On May 3, 2023 Taiho Oncology, Inc. and Servier reported the publication of results from the pivotal Phase 3 SUNLIGHT* clinical trial of trifluridine/tipiracil (LONSURF), alone or in combination with bevacizumab, in refractory metastatic colorectal cancer (mCRC) in the May 4, 2023, issue of the New England Journal of Medicine (NEJM) (Press release, Taiho, MAY 3, 2023, View Source [SID1234630947]).

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Results of this multinational trial, led by Professor Josep Tabernero, MD, PhD, Head of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain, showed that treatment with the investigational combination of trifluridine/tipiracil and bevacizumab resulted in statistically significant and clinically meaningful improvements in overall survival and progression-free survival for patients with refractory mCRC following disease progression or intolerance on two prior chemotherapy regimens compared to trifluridine/tipiracil alone. In addition, the median time to worsening of ECOG (Eastern Cooperative Oncology Group) performance-status score was significantly delayed in patients receiving the investigational combination of trifluridine/tipiracil and bevacizumab. The safety profile of the investigational combination was consistent with that of each agent.

"Individuals living with metastatic colorectal cancer and who have progressed following fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and anti-Epidermal Growth Factor Receptor (EGFR) antibodies – if RAS wild-type – have limited treatment options. There is a growing need for new approaches that improve survival in this population," said Marwan Fakih, MD, Professor, Medical Oncology and Therapeutics Research, City of Hope, and lead U.S. investigator for the SUNLIGHT trial. "The publication of the SUNLIGHT results in the New England Journal of Medicine speaks to the quality of the science and potential impact of this investigational combination on the treatment of metastatic colorectal cancer."

Added Professor Tabernero: "Trifluridine/tipiracil plus bevacizumab may represent a meaningful new treatment option in patients with mCRC who have progressed after two lines of therapy."

Based on results of the SUNLIGHT trial, Servier and Taiho Oncology submitted respectively a type II variation for approval to the European Medicines Agency (EMA) and a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for trifluridine/tipiracil in combination with bevacizumab for the treatment of adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. Taiho Oncology announced on April 18, 2023, that the FDA accepted the sNDA for Priority Review and set an anticipated Prescription Drug User Fee Act (PDUFA) action date of August 13, 2023.

Please click here for the Original Article, "Trifluridine–Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer."

Please click here for a NEJM "Quick Take" video summarizing the article findings.

About Colorectal Cancer
Colorectal cancer is the third most common cancer worldwide1 with nearly 1.4 million people diagnosed with colorectal cancer (CRC) each year equating to 10% of the global cancer cases.1 CRC is the second most common cause of cancer mortality, accounting for 881,000 deaths globally in 2018.2 The worldwide incidence of colorectal cancer is expected to exceed 3 million cases annually by 2040,3 and the number of deaths is predicted to increase by more than 70% to 1.6 million per year.3

About the SUNLIGHT Trial
SUNLIGHT is a multinational, randomized, active-controlled, open-label, two-arm Phase 3 clinical trial to investigate the efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil alone, in patients with refractory mCRC following two chemotherapy regimens. A total of 492 patients were randomly allocated (in a 1:1 ratio) to receive trifluridine/tipiracil in combination with bevacizumab or trifluridine/tipiracil monotherapy. The primary objective was to assess trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil alone, in terms of OS (primary endpoint). Key secondary endpoints were PFS, overall response rate (ORR), disease control rate (DCR) and quality of life (QoL), as well as the safety and tolerability of trifluridine/tipiracil used in combination with bevacizumab in comparison with trifluridine/tipiracil monotherapy.

The SUNLIGHT trial was conducted by Servier and Taiho Oncology, Inc. For more information on SUNLIGHT, please visit: View Source

About LONSURF
LONSURF is an oral nucleoside antitumor agent discovered and developed by Taiho Pharmaceutical Co., Ltd. LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase (TP) inhibitor, tipiracil, which increases trifluridine exposure by inhibiting its metabolism by TP. Trifluridine is incorporated into DNA, resulting in DNA dysfunction and inhibition of cell proliferation.

Indications and Use in the United States
LONSURF is indicated for the treatment of adult patients with:

Metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy; and
Metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy
IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS

Indications and Use
LONSURF is indicated for the treatment of adult patients with:

Metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy
metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.
IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Severe Myelosuppression:
LONSURF caused severe and life-threatening myelosuppression (Grade 3-4) consisting of neutropenia (38%), anemia (18%), thrombocytopenia (5%), and febrile neutropenia (3%). Two patients (0.2%) died due to neutropenic infection. A total of 12% of LONSURF-treated patients received granulocyte-colony stimulating factors. Obtain complete blood counts prior to and on day 15 of each cycle of LONSURF and more frequently as clinically indicated. Withhold LONSURF for febrile neutropenia, absolute neutrophil count less than 500/mm3, or platelets less than 50,000/mm3. Upon recovery, resume LONSURF at a reduced dose as clinically indicated.

Embryo-Fetal Toxicity:
LONSURF can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the final dose.

USE IN SPECIFIC POPULATIONS

Lactation: It is not known whether LONSURF or its metabolites are present in human milk. There are no data to assess the effects of LONSURF or its metabolites on the breast-fed infant or the effects on milk production. Because of the potential for serious adverse reactions in breast-fed infants, advise women not to breastfeed during treatment with LONSURF and for 1 day following the final dose.

Male Contraception: Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment with LONSURF and for at least 3 months after the final dose.

Geriatric Use: Patients 65 years of age or over who received LONSURF had a higher incidence of the following compared to patients younger than 65 years: Grade 3 or 4 neutropenia (46% vs 32%), Grade 3 anemia (22% vs 16%), and Grade 3 or 4 thrombocytopenia (7% vs 4%).

Hepatic Impairment: Do not initiate LONSURF in patients with baseline moderate or severe (total bilirubin greater than 1.5 times ULN and any AST) hepatic impairment. Patients with severe hepatic impairment (total bilirubin greater than 3 times ULN and any AST) were not studied. No adjustment to the starting dose of LONSURF is recommended for patients with mild hepatic impairment.

Renal Impairment: No adjustment to the starting dosage of LONSURF is recommended in patients with mild or moderate renal impairment (CLcr of 30 to 89 mL/min). Reduce the starting dose of LONSURF for patients with severe renal impairment (CLcr of 15 to 29 mL/min) to a recommended dosage of 20 mg/m2.

ADVERSE REACTIONS

Most Common Adverse Drug Reactions in Patients Treated With LONSURF (≥5%): The most common adverse drug reactions in LONSURF-treated patients vs placebo-treated patients with mCRC, respectively, were asthenia/fatigue (52% vs 35%), nausea (48% vs 24%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%), vomiting (28% vs 14%), infections (27% vs 16%), abdominal pain (21% vs 18%), pyrexia (19% vs 14%), stomatitis (8% vs 6%), dysgeusia (7% vs 2%), and alopecia (7% vs 1%). In metastatic gastric cancer or gastroesophageal junction (GEJ), the most common adverse drug reactions, respectively were, nausea (37% vs 32%), decreased appetite (34% vs 31%), vomiting (25% vs 20%), infections (23% vs 16%) and diarrhea (23% vs 14%).

Pulmonary emboli occurred more frequently in LONSURF-treated patients compared to placebo: in mCRC (2% vs 0%) and in metastatic gastric cancer and GEJ (3% vs 2%).

Interstitial lung disease (0.2%), including fatalities, has been reported in clinical studies and clinical practice settings in Asia.

Laboratory Test Abnormalities in Patients Treated With LONSURF: The most common laboratory test abnormalities in LONSURF-treated patients vs placebo-treated patients with mCRC, respectively, were anemia (77% vs 33%), neutropenia (67% vs 1%), and thrombocytopenia (42% vs 8%). In metastatic gastric cancer or GEJ, the test abnormalities, respectively, were neutropenia (66% vs 4%), anemia (63% vs 38%), and thrombocytopenia (34% vs 9%).

On May 3, 2023 Bio-Techne Corporation (NASDAQ: TECH) reported its financial results for the third quarter ended March 31, 2023 (Press release, Bio-Techne, MAY 3, 2023, View Source [SID1234630946]).

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Third Quarter FY2023 Highlights

Third quarter organic revenue increased by 3% (1% reported) to $294.1 million and 4% (2% reported) in the first nine months of fiscal 2023 to $835.4 million.

GAAP earnings per share1) (EPS) was $0.43 versus $0.37 one year ago. Delivered adjusted EPS1) of $0.53, consistent with prior year adjusted EPS.

Successful execution within our cell and gene therapy growth platform with another record quarter in GMP protein sales and completion of a 20% ownership stake in Wilson Wolf.

Increased ExoDx Prostate test adoption and utilization continued to accelerate with test volume and associated revenue growing over 70%. The ExoDx Prostate test increased its addressable market by approximately 50% after receiving expanded Medicare coverage to include an annual test for patients with a prior negative biopsy but are thought to be at high risk for prostate cancer and are considering a repeat biopsy.

Expansion of our spatial biology platform through a strategic partnership with Lunaphore to develop the first fully automated same-slide spatial multiomics solution.
1)On November 29, 2022, the company executed a four-for-one split of Bio-Techne’s common stock in the form of a stock dividend to all shareholders of record on November 14, 2022. All references made to share or per share amounts in this press release have been retroactively adjusted to reflect the effects of the stock split.

The Company’s financial statements are prepared in accordance with accounting principles generally accepted in the United States (GAAP). Adjusted diluted EPS, adjusted net earnings, adjusted gross margin, adjusted operating income, adjusted tax rate, organic growth, adjusted operating margin, earnings before interest, taxes, depreciation, and amortization (EBITDA), and adjusted EBITDA are non-GAAP measures that exclude certain items detailed later in this press release under the heading "Use of non-GAAP Adjusted Financial Measures." A reconciliation of GAAP to non-GAAP financial measures is included in this press release.

"Our third quarter performance was consistent with our expectations, as we continue to lap high growth rates from the prior year, China continued to recover from Covid-related restrictions, and biotech funding considerations impacted a subset of our biopharma customers," said Chuck Kummeth, President and Chief Executive Officer of Bio-Techne. "The team continued to effectively execute our strategy across the organization, enabling a 150 basis point sequential adjusted operating margin expansion to 37.0%."

Kummeth continued, "Two of our highest growth businesses, Cell Therapy and Exosome Diagnostics, both had strong quarters. Our broad portfolio of Cell Therapy enabling workflow solutions remained in high demand, once again delivering double-digit growth, including a second consecutive record quarter for our GMP Proteins business. Our ExoDx Prostate test continued its streak of record-breaking quarters, as test volume increased over 70% for the fifth consecutive quarter and associated revenue grew over 85%."

Kummeth concluded, "We are already seeing encouraging signs of a strong recovery in China, which combined with continued traction of our portfolio of innovative tools, bioactive reagents, and technologies positions the Company incredibly well for the future. We will continue to execute our long-term strategic plan, with a focus on delivering value to all of our stakeholders."

Third Quarter Fiscal 2023

Revenue

Net sales for the third quarter increased 1% to $294.1 million. Organic growth was 3% compared to the prior year with foreign currency exchange having an unfavorable impact of 2% and acquisitions having an immaterial impact.

GAAP Earnings Results

GAAP EPS was $0.43 per diluted share, versus $0.37 in the same quarter last year. Prior year GAAP EPS was unfavorably impacted by a non-recurring loss of approximately $17.2 million on our ChemoCentryx investment. GAAP operating income for the third quarter of fiscal 2023 decreased 11% to $80.2 million, compared to $90.4 million in the third quarter of fiscal 2022. GAAP operating margin was 27.3%, compared to 31.1% in the third quarter of fiscal 2022. Prior year GAAP operating margin was favorably impacted by a non-recurring benefit related to the change in fair value of contingent consideration.

Non-GAAP Earnings Results

Adjusted EPS remained consistent with the same quarter in the prior year at $0.53 per diluted share with a reduction in adjusted operating income being offset by reduced net interest expense. Adjusted operating income for the third quarter of fiscal 2023 decreased 5% compared to the third quarter of fiscal 2022. Adjusted operating margin was 37.0%, compared to 39.6% in the third quarter of fiscal 2022. The decrease from the prior year was due to the non-recurring prior year revenue related to the ExoTru kidney transplant rejection agreement, unfavorable foreign currency exchange, and strategic growth investments including the Namocell acquisition.

Segment Results

Management uses adjusted operating results to monitor and evaluate performance of the Company’s business segments, as highlighted below.

Protein Sciences Segment

The Company’s Protein Sciences segment is one of the world’s leading suppliers of specialized proteins such as cytokines and growth factors, immunoassays, antibodies and reagents, to the biotechnology and academic research communities. Additionally, the segment provides an array of platforms useful in various areas of protein analysis. Protein Sciences segment’s third quarter fiscal 2023 net sales were $218.9 million, an increase of 3% from $213.2 million for the third quarter of fiscal 2022. Organic growth for the segment was 5%, with foreign currency exchange having an unfavorable impact of 2% and acquisitions having an immaterial impact. Protein Sciences segment’s operating margin was 45.1% in the third quarter of fiscal 2023 compared to 45.4% in the third quarter of fiscal 2022. The segment’s operating margin compared to the prior year was negatively impacted by unfavorable foreign currency exchange and the Namocell acquisition.

Diagnostics and Genomics Segment

The Company’s Diagnostics and Genomics segment provides blood chemistry and blood gas quality controls, hematology instrument controls, immunoassays and other bulk and custom reagents for the in vitro diagnostic market. The Diagnostics and Genomics segment also develops and provides in situ hybridization products as well as exosome-based diagnostics for various pathologies, including prostate cancer. The Diagnostics and Genomics segment’s third quarter fiscal 2023 net sales were $75.7 million, a decrease of 3% from $77.7 million for the third quarter of fiscal 2022. Organic revenue for the segment reduced by 2% from the prior year, with foreign exchange having an unfavorable impact of 1%. The Diagnostics and Genomics segment’s operating margin was 15.2% in the third quarter of fiscal 2023 compared to 25.0% in the third quarter of fiscal 2022. The segment’s operating margin declined due to the prior year revenue related to the ExoTru kidney transplant rejection agreement as well as strategic investments to drive future revenue growth.

Conference Call

Bio-Techne will host an earnings conference call today, May 3, 2023 at 8:00 a.m. CDT. To listen, please dial 1-877-300-8521 or 1-412-317-6026 for international callers, and reference conference ID 10177426. The earnings call can also be accessed via webcast through the following link View Source

A recorded rebroadcast will be available for interested parties unable to participate in the live conference call by dialing 1-844-512- 2921 or 1-412-317-6671 (for international callers) and referencing Conference ID 10177426. The replay will be available from 11:00 a.m. CDT on Wednesday, May 3, 2023, until 11:00 p.m. CDT on Saturday, June 3, 2023.

Use of non-GAAP Adjusted Financial Measures:

This press release contains financial measures that have not been calculated in accordance with accounting principles generally accepted in the U.S. (GAAP). These non-GAAP measures include:

Organic growth
Adjusted diluted earnings per share
Adjusted net earnings
Adjusted tax rate
Adjusted gross margin
Adjusted operating income
Adjusted operating margin
Earnings before interest, taxes, depreciation, and amortization (EBITDA)
Adjusted EBITDA
We provide these measures as additional information regarding our operating results. We use these non-GAAP measures internally to evaluate our performance and in making financial and operational decisions, including with respect to incentive compensation. We believe that our presentation of these measures provides investors with greater transparency with respect to our results of operations and that these measures are useful for period-to-period comparison of results.

Our non-GAAP financial measure of organic growth represents revenue growth excluding revenue from acquisitions within the preceding 12 months, the impact of foreign currency, as well as the impact of partially-owned consolidated subsidiaries. Excluding these measures provides more useful period-to-period comparison of revenue results as it excludes the impact of foreign currency exchange rates, which can vary significantly from period to period, and revenue from acquisitions that would not be included in the comparable prior period. Revenues from partially-owned subsidiaries consolidated in our financial statements are also excluded from our organic revenue calculation, as those revenues are not fully attributable to the Company. There was no revenue from partially-owned consolidated subsidiaries for the quarter ended March 31, 2023 due to the sale of Changzhou Eminence Biotechnology Co., Ltd. (Eminence) in the first quarter of fiscal 2023. Revenue from partially-owned consolidated subsidiaries was $2.0 million for the nine months ended March 31, 2023.

Our non-GAAP financial measures for adjusted gross margin, adjusted operating margin, adjusted EBITDA, and adjusted net earnings, in total and on a per share basis, exclude stock-based compensation, the costs recognized upon the sale of acquired inventory, amortization of acquisition intangibles, acquisition related expenses inclusive of the changes in fair value of contingent consideration, and other non-recurring items including non-recurring costs, goodwill and long-lived asset impairments, and gains. Stock-based compensation is excluded from non-GAAP adjusted net earnings because of the nature of this charge, specifically the varying available valuation methodologies, subjection assumptions, variety of award types, and unpredictability of amount and timing of employer related tax obligations. The Company excludes amortization of purchased intangible assets, purchase accounting adjustments, including costs recognized upon the sale of acquired inventory and acquisition-related expenses inclusive of the changes in fair value contingent consideration, and other non-recurring items including gains or losses on legal settlements, goodwill and long-lived asset impairment charges, and one-time assessments from this measure because they occur as a result of specific events, and are not reflective of our internal investments, the costs of developing, producing, supporting and selling our products, and the other ongoing costs to support our operating structure. Additionally, these amounts can vary significantly from period to period based on current activity. The Company also excludes revenue and expense attributable to partially-owned consolidated subsidiaries in the calculation of our non-GAAP financial measures as the revenues and expenses are not fully attributable to the Company.

The Company’s non-GAAP adjusted operating margin and adjusted net earnings, in total and on a per share basis, also excludes stock-based compensation expense, which is inclusive of the employer portion of payroll taxes on those stock awards, restructuring, impairments of equity method investments, gain and losses from investments, and certain adjustments to income tax expense. Impairments of equity investments are excluded as they are not part of our day-to-day operating decisions. Additionally, gains and losses from other investments that are either isolated or cannot be expected to occur again with any predictability are excluded. Costs related to restructuring activities, including reducing overhead and consolidating facilities, are excluded because we believe they are not indicative of our normal operating costs. The Company independently calculates a non-GAAP adjusted tax rate to be applied to the identified non-GAAP adjustments considering the impact of discrete items on these adjustments and the jurisdictional mix of the adjustments. In addition, the tax impact of other discrete and non-recurring charges which impact our reported GAAP tax rate are adjusted from net earnings. We believe these tax items can significantly affect the period-over-period assessment of operating results and not necessarily reflect costs and/or income associated with historical trends and future results.

Investors are encouraged to review the reconciliations of adjusted financial measures used in this press release to their most directly comparable GAAP financial measures as provided with the financial statements attached to this press release.

On May 3, 2023 Agenus (Nasdaq: AGEN), a leading immuno-oncology company dedicated to developing innovative treatments for cancer and infectious diseases, reported a data update on botensilimab (multifunctional CTLA-4 antibody) in combination with balstilimab (PD-1 antibody) for patients with non-microsatellite instability-high metastatic colorectal cancer (non-MSI-H mCRC) has been selected for a late-breaking oral presentation at the upcoming ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer (ESMO GI), to be held June 28 – July 1, 2023 in Barcelona, Spain (Press release, Agenus, MAY 3, 2023, View Source [SID1234630945]).

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Presentation Details:

Abstract Title: Results from an expanded phase 1 trial of botensilimab, a multifunctional anti-CTLA-4, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer (NCT03860272)
Abstract Number: LBA-4
Presenting Author: Andrea J. Bullock, MD, MPH, Assistant Professor of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center
Presentation Date and Time: 6/30/2023, 6:00pm – 6:10pm CEST

Data presented at the conference will be available to view in the Publications section of the Agenus website (View Source) following the ESMO (Free ESMO Whitepaper) GI Conference.

About Botensilimab
Botensilimab is a novel, multifunctional CTLA-4 investigational antibody that has been designed to extend clinical benefits to "cold" tumors that have not historically responded to standard of care or investigational therapies. In addition to binding to the CTLA-4 receptor, its Fc-enhanced structure induces a memory immune response, downregulates regulatory T cells, and delivers better priming and activation of T cells, thereby amplifying immune responses.

In a Phase 1b clinical study of more than 350 patients, botensilimab has demonstrated clinical responses in nine, previously IO unresponsive, solid tumor cancers, either alone or in combination with Agenus’ PD-1 antibody, balstilimab (data presented at ASCO (Free ASCO Whitepaper) GI 2023, SGO 2023, CTOS 2022, SITC (Free SITC Whitepaper) 2022). Agenus is conducting global, randomized Phase 2 trials in non-MSI-H mCRC, melanoma, and pancreatic cancer as part of its ACTIVATE trial programs. Additional information about these botensilimab trials can be found at www.clinicaltrials.gov under the identifiers NCT05608044, NCT05630183, and NCT05529316, respectively. A global Phase 3 trial in non-MSI-H mCRC is expected to launch in 2023.

On May 3, 2023 Veracyte, Inc. (Nasdaq: VCYT) reported that data published in the journal Cancer show the ability of a novel gene expression signature to classify prostate cancer into distinct molecular subtypes that may inform which tumors are more likely to respond to different treatments (Press release, Veracyte, MAY 3, 2023, View Source [SID1234630943]). The findings suggest that the novel biomarker, derived largely using Veracyte’s Decipher Genomics Resource for Intelligent Discovery (GRID) database, could potentially enable physicians to further personalize care for their patients with prostate cancer.

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"Prostate cancer is a heterogeneous disease with multiple, available therapeutic approaches in both its early and late stages, and insufficient tools to guide therapeutic selection and sequencing for individual patients," said Edward M. Schaeffer, MD, PhD, chair of Urology at Northwestern University, and senior author on the Cancer manuscript. "Our findings suggest that a molecular subtyping tool based on prostate cancer-specific biological processes could help guide treatment decisions and fuel precision medicine approaches for this disease."

Dr. Schaeffer and colleagues used 32,000 prostate cancer gene expression profiles from Veracyte’s Decipher GRID database to create a prostate subtyping classifier (PSC) model that identified four prostate cancer subtypes with distinct biological and clinical features: luminal differentiated, luminal proliferating, basal immune, and basal neuroendocrine-like. They then used data from 68,547 Decipher GRID profiles, along with those from five additional clinical cohorts, to evaluate the ability of the PSC to provide information about tumor aggressiveness and susceptibility to specific treatments.

The researchers identified many distinct differences within and between the four subtypes in terms of molecular features and pathways, including higher or lower frequency of gene loss and gene mutations that are known to contribute to tumor aggressiveness and/or treatment response. Additionally, the four subtypes demonstrated differences in clinicopathological features such as prostate specific antigen (PSA) values, frequency of non-organ confined disease, lower- or higher-grade disease, tumor aggressiveness, and time to metastasis following radical prostatectomy. Finally, the researchers report associations between individual subtypes and response to specific treatments, such as androgen deprivation therapy (ADT), radiotherapy, and docetaxel chemotherapy, as well as predicted responses to multiple novel systemic therapies.

"These findings reinforce the value of our Decipher GRID database for providing researchers with new insights that could advance understanding about the molecular origins and pathways specific to prostate cancer and their impact on patients’ response to treatment," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology.

The Decipher GRID database includes more than 100,000 whole-transcriptome profiles from patients with urologic cancers and is used by Veracyte and its research partners to help advance understanding of prostate and other urologic cancers. GRID-derived information is available on a Research Use Only basis to physicians who have ordered the Decipher Prostate Genomic Classifier.

On May 3, 2023 United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, reported its financial results for the quarter ended March 31, 2023 (Press release, United Therapeutics, MAY 3, 2023, View Source [SID1234630942]). Total revenues in the first quarter of 2023 grew 10% year-over-year to $506.9 million, compared to $461.9 million in the first quarter of 2022.

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"The hard work and determination of our over 1,000 Unitherians during the first quarter of this year allowed us to reach over $500 million in revenue for the second quarter ever," said Martine Rothblatt, Ph.D., Chairperson and Chief Executive Officer. "And to sustain our mission to help patients in need, our clinical team continues to progress our four registration studies in progress: the two TETON studies of Tyvaso in idiopathic pulmonary fibrosis, the ADVANCE OUTCOMES study of ralinepag in pulmonary arterial hypertension, and the clinical study of our CLES ex vivo lung perfusion technology."

"We are extremely pleased with the underlying strength of our Tyvaso franchise, highlighted by record referrals and starts during the quarter and net patient additions in line with prior quarters," said Michael Benkowitz, President and Chief Operating Officer. "Our other core products also performed well, led by Orenitram which achieved record revenues in the first quarter."

First Quarter 2023 Financial Results

Key financial highlights include (dollars in millions, except per share data):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Total revenues

$

506.9

$

461.9

$

45.0

10

%

Net income

$

240.9

$

239.9

$

1.0

—

%

Net income, per basic share

$

5.20

$

5.31

$

(0.11)

(2

) %

Net income, per diluted share

$

4.86

$

5.03

$

(0.17)

(3

) %

Revenues

The table below presents the components of total revenues (dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Net product sales:

Tyvaso(1)

$

238.4

$

172.0

$

66.4

39

%

Remodulin(2)

121.4

131.7

(10.3)

(8

) %

Orenitram

88.2

82.8

5.4

7

%

Unituxin

49.1

55.6

(6.5)

(12

) %

Adcirca

7.3

9.8

(2.5)

(26

) %

Other

2.5

10.0

(7.5)

(75

) %

Total revenues

$

506.9

$

461.9

$

45.0

10

%

(1)

Net product sales include both the drug product and the respective inhalation devices for both nebulized Tyvaso Inhalation Solution and the dry powder version known as Tyvaso DPI.

(2)

Net product sales include sales of infusion devices, such as the Remunity Pump.

Net product sales from our treprostinil-based products (Tyvaso, Remodulin, and Orenitram) grew by $61.5 million, or 16%, for the first quarter of 2023, as compared to the first quarter of 2022. The growth in Tyvaso revenues resulted primarily from an increase in quantities sold. The increase in quantities sold was driven by our launch of sales of Tyvaso DPI in June 2022 and continued growth in the number of patients following the Tyvaso label expansion in March 2021 to include the treatment of pulmonary hypertension associated with interstitial lung disease.

Expenses

Cost of sales. The table below summarizes cost of sales by major category (dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Category:

Cost of sales

$

52.7

$

26.6

$

26.1

98

%

Share-based compensation benefit(1)

(0.4

)

(0.7

)

0.3

43

%

Total cost of sales

$

52.3

$

25.9

$

26.4

102

%

(1)

Refer to Share-based compensation below.

Cost of sales, excluding share-based compensation. Cost of sales for the three months ended March 31, 2023 increased as compared to the same period in 2022, primarily due to an increase in Tyvaso DPI royalty expense and product costs, following the commercial launch of the product in June 2022.

Research and development expense. The table below summarizes the nature of research and development expense by major expense category (dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Category:

External research and development(1)

$

45.1

$

40.6

$

4.5

11

%

Internal research and development(2)

34.4

32.0

2.4

8

%

Share-based compensation expense (benefit)(3)

1.3

(3.6

)

4.9

136

%

Impairments(4)

%

Other(5)

2.1

—

2.1

NM(6)

Total research and development expense

$

82.9

$

69.0

$

13.9

20

%

(1)

External research and development primarily includes fees paid to third parties (such as clinical trial sites, contract research organizations, and contract laboratories) for preclinical and clinical studies and payments to third-party contract manufacturers before FDA approval of the relevant product.

(2)

Internal research and development primarily includes salary-related expenses for research and development functions, internal costs to manufacture product candidates before FDA approval, and internal facilities-related expenses, including depreciation, related to research and development activities.

(3)

Refer to Share-based compensation below.

(4)

Impairments primarily includes impairment charges to write down the carrying value of in-process research and development and of certain property, plant, and equipment as a result of research and development activities. There were no impairment charges during the three months ended March 31, 2023 and March 31, 2022.

(5)

Other primarily includes upfront fees and milestone payments to third parties under license agreements related to development-stage products and adjustments to the fair value of our contingent consideration obligations.

(6)

Calculation is not meaningful.

Research and development expense, excluding share-based compensation. Research and development expense for the three months ended March 31, 2023 increased as compared to the same period in 2022, primarily due to increased expenditures related to the TETON clinical studies of Tyvaso in patients with idiopathic pulmonary fibrosis.

Selling, general, and administrative expense. The table below summarizes selling, general, and administrative expense by major category (dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage Change

2023

2022

Category:

General and administrative

$

83.7

$

81.3

$

2.4

3

%

Sales and marketing

16.9

14.5

2.4

17

%

Share-based compensation benefit(1)

(13.3

)

(16.8

)

3.5

21

%

Total selling, general, and administrative expense

$

87.3

$

79.0

$

8.3

11

%

(1)

Refer to Share-based compensation below.

Share-based compensation. The table below summarizes share-based compensation benefit by major category

(dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Category:

Stock options

$

4.9

$

5.5

$

(0.6

)

(11

) %

Restricted stock units

12.2

6.3

5.9

94

%

Share tracking awards plan (STAP)

(30.0

)

(33.4

)

3.4

10

%

Employee stock purchase plan

0.5

0.5

—

—

%

Total share-based compensation benefit

$

(12.4

)

$

(21.1

)

$

8.7

41

%

The decrease in share-based compensation benefit for the three months ended March 31, 2023, as compared to the same period in 2022, was primarily due to: (1) an increase in restricted stock unit expense driven by an increase in the number of awards granted and remaining outstanding for the three months ended March 31, 2023, as compared to the same period in 2022; and (2) a decrease in STAP benefit driven by a 19 percent decrease in our stock price and fewer awards remaining outstanding for the three months ended March 31, 2023, as compared to the same period in 2022.

Other (expense) income, net. The change in other (expense) income, net for the three months ended March 31, 2023, as compared to the same period in 2022, was primarily due to net unrealized gains and losses on equity securities.

Income tax expense. Income tax expense for the three months ended March 31, 2023 and 2022 was $51.0 million and $68.8 million, respectively. Our effective income tax rate (ETR) for the three months ended March 31, 2023 and 2022 was 17 percent and 22 percent, respectively. Our ETR for the three months ended March 31, 2023 decreased compared to our ETR for the three months ended March 31, 2022 primarily due to increased excess tax benefits from share-based compensation.

Webcast

We will host a webcast to discuss our first quarter 2023 financial results on Wednesday, May 3, 2023, at 9:00 a.m. Eastern Time. The webcast can be accessed live via our website at View Source A replay of the webcast will also be available at the same location on our website.