Arvinas and Pfizer’s Vepdegestrant (ARV-471) Receives FDA Fast Track Designation for the Treatment of Patients with ER+/HER2- Metastatic Breast Cancer

On February 6, 2024 Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the investigation of vepdegestrant (ARV-471) for monotherapy in the treatment of adults with estrogen receptor (ER) positive/human growth epidermal growth factor 2 (HER2) negative (ER+/HER2-) locally advanced or metastatic breast cancer previously treated with endocrine-based therapy (Press release, Arvinas, FEB 6, 2024, View Source [SID1234639865]). Vepdegestrant is a novel oral PROteolysis Targeting Chimera (PROTAC) ER degrader that is being jointly developed by Arvinas and Pfizer.

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As described by the FDA, Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to patients earlier. Vepdegestrant as a monotherapy is being studied in the ongoing Phase 3 VERITAC-2 clinical trial, which is evaluating vepdegestrant or fulvestrant in patients with locally advanced or metastatic ER+/HER2- breast cancer who have been previously treated with an endocrine-based therapy.

"We are focused on the persisting unmet needs of people with ER+/HER2- breast cancer and doing all that we can to expedite the development of vepdegestrant as a novel, oral ER-targeted potential therapy for this patient community," said John Houston, Ph.D., Arvinas Chairperson, Chief Executive Officer, and President. "We are pleased the FDA has granted Fast Track designation for vepdegestrant, and we continue to believe this investigational drug has the potential to harness the body’s own natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins."

"The receipt of Fast Track designation reinforces the potential of vepdegestrant to provide an important new therapeutic option for people with ER+/HER2- breast cancer whose disease has progressed," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "We are proud to continue our legacy of developing innovative treatment options for people impacted by metastatic breast cancer and look forward to working with the FDA as we advance our development program for vepdegestrant."

About Vepdegestrant (ARV-471) and its Clinical Trials
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.

In preclinical studies, vepdegestrant demonstrated up to 97% ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed increased 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 vepdegestrant; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits. Ongoing and planned clinical trials will continue to monitor and evaluate the safety and anti-tumor activity of vepdegestrant.

Vepdegestrant is currently being evaluated as a monotherapy in the second-line setting in the ongoing Phase 3 VERITAC-2 clinical trial and in the first-line setting in combination with palbociclib in the ongoing study lead-in cohort of the Phase 3 VERITAC-3 clinical trial. Vepdegestrant is also being evaluated for potential combination therapy with abemaciclib, ribociclib, samuraciclib, everolimus, and with Pfizer’s investigational novel CDK4 inhibitor, PF-07220060.

Arrowhead Pharmaceuticals Reports Fiscal 2024 First Quarter Results

On February 6, 2024 Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) reported financial results for its fiscal 2024 first quarter ended December 31, 2023 (Press release, Arrowhead Research Corporation, FEB 6, 2024, View Source [SID1234639864]). The company is hosting a conference call today, February 6, 2024, at 4:30 p.m. ET to discuss the results.

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Webcast and Conference Call and Details
Investors may access a live audio webcast on the Company’s website at View Source A replay of the webcast will be available approximately two hours after the conclusion of the call.
For analysts that wish to participate in the conference call, please register at https://register.vevent.com/register/BId9fba8b41eb34305a8f07de301a9d42c. Once registered, you will receive the dial-in number and a personalized PIN code that will be required to access the call.
Selected Recent Events
•Continued to build the cardiometabolic vertical to include two new additional complementary medicines designed to treat obesity and metabolic disease, both of which are on schedule for clinical trial application (CTA) filings before the end of 2024
◦ARO-INHBE utilizes the liver targeted TRiMTM platform and targets the INHBE gene. INHBE expression is increased in obesity and INHBE loss-of-function variants identified in human genetic databases are protective of type 2 diabetes and are associated with reduced visceral fat and a reduced waste to hip ratio
◦The second is based on Arrowhead’s adipose tissue targeting TRiMTM platform and addresses an undisclosed gene target
•Performed a portfolio review and R&D organization restructuring resulting in key changes, including:
◦Arrowhead will focus investment in late-stage clinical development and build out commercial infrastructure to support sales and marketing of medicines primarily in the cardiometabolic and pulmonary verticals
◦Engaged Bruce Given, M.D., Arrowhead’s former chief operating officer and head of R&D for Arrowhead for several years before his retirement in 2020 after a more than 30-year career in biotechnology and pharmaceutical research, development, and sales and marketing, on an interim basis to serve as chief medical scientist to help with restructuring efforts and the process to recruit new therapeutic area experts to decentralize the chief medical officer function
◦Identified opportunities to reduce forward operating cash burn guidance by up to $100 million, approximately $30 million per quarter, while retaining full funding and investment in core cardiometabolic and pulmonary programs
◦Focused R&D spending for non-core programs on development activities that advance candidates to an attractive stage for potential partnerships

◦Terminated development of ARO-SOD1 and HZN-457
•Strengthened the balance sheet through an underwritten registered offering of common stock gross proceeds of approximately $450 million, before deducting underwriting discounts, commissions, and other offering expenses payable by the company
•Presented data on cardiometabolic pipeline at the American Heart Association Scientific Sessions in November 2023
◦Presented new Phase 2 clinical data from the ongoing SHASTA-2 and MUIR studies of plozasiran (ARO-APOC3) and the ARCHES-2 study of zodasiran (ARO-ANG3)
◦Hosted a webinar to discuss plozasiran featuring experts in the treatment and management of lipid and lipoprotein disorders
•Completed chronic GLP toxicology for pulmonary candidates ARO-RAGE, designed to reduce expression of the receptor for advanced glycation end products as a potential treatment for inflammatory pulmonary diseases, and ARO-MMP7, designed to reduce expression of matrix metalloproteinase 7 as a potential treatment for idiopathic pulmonary fibrosis
◦Results were highly encouraging and suggest sufficient safety margins to proceed to Phase 2 studies
•Filed for regulatory clearance to initiate a Phase 1/2a study of ARO-CFB, Arrowhead’s RNAi therapeutic candidate for patients with complement renal disease such as immunoglobulin A nephropathy (IgAN), which is the world’s most common glomerular disease
•Filed for regulatory clearance to initiate a Phase 1/2a study of Arrowhead’s second RNAi therapeutic candidate targeting skeletal muscle, ARO-DM1, for patients with type 1 myotonic dystrophy

Selected Fiscal 2024 Financial Results
ARROWHEAD PHARMACEUTICALS, INC.
CONSOLIDATED CONDENSED FINANCIAL INFORMATION
(in thousands, except per share amounts)


Year Ended
December 31,
OPERATING SUMMARY 2023 2022
(Unaudited)
Revenue $ 3,551 $ 62,546
Operating Expenses:
Research and development 116,491 83,695
General and administrative expenses 23,605 20,985
Total Operating Expenses 140,096 104,680
Operating loss (136,545) (42,134)
Total other (expense) income (2,144) 340
Loss before income tax (benefit) expense and noncontrolling interest (138,689) (41,794)
Income tax (benefit) expense (3,313) 17
Net loss including noncontrolling interest (135,376) (41,811)
Net loss attributable to noncontrolling interest, net of tax (2,512) (486)
Net loss attributable to Arrowhead Pharmaceuticals, Inc. $ (132,864) $ (41,325)

Net loss per share attributable to Arrowhead Pharmaceuticals, Inc. – Diluted $ (1.24) $ (0.39)
Weighted-average shares used in calculating – Diluted 107,415 106,039

FINANCIAL POSITION SUMMARY December 31,
2023 September 30,
2023
(unaudited)
Cash, cash equivalents and restricted cash $ 58,215 $ 110,891
Investments 162,064 292,735
Total cash resources (cash and investments) 220,279 403,626
Other assets 406,007 361,926
Total Assets $ 626,286 $ 765,552
Current deferred revenue $ — $ 866
Other liabilities 452,572 477,524
Total Liabilities $ 452,572 $ 478,390
Total Arrowhead Pharmaceuticals, Inc. Stockholders’ Equity $ 160,407 $ 271,343
Noncontrolling Interest 13,307 15,819
Total Noncontrolling Interest and Stockholders’ Equity $ 173,714 $ 287,162
Total Liabilities, Noncontrolling Interest and Stockholders’ Equity $ 626,286 $ 765,552
Shares Outstanding 107,500 107,312

Precision Oncology through synthetic lethality

On February 6, 2024 Aprea therapeutics presented its corporate presentation (Presentation, Aprea, FEB 6, 2024, View Source [SID1234639863]).

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AMGEN REPORTS FOURTH QUARTER AND FULL YEAR 2023 FINANCIAL RESULTS

On February 6, 2024 Amgen (NASDAQ:AMGN) reported financial results for the fourth quarter and full year 2023 versus comparable periods in 2022 (Press release, Amgen, FEB 6, 2024, View Source [SID1234639862]).

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"2023 was another year of performance and progress for our company," said Robert A. Bradway, chairman and chief executive officer. "Our marketed products are reaching many more patients around the world, and we anticipate more than a dozen significant pipeline milestones in 2024."

Key results include:

For the fourth quarter, total revenues increased 20% to $8.2 billion in comparison to the fourth quarter of 2022. Product sales grew 20%, driven by 23% volume growth, partially offset by 3% lower net selling price.
Nine brands(1) achieved record sales in the quarter, and Repatha (evolocumab), EVENITY (romosozumab-aqqg), Prolia (denosumab) and BLINCYTO (blinatumomab) delivered double-digit volume growth globally.
U.S. volume grew 26% and ex-U.S. volume grew 15%, including 46% volume growth in the Asia Pacific region.
Our performance included $954 million of sales for the period of Oct. 6 – Dec. 31 from our recent Horizon Therapeutics (Horizon) acquisition, driven by several first-in-class, early-in-lifecycle medicines such as TEPEZZA (teprotumumab-trbw), KRYSTEXXA (pegloticase) and UPLIZNA (inebilizumab-cdon). Excluding the impact of these sales from Horizon, our product sales grew 5%, driven by volume growth of 9%.
For the full year, total revenues increased 7% to $28.2 billion, resulting from a 9% increase in product sales. Product sales growth was driven by 15% volume growth, partially offset by 3% lower net selling price, 1% unfavorable changes from estimated sales deductions and 1% negative impact from foreign exchange.
GAAP earnings per share (EPS) decreased 53% from $3.00 to $1.42 in the fourth quarter, driven by acquisition-related expenses and incremental operating expenses from Horizon, partially offset by increased revenues. For the full year, GAAP EPS increased 3% from $12.11 to $12.49 driven by net gains on our BeiGene, Ltd equity investment in 2023 and higher revenues, partially offset by higher operating expenses, including acquisition-related expenses and incremental expenses from Horizon.
For the fourth quarter, GAAP operating income decreased from $2.2 billion to $1.3 billion, and GAAP operating margin decreased 17.8 percentage points to 16.2%. For the full year, GAAP operating income decreased from $9.6 billion to $7.9 billion, and GAAP operating margin decreased 9.3 percentage points to 29.3%.
Non-GAAP EPS increased 15% from $4.09 to $4.71 in the fourth quarter and increased 5% from $17.69 to $18.65 for the full year, driven by increased revenues, partially offset by higher operating expenses, including incremental expenses from Horizon. Fourth quarter non-GAAP EPS was also unfavorably impacted by higher interest expense.
For the fourth quarter, non-GAAP operating income increased from $3.0 billion to $3.7 billion, and non-GAAP operating margin increased 0.8 percentage points to 46.7%. For the full year, non-GAAP operating income increased from $12.8 billion to $13.4 billion, and non-GAAP operating margin decreased 1.7 percentage points to 49.8%.
The Company generated $7.4 billion of free cash flow for the full year versus $8.8 billion in 2022. The decrease in 2023 was primarily driven by transaction expenses related to the Horizon acquisition and higher repatriation tax payments.
(1) Includes product sales for the full fourth quarter of 2023 from UPLIZNA and KRYSTEXXA in connection with Horizon acquisition.

References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis," "free cash flow" (computed by subtracting capital expenditures from operating cash flow), "EBITDA, or earnings before interest, taxes, depreciation and amortization" (computed by adding interest expense, provision for income taxes, and depreciation and amortization expense to GAAP net income) and "debt leverage ratio" (calculated as the ratio of GAAP total debt to EBITDA) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented on the attached reconciliations. Refer to Non-GAAP Financial Measures below for further discussion.

Product Sales Performance

Total product sales increased 20% for the fourth quarter of 2023 versus the fourth quarter of 2022. Volume grew 23%, partially offset by 3% lower net selling price. Full year product sales increased 9% versus 2022, driven by 15% volume growth, partially offset by 3% lower net selling price, 1% unfavorable changes from estimated sales deductions and 1% negative impact from foreign exchange.

General Medicine

Repatha sales increased 25% year-over-year for the fourth quarter, driven by 35% volume growth, partially offset by lower net selling price. Full year sales increased 26%, driven by 37% volume growth, partially offset by lower net selling price. Repatha remains the global proprotein convertase subtilisin/kexin type 9 (PCSK9) segment leader, with over 2.5 million patients treated since launch.

Prolia sales increased 12% year-over-year, to a record $1.1 billion for the fourth quarter, and 12% for the full year, primarily driven by volume growth and higher net selling price. Volume grew 10% for the quarter and 9% for the full year. In 2023, over 7.5 million patients were treated with Prolia.

EVENITY sales increased 41% year-over-year to a record $318 million for the fourth quarter and 47% for the full year, driven by strong volume growth. U.S. volume grew 44% year-over-year and volume outside the U.S. grew 55% for the full year.

Aimovig (erenumab-aooe) sales decreased 32% year-over-year for the fourth quarter and 22% for the full year, driven by lower net selling price.
Oncology

BLINCYTO sales increased 47% year-over-year to a record $241 million for the fourth quarter and 48% for the full year, driven by 55% and 49% volume growth, respectively. Volume growth was supported by broad prescribing across academic and community settings for patients with B-cell precursor acute lymphoblastic leukemia.

Vectibix (panitumumab) sales increased 5% year-over-year for the fourth quarter and 10% for the full year, driven by 5% and 10% volume growth, respectively.

KYPROLIS (carfilzomib) sales increased 8% year-over-year for the fourth quarter and 13% for the full year, driven by 8% and 12% volume growth, respectively.

LUMAKRAS/LUMYKRAS (sotorasib) sales increased 8% year-over-year for the fourth quarter, driven by 5% volume growth and higher net selling price. Full year sales decreased 2%, driven by unfavorable changes to estimated sales deductions, including changes related to ongoing reimbursement negotiations in France. Full year sales were also impacted by lower net selling price and lower inventory levels, partially offset by 16% volume growth.

XGEVA (denosumab) sales increased 9% year-over-year for the fourth quarter and 5% for the full year, primarily driven by higher net selling price.

Nplate (romiplostim) sales decreased 18% year-over-year for the fourth quarter, driven by volume decline related to timing of orders placed by the U.S. government, partially offset by volume growth across our U.S. and ex-U.S. regions. U.S. government orders were $207 million in Q4’22 compared to $62 million in Q4’23. Full year sales increased 13%, primarily driven by volume growth, including U.S. government orders. U.S. government orders were $207 million for FY’22 compared to $286 million for FY’23. Excluding these U.S. government orders, Nplate sales grew 23% year-over-year for the fourth quarter and 8% for the full year.

MVASI (bevacizumab-awwb) sales decreased 8% year-over-year for the fourth quarter, primarily driven by lower net selling price, partially offset by 12% volume growth. Full year sales decreased 11%, primarily driven by lower net selling price, partially offset by 13% volume growth. Going forward, we expect continued net selling price erosion driven by increased competition.

KANJINTI (trastuzumab-anns) sales decreased 33% year-over-year for the fourth quarter and 50% for the full year, driven by lower net selling price and volume decline.
Inflammation

TEZSPIRE (tezepelumab-ekko) generated $177 million of sales in the fourth quarter. Quarter-over-quarter sales increased 10%, driven by 18% volume growth that benefited from the pre-filled, single-use pen, which was approved for self-administration by the U.S. Food and Drug Administration (FDA) in the first quarter. Healthcare providers recognize TEZSPIRE’s unique, differentiated profile and its broad potential to treat the 2.5 million patients worldwide with severe asthma who are uncontrolled, without any phenotypic or biomarker limitation.

Otezla (apremilast) sales increased 2% year-over-year for the fourth quarter, driven by favorable changes to estimated sales deductions and 3% volume growth, partially offset by lower inventory levels and lower net selling price. Full year sales decreased 4%, driven by lower net selling price and lower inventory levels, partially offset by 2% volume growth.

We expect future growth for Otezla to be driven by its established efficacy and safety profile, strong payer coverage with limited prior authorization requirements and ease of administration. Otezla remains the only approved oral systemic therapy with a broad indication and is well-positioned to help the 1.5 million U.S. patients with mild-to-moderate psoriasis who cannot be optimally addressed by a topical and can benefit from a systemic treatment like Otezla.

Enbrel (etanercept) sales decreased 8% year-over-year for the fourth quarter, driven by a 4% impact from unfavorable changes to estimated sales deductions and lower net selling price. Full year sales decreased 10%, driven by lower net selling price, lower inventory levels and a 3% impact from unfavorable changes to estimated sales deductions. Year-over-year volume remained flat, with U.S. volume growing 1% in the fourth quarter, supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward, we expect net selling price to continue to decline year-over-year, driven by higher rebates to maintain broad first-line payer coverage and changes in patient mix.

We expect Otezla and Enbrel to follow the historical pattern of lower sales in the first quarter relative to subsequent quarters due to the impact of benefit plan changes, insurance reverification and increased co-pay expenses as U.S. patients work through deductibles.

AMJEVITA/AMGEVITA (adalimumab) sales increased 34% year-over-year for the fourth quarter and 36% for the full year, primarily driven by 35% and 46% volume growth, respectively. Ex-U.S. sales increased 9% for the full year, driven by 20% volume growth, partially offset by lower net selling price. U.S. sales increased 43% quarter-over-quarter, driven by higher inventory levels and higher net selling price, partially offset by volume decline.
Rare Disease

Excluding TAVNEOS, the products listed below were acquired from our Horizon transaction on Oct. 6, 2023. Sales figures reflect only sales in the period from Oct. 6 2023 through the end of the year, and not the full quarter.

TEPEZZA (teprotumumab-trbw) generated $448 million of sales for the period. TEPEZZA is the first and only FDA-approved treatment for thyroid eye disease (TED).

KRYSTEXXA (pegloticase) generated $272 million of sales for the period. KRYSTEXXA is the first and only FDA-approved treatment for chronic refractory gout.

UPLIZNA (inebilizumab-cdon) generated $65 million of sales for the period. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorders (NMOSD).

TAVNEOS (avacopan) generated $44 million of sales in the fourth quarter. Quarter-over-quarter sales increased 19%, primarily driven by volume growth. U.S. volume grew 23% quarter-over-quarter. In the U.S., approximately 2,700 patients have now been treated with TAVNEOS.

Ultra rare products, which consist of RAVICTI (glycerol phenylbutyrate), PROCYSBI (cysteamine bitartrate), ACTIMMUNE (interferon gamma-1b), BUPHENYL (sodium phenylbutyrate) and QUINSAIR (levofloxacin) generated $164 million of sales for the period.
Established Products

Total sales of our established products, which consist of EPOGEN (epoetin alfa), Aranesp (darbepoetin alfa), Parsabiv (etelcalcetide) and Neulasta (pegfilgrastim), decreased 10% year-over-year for the fourth quarter, primarily driven by lower net selling price and volume declines, partially offset by favorable changes to estimated sales deductions. Full year sales decreased 19%, driven by lower net selling price and volume declines. In the aggregate, we expect the year-over-year net selling price and volume declines for this portfolio of products to continue.
Product Sales Detail by Product and Geographic Region

$Millions, except percentages


Q4 ’23


Q4 ’22


YOY Δ


US


ROW


TOTAL


TOTAL


TOTAL

Repatha


$ 201


$ 216


$ 417


$ 333


25 %

Prolia


746


361


1,107


992


12 %

EVENITY


239


79


318


225


41 %

Aimovig


73


5


78


114


(32 %)

BLINCYTO


148


93


241


164


47 %

Vectibix


116


135


251


238


5 %

KYPROLIS


222


128


350


325


8 %

LUMAKRAS/LUMYKRAS


51


26


77


71


8 %

XGEVA


382


145


527


484


9 %

Nplate


252


134


386


469


(18 %)

MVASI


127


61


188


205


(8 %)

KANJINTI


31


11


42


63


(33 %)

TEZSPIRE


177



177


79


*

Otezla


526


103


629


616


2 %

Enbrel


1,005


10


1,015


1,098


(8 %)

AMJEVITA/AMGEVITA


33


127


160


119


34 %

TEPEZZA**


441


7


448



NM

KRYSTEXXA**


272



272



NM

UPLIZNA**


60


5


65



NM

TAVNEOS


42


2


44


21


*

Ultra rare products**


162


2


164



NM

EPOGEN


55



55


114


(52 %)

Aranesp


107


212


319


348


(8 %)

Parsabiv


57


32


89


93


(4 %)

Neulasta


208


31


239


221


8 %

Other products***


137


38


175


160


9 %

Total product sales


$ 5,870


$ 1,963


$ 7,833


$ 6,552


20 %


*Change in excess of 100%

**Products were acquired from our Horizon acquisition on Oct. 6, 2023, and include product sales from the
acquisition date through Dec. 31, 2023. Ultra rare products consist of RAVICTI, PROCYSBI, ACTIMMUNE,
BUPHENYL and QUINSAIR

***Consists of (i) RIABNI, AVSOLA, Corlanor, NEUPOGEN, IMLYGIC, Sensipar/Mimpara and BEKEMV,
where Biosimilars total $93 million in Q4 ’23 and $52 million in Q4 ’22; (ii) RAYOS, PENNSAID and DUEXIS
product sales from our Horizon acquisition on Oct. 6, 2023 through Dec. 31, 2023; and (iii) sales prior to the
divestiture of our Bergamo and Gensenta subsidiaries in the second quarter of 2023 and fourth quarter of
2022, respectively

NM = not meaningful

$Millions, except percentages


FY ’23


FY ’22


YOY Δ


US


ROW


TOTAL


TOTAL


TOTAL

Repatha


$ 793


$ 842


$ 1,635


$ 1,296


26 %

Prolia


2,733


1,315


4,048


3,628


12 %

EVENITY


809


351


1,160


787


47 %

Aimovig


303


20


323


414


(22 %)

BLINCYTO


566


295


861


583


48 %

Vectibix


461


523


984


893


10 %

KYPROLIS


921


482


1,403


1,247


13 %

LUMAKRAS/LUMYKRAS


197


83


280


285


(2 %)

XGEVA


1,527


585


2,112


2,014


5 %

Nplate


996


481


1,477


1,307


13 %

MVASI


511


289


800


901


(11 %)

KANJINTI


109


50


159


316


(50 %)

TEZSPIRE


567



567


170


*

Otezla


1,777


411


2,188


2,288


(4 %)

Enbrel


3,650


47


3,697


4,117


(10 %)

AMJEVITA/AMGEVITA


126


500


626


460


36 %

TEPEZZA**


441


7


448



NM

KRYSTEXXA**


272



272



NM

UPLIZNA**


60


5


65



NM

TAVNEOS


126


8


134


21


*

Ultra Rare products**


162


2


164



NM

EPOGEN


226



226


506


(55 %)

Aranesp


452


910


1,362


1,421


(4 %)

Parsabiv


228


134


362


382


(5 %)

Neulasta


710


138


848


1,126


(25 %)

Other products***


549


160


709


639


11 %

Total product sales


$ 19,272


$ 7,638


$ 26,910


$ 24,801


9 %


*Change in excess of 100%



**Products were acquired from our Horizon acquisition on Oct. 6, 2023, and include product sales from the acquisition date through Dec. 31, 2023. Ultra rare products consist of RAVICTI, PROCYSBI, ACTIMMUNE, BUPHENYL and QUINSAIR

***Consists of (i) AVSOLA, RIABNI, Corlanor, NEUPOGEN, IMLYGIC, Sensipar/Mimpara and BEKEMV, where Biosimilars total $331 million in FY ’23 and $154 million in FY ’22; (ii) RAYOS, PENNSAID and DUEXIS product sales from our Horizon acquisition on Oct. 6, 2023 through Dec. 31, 2023; and (iii) sales prior to the divestiture of our Bergamo and Gensenta subsidiaries in the second quarter of 2023 and fourth quarter of 2022, respectively

NM = not meaningful


Operating Expense, Operating Margin and Tax Rate Analysis

On a GAAP basis:

Total Operating Expenses increased 50% year-over-year for the fourth quarter. For the full year, Total Operating Expenses increased 21%. Cost of Sales as a percentage of product sales increased 13.0 percentage points in the fourth quarter primarily driven by higher amortization expense from acquisition-related assets as well as higher profit share and royalties, partially offset by Puerto Rico excise tax, changes in product mix, and lower manufacturing cost. For the full year, cost of sales as a percentage of product sales increased 5.6 percentage points primarily driven by higher amortization expense from acquisition-related assets, higher profit share and royalties, and changes in product mix, partially offset by Puerto Rico excise tax. Research & Development (R&D) expenses increased 16% in the fourth quarter and increased 8% for the full year driven by higher spend in later-stage clinical programs and marketed products support, including spend from programs acquired from the Horizon acquisition. Selling, General & Administrative (SG&A) expenses increased 45% in the fourth quarter and increased 14% for the full year primarily driven by higher acquisition-related costs, in addition to commercial and general administrative expenses related to the Horizon acquisition. For the full year, this was partially offset by a decline in other marketed product spend. Other operating expenses for the full year consisted of net impairment charges for AMG 340 and Teneobio IPR&D assets in addition to expenses related to our restructuring plan initiated in the first quarter of 2023.

Operating Margin as a percentage of product sales decreased 17.8 percentage points to 16.2% in the fourth quarter and decreased 9.3 percentage points for the full year to 29.3%.

Tax Rate increased 2.4 percentage points in the fourth quarter and increased 3.7 percentage points for the full year, primarily driven by the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023. For the fourth quarter this was partially offset by the change in earnings mix.
On a non-GAAP basis:

Total Operating Expenses increased 18% for the fourth quarter and increased 9% for the full year. Cost of Sales as a percentage of product sales remained flat in the fourth quarter primarily driven by higher profit share and royalties, offset by Puerto Rico excise tax, changes in product mix, and lower manufacturing cost. For the full year, cost of sales as a percentage of product sales increased 1.1 percentage points primarily driven by higher profit share and royalties and changes in product mix, partially offset by Puerto Rico excise tax. R&D expenses increased 16% in the fourth quarter and increased 8% for the full year driven by higher spend in later-stage clinical programs and marketed products support, including spend from programs acquired from the Horizon acquisition. SG&A expenses increased 20% in the fourth quarter and increased 5% for the full year primarily driven by higher commercial and general administrative expenses related to the Horizon acquisition. For the full year, this was partially offset by a decline in other marketed product spend.

Operating Margin as a percentage of product sales increased 0.8 pts. percentage points to 46.7% in the fourth quarter and decreased 1.7 percentage points for the full year to 49.8%.

Tax Rate increased 2.5 percentage points in the fourth quarter and increased 2.7 percentage points for the full year primarily due to the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023.
$Millions, except percentages


GAAP


Non-GAAP


Q4 ’23


Q4 ’22


YOY Δ


Q4 ’23


Q4 ’22


YOY Δ

Cost of Sales


$ 3,112


$ 1,747


78 %


$ 1,278


$ 1,071


19 %

% of product sales


39.7 %


26.7 %


13.0 pts


16.3 %


16.3 %


— pts

Research & Development


$ 1,534


$ 1,324


16 %


$ 1,494


$ 1,291


16 %

% of product sales


19.6 %


20.2 %


(0.6) pts


19.1 %


19.7 %


(0.6) pts

Selling, General & Administrative


$ 2,274


$ 1,572


45 %


$ 1,764


$ 1,468


20 %

% of product sales


29.0 %


24.0 %


5.0 pts


22.5 %


22.4 %


0.1 pts

Other


$ 5


$ (34)


*


$ —


$ —


NM

Total Operating Expenses


$ 6,925


$ 4,609


50 %


$ 4,536


$ 3,830


18 %


Operating Margin


operating income as % of product sales


16.2 %


34.0 %


(17.8) pts


46.7 %


45.9 %


0.8 pts


Tax Rate


10.0 %


7.6 %


2.4 pts


15.9 %


13.4 %


2.5 pts


pts: percentage points


* change in excess of 100%


NM = not meaningful

$Millions, except percentages


GAAP


Non-GAAP


FY ’23


FY ’22


YOY Δ


FY ’23


FY ’22


YOY Δ

Cost of Sales


$ 8,451


$ 6,406


32 %


$ 4,573


$ 3,951


16 %

% of product sales


31.4 %


25.8 %


5.6 pts


17.0 %


15.9 %


1.1 pts

Research & Development


$ 4,784


$ 4,434


8 %


$ 4,700


$ 4,341


8 %

% of product sales


17.8 %


17.9 %


(0.1) pts


17.5 %


17.5 %


— pts

Selling, General & Administrative


$ 6,179


$ 5,414


14 %


$ 5,518


$ 5,270


5 %

% of product sales


23.0 %


21.8 %


1.2 pts


20.5 %


21.2 %


(0.7) pts

Other


$ 879


$ 503


75 %


$ —


$ —


NM

Total Operating Expenses


$ 20,293


$ 16,757


21 %


$ 14,791


$ 13,562


9 %


Operating Margin


operating income as % of product sales


29.3 %


38.6 %


(9.3) pts


49.8 %


51.5 %


(1.7) pts


Tax Rate


14.5 %


10.8 %


3.7 pts


16.5 %


13.8 %


2.7 pts


pts: percentage points


NM = not meaningful


Cash Flow and Balance Sheet

The Company generated $0.3 billion of free cash flow in the fourth quarter of 2023 versus $2.3 billion in the fourth quarter of 2022, primarily driven by timing of federal and repatriation tax payments. The Company generated $7.4 billion of free cash flow for the full year 2023 versus $8.8 billion in 2022.
The Company’s fourth quarter 2023 dividend of $2.13 per share was declared on October 24, 2023, and was paid on December 8, 2023, to all stockholders of record as of November 17, 2023, representing a 10% increase from 2022.
During the fourth quarter, there were no repurchases of shares of common stock.
Cash and investments totaled $10.9 billion and debt outstanding totaled $64.6 billion as of December 31, 2023. Debt leverage was approximately 4.4 times EBITDA as of December 31, 2023.
$Billions, except shares


Q4 ’23


Q4 ’22


YOY Δ

FY ’23


FY ’22


YOY Δ

Operating Cash Flow


$ 0.5


$ 2.6


$ (2.1)

$ 8.5


$ 9.7


$ (1.3)

Capital Expenditures


$ 0.2


$ 0.3


$ (0.1)

$ 1.1


$ 0.9


$ 0.2

Free Cash Flow


$ 0.3


$ 2.3


$ (2.0)

$ 7.4


$ 8.8


$ (1.4)

Dividends Paid


$ 1.1


$ 1.0


$ 0.1

$ 4.6


$ 4.2


$ 0.4

Share Repurchases


$ —


$ —


$ 0.0

$ —


$ 6.3


$ (6.3)

Average Diluted Shares (millions)


540


539


1

538


541


(3)


Note: Numbers may not add due to rounding

$Billions


12/31/23


12/31/22


YTD Δ

Cash and Investments


$ 10.9


$ 9.3


$ 1.6

Debt Outstanding


$ 64.6


$ 38.9


$ 25.7


Note: Numbers may not add due to rounding


2024 Guidance

For the full year 2024, the Company expects:

Total revenues in the range of $32.4 billion to $33.8 billion.
On a GAAP basis, EPS in the range of $8.42 to $9.87, and a tax rate in the range of 11.5% to 13.0%.
On a non-GAAP basis, EPS in the range of $18.90 to $20.30, and a tax rate in the range of 16.0% to 17.0%.
Capital expenditures to be approximately $1.1 billion.
Share repurchases not to exceed $500 million.
Fourth Quarter Product and Pipeline Update

The Company provided the following updates on selected product and pipeline programs:

General Medicine

Maridebart cafraglutide (AMG 133)

A Phase 2 study of maridebart cafraglutide, a multispecific molecule that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon like peptide 1 (GLP-1) receptor, in overweight or obese adults with or without type 2 diabetes mellitus has completed enrollment, with topline data anticipated in late 2024. The Company recently added a Part 2 to this study which explores durable weight loss beyond 52 weeks.
Planning for a comprehensive Phase 3 program across multiple indications remains on track.
In February 2024, results of preclinical studies and the Phase 1 study of maridebart cafraglutide were published in Nature Metabolism.
AMG 786

A Phase 1 study of AMG 786, a small molecule obesity program, is ongoing with initial data readout anticipated in H1 2024. This molecule has a different target than maridebart cafraglutide and is not an incretin-based therapy.
Olpasiran (AMG 890)

A Phase 3 cardiovascular outcomes study of olpasiran, a potentially best-in-class small interfering ribonucleic acid (siRNA) molecule that reduces lipoprotein(a) (Lp(a)) synthesis in the liver, in patients with atherosclerotic cardiovascular disease and elevated Lp(a) continues to enroll patients. To date, over 7,000 patients have been enrolled, with enrollment completion anticipated in H1 2024.
Repatha

EVOLVE-MI, a Phase 4 study of Repatha administered within 10 days of an acute myocardial infarction to reduce the risk of cardiovascular events, continues to enroll patients.
A Phase 3 cardiovascular outcomes study (VESALIUS-CV) in patients at high cardiovascular risk without prior myocardial infarction or stroke is ongoing.
Oncology

Tarlatamab (AMG 757)

The U.S. Food and Drug Administration (FDA) has granted Priority Review for the Company’s Biologics License Application (BLA) for tarlatamab, a first-in-class investigational delta-like ligand 3 (DLL3) targeting BiTE (bispecific T-cell engager) molecule. The BLA is based on the results from the Phase 2 DeLLphi-301 clinical trial, which demonstrated antitumor activity with a durable response and encouraging survival outcomes in previously treated small cell lung cancer (SCLC). The safety profile was consistent with the Phase 1 trial. Based on the Priority Review designation, the Prescription Drug User Fee Act (PDUFA) date for tarlatamab is June 12, 2024.
DeLLphi-304, a Phase 3 study comparing tarlatamab with standard of care chemotherapy in second-line SCLC, continues to enroll patients.
DeLLphi-306, a Phase 3 study comparing tarlatamab with placebo in limited-stage SCLC, was initiated.
DeLLphi-305, a Phase 3 study comparing tarlatamab and durvalumab with durvalumab alone in first-line, extensive-stage SCLC, will be initiated in H1 2024.
DeLLphi-300, a Phase 1 study of tarlatamab in relapsed/refractory SCLC, continues to enroll patients.
DeLLphi-302, a Phase 1b study of tarlatamab in combination with AMG 404, an anti-programmed cell death protein 1 (PD1) monoclonal antibody, in second-line or later SCLC, is ongoing.  
DeLLphi-303, a Phase 1b study of tarlatamab in combination with standard of care in first-line SCLC, continues to enroll patients.
DeLLpro-300, a Phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer, is ongoing.
BLINCYTO

The FDA granted Priority Review for the Company’s supplemental BLA for BLINCYTO in early-stage, CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) based in part on the Phase 3 E1910 study conducted by the National Cancer Institute, the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network Cancer Research Group. Based on the Priority Review designation, the PDUFA date for BLINCYTO is June 21, 2024. Additional global regulatory authority submissions are underway.
Golden Gate, a Phase 3 study of BLINCYTO alternating with low-intensity chemotherapy in older adults with newly diagnosed Philadelphia chromosome-negative (Ph-) B-ALL, continues to enroll patients.
The Company is planning to amend the Golden Gate Phase 3 study to include an evaluation of blinatumomab subcutaneous administration with initiation anticipated in H2 2024.
A Phase 1/2 study of subcutaneous blinatumomab in adults with relapsed or refractory Ph- B-ALL continues to enroll patients.
Xaluritamig (AMG 509)

A Phase 1b monotherapy and combination dose-escalation and -expansion study of xaluritamig, a first-in-class bispecific T-cell engager targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1) in metastatic castrate resistant prostate cancer continues to enroll patients in the dose-expansion portion of the study, where enrollment is almost complete. A reduced monitoring cohort was also initiated.
Two additional Phase 1 studies of xaluritamig to evaluate preliminary efficacy and safety in patients with early prostate cancer are planned.
AMG 193

The Phase 1/1b/2 study of AMG 193, a first-in-class small molecule methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, continues to enroll patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors. To date, responses have been seen in nine patients across seven tumor types.
Master protocols in thoracic and gastrointestinal malignancies exploring combinations with standard of care will be initiated in H1 2024.
A Phase 1/2 study of AMG 193 in combination with IDE397, an investigational methionine adenosyltransferase 2A (MAT2A) inhibitor, is enrolling patients.
Nplate

A Phase 3 study of Nplate in chemotherapy-induced thrombocytopenia in gastrointestinal, pancreatic, or colorectal malignancies is fully enrolled. Data readout is anticipated in H2 2024.
LUMAKRAS/LUMYKRAS

A U.S. regulatory submission is planned for the Phase 3 CodeBreaK 300 trial in H1 2024. This study evaluated two doses of LUMAKRAS (960 mg or 240 mg) in combination with Vectibix in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (CRC).
A Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI in first-line KRAS G12C-mutated CRC was initiated.
A Phase 3 study of LUMAKRAS plus chemotherapy vs. pembrolizumab plus chemotherapy in first-line KRAS G12C-mutated and programmed cell death protein ligand-1 (PD-L1) negative advanced non-small cell lung cancer (NSCLC) is enrolling patients.
Regulatory review by the European Medicines Agency (EMA) of the CodeBreaK 200 Phase 3 trial of adults with previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC along with data from the Phase 2 dose-comparison substudy is ongoing.
The FDA completed its review of the Company’s supplemental New Drug Application seeking full approval of LUMAKRAS based on the CodeBreaK 200 trial results. The FDA issued a new postmarketing requirement for an additional confirmatory study to support full approval to be completed no later than February 2028, while also concluding that LUMAKRAS at 960 mg once-daily will remain the dose for patients with KRAS G12C-mutated NSCLC under accelerated approval.
Bemarituzumab

FORTITUDE-101, a Phase 3 study of bemarituzumab, a first-in-class fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody, plus chemotherapy in first-line gastric cancer, continues to enroll patients.
FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab in first-line gastric cancer, continues to enroll patients in the Phase 3 portion of the study.
FORTITUDE-103, a Phase 1b/2 study of bemarituzumab plus oral chemotherapy regimens with or without nivolumab in first-line gastric cancer, continues to enroll patients.
FORTITUDE-301, a Phase 1b/2 basket study of bemarituzumab monotherapy in solid tumors with FGFR2b overexpression, is ongoing.
Inflammation

TEZSPIRE

In severe asthma, the WAYFINDER Phase 3b study is fully enrolled. The PASSAGE Phase 4 real-world effectiveness study and the SUNRISE Phase 3 study continue to enroll patients.
A Phase 3 study of TEZSPIRE in chronic rhinosinusitis with nasal polyps is fully enrolled. Primary analysis is anticipated in H2 2024.
A Phase 3 study of TEZSPIRE in eosinophilic esophagitis continues to enroll patients.
A Phase 2 study of TEZSPIRE in chronic obstructive pulmonary disease is fully enrolled. Data readout is anticipated in H1 2024.
Rocatinlimab (AMG 451/KHK4083)

The ROCKET Phase 3 program, now composed of eight studies evaluating rocatinlimab, a first in class monoclonal antibody targeting OX40, in moderate to severe atopic dermatitis, continues to enroll adult and adolescent patients. To date, over 2,400 patients have been enrolled in the ROCKET program.
The Phase 3 HORIZON study (part of the ROCKET program) evaluating rocatinlimab monotherapy vs. placebo in adults with moderate to severe atopic dermatitis is fully enrolled. Data readout is anticipated in H2 2024.
A Phase 2 study of rocatinlimab in asthma will be initiated in H1 2024 and a Phase 3 study of rocatinlimab in prurigo nodularis will be initiated in H2 2024.
Otezla

In November 2023, data were presented from the MOSAIC and FOREMOST studies:
In the MOSAIC Phase 4 study, primary and key secondary outcomes highlighted that Otezla led to better inflammatory disease control in psoriatic arthritis patients with moderate clinical disease activity than in patients with high disease activity.
In the FOREMOST Phase 4 study, Otezla when added to standard of care, significantly improved disease activity in patients with early oligoarticular (few joints involved) psoriatic arthritis at 16 weeks compared to placebo.
Efavaleukin alfa (AMG 592)

A Phase 2b study of efavaleukin alfa, an interleukin 2 (IL 2) mutein Fc fusion protein, in ulcerative colitis continues to enroll patients.
Ordesekimab (AMG 714/PRV-015)

A Phase 2b study of AMG 714, a monoclonal antibody that binds interleukin-15, in nonresponsive celiac disease has completed enrollment.
Rare Disease

TAVNEOS

In November 2023, data were presented from the Phase 3 ADVOCATE trial demonstrating that outcomes in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis favored TAVNEOS versus a prednisone taper across subgroups of patients 65 years and older, patients with kidney involvement and albuminuria, and patients with diffuse alveolar hemorrhage at baseline.
TEPEZZA

In December 2023, TEPEZZA received orphan drug designation in Japan for patients with moderate to severe active thyroid eye disease (TED).
A New Drug Application was submitted for TEPEZZA in Japan based on the results from the OPTIC-J study evaluating TEPEZZA in patients with active TED.
A Phase 3 study of TEPEZZA in Japan for chronic or low clinical activity score (CAS) TED continues to enroll patients.
The Company plans to initiate a Phase 3 study evaluating the subcutaneous route of administration of TEPEZZA in patients with TED in H1 2024.
UPLIZNA

A Phase 3 study of UPLIZNA in myasthenia gravis is fully enrolled. Data readout is anticipated in H2 2024.
A Phase 3 study of UPLIZNA for the prevention of flare in immunoglobulin G4- (IgG4) related disease is fully enrolled. Data readout is anticipated in H2 2024.
Dazodalibep

A Phase 3 study of dazodalibep, a cluster of differentiation 40 (CD40) ligand inhibitor fusion protein in Sjögren’s syndrome is enrolling patients.
Daxdilimab

A Phase 2 study of daxdilimab, a fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7), in moderate-to-severe active primary discoid lupus erythematosus refractory to standard of care is enrolling patients.
A Phase 2 study of daxdilimab in dermatomyositis and antisynthetase inflammatory myositis is enrolling patients.
Fipaxalparant (formerly AMG 670 / HZN 825)

A Phase 2 study of fipaxalparant, a lysophosphatidic acid receptor 1 (LPAR1) antagonist, in idiopathic pulmonary fibrosis is enrolling patients. Data readout is anticipated in H2 2024.
A Phase 2 study of fipaxalparant in diffuse cutaneous systemic sclerosis is enrolling patients.
Biosimilars

The clinical comparative study portion of a randomized, double-blind pivotal study evaluating pharmacokinetic (PK) similarity of ABP 206 compared with OPDIVO (nivolumab) in resected stage III or stage IV melanoma patients in the adjuvant setting is enrolling patients.
TEZSPIRE is being developed in collaboration with AstraZeneca.
Rocatinlimab, formerly AMG 451/KHK4083, is being developed in collaboration with Kyowa Kirin.
Ordesekimab, formerly AMG 714 and also known as PRV-015, is being developed in collaboration with Provention Bio, a Sanofi Company. For the purposes of the collaboration, Provention Bio conducts a clinical trial and leads certain development and regulatory activities for the program.
Xaluritamig, formerly AMG 509, is being developed pursuant to a research collaboration with Xencor, Inc.
IDE397 is an investigational MAT2A inhibitor from IDEAYA Biosciences.
OPDIVO is a registered trademark of Bristol-Myers Squibb Company.

Non-GAAP Financial Measures

In this news release, management has presented its operating results for the fourth quarters and full years of 2023 and 2022, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2024 EPS and tax guidance in accordance with GAAP and on a non-GAAP basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, divestitures, restructuring and certain other items from the related GAAP financial measures. Beginning January 1, 2022, following industry guidance from the U.S. Securities and Exchange Commission, the Company no longer excludes adjustments for upfront license fees, development milestones and in-process research and development (IPR&D) expenses of pre-approval programs related to licensing, collaboration and asset acquisition transactions from its non-GAAP financial measures. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the fourth quarters and full years of 2023 and 2022. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. Management has also presented Earnings Before Interest, Taxes, Depreciation and Amortization (EBITDA) and debt leverage ratio for 2023, both of which are non-GAAP financial measures. EBITDA is computed by adding interest expense, provision for income taxes, and depreciation and amortization expense to GAAP net income. Debt leverage ratio is calculated as the ratio of GAAP total debt to EBITDA.

The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor’s overall understanding of the financial performance and prospects for the future of the Company’s normal and recurring business activities by facilitating comparisons of results of normal and recurring business operations among current, past and future periods. The Company believes that FCF provides a further measure of the Company’s liquidity. The Company believes its debt leverage ratio provides a supplemental operating metric for the full year period as it compares the amount of cash generated by our operations for the year.

The Company uses the non-GAAP financial measures set forth in the news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP.

Obsidian Therapeutics Announces Clinical & Preclinical Presentations at the American Association of Cancer Research Annual Meeting

On March 5, 2024 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported presentations reporting initial clinical data from the ongoing first-in-human study of OBX-115 and preclinical data from our cytoDRiVE platform demonstrating regulatable cytoTIL15 signal transduction in cis and trans, as well as the ability of a single drug-responsive domain (DRD) to coregulate two cytokines, LIGHT and mbIL15, in tumor-infiltrating lymphocytes (TIL) during the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which will be held April 5-10, 2024 in San Diego, CA (Press release, Obsidian Therapeutics, FEB 5, 2024, View Source [SID1234640838]).

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These data follow the announcement of positive top-line results from the ongoing first-in-human, Phase 1 clinical trial evaluating the safety and efficacy of OBX-115, Obsidian’s lead engineered TIL cell therapy candidate, in patients with metastatic melanoma that has relapsed and/or is refractory to prior immune checkpoint inhibitor (ICI) therapy (NCT05470283).

The details of these posters are as follows:

Title: OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy induced deepening and durable responses without interleukin 2 (IL2) in patients (pts) with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma
Presenting Author: Rodabe N Amaria, The University of Texas MD Anderson Cancer Center, Houston, TX
Poster: CT176, Tuesday April 9, 9:00 AM-12:30 PM PDT

Title: Trial in progress: A phase 1/2 study to investigate the safety and efficacy of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma
Presenting Author: Sajeve S Thomas, Orlando Health Cancer Institute, Orlando, FL
Poster: CT285, Tuesday April 9, 1:30 PM-5:00 PM PDT

Title: Tumor-infiltrating lymphocytes (TIL) engineered with membrane-bound IL15 (cytoTIL15 cells) exhibit pharmacologically regulatable signal transduction in cis and trans
Presenting Author: Rachel Burga, Obsidian Therapeutics, Inc., Cambridge, MA
Poster: LB072, Sunday April 7, 1:30-5:00 PM PDT

Title: Tumor-infiltrating lymphocytes (TIL) engineered with regulatable membrane-bound IL15 (mbIL15) and LIGHT (TNFSF14) show enhanced efficacy in fibroblast-containing cold tumors
Presenting Author: Balazs Koscso, Obsidian Therapeutics, Inc., Cambridge, MA
Poster: LB065, Sunday April 7, 1:30-5:00 PM PDT

About OBX-115

Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, anti-tumor activity, and clinical safety of TIL cell therapy. OBX-115 is being investigated in two ongoing and enrolling clinical trials in advanced or metastatic melanoma and NSCLC (NCT05470283 and NCT06060613).