On May 6, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI343 as monotherapy for the treatment of claudin18.2-positive advanced gastric/gastro-esophageal junction adenocarcinoma (GC) patients who have progressed after at least 2 lines of prior systematic treatments (Press release, Innovent Biologics, MAY 6, 2024, View Source [SID1234642698]).

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The BTD for IBI343 was based on the data from an ongoing Phase 1 study (NCT05458219), in which favorable safety and tolerability and promising antitumor activity of IBI343 monotherapy in advanced GC patients were observed. The study results will be published at an upcoming medical conference later in 2024.

Innovent is preparing for a registrational Phase 3 multi-regional clinical trial (MRCT) of IBI343 in patients with claudin18.2-positive, HER2-negative GC (G-HOPE-001, NCT06238843) to be initiated soon.

Dr. Hui Zhou, Senior Vice President of Innovent, said, "GC patients tend to progress after second-line systematic therapies with poor prognosis and have only a half year of survival expectancy. They are in urgent need of effective third-line treatment options. We are glad to see the NMPA granted BTD for IBI343 monotherapy based on the PoC clinical results in GC, and we will continue to validate its efficacy and safety in the registrational MRCT trial. Innovent has a comprehensive and robust oncology pipeline, and, particularly in GC, we have PD-1 inhibitor (TYVYT) for first-line GC treatment and anti-angiogenic drug (CYRAMZA) for second-line GC treatment. We will further explore IBI343’s potential in combination therapy as well as in other solid tumors such as pancreatic cancer."

NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of an investigational drug to treat a serious disease or condition when preliminary clinical evidence indicates that the drug has demonstrated substantial improvement over current therapies. The BTD will not only qualify a drug candidate to receive status for rapid review by the CDE, but it will also allow the sponsor to obtain timely advice and communication from the CDE to accelerate the approval and launch to address the unmet clinical need of patients at an accelerated pace. Click here for the published list of drugs that have been granted BTD by NMPA.

About Gastric/ Gastroesophageal Junction Adenocarcinoma

Gastric cancer is one of the most common malignant tumors in the world and is one of the leading causes of cancer-related deaths globally. The 5-year survival rate of patients with metastatic gastric cancer is less than 5%[i]. China and Japan are countries with highest incidence of gastric cancer[ii]. Currently, chemotherapy combination of fluoropyrimidine and platinum and immune checkpoint inhibitor therapy are the standard-of-care treatments for patients with advanced metastatic gastric cancer. However, systemic therapy has limited efficacy in advanced gastric cancer. In particular, the prognosis for patients with third-line or higher gastric cancer is usually poor, with fewer treatment options and shorter survival expectations. The median survival times for these patients is only about 0.5 year[iii].

Claudin, a member of the tight junction molecule family, is a key structural and functional component of epithelial tight junctions. Among them, CLDN18.2 is normally buried in the gastric mucosa, but the development of malignancy leads to disruption of tight junctions and exposure of CLDN18.2 epitopes on the membrane of tumor cells[iv]. CLDN18.2 is expressed in up to 80% of patients with gastric cancer.

About IBI343 (Claudin18.2 ADC)

IBI343 is an antibody-drug conjugate composed of an anti-claudin18.2 antibody, and a cytotoxic drug exatecan. As a topoisomerase I inhibitor, exatecan effectively kills tumor cells by inhibiting DNA synthesis. Binding of IBI343 to claudin18.2-expressing tumor cells results in claudin18.2-dependent internalization of IBI343. Degradation of the cleavable linker will release the drug that causes DNA damage, leading to apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring tumor cells, resulting in a strong "bystander killing effect" of IBI343.

On May 6, 2024 Lantern Pharma Inc. (NASDAQ: LTRN), a leading artificial intelligence (AI) oncology drug discovery and development company, reported a strategic AI-driven collaboration with French biotechnology company, Oregon Therapeutics to optimize the development of its first-in-class protein disulfide isomerase (PDI)(1) inhibitor drug candidate XCE853 in novel and targeted cancer indications (Press release, Lantern Pharma, MAY 6, 2024, View Source [SID1234642697]). Lantern will be leveraging its proprietary RADR AI platform to uncover biomarkers and efficacy-associated signatures of XCE853 across solid tumors that can aid in precision development. Collaborative efforts are expected to identify biomarker signatures that can be used to stratify tumors most responsive to XCE853 and guide potential future clinical development and patient selection. Oregon Therapeutics is developing XCE853 in various cancer indications, including drug-resistant ovarian and pancreatic cancer, certain hematological cancers and several pediatric cancers including CNS cancers.

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PDIs are promising targets for cancer therapy raising clinical interest recently2 notably for their potential in cancers of poor prognosis like breast cancer3 or ovarian cancer. Up-regulated expression of PDIs was found to be associated with worse clinical outcome in numerous cancers such as hepatocellular carcinoma(4), as well as breast and ovarian cancers(5). PDIs are protein chaperones and are central to maintaining cancer cell metabolism, additionally PDI inhibitors can cause cancer cell death through the accumulation of impaired proteins and dysregulated cellular stress responses. A combination of these effects is known as proteotoxicity, a unique and promising therapeutic strategy that may be especially effective in targeting cancers that are resistant to therapy.

In the US, nearly 612,000 people(6) are projected to die from cancer in 2024 and, resistance to anticancer drugs will be implicated in 90% of those deaths(7). To date, no PDI inhibitor has reached the clinic due to the complexities related to selecting and mapping the molecules that will most accurately target the right PDI enzymes. There are more than 20 PDI enzymes, with each playing a slightly different and often biologically redundant role. Oregon Therapeutic’s lead drug-candidate XCE853 is known to target PDIs of specific interest for cancer. Lantern Pharma and Oregon Therapeutics believe that computational tools, including foundational models, machine learning and large-scale molecular analysis can offer an ideal and streamlined pathway for breaking through these data and decision complexities – making RADR the perfect platform for better informing the role XCE853 can play in effective cancer treatment. (8, 9)

"To date, our first-in-class metabolic inhibitor, XCE853, has exhibited robust preclinical efficacy in both in vitro and in vivo models across multiple cancer types," said Marc-Henry PITTY, MD, CEO of Oregon Therapeutics. "Lantern’s RADR AI platform will leverage the in vitro and in vivo data to potentially advance XCE853 development in a highly targeted manner and will help inform disease indications and biomarker signatures that can aid in the design of future clinical trials and in the pursuit of combination therapies with other approved cancer drugs. Our team is looking forward to efficiently selecting among the landscape of ideal development options and efficiently de-risking future clinical development decisions." Oregon Therapeutics has previously performed preclinical studies indicating that in addition to ovarian and pancreatic cancer, XCE853 may also be particularly active in renal, prostate, lung, breast, and head and neck cancers, and leukemia based on preclinical cell-line studies. Oregon project leader, Sandrine Courtès PhD, who has been developing the collaboration with Lantern Pharma, stated: "PDIs Inhibitors have a great potential, since this molecular target is highly expressed in several cancer types, supports tumor growth and is associated with clinical outcomes."

The collaboration focuses on the integration and interrogation of molecular, genetic and transcriptomic data pertaining to XCE853. This analysis will be powered by RADR and its growing library of over 60 billion data points from many diverse types of biological measurements and oncology experiments, as well as more than 200 ML algorithms focused on problems that are central to real-world cancer drug development. The initial objectives of the collaboration are to:

1) uncover biomarkers and efficacy-associated gene signatures to guide in the eventual stratification and selection of patients for future clinical trials,

2) identify tumor-based response and resistance mechanisms to XCE853 and strategies to overcome treatment resistance, and

3) expand the use of XCE853 in additional therapeutic cancer indications for XCE853.

"Drug development teams have found significant data and modeling challenges in regard to tackling the complexities associated with PDI inhibitors given the challenges with creating meaningful models, and accumulating and deciphering the data," said Panna Sharma, CEO and President of Lantern Pharma. "Our AI platform, RADR, can increase the confidence, insights, and comfort levels in developing data-driven development paths by modeling highly complex scenarios at a scale that only has become possible recently. It’s an ideal approach for Oregon Therapeutics, which has executed a series of highly targeted in vivo and in vitro experiments and is poised to make incredibly important and patient-centric decisions about the clinical future of the molecule. That’s where RADR can play a highly essential and market defining role."

Under the terms of the collaboration, Lantern Pharma is receiving equal IP co-ownership and drug development rights in newly discovered biomarkers, novel indications, and/or new pharmacological use strategies for XC853 and related analogues. Oregon Therapeutics is entitled to financial benefits resulting from the out licensing of the background IP to Lantern Pharma. Lantern Pharma and Oregon Therapeutics are both entitled to additional financial benefits resulting from the out licensing of any collaboration IP to a third party. No further financial details regarding the collaboration were disclosed.

About RADR

RADR is Lantern Pharma’s proprietary integrated AI platform for large-scale biomarker and drug-tumor interaction data analytics that leverages machine learning. It is used to provide mechanistic insights about drug-tumor interactions, predict the potential response of cancer types and subtypes to existing drugs and drug candidates, and uncover patient groups that may respond to potential therapies being developed by Lantern Pharma and its collaborators.

RADR uses an ensemble-based approach to apply its library of algorithms to statistical, correlative, and inferential problems in drug-tumor interactions. This allows the platform to rapidly analyze large amounts of complex data and predict how both patients and tumors will respond to therapeutic combinations. RADR also evolves as new datasets are added, which improves and sharpens the insights generated from the algorithms.

RADR’s highly scalable machine-learning methods are designed to guide drug development and yield new biological insights, while also having the potential to increase response rates and improve outcomes in clinical trials. The robustness and growing number of datasets powering RADR is anticipated to continue to improve machine-learning results, accelerate automation of other features and aid oncology drug development for Lantern and its partners with an ultimate focus on benefitting cancer patients.

On May 6, 2024 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported that the U.S. Food and Drug Administration (FDA) has accepted for priority review a Biologics License Application (BLA) for the bispecific antibody zenocutuzumab (Zeno) in patients with neuregulin 1 fusion (NRG1+) non-small cell lung (NSCLC) and NRG1+ pancreatic (PDAC) cancer (Press release, Merus, MAY 6, 2024, View Source [SID1234642696]).

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"FDA acceptance of our first BLA represents an important achievement for Merus and an important potential treatment opportunity for patients with NRG1+ cancer, a disease with poor prognosis and high unmet need," said Dr. Andrew Joe, Chief Medical Officer at Merus. "Zenocutuzumab has the potential to be the first and only targeted therapy for patients with NRG1+ lung and pancreatic cancer, and may offer a substantial improvement over currently available therapies."

The BLA includes a comprehensive clinical data package, including data from the phase 1/2 eNRGy trial, which is investigating the safety and anti-tumor activity of Zeno monotherapy in NRG1+ NSCLC, PDAC and other solid tumors. Data from the open-label trial were presented previously at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, and subsequently updated at ASCO (Free ASCO Whitepaper) 2022 and the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023.

The FDA has granted Breakthrough Therapy Designation (BTD) to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ pancreatic cancer following progression with prior systemic therapy or who have no satisfactory alternative treatment options. Additionally, the FDA has granted BTD to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ NSCLC, following progression with prior systemic therapy.

Zeno is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.

About Zeno

Zeno is a Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 fusions (NRG1+ cancer). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancer. In preclinical studies, Zeno potently inhibits HER2/HER3 heterodimer formation thereby inhibiting oncogenic signaling pathways, leading to inhibition of tumor cell proliferation and blocking tumor cell survival. In clinical studies, Zeno has demonstrated anti-tumor activity in multiple types of NRG1+ cancer, including NRG1+ NSCLC and NRG1+ PDAC.

About NRG1 Fusions

The NRG1 gene encodes neuregulin (also known as heregulin), the ligand for HER3. Fusions between NRG1 and partner genes are rare, tumorigenic genomic events occurring in certain cancer types including NSCLC and PDAC.

On May 6, 2024 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported that it has entered into a securities purchase agreement with new institutional investors and Company insiders to raise up to approximately $18 million in gross proceeds, including initial upfront funding of approximately $6.5 million, and up to an additional approximately $11.5 million upon cash exercise of accompanying warrants at the election of the investors (Press release, Plus Therapeutics, MAY 6, 2024, View Source [SID1234642695]).

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The financing includes participation from AIGH Capital Management LLC with additional participation from new healthcare-focused institutional investors as well as certain Company insiders.

"The capital from this transaction, funded by experienced institutional investors and insiders, in conjunction with existing cash and grant support, provides the company with up to approximately $34 million in cash runway, assuming full exercise of the warrants, to support achievement of our corporate objectives," said Marc Hedrick, M.D. President and CEO.

Pursuant to terms of the securities purchase agreement, the Company will issue up to an aggregate of 3,238,627 shares of its common stock (or pre-funded warrants in lieu thereof) and accompanying warrants to purchase up to an aggregate of 6,477,254 shares of its common stock at a combined purchase price of $2.022 per share and accompanying warrants, in accordance with the "Minimum Price" requirement as defined in the Nasdaq rules. The accompanying warrants will consist of two series:

Series A warrants to purchase up to an aggregate of 3,238,627 shares of common stock at an exercise price of $1.772 per share for an aggregate of up to approximately $5.7 million and will be exercisable until the five-year anniversary of closing of the financing.
Series B warrants to purchase up to 3,238,627 shares of common stock at an exercise price of $1.772 per share for an aggregate of up to approximately $5.7 million. The Series B warrants will be exercisable until the one-year anniversary of the effectiveness of a registration statement covering the resale of shares of common stock underlying the Series B warrants.
In lieu of shares of common stock, certain investors are purchasing pre-funded warrants at a combined purchase price of $2.021 per pre-funded warrant and accompanying warrants, which equals the purchase price per share of common stock and accompanying warrant, less the $0.001 per share exercise price of each pre-funded warrant. The private placement is expected to close on or about May 8, 2024, subject to satisfaction of customary closing conditions.

The Company intends to use the upfront net proceeds from the private placement for general corporate purposes and to fund the Re-SPECT LM clinical development program.

This offer and sale of the foregoing securities are being made in a transaction not involving a public offering, and the securities have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or applicable state securities laws. Accordingly, the securities may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws. The Company has agreed to file a registration statement with the SEC registering the resale of the shares of common stock purchased in the financing and shares of common stock underlying the warrants.

This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

On May 6, 2024 Sandoz (SIX:SDZ/OTCQX:SDZNY), the global leader in generic and biosimilar medicines, reported net sales for the first quarter 2024 (Press release, Sandoz, MAY 6, 2024, View Source [SID1234642694]). Net sales were USD 2.5 billion, an increase of 6% in constant currencies compared to the same quarter of the prior year. Biosimilars saw another quarter of double-digit net sales growth, an increase of 21% in constant currencies. Generics sales remained in line with prior year levels.

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Richard Saynor, Chief Executive Officer of Sandoz, said: "We saw a strong start to the year as we report our 10th consecutive quarter of topline growth. The momentum in our business continues as demonstrated by double-digit growth in biosimilars and a positive contribution by all regions."

Mr. Saynor continued: "Biosimilars are a key element of performance, driven by strong results in our existing portfolio, demand for our recently launched product Hyrimoz (adalimumab-adaz) in the US and the recent acquisition of CIMERLI (ranibizumab-eqrn), which closed in early March. Generics remained in line with the strong prior year sales. Looking forward, we are confident in our ability to continue to grow our top line and meet our full-year net sales guidance of mid-single digits in constant currencies."

FIRST QUARTER NET SALES RESULTS
Net sales for the first quarter were USD 2.5 billion, up 6% in constant currencies, compared to the first quarter of 2023. Volume contributed 10 percentage points of growth, partially offset by price erosion of 4 percentage points. Biosimilars were a key driver of growth in the quarter, while generics remained in line with the strong prior year sales.

Net sales by business

Three months ended March 31 Change %
USD millions unless indicated otherwise 2024 2023 USD cc*
Generics 1869 1868 0 1
Biosimilars 623 516 21 21
Net sales to third parties 2492 2384 5 6
*Constant currencies

Generics overview
Net sales for the first quarter were USD 1.9 billion, up 1% in constant currencies, compared to the first quarter of 2023. Solid volume demand was partly offset by the impact from the withdrawal of apixaban in the Netherlands following a court decision in August 2023, an exceptional cough and cold season in the first half of 2023 and the timing of new launches in the US.

Biosimilars overview
Net sales for the first quarter were USD 623 million, up 21% in constant currencies, compared to the first quarter of 2023. This strong double-digit biosimilar growth reflects the ongoing launch of Hyrimoz high-concentration formulation, the acquisition of CIMERLI as well as continued strong demand for our first-ever biosimilar, Omnitrope.

Net sales by region

Three months ended March 31 Change %
USD millions unless indicated otherwise 2024 2023 USD cc
Europe 1326 1270 4 2
North America 524 496 6 6
International 642 618 4 12
Net sales to third parties 2492 2384 5 6
Europe overview
Net sales for the first quarter were USD 1.3 billion, up 2% in constant currencies, compared to the first quarter of 2023. Generic volume growth remained positive despite a strong prior year comparison from peak sales of apixaban and an exceptional cough and cold season. Biosimilars showed strong sales growth, led by demand for Omnitrope and contribution from the recent launch of Tyruko (natalizumab) in several key countries.

North America overview
Net sales for the first quarter were USD 524 million, up 6% in constant currencies, compared to the first quarter of 2023. Growth was driven by the ongoing launch of Hyrimoz in the US, continued demand for Omnitrope, the acquisition of CIMERLI which closed in early March, and the transfer of mature brands from our former parent in the fourth quarter of 2023. This was partly offset by a decline in generics sales due to the timing of new launches in the US.

International overview
Net sales for the first quarter were USD 642 million, up 12% in constant currencies, compared to the first quarter of 2023. This was primarily a result of strong volume growth across both generics and biosimilars, the acquisition of Mycamine in the prior year and favorable price dynamics.

GUIDANCE 2024
The company reiterates its full-year 2024 guidance, expecting net sales to grow mid-single digit in constant currencies versus prior year and core EBITDA margin around 20%.

FIRST QUARTER STRATEGIC MILESTONES
On January 31, we announced the launch of Tyruko in Germany. Developed by Polpharma Biologics, Tyruko is the first and only biosimilar to treat relapsing remitting multiple sclerosis. The availability of Tyruko is a crucial milestone in improving access to effective and safe therapies for those in Europe that need them most.

On March 4, we announced the completion of the US biosimilar CIMERLI acquisition from Coherus BioSciences, Inc, ahead of anticipated timelines. The acquisition builds on the leading Sandoz ophthalmic platform in the US and lays an even stronger foundation for future product launches.

On March 5, we announced that Remco Steenbergen, currently a Sandoz Board member, will become a member of the Executive Committee and take on the responsibility of Sandoz CFO as of July 1, 2024. Remco will succeed Colin Bond who will step down from his position as of June 30, 2024, and retire in January 2025 per Swiss employment practice. Colin will be available for transition as a senior advisor through the end of 2024.

On March 5, we also announced that the US Food and Drug Administration (FDA) approved Wyost (denosumab-bbdz) and Jubbonti (denosumab-bbdz), the first and only FDA-approved denosumab biosimilars, to treat all indications of the reference medicines including osteoporosis and cancer-related skeletal events.

KEY LINKS
Webcast – Live at 9am CET
Analyst Call Presentation
Analyst Consensus

NON-IFRS MEASURES IN THIS DOCUMENT AS DEFINED BY SANDOZ
Sandoz uses certain non-IFRS metrics when measuring performance, especially when measuring current period results against prior periods, including core results, constant currencies and free cash flow. Despite the use of these measures by management in setting goals and measuring Sandoz performance, these are non-IFRS measures that have no standardized meaning prescribed by IFRS Accounting Standards. As a result, such measures have limits in their usefulness to investors. Because of their non-standardized definitions, the non-IFRS measures (unlike IFRS measures) may not be comparable to the calculation of similar measures of other companies. These non-IFRS measures are presented solely to permit investors to more fully understand how Sandoz management assesses underlying performance. These non-IFRS measures are not, and should not be viewed as, a substitute for IFRS measures, and should be viewed in conjunction with IFRS financials. As an internal measure of Group performance, these non-IFRS measures have limitations, and Sandoz performance management process is not solely restricted to these metrics.

The definitions of the non-IFRS financial metrics as used by Sandoz are as follows:

Core results
Sandoz core results – including core EBITDA, core operating income, core net income and core earnings per share – exclude fully:

The amortization and impairment charges of intangible assets other than software;
Net gains and losses on fund investments and equity securities valued at fair value through profit and loss;
Certain acquisition and divestment- related items;
Tax liabilities for uncertain tax positions.
The following items that exceed a threshold of USD 25 million are also excluded:

Integration- and divestment- related income and expenses;
Divestment gains and losses;
Restructuring charges/releases and related items;
Legal related items;
Impairments of property, plant and equipment, software and financial assets;
And income and expense items that management deems exceptional and that are or are expected to accumulate within the year to be over a USD 25 million threshold. Income tax impacts of such items are also excluded from core measures.
Sandoz believes that investor understanding of its performance is enhanced by disclosing core measures of performance because, since core measures exclude items that can vary significantly from year to year, they enable a better comparison of business performance across years. For this same reason, Sandoz uses these core measures in addition to IFRS and other measures as important factors in assessing its performance.

The following are examples of how these core measures are utilized:

In addition to monthly reports containing financial information prepared under IFRS, senior management receives a monthly analysis incorporating these core measures;
Annual budgets are prepared for both IFRS and core measures.
As an internal measure of Sandoz performance, the core results measures have limitations, and the Sandoz performance management process is not solely restricted to these metrics.

A limitation of the core results measures is that they provide a view of the Sandoz operations without including all events during a period, such as the effects of an acquisition, divestment, or amortization/impairments of purchased intangible assets, impairments to property, plant and equipment and restructurings and related items.

Constant currencies
Changes in the relative values of non-US currencies to the US dollar can affect Sandoz financial results and financial position. To provide additional information that may be useful to investors, including changes in sales volume, Sandoz presents information about its net sales and various values relating to operating and net income that are adjusted for such foreign currency effects. Constant currency calculations have the goal of eliminating two exchange rate effects so that an estimate can be made of underlying changes in the consolidated income statement excluding the impact of fluctuations in exchanges rates:

The impact of translating the income statements of consolidated entities from their non-USD functional currencies to USD;
The impact of exchange rate movements on the major transactions of consolidated entities performed in currencies other than their functional currency.
Sandoz calculates constant currency measures by translating the current year’s foreign currency values for sales and other income statement items into USD (excluding the IAS 29 "Financial Reporting in Hyperinflationary Economies" adjustments to the local currency income statements of subsidiaries operating in hyperinflationary economies), using the average exchange rates from the prior year and comparing them to the prior year values in USD. Sandoz uses these constant currency measures in evaluating its performance, since they may assist the Group in evaluating its ongoing performance from year to year. However, in performing its evaluation, Sandoz also considers equivalent measures of performance that are not affected by changes in the relative value of currencies.

EBITDA
Sandoz defines earnings before interest, tax, depreciation, and amortization (EBITDA) as operating income, excluding depreciation of property, plant and equipment and right-of-use assets, amortization of intangible assets, impairments of property, plant and equipment, right-of-use assets, and intangible assets.

Core EBITDA margin
Sandoz defines core EBITDA margin as the percentage of core EBITDA over net sales to third parties. It is an indicator to measure the profitability of the Group.

Currencies
References to "USD" or "U.S. dollars" are to the lawful currency of the United States of America.

Rounding
Certain figures contained in the media release, including financial information presented in millions or thousands, certain operating data and percentages describing financial information or market shares, have been subject to rounding. Accordingly, in certain instances, the amounts shown as totals in tables or elsewhere may not conform exactly to the arithmetic total of the figures that precede them. In addition, certain percentages reflect calculations based upon the underlying information prior to rounding and, accordingly, may not conform exactly to the percentages that would be derived if the relevant calculations were based upon the rounded numbers.