-C data in the label.
Inclisiran (the non-proprietary name for Leqvio), for the treatment of hypercholesterolemia or mixed dyslipidemia, in collaboration with Novartis.

New long-term data from the ORION-3 open-label study demonstrated effective and sustained reductions in LDL cholesterol over four years of treatment. At any time throughout the trial, approximately 80% of patients reached an LDL-C level of <70mg/dL. Data presented at AHA 2022.
Early- and mid-stage investigational RNAi therapeutic pipeline programs and RNAi platform.

Completed enrollment in the KARDIA-1 Phase 2 monotherapy study of zilebesiran in patients with mild-to-moderate hypertension.
Submitted Clinical Trial Authorization (CTA) filings for ALN-KHK for the treatment of type 2 diabetes, and ALN-PNP for the treatment of NASH in collaboration with Regeneron. Regeneron announced that dosing in a Phase 1 study of ALN-PNP has been initiated.
Submitted a CTA application for ALN-TTRsc04, in development for the treatment of ATTR amyloidosis. The Company announces today that dosing in a Phase 1 study has been initiated.
Announced pipeline prioritization decisions at 2022 R&D Day, including discontinuation of ALN-XDH in gout and lumasiran in recurrent renal stones, and pausing development of cemdisiran in IgA nephropathy.
Additional Business Updates

Appointed Carolyn Bertozzi, Ph.D. to its Board of Directors. Also, Amy W. Schulman, previously the Lead Independent Director, assumed the role of Chair of the Board from Michael W. Bonney, who has continued on the Board as a non-independent director. Mr. Bonney stepped down from his interim role as Executive Chair.
Ranked #1 on The Boston Globe’s 2022 list of Great Places to Work in the "Largest Employer category.
Ranked #2 in Science Magazine’s 2022 Top Employer survey, marking the fourth year Alnylam was featured as one of the top three companies.
Recognized on Newsweek’s 2023 list of America’s Most Responsible Companies.
Upcoming Events

In early 2023:

Alnylam intends to complete enrollment in the KARDIA-2 Phase 2 study of zilebesiran.
Alnylam intends to report preliminary topline results from the Phase 1 study of ALN-APP in patients with early onset Alzheimer’s Disease.
Alnylam intends to initiate a Phase 1 study of ALN-KHK in normal healthy volunteers.
Vir intends to report additional results from Part A of the MARCH trial evaluating the combination of ALN-HBV02 (VIR-2218) and VIR-3434, an anti-HBV monoclonal antibody, for the treatment of patients with chronic HBV infection in the first half of 2023.
Vir also plans to report additional results from a Phase 2 study evaluating the combination of ALN-HBV02 (VIR-2218) and PEG-IFN alpha in the first half of 2023.
Regeneron plans to initiate a Phase 2 study of ALN-HSD in patients with NASH.
Financial Results for the Quarter and Year Ended December 31, 2022

Financial Highlights

Three Months Ended
December 31,

Twelve Months Ended
December 31,

(In thousands, except per share amounts)

2022

2021

2022

2021

Net product revenues

$

261,675

$

198,514

$

894,329

$

662,138

Net revenue from collaborations

$

70,645

$

59,625

$

134,912

$

180,953

Royalty revenue

$

2,715

$

396

$

8,177

$

1,196

GAAP Operating loss

$

(188,614

)

$

(194,561

)

$

(785,072

)

$

(708,652

)

Non-GAAP Operating loss

$

(145,847

)

$

(149,979

)

$

(554,423

)

$

(542,935

)

GAAP Other expense, net

$

(18,407

)

$

(65,741

)

$

(341,921

)

$

(143,492

)

Non-GAAP Other expense, net

$

(25,203

)

$

(60,163

)

$

(232,023

)

$

(199,187

)

GAAP Net loss

$

(207,493

)

$

(258,460

)

$

(1,131,156

)

$

(852,824

)

Non-GAAP Net loss

$

(171,522

)

$

(208,300

)

$

(790,609

)

$

(742,802

)

GAAP Net loss per common share – basic and diluted

$

(1.68

)

$

(2.16

)

$

(9.30

)

$

(7.20

)

Non-GAAP Net loss per common share – basic and diluted

$

(1.39

)

$

(1.74

)

$

(6.50

)

$

(6.27

)

Net Product Revenues

Three Months Ended
December 31,

Twelve Months Ended
December 31,

(In thousands)

2022

2021

2022

2021

ONPATTRO net product revenues

$

122,221

$

138,630

$

557,608

$

474,737

AMVUTTRA net product revenues

68,566

93,795

Total TTR net product revenues

190,787

138,630

651,403

474,737

GIVLAARI net product revenues

47,058

40,679

173,144

127,815

OXLUMO net product revenues

23,830

19,205

69,782

59,586

Total net product revenues

$

261,675

$

198,514

$

894,329

$

662,138

Year over Year % Growth

Three Months Ended
December 31,

Twelve Months Ended
December 31,

As
Reported

At CER*

As
Reported

At CER*

Total TTR net product revenues

38%

48%

37%

46%

GIVLAARI net product revenues

16%

22%

35%

41%

OXLUMO net product revenues

24%

33%

17%

25%

Total net product revenues

32%

41%

35%

43%

* CER = Constant Exchange Rate, representing growth calculated as if the exchange rates had remained unchanged from those used in the three and twelve months ended December 31, 2021. CER is a Non-GAAP measure.

Net product revenues increased 32% and 35% at actual currency during the three and twelve months ended December 31, 2022, respectively, compared to the same periods in 2021, and 41% and 43% at CER, respectively. The increases are primarily due to increased patients on our commercial TTR products as well as increased patients on GIVLAARI and OXLUMO.
Net Revenues from Collaborations

Net revenues from collaborations increased 18% during the fourth quarter 2022, as compared to the prior year, primarily due to increased revenue from our collaboration with Regeneron from increased manufacturing activities.
Net revenues from collaborations decreased 25% for the twelve months ended December 31, 2022, as compared to the prior year, primarily due to a decrease in revenue recognized in connection with our collaboration agreements with Regeneron and Vir, attributed to reduced research and manufacturing activities and timing of reimbursable activities.
Operating Expenses

Three Months Ended
December 31,

Twelve Months Ended
December 31,

(in thousands)

2022

2021

2022

2021

GAAP research and development expenses

$

262,039

$

229,050

$

883,015

$

792,156

Non-GAAP research and development expenses

$

245,095

$

210,513

$

790,854

$

723,741

GAAP selling, general and administrative expenses

$

210,344

$

186,382

$

770,658

$

620,639

Non-GAAP selling, general and administrative expenses

$

184,521

$

160,337

$

632,170

$

523,337

Research & Development (R&D) Expenses

GAAP and non-GAAP R&D expenses increased during the three and twelve months ended December 31, 2022, compared to the same periods in 2021, primarily due to increases in headcount to support our R&D pipeline, development expenses associated with the KARDIA-1 and KARDIA-2 zilebesiran Phase 2 studies, and manufacturing and research related expenses associated with our pre-clinical and developmental activities. GAAP R&D expenses further increased during the twelve month period due to increased stock-based compensation expense related to the accounting for certain performance-based awards that vested during the period.
Selling, General & Administrative (SG&A) Expenses

GAAP and non-GAAP SG&A expenses increased during the three and twelve months ended December 31, 2022, compared to the same periods in 2021, primarily due to increased headcount and other strategic investments in support of the global launch of AMVUTTRA and other expenses to support our strategic growth. GAAP SG&A expenses further increased during the twelve month period due to stock-based compensation expense related to the accounting for certain performance-based awards that vested during the period.
Other Financial Highlights

GAAP other expense, net, decreased during the fourth quarter 2022, as compared to the prior year, primarily due to foreign currency gains as a result of the U.S. Dollar weakening against key global currencies, increased interest income, and unrealized gains on marketable equity securities.
GAAP other expense, net, increased during the twelve months ended December 31, 2022, compared to the same period in 2021, primarily due to a loss on the extinguishment of the Blackstone credit agreement, increased realized and unrealized losses on our marketable equity securities, and an increased loss from the fair value adjustment on the development derivative liability, offset by an increase in interest income.
Cash, cash equivalents and marketable securities were $2.19 billion as of December 31, 2022 compared to $2.44 billion as of December 31, 2021 with the decrease primarily due to our year-to-date operating loss in 2022. This decrease was largely offset by approximately $265 million received from employee option award exercises and approximately $135 million received from the issuance of convertible debt, net of repayment borrowings, inclusive of prepayment premiums under the credit facility, the purchase of capped call transactions, and underwriter fees.
The adjustments to the non-GAAP measures provided in the financial results above and in the financial guidance below are described under "Use of Non-GAAP Financial Measures" later in this press release. A reconciliation of our GAAP to non-GAAP results presented in this release is included in the tables of this press release.

2023 Financial Guidance1

Full year December 31, 2023 financial guidance consists of the following:

Combined net product revenues for ONPATTRO, AMVUTTRA, GIVLAARI and OXLUMO1,2

$1,200 million – $1,285 million

Net Product Revenue Growth vs. 2022 at reported Fx rates1

34% to 44%

Net Product Revenue Growth vs. 2022 at constant exchange rates*

34% to 44%

Net revenues from collaborations and royalties

$100 million – $175 million

GAAP R&D and SG&A expenses

$1,790 million – $1,885 million

Non-GAAP R&D and SG&A expenses3

$1,575 million – $1,650 million

1 Uses December 31, 2022 Fx rates including: 1 EUR = 1.07 USD and 1 USD = 131 JPY

2 Assumes U.S. sNDA approval of patisiran for ATTR amyloidosis with cardiomyopathy by the PDUFA date on October 8, 2023

3 Excludes $215-$235 million of stock-based compensation expense from estimated GAAP R&D and SG&A expenses

* CER = Constant Exchange Rate, representing growth calculated as if the exchange rates had remained unchanged from those used in the twelve months ended December 31, 2022. CER is a Non-GAAP measure.

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses and non-recurring gains and expenses outside the ordinary course of the Company’s business. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies.

The items included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in this press release are stock-based compensation expenses, realized and unrealized (gains) losses on marketable equity securities and loss on the extinguishment of debt. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards. The Company has excluded the impact of the realized and unrealized (gains) losses on marketable equity securities because the Company does not believe these adjustments accurately reflect the performance of the Company’s ongoing operations for the period in which such gains or losses are reported, as their sole purpose is to adjust amounts on the balance sheet. The Company has excluded the loss on the extinguishment of debt because the Company believes the item is a non-recurring transaction outside the ordinary course of the Company’s business.

Percentage changes in revenue growth at CER, also a non-GAAP financial measure, are presented excluding the impact of changes in foreign currency exchange rates for investors to understand the underlying business performance. The current period’s foreign currency revenue values are converted into U.S. dollars using the average exchange rates from the prior period.

The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between historical GAAP and non-GAAP measures presented in this release is provided later in this press release.

Conference Call Information

Management will provide an update on the Company and discuss fourth quarter and year-end 2022 results as well as expectations for the future via conference call on Thursday, February 23, 2023 at 8:30 am ET. To access the call, please register online at https://register.vevent.com/register/BI050ad56309204f0a836ec037dd396473. Participants are requested to register at a minimum 15 minutes before the start of the call. A replay of the call will be available two hours after the call and archived on the same web page for six months.

A live audio webcast of the call will be available on the Investors section of the Company’s website at www.alnylam.com/events. An archived webcast will be available on the Alnylam website approximately two hours after the event.

On February 23, 2023 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, reported business highlights and financial results for the fourth quarter and year ended Dec. 31, 2022 (Press release, Agios Pharmaceuticals, FEB 23, 2023, View Source [SID1234627595]).

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"Over the past year, Agios has made significant progress toward our vision of transforming the lives of patients with rare diseases as we build a hematology franchise focused on diseases that share a common underlying pathophysiology, limited treatment options and profound unmet need," said Brian Goff, chief executive officer at Agios. "In 2022, we received regulatory approvals in the U.S., EU and Great Britain for PYRUKYND as the first and only disease-modifying treatment for adults with pyruvate kinase (PK) deficiency. We achieved our ambitious enrollment targets for our pivotal trials in thalassemia and sickle cell disease. We strengthened our company leadership with the appointments of new management team and Board members with deep expertise in rare diseases and global commercial strategy. We are poised for significant near- and long-term growth and look forward to a productive 2023, anticipating the readout of our Phase 2 sickle cell disease study and the completion of enrollment in our Phase 3 thalassemia studies, driving toward two additional PYRUKYND indications by 2026."

Fourth Quarter 2022 & Recent Highlights

PYRUKYND U.S. Launch: Continued to execute launch, generating $4.3 million in U.S. net revenue for the fourth quarter of 2022, the third full quarter following FDA approval. A total of 105 unique patients have completed prescription enrollment forms, representing an increase of 25 percent over the third quarter. A total of 78 patients are on PYRUKYND therapy, representing a 39 percent increase over the third quarter.
PYRUKYND Global Approvals: Received marketing authorization for adults with PK deficiency in the EU and Great Britain.
Sickle Cell Disease: Completed enrollment in the Phase 2 portion of the RISE UP study of PYRUKYND in adults with sickle cell disease.
Thalassemia: Enrolled more than half of patients in the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND in not regularly transfused and regularly transfused adults with thalassemia, respectively.
Data Presentations: Presented broad set of clinical and translational data at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, including long-term PYRUKYND data in adults with non-transfusion-dependent thalassemia and in adults with PK deficiency.
Leadership: Appointed Tsveta Milanova to the role of chief commercial officer, bringing two decades of experience in rare disease commercial strategy and global market access.
Anticipated 2023 Milestones

Thalassemia: Complete enrollment of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND by mid-year.
Sickle Cell Disease: Announce data readout from the Phase 2 portion of the RISE UP study of PYRUKUND and go/no-go to Phase 3 decision by mid-year.
Pediatric PK Deficiency: Enroll more than half of patients in the Phase 3 ACTIVATE-kids and ACTIVATE-kidsT studies of PYRUKYND by year-end.
Lower-risk Myelodysplastic Syndromes (LR-MDS): Complete enrollment of the Phase 2a study of novel PK activator AG-946 by year-end.
Pipeline: File investigational new drug (IND) application for phenylalanine hydroxylase (PAH) stabilizer for the treatment of phenylketonuria (PKU) by year-end.
Fourth Quarter 2022 Financial Results

The financial results discussion compares Agios’ continuing operations. All periods have been adjusted to exclude discontinued operations related to the divested oncology business.

Revenue: Net U.S. product revenue from sales of PYRUKYND was $4.3 million for the fourth quarter of 2022, and $11.7 million for the full year ended Dec. 31, 2022. PYRUKYND was approved by the FDA on February 17, 2022.

Cost of Sales: Cost of sales was $0.4 million for the fourth quarter of 2022 and $1.7 million for the full year ended Dec. 31, 2022.

Non-Operating Income: Non-operating income included $127.9 million as gain on sale of contingent payments from the sale of TIBSOVO royalty rights to Sagard Healthcare Partners. Non-operating income also included approximately $9.9 million from TIBSOVO royalties for the full year ended Dec. 31, 2022, with royalty income ceasing after the third quarter of 2022 due to the sale of these rights to Sagard.

Research and Development (R&D) Expenses: R&D expenses were $70.3 million for the fourth quarter of 2022 compared to $73.3 million for the fourth quarter of 2021, and $279.9 million for the year ended Dec. 31, 2022 compared to $257.0 million for the year ended Dec. 31, 2021. The year-over-year increase in R&D expense was primarily driven by increased costs for PYRUKYND and AG-946 studies and increased workforce spend across R&D.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $32.8 million for the fourth quarter of 2022 compared to $31.5 million for the fourth quarter of 2021, and $121.7 million for the year ended Dec. 31, 2022 compared to $121.4 million for the year ended Dec. 31, 2021.

Net Income (Loss) from Continuing Operations: Net income was $36.5 million for the fourth quarter of 2022 compared to a net loss of $98.6 million for the fourth quarter of 2021, and net loss was $231.8 million for the year ended Dec. 31, 2022 compared to $356.5 million for the year ended Dec. 31, 2021.

Cash Position and Guidance: Cash, cash equivalents and marketable securities as of Dec. 31, 2022, were $1.1 billion compared to $1.3 billion as of Dec. 31, 2021. This cash position includes the receipt of a one-time payment of $131.8 million associated with the sale of our rights to 5% royalties on U.S. net sales of Servier’s TIBSOVO. Agios expects that its cash, cash equivalents and marketable securities together with anticipated product revenue and interest income will enable the company to execute its operating plan, including funding the currently planned development programs for mitapivat, AG-946 and PAH stabilization and commercializing mitapivat outside of the U.S. through one or more partnerships, to cash-flow positivity without the need to raise additional equity.

Conference Call Information
Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss fourth quarter and year end 2022 financial results and recent business activities. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.