On August 30, 2022 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a platform-driven, clinical-stage biotechnology company transforming the discovery and development of novel antibody-based therapies, reported financial results for the six months ended June 30, 2022 and provided corporate updates (Press release, Adagene, AUG 30, 2022, View Source [SID1234618819]).

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"We are prioritizing development of two anti-CTLA-4 antibodies, which have best-in-class profiles and are on track to deliver proof-of-concept clinical results in combination therapy in 2023. Anti-CTLA-4 therapy is known for dose dependent toxicity, making it extremely difficult to optimize dosing levels, dosing frequency and dosing intervals for prevailing anti-CTLA-4 therapy, especially in combination therapy with anti-PD-1. We have solved this problem with differentiated candidates suitable for the massive market opportunity for next generation anti-CTLA-4 therapies, increasing market penetration into known and new indications with enhanced safety and efficacy, especially for tumor types not addressed with the currently available therapy, and rapid entry into new markets such as China with few approved indications for anti-CTLA-4 in combination with widely accessible anti-PD-1 therapy," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "We are also excited to advance our next generation anti-CD137 agonistic antibody, ADG206, into clinic given its first- and best-in-class potential in both monotherapy and in combination with multiple agents."

Dr. Luo continued: "On the longer-term horizon, we have developed a portfolio of masked, bispecific T cell engagers (TCEs) for tumor directed T cell therapies, armed with proprietary, tailor-made anti-CD3 and CD28 by leveraging our NEObody and SAFEbody technologies, that aim to push the boundaries of what is possible with TCEs – to achieve safe, potent and durable responses for patients by combining our novel modalities with the fundamental pathways across the cancer immunity cycle."

He concluded: "Building on success of existing technology licensing deals, we are also pursuing additional collaboration agreements that leverage our pipeline, our integrated AI-powered antibody discovery platform, and our SAFEbody precision masking technology, to bring potential non-dilutive funding to Adagene. We believe that the combination of our proprietary technology platforms and our highly differentiated clinical and preclinical pipelines presents us with many value-creating levers to navigate today’s turbulent financial markets."

PIPELINE & BUSINESS HIGHLIGHTS

ADG116 (anti-CTLA-4 NEObody targeting a unique epitope)

Encouraging efficacy demonstrated as a single agent and in combination with anti-PD-1:
Observed one partial response with ADG116 monotherapy in a tumor type where no anti-CTLA-4 therapy is currently approved.
Observed one confirmed rapid complete response with repeat dosing for ADG116 in combination with toripalimab in a tumor type where no anti-CTLA-4 therapy is currently approved.
Presentation of data from this phase 1b/2 trial will take place at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 37th Annual Meeting (SITC 2022) in Boston, November 8-12, 2022.
For competitive reasons, Adagene is currently not disclosing the dose or tumor types of these objective responses.
Compelling safety demonstrated as a single agent and in combination with anti-PD-1:
Completed monotherapy dose escalation of ADG116 in 30 patients up to 15 mg/kg administered every three weeks with repeat dosing, and continued to enroll patients in dose expansion at 10 mg/kg.
Only one dose-limiting toxicity event reported at ESMO (Free ESMO Whitepaper)-IO 2021 for the 10 mg/kg dose. As of this release, no additional or late-onset dose-limiting toxicities reported with ADG116 monotherapy, including in patients who received more than four cycles.
A safety review committee cleared advancement to dose expansion with 3 mg/kg of ADG116 for combination cohorts with toripalimab.
Continued advancement of combinations with anti-PD-1 or anti-CD137:
Completing dose escalation of ADG116 in combination with the anti-PD-1 antibody, pembrolizumab (ADG116-P001 / KEYNOTE-C97). Presentation of data from this phase 1b/2 trial will take place at SITC (Free SITC Whitepaper) 2022.
Evaluation ongoing of ADG116 in combination with the anti-CD137 therapy, ADG106, to optimize the dose and schedule for this novel, proprietary combination. Adagene is a global leader in exploring the synergistic clinical effects for the dual pathway targeting CTLA-4 and CD137 given the compelling preclinical rationale for this powerful combination.
Paving the way for combination trials in China, advanced dose escalation to 10 mg/kg in phase 1 monotherapy trial (ADG116-1002). A significant untapped clinical and market opportunity exists for the proven combination of anti-CTLA-4 and anti-PD-1 therapies as the combination is only approved in one tumor type in China.
ADG126 (anti-CTLA-4 SAFEbody targeting a unique epitope with precision masking)

Compelling clinical safety demonstrated at unprecedented dosing levels with repeat dosing:
Completed monotherapy dose escalation of ADG126 in 19 patients up to 20 mg/kg administered every three weeks with repeat dosing, and continued to enroll patients in dose expansion at 10 mg/kg.
ADG126 monotherapy was well tolerated with no dose-limiting toxicities or treatment-related serious adverse events observed following repeat dosing across all dose levels, as reported in an abstract at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting.
Clinical evaluation with anti-PD-1 therapies is ongoing to establish the dose and schedule for phase 2 combination cohorts. In combination cohorts with toripalimab, the safety review committee has cleared the 6 mg/kg dose administered every three weeks, approved dose expansion at 6 mg/kg, and recommended further dose escalation to 10 mg/kg, the highest dose level ever reported for the combination of anti-CTLA-4 and anti-PD-1 therapies.
Encouraging antitumor activity observed as monotherapy in cold tumors:
In a cohort of heavily pre-treated patients, ADG126 monotherapy resulted in durable reductions in target lesions over 20% in two patients with cold tumors:
One ovarian cancer patient who experienced significant, continued reduction of an established ovarian cancer biomarker, CA125, dropping 90% to within the normal range for full clinical benefit after receiving up to 18 cycles of treatment at 1 mg/kg, as of this release.
One uveal melanoma patient who received prior immuno-oncology treatment, having progressed after the combination of nivolumab and ipilimumab.
Updated interim results will be presented in a poster on September 12 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 in Paris, September 9 – 13, 2022
Both monotherapy and combination trials continue to enroll patients with advanced, metastatic tumors in the US, China and APAC, evaluating optimized doses of ADG126 in targeted tumors.
Pharmacokinetics show effectiveness of precision masking technology:
In monotherapy evaluation, ADG126 plasma pharmacokinetics (PK) were approximately linear and activated ADG126 accumulated steadily during repeat dosing across different dose levels.
This reflects prolonged exposures of activated ADG126 in the tumor microenvironment (TME), with cleaved ADG126 in plasma on average accumulating >2-fold during repeat dosing.
ADG106 (agonistic anti-CD137 NEObody)

Given prioritization of anti-CTLA-4 programs, combination trial with toripalimab in China is winding down:
Results from the phase 1b/2 trial (ADG106-1008) in China evaluating ADG106 in combination with toripalimab, showed one observed partial response in a nasopharyngeal carcinoma (NPC) patient out of 20 patients enrolled. Currently, four patients remain on therapy.
Given prioritization of its two anti-CTLA-4 clinical programs and potential of its next generation anti-CD137 therapy, ADG206, Adagene is winding down the ADG106-1008 trial and does not intend to proceed with the previously planned trial of ADG106 and pembrolizumab.
Focusing clinical development on investigator-initiated trials (IITs) in selected indications:
Reflecting its strategic presence and collaborations in Singapore, Adagene continues to support the ongoing IITs in Singapore and explore the anti-CD137 opportunity with ADG106 in selected indications in a combination setting, including:
An ongoing phase 1b/2 clinical trial (ADG106-T6001) evaluating ADG106 in combination with the anti-PD-1 antibody, nivolumab, for patients with advanced non-small cell lung cancer (NSCLC) who have progressed after prior treatment. Dose escalation is complete and dose expansion is ongoing.
An ongoing Phase 1b/2 clinical trial (ADG106-T6002) evaluating ADG106 in combination with neoadjuvant chemotherapy (doxorubicin and cyclophosphamide followed by paclitaxel) in patients with early-stage, HER2 negative breast cancer.
ADG206 (masked, IgG1 FC engineered anti-CD137 POWERbody)

On track for clinical development as a next generation anti-CD137 candidate that combines masking, Fc-engineering and novel epitope to deliver balance between safety and efficacy:
Adagene submitted a Human Research Ethics Committee (HREC) regulatory filing in Australia to advance this anti-CD137 POWERbody, ADG206, into a phase 1 clinical trial in patients with advanced metastatic solid tumors.
Patient dosing is planned in early 2023.
ADG206 is designed to solve the safety and efficacy challenges of anti-CD137 therapy, leveraging the same novel epitope as ADG106 and learnings from development of urelumab (another company’s anti-CD137 targeting antibody), which showed single agent clinical efficacy and dose-dependent liver toxicity in clinic.
Preclinical data demonstrated that ADG206 was well tolerated and had robust anti-tumor activity as a single agent in multiple tumor models, with approximately 4-fold stronger anti-CD137 agonistic activity of its activated form than a urelumab analog; ADG206 also demonstrated enhanced anti-tumor activity in combination with other agents, including checkpoint inhibitors and anti-CTLA-4 therapy.
Preclinical Discovery Programs

ADG153: Given updated program timelines and ongoing business development activities, Adagene now plans the regulatory submission for its masked, IgG1 anti-CD47 SAFEbody, ADG153, in the first half of 2023. This candidate is differentiated by its strong antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity designed to realize the full potential of anti-CD47 therapy for both hematologic and solid tumor indications. Preclinical data demonstrated that ADG153 IgG1 was well tolerated, did not induce human hemagglutination and significantly reduced anemia-related and antigen sink liabilities; ADG153 IgG1 also demonstrated greater anti-tumor activity than the benchmark (magrolimab analog).
American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022: Data demonstrated the potential best-in-class profiles for three differentiated preclinical product candidates in IND-enabling studies (ADG206, ADG153, ADG138), which all apply SAFEbody precision masking technology. The robust preclinical poster presentations for these and other product candidates are available on the Publications page of the company’s website.
CD28 T-cell engagers (TCEs): Data at AACR (Free AACR Whitepaper) introduced a new capability for Adagene’s proprietary bispecific TCEs with CD28. CD28 bispecific POWERbody TCEs exhibit enormous potential to fulfill the promises of safe and durable T cell-mediated synergistic immunotherapies when combined with CD3 bispecific TCEs and/or checkpoint inhibitors. Preclinical data demonstrated the potential to mitigate the serious safety concerns of CD28 activation and make custom designed antibodies targeting a highly conserved epitope with broad species reactivity. Multiple tumor associated antigen (TAA) x CD28 POWERbodies are in progress, such as B7-H3xCD28 and TROP2xCD28, which can also be combined with the company’s CD3 TCEs and/or checkpoint inhibitors to achieve safe, powerful and durable immunotherapy for solid tumors. The full poster presentation may be viewed here.
Collaborations

Sanofi: Established a technology licensing agreement with Sanofi in March 2022 to generate masked versions of antibodies provided by Sanofi, including monoclonal and bispecific candidate antibodies, with a potential transaction value of US$2.5 billion. The collaboration includes an upfront payment of US$17.5 million received in April 2022 for the initial two programs (US$8.75 million per program), an option fee for two additional programs, potential milestone payments of up to US$2.5 billion (US$625 million per program), and tiered royalties.
Exelixis: Received a US$3.0 million milestone payment from Exelixis in January 2022 for the successful nomination of lead SAFEbody candidates for one of the collaboration programs and an additional $1.1 million upfront payment in June 2022, based on a technology licensing agreement to develop novel masked antibody-drug conjugate candidates. Terms of the agreement, which was executed in February 2021, include an upfront payment of US$11 million for two programs, potential milestones and tiered royalties.
China: Advanced global partnerships and collaboration with Sanjin and Dragon Boat Biopharmaceutical for two antibodies out-licensed in Greater China, including an anti-PD-L1 (ADG104) in phase 2 development, and a novel anti-CSF-1R (ADG125/BC006) in phase 1.
Corporate

Adagene is making progress to evaluate business processes that meet the requirements of the Holding Foreign Companies Accountable Act (HFCAA) and the Accelerating Holding Foreign Companies Accountable Act (AHFCAA) in the event that AHFCAA becomes enacted prior to the filing of annual report for the year of 2023 on Form 20-F. The company is closely monitoring the status and implications of HFCAA and AHFCAA in order to take decisive action to minimize its impact on the company.
Adagene continues to streamline its operations while focusing on its most advanced and promising clinical and preclinical programs to reduce its cash burn.
UPDATED MILESTONES & OUTLOOK

Adagene is updating its business outlook to reflect prioritization of its anti-CTLA-4 clinical development programs and achievement of meaningful milestones with its current cash resources. Based on current plans, Adagene expects its cash balance to sufficiently fund operations into late 2024, with the following upcoming milestones:

2022

Present ADG126 monotherapy dose escalation data at ESMO (Free ESMO Whitepaper) 2022
Present additional ADG116 data at SITC (Free SITC Whitepaper) 2022
ADG116 results of dose escalation in combination with anti-PD-1 therapy to establish the dose(s) and schedule(s) for dose expansion; advance phase 2a dose expansion cohorts in targeted tumors
ADG126 results of dose escalation in combination with anti-PD-1 therapy to establish the dose(s) and schedule(s) for dose expansion; advance phase 2a dose expansion cohorts in targeted tumors
2023

ADG116 phase 2a proof-of-concept data from combination dose expansion cohorts
ADG126 phase 2a proof-of-concept data from combination dose expansion cohorts
Establish registration path and strategy (e.g., recommended phase 2 dose, indication and design) for phase 2/3 pivotal trial of anti-CTLA-4 in combination with anti-PD-1 therapy in targeted tumors
Initiate patient dosing in ADG206 phase 1 trial
Submit IND or equivalent for ADG153, and initiate phase 1 trial
Results from IIT combination studies of ADG106
Additional collaborations and/or technology licensing agreements
FINANCIAL HIGHLIGHTS

Cash and Cash Equivalents:
Cash and cash equivalents were US$168.0 million as of June 30, 2022, compared to US$174.4 million as of December 31, 2021. The 2022 cash balance includes an upfront payment of US$17.5 million from Sanofi, and a milestone payment of US$3.0 million and upfront payment of US$1.1 million from Exelixis, related to Adagene’s respective collaboration and technology licensing agreements with those companies.

Net Revenue:
Net revenue was US$3.9 million for the six months ended June 30, 2022, compared to US$1.4 million for the same period in 2021. The increase was related to revenue recognized due to fulfillment of performance obligations over time associated with the collaboration and technology licensing agreement with Sanofi to develop antibody-based therapies. Due to the Sanofi and Exelixis collaborations, contract liabilities also increased to US$20.2 million as of June 30, 2022, compared to US$5.5 million as of December 31, 2021.

Research and Development (R&D) Expenses:
R&D expenses were US$45.1 million for the six months ended June 30, 2022, compared to US$31.5 million for the same period in 2021. The rise in R&D expenses was primarily due to increased R&D activities for the company’s clinical programs, as well as preclinical testing for candidates in the IND-enabling phase.

Administrative Expenses:
Administrative expenses were US$6.8 million for the six months ended June 30, 2022, compared to US$7.4 million for the same period in 2021. The decrease was primarily due to reduction in share-based compensation expenses.

Net Loss:
The net loss attributable to Adagene Inc.’s shareholders was US$47.6 million for the six months ended June 30, 2022, compared to US$37.2 million for the six months ended June 30, 2021.

Ordinary Shares Outstanding:
As of June 30, 2022, there were 54,278,981 ordinary shares issued and outstanding. Please note that each American depository share, or ADS, represents one and one quarter (1.25) ordinary shares of the company.

Non-GAAP Net Loss:
Non-GAAP net loss, which is defined as net loss attributable to ordinary shareholders for the period after excluding (i) share-based compensation expenses and (ii) accretion of convertible redeemable preferred shares to redemption value, as appliable, was US$41.9 million for the six months ended June 30, 2022, compared to US$27.0 million for the six months ended June 30, 2021. Please refer to the section in this press release titled "Reconciliation of GAAP and Non-GAAP Results" for details.

Non-GAAP Financial Measures

The Company uses non-GAAP net loss and non-GAAP net loss per ordinary shares for the year, which are non-GAAP financial measures, in evaluating its operating results and for financial and operational decision-making purposes. The Company believes that non-GAAP net loss and non-GAAP net loss per ordinary shares for the year help identify underlying trends in the Company’s business that could otherwise be distorted by the effect of certain expenses that the Company includes in its loss for the year. The Company believes that non-GAAP net loss and non-GAAP net loss per ordinary shares for the year provide useful information about its results of operations, enhances the overall understanding of its past performance and future prospects and allows for greater visibility with respect to key metrics used by its management in its financial and operational decision-making.

Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year should not be considered in isolation or construed as an alternative to operating profit, loss for the year or any other measure of performance or as an indicator of its operating performance. Investors are encouraged to review non-GAAP net loss and non-GAAP net loss per ordinary shares for the year and the reconciliation to their most directly comparable GAAP measures. Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year here may not be comparable to similarly titled measures presented by other companies. Other companies may calculate similarly titled measures differently, limiting their usefulness as comparative measures to the Company’s data. The Company encourages investors and others to review its financial information in its entirety and not rely on a single financial measure.

Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year represent net loss attributable to ordinary shareholders for the year excluding (i) share-based compensation expenses, and (ii) accretion of convertible redeemable preferred shares to redemption value. Share-based compensation expense is a non-cash expense arising from the grant of stock-based awards to employees. The Company believes that the exclusion of share-based compensation expenses from the net loss in the Reconciliation of GAAP and Non-GAAP Results assists management and investors in making meaningful period-to-period comparisons in the Company’s operating performance or peer group comparisons because (i) the amount of share-based compensation expenses in any specific period may not directly correlate to the Company’s underlying performance, (ii) such expenses can vary significantly between periods as a result of the timing of grants of new stock-based awards, and (iii) other companies may use different forms of employee compensation or different valuation methodologies for their share-based compensation.

Please see the "Reconciliation of GAAP and Non-GAAP Results" included in this press release for a full reconciliation of non-GAAP net loss and non-GAAP net loss per ordinary shares for the year to net loss attributable to ordinary shareholders for the year/period.

On August 30, 2022 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3 related immunotherapy treatments for cancer and autoimmune disease, reported the grant of a new patent (number 7116547) entitled "Combined Preparations for the Treatment of Cancer or Infection" by the Japanese Patent Office (Press release, Immutep, AUG 30, 2022, View Source [SID1234618810]).

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This new Japanese patent follows the grant of the corresponding Australian, European, United States and Chinese patents announced in 2018 through 2022.

The claims of the new patent protect Immutep’s intellectual property relating to combined therapeutic preparations comprising (a) its lead active immunotherapy candidate eftilagimod alpha ("efti" or "IMP321"), which is a LAG-3 fusion protein (LAG-3Ig), and (b) an anti-PD-(L)1 antibody. The claims are also directed to related methods of use in the treatment of cancer and infection.

In addition to broader style claims, the granted claims include narrower claims drawn to specific combinations of efti with various approved PD-(L)1 antibodies.

In all, the claims provide comprehensive coverage of both combination products and combination therapies comprising efti and an anti-PD-(L)1 antibody.

The patent expiry date is 8 January 2036.

Immutep CEO, Marc Voigt, noted: "We are pleased to see continued progress in building our global patent estate around efti. This is especially meaningful when coupled with the very promising data we have reported from TACTI-002 in three cancer indications, along with the initiation of TACTI-003 in the past 12 months. This Japanese patent, along with the equivalent patents granted in other key global markets, underpin the investments we have made to develop this unique candidate and give Immutep important strategic options."

On August 30, 2022 Amgen (NASDAQ: AMGN) reported that the global Phase 3 CodeBreaK 200 trial evaluating once daily oral LUMAKRAS (sotorasib) met its primary endpoint of progression-free survival (PFS), demonstrating statistical significance and superiority over standard of care chemotherapy, intravenous docetaxel (Press release, Amgen, AUG 30, 2022, View Source [SID1234618795]). The first randomized clinical trial for a KRASG12C inhibitor assessed the efficacy and safety of LUMAKRAS in 345 previously treated patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC) who had received at minimum, prior platinum-based doublet chemotherapy and checkpoint inhibitor therapy.

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"Further analyses of the data are ongoing, and we look forward to sharing detailed data at an upcoming medical meeting," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We are grateful to all of the investigators and patients who participated in this first randomized, controlled clinical trial of a KRASG12C inhibitor."

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.1 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.2

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 6,500 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program, expanded access and commercial use.

In total, LUMAKRAS/LUMYKRAS is approved in over 44 markets around the world, including the United States, the European Union, Japan, United Arab Emirates, South Korea, Hong Kong, Switzerland, Taiwan and Qatar, and in Australia, Brazil, Canada, Great Britain, Israel and Singapore under the U.S. FDA’s Project Orbis. Amgen has submitted MAAs in Argentina, Colombia, Kuwait, Malaysia, Mexico, Saudi Arabia, Thailand and Turkey.

LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.3

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.4 Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease, and 5-year survival is only 8% for those with metastatic disease.5

KRAS G12C is the most common KRAS mutation in NSCLC.6 About 13% of patients with NSCLC harbor the KRAS G12C mutation.7 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 other approved therapies are suboptimal, with a median progression-free survival of approximately four months following second-line treatment of KRAS G12C-mutated NSCLC.8

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.9 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.2 The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and results have been published.10

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.11

Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.12 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).13

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

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.

On August 30, 2022 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported that management will participate in fireside chats at the following investor conferences (Press release, Ionis Pharmaceuticals, AUG 30, 2022, View Source [SID1234618794]):

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2022 Wells Fargo Healthcare Conference on Wednesday, September 7, 2022
Citi’s 17th Annual BioPharma Conference on Thursday, September 8, 2022
Morgan Stanley 20th Annual Global Healthcare Conference on Monday, September 12, 2022
A live webcast and additional information about each fireside chat can be accessed on the Investors & Media section of the Ionis website at www.ionispharma.com. Replays will be available on the Ionis website within 48 hours of each event.

On August 30, 2022 Shanghai Fosun Pharmaceutical (Group) Co., Ltd. ("Fosun Pharma" or "the Group"; Stock Code: 600196.SH, 02196.HK), a global innovation-driven pharmaceutical and healthcare industry group deep-rooted in China, reported its interim results for the first half of 2022 (Press release, Fosun Pharma, AUG 30, 2022, View Source [SID1234618793]).

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In the first half of 2022, Fosun Pharma achieved stable growth in revenue and recurring income. The proportion of revenue from new and sub-new products and the revenue from countries and regions outside Chinese mainland continued to increase, and the revenue structure constantly improved. During the reporting period, the revenue of the Group amounted to RMB2,1340 million, an increase of 25.88% YOY; net profit (after extraordinary gain or loss) attributable to shareholders of the listed company amounted to RMB1,862 million, an increase of 18.57% YOY; net cash flow from operating activities amounted to RMB 1,820 million, an increase of 6.66% YOY. The Group’s global operation capability was further enhanced, and revenue from regions and countries outside Chinese mainland reached RMB7,592 million, accounting for 35.58% of the total revenue and a YOY increase of 4.92 percentage points.

"In the first half of 2022, despite the pressure arising from Covid-19 resurgence in various regions of China, Fosun Pharma continued to promote innovation and transformation, comprehensively accelerated its international layout, strengthened the product pipelines, promoted the integration of operation, improved the efficiency in business divisions, and achieved solid growth." said Wu Yifang, Chairman of Fosun Pharma. "Fosun Pharma’s core competitiveness is embodied in its open R&D ecology, forward-looking international layout, and systematic commercialization team. In the second half of 2022, Fosun Pharma will continue implementing the 4IN strategy, increasing R&D investment, continuously optimizing operational control, improving asset operational efficiency, and actively expanding cooperation opportunities with leading global pharmaceutical companies. With patient-centered and clinical needs-oriented, the Group will continue to innovate and promote more good products into the global market, and bring health to all families."

Continuously Promoting Innovation & Transformation, Revenue Contribution of New Products and Sub-New Products Reached over 25%

Fosun Pharma’s innovative R&D is always based on satisfying unmet clinical needs, adhering to technology-driven and product-driven, and accessing global outstanding scientific talents, leading technologies and high-value products through diversified and multi-level cooperation modes such as independent R&D, co-development, license-in projects and deep incubation. By the end of June 2022, Fosun Pharma has over 2,800 R&D personnel, of which over 1,500 have master’s degrees or above. More than 260 pipeline projects, including innovative drugs, biosimilars, generic drugs and consistency evaluation items are under research.

Fosun Pharma continues to increase its investment in R&D. In the first half of 2022, R&D expenditures reached RMB 2,399 million, an increase of 22.77 % YOY. Among them, R&D expenses reached RMB 1,818 million, representing a period-on-period increase of RMB256 million or 16.39%. The R&D expenditures in the pharmaceutical manufacturing segment reached RMB 2,062 million, representing a period-on-period increase of 16.04%. Total R&D expenditures in the pharmaceutical manufacturing segment accounted for 14.39% of the revenue from the pharmaceutical manufacturing segment. In particular, R&D expenses amounted to RMB 1,491 million, accounting for 10.41% of the revenue from the pharmaceutical manufacturing segment.

Product structure optimization and sales growth from new product launches were the key drivers of Fosun Pharma’s results. In the first half of 2022, the revenue of new products and sub-new products, including COMIRNATY (in Hong Kong, Macau, and Taiwan region), Han Li Kang, Han Qu You, Su Ke Xin and Han Si Zhuang accounted for more than 25% of the revenue from the pharmaceutical manufacturing segment.

Yi Kai Da (Axicabtagene Ciloleucel Injection) of Fosun Kite, a joint venture, as the first CAR-T cell therapy product approved for launch in China, has been launched for more than one year. As of the end of July 2022, Yi Kai Da has been included in the urban customized commercial health insurance of 44 provinces and municipalities and over 50 commercial insurances, while the number of treatment centers on file had reached nearly 100.

Deepening Global Operation and Becoming a Preferred Domestic World-renowned Partner of Multinational Pharmaceutical Companies

Fosun Pharma continuously strengthened its global operation capability, and implemented a multi-dimensional internationalization strategy in innovation and research, license-in, production and operation, as well as commercialization. Significant progress has been made in its market access capability by establishing commercialization team building in the United States, Africa, Hong Kong and Macau markets. By the end of June 2022, the overseas commercial team of Fosun Pharma comprised more than 1,400 employees. Fosun Pharma has established marketing platforms in the United States, Africa and Europe, and achieved the direct sales of preparations to the United States market. Sisram Medical, Breas and other medical device business have covered major regions such as China, the United States and Europe, and Fosun Diagnosis’ COVID-19 nucleic acid test kits and COVID-19 antigen test kits have been sold in more than ten countries.

Relying on years of domestic industry experience and global channel network, Fosun Pharma has become the preferred domestic partner of world-renowned multinational pharmaceutical companies.

In the first half of 2022, Fosun Pharma and Amgen’s subsidiary entered into a licensing agreement regarding the exclusive commercialization of its 2 innovative drugs, namely Otezla (apemilast tablets) and Parsabiv (etelcalcetide), in Chinese Mainland (excluding Hong Kong, Macau and Taiwan region) to further enrich the Group’s innovative product layout in the non-oncology field.

Fosun Pharma’s industry-leading License-In & Out capabilities maximize the value of independently developed products and innovative products of partners. In the first half of 2022, Shanghai Henlius, a subsidiary, has successively granted various product licenses to Organon, Eurofarma, Getz Pharma and other companies, in order to cover incremental markets with the help of leading international partners.

Relying on the Fosun Pharma’s international production standards and quality system certifications, together with overseas product access and marketing capabilities, in January and March 2022, Fosun Pharma’s subsidiary Fosun Pharmaceutical Industrial was licensed to manufacture and supply the generic versions of Molnupiravir, a COVID-19 oral drug of Merck, and Nirmatrelvir, a COVID-19 oral drug of Pfizer, and a combination of Nirmatrelvir/Ritonavir by MPP for certain mid- and low-income countries in the world. The license allows the production of the active pharmaceutical ingredient and the finished drug, continuing to contribute to the global efforts to fight COVID-19.

In order to further improve the cost competitiveness of products and to enhance the rational allocation of production resources, Fosun Pharma is actively integrating manufacturing capacities to build a large-scale, cost-competitive manufacturing system. In China, Fosun Pharma is building two comprehensive pharmaceutical preparation manufacturing centers and three raw pharmaceutical production bases to consolidate the strength in the integrated production of APIs gradually. Overseas, several injectables manufacturing lines of Gland Pharma have passed GMP certification in the US, EU, Japan, Australia and other major regulatory markets, supplying the global market.

Fighting Against Epidemic Together to Secure Production and Actively Fulfilling Corporate Social Responsibility

In the first half of 2022, the domestic epidemic spread in various provinces and cities, and the production, supply chain, logistics as well as the number of hospital offline diagnosis and treatment faced staged pressure. Fosun Pharma responded to the local pandemic prevention and control policies and actively took countermeasures to ensure production and operation activities were conducted orderly. Fosun Pharma secured the production and supply of key drugs such as Han Qu You, Han Li Kang and Yi Kai Da as well as anti-epidemic materials such as nucleic acid test kits and antigen test kits for COVID-19 during the pandemic through centralized closed-loop management of front-line production personnel, increased supply chain and logistics options and other means, comprehensively assisting the prevention and control of the pandemic by focusing on prevention, detection and treatment of COVID-19.

The Group continued to ensure the supply of Comirnaty (mRNA COVID-19 vaccine) to Hong Kong, Macau and Taiwan region, to meet the local needs for epidemic prevention and control. In July 2022, Fosun Pharmaceutical Industrial, a subsidiary of Fosun Pharma, and Genuine Biotech entered into an agreement in relation to the strategic cooperation on, among other things, the joint development and Fosun Pharmaceutical Industrial’s exclusive commercialization of Azvudine. The cooperation scope includes the treatment and prevention of Novel Coronavirus (2019- nCoV) and AIDS. The Azvudine tablets, independently developed by China, is the first small molecular oral medication for COVID-19 approved for launch. On 25 July 2022, the drug obtained the emergency conditional approval from the NMPA for use in treatment of adult patients suffering moderate COVID-19.

Since August 2022, there have been epidemic resurgences in Hainan and Henan provinces, Xinjiang and Tibet autonomous regions, and other regions in China. Prevention and control situation of COVID-19 remain severe and complex. Fosun Pharma and Genuine Biotech actively responded to the needs of local governments and deployed Azvudine tablets to many places across the country urgently and helped build a solid barrier for epidemic prevention and control, to protect people’s health.

With remarkable achievements in environmental, social, and corporate governance (ESG) and positive contributions in the fight against the COVID-19 pandemic, Fosun Pharma topped the 2022 Fortune China ESG Impact List.