On February 16, 2023 Bayer reported that Subgroup analyses from the pivotal Phase III ARASENS trial support overall survival (OS) benefits of NUBEQA (darolutamide) plus androgen deprivation therapy (ADT) and docetaxel compared to ADT and docetaxel in patients with high-volume and high and low-risk metastatic hormone-sensitive prostate cancer (mHSPC) (Press release, Bayer, FEB 16, 2023, View Source [SID1234627350]). Low-volume disease was also assessed with results suggestive of a survival benefit.1 NUBEQA is currently indicated in the U.S. for the treatment of adult patients with mHSPC in combination with docetaxel and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC).2 The full results were presented as an oral presentation during the ASCO (Free ASCO Whitepaper) GU Cancers Symposium and simultaneously published in the Journal of Clinical Oncology.1

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These results build on existing data from the ARASENS trial, which show that NUBEQA plus ADT and docetaxel compared to ADT and docetaxel significantly reduces the risk of death in patients with mHSPC by 32% (HR=0.68; 95% CI 0.57-0.80; P<0.0001).3 Pre-specified secondary endpoints, including time to pain progression, were evaluated in the subgroup analyses.1

"These latest findings from the ARASENS trial continue to reinforce the strong efficacy and favorable safety profile of NUBEQA in mHSPC," said Maha Hussain, M.D., Genevieve Teuton Professor of Medicine in the Division of Hematology Oncology, Department of Medicine, and the Deputy Director at the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, Chicago, IL. "The growing analyses from the ARASENS trial continue to demonstrate NUBEQA’s value in treating patients with mHSPC. The benefit is especially in those with high-volume or high-risk disease. They also provide treating physicians with greater insight into the mHSPC patient population that may benefit from this therapy."

"Despite recent advances, there still remains a need for treatments that extend survival and delay disease progression. These analyses highlight the potential of NUBEQA to become a foundational therapy for mHSPC patients with various types of metastatic disease burden," said Tara Frenkl, M.D., Senior Vice President and Head of Oncology Development at Bayer. "An important part of our mission at Bayer is prostate cancer care and improving patient outcomes at different stages of the disease. We are working to ensure that as many eligible patients as possible have the opportunity to benefit from NUBEQA."

In the ARASENS trial, patients were randomized 1:1 to receive NUBEQA plus ADT and docetaxel versus placebo plus ADT and docetaxel. High-volume disease was defined as visceral metastases and/or ≥4 bone metastases with ≥1 beyond the vertebral column/pelvis, as delineated in the CHAARTED criteria. High-risk disease was defined using the LATITUDE criteria, which includes ≥2 risk factors: a Gleason score of ≥8, ≥3 bone lesions, and the presence of measurable visceral metastasis. Of 1,305 patients in the full analysis set, 1,005 (77%) had high-volume disease, 912 (70%) had high-risk disease, 300 (23%) had low-volume disease, and 393 (30%) had low-risk disease.1

Results showed that NUBEQA with docetaxel prolonged OS in high-volume disease (HR=0.69; 95% CI 0.57-0.82; n=1,005). A consistent OS benefit was observed in both high-risk (HR=0.71; 95% CI 0.58-0.86; n=912) and low-risk (HR=0.62; 95% CI 0.42-0.90; n=393) disease. In the smaller group of patients with low-volume disease, the results are suggestive of a survival benefit with NUBEQA (HR=0.68; 95% CI 0.41-1.13; n=300).1

Incidence of treatment-emergent adverse events (TEAEs) across subgroups were consistent with the overall ARASENS population. Serious adverse events in patients receiving NUBEQA compared with placebo were 45.4% versus 43.5% for those with high-volume disease, 42.9% versus 38.2% for patients with low-volume disease, 45.3% versus 42.9% for patients with high-risk disease, and 43.7% versus 40.9% for patients with low-risk disease.1

About the ARASENS Trial4

The ARASENS trial (NCT02799602) is the only randomized, Phase III, multi-center, double-blind, placebo-controlled trial prospectively designed to compare the use of a second-generation androgen receptor inhibitor (ARi) (NUBEQA) plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel to ADT and docetaxel (a guideline recommended treatment) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of NUBEQA twice a day or matching placebo, plus ADT and 75mg/m2 of docetaxel, for 6 cycles. Treatment with NUBEQA plus ADT or ADT continued until symptomatic progressive disease, change of antineoplastic therapy, unacceptable toxicity, death, or withdrawal.

The primary endpoint of this trial was overall survival (OS). Time to pain progression was a secondary endpoint.

About NUBEQA (darolutamide)2

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.2

On July 30, 2019, the FDA approved NUBEQA (darolutamide) based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral NUBEQA in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

NUBEQA is also being investigated in additional studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating NUBEQA plus ADT versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as in the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating NUBEQA as an adjuvant treatment for localized prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov.

Developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company, NUBEQA is indicated for the treatment of adults with nmCRPC or with mHSPC in combination with docetaxel.2 Filings in other regions are underway or planned.

INDICATIONS

NUBEQA (darolutamide) is an androgen receptor inhibitor indicated for the treatment of adult patients with:

Non-metastatic castration-resistant prostate cancer (nmCRPC)
Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
IMPORTANT SAFETY INFORMATION

Warnings & Precautions

Ischemic Heart Disease – In a study of patients with nmCRPC (ARAMIS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA versus 2.5% receiving placebo, including Grade 3-4 events in 1.7% vs. 0.4%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA vs. 0.2% receiving placebo. In a study of patients with mHSPC (ARASENS), ischemic heart disease occurred in 2.9% of patients receiving NUBEQA with docetaxel vs. 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel vs. 0.0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease.

Seizure – In ARAMIS, Grade 1-2 seizure occurred in 0.2% of patients receiving NUBEQA vs. 0.2% receiving placebo. Seizure occurred 261 and 456 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.6% of patients receiving NUBEQA with docetaxel, including one Grade 3 event, vs. 0.2% receiving placebo with docetaxel. Seizure occurred 38 to 340 days after initiation of NUBEQA. It is unknown whether anti-epileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment.

Embryo-Fetal Toxicity – Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

In ARAMIS, serious adverse reactions occurred in 25% of patients receiving NUBEQA vs. 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA vs. 3.2% of patients receiving placebo. Fatal adverse reactions in patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common adverse reactions (>2% with a ≥2% increase over placebo), including laboratory test abnormalities, were increased AST, decreased neutrophil count, fatigue, increased bilirubin, pain in extremity, and rash. Clinically relevant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease and heart failure.

In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel vs. 42% of patients receiving placebo with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), decreased neutrophil count (2.8%), musculoskeletal pain (2.6%), and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel vs. 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with docetaxel) were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia. Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures, ischemic heart disease, seizures, and drug-induced liver injury.

Drug Interactions

Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.

Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.

Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.

NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.

Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

About Metastatic Hormone-Sensitive Prostate Cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.5 Rates of advanced prostate cancer diagnoses have risen 4.5% annually since 2011.6

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy.7,8 Upon relapse, when the disease will metastasize or spread, the disease is hormone-sensitive and androgen deprivation therapy (ADT) is the cornerstone of treatment. Current treatment options for men with metastatic hormone-sensitive prostate cancer (mHSPC) include hormone therapy, such as ADT, androgen receptor pathway inhibitors plus ADT or a combination of docetaxel chemotherapy and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually experience progression to metastatic castration-resistant prostate cancer (mCRPC), a condition with high morbidity and limited survival.9,10

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On February 16, 2023 Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative PET radiopharmaceuticals, reported additional results from its Phase 3 LIGHTHOUSE trial that evaluated the diagnostic performance and safety of 18F-rhPSMA-7.3 in newly diagnosed prostate cancer (Press release, Blue Earth Diagnostics, FEB 16, 2023, View Source [SID1234627349]). 18F-rhPSMA-7.3 is an investigational high affinity radiohybrid (rh) Prostate-Specific Membrane Antigen-targeted PET imaging agent. The results were reported in a presentation at the 2023 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU), held February 16 -18, in San Francisco, Calif.

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"Up to 25% of patients with primary prostate cancer may have detectable regional pelvic lymph node metastases, which are correlated with a risk for recurrence and associated overall survival," said Brian F. Chapin, MD, Associate Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, and Coordinating Investigator of the LIGHTHOUSE study. "Effective staging in primary disease − determining its presence and whether it may have metastasized − is critical in establishing optimal clinical management strategies. Pelvic lymph node dissection (PLND), or pelvic lymphadenectomy, is considered the gold standard in assessing pelvic node lesions, but its use is limited to the planned surgical area. Conventional imaging techniques such as CT and MRI are limited in the information they may provide. An ideal staging technique for detecting metastatic prostate cancer should include both pelvic nodes as well as more distant soft tissue and skeletal findings. The LIGHTHOUSE study looked at unfavorable intermediate, high and very high risk patients who were scheduled for radical prostatectomy plus PLND prior to 18F-rhPSMA-7.3 PET. Results were encouraging and showed that between 9% – 13% (28 and 42/314, respectively), across the readers, of patients for whom conventional imaging was negative, actually had distant (M1) metastatic lesions that were visible on 18F-rhPSMA-7.3 PET. Thus, 18F-rhPSMA-7.3 PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients."

"We are pleased to share these results from the Phase 3 LIGHTHOUSE study with the clinical community at ASCO (Free ASCO Whitepaper) GU 2023, as they are included in our New Drug Application for 18F-rhPSMA-7.3 PET imaging, which is currently under review by the U.S. Food and Drug Administration," said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Diagnostics. "18F-rhPSMA-7.3 represents a new class of PSMA-targeted PET radiopharmaceuticals based on novel radiohybrid technology PSMA technology, which offers potential theranostic utility in both diagnostic PET imaging and therapy. Early studies with 18F-rhPSMA-7.3 potentially show a high binding affinity for PSMA, and biodistribution data suggest the potential for low bladder activity. We believe that these attributes will make it a valuable diagnostic tool that is radiolabeled with 18F for high image quality and readily available patient access."

The findings presented at ASCO (Free ASCO Whitepaper) GU 2023 included assessment of the Verified Detection Rate (VDR) of distant metastatic (M1) lesions by 18F-rhPSMA-7.3 PET imaging. VDR was the proportion of patients with M1 lesions identified by blinded image evaluation and also subsequently confirmed as True Positive (TP) by biopsy (used in ~15% of M1 positive cases) or follow-up conventional imaging (used in ~85% of M1 positive cases). Findings were based on individual read results from 3 blinded, independent PET readers. Men with treatment-naïve, unfavorable intermediate to very high-risk prostate cancer who were scheduled to undergo radical prostatectomy and PLND underwent PET imaging after administration of 18F-rhPSMA-7.3. Onsite readers interpreted the images before submission for blinded interpretation and evaluation by the central readers.

Of the 335 men analyzed (median [range] PSA, 8.89 [1.15-120] ng/mL), 16-28% (53-93) had M1 lesions across the 3 readers. In total, 10-15% (35-49) had verified M1 lesions. By region, verified M1 lesions were most common in bone, ranging from 6.0-11% across readers. Similar data were shown among a subgroup who had negative baseline conventional imaging. In these 314 patients, the VDR ranged from 9-13% across readers, with bone showing the highest regional VDR, ranging from 5-9%.

The LIGHTHOUSE Phase 3 clinical trial (NC04186819) was a prospective, Phase 3, multi-center, single-arm, imaging study conducted in the United States and Europe to evaluate the safety and diagnostic performance of 18F-rhPSMA-7.3 PET in men with newly diagnosed prostate cancer. Results for the co-primary endpoints of efficacy and safety for the LIGHTHOUSE trial were previously presented at the 23rd Annual Scientific Meeting in Urologic Oncology (SUO) in December 2022.1

The most recent findings, which reflect an analysis of additional LIGHTHOUSE study endpoints, "Detection of true positive M1 lesions by 18F-rhPSMA-7.3 PET in newly diagnosed prostate cancer: Results from the phase 3 prospective LIGHTHOUSE study," were presented at ASCO (Free ASCO Whitepaper) GU 2023 on February 16, 2023, by Brian F. Chapin, MD, Associate Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, on behalf of Bridget F. Koontz, MD, Duke University Medical Center (at the time of the study), for the LIGHTHOUSE Study Group. Full session details and the abstract are available in the ASCO (Free ASCO Whitepaper) GU 2023 online program here.

About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)
rhPSMA compounds consist of a radiohybrid ("rh") Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells and they may be radiolabeled with 18F for PET imaging, or with isotopes such as 177Lu or 225Ac for therapeutic use – creating a true theranostic technology. They may play an important role in patient management in the future, and offer the potential for precision medicine for men with prostate cancer. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Diagnostics has completed two Phase 3 clinical studies evaluating the safety and diagnostic performance of 18F-rhPSMA-7.3 PET imaging in prostate cancer: ("SPOTLIGHT," NCT04186845), in men with recurrent disease and ("LIGHTHOUSE," NCT04186819), in men with newly diagnosed prostate cancer. Currently, rhPSMA compounds are investigational and have not received regulatory approval.

About Blue Earth Diagnostics

On February 16, 2023 Bio-Rad Laboratories, Inc. (NYSE: BIO and BIOb), a global leader in life science research and clinical diagnostic products, reported financial results for the fourth quarter and full year ended December 31, 2022 (Press release, Bio-Rad – Clinical Diagnostics Group, FEB 16, 2023, View Source [SID1234627348]).

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Fourth-quarter 2022 net sales were $730.3 million, a decrease of 0.3 percent compared to $732.8 million reported for the fourth quarter of 2021. COVID-related revenue was approximately $13 million in the fourth quarter of 2022 versus approximately $46 million reported in the year-ago period. On a currency-neutral basis, quarterly sales increased 5.8 percent compared to the same period in 2021. Fourth-quarter 2022 revenue increased 10.6 percent on a currency-neutral basis when excluding COVID-related sales.

Fourth-quarter 2022 gross margin was 54.4 percent compared to 54.6 percent for the fourth quarter of 2021.

Life Science segment net sales for the fourth quarter were $359.7 million, an increase of 10.1 percent compared to the same period in 2021. On a currency-neutral basis, the segment sales increased 16.4 percent compared to the same quarter in 2021. When also excluding COVID-related sales, Life Science revenue increased 28.1 percent, and were primarily driven by Droplet Digital PCR, process chromatography, Western blotting, and qPCR products.

Clinical Diagnostics segment net sales for the fourth quarter were $369.6 million, a decrease of 8.7 percent compared to the same period in 2021. On a currency-neutral basis, net sales decreased 2.9 percent versus the same quarter last year. Excluding COVID-related sales, Clinical Diagnostics revenue decreased 1.9 percent from the year-ago period, on a currency-neutral basis. The decrease was primarily driven by continuing supply chain constraints, which impacted instrument placements and sales of related consumables.

Income from operations for the fourth quarter of 2022 was $118.7 million versus $108.9 million during the same quarter last year.

Net income for the fourth quarter of 2022 was $827.7 million, or $27.78 per share, on a diluted basis, versus a net loss of $1,572.2 million, or $52.54 per share, on a diluted basis, during the same period in 2021. Net income (loss) amounts for the fourth quarter of 2022 and 2021 were predominantly impacted by the recognition of changes in the fair market value of equity securities related to the holdings of the company’s investment in Sartorius AG.

The effective tax rate for the fourth quarter of 2022 was 24.2%, compared to 22.8% for the same period in 2021. The effective tax rate reported in Q4 of 2022 was primarily affected by an unrealized gain in equity securities, and the tax rate reported in Q4 of 2021 was primarily affected by unrealized loss in equity securities.

"During the fourth quarter, we continued to make progress, working through the ongoing global supply chain challenges," said Norman Schwartz, Bio-Rad’s President, and Chief Executive Officer. "We also saw positive market response to new product introductions, setting the stage for 2023."

GAAP Results

Q4 2022

Q4 2021

Revenue (millions)

$730.3

$732.8

Gross margin

54.4%

54.6%

Operating margin

16.2%

14.9%

Net income (loss) (millions)

$827.7

$(1,572.2)

Income (loss) per diluted share

$27.78

$(52.54)

Non-GAAP Results

Q4 2022

Q4 2021

Revenue (millions)

$730.3

$732.8

Gross margin

54.9%

55.2%

Operating margin

17.4%

15.7%

Net income (millions)

$98.5

$98.5

Income per diluted share

$3.31

$3.26

A reconciliation between GAAP operating results and non-GAAP operating results is provided following the financial statements that are part of this press release. Non-GAAP adjustments include amortization of purchased intangibles; acquisition-related expenses and benefits; restructuring, impairment charges and gains and losses from change in fair market value of equity securities and loan receivable; gains and losses on equity-method investments; significant litigation charges or benefits and legal costs; and discrete income tax events and the income tax effect on these non-GAAP adjustments.

Non-GAAP net income and non-GAAP diluted income per share (non-GAAP EPS) are non-GAAP measures that exclude certain items detailed later in this press release under the heading "Non-GAAP and Currency-Neutral Reporting."

Non-GAAP net income for the fourth quarter of 2022 was $98.5 million, or $3.31 per share, on a diluted basis, compared to $98.5 million, or $3.26 per share, on a diluted basis, during the same period in 2021.

The non-GAAP effective tax rate for the fourth quarter of 2022 was 28.1 compared to 20.4 percent for the same period in 2021. The higher tax rate in 2022 was driven by a geographical mix of earnings.

The following table represents a reconciliation of Bio-Rad’s reported net income (loss) and diluted income (loss) per share to non-GAAP net income and non-GAAP diluted income per share for the three and twelve months ended December 31, 2022, and 2021:

In thousands, except per share data

Three Months Ended
December 31, 2022

Three Months Ended
December 31, 2021

Year Ended
December 31, 2022

Year Ended
December 31, 2021

GAAP net income (loss)

$ 827,734

$ (1,572,163)

$ (3,627,535)

$ 4,254,257

Legal settlements

–

–

–

(28,619)

Amortization of purchased intangibles

6,069

6,498

24,904

27,530

Legal matters

308

874

2,374

16,375

Acquisition related benefits

(494)

–

(494)

(40)

Restructuring (benefits) costs

31

(3,510)

4,594

64,289

(Gains) losses from change in fair market value of equity securities and loan receivable

(978,752)

2,152,505

5,193,554

(4,926,248)

Losses on equity-method investments

16,133

1,615

25,310

7,194

Other non-recurring items (2) (3)

2,454

1,909

8,600

1,909

Income tax effect of non-GAAP adjustments (1)

225,007

(489,230)

(1,198,728)

1,064,912

Non-GAAP net income

$ 98,490

$ 98,498

$ 432,579

$ 481,559

GAAP diluted income (loss) per share

$ 27.78

$ (52.54)

$ (121.79)

$ 140.83

Non-GAAP diluted income per share

$ 3.31

$ 3.26

$ 14.42

$ 15.94

(1)

Excluded items identified in the reconciliation schedule are tax effected by application of a non-GAAP effective tax rate. The non-GAAP tax provision is adjusted for items, the nature of which and/or tax jurisdiction requires the application of a specific tax rate or treatment.

(2)

Incremental costs to comply with the European Union’s In Vitro Diagnostics Regulation ("IVDR") for previously approved products.

(3)

Gain from the release of an escrow for the sale of a division in 2020.

Full-Year 2022 Results

On a reported basis, net sales for the full year 2022 decreased 4.1 percent to $2,802.2 million compared to $2,922.5 million for the prior year. On a currency-neutral basis, net sales grew 0.3 percent. When excluding a royalty-related legal settlement totaling $32 million in 2021, full-year 2022 sales grew 1.5 percent on a currency-neutral basis.

COVID-related sales for the full year were approximately $109 million, compared to $266 million in the year-ago period. Excluding COVID-related sales and the royalty-related legal settlement of $32 million, full-year 2022 revenue increased 7.2 percent year-over-year on a currency-neutral basis.

Full-year 2022 reported net sales for the Life Science segment were $1,347.2 million, an increase of 2.7 percent compared to the same period in 2021 on a currency-neutral basis and excluding the legal settlement in 2021. Life Science revenue grew 15.2 percent on a currency-neutral basis in 2022 versus 2021 when excluding COVID-related sales and the legal settlement.

Full-year 2022 reported net sales for the Clinical Diagnostics segment were $1,451.0 million, an increase of 0.4 percent compared to the prior year on a currency-neutral basis. When excluding COVID-related sales, full-year Clinical Diagnostics revenue grew 1.3 percent compared to 2021 on a currency-neutral basis.

Full-year 2022 gross margin was 55.9 percent, compared to 56.1 percent in 2021.

Net loss for full-year 2022 was $3,627.5 million, or $121.79 per share, on a fully diluted basis, compared to net income of $4,254.3 million, or $140.83 per share, in 2021.

The effective tax rate for the full year of 2022 was 22.9 percent compared to 21.9 percent in 2021. The effective tax rate reported in 2022 was primarily affected by an unrealized loss in equity securities and the tax rate reported in 2021 was primarily affected by unrealized gain in equity securities.

The non-GAAP effective tax rate for the full year of 2022 was 22.0 percent compared to 21.2 percent in 2021.

Non-GAAP net income for 2022 was $432.6 million, or $14.42 per share, compared to $481.6 million, or $15.94 per share in 2021.

"While 2022 financial results were largely in line with our expectations, it is also important to recognize the measurable progress achieved on our operational initiatives," said Mr. Schwartz. "Looking forward to 2023, we remain focused on leveraging our operational scale, operational improvements, and continued innovation. Our markets are strong and have largely recovered from the pandemic, giving us a positive outlook for growth. We extend sincere thanks to our employees across the globe for their ongoing commitment to supporting our customers as we continue our transformation and growth."

Full-Year 2022 Highlights

Full-year 2022 reported net sales were $2,802.2 million compared to $2,922.5 million for the full year of 2021. Excluding COVID-related sales and a royalty-related legal settlement in 2021, full-year 2022 revenue increased 7.2 percent year-over-year on a currency neutral basis.
Full-year 2022 reported net loss was $3,627.5 million, or $121.79 per share, on a fully diluted basis, compared to net income of $4,254.3 million, or $140.83 per share, in 2021.
In early 2022, during its Investor Day event, Bio-Rad’s management outlined a three-phased approach to the company’s continued transformation, including standardizing global operations, improving operational performance, and accelerating growth.
During 2022, the company continued to expand its portfolio of qPCR instruments, including the CFX Duet Real-Time PCR and CFX Opus Deepwell Systems, which provide greater workflow flexibility.
In June, the company introduced its CHT prepacked Foresight Pro Columns to support downstream process-scale chromatography applications in biological drug development and production.
During the second quarter, Bio-Rad introduced its Genesis Cell Isolation System, utilizing Celselect Slides technology offering an improved method for the enrichment and enumeration of circulating tumor cells (CTCs) in liquid biopsies.
In August, Bio-Rad released new, proprietary tools for discovery and drug development and expanded its libraries of dyes and antibodies (StarBright Dyes and Pioneer Antibody Discovery Platform).
In September, as part of the company’s molecular diagnostics strategy, Bio-Rad acquired an innovative, "sample-to-result" rapid PCR technology from Curiosity Diagnostics for syndromic infectious disease testing.
During the third quarter, the company introduced its QX600 Droplet Digital PCR platform to enable new, advanced multiplexing applications.
During the fourth quarter, Bio-Rad secured an exclusive licensing agreement with NuProbe USA, a genomics and molecular diagnostics company, to develop next-generation, highly multiplexed digital PCR assays for oncology applications.
Throughout 2022, Bio-Rad installed its IH-500 immunohematology systems across South Africa’s National Blood Services (SANBS) network addressing the country’s need for high-quality blood products and services.
2023 Financial Outlook

For the full year 2023, the company anticipates non-GAAP, currency-neutral revenue growth of approximately 6.0 to 7.0 percent and an estimated non-GAAP operating margin of approximately 19.5 percent. Bio-Rad’s management will discuss this outlook in greater detail during the fourth-quarter and full-year 2022 financial results conference call.

Conference Call and Webcast

Bio-Rad’s management will review the results for the fourth quarter and full year ended December 31, 2022, in a conference call scheduled for 2 PM Pacific Time (5 PM Eastern Time) on February 16, 2023. To participate, call 844-200-6205 within the U.S. or +1 929-526-1599 outside the U.S., access code: 143970. A live webcast of the conference call will be accessible in the "Investor Relations" section of the company’s website under "Events & Presentations" at investors.bio-rad.com. A replay of the webcast will be available for up to a year.

Use of Non-GAAP and Currency-Neutral Reporting

In addition to the financial measures prepared in accordance with generally accepted accounting principles (GAAP), we use certain non-GAAP financial measures, including non-GAAP net income and non-GAAP EPS, which exclude amortization of acquisition-related intangible assets, certain acquisition-related expenses and benefits, restructuring charges, asset impairment charges, gains and losses from change in fair market value of equity securities and loan receivable, gains and losses on equity-method investments, and significant legal-related charges or benefits and associated legal costs. Non-GAAP net income and non-GAAP EPS also exclude certain other gains and losses that are either isolated or cannot be expected to occur again with any predictability, tax provisions/benefits related to the previous items, and significant discrete tax events. We exclude the above items because they are outside of our normal operations and/or, in certain cases, are difficult to forecast accurately for future periods.

We utilize a number of different financial measures, both GAAP and non-GAAP, in analyzing and assessing the overall performance of our business, in making operating decisions, forecasting and planning for future periods, and determining payments under compensation programs. We consider the use of the non-GAAP measures to be helpful in assessing the performance of the ongoing operation of our business. We believe that disclosing non-GAAP financial measures provides useful supplemental data that, while not a substitute for financial measures prepared in accordance with GAAP, allows for greater transparency in the review of our financial and operational performance. We also believe that disclosing non-GAAP financial measures provides useful information to investors and others in understanding and evaluating our operating results and future prospects in the same manner as management and in comparing financial results across accounting periods and to those of peer companies. More specifically, management adjusts for the excluded items for the following reasons:

Amortization of purchased intangible assets: we do not acquire businesses and assets on a predictable cycle. The amount of purchase price allocated to purchased intangible assets and the term of amortization can vary significantly and are unique to each acquisition or purchase. We believe that excluding amortization of purchased intangible assets allows the users of our financial statements to better review and understand the historic and current results of our operations, and also facilitates comparisons to peer companies.

Acquisition-related expenses and benefits: we incur expenses or benefits with respect to certain items associated with our acquisitions, such as transaction costs, professional fees for assistance with the transaction; valuation or integration costs; changes in the fair value of contingent consideration, gain or loss on settlement of pre-existing relationships with the acquired entity; or adjustments to purchase price. We exclude such expenses or benefits as they are related to acquisitions and have no direct correlation to the operation of our ongoing business.

Restructuring, impairment charges, and gains and losses from change in fair market value of equity securities and loan receivable, and gains and losses on equity-method investments: we incur restructuring and impairment charges on individual or groups of employed assets and charges and benefits arising from gains and losses from change in fair market value of equity securities and loan receivable, and gains and losses (including impairments) on equity-method investments, which arise from unforeseen circumstances and/or often occur outside of the ordinary course of our on-going business. Although these events are reflected in our GAAP financials, these unique transactions may limit the comparability of our ongoing operations with prior and future periods.

Significant litigation charges or benefits and legal costs: we may incur charges or benefits as well as legal costs in connection with litigation and other contingencies unrelated to our core operations. We exclude these charges or benefits, when significant, as well as legal costs associated with significant legal matters because we do not believe they are reflective of ongoing business and operating results.

Income tax expense: we estimate the tax effect of the excluded items identified above to determine a non-GAAP annual effective tax rate applied to the pretax amount in order to calculate the non-GAAP provision for income taxes. We also adjust for items for which the nature and/or tax jurisdiction requires the application of a specific tax rate or treatment.

From time to time in the future, there may be other items excluded if we believe that doing so is consistent with the goal of providing useful information to investors and management.

Percentage sales growth in currency-neutral amounts are calculated by translating prior period sales in each local currency using the current period’s monthly average foreign exchange rates for that currency and comparing that to current period sales.

There are limitations in using non-GAAP financial measures because the non-GAAP financial measures are not prepared in accordance with generally accepted accounting principles and may be different from non-GAAP financial measures used by other companies. The non-GAAP financial measures are limited in value because they exclude certain items that may have a material impact on our reported financial results. The presentation of this additional information is not meant to be considered in isolation or as a substitute for the directly comparable financial measures prepared in accordance with GAAP in the United States. Investors should review the reconciliation of the non-GAAP financial measures to their most directly comparable GAAP financial measures as provided in the tables accompanying this press release.

BIO-RAD, CELSELECT SLIDES, DROPLET DIGITAL, IH-500, PIONEER, QX600 and STARBRIGHT are trademarks of Bio-Rad Laboratories, Inc. or Bio-Rad Medical Diagnostics GmbH in certain jurisdictions. NUPROBE is a trademark of NuProbe USA, Inc.

On February 16, 2023 Group consolidated reported it have been prepared for the fourth quarter, and full year, which includes the consolidation of NeoDynamics AB, NeoDynamics GmbH and NeoDynamics Inc (Press release, NeoDynamics, FEB 16, 2023, View Source [SID1234627347]). These are represented in the financial statements as adjusted numbers, and are the comparative figures used for last year.

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Fourth Quarter 2022

Revenues amounted to SEK 130 (931) thousand, of which SEK 0 (1,039) thousand were net sales
Net loss amounted to SEK -26,857 (-19,957) thousand.
Loss per share amounted to SEK -0.22 (-0.33).
Cash and cash equivalents amounted to SEK 20,067 (24,960 at year-end) thousand.
Full Year 2022

Revenues amounted to SEK 903 (2,086) thousand, of which SEK 135 (1,162) thousand were net sales
Net loss amounted to SEK -74,514 (-68,553) thousand.
Loss per share amounted to SEK -0.73 (-1.14).
Cash and cash equivalents amounted to SEK 20,067 (24,960 at year-end) thousand.
Significant events during the quarter

In early November, NeoDynamics hired National Sales Director in the USA, Brendan Carney, for the launch of its NeoNavia Biopsy System. Brendan has more than 20 years of experience including Genentech and Pharmacia, leading teams and product launches in oncology, infectious diseases, endocrinology, and medical devices
In late November, NeoDynamics geared up for the US launch by partnering with Diligent Health Solutions. Diligent will assist NeoDynamics in communicating with patients, caregivers, and health care professionals, from initial consultation to strategic implementation and daily operations. Their specialists will support the company’s efforts to manage medical information, reimbursement and coding services.
In December, NeoDynamics appointed Matthew Colpoys, to lead US operations. Matt will remain on the board and reports to CEO Anna Eriksrud.
Significant events after the end of the quarter

In January, NeoDynamics Partnered with Uniphar for US Distribution and Logistics support. Uniphar is a global distribution and logistics giant and will help to ensure a successful US launch of NeoNavia
In February NeoDynamics’ largest owner secures the launch of NeoNavia in the US. Gryningskust Holding AB, offered the company a loan of SEK 14 million. The loan is intended to be converted into shares if the company issues new shares in the future, subject to shareholder approval.
NeoDynamics announed that Jie Bao and Xiaojun Xu will step down from the Board of Directors as of 2023-02-14 based on a mutual agreement. They will instead focus on supporting the company and its plans for the Chinese market.
CEO Comment

Ready for commercialisation in the US

In September 2022, we reached an essential milestone with the FDA clearance of NeoNavia. The US approval is a cornerstone in our strategic way forward and path to profitability.

The covid pandemic delayed all FDA applications and made the timing of approvals unpredictable. Thus, it was prudent for a small company such as NeoDynamics to wait for the go-ahead from the FDA before starting to build the US organization.

The recently deployed management team is preparing for fullscale commercialization of Neonavia in 2023. This includes identifying and hiring personnel, locking in attendance at key scientific congresses and building the infrastructure to support sales activities in the field. The first product to market is FlexiPulse. The FlexiPulse needle is unique in its design and allows insertion into challenging locations. Checking lymph nodes in the axilla (armpit) is critical to assessing whether cancer has spread. The introduction of FlexiPulse will allow physicians to safely and effectively simplify biopsy of the lymph nodes in the axilla in a minimally invasive fashion. Shortcomings of existing biopsy systems result in most axillary nodes being removed surgically. A common side effect of surgical removal of axilla lymph nodes is persistent swelling (edema) of the arm, and a FlexiPulse biopsy minimizes this risk. Further, the design of the FlexiPulse makes it ideal for tissue sampling in suspected lesions in the proximity of breast implants, which is an increasingly common problem, especially in the United States.

An ever more critical stakeholder in breast cancer treatment is the patient themselves and related patient advocacy groups. Patient empowerment is an increasingly important aspect of delivering breast cancer care. For this reason, NeoDynamics’ hired a US management team with significant backgrounds working with specialty products and associated patient associations. Another advantage of the organization’s special markets background is working with key-opinion-leading physicians at the most prestigious treatment centers in the United States.

To ensure cost-effectiveness, NeoDynamics Inc. outsources customer care and logistics functions to its partners Diligent Health Solutions and Uniphar Logistics, both divisions of Uniphar Group of Ireland.

Of course, the deep experience gained in Europe is vital for success in the USA. In more than 30 cancer research centres in Germany, the UK and Sweden, we continue our work and collaboration with key opinion leaders. From this ongoing experience we can conclude that clinics in Europe remain very engaged. We have fine-tuned two needles during 2022, which has resulted in better products, but also in postponed deliveries. It is our firm commitment to make no compromise on product quality.

Also, we continue to run our clinical study program to document the pulse technology and our different needles in clinical practice. The clinical program has resulted in several presentations at congresses during 2022 including the prestigious SBI congress in Savannah in May.

Organisational development

In 2022, we added several senior and experienced members to our team. On December 1, 2022, Matthew E. Colpoys, Jr. (member of the Board of Directors) assumed the position of US CEO for NeoDynamics Inc. We also welcomed Brendan Carney, our national sales director in the US. In February 2022, we also onboarded Aaron Wong as our Group CFO of NeoDynamics AB. We now have an organization that is capable of executing the strategy in both the short and long term.

Our performance in 2022

Our revenue is still modest while we continue to deploy resources in a controlled fashion to develop our products in Europe and the US. We are pleased to have secured short-term funding for the launch in the US.

On February 16, 2023 Lytix Biopharma ("Lytix") (Euronext Growth Oslo: LYTIX), a Norwegian immuno-oncology company, reported its fourth quarter and second half 2022 results – Steady progress towards improving cancer treatment outcomes (Press release, Lytix Biopharma, FEB 16, 2023, View Source [SID1234627346]).

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"Our molecules have a unique dual mode of action and can kill cancer cells in a way that activates a broad T-cell response that has the potential to target all cancer cells within heterogeneous tumors and thereby increase the number of patients responding to immunotherapy. We have seen very promising effects in cancer patients and are now eagerly looking forward to receiving the results from the clinical Phase II studies with our lead candidate", says Dr. Øystein Rekdal, CEO of Lytix Biopharma.

Highlights from the fourth quarter and second half 2022 and post period events:

Business and Partnership:

Verrica Pharmaceuticals recently completed treatment in Part 1 of their ongoing Phase II study evaluating LTX-315 in basal cell carcinoma. Part 1 has enrolled 10 patients and demonstrated a favorable safety and tolerability profile with no reported serious adverse events. Patients receiving the higher range of dosing experienced a consistent response of clinical tumor necrosis.
Lytix Biopharma appointed Stephen Worsley as Chief Business Officer as part of the company’s strong focus on exploring commercial opportunities for its drug candidates. Stephen brings a great track record of successful deals in oncology on assets in development and is now introducing Lytix’ assets to key opinion leaders and companies within the industry.
R&D:

Following approval of the clinical trial application (CTA) for ATLAS-IT-05 in Europe in Q3 2022, the Phase II study in the US has expanded to an additional three European countries; Norway, France and Spain. All sites are open and recruiting patients with the aim of completing enrollment by mid-2023.
Activities are ongoing to prepare for a regulatory submission, which is required to start a Phase I study with LTX-401.
The Clinical Study Report for ATLAS-IT-04 has been completed. ATLAS-IT-04 showed encouraging data demonstrating that LTX-315 improved the outcome of adoptive cell transfer treatment, stabilizing the disease in patients with progressive metastatic soft tissue sarcoma.
Compelling data from Lytix’ collaboration with research groups at National Cancer Institute and Weill Cornell Medicine were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting.
Financial:

Total operating expenses for the six months that ended 31 December 2022 was NOK 46.4 million compared to NOK 37.8 million in the same period in 2021. Compared to the six months ending 31 December 2021, there has been an increase in activities in connection to the ongoing ATLAS-IT-05 trial in the US and EU and the preclinical development of LTX-401. The important expansion of ATLAS-IT-05 to the EU has been driving costs during this period. In parallel, personnel expenses have decreased.
Cash position at the end of the period was NOK 94.6 million compared to NOK 197.3 million as of 31 December 2021. In addition to the cash position, Lytix has NOK 50.6 million placed in a liquidity fund as of 31 December 2022. In total Lytix has NOK 145.2 in cash and short-term financial investments at the end of the year.
Key figures (unaudited):

The full report is linked to this press release (and together with a presentation available at View Source).

The results will be presented in a webcast with CEO Øystein Rekdal, CDO Graeme Currie and CFO Gjest Breistein today at 14.30 CEST.

The presentation and subsequent Q&A session will be held in English and may be viewed live by registering here: View Source

A recording of the presentation will be made available on View Source (after the presentation).