On February 15, 2024 Astellas Pharma Inc. (TSE:4503, President and CEO: Naoki Okamura, "Astellas") reported that Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted priority review for the company’s Supplemental New Drug Application (sNDA) for PADCEV (enfortumab vedotin (genetical recombination)) with KEYTRUDA (pembrolizumab (genetical recombination)) as a combination therapy for the first-line treatment of adult patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC) (Press release, Astellas, FEB 15, 2024, View Source,-Labour-and-Welfare-for-First-Line-Treatment-of-Advanced-Bladder-Cancer [SID1234640160]). The sNDA was submitted in January 2024. If approved, PADCEV with KEYTRUDA has the potential to change the treatment paradigm, becoming the first combination treatment to offer an alternative to platinum-containing chemotherapy, the current standard of care in first-line la/mUC.

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Priority reviews are granted by MHLW for applications based on their clinical usefulness and the seriousness of the diseases for which they are indicated.i The sNDA for the first-line use of this combination is based on results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39). The study found the combination improved overall survival (OS) and progression-free survival (PFS) with statistically significant and clinically meaningful results in patients with previously untreated la/mUC compared to platinum-containing chemotherapy. The safety results were consistent with those previously reported with this combination, and no new safety issues were identified.

Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas
"The MHLW’s priority review for our application for PADCEV in combination with pembrolizumab reflects the significance of the EV-302 trial findings and the urgent need for innovative new treatment options. We are pleased by this review designation and hope to quickly bring this treatment option to those who need it most."

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency is also reviewing the combination therapy. The U.S. Food and Drug Administration approved the combination therapy in December 2023.

Globally, approximately 614,000 new cases of bladder cancer and approximately 220,000 deaths are reported annually.ii It is estimated that approximately 25,000 people in Japan are diagnosed with bladder cancer each year and approximately 10,000 deaths were reported in 2022.iii

About EV-302
The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or platinum-containing chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Select secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.

The EV-302 trial is part of an extensive clinical program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Findings from EV-302 were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in October 2023.

About Bladder and Urothelial Cancer

Urothelial cancer, or bladder cancer, begins in the urothelial cells, which line the urethra, bladder, ureters, renal pelvis, and some other organs.iv
If bladder cancer has spread to surrounding organs or muscles, it is called locally advanced disease. If the cancer has spread to other parts of the body, it is called metastatic disease.v
Urothelial cancer accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter, and urethra.iii
Approximately 12% of cases are locally advanced or metastatic urothelial cancer at diagnosis.vi
Ongoing Investigational Trials
The EV-302 trial (NCT04223856) is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC) who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status.

The EV-103 trial (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter Phase 1b/2 study investigating enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with la/mUC and patients with muscle-invasive bladder cancer (MIBC).

Enfortumab vedotin in combination with pembrolizumab is being investigated in an extensive program in multiple stages of urothelial cancer, including two Phase 3 clinical trials in MIBC in EV-304 (NCT04700124, also known as KEYNOTE-B15) and EV-303 (NCT03924895, also known as KEYNOTE-905). The use of enfortumab vedotin in combination with pembrolizumab in second-line urothelial cancer and MIBC has not been proven safe or effective.

The EV-202 trial (NCT04225117) is an ongoing, multi-cohort, open-label, multicenter Phase 2 study investigating enfortumab vedotin alone in patients with previously treated advanced solid tumors. This study also has a cohort that is investigating enfortumab vedotin in combination with pembrolizumab in patients with previously untreated recurrent/ metastatic head and neck squamous cell carcinoma.

About PADCEV (enfortumab vedotin (genetical recombination))
PADCEV (enfortumab vedotin (genetical recombination)) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.vi Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which results in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).vii

PADCEV (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information

BOXED WARNING: SERIOUS SKIN REACTIONS

PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occur predominantly during the first cycle of treatment but may occur later.
Closely monitor patients for skin reactions.
Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.
Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.
Indication

PADCEV, in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC).

PADCEV, as a single agent, is indicated for the treatment of adult patients with locally advanced or mUC who:

have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or
are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.
IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 70% (all grades) of the 564 patients treated with PADCEV in combination with pembrolizumab in clinical trials. When PADCEV was given in combination with pembrolizumab, the incidence of skin reactions, including severe events, occurred at a higher rate compared to PADCEV as a single agent. The majority of the skin reactions that occurred with combination therapy included maculo-papular rash, macular rash and papular rash. Grade 3-4 skin reactions occurred in 17% of patients (Grade 3: 16%, Grade 4: 1%), including maculo-papular rash, bullous dermatitis, dermatitis, exfoliative dermatitis, pemphigoid, rash, erythematous rash, macular rash, and papular rash. A fatal reaction of bullous dermatitis occurred in one patient (0.2%). The median time to onset of severe skin reactions was 1.7 months (range: 0.1 to 17.2 months). Skin reactions led to discontinuation of PADCEV in 6% of patients.

Skin reactions occurred in 58% (all grades) of the 720 patients treated with PADCEV as a single agent in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 34% had pruritus. Grade 3-4 skin reactions occurred in 14% of patients, including maculo-papular rash, erythematous rash, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. The median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 8 months). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=75), 24% of patients restarting at the same dose and 24% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 3.1% of patients.

Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. For persistent or recurrent Grade 2 skin reactions, consider withholding PADCEV until Grade ≤1. Withhold PADCEV and refer for specialized care for suspected SJS, TEN or for Grade 3 skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. In clinical trials of PADCEV as a single agent, 17% of the 720 patients treated with PADCEV developed hyperglycemia of any grade; 7% of patients developed Grade 3-4 hyperglycemia (Grade 3: 6.5%, Grade 4: 0.6%). Fatal events of hyperglycemia and DKA occurred in one patient each (0.1%). The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. The median time to onset of hyperglycemia was 0.5 months (range: 0 to 20 months). Hyperglycemia led to discontinuation of PADCEV in 0.7% of patients. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. Of the patients who initiated insulin therapy for treatment of hyperglycemia, 66% (23/35) discontinued insulin at the time of last evaluation. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

Pneumonitis/Interstitial Lung Disease (ILD) Severe, life-threatening or fatal pneumonitis/ILD occurred in patients treated with PADCEV. When PADCEV was given in combination with pembrolizumab, 10% of the 564 patients treated with combination therapy had pneumonitis/ILD of any grade and 4% had Grade 3-4. A fatal event of pneumonitis/ILD occurred in two patients (0.4%). The incidence of pneumonitis/ILD, including severe events, occurred at a higher rate when PADCEV was given in combination with pembrolizumab compared to PADCEV as a single agent. The median time to onset of any grade pneumonitis/ILD was 4 months (range: 0.3 to 26 months).

In clinical trials of PADCEV as a single agent, 3% of the 720 patients treated with PADCEV had pneumonitis/ILD of any grade and 0.8% had Grade 3-4. The median time to onset of any grade pneumonitis/ILD was 2.9 months (range: 0.6 to 6 months).

Monitor patients for signs and symptoms indicative of pneumonitis/ILD such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop Grade 2 pneumonitis/ILD and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis/ILD.

Peripheral neuropathy (PN) When PADCEV was given in combination with pembrolizumab, 67% of the 564 patients treated with combination therapy had PN of any grade, 36% had Grade 2 neuropathy, and 7% had Grade 3 neuropathy. The incidence of PN occurred at a higher rate when PADCEV was given in combination with pembrolizumab compared to PADCEV as a single agent. The median time to onset of Grade ≥2 PN was 6 months (range: 0.3 to 25 months).
PN occurred in 53% of the 720 patients treated with PADCEV as a single agent in clinical trials including 38% with sensory neuropathy, 8% with muscular weakness and 7% with motor neuropathy. Thirty percent of patients experienced Grade 2 reactions and 5% experienced Grade 3-4 reactions. PN occurred in patients treated with PADCEV with or without preexisting PN. The median time to onset of Grade ≥2 PN was 4.9 months (range: 0.1 to 20 months). Neuropathy led to treatment discontinuation in 6% of patients.

Monitor patients for symptoms of new or worsening PN and consider dose interruption or dose reduction of PADCEV when PN occurs. Permanently discontinue PADCEV in patients who develop Grade ≥3 PN.

Ocular disorders were reported in 40% of the 384 patients treated with PADCEV as a single agent in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry eye symptoms occurred in 30% of patients, and blurred vision occurred in 10% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.7 months (range: 0 to 30.6 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 720 patients treated with PADCEV as a single agent in clinical trials, 1% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

ADVERSE REACTIONS

Most common adverse reactions, including laboratory abnormalities (≥20%) (PADCEV in combination with pembrolizumab) Increased aspartate aminotransferase (AST), increased creatinine, rash, increased glucose, PN, increased lipase, decreased lymphocytes, increased alanine aminotransferase (ALT), decreased hemoglobin, fatigue, decreased sodium, decreased phosphate, decreased albumin, pruritus, diarrhea, alopecia, decreased weight, decreased appetite, increased urate, decreased neutrophils, decreased potassium, dry eye, nausea, constipation, increased potassium, dysgeusia, urinary tract infection and decreased platelets.

Most common adverse reactions, including laboratory abnormalities (≥20%) (PADCEV monotherapy) Increased glucose, increased AST, decreased lymphocytes, increased creatinine, rash, fatigue, PN, decreased albumin, decreased hemoglobin, alopecia, decreased appetite, decreased neutrophils, decreased sodium, increased ALT, decreased phosphate, diarrhea, nausea, pruritus, increased urate, dry eye, dysgeusia, constipation, increased lipase, decreased weight, decreased platelets, abdominal pain, dry skin.

EV-302 Study: 440 patients with previously untreated la/mUC (PADCEV in combination with pembrolizumab)

Serious adverse reactions occurred in 50% of patients treated with PADCEV in combination with pembrolizumab. The most common serious adverse reactions (≥2%) were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%). Fatal adverse reactions occurred in 3.9% of patients treated with PADCEV in combination with pembrolizumab including acute respiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%).
Adverse reactions leading to discontinuation of PADCEV occurred in 35% of patients. The most common adverse reactions (≥2%) leading to discontinuation of PADCEV were PN (15%), rash (4.1%) and pneumonitis/ILD (2.3%). Adverse reactions leading to dose interruption of PADCEV occurred in 73% of patients. The most common adverse reactions (≥2%) leading to dose interruption of PADCEV were PN (22%), rash (16%), COVID-19 (10%), diarrhea (5%), pneumonitis/ILD (4.8%), fatigue (3.9%), hyperglycemia (3.6%), increased ALT (3%) and pruritus (2.5%). Adverse reactions leading to dose reduction of PADCEV occurred in 42% of patients. The most common adverse reactions (≥2%) leading to dose reduction of PADCEV were rash (16%), PN (13%) and fatigue (2.7%).

EV-103 Study: 121 patients with previously untreated la/mUC who were not eligible for cisplatin-containing chemotherapy (PADCEV in combination with pembrolizumab)

Serious adverse reactions occurred in 50% of patients treated with PADCEV in combination with pembrolizumab; the most common (≥2%) were acute kidney injury (7%), urinary tract infection (7%), urosepsis (5%), sepsis (3.3%), pneumonia (3.3%), hematuria (3.3%), pneumonitis/ILD (3.3%), urinary retention (2.5%), diarrhea (2.5%), myasthenia gravis (2.5%), myositis (2.5%), anemia (2.5%), and hypotension (2.5%). Fatal adverse reactions occurred in 5% of patients treated with PADCEV in combination with pembrolizumab, including sepsis (1.6%), bullous dermatitis (0.8%), myasthenia gravis (0.8%), and pneumonitis/ILD (0.8%). Adverse reactions leading to discontinuation of PADCEV occurred in 36% of patients; the most common (≥2%) were PN (20%) and rash (6%). Adverse reactions leading to dose interruption of PADCEV occurred in 69% of patients; the most common (≥2%) were PN (18%), rash (12%), increased lipase (6%), pneumonitis/ILD (6%), diarrhea (4.1%), acute kidney injury (3.3%), increased ALT (3.3%), fatigue (3.3%), neutropenia (3.3%), urinary tract infection (3.3%), increased amylase (2.5%), anemia (2.5%), COVID-19 (2.5%), hyperglycemia (2.5%), and hypotension (2.5%). Adverse reactions leading to dose reduction of PADCEV occurred in 45% of patients; the most common (≥2%) were PN (17%), rash (12%), fatigue (5%), neutropenia (5%), and diarrhea (4.1%).

EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy (PADCEV monotherapy)

Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (≥2%) were urinary tract infection, acute kidney injury (7% each), and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis/ILD, and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (≥4%) were PN (23%), rash (11%), and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (≥2%) were PN (10%), rash (8%), decreased appetite, and fatigue (3% each).

EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for cisplatin-based chemotherapy (PADCEV monotherapy)

Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (≥3%) were pneumonia, sepsis, and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia, and pneumonitis/ILD (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (≥2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (≥3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), increased AST, and hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (≥3%) were PN (19%), rash (11%), and fatigue (7%).

DRUG INTERACTIONS

Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors)
Concomitant use with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

SPECIFIC POPULATIONS

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for 3 weeks after the last dose.

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

For more information, please see the U.S. full Prescribing Information including BOXED WARNING for PADCEV here.

On February 15, 2024 Hox Therapeutics Ltd ("Hox") a private biotechnology company developing highly targeted cancer therapies and Vernalis (R&D) Ltd ("Vernalis"), a fully owned subsidiary of HitGen Inc., reported a collaboration to identify inhibitors against an undisclosed oncology target (Press release, Vernalis, FEB 15, 2024, View Source;utm_medium=rss&utm_campaign=hox-therapeutics-and-vernalis-announce-a-drug-discovery-collaboration-in-oncology [SID1234640156]).

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Under the terms of the agreement, Vernalis will use its state-of-the-art protein science and Hit ID platforms to produce the target protein, and to identify and characterise small molecule inhibitors of the target. The research at Vernalis will be funded by Hox. Financial terms have not been disclosed.

James Murray, Research Director of Vernalis, said, "This partnership is built on Vernalis’s strong record for innovation in drug discovery to generate clinical candidates. We look forward to working closely with Hox to successfully achieve the goals of this collaboration".

Nicholas Adams, CEO of Hox Therapeutics, said, "We are delighted to be working with Vernalis on this project. They have proven expertise in being able to identify inhibitors against the protein target that we’re interested in".

On February 15, 2024 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, reported its financial results for the quarter and full year ended December 31, 2023 and reaffirmed its financial guidance for 2024 (Press release, Ultragenyx Pharmaceutical, FEB 15, 2024, View Source [SID1234640155]).

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"Last year, we made significant progress across our pipeline and look forward to multiple catalysts in 2024 with substantive data in Angelman syndrome that could enable a Phase 3 study, pivotal Phase 3 data from our GSDIa gene therapy program, dose-finding data from our seamless study in Wilson disease, and longer-term Phase 2 data in Osteogenesis Imperfecta," said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. "In 2023, we saw increased demand for both Crysvita and Dojolvi, and achieved multiple regulatory and reimbursement milestones for our commercial products to support continued revenue growth of approximately 20% in 2024."

Fourth Quarter and Full Year 2023 Selected Financial Data Tables and Financial Results

Revenues (dollars in thousands), (unaudited)
Three Months Ended December 31, Year Ended December 31,
2023 2022 2023 2022
Crysvita
Product sales $ 18,379 $ 7,698 $ 75,697 $ 42,678
Revenue in Profit-Share Territory 70,124 66,903 231,574 215,024
Royalty revenue in European Territory 5,612 6,058 20,783 21,692
Total Crysvita Revenue 94,115 80,659 328,054 279,394
Dojolvi 23,286 16,412 70,633 55,612
Mepsevii 7,889 4,798 30,441 20,637
Evkeeza 2,102 — 3,642 —
Daiichi Sankyo — 1,479 1,479 7,686
Total revenues $ 127,392 $ 103,348 $ 434,249 $ 363,329

Total Revenues
Ultragenyx reported $127 million in total revenue for the fourth quarter 2023, which represents 23% growth compared to the same period in 2022. Fourth quarter 2023 Crysvita revenue was $94 million, which represents 17% growth compared to the same period in 2022. This includes product sales of $18 million from Latin America and Turkey, which represents 139% growth compared to the same period in 2022. Dojolvi revenue in the fourth quarter 2023 was $23 million, which represents 42% growth compared to the same period in 2022.

Total revenue for the year ended December 31, 2023 was $434 million, which represents 20% growth compared to the prior year. Full year 2023 Crysvita revenue was $328 million, which represents 17% growth compared to the same period in 2022. This includes product sales of $76 million from Latin America and Turkey, which represents 77% growth compared to the same period in 2022. Dojolvi revenue in 2023 was $71 million, which represents 27% growth compared to the same period in 2022.

Selected Financial Data (dollars in thousands, except per share amounts), (unaudited)
Three Months Ended December 31, Year Ended December 31,
2023 2022 2023 2022
Total revenues $ 127,392 $ 103,348 $ 434,249 $ 363,329
Operating expenses:
Cost of sales 12,051 5,319 45,209 28,320
Research and development 160,557 170,808 648,449 705,789
Selling, general and administrative 76,833 72,849 309,799 278,139
Total operating expenses 249,441 248,976 1,003,457 1,012,248
Net loss $ (123,190 ) $ (151,833 ) $ (606,639 ) $ (707,421 )
Net loss per share, basic and diluted $ (1.52 ) $ (2.16 ) $ (8.25 ) $ (10.12 )

Operating Expenses
Total operating expenses for the fourth quarter of 2023 were $249 million, including non-cash stock-based compensation of $34 million. Total operating expenses for the year ended December 31, 2023 were $1,003 million, including $135 million of non-cash stock-based compensation. In 2024, annual operating expenses are expected to be stable or to decrease as the company continues to manage its costs, focus its investment on advancing multiple Phase 3 programs, and execute on commercial product launches.

Net Loss
For the fourth quarter of 2023, Ultragenyx reported net loss of $123 million, or $1.52 per share basic and diluted, compared with a net loss for the fourth quarter of 2022 of $152 million, or $2.16 per share, basic and diluted. For the year ended December 31, 2023, Ultragenyx reported net loss of $607 million, or $8.25 per share basic and diluted, compared with a net loss the prior year of $707 million, or $10.12 per share, basic and diluted.

Net Cash Used in Operations and Cash Balance
Net cash used in operations for the year ended December 31, 2023 was $475 million. Cash, cash equivalents, and marketable debt securities were $777 million as of December 31, 2023.

2024 Financial Guidance
For the full year 2024, the company reaffirms:

Total revenue in the range of $500 million to $530 million
Crysvita revenue in the range of $375 million to $400 million. This includes all regions where Ultragenyx will recognize revenue: product sales in Latin America and Turkey, royalties in Europe, which have been ongoing, and royalties in North America, which began in April 2023.
Dojolvi revenue in the range of $75 million to $80 million
Net Cash Used in Operations to be less than $400 million
Recent Updates and Clinical Milestones

UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Phase 3 portion of Orbit study expected to be fully enrolled around the end of the first quarter of 2024
Patients are being dosed in the late-stage clinical trials, Orbit and Cosmic, which are evaluating setrusumab in pediatric and young adult patients with OI. The randomized, placebo-controlled Phase 3 portion of the Orbit study is expected to enroll approximately 150 patients and be fully enrolled around the end of the first quarter of 2024. Additional longer-term Phase 2 safety and efficacy data from the Orbit study are expected in the second half of 2024.

The Phase 3 Cosmic study is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients age 2 to <5 years. Cosmic is expected to enroll approximately 50 patients or more at more than 20 global sites and is expected to complete enrollment in the first half of 2024.

GTX-102 antisense oligonucleotide for Angelman syndrome: Phase 1/2 fully enrolled; expansion data expected in the first half of 2024
Enrollment in the expansion cohorts was completed in December 2023 with a total of 53 new patients enrolled. A total of 74 patients are enrolled in the Phase 1/2 study including the dose-escalation/extension study patients. The expansion cohorts will evaluate many of the same safety, pharmacokinetic, and efficacy measures as the previously enrolled dose-escalation/extension cohorts plus some new evaluations. The next safety and efficacy update is expected in the first half of 2024 and is planned to include data from at least 20 expansion cohort patients with a minimum of Day 170 data.

In January 2024, GTX-102 was accepted into the Priority Medicines (PRIME) program by the European Medicines Agency (EMA). PRIME is granted by the EMA to medicines that show the potential to benefit patients with unmet needs based on early clinical data. Through PRIME, the EMA offers early and proactive support to optimize development plans and the generation of robust data on a medicine’s benefits and risks, and enables accelerated assessment of medicines applications.

UX701 AAV gene therapy for Wilson disease: Last patient in Cohort 3 dosed; expect interim Stage 1 data in mid-2024
All patients in the three dose-escalation cohorts of Stage 1 have been dosed. During Stage 1, the safety and efficacy of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2, the pivotal, randomized, placebo-controlled stage of the study. Data from Stage 1 are expected in mid-2024, which will be followed by dose selection and initiation of Stage 2 in the second half of 2024.

UX111 AAV gene therapy for Sanfilippo syndrome (MPS IIIA): Updated data from pivotal Transfer A study presented at WORLDSymposiumTM
New positive data from the ongoing pivotal Transfer A study evaluating the safety and efficacy of UX111 in children with MPS IIIA were presented at the 20th Annual WORLDSymposium earlier this month showing that a single infusion of UX111 can substantially correct the underlying metabolic disease and maintain cognitive function in nearly all patients. The presentation also showed that the observed reductions of heparan sulfate exposure in cerebrospinal fluid can predict improved long-term cognitive function in patients with MPS IIIA following treatment with UX111. With these data and other data, discussions are ongoing with the FDA seeking an accelerated review path for UX111.

DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Dosing in Phase 3 study complete; Phase 3 data readout expected in the first half of 2024
In May 2023, Ultragenyx announced the last patient had been dosed in the Phase 3 study. The 48-week study has fully enrolled patients eight years of age and older, randomized 1:1 to DTX401 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. Phase 3 safety and efficacy data are expected in the first half of 2024.

DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patients; expect enrollment to be completed in the first half of 2024
Ultragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Enrollment is currently expected to be completed in the first half of 2024.

Conference Call and Webcast Information

Ultragenyx will host a conference call today, Thursday, February 15, 2024, at 2 p.m. PT/5 p.m. ET to discuss the fourth quarter and full year 2023 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call, please register by clicking on the following link (https://register.vevent.com/register/BI177d5c166d3045ddaa4dcd3b3ec136ba) and you will be provided with dial-in details. The replay of the call will be available for one year.

On February 15, 2024 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported completion of enrollment of the first six participants in Part 3 of its Phase 1 clinical trial of sudocetaxel zendusortide in patients with advanced ovarian cancer (Press release, Theratechnologies, FEB 15, 2024, View Source [SID1234640154]). Sudocetaxel zendusortide, also known as TH1902, is an investigational, first-in-class peptide-drug conjugate (PDC) that targets the sortilin receptor (SORT1) and aims to expedite the internalization and delivery of the cytotoxic payload (docetaxel) directly into cancer cells.

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"Reaching this important milestone gives fresh momentum to the Phase 1 trial of sudocetaxel zendusortide, and to our overall oncology clinical development program," said Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer at Theratechnologies. "As we gear up for the next round of screening, we look forward to adding patients at the next dose level and further characterizing the safety and efficacy of this novel peptide-drug conjugate."

Theratechnologies announced dosing of the first patient in Part 3 of the Phase 1 trial in October 2023. In June 2023, the U.S. Food and Drug Administration (FDA) accepted the Company’s amended protocol for the Phase 1 trial, which is designed to optimize the dosing, improve the therapeutic window and extend the duration of therapy of sudocetaxel zendusortide. The amendment, which the Company submitted in May 2023, also narrows the patient population to focus on individuals with high-grade serous ovarian cancer, including high-grade peritoneal or fallopian tube cancer, or high-grade endometrioid cancer — a population in which sudocetaxel zendusortide has demonstrated preliminary efficacy. After establishing the safety of the initial dose in the first six patients for a period of three months, the enrollment of the next cohort of six patients at a higher dose will be initiated.

"I am encouraged by the progress made in the Phase 1 trial of sudocetaxel zendusortide, from acceptance of the protocol amendment, to dosing the first patient, to completing enrollment of the first six women in this part of the study," commented Ira Winer, M.D., Ph.D., FACOG, Gynecologic Oncology and Phase I multidisciplinary member at Karmanos Cancer Center and trial investigator. "The ongoing study will yield important information about this agent’s utility in treating patients with platinum-resistant ovarian cancer, a population with few effective therapeutic options."

Parts 1 and 2 of the Phase 1 trial provided preliminary evidence of the antitumor activity of sudocetaxel zendusortide, as presented at the 2023 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). Details about the study design, participation criteria and contact information for the sites can be found at: View Source

About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology

Sudocetaxel zendusortide is a first-of-its-kind sortilin receptor (SORT1)-targeting PDC, and the first compound to emerge from the Company’s broader licensed oncology platform. A new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial.

Theratechnologies has established the SORT1+ Technology platform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumor types. SORT1 is a "scavenger" receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development.

On February 15, 2024 Royalty Pharma plc (Nasdaq: RPRX) reported financial results for the fourth quarter and full year of 2023 and introduced full year 2024 guidance for Portfolio Receipts. "Royalty Pharma delivered outstanding results in 2023," said Pablo Legorreta, Royalty Pharma’s founder and Chief Executive Officer (Press release, Royalty Pharma , FEB 15, 2024, View Source [SID1234640151]).

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"We reported another year of strong growth in royalty receipts and deployed substantial capital in value-enhancing transactions, including our strongest year ever for synthetic royalty transactions. Furthermore, a number of positive clinical and regulatory milestones strengthened the outlook for our diversified royalty portfolio. Based on the strong fundamental tailwinds underpinning our business, our strong balance sheet and robust deal pipeline, I am confident we are in an excellent position to fund life sciences innovation and deliver attractive, long-term compounding growth."

Portfolio Receipts show strong growth for full year 2023

Portfolio Receipts (previously referred to as Adjusted Cash Receipts) decreased 31% to $736 million in the fourth quarter, reflecting the accelerated Biohaven payments received in the fourth quarter of 2022.

Portfolio Receipts increased 9% to $3,049 million for full year 2023, driven primarily by strong portfolio performance and new royalty acquisitions, and consistent with the raised guidance provided on January 8, 2024.

Royalty receipts grew 10% for the quarter and 8% for the full year.

Significant transaction activity in 2023 with eight potentially transformative therapies added to portfolio

Announced value of new transactions was $4.0 billion for full year 2023.

Transactions since 2020 expected to add approximately $1.2 billion to Portfolio Receipts in 2025.

Positive updates in the fourth quarter across development-stage royalty portfolio

Phase 3 results for Cytokinetics’ aficamten met the primary endpoint for hypertrophic cardiomyopathy.

Bristol Myers Squibb announced the acquisition of Karuna (marketer of KarXT for schizophrenia).

Phase 3 results for MorphoSys’ pelabresib met the primary endpoint in myelofibrosis; Novartis announced the acquisition of MorphoSys.

Financial guidance for full year 2024 (excludes contribution from future transactions)

Royalty Pharma expects 2024 Portfolio Receipts to be between $2,600 million and $2,700 million.

2024 Portfolio Receipts guidance includes expected growth in royalty receipts of 5% to 9%.

Financial & Liquidity Summary

Three Months Ended
December 31,

Twelve Months Ended
December 31,

(unaudited)

($ and shares in millions)

2023

2022

2023

2022

Portfolio Receipts

736

1,064

3,049

2,789

Net cash provided by operating activities

773

570

2,988

2,144

Adjusted EBITDA (non-GAAP)*

682

983

2,806

2,566

Portfolio Cash Flow (non-GAAP)*

687

996

2,708

2,421

Weighted average/fully diluted Class A ordinary shares outstanding

598

607

603

607

* See "Liquidity and Capital Resources" section. Adjusted EBITDA and Portfolio Cash Flow are non-GAAP liquidity measures calculated in accordance with the credit agreement. Portfolio Cash Flow is a non-GAAP measure that is calculated as Adjusted EBITDA minus interest paid or received, net.

Fourth Quarter 2023 Portfolio Receipts

As previously announced (January 8, 2024 press release), Portfolio Receipts is now being reported as a key performance metric. The calculation of Portfolio Receipts will result in the same amount as Royalty Pharma’s previous presentation of Adjusted Cash Receipts (which will no longer be reported).

This change of presentation will facilitate increased transparency into the economics of individual royalties as royalty receipts by product and franchise will now be reported net of legacy non-controlling interests. In addition, Royalty receipts and Milestones and other contractual receipts will be reported as two separate subtotals summing to Portfolio Receipts. This change will provide greater clarity on the underlying trends of Royalty Pharma’s royalty portfolio versus other contractual payments which may be more variable over time. Prior-period results using this updated presentation are available for download on the Quarterly Results page of the company’s website under Supplemental Financial Information (link here).

Portfolio Receipts Highlights

Three Months Ended December 31,

(unaudited)

($ in millions)

2023

2022

Change

Products:

Marketers:

Therapeutic Area:

Cystic fibrosis franchise

Vertex

Rare disease

208

187

11%

Tysabri

Biogen

Neuroscience

68

73

(7)%

Trelegy

GSK

Respiratory

60

47

28%

Imbruvica

AbbVie, Johnson & Johnson

Cancer

50

58

(13)%

Promacta

Novartis

Hematology

44

40

9%

Xtandi

Pfizer, Astellas

Cancer

38

38

1%

Tremfya

Johnson & Johnson

Immunology

35

29

21%

Evrysdi

Roche

Rare disease

20

14

44%

Cabometyx/Cometriq

Exelixis, Ipsen, Takeda

Cancer

18

15

18%

Spinraza

Biogen

Rare disease

17

—

n/a

Trodelvy

Gilead

Cancer

10

6

64%

Erleada

Johnson & Johnson

Cancer

9

5

72%

Orladeyo

BioCryst

Rare disease

8

6

29%

Nurtec ODT/Zavzpret

Pfizer

Neuroscience

5

4

20%

Other products(5)

63

71

(12)%

Royalty receipts

651

593

10%

Milestones and other contractual receipts

84

470

(82)%

Portfolio Receipts

736

1,064

(31)%

Results for full year 2023 and 2022 are shown in Table 4. Amounts shown in the table may not add due to rounding.

Portfolio Receipts was $736 million in the fourth quarter of 2023, a decrease of 31% compared to the same period in 2022. The decrease in the fourth quarter was attributable to the accelerated redemption of all outstanding Series A and Series B Biohaven Preferred Shares following Pfizer’s acquisition of Biohaven in October 2022, which is reflected within milestones and other contractual receipts. Royalty receipts increased 10%, primarily driven by growth in the cystic fibrosis franchise, Trelegy and Evrysdi, and the addition of new royalties on Spinraza. These positive factors were partially offset by declining royalty receipts on Imbruvica, Tysabri and other products.

Liquidity and Capital Resources

Royalty Pharma’s liquidity and capital resources are summarized below:

As of December 31, 2023, Royalty Pharma had cash and cash equivalents of $477 million and total debt with principal value of $6.3 billion.

Liquidity Summary

Three Months Ended
December 31,

Twelve Months Ended
December 31,

($ in millions)

2023

2022

2023

2022

Portfolio Receipts

736

1,064

3,049

2,789

Payments for operating and professional costs

(54)

(81)

(243)

(223)

Adjusted EBITDA (non-GAAP)*

682

983

2,806

2,566

Interest received/(paid), net

5

14

(98)

(145)

Portfolio Cash Flow (non-GAAP)*

687

996

2,708

2,421

Amounts may not add due to rounding.
*Adjusted EBITDA and Portfolio Cash Flow are calculated in accordance with the credit agreement.

Adjusted EBITDA and Portfolio Cash Flow are supplemental non-GAAP liquidity measures that are key components of certain material covenants contained in Royalty Pharma’s credit agreement.

Adjusted EBITDA (non-GAAP) was $682 million in the fourth quarter of 2023. Adjusted EBITDA is calculated in accordance with the credit agreement as Portfolio Receipts minus payments for operating and professional costs. The calculation of Adjusted EBITDA results in the same total as under Royalty Pharma’s previous presentation of Adjusted EBITDA.

Portfolio Cash Flow (non-GAAP) was $687 million in the fourth quarter of 2023. Portfolio Cash Flow is calculated in accordance with the credit agreement as Adjusted EBITDA minus interest paid or received, net. This non-GAAP measure was added to our disclosure to align with a material covenant contained in Royalty Pharma’s credit agreement. This measure reflects the cash generated by Royalty Pharma’s business that can be redeployed into value-enhancing royalty acquisitions, used to repay debt, returned to shareholders through dividends or share purchases or utilized for other discretionary investments. The calculation of Portfolio Cash Flow does not include development-stage funding payments – upfront and milestone. This is the primary material difference from Royalty Pharma’s previous presentation of Adjusted Cash Flow (which will no longer be reported).

Royalty Pharma has provided a reconciliation of each non-GAAP measure to the most directly comparable GAAP financial measure, net cash provided by operating activities in Table 5.

Royalty Pharma announced new transactions of up to $4.0 billion in 2023, which includes upfront payments and potential future milestones. Royalty Pharma is now providing an aggregate amount for total Capital Deployment, which reflects cash payments during the period for new and previously announced transactions. Capital Deployment was $1.0 billion in the fourth quarter and $2.2 billion in 2023. See the detail of Capital Deployment by category below.

Capital Deployment Details

Three Months Ended
December 31,

Twelve Months Ended
December 31,

($ in millions)

2023

2022

2023

2022

Acquisitions of financial royalty assets

(1,002)

(250)

(2,116)

(1,742)

Development-stage funding payments – upfront and milestone

—

(50)

(50)

(175)

Development-stage funding payments – ongoing

(1)

(1)

(2)

(2)

Purchases of available for sale debt securities

—

(86)

—

(480)

Milestone payments

—

—

(12)

—

Investments in equity method investees

(2)

—

(13)

(10)

Acquisitions of other financial assets

—

—

—

(21)

Contributions from legacy non-controlling interests – R&D

0

0

1

1

Total Capital Deployment

(1,005)

(386)

(2,192)

(2,428)

Amounts may not add due to rounding.

In October 2023, Royalty Pharma drew $350 million under its existing unsecured revolving credit facility, which was repaid during the fourth quarter of 2023. Royalty Pharma also executed an amendment to its credit agreement during the fourth quarter of 2023 to increase its borrowing capacity under the revolving credit facility to $1.8 billion and to extend the maturity for a portion of the commitments.

Royalty Pharma began repurchasing its Class A ordinary shares in April 2023 under a $1.0 billion multi-year share repurchase program. During the fourth quarter of 2023, Royalty Pharma repurchased approximately 957,000 shares for $26 million. The weighted-average diluted Class A ordinary shares outstanding for the fourth quarter of 2023 was approximately 598 million and the fully diluted Class A ordinary shares outstanding was approximately 607 million for the fourth quarter of 2022. Royalty Pharma repurchased approximately 10 million shares for $305 million in 2023 under this repurchase program.

Recent Transactions

During the fourth quarter of 2023, Royalty Pharma announced new transactions of up to $1.6 billion. Announced transactions amount reflects the entire amount of capital committed for new transactions during the year, including potential future milestones.

Recent transactions include:

In November 2023, Royalty Pharma acquired a royalty interest in long-acting injectable olanzapine (TEV-’749), a Phase 3 development-stage product for the treatment of schizophrenia, from Teva Pharmaceuticals Industries Ltd. (press release). Under the terms of the agreement, Royalty Pharma will provide R&D funding of up to $125 million to support the development of TEV-’749.

In October 2023, Royalty Pharma acquired additional royalties on Roche’s Evrysdi (press release), an approved product for the treatment of spinal muscular atrophy, from PTC Therapeutics, Inc. (PTC) for an upfront payment of $1.0 billion. Until December 31, 2025, PTC will have the option to sell the remainder of the Evrysdi royalty retained by PTC to Royalty Pharma for $500 million less royalties received in five equal tranches. If PTC exercises fewer than three of these options, Royalty Pharma has the option to purchase 50% of the remaining PTC royalty for $250 million less royalties received until March 31, 2026.

Additionally, in January 2024, Royalty Pharma acquired a royalty interest in ecopipam for an upfront payment of $49 million and up to $44 million in milestone payments contingent on the achievement of certain regulatory milestones. Ecopipam is in Phase 3 development by Emalex Biosciences for the treatment of Tourette Syndrome.

The information in this section should be read together with Royalty Pharma’s reports and documents filed with the SEC at www.sec.gov and the reader is also encouraged to review all other press releases and information available in the Investors section of Royalty Pharma’s website at www.royaltypharma.com.

Key Developments Relating to the Portfolio
The key developments related to Royalty Pharma’s royalty interests are discussed below based on disclosures from the marketers of the products.

Pelabresib

In February 2024, Novartis announced that it has entered into an agreement to make a voluntary public takeover offer to acquire MorphoSys at an offer price of €68.00 per share in cash, for a total equity value of €2.7 billion. The closing is expected in the first half of 2024.

In November 2023, MorphoSys announced positive topline results from the Phase 3 MANIFEST-2 study investigating pelabresib in combination with ruxolitinib compared with placebo plus ruxolitinib in JAK inhibitor-naive patients with myelofibrosis. A New Drug Application (NDA) is expected to be submitted to the U.S. Food and Drug Administration (FDA) in the second half of 2024.

Cystic fibrosis franchise

In February 2024, Vertex announced positive Phase 3 results from its new triple combination therapy for the treatment of cystic fibrosis (CF). Vertex plans to file for approval with global regulators for people with CF ages 6 years and older by mid-2024.

In November 2023, Vertex announced that the European Commission granted approval for the label expansion of Kaftrio in a combination regimen with ivacaftor for the treatment of children with CF ages 2 through 5 years old.

Trodelvy

In January 2024, Gilead announced that the Phase 3 EVOKE-01 study evaluating Trodelvy compared to docetaxel did not meet its primary endpoint of overall survival in patients with previously treated metastatic non-small cell lung cancer.

Aficamten

In December 2023, Cytokinetics announced positive topline results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy. The full results will be presented at an upcoming conference.

KarXT

In December 2023, Bristol Myers Squibb announced it has agreed to acquire Karuna for $330 per share in cash, for a total equity value of $14.0 billion with an expected closing in the first half of 2024.

In November 2023, Karuna announced that the FDA accepted its NDA for KarXT for the treatment of schizophrenia with an FDA action date of September 26, 2024.

Skytrofa

In December 2023, Ascendis Pharma announced positive topline results from foresiGHt, its Phase 3 trial to compare TransCon hGH with placebo and daily hGH in adults with growth hormone deficiency. Ascendis plans to submit a supplemental Biologics License Application to the FDA in 2024.

Xtandi

In November 2023, Astellas and Pfizer announced that the companies received an approval by the FDA of a supplemental NDA for Xtandi for the treatment of patients with nonmetastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis.

Trontinemab

In October 2023, Roche presented interim results of a Phase 1b/2a study for trontinemab, a novel brainshuttle Aβ antibody for the treatment of Alzheimer’s disease. This study demonstrated that trontinemab rapidly reduces amlyoid plaque reduction in patients with Alzheimer’s disease.

2024 Financial Outlook

Royalty Pharma has provided guidance for full year 2024, excluding transactions and borrowings announced after the date of this release, as follows:

Provided February 15, 2024

Portfolio Receipts

$2,600 million to $2,700 million

Payments for operating and professional costs

8% to 9% of Portfolio Receipts

Interest Paid

$160 million

The above Portfolio Receipts guidance includes expected royalty receipts growth of 5% to 9% in 2024.

Royalty Pharma’s full-year 2024 guidance reflects a negligible estimated foreign exchange impact to Portfolio Receipts, assuming current foreign exchange rates prevail for 2024.

Total interest paid is based on the semi-annual interest payment schedule of Royalty Pharma’s existing notes and is anticipated to be approximately $160 million in 2024. Interest paid is anticipated to be approximately $79 million in each of the first and third quarters of 2024 with de minimis amounts being recorded in the second and fourth quarters of 2024. The projection assumes no additional debt financing in 2024, including no drawdown on the revolving credit facility. In 2023, Royalty Pharma also collected interest of $72 million on its cash and cash equivalents, which partially offsets interest paid.

Royalty Pharma today provides this guidance based on its most up-to-date view on its prospects. This guidance assumes no major unforeseen adverse events and excludes the contributions from transactions announced subsequent to the date of this press release. Furthermore, Royalty Pharma may amend its guidance in the event it engages in new royalty transactions which have a material near-term financial impact on the company.

Financial Results Call

Royalty Pharma will host a conference call and simultaneous webcast to discuss its fourth quarter and full year 2023 results today at 8:00 a.m., Eastern Time. Please visit the "Investors" page of the company’s website at View Source to obtain conference call information and to view the live webcast. A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.