On August 5, 2022 Bayer reported the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for the oral androgen receptor inhibitor (ARi) NUBEQA (darolutamide) with docetaxel for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) (Press release, Bayer, AUG 5, 2022, View Source [SID1234617710]).1

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The approval is based on results of the Phase III ARASENS trial that demonstrated a statistically significant increase in overall survival (OS), the trial’s primary endpoint, with a reduction in the risk of death by 32% for those treated with NUBEQA plus androgen deprivation therapy (ADT) and docetaxel compared to ADT and docetaxel (HR=0.68, 95% CI 0.57-0.80; P<0.0001). Treatment with NUBEQA plus ADT and docetaxel also resulted in a statistically significant delay in time to pain progression (HR=0.79, 95% CI 0.66-0.95; P=0.006).1

The ARASENS results were presented earlier this year at the 2022 ASCO (Free ASCO Whitepaper) GU Cancers Symposium and simultaneously published in The New England Journal of Medicine.2 NUBEQA is also indicated for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). NUBEQA is being investigated in further studies across various stages of prostate cancer.

Incidence of adverse reactions was similar between both study arms. Adverse reactions reported for NUBEQA with docetaxel above 10% with a ≥2% increase over placebo with docetaxel were constipation (23% versus 20%), decreased appetite (19% versus 13%), rash (19% versus 15%), hemorrhage (18% versus 13%), increased weight (18% versus 16%), and hypertension (14% versus 9%). Serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel and in 42% of patients receiving placebo with docetaxel. Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel and in 4% of patients receiving placebo with docetaxel.1

"NUBEQA plus ADT and docetaxel has shown significant benefit in overall survival and a favorable safety profile for patients with metastatic hormone-sensitive prostate cancer," said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center. "This new indication for NUBEQA is particularly meaningful, as it highlights its proven tolerability and provides a new option for patients."

Prostate cancer remains the second leading cancer-related cause of death among men in the U.S., with up to one-third of patients developing metastatic disease.3,4 The incidence of mHSPC has increased by 72% in the U.S. over the past 10 years.5 Approximately one in three patients who are diagnosed with mHSPC survive the disease five years or longer, with most eventually experiencing progression to castration-resistant prostate cancer (CRPC).4,5

"With compelling data from the Phase III ARASENS and ARAMIS trials, NUBEQA has demonstrated significant efficacy in mHSPC and nmCRPC," said Christine Roth, Member of the Executive Committee of Bayer’s Pharmaceutical Division and Head of the Oncology SBU at Bayer. "The expansion of NUBEQA’s indication to reach a broader population in the U.S. reaffirms Bayer’s commitment to provide proven and tolerable treatment options to eligible patients across different stages of prostate cancer."

"Prostate cancer is the most common cancer among men in the U.S., with chances of survival decreasing dramatically for those diagnosed with mHSPC compared to localized prostate cancer," said Charles J. Ryan, M.D., President and Chief Executive Officer, Prostate Cancer Foundation (PCF). "This approval adds a different treatment approach for mHSPC patients and their physicians to choose from."

The application received Priority Review designation granted by the FDA and was submitted under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to provide a more efficient review process of applications to ensure that safe and effective cancer treatments are available to patients as early as possible. Ongoing reviews are also being conducted under the FDA Oncology Center of Excellence’s (OCE) Project Orbis initiative, which provides a framework for concurrent submission and review of cancer treatments among participating international health authorities.

About the ARASENS Trial6

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 75 mg/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.

Permanent discontinuation of NUBEQA due to adverse reactions occurred in 14% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions which resulted in permanent discontinuation of NUBEQA were rash (1.1%), musculoskeletal pain (0.9%), and increased aspartate aminotransferase (AST) (0.9%). Dosage interruptions of NUBEQA due to adverse reactions occurred in 23% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions (>2%) requiring dosage interruption of NUBEQA were increased alanine aminotransferase (ALT) (3.2%), increased AST (3.1%) and febrile neutropenia (2.1%). Dosage reductions of NUBEQA due to adverse reactions occurred in 9% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions (>2%) requiring dosage reduction of NUBEQA were increased ALT (2.8%) and increased AST (2.5%). 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.

About NUBEQA (darolutamide)1

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.1

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) who were receiving a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of NUBEQA orally twice daily in combination with androgen deprivation therapy (ADT), or ADT alone. The primary efficacy endpoint was metastasis-free survival (MFS). NUBEQA is also being investigated in further 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 and mHSPC.1 The approvals of NUBEQA for nmCRPC in the U.S., European Union (EU), and other global markets have been based on the pivotal Phase III ARAMIS trial data evaluating the efficacy and safety of NUBEQA plus ADT compared to ADT alone.1 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. 0.1% 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.7

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.8,9 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.3,5

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 August 5, 2022 AstraZeneca and Daiichi Sankyo reported that it’s ENHERTU (fam-trastuzumab deruxtecan-nxki) has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy (Press release, AstraZeneca, AUG 5, 2022, View Source [SID1234617709]).

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ENHERTU is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.

The approval by the Food and Drug Administration (FDA) was based on the results from the DESTINY-Breast04 Phase III trial. In the trial, ENHERTU reduced the risk of disease progression or death by 50% versus physician’s choice of chemotherapy in patients with HER2-low metastatic breast cancer with hormone receptor (HR)-positive disease or HR-negative disease (median progression-free survival [PFS] 9.9 versus 5.1 months; hazard ratio [HR] 0.50; 95% confidence interval [CI] 0.40-0.63; p<0.0001). A median overall survival (OS) of 23.4 months was seen in patients treated with ENHERTU versus 16.8 months in those treated with chemotherapy, a 36% reduction in the risk of death (HR 0.64; 95% CI 0.49-0.84; p=0.001).

Shanu Modi, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, US, said: "Approximately half of all patients with breast cancer have tumors that are HER2-low, which have previously been classified as HER2-negative and have not had effective treatment options with HER2-targeted medicines. Based on the promising results of the DESTINY-Breast04 trial, clinicians are starting to differentiate levels of HER2 expression and redefine how metastatic breast cancer is classified with a distinct HER2-low patient population that may be eligible for trastuzumab deruxtecan."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "The rapid approval of ENHERTU in HER2-low metastatic breast cancer by the FDA underscores the urgency to bring this transformational medicine to patients as quickly as possible. Patients with HER2-low tumors, who are identified through existing HER2 testing methods, will now have the opportunity to be treated based upon their HER2 status."

Ken Keller, Global Head of Oncology Business and President and CEO, Daiichi Sankyo, Inc, said: "Today’s FDA approval marks a monumental moment in breast cancer treatment as ENHERTU is the first-ever HER2-directed medicine to be approved for the treatment of patients with HER2-low metastatic breast cancer. With the ground-breaking survival benefit seen in the DESTINY-Breast04 trial, this milestone confirms the importance of targeting lower levels of HER2 expression in the treatment of metastatic breast cancer and we are thrilled that we can now offer ENHERTU to even more patients."

The approval was granted under the FDA’s Real-Time Oncology Review program after securing Priority Review and Breakthrough Therapy Designation of ENHERTU in the US in this setting. The expanded approval for ENHERTU in the US, following its previous approval in 2nd-line HER2-positive metastatic breast cancer, enables its use across a wide-spectrum of HER2-expressing breast cancer, including patients with HER2-low disease.

The DESTINY-Breast04 Phase III trial results were presented at the presidential plenary session of the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting and simultaneously published in The New England Journal of Medicine (NEJM).1

The safety profile of ENHERTU was consistent with previous clinical trials with no new safety concerns identified. Interstitial lung disease (ILD) or pneumonitis rates were consistent with those observed in late-line HER2-positive breast cancer trials of ENHERTU. Overall, 12% of patients had confirmed ILD or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD events were Grade 1 or 2 (10%), with five Grade 3 (1.3%) and no Grade 4 events reported. There were three (0.8%) ILD-related deaths (Grade 5).

In June 2022, fam-trastuzumab deruxtecan-nxki (ENHERTU) was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines) as the Category 1 preferred regimen for patients with tumors that are HER2 IHC 1+ or 2+ and ISH- who have received at least one prior line of chemotherapy for metastatic disease and, if tumor is HR-positive, are refractory to endocrine therapy, based on the data from DESTINY-Breast04.2

The US regulatory submission for DESTINY-Breast04 was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, ENHERTU is also under regulatory review for the same indication by the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada and Switzerland’s Swissmedic.

Regulatory applications for ENHERTU are also currently under review in Europe, Japan and several other countries based on the DESTINY-Breast04 results.

U.S. Important Safety Information for ENHERTU

Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

Unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either:
– In the metastatic setting, or
– In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy

Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.
Contraindications
None.

Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Metastatic Breast Cancer and HER2-Mutant Solid Tumors (5.4 mg/kg)
In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU. Median time to first onset was 5 months (range: 0.9 to 23).

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21.0).

Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level.

Metastatic Breast Cancer and HER2-Mutant Solid Tumors (5.4 mg/kg)
In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Sixteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 664). Febrile neutropenia was reported in 1.1% of patients.

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU.
Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Metastatic Breast Cancer and HER2-Mutant Solid Tumors (5.4 mg/kg)
In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.6% of patients, of which 0.4% were Grade 3.

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.

Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by one level.

Adverse Reactions
Metastatic Breast Cancer and HER2-Mutant Solid Tumors (5.4 mg/kg)
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 984 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, and NCT04644237. Among these patients 65% were exposed for >6 months and 39% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (71%), decreased hemoglobin (66%), decreased neutrophil count (65%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (47%), increased aspartate aminotransferase (48%), vomiting (44%), increased alanine aminotransferase (42%), alopecia (39%), increased blood alkaline phosphatase (39%), constipation (34%), musculoskeletal pain (32%), decreased appetite (32%), hypokalemia (28%), diarrhea (28%), and respiratory infection (24%).

Metastatic Breast Cancer
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg intravenously every three weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30).

Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (one patient each).

ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), hypokalemia (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), respiratory infection (22%), headache (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%).

HER2-Low Metastatic Breast Cancer
DESTINY-Breast04
The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.

Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each).

ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and hypokalemia (25%).

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU.

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%).

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%).

Use in Specific Populations

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
Geriatric Use: Of the 883 patients with breast cancer treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years and 3.6% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (60%) as compared to younger patients (48%). Of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.
Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate or severe renal impairment.
Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

Notes

Financial considerations
Following this approval for ENHERTU in the US, an amount of $200m is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the HER2-low breast cancer post chemotherapy indication. The milestone will be capitalized as an addition to the upfront payment made by AstraZeneca to Daiichi Sankyo in 2019 and subsequent capitalized milestones, and will be amortized through the profit and loss statement.

Sales of ENHERTU in the US are recognized by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from ENHERTU sales in the US as collaboration revenue in the Company’s financial statements.

Further details on the financial arrangements were set out in the March 2019 announcement of the collaboration.

Breast cancer and HER2 expression
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide and in the US.3,4 More than two million patients with breast cancer were diagnosed in 2020 resulting in nearly 685,000 deaths globally.3 In the US, more than 290,000 patients are expected to be diagnosed in 2022, resulting in more than 43,000 deaths.5

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers, and is one of many biomarkers expressed in breast cancer tumors.6

HER2 expression is currently determined by an immunohistochemistry (IHC) test which estimates the amount of HER2 protein on a cancer cell, and/or an in-situ hybridization (ISH) test, which counts the copies of the HER2 gene in cancer cells.6,7 HER2 tests provide IHC and ISH scores across the full HER2 spectrum and are routinely used to determine appropriate treatment options for patients with metastatic breast cancer.

HER2-positive cancers are currently defined as HER2 expression measured as IHC 3+ or IHC 2+/ISH+, and HER2-negative cancers are defined as HER2 expression measured as IHC 0, IHC 1+ or IHC 2+/ISH-.6 However, approximately half of all breast cancers are HER2-low, defined as an HER2 score of IHC 1+ or IHC 2+/ISH-.8-10 HER2-low occurs in both HR-positive and HR-negative disease.11

Previously, patients with HR-positive metastatic breast cancer and HER2-low disease had limited effective treatment options following progression on endocrine (hormone) therapy.9,12 Additionally, few targeted options were available for those with HR-negative disease.13 Now with the approval of ENHERTU, patients with HER2-low tumors may be eligible for HER2-directed therapy.

DESTINY-Breast04
DESTINY-Breast04 is a global, randomized, open-label, Phase III trial evaluating the efficacy and safety of ENHERTU (5.4mg/kg) versus physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive or HR-negative, HER2-low unresectable and/or metastatic breast cancer previously treated with one or two prior lines of chemotherapy. Patients were randomized 2:1 to receive either ENHERTU or chemotherapy.

The primary endpoint of DESTINY-Breast04 is PFS in patients with HR-positive disease based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomized patients (HR-positive and HR-negative disease), OS in patients with HR-positive disease and OS in all randomized patients (HR-positive and HR-negative disease). Other secondary endpoints include PFS based on investigator assessment, objective response rate based on BICR and on investigator assessment, duration of response based on BICR and safety.

DESTINY-Breast04 enrolled 557 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

ENHERTU
ENHERTU is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

ENHERTU (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

ENHERTU (5.4mg/kg) is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

ENHERTU (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

ENHERTU development program
A comprehensive development program is underway globally, evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for ENHERTU in breast, gastric and non-small cell lung cancer are currently under review in several other countries based on the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01, DESTINY-Gastric02 and DESTINY-Lung01 trials, respectively.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging and redefining the current clinical paradigm for how breast cancer is classified and treated to deliver even more treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment.

AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines fulvestrant and goserelin and the next-generation oral selective estrogen receptor degrader (SERD) and potential new medicine camizestrant.

PARP inhibitor olaparib is a targeted treatment option that has been studied in HER2-negative early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with Merck & Co., Inc. (MSD outside the US and Canada) continue to research olaparib in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the initial approvals of ENHERTU, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy durvalumab in combination with other oncology medicines, including olaparib and ENHERTU, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On August 5, 2022 Pillar Biosciences, the leader in Decision Medicine, which develops and distributes next-generation sequencing (NGS) products and technologies to localize testing and reduce time to treatment initiation and overall testing costs, reported that Randy Pritchard, Chief Executive Officer, will participate in the "Liquid Biopsy in Clinical Practice" panel discussion at the 2022 UBS Genomics 2.0 and MedTech Innovations Summit in Dana Point, California on Tuesday, August 9, 2022 at 7:00pm Eastern Time / 4:00pm Pacific Time (Press release, Pillar Biosciences, AUG 5, 2022, View Source [SID1234617708]). Randy Pritchard and Vincent Ricci, Chief Financial Officer, will also participate in investor meetings at the conference.

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On August 5, 2022 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, reported financial results and business highlights for the third quarter of fiscal 2022 ended June 30, 2022 (Press release, Twist Bioscience, AUG 5, 2022, View Source [SID1234617701]).

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"We are the high quality, low cost leader and as the macroeconomic environment continues to hold uncertainty, Twist’s product offerings are resonating with customers," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. "We continue to see large accounts expanding their footprint while we also focus on diversifying our risk across an increasing number of customers, particularly in biopharma. We entered into our first exclusive option and license agreement for a Twist-discovered antibody and continue to build a robust ecosystem for DNA data storage through educational materials, including the most recently published white paper, and by driving toward an interoperable system through the development of industry standards."

Dr. Leproust continued, "Moving forward, we plan to launch the Factory of the Future in January 2023, which will facilitate growth across all areas of our business. We are well positioned to take market share in synbio and NGS, deliver new antibody targets for our biopharma customers and advance our efforts in DNA data storage toward our first commercial solution, all while targeting toward adjusted EBITDA breakeven at $300 million annual revenue for the core business."

FISCAL 2022 THIRD QUARTER FINANCIAL RESULTS

Orders: Total orders received for the third quarter of fiscal 2022 were $59.7 million compared to $39.1 million for the same period of fiscal 2021.
Revenue: Total revenues for the third quarter of fiscal 2022 were $56.1 million compared to $35.0 million for the same period of fiscal 2021.
Cost of Revenues: Cost of revenues for the third quarter of fiscal 2022 was $31.0 million compared to $20.9 million for the same period of fiscal 2021.
Research and Development Expenses: Research and development expenses for the third quarter of fiscal 2022 were $36.8 million compared to $19.8 million for the same period of fiscal 2021.
Selling, General and Administrative Expenses: Selling, general and administrative expenses for the third quarter of fiscal 2022 were $53.7 million compared to $34.5 million for the same period of fiscal 2021.
Net Loss: Net loss attributable to common stockholders for the third quarter of fiscal 2022 was $60.5 million, or $1.08 per share, compared to $40.0 million, or $0.82 per share, for the same period of fiscal 2021.
Cash Position: As of June 30, 2022, the company had $527.6 million in cash, cash equivalents and investments.
Recent Highlights:

SynBio and NGS

Shipped products to approximately 1,900 customers in the third quarter of fiscal 2022, versus approximately 1,800 in the third quarter of fiscal 2021.
Shipped approximately 163,000 genes during the third quarter of fiscal 2022, compared with approximately 107,000 in the third quarter of fiscal 2021.
Launched two human monkeypox synthetic DNA controls, expanding Twist’s portfolio of synthetic controls and reference standards.
Offered two new SARS-CoV-2 controls for the BA.2.12.1 sublineage of the omicron variant.
Received expanded Emergency Use Authorization from the U.S. Food and Drug Administration for the SARS-CoV-2 Next-Generation Sequencing (NGS) Assay developed with Biotia for the qualitative detection, identification and differentiation of SARS-CoV-2 lineages and identification of specific genomic mutations.
Launched Twist MRD Rapid 500 Panel to enable customers to implement fully customizable panels for $50 per sample.
Launched the Twist Human Methylome Panel covering 84.2% of GpC islands to support the discovery of differentially methylated regions and epigenetic target identification for cancer metastasis and human development research.
Entered into a collaboration with DNAnexus to integrate DNAnexus’ biomedical data analysis platform with Twist’s NGS Methylation Detection and Unique Molecular Identifier Adapter Systems.
BioPharma and DNA Data Storage

Entered into a research, exclusive option and license agreement with Astellas for a Twist-discovered antibody targeting an undisclosed checkpoint inhibitor.
Entered into a collaboration with Ildong Pharmaceutical, Twist’s first collaboration with a South Korea-based company, under which Ildong will license a suite of Twist VHH antibody libraries to use to discover and develop antibodies for applications in immuno-oncology.
Entered into an antibody discovery agreement with Xilio Therapeutics to advance the development of novel immunotherapies.
Hosted a ribbon-cutting ceremony for the new location of Twist Boston, also known as Abveris, in Quincy, MA.
The DNA Data Storage Alliance joined SNIA as a Technology Affiliate group to accelerate its mission to create an interoperable ecosystem for DNA-based data storage solutions.
Participated in panels and presentations at key data storage and industry conferences including Fujifilm’s 12th Annual Global IT Executive Summit, the 2022 MRS Spring Meeting and Exhibit, and the Flash Memory Summit.
Highlighted a DNA data storage white paper that quantifies the need for new storage mediums to address the zone of potential insufficiency where current methods of storing data, even when scaled, will not meet future demand.
Updated Fiscal 2022 Financial Guidance

The following statements are based on Twist’s current expectations for fiscal 2022. The following statements are forward-looking, and actual results could differ materially depending on market conditions and the factors set forth under "Forward-Looking Statements" below.

For the full fiscal year 2022, Twist provided the following updated financial guidance:

Revenue is now expected to be approximately $203 million, an increase from previous guidance of $191 million to $199 million
SynBio revenue including Ginkgo Bioworks is expected to be $80 million, an increase from previous guidance of $71 million to $73 million
NGS revenue is estimated to be approximately $97 million, an increase from previous guidance of $94 million to $96 million
Biopharma revenue is estimated to be approximately $26 million, at the low end of the previous guidance range of $26 million to $30 million
Gross margin is expected to be 40% for fiscal 2022
Operating expenses including R&D and SG&A are expected to be approximately $330 million for the year
Net loss is expected to be approximately $250 million, reflecting the impact of the Abveris acquisition in stock-based compensation and includes:
R&D expense is expected to be approximately $125 million, a decrease from previous guidance of $130 million
Approximately $40 million of R&D expense is expected to be for DNA data storage
Stock-based compensation is expected to be approximately $80 million
Depreciation is expected to be $14 million
Capital expenditures are expected to be in the range of $95 to $100 million, including building out the "Factory of the Future"
Conference Call Information

The company plans to hold a conference call and live audio webcast for analysts and investors at 8:00 a.m. Eastern Time today to discuss its financial results and provide an update on the company’s business. The conference call will be webcast live through the Investor Relations section under the "Company" tab at www.twistbioscience.com. Those parties interested in participating via telephone must register on the Company’s Investor Relations website or by clicking here. Upon registration, all telephone participants will receive the dial-in number along with a unique PIN number that can be used to access the call. To avoid delays, we encourage participants to dial into the conference call fifteen minutes ahead of the scheduled start time. The webcast replay will be available for two weeks.

On August 5, 2022 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that a conference call will be held on Monday, August 8, 2022 at 8:30 AM ET to discuss results for the second quarter of 2022 (Press release, TG Therapeutics, AUG 5, 2022, https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-host-conference-call-second-quarter-2022 [SID1234617700]). Michael S. Weiss, Executive Chairman and Chief Executive Officer, will host the call.

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In order to participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics. A live webcast of this presentation will be available on the Events page, located within the Investors & Media section, of the Company’s website at www.tgtherapeutics.com. An audio recording of the conference call will also be available for replay at www.tgtherapeutics.com, for a period of 30 days after the call.

TG Therapeutics will announce its financial results for this period in a press release to be issued prior to the call.