On January 9, 2022 Exact Sciences Corp. (Nasdaq: EXAS) reported that the company expects to report revenue between $472 million and $475 million for the fourth quarter ended Dec. 31, 2021 (Press release, Exact Sciences, JAN 9, 2022, View Source [SID1234598443]).

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"The Exact Sciences team delivered outstanding results to finish 2021, setting us up for years of strong growth and a clear path to profitability," said Kevin Conroy, chairman and CEO of Exact Sciences. "Our goal is to make earlier cancer detection a routine part of medical care. Led by our top brands, Cologuard and Oncotype DX, and an exciting pipeline of tests in colon cancer screening, multi-cancer early detection, and minimal residual disease and recurrence monitoring, we plan to fundamentally change how cancer patients are diagnosed and treated."

Preliminary, Unaudited Fourth Quarter 2021 Financial Results

For the three-month period ended Dec. 31, 2021, as compared to the same period of 2020:

Total revenue between $472 million and $475 million, an increase of 2 percent
Total revenue, excluding COVID-19 testing, increased 16 percent
Screening revenue between $277 million and $278 million, an increase of 11 percent
Precision Oncology revenue between $148.5 million and $149.5 million, an increase of 27 percent
COVID-19 testing revenue between $46.5 million and $47.5 million, a decrease of 53 percent
Preliminary, Unaudited 2021 Financial Results

For the twelve-month period ended Dec. 31, 2021, as compared to the same period of 2020:

Total revenue between $1,765.3 million and $1,768.3 million, an increase of 18 percent
Total revenue, excluding COVID-19 testing, increased 29 percent
Screening revenue between $1,061.6 million and $1,062.6 million, an increase of 30 percent
Precision Oncology revenue between $561.1 million and $562.1 million, an increase of 27 percent
COVID-19 testing revenue between $142.5 million and $143.5 million, a decrease of 39 percent
For the fourth quarter and 2021, Screening includes laboratory service revenue from Cologuard tests and revenue from Biomatrica products. Precision Oncology includes laboratory service revenue from global Oncotype and GEM ExTra laboratory service revenue.

Exact Sciences has not completed preparation of its financial statements for the fourth quarter or full year of 2021. The revenue ranges presented in this news release for the fourth quarter of 2021 and for the year ended Dec. 31, 2021 are preliminary and unaudited and are thus inherently uncertain and subject to change as we complete our financial results for the fourth quarter of 2021. Exact Sciences is in the process of completing its customary year-end close and review procedures as of and for the year ended Dec. 31, 2021, and there can be no assurance that final results for this period will not differ from these estimates. During the course of the preparation of Exact Sciences’ consolidated financial statements and related notes as of and for the year ended Dec. 31, 2021, the company’s independent registered public accountants may identify items that could cause final reported results to be materially different from the preliminary financial estimates presented herein.

Exact Sciences plans to report 2021 financial results during its February 2022 earnings call.

About Cologuard

The Cologuard test was approved by the FDA in August 2014, and results from Exact Sciences’ prospective 90-site, point-in-time, 10,000-patient pivotal trial were published in the New England Journal of Medicine in March 2014. The Cologuard test is included in the American Cancer Society’s (2018) colorectal cancer screening guidelines and the recommendations of the U.S. Preventive Services Task Force (2021) and National Comprehensive Cancer Network (2016). The Cologuard test is indicated to screen adults 45 years of age and older who are at average risk for colorectal cancer by detecting certain DNA markers and blood in the stool. Do not use the Cologuard test if you have had precancer, have inflammatory bowel disease and certain hereditary syndromes, or have a personal or family history of colorectal cancer. The Cologuard test is not a replacement for colonoscopy in high risk patients. The Cologuard test performance in adults ages 45-49 is estimated based on a large clinical study of patients 50 and older. The Cologuard test performance in repeat testing has not been evaluated.

The Cologuard test result should be interpreted with caution. A positive test result does not confirm the presence of cancer. Patients with a positive test result should be referred for diagnostic colonoscopy. A negative test result does not confirm the absence of cancer. Patients with a negative test result should discuss with their doctor when they need to be tested again. Medicare and most major insurers cover Cologuard. For more information about Cologuard, visit www.cologuardtest.com. Rx only.

About Oncotype DX

The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. In breast cancer, the Oncotype DX Breast Recurrence Score test is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. In prostate cancer, the Oncotype DX Genomic Prostate Score test predicts disease aggressiveness and further clarifies the current and future risk of the cancer prior to treatment intervention, and the Oncotype DX AR-V7 Nucleus Detect test helps determine which patients with metastatic castration-resistant prostate cancer (mCRPC) are resistant to androgen receptor (AR)-targeted therapies. The Oncotype DX AR-V7 Nucleus Detect test is performed by Epic Sciences at its centralized, CLIA-certified laboratory in San Diego and offered exclusively by Exact Sciences. The Oncotype MAP Pan-Cancer Tissue test is a rapid, comprehensive tumor profiling panel that aids therapy selection for patients with advanced, metastatic, refractory, or recurrent cancer. With more than 1 million patients tested in more than 90 countries, the Oncotype tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype tests, visit www.OncotypeIQ.com, www.MyBreastCancerTreatment.org or www.MyProstateCancerTreatment.org.

On January 9, 2022 Laekna Therapeutics reported that the investigational new drug (IND) application of a combination therapy for the phase 1/2 clinical trial in patients with solid tumors who have been refractory to treatment with PD-1/PD-L1 inhibitors has been approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China (Press release, Laekna Therapeutics, JAN 9, 2022, View Source [SID1234598447]). Laekna Therapeutics is an emerging innovative biopharmaceutical company focused on developing groundbreaking and innovative therapies to treat cancer and liver diseases. The IND approval marks a key milestone under the clinical research partnership Laekna and Innovent formed in July 2021.

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The imminent phase 1/2 dose escalation study will evaluate the efficacy and safety of the combination of afuresertib (LAE002), sintilimab and chemotherapy in patients with specific types of solid tumors who have been refractory to treatment with PD-1/PD-L1 inhibitors. The Principal Investigator of the study is Professor Shen Lin, Vice President of Peking University Hospital and Cancer Institute and Director of the Department of Gastrointestinal Oncology. The combination therapy includes Laekna Therapeutics’ pan-AKT kinase inhibitor afresertib, Innovent’s sintilimab, and albumin-bound paclitaxel or docetaxel.

The phase 1 study aims to evaluate the safety of the three-drug combination, and determine the recommended phase 2 dose (RP2D). The phase 2 study will aim to evaluate the clinical efficacy and safety of the combination therapy in patients who have been refractory to treatment with PD-1/PD-L1 inhibitors (monotherapy or in combination with other oncology drugs) and who have suffered from one of the following five types of tumors:

Non-small cell lung cancer (NSCLC)
Gastric cancer/gastro-oesophageal junction cancer (GC/GEJC)
Esophageal cancer (EsC)
Cervical cancer (CC)
Endometrial cancer (EC)
Professor Shen Lin explains, "As a serine/threonine kinase, AKT is a potential new target for cancer treatment. The results of multiple preclinical studies has showed that inhibiting AKT has the potential to restore the sensitivity of cancer cells to oncology therapies. Therapy resistance remains a common clinical problem and challenge for the further application of PD-1/PD-L1 blockade therapies despite their promising prospects. Statistics has showed that only some patients are estimated to have a positive response to PD-1/PD-L1 blockade therapies. In additional, for most patients with initial clinical response, acquired resistance remains a significant challenge. I have high expectations for this clinical trial involving an AKT inhibitor, and I hope it will provide a new treatment option for patients with specific solid tumors refractory to treatment with PD-1/PD-L1 inhibitors."

"After partnering with Innovent in July last year, we worked together closely to identify a development strategy and design the clinical study. With the support of our partners and Principal Investigator, we have succeeded in obtaining the IND approval from the CDE. For next step, our team will redouble our efforts to advance the clinical research," says Dr. Yue Yong, Chief Medical Officer of Laekna Therapeutics. "As immuno-oncology combination therapies have been approved for multiple types of early-stage cancers, patients’ survival and quality of life have been significantly improved. But still, quite a few patients are refractory to immunotherapies. Through this clinical trial, we will work with Innovent to explore the potential of afuresertib, sintilimab, and chemotherapy in the treatment of patients with solid tumors who have been refractory to immunotherapies. The success of this study is expected to benefit more cancer patients resistant to immunotherapies."

Laekna Therapeutics Chairman and CEO Dr. Chris Lu commented, "A document recently released by the CDE, ‘Guiding Principles for Clinical Research of Antitumor Pharmaceuticals Based on Clinical Value’, specifically mentions that ‘tumor resistance is a major challenge that cancer treatments and new medicines face during development’. These joint clinical trials conducted by Laekna Therapeutics and Innovent responds to the advice of those guiding principles, which state that ‘attention should be given to the needs of patients with refractory conditions in order to find a new generation of breakthrough antitumor medicines to overcome the tumor resistance, or antitumor combination treatments that can overcome the refractory condition’. The team at Laekna Therapeutics will do everything we can to make rapid progress in advancing these clinical trials."

About Afuresertib
Afuresertib (LAE002) is a Class 1 new drug candidate in clinical development, for which Laekna Therapeutics has obtained the global exclusive licenses from Novartis. It is a potent next-generation small molecule pan-AKT kinase inhibitor.

In recent years, AKT (a serine/threonine-protein kinase) has emerged as an important mechanism in oncology, as it plays an important role in regulating various cell functions such as metabolism, survival, proliferation, tissue invasion, and chemotherapy resistance. PTEN deletion and AKT/PIK3CA alteration may lead to excessive activation of the AKT signaling pathways, which is one of the key drivers for cancer growth. The increased activation of the AKT signaling pathway is particularly common in recurrent ovarian cancer, breast cancer, and prostate cancer.

About Sintilimab
Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab worldwide, to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved and included in the National Reimbursement Drug List (NRDL) for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy;
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of non-squamous non-small cell lung cancer;
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer;
In combination with bevacizumab biosimilar for the first-line treatment of unresectable or advanced hepatocellular carcinoma.
Additionally, sintilimab currently has three regulatory submissions accepted for review in NMPA, including:
In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma;
In combination with chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
In combination with bevacizumab biosimilar and chemotherapy for EGFR-mutated non-squamous NSCLC following EGFR-TKI treatment.
Additionally, two clinical studies of sintilimab have met their primary endpoints:
Phase 2 study as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of non-squamous non-small cell lung cancer.

On January 9, 2022 Amgen (NASDAQ: AMGN) reported that the European Commission (EC) has granted conditional marketing authorization for LUMYKRAS (sotorasib), a first-in-class KRASG12C inhibitor, for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and who have progressed after at least one prior line of systemic therapy (Press release, Amgen, JAN 9, 2022, View Source [SID1234598448]). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

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"The approval of LUMYKRAS, the first and only targeted therapy for KRAS G12C-mutated NSCLC with proven efficacy, has the potential to transform treatment outcomes for people in the European Union living with this notoriously difficult-to-treat cancer," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Amgen’s landmark scientific discovery allowed investigators to advance the first KRASG12C inhibitor into the clinic, and we look forward to bringing this critical innovation to more patients across the globe."

The EC decision follows the recommendation for approval by the Committee for Medicinal Products for Human Use (CHMP) and is based on the positive results from the Phase 2 CodeBreaK 100 clinical trial in NSCLC, the largest trial conducted to date for patients with the KRAS G12C mutation. LUMYKRAS 960 mg, administered orally once-daily, demonstrated an objective response rate of 37.1% (95% CI: 28.6-46.2) and a median duration of response (DoR) of 11.1 months. The most common adverse reactions were diarrhea (34%), nausea (25%), and fatigue (21%). The most common severe (grade ≥ 3) adverse reactions were increased alanine aminotransferase level (ALT; 5%), increased aspartate aminotransferase (AST; 4%), and diarrhea (4%).

NSCLC accounts for approximately 84% of the 2.2 million new lung cancer diagnoses globally each year, including approximately 400,000 new cases in Europe 1,2 KRAS G12C is one of the most prevalent driver mutations in NSCLC, with about 13-15% of European patients with non-squamous NSCLC having the KRAS G12C mutation.3,4 With EC approval, and subject to local reimbursement applications, clinicians in all European Union member countries, as well as Norway, Iceland, and Liechtenstein, will be able to offer LUMYKRAS to appropriate patients with NSCLC.

About LUMAKRAS/LUMYKRAS (sotorasib)
Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.5 LUMAKRAS/LUMYKRAS has demonstrated a positive benefit-risk profile with rapid, deep and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.6

Amgen is progressing the largest and broadest global KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, including triplets, with clinical trial sites spanning five continents. To date, over 4,000 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use.

In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval anywhere in the world with its approval in the U.S., under accelerated approval.

Regulatory approvals have also been received in the United Arab Emirates (LUMAKRAS), Switzerland (LUMYKRAS), and under the FDA’s Project Orbis in Canada (LUMAKRAS) and Great Britain (LUMYKRAS). Through Project Orbis, Amgen also has Marketing Authorization Applications (MAAs) for sotorasib in review in Australia, Brazil, Singapore and Israel. Additionally, Amgen has submitted MAAs in Japan, South Korea, Turkey, Taiwan, Colombia, Thailand, Mexico, Hong Kong, Saudi Arabia, Argentina, Kuwait and Qatar.

LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.7

About Non-Small Cell Lung Cancer and the KRAS G12C Mutation
Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.8 Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease and 5-year survival is only 7% for those with metastatic disease.9

KRAS G12C is the most common KRAS mutation in NSCLC.10 About 13% of patients with non-squamous NSCLC harbor the KRAS G12C mutation.4 Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. The outcomes with current therapies are suboptimal with a median progression-free survival of approximately 4 months following second-line treatment of KRAS G12C-mutated NSCLC.11

About CodeBreaK
The CodeBreaK clinical development program for Amgen’s drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.11 Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline.7 The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and results have been submitted for publication.12

CodeBreaK 200, the global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in KRAS G12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated, locally-advanced and unresectable or metastatic KRAS G12C-mutated NSCLC. The primary endpoint is progression-free survival and key secondary endpoints include overall survival, objective response rate, and patient-reported outcomes.

Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment. A Phase 2 randomized study will evaluate sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).

For information, please visit www.hcp.codebreaktrials.com.

Important EU/EEA Product Information

LUMYKRAS (sotorasib) as monotherapy is indicated for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and who have progressed after at least one prior line of systemic therapy.

Important EU/EEA Safety information

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Contraindications

LUMYKRAS is contraindicated in patients with a history of hypersensitivity to the active substance or to any of the excipients.

Special Warning and Precautions for Use

Hepatotoxicity: Sotorasib can cause hepatotoxicity, which may lead to drug-induced liver injury (DILI) and hepatitis. Sotorasib has been associated with transient elevations of serum transaminases (ALT and AST). These elevations improved or resolved with dose modification or permanent discontinuation of treatment and did not result in any cases of liver failure or fatal cases in clinical studies. Among patients who experienced hepatotoxicity, 38% had hepatotoxicity leading to dose interruption or dose reduction. Overall, 26% of patients with hepatotoxicity received concurrent corticosteroids. Cases of liver enzyme increase can be asymptomatic. Patients should be monitored for liver function (ALT, AST, and total bilirubin) prior to the start of LUMYKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Based on the severity of the laboratory abnormalities, treatment with LUMYKRAS must be stopped until recovered to ≤ grade 1 or to baseline grade, and the dose must either be modified or permanently discontinue treatment as recommended (see section 4.2).

Interstitial Lung Disease (ILD)/pneumonitis: ILD/pneumonitis occurred in patients treated with LUMYKRAS with prior exposure to immunotherapy or radiotherapy (see section 4.8). Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g. dyspnoea, cough, fever). Immediately withhold LUMYKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMYKRAS if no other potential causes of ILD/pneumonitis are identified (see section 4.2).

Lactose intolerance: LUMYKRAS contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose–galactose malabsorption should not take this medicinal product.

Adverse Reactions

The most common adverse reactions were diarrhoea (34%), nausea (25%) and fatigue (21%). The most common severe adverse reactions were increased alanine aminotransferase (ALT) (5%), increased aspartate aminotransferase (AST) (4%), and diarrhoea (4%). The most common adverse reactions leading to permanent discontinuation of treatment were increased ALT (1%) and increased AST (1%) and drug-induced liver injury (1%). The most common adverse reactions leading to dose modification were increased ALT (6%), diarrhoea (6%), increased AST (6%), nausea (3%), increased blood alkaline phosphatase (3%) and vomiting (2%).

LUMAKRAS (sotorasib) U.S. Indication

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

LUMAKRAS (sotorasib) Important U.S. Safety Information

Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis

LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions

The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.
Drug Interactions

Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.
Please see LUMAKRAS full Prescribing Information.

About Amgen Oncology
At Amgen Oncology, our mission to serve patients drives all that we do. That’s why we’re relentlessly focused on accelerating the delivery of medicines that have the potential to empower all angles of care and transform lives of people with cancer.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we’re advancing oncology at the speed of life.

For more information, follow us on www.twitter.com/amgenoncology.

On January 7, 2022 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Ultragenyx Pharmaceutical Inc. reported a license and collaboration agreement for Ultragenyx to clinically develop, commercialize and distribute Evkeeza (evinacumab) in countries outside of the U.S (Press release, Regeneron, JAN 7, 2022, View Source [SID1234598413]). This includes the European Economic Area, where Evkeeza was approved in June 2021 as a first-in-class therapy for use together with diet and other low-density lipoprotein-cholesterol (LDL-C) lowering therapies to treat adults and adolescents aged 12 years and older with homozygous familial hypercholesterolemia (HoFH). Regeneron discovered and developed Evkeeza, and launched the medicine in the U.S. in February 2021 when it was approved by the FDA.

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"Evkeeza is a transformational medicine for those living with homozygous familial hypercholesterolemia, as previous therapies were insufficient for many patients who still faced extremely high LDL cholesterol levels and treatment-related tolerability issues," said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer and President of Regeneron. "With its focus on rare, debilitating genetic conditions, Ultragenyx is an ideal partner for us, and we look forward to working together to bring this much needed medicine to patients around the world."

Under the terms of the agreement, Regeneron will receive a $30 million upfront payment and is eligible to receive up to $63 million in additional potential regulatory and sales milestones. Ultragenyx will receive the rights to develop, commercialize and distribute the medicine in countries outside of the U.S. and make payments to Regeneron based on net sales. Ultragenyx will share in certain costs for global trials led by Regeneron and also have the right to continue to clinically develop Evkeeza in countries outside of the U.S. for HoFH and other potential indications.

Regeneron has also granted Ultragenyx an exclusive option to negotiate a separate agreement to collaborate on the development and commercialization outside of the U.S. of Regeneron’s investigational antibody currently in Phase 2/3 development for the treatment of the ultra-rare disease, fibrodysplasia ossificans progressiva (FOP) under terms to be agreed upon by both companies.

"Evkeeza utilizes a novel, potent biological mechanism to significantly reduce LDL cholesterol levels beyond historical standard of care for people with HoFH. This is a highly complementary partnership that combines Regeneron’s bold science with our proficiency in rare disease," said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. "We have developed our commercial expertise to support patient identification and access across regions and we believe we can make a real difference for the HoFH community outside of the U.S."

Regeneron will continue to solely commercialize Evkeeza in the U.S., where more patients with HoFH are now being treated with Evkeeza than the prior standard-of-care. In countries outside of the U.S., Ultragenyx will be responsible for commercialization efforts.

About Homozygous Familial Hypercholesterolemia (HoFH)
HoFH, also known as homozygous FH, is an ultra-rare inherited condition that affects 1 in 160,000 to 300,000 people worldwide. HoFH occurs when two copies of the familial hypercholesterolemia (FH)-causing genes are inherited, one from each parent, resulting in dangerously high levels (>400 mg/dL) of LDL-C, or bad cholesterol. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years.

About Evkeeza (evinacumab)
Evkeeza is a fully human monoclonal antibody that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3), a protein that plays a key role in lipid metabolism. Regeneron scientists discovered the angiopoietin gene family more than two decades ago. Human genetics research published in New England Journal of Medicine (NEJM) in 2017 by scientists from the Regeneron Genetics Center found that patients whose ANGPTL3 gene did not function properly (called a "loss-of function mutation") have significantly lower levels of key blood lipids, including LDL-C, and that this is associated with a significantly lower risk of coronary artery disease.

In the U.S., Evkeeza is indicated as an adjunct to other LDL-C lowering therapies for the treatment of adult and pediatric patients, aged 12 years and older with HoFH. The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH). The effect of Evkeeza on cardiovascular morbidity and mortality has not been determined.

Evkeeza was invented using Regeneron’s VelocImmune technology and is the first ANGPTL3-targeted therapy approved by the European Commission and U.S. FDA. The approvals were based on results from the Phase 3 ELIPSE HoFH trial, which was published in the NEJM in August 2020.

The generic name for Evkeeza in its approved U.S. indications is evinacumab-dgnb, with dgnb the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. FDA.

About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately a quarter of all original, FDA-approved fully human monoclonal antibodies currently available. This includes Evkeeza (evinacumab-dgnb), REGEN-COV (casirivimab and imdevimab), Dupixent (dupilumab), Libtayo (cemiplimab-rwlc), Praluent (alirocumab), Kevzara (sarilumab) and Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn).

IMPORTANT SAFETY INFORMATION FOR EVKEEZA (evinacumab-dgnb) INJECTION

Who should not use EVKEEZA?

Do not use EVKEEZA if you are allergic to evinacumab-dgnb or to any of the ingredients in EVKEEZA.

Before receiving EVKEEZA, tell your healthcare provider about all of your medical conditions, including if you:

Are pregnant or plan to become pregnant. EVKEEZA may harm your unborn baby. Tell your healthcare provider if you become pregnant while using EVKEEZA. People who are able to become pregnant:
Your healthcare provider may do a pregnancy test before you start treatment with EVKEEZA
You should use an effective method of birth control during treatment and for at least 5 months after the last dose of EVKEEZA. Talk with your healthcare provider about birth control methods that you can use during this time.
Are breastfeeding or plan to breastfeed. It is not known if EVKEEZA passes into your breast milk. You and your healthcare provider should decide if you will receive EVKEEZA or breastfeed.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of EVKEEZA?

EVKEEZA can cause serious side effects, including:
Allergic reactions (hypersensitivity), including a severe reaction known as anaphylaxis. Tell your healthcare provider right away if you get any of the following symptoms: swelling (mainly of the lips, tongue or throat which makes it difficult to swallow or breathe), breathing problems or wheezing, feeling dizzy or fainting, rash, hives, and itching.

The most common side effects of EVKEEZA include symptoms of the common cold, flu-like symptoms, dizziness, pain in legs or arms, nausea, and decreased energy.

Tell your healthcare provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of EVKEEZA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

On January 7, 2022 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported that John Climaco, Chief Executive Officer of CNS Pharmaceuticals, will present at the virtual H.C. Wainwright BioConnect Conference taking place January 10-13, 2022 (Press release, CNS Pharmaceuticals, JAN 7, 2022, https://www.prnewswire.com/news-releases/cns-pharmaceuticals-to-present-at-the-hc-wainwright-bioconnect-conference-301456183.html [SID1234598430]).

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A video webcast of the presentation will be accessible for viewing on-demand beginning on Monday, January 10, 2022, at 7:00 AM ET for those registered for the event and will be available on the Events page in the Investors section of the Company’s website (www.cnspharma.com). The webcast replay will be archived for 90 days following the event.