On January 10, 2022 Bristol Myers Squibb (NYSE:BMY) reported that it will highlight progress against the Company’s growth strategy and outlook for 2022 during a presentation scheduled at 7:30 a.m. ET at the 40th Annual J.P. Morgan Healthcare Conference (Press release, Bristol-Myers Squibb, JAN 10, 2022, View Source [SID1234598451]).

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"We are successfully transforming the company by further diversifying our product portfolio, launching breakthrough new medicines that benefit our patients and advancing a robust product pipeline that will help us deliver sustained growth," said Giovanni Caforio, M.D., board chair and chief executive officer, Bristol Myers Squibb. "We are entering 2022 excited about the growth opportunities in our in-line brands and new product portfolio. With our strong financial position, we continue to invest in internal and external innovation to further enhance and diversify our pipeline, while delivering new medicines to patients with serious disease and creating long-term value for our shareholders."

Highlights of the presentation

Bristol Myers Squibb’s presentation will focus on four key drivers positioning the Company for sustained growth and value creation, helping to offset losses of exclusivity in the coming years. The drivers build upon a strong foundation of existing in-line products, including Opdivo(nivolumab), Yervoy(ipilimumab)and Eliquis(apixaban), which are expected to contribute approximately $8-$10 billion in revenue growth during the period of 2020-2025. The drivers include:

New product portfolio with significant growth potential. With six recent launches (Abecma(idecabtagene vicleucel),Breyanzi (lisocabtagene maraleucel), Inrebic(fedratinib), Onureg(azacytidine), Reblozyl (luspatercept-aamt)andZeposia(ozanimod)) and three launches anticipated in 2022 (relatimab and nivolumab fixed dose combination,mavacamten, deucravacitinib), Bristol Myers Squibb’s renewed and diverse product portfolio has the potential to deliver:
$10-$13 billion of risk-adjusted revenue in 2025;
More than $25 billion non-risk-adjusted revenue in 2029; and
At least $4 billion of non-risk adjusted revenue in 2029 for each of the following recent or anticipated new products: Reblozyl,relatimab and nivolumab fixed dose combination,mavacamten and deucravacitinib.
Promising mid- to late-stage assets with large commercial opportunities. Bristol Myers Squibb has seven key assets in its mid-to-late-stage pipeline focused on disease areas where there are meaningful opportunities to improve outcomes for patients. These assets include milvexian, which has demonstrated a differentiated profile as a next generation anti-thrombotic therapy, and two novel CELMoDs, iberdomide and CC-92480, with potential to be new foundational treatments in multiple myeloma.
Powerful innovation engine driving a broad early-stage pipeline. With more than 50 assets in its early-stage pipeline and the opportunity for more than 20 proof of concept decisions over the next three years, Bristol Myers Squibb is advancing one of the most exciting pipelines in the industry, amplified by the Company’s strong external partnerships.
Strong cash flow generation provides significant financial strength and flexibility. Bristol Myers Squibb plans to leverage its $45-$50 billion in expected free cash flow between 2022 and 2024 to execute a consistent, balanced capital allocation strategy, prioritizing business development and returning cash to shareholders through the Company’s dividend and share repurchase program. The Company remains committed to maintaining a strong investment grade rating and reducing debt.
Announcement of Accelerated Share Repurchase Program

Today, the Company also announced that it plans to execute an accelerated share repurchase (ASR) agreement during the first quarter of 2022 to repurchase up to $5 billion of Bristol Myers Squibb common stock. The ASR is part of the Company’s previously disclosed multi-year $15 billion share repurchase authorization.

The total number of shares ultimately repurchased will be determined upon final settlement and will be based on a discount to the volume-weighted average price of Bristol Myers Squibb’s common stock during the ASR period.

Introduction of 2022 Financial Guidance

Bristol Myers Squibb is introducing the following guidance metrics for 2022:

Total company revenues are expected to be approximately $47 billion, representing an increase in the low-single digits.
Sales from key loss of exclusivity (LOE) brands, which represent Revlimid and Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin-bound), are expected to be approximately $10.5 billion. Revlimid sales are expected to be $9.5-$10 billion.
Our Continuing Business is expected to grow in the low-double digits and contribute approximately $36.5 billion in 2022 with growth from the new product portfolio and in-line products.
The Company’s non-GAAP EPS guidance is expected to be in the range of $7.65 – $7.95. Non-GAAP EPS guidance assumes current exchange rates.
The Company intends to provide additional 2022 financial guidance during its 2021 fourth quarter earnings conference call on February 4, 2022.

The 2022 financial guidance excludes the impact of any potential future strategic acquisitions and divestitures, and any specified items that have not yet been identified and quantified. The 2022 non-GAAP EPS guidance is further explained under "Use of Non-GAAP Financial Information." The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

Reaffirms Long-Term Financial Targets

Bristol Myers Squibb is also reaffirming its 2020-2025 long-term revenue and operating margin targets communicated in January 2021. The Company is extending its previously communicated guidance for free cash flow for an additional year as detailed below:

Expects low to mid-single digit revenue CAGR and low double-digit revenue CAGR excluding Revlimid and Pomalyst (pomalidomide)at constant exchange rates
Expects to maintain low to mid-40s percent non-GAAP operating margin
Expects significant cash flow generation of $45-$50 billion dollars from 2022-2024 compared to prior guidance of $45-$50 billion dollars from 2021-2023
This financial guidance excludes the impact of any potential future strategic acquisitions and divestitures as well as any specified items as discussed under "Use of Non-GAAP Financial Information." There is no reliable or reasonably estimable comparable GAAP measures for this non-GAAP financial guidance. The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

Company and Webcast Information

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook, and Instagram.

Investors and the general public are invited to listen to a live webcast of the J.P. Morgan presentation at View Source Materials related to the presentation will be available at the same website at the start of the live webcast. An archived edition of the presentation will be available later that day.

Corporate-Financial News

Use of Non-GAAP Financial Information

In discussing financial results and guidance, the company refers to financial measures that are not in accordance with U.S. Generally Accepted Accounting Principles (GAAP), including non-GAAP EPS, operating margin and free cash flow. These non-GAAP financial measures may provide investors with additional useful information. For example, non-GAAP earnings and EPS information are indications of the company’s baseline performance before items that are considered by us to not be reflective of the company’s ongoing results. This information is among the primary indicators that we use as a basis for evaluating performance, allocating resources, setting incentive compensation targets and planning and forecasting for future periods. In addition, non-GAAP operating margin, which is operating income excluding certain specified items as a percentage of revenues, is relevant and useful for investors because it allows investors to view performance in a manner similar to the method used by our management and make it easier for investors, analysts and peers to compare our operating performance to other companies in our industry and to compare our year-over-year results.

Because the non-GAAP financial measures are not calculated in accordance with GAAP, they should not be considered superior to and are not intended to be considered in isolation or as a substitute for the related GAAP financial measures and may not be the same as or comparable to similarly titled measures presented by other companies due to possible differences in method and in the items being adjusted. We encourage investors to review our financial statements and publicly-filed reports in their entirety and not to rely on any single financial measure.

Also note that a reconciliation of the forward-looking non-GAAP EPS, free cash flow, and operating margin measures is not provided due to no reasonably accessible or reliable comparable GAAP measures and the inherent difficulty in forecasting and quantifying such measures that are necessary for such reconciliation. Namely, we are not able to reliably predict the impact of specified items or currency exchange rates beyond the next twelve months. As a result, the reconciliation of these non-GAAP measures to the most directly comparable GAAP measures is not available without unreasonable effort. In addition, the company believes such a reconciliation would imply a degree of precision and certainty that could be confusing to investors. The variability of the specified items may have a significant and unpredictable impact on our future GAAP results.

Website Information

We routinely post important information for investors on our website, BMS.com, in the "Investors" section. We may use this website as a means of disclosing material, non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investors section of our website, in addition to following our press releases, SEC filings, public conference calls, presentations and webcasts. We may also use social media channels to communicate with our investors and the public about our company, our products and other matters, and those communications could be deemed to be material information. The information contained on, or that may be accessed through, our website or social media channels are not incorporated by reference into, and are not a part of, this document.

On January 10, 2022 LUMICKS, a next generation life science tools provider, reported that two major centers of excellence in cancer immunology have adopted LUMICKS’ z-Movi Cell Avidity Analyzer instrument (Press release, LUMICKS, JAN 10, 2022, View Source;utm_medium=rss&utm_campaign=z-movi-cell-avidity-analyzer-fred-hutch-oxford-university [SID1234598450]).

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The first placement is at Fred Hutchinson Cancer Research Center ("Fred Hutch") in Seattle, Washington, USA, a leading research institute dedicated to the eradication of cancer. The instrument is housed at the Immune Monitoring Core Facility and serves multiple immuno-oncology and cell therapy research groups from the Center to accelerate immunotherapy development for cancer treatments.

The second z-Movi is placed at the University of Oxford, in Oxford, UK, in the lab of Prof. Tim Elliott, a world leader in the field of antigen presentation and T cell biology. The teams of Prof. Elliott and Prof. Persephone Borrow are using the instrument to investigate a broad range of T cell–target interactions including the potency and longevity of T cells in solid tumors.

"The z-Movi Cell Avidity Analyzer provides an excellent platform for quantitating the avidity of interactions occurring between T cells and cognate antigen-presenting target cells during the induction and effector phases of an immune response." said Prof. Elliott and Prof. Borrow. "This enables dissection of attributes of both T cells and their interaction partners that influence the response to viral infections and cancer."

"We are delighted that our z-Movi instrument will be adopted into the workflows at Fred Hutch and University of Oxford, two institutions devoted to the development of promising immunotherapeutic strategies," said LUMICKS CSO Dr. Andrea Candelli. "At LUMICKS, we are focused on developing new technologies that help cancer researchers discover new therapies. We believe that cell avidity measurements provide unique insights into the mechanism of action of cell therapy products, ultimately leading to higher success rates for novel cancer immunotherapies."

On January 10, 2022 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that it has initiated a Phase I study in China of HMPL-760, a highly potent, selective, and reversible inhibitor with long target engagement against Bruton’s tyrosine kinase ("BTK"), including wild-type and C481S-mutated BTK. The first patient received their first dose on January 4, 2022.

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The clinical study is a multi-center, open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy profile of HMPL-760. The study is enrolling patients with previously treated chronic lymphocytic leukemia/​small lymphocytic lymphoma (CLL/SLL) or other types of Non-Hodgkin Lymphoma ("NHL"), including patients treated with a prior regimen containing a BTK inhibitor, whose disease carries either wild-type BTK or acquired resistance to first generation BTK inhibitors due to additional mutations to BTK.

An initial dose escalation stage to determine the maximum tolerated dose (MTD) and/or the recommended Phase II dose ("RP2D") is planned, to be followed by a dose expansion phase where patients will receive HMPL‑760 to further evaluate the safety, tolerability, and clinical activity at the RP2D. Approximately 100 patients are expected to be enrolled.

HMPL-760 is HUTCHMED’s fifth investigational drug candidate targeting hematological malignancies in clinical development. Amdizalisib (HMPL-689, targeting the delta isoform of phosphoinositide 3-kinase or PI3K delta) and HMPL-523 (targeting spleen tyrosine kinase or Syk) are also being studied in several Phase II trials against B-cell dominant malignancies. Phase II registration studies are underway in China for amdizalisib in patients with follicular lymphoma (FL), for which it has been granted Breakthrough Therapy Designation in China, and marginal zone lymphoma (MZL).

In addition to the three BCR inhibitors, for hematological malignancies HUTCHMED is also developing its in-house discovered drug candidate HMPL-306, a dual-inhibitor of mutant isocitrate dehydrogenase 1 and 2, and tazemetostat, a methyl­transferase inhibitor of EZH2 (being developed in Greater China by HUTCHMED pursuant to a strategic collaboration with Epizyme).

About BTK and Non-Hodgkin Lymphoma
BTK is a key component of the B-cell receptor signaling pathway and is an important regulator of cell prolifera­tion and cell survival in various lymphomas. The abnormal activation of B-cell receptor signaling is closely related to the development of B-cell type hemato­logical cancers, which represent approximately 85% of all NHL cases.[1] BTK is considered a validated target for drugs that aim to treat certain hemato­logical cancers, however C481S mutation of BTK is a known resistance mechanism for first and second generation BTK inhibitors. In 2020, approximately 93,000 new cases of NHL are estimated to have been diagnosed in China.[2]

About HMPL-760
HMPL-760 is an investigational, highly selective, non-covalent, third-generation inhibitor of BTK, both wild-type and C481S mutant enzymes, with pre-clinical data suggesting high target specificity and higher potency versus first generation BTK inhibitors. BTK C481S mutation plays an important role in resistance to certain BTK inhibitors.[3],[4]

HMPL-760 is HUTCHMED’s eleventh innovative potential oncology drug candidate to enter clinical develop­ment. HUTCHMED currently retains all rights to HMPL-760 worldwide.

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 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.