Octreotide oral film(Connexios Life Sciences Pvt Ltd.)

Phase 3 PATHFNDR-1 Study Met Primary and All Secondary Endpoints as Reported in September Phase 3 PATHFNDR-2 Study Topline Data Expected in 1Q 2024 Initial Data from Phase 2 Study of Paltusotine in Carcinoid Syndrome Expected in December 2023 SAN DIEGO, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today reported financial results for the third quarter ended September 30, 2023. “The resounding success of paltusotine in our PATHFNDR-1 Phase 3 study for acromegaly is a significant step toward fulfilling our strategic vision of building a premier, fully integrated endocrine company that can consistently create pioneering therapies for people around the world,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “We intend to build additional momentum around our investigational compound paltusotine in the next few months. In December, we plan to analyze initial data from approximately half of the study participants in our ongoing Phase 2 study in carcinoid syndrome that should provide a preliminary indication of pharmacokinetic exposure, safety, and efficacy in this important second indication. We anticipate the full Phase 2 dataset from carcinoid to be available in the first half of 2024, and we remain on track to announce Phase 3 data from the PATHFNDR-2 study in the first quarter of 2024. We are enthusiastic about these upcoming key milestones for the paltusotine franchise.” Third Quarter 2023 and Operating Highlights: Phase 3 PATHFNDR-1 study met primary and all secondary endpoints. In September 2023, Crinetics reported positive topline results from its placebo-controlled Phase 3 clinical study of paltusotine in participants with acromegaly switching from standard-of-care injected depot somatostatin analogs which is designed to support an indication for the maintenance of acromegaly treatment. The study met statistical significance (p<0.0001) on the primary endpoint, based on the proportion of participants taking paltusotine (83%) who maintained an insulin-like growth factor 1 (IGF-1) level ≤ 1.0 times the upper limit of normal (xULN) compared to those taking placebo (4%). All secondary endpoints also met statistical significance as compared to placebo: change from baseline in IGF-level (p<0.0001), change from baseline in acromegaly symptoms diary (ASD) total score (p=0.02), and proportion of participants who maintained growth hormone level of <1.0 ng/mL (p=0.0003).Completed enrollment in paltusotine’s Phase 3 PATHFNDR-2 study. PATHFNDR-2 is a placebo-controlled Phase 3 clinical study of oral paltusotine in participants with acromegaly who are treatment-naïve or not currently receiving medical therapy which is designed to support an indication for the treatment of acromegaly. The study completed enrollment of 112 participants with acromegaly who were either treatment-naïve or untreated for at least four months (Stratum 1: n=82), or who washed out of prior octreotide or lanreotide monotherapy (Stratum 2: n=30). Topline data from the study is expected in the first quarter of 2024.Hosted Key Opinion Leader (KOL) webinar discussing acromegaly unmet need. In August 2023, Crinetics hosted a webinar featuring presentations by KOLs Beverly MK Biller, M.D. and Karen JP Liebert, R.N., BSN, both of Massachusetts General Hospital, who discussed the current landscape and unmet medical need in acromegaly, as well as the treatment burden associated with standard-of-care injectable somatostatin receptor ligands (SRLs). A replay of the webinar can be accessed here.Paltusotine NDA submission anticipated in 2024. Pending successful data from the PATHFNDR-2 study, Crinetics plans to submit a new drug application (NDA) to the Food and Drug Administration seeking regulatory approval for both the treatment of acromegaly and maintenance of acromegaly treatment indications.Initial data from Phase 2 study of paltusotine in carcinoid syndrome expected December 2023. The Phase 2 open-label study of paltusotine in carcinoid syndrome associated with neuroendocrine tumors is completing enrollment. A preliminary analysis from a subset of approximately half of the expected 30 participants is anticipated in December 2023. The study is designed primarily to assess the pharmacokinetic exposure and safety profile of paltusotine in participants with carcinoid syndrome. In addition, the study should provide descriptive efficacy information on the frequency of bowel movements and flushing episodes. CRN04894 studies for Cushing’s disease and congenital adrenal hyperplasia (CAH). Based on successful Phase 1 studies demonstrating pharmacologic proof-of-concept, Crinetics is advancing clinical studies of CRN04894 in both Cushing’s disease and congenital adrenal hyperplasia. Data from the ongoing studies are expected in the second half of 2024.Strengthened balance sheet with $350 million public offering. In September 2023, Crinetics announced the pricing of an upsized underwritten public offering of 11,441,648 shares of its common stock at $30.59 per share. Gross proceeds from the offering were $350.0 million. Third Quarter 2023 Financial Results Research and development expenses were $43.8 million for the three months ended September 30, 2023, compared to $32.0 million for the same period in 2022. The change was primarily due to an increase in personnel costs of $8.3 million, increased net spending on manufacturing and development activities of $1.8 million associated with our clinical and nonclinical programs, and increased outside services of $1.2 million.General and administrative expenses were $15.5 million for the three months ended September 30, 2023, compared to $11.9 million for the same period in 2022. The change was primarily due to an increase in personnel costs of $3.2 million.Net loss for the three months ended September 30, 2023, was $57.5 million, compared to a net loss of $41.9 million for the same period in 2022.Revenues were $0.3 million for the three months ended September 30, 2023, compared to $0.5 million for the same period in 2022. Revenues in both periods were primarily derived from the paltusotine licensing arrangement with Sanwa Kagaku Kenkyusho Co., Ltd.Unrestricted cash, cash equivalents, and investments totaled $554.7 million as of September 30, 2023, compared to $334.4 million as of December 31, 2022. Based on its current projections, the company now expects that its cash, cash equivalents and short-term investments will be sufficient to fund its current operating plan into 2026.The company had 66,799,257 common shares outstanding as of October 31, 2023. About Crinetics Pharmaceuticals Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors. Paltusotine, an investigational, first-in-class, oral somatostatin receptor type 2 (SST2) agonist, is in Phase 3 clinical development for acromegaly and Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics has demonstrated pharmacologic proof-of-concept in a Phase 1 clinical study for CRN04894 a first-in-class, investigational, oral ACTH antagonist, that is currently in Phase 2 clinical studies for the treatment of Cushing’s disease and congenital adrenal hyperplasia. All of the Company’s drug candidates are orally delivered, small molecule new chemical entities resulting from in-house drug discovery efforts, including additional discovery programs addressing a variety of endocrine conditions such as hyperparathyroidism, polycystic kidney disease, Graves’ disease, thyroid eye disease, hyperinsulinism, diabetes and obesity. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of paltusotine and CRN04894, including the therapeutic potential and clinical benefits or safety profile thereof; the expected timing of topline data from the ongoing Phase 3 clinical studies of paltusotine in acromegaly and Phase 2 study of paltusotine in carcinoid syndrome; plans to submit data from the ongoing Phase 3 clinical studies of paltusotine in acromegaly to regulators in support of applications seeking approval for the use of paltusotine in acromegaly patients and the expected timing of an NDA submission for paltusotine for the treatment or maintenance of treatment of acromegaly in the United States; the expected timing of data from studies of CRN04894 in Cushing’s disease and congenital adrenal hyperplasia; and the expected timing through which our cash, cash equivalents, and short-term investments will fund our operating plans. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including, without limitation, topline data that we report may change following a more comprehensive review of the data related to the clinical studies and such data may not accurately reflect the complete results of a clinical study, and the FDA and other regulatory authorities may not agree with our interpretation of such results; we may not be able to obtain, maintain and enforce our patents and other intellectual property rights, and it may be prohibitively difficult or costly to protect such rights; the COVID-19 pandemic and other geopolitical events may disrupt Crinetics’ business and that of the third parties on which it depends, including delaying or otherwise disrupting its clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity; unexpected adverse side effects or inadequate efficacy of the company’s product candidates that may limit their development, regulatory approval and/or commercialization; the company’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the success of Crinetics’ clinical studies and nonclinical studies; regulatory developments in the United States and foreign countries; clinical studies and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development or be approved for marketing; Crinetics may use its capital resources sooner than expected; any future impacts to our business resulting from geopolitical developments outside our control; and the other risks and uncertainties described in the company’s periodic filings with the SEC. The events and circumstances reflected in the company’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading “Risk Factors” in Crinetics’ periodic reports, including its annual report on Form 10-K for the year ended December 31, 2022. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. CRINETICS PHARMACEUTICALS, INC.CONDENSED CONSOLIDATED FINANCIAL STATEMENT DATA(In thousands, except per share data)(Unaudited) Three months endedSeptember 30, Nine months endedSeptember 30, STATEMENTS OF OPERATIONS DATA: 2023 2022 2023 2022 Revenues $346 $458 $4,013 $4,028 Operating expenses: Research and development 43,839 31,987 122,947 93,234 General and administrative 15,484 11,925 41,016 31,120 Total operating expenses 59,323 43,912 163,963 124,354 Loss from operations (58,977) (43,454) (159,950) (120,326)Total other income, net 2,516 1,529 6,515 2,409 Loss before equity method investment (56,461) (41,925) (153,435) (117,917)Loss on equity method investment (997) — (997) (1,010)Net loss $(57,458) $(41,925) $(154,432) $(118,927)Net loss per share - basic and diluted $(1.01) $(0.78) $(2.81) $(2.32)Weighted-average shares - basic and diluted 56,808 53,768 55,003 51,356 BALANCE SHEET DATA: September 30,2023 December 31,2022 Cash, cash equivalents and investments $554,653 $334,425 Working capital $535,297 $317,461 Total assets $641,537 $352,176 Total liabilities $93,789 $35,848 Accumulated deficit $(593,605) $(439,173)Total stockholders’ equity $547,748 $316,328 Contact: Chas SchultzVP, IR & Corporate Communicationscschultz@crinetics.com(858) 450-6464 Investors / Media: Corey Davis LifeSci Advisors, LLC cdavis@lifesciadvisors.com (212) 915-2577 Jenn GordonSpectrum Sciencejgordon@spectrumscience.com (202) 957-7795

Ad hoc announcement pursuant to Art. 53 LR Transformation into a “pure-play” innovative medicines business is complete, with the spin-off of Sandoz; commentary below is on continuing operations2Q3 sales grew +12% (cc, +12% USD) with core operating income growing +21% (cc, +17% USD) Growth driven by continued strong performance from Kesimpta (+124% cc), Entresto (+31% cc), Kisqali (+76% cc), Pluvicto (+217% cc) and Scemblix (+157% cc) Q3 operating income grew +13% (cc, -4% USD) driven by higher sales and lower restructuring charges, partly offset by higher impairments through discontinuation of early stage development projects Q3 net income grew +37% (cc, +14% USD) mainly due to higher operating incomeQ3 free cash flow3 was USD 5.0 billion (+24% USD) driven by higher net cash flows from operating activitiesQ3 core EPS grew +29% (cc, +24% USD) to USD 1.74Strong nine months performance with sales growing +10% (cc, +8% USD) and core operating income growing +19% (cc, +13% USD)Q3 key innovation milestones, including positive Ph3 data for multiple pipeline assets with blockbuster potential: Cosentyx – FDA approval for intravenous formulation in three indications (PsA, AS, nr-axSpA)Demonstrated clinically meaningful and statistically significant Ph3 data for: 1) Pluvicto (mCRPC pre-taxane), 2) iptacopan (IgAN), 3) remibrutinib (CSU), 4) Lutathera (GEP-NETs) Kisqali – Ph3 NATALEE iDFS 500 event analysis complete; file submitted in EU, US submission planned for Q4 2023 Initiated previously announced, up-to USD 15 billion share buyback to be completed by year-end 2025Full-year 2023 guidance raised for core operating income based on strong momentum4 Net sales expected to grow high single digitCore operating income expected to grow mid to high teens (from low double digit to mid teens) Basel, October 24, 2023 – commenting on the quarter, Vas Narasimhan MD, CEO of Novartis, said: “Novartis delivered a very strong quarter, with double-digit sales and core operating income growth leading to a further upgrade to 2023 guidance. We have successfully executed the spin-off of Sandoz, allowing us to fully focus on high-value innovative medicines. Our growth drivers, including Kesimpta, Entresto, Kisqali and Pluvicto, continue to perform well in the market. Our robust pipeline also continues to deliver, and we have achieved important innovation milestones for Pluvicto, iptacopan, remibrutinib and Lutathera. We are confident in our mid-term growth outlook and remain committed to creating value for our shareholders.” Key figures1 Continuing operations2 Q3 2023 Q3 2022 % change 9M 2023 9M 2022 % change USD m USD m USD cc USD m USD m USD cc Net sales 11 782 10 492 12 12 34 017 31 630 8 10 Operating income 1 762 1 826 -4 13 7 187 6 191 16 31 Net income 1 513 1 330 14 37 5 934 4 734 25 41 EPS (USD) 0.73 0.61 20 45 2.84 2.16 31 49 Free cash flow 5 043 4 054 24 11 019 8 661 27 Core operating income 4 405 3 772 17 21 12 551 11 149 13 19 Core net income 3 585 3 035 18 23 10 320 8 983 15 22 Core EPS (USD) 1.74 1.40 24 29 4.95 4.09 21 28 1 Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 48 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year. 2 As defined on page 37 of the Condensed Interim Financial Report, Continuing operations include the retained business activities of Novartis, comprising the Innovative Medicines Division and the continuing Corporate activities and Discontinued operations include operational results from the Sandoz business. 3 Effective January 1, 2023, Novartis revised its definition of free cash flow, to define free cash flow as net cash flows from operating activities less purchases of property, plant and equipment. To aid in comparability, the prior year free cash flow amounts have been revised to conform with the new free cash flow definition. See page 48 of the Condensed Interim Financial Report. 4 Please see detailed guidance assumptions on page 8. Strategy update Our focus Novartis has completed its transformation into a “pure-play” innovative medicines business, with the successful spin-off of Sandoz. Our focus is now centered on four core therapeutic areas (cardiovascular, renal and metabolic; immunology; neuroscience, and oncology). In each of these areas, we have multiple significant in-market and pipeline assets, all of which address diseases with a high burden and have substantial growth potential. In addition to two established technology platforms (chemistry and biotherapeutics), three emerging platforms (gene & cell therapy, radioligand therapy, and xRNA) are being prioritized for continued investment into new R&D capabilities and manufacturing scale. Geographically, we are focused on growing in our priority geographies – the US, China, Germany and Japan. Financials Following the September 15, 2023, shareholders’ approval of the spin-off of the Sandoz business the Company reported its consolidated financial statements for the current and prior years as “continuing operations” and “discontinued operations.” Continuing operations include the retained business activities of Novartis, comprising the Innovative Medicines Division and the continuing corporate activities. Discontinued operations include the Sandoz Division and selected portions of corporate activities attributable to Sandoz’s business, as well as certain expenses related to the spin-off. With the spin-off of the Sandoz business, Novartis operates as a single global operating segment, being a focused innovative medicines company. The commentary below focuses on continuing operations. We also provide information on discontinued operations, which mainly includes Sandoz and allocated corporate activities. Continuing operations Third quarter Net sales were USD 11.8 billion (+12%, +12% cc) driven by volume growth of 17 percentage points. Pricing had a negative impact of 1 percentage point and generic competition had a negative impact of 4 percentage points. Operating income was USD 1.8 billion (-4%, +13% cc), mainly driven by higher sales and lower restructuring charges, partly offset by higher impairments through discontinuation of early stage development projects. Net income was USD 1.5 billion (+14%, +37% cc), mainly due to higher operating income and lower tax rate driven by non-recurring items. EPS was USD 0.73 (+20%, +45% cc), growing faster than net income, benefiting from lower weighted average number of shares outstanding. Core operating income was USD 4.4 billion (+17%, +21% cc), mainly driven by higher sales. Core operating income margin was 37.4% of net sales, increasing by 1.4 percentage points (+2.7 percentage points cc). Core net income was USD 3.6 billion (+18%, +23% cc), mainly due to higher core operating income. Core EPS was USD 1.74 (+24%, +29% cc), growing faster than core net income, benefiting from lower weighted average number of shares outstanding. Free cash flow amounted to USD 5.0 billion (+24% USD), compared with USD 4.1 billion in the prior year quarter driven by higher net cash flows from operating activities. Nine months Net sales were USD 34.0 billion (+8%, +10% cc) driven by volume growth of 16 percentage points. Pricing had a negative impact of 2 percentage points and generic competition had a negative impact of 4 percentage points. Operating income was USD 7.2 billion (+16%, +31% cc), mainly driven by higher sales, other income from legal matters, lower restructuring charges, partly offset by higher impairments through discontinuation of early stage development projects. Net income was USD 5.9 billion (+25%, +41% cc), mainly due to higher operating income. EPS was USD 2.84 (+31%, +49% cc), growing faster than net income, benefiting from lower weighted average number of shares outstanding. Core operating income was USD 12.6 billion (+13%, +19% cc), mainly driven by higher sales. Core operating income margin was 36.9% of net sales, increasing by 1.7 percentage points (+2.9 percentage points cc). Core net income was USD 10.3 billion (+15%, +22% cc), mainly due to higher core operating income. Core EPS was USD 4.95 (+21%, +28% cc), growing faster than core net income, benefiting from lower weighted average number of shares outstanding. Free cash flow amounted to USD 11.0 billion (+27% USD), compared with USD 8.7 billion in the prior year period driven by higher net cash flows from operating activities. Discontinued operations Results for discontinued operations in the third quarter and nine-months 2023 include the results of the Sandoz Division and selected portions of corporate activities attributable to Sandoz business, as well as certain expenses related to the spin-off. In connection with the Sandoz spin-off on October 4, 2023, the Company will report as part of its Q4 discontinued operations results a one-time non-cash non-taxable IFRS gain of approximately USD 5.9 billion. This IFRS gain represents mainly the excess amount of the IFRS distribution liability, which is the estimated fair value of the Sandoz business distributed to Novartis AG shareholders, over the then carrying value of Sandoz business net assets. Third quarter Discontinued operations net sales were USD 2.5 billion (+8%, +6% cc), mainly driven by ex-US growth. Operating loss amounted to USD 86 million, compared to an operating income of USD 342 million in the previous year. The operating loss in third quarter was driven by the discontinued corporate transaction cost related to spin-off of the Sandoz business, which were core adjustments. Core operating income was USD 250 million (-51%, -38% cc), mainly driven by lower gross margin and higher SG&A expenses. Net income from discontinued operations amounted to USD 250 million, compared to USD 245 million in the previous year. Nine months Discontinued operations net sales were USD 7.4 billion (+6%, +8% cc), mainly driven by ex-US growth. Operating income amounted to USD 265 million, compared to USD 1.1 billion in the previous year. The current year period includes the discontinued corporate transaction cost related to spin-off of the Sandoz business, which were core adjustments. Core operating income was USD 1.2 billion (-20%, -11% cc), mainly driven by higher SG&A expenses and R&D investments. Net income from discontinued operations amounted to USD 440 million, compared to USD 755 million in the previous year. Total company Third quarter Total company net income was USD 1.8 billion, mainly due to higher operating income and lower tax rate driven by non-recurring items compared to USD 1.6 billion in the prior year. EPS increased to USD 0.85 from USD 0.73 in prior year. Cash flows from operating activities amounted to USD 5.4 billion compared to USD 4.7 billion in the prior year. Free cash flow amounted to USD 5.0 billion compared to USD 4.4 billion in the prior year. Nine months Total company net income was USD 6.4 billion, mainly due to higher operating income compared to USD 5.5 billion in the prior year. EPS increased to USD 3.05 from USD 2.50 in prior year. Cash flows from operating activities amounted to USD 11.9 billion compared to USD 10.1 billion in the prior year. Free cash flow amounted to USD 11.0 billion compared to USD 9.3 billion in the prior year. Q3 key growth drivers Underpinning our financial results in the quarter is a continued focus on key growth drivers including: Kesimpta (USD 657 million, +124% cc) sales growth was driven by increased demand, strong access and benefitting from a one-time revenue deduction adjustment in Europe Entresto (USD 1 485 million, +31% cc) sustained robust demand-led growth, benefitting from the adoption of guideline-directed medical therapy across regions Kisqali (USD 562 million, +76% cc) sales grew strongly across all regions, based on increasing recognition of consistent overall survival and quality of life benefits Pluvicto (USD 256 million, +217% cc) continued sales growth in the US. Supply now unconstrained, focusing on initiating new patients Ilaris (USD 335 million, +24% cc) sales grew across all regions Scemblix (USD 106 million, +157% cc) sales grew across all regions, demonstrating the high unmet need in CML Leqvio (USD 90 million, +165% cc) launch in the US and other markets ongoing, with focus on patient on-boarding, removing access hurdles and enhancing medical education Cosentyx (USD 1 329 million, +4% cc) continued demand growth across key regions, partly offset by US revenue deduction fluctuations across periods. Ex-US sales grew +15% (cc) Promacta/Revolade (USD 576 million, +10% cc) grew across all regions, driven by increased use in chronic ITP and severe aplastic anemia Xolair (USD 369 million, +13% cc) sales grew across most regions Jakavi (USD 427 million, +9% cc) sales grew in Emerging Growth Markets, Europe and Japan, driven by strong demand in both myelofibrosis and polycythemia vera Tafinlar + Mekinist (USD 482 million, +8% cc) sales grew in the US and Emerging Growth Markets, driven by demand in BRAF+ adjuvant melanoma and NSCLC indications Lutathera (USD 159 million, +19% cc) sales grew mainly in the US, Japan and Europe due to increased demand Emerging Growth Markets* Overall, grew +17% (cc). Growth in China (+14% cc, USD 848 million) *All markets except the US, Canada, Western Europe, Japan, Australia, and New Zealand Net sales of the top 20 products in 2023 Q3 2023 % change 9M 2023 % change USD m USD cc USD m USD cc Entresto 1 485 31 31 4 400 31 33 Cosentyx 1 329 4 4 3 677 -1 1 Promacta/Revolade 576 10 10 1 706 10 12 Kesimpta- excl. revenue deduction adjust.* 657 12787 124 86 1 530 112 95 112 96 Kisqali 562 72 76 1 470 68 74 Tafinlar + Mekinist 482 7 8 1 436 10 13 Tasigna 464 -5 -5 1 402 -3 -1 Jakavi 427 11 9 1 276 9 11 Lucentis 363 -20 -22 1 174 -20 -19 Xolair 369 15 13 1 085 4 6 Sandostatin 338 15 15 998 7 8 Ilaris 335 23 24 979 18 20 Zolgensma 308 -3 -2 928 -13 -11 Gilenya 270 -47 -48 771 -54 -53 Pluvicto 256 220 217 707 nm nm Exforge Group 187 1 3 557 -5 -1 Galvus Group 181 -15 -4 539 -17 -10 Diovan Group 153 -4 -1 466 -9 -4 Lutathera 159 20 19 458 34 34 Gleevec/Glivec 144 -19 -17 433 -24 -21 Top 20 brands total 9 045 13 13 25 992 9 11 nm= not meaningful* Sales growth benefiting from a one-time revenue deduction adjustment in Europe R&D update - key developments from the third quarter New approvals Leqvio Approved in China and Japan as the first and only small interfering RNA (siRNA) therapy for LDL-C reduction Cosentyx In October, FDA approved the intravenous formulation in three indications: Psoriatic Arthritis, Ankylosing Spondylitis, and non-radiographic axial SpA Regulatory updates Kisqali EU file submission in adjuvant early breast cancer setting; US submission planned for Q4 2023 Adakveo EC adopts decision endorsing CHMP recommendation to revoke conditional marketing authorization Results from ongoing trials and other highlights iptacopan In October, Ph3 APPLAUSE-IgAN study interim analysis demonstrated clinically meaningful and highly statistically significant proteinuria reduction in patients with IgA nephropathy. The trial met its pre-specified interim analysis (9 months) primary endpoint, demonstrating superiority vs. placebo in proteinuria reduction, with safety consistent with previously reported data. Novartis plans to review interim data with regulatory authorities for accelerated approval; study continues with final readout at 24 months remibrutinib Ph3 REMIX-1 and REMIX-2 studies met all primary and secondary endpoints, showing fast, clinically meaningful improvements across urticaria disease activity scores. Remibrutinib demonstrated a favorable safety profile with rates of adverse events comparable to placebo and balanced liver function tests across both studies.Final (52 weeks) readout and submissions to health authorities are expected in 2024. Full data will be presented at upcoming medical meetings Pluvicto Ph3 PSMAfore study demonstrated clinically meaningful and statistically significant rPFS benefit in patients with PSMA+ mCRPC in the pre-taxane setting. Per updated analysis presented at ESMO, median rPFS more than doubled compared to ARPI switch. Patients on Pluvicto showed improved quality of life compared to daily oral ARPI, along with improvements in other clinically meaningful efficacy endpoints including PSA response, ORR, DOR and time to symptomatic skeletal event, with favorable safety. Pre-specified crossover-adjusted OS analysis demonstrated a HR of 0.80 (0.48, 1.33); the unadjusted ITT OS analysis was confounded by a high rate of crossover. Novartis is continuing to collect OS data, regulatory filings are anticipated in 2024 Lutathera Ph3 NETTER-2 study demonstrated clinically meaningful and statistically significant improvement in PFS (primary endpoint) in patients with newly diagnosed somatostatin receptor (SSTR)-positive, Grade 2 and 3, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) vs. high-dose long-acting octreotide alone. The trial also met its key secondary endpoint of ORR. No new or unexpected safety findings were observed and data are consistent with the already well-established safety profile of Lutathera.Data to be presented at an upcoming medical meeting and discussed with regulatory authorities, with submissions to follow Kisqali Ph3 NATALEE iDFS 500 event analysis complete. Updated data is consistent with the interim analysis results announced in March 2023 and will be communicated at an upcoming medical meeting.Health-related quality of life (HRQoL) analyses from Ph3 NATALEE trial demonstrated that patients with early breast cancer receiving adjuvant Kisqali plus ET for up to 3 years maintained physical and social functioning; psychological well-being; and overall health scores, compared to baseline. Data was presented at the ESMO Virtual Plenary 2023 Leqvio Long-term data from Ph3 ORION-8 demonstrated that Leqvio, in addition to statin therapy, provides consistent low-density lipoprotein cholesterol (LDL-C) reduction beyond six years of treatment in patients with atherosclerotic cardiovascular disease (ASCVD), increased risk of ASCVD or heterozygous familial hypercholesterolemia. Efficacy and safety were consistent with previously reported Ph3 results. Data was presented at ESC 2023 GT005 (PPY988) Development in Geographic Atrophy secondary to dry-Age-related Macular Degeneration discontinued based on benefit-risk assessment. No new safety signals identified. Patients treated will be provided with long term safety follow up Tislelizumab Novartis and BeiGene mutually agreed to terminate the collaboration and license agreement for tislelizumab for certain markets. With the termination, BeiGene will re-assume all development and commercialization rights for tislelizumab, and Novartis will manufacture tislelizumab for certain markets. BeiGene will also provide Novartis with ongoing clinical supply of tislelizumab to support its clinical trials ‘Front of Eye’ Assets Divestment completed of ‘front of eye’ ophthalmology assets to Bausch + Lomb Capital structure and net debt Retaining a good balance between investment in the business, a strong capital structure and attractive shareholder returns remains a priority. During the first nine months of 2023, Novartis repurchased a total of 74.9 million shares for USD 7.2 billion on the SIX Swiss Exchange second trading line. These repurchases included 52.8 million shares (USD 4.9 billion) under the USD 15 billion share buyback (announced in December 2021 and completed in June 2023) and 10.4 million shares (USD 1.1 billion) under the new up-to USD 15 billion share buyback announced in July 2023. In addition, 11.7 million shares (USD 1.2 billion) were repurchased to mitigate dilution related to participation plans of associates. Furthermore, 1.4 million shares (for an equity value of USD 0.1 billion) were repurchased from associates. In the same period, 12.2 million shares (for an equity value of USD 0.8 billion) were delivered as a result of options exercised and share deliveries related to participation plans of associates. Consequently, the total number of shares outstanding decreased by 64.1 million versus December 31, 2022. These treasury share transactions resulted in an equity decrease of USD 6.5 billion and a net cash outflow of USD 7.3 billion. As of September 30, 2023, net debt excluding net debt related to discontinued operations increased to USD 10.8 billion compared to USD 7.2 billion total net debt at December 31, 2022. The increase was mainly due to the USD 7.3 billion annual dividend payment, net cash outflow for treasury share transactions of USD 7.3 billion and net M&A / intangible assets transactions of USD 2.9 billion. This increase in net debt was partially offset by USD 11.0 billion free cash flow. As part of the spin-off, Sandoz incurred total bank debt of approximately USD 3.7 billion and paid approximately USD 3.0 billion in cash, including payment in satisfaction of certain intercompany indebtedness owed by Sandoz and its subsidiaries to Novartis and its affiliates as of September 30, 2023. This reduced the net debt position of Novartis by USD 3.0 billion. As of Q3 2023, the long-term credit rating for the company is A1 with Moody’s Investors Service and AA- with S&P Global Ratings. 2023 outlook raised due to strong momentum Barring unforeseen events; growth vs prior year in cc Previous Guidance Net sales Expected to grow high single digit Unchanged Core operating income Expected to grow mid to high teens (from low double digit to mid teens) Key assumptions: No US Entresto Gx at risk launch in 2023No Sandostatin LAR generics enter in the US in 2023 Entresto patent update Novartis has appealed to reverse the negative US District Court decision and to uphold the validity of its combination patent covering Entresto and other combinations of sacubitril and valsartan, which expires in 2025 (with pediatric exclusivity). No generics have tentative or final approval in the US. Any US commercial launch of a generic Entresto product prior to the final outcome of Novartis combination patent appeal, or ongoing litigations involving other patents, may be at risk of later litigation developments. Foreign exchange impactIf late-October exchange rates prevail for the remainder of 2023, the foreign exchange impact for the year would be negative 2 percentage point on net sales and negative 6 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website. Key figures1 Continuing operations2 Q3 2023 Q3 2022 % change 9M 2023 9M 2022 % change USD m USD m USD cc USD m USD m USD cc Net sales 11 782 10 492 12 12 Net sales 34 017 31 630 8 10 Operating income 1 762 1 826 -4 13 Operating income 7 187 6 191 16 31 As a % of sales 15.0 17.4 As a % of sales 21.1 19.6 Net income 1 513 1 330 14 37 Net income 5 934 4 734 25 41 EPS (USD) 0.73 0.61 20 45 EPS (USD) 2.84 2.16 31 49 Cash flows from operating activities 5 304 4 275 24 Cash flows from operating activities 11 673 9 271 26 Non-IFRS measures Non-IFRS measures Free cash flow 5 043 4 054 24 Free cash flow 11 019 8 661 27 Core operating income 4 405 3 772 17 21 Core operating income 12 551 11 149 13 19 As a % of sales 37.4 36.0 As a % of sales 36.9 35.2 Core net income 3 585 3 035 18 23 Core net income 10 320 8 983 15 22 Core EPS (USD) 1.74 1.40 24 29 Core EPS (USD) 4.95 4.09 21 28 Discontinued operations2 Q3 2023 Q3 2022 % change 9M 2023 9M 2022 % change USD m USD m USD cc USD m USD m USD cc Net sales 2 476 2 286 8 6 Net sales 7 428 6 998 6 8 Operating (loss)/income -86 342 nm nm Operating income 265 1 057 -75 -60 As a % of sales nm 15.0 As a % of sales 3.6 15.1 Net income 250 245 2 79 Net income 440 755 -42 -18 Non-IFRS measures Non-IFRS measures Core operating income 250 510 -51 -38 Core operating income 1 185 1 486 -20 -11 As a % of sales 10.1 22.3 As a % of sales 16.0 21.2 Total company Q3 2023 Q3 2022 % change 9M 2023 9M 2022 % change USD m USD m USD cc USD m USD m USD cc Net income 1 763 1 575 12 44 Net income 6 374 5 489 16 33 EPS (USD) 0.85 0.73 16 51 EPS (USD) 3.05 2.50 22 40 Cash flows from operating activities 5 378 4 721 14 Cash flows from operating activities 11 911 10 125 18 Non-IFRS measures Non-IFRS measures Free cash flow 5 043 4 435 14 Free cash flow 11 038 9 325 18 Core net income 3 784 3 419 11 16 Core net income 11 209 10 101 11 18 Core EPS (USD) 1.83 1.58 16 22 Core EPS (USD) 5.37 4.60 17 24 nm= not meaningful 1 Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 48 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.2 As defined on page 37 of the Condensed Interim Financial Report, Continuing operations include the retained business activities of Novartis, comprising the Innovative Medicines Division and the continuing Corporate activities and Discontinued operations include operational results from the Sandoz business. Detailed financial results accompanying this press release are included in the Condensed Interim Financial Report at the link below:https://ml-eu.globenewswire.com/resource/download/1a97fd38-edbc-49ea-9350-8042dc006c1c/ Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995, that can generally be identified by words such as “guidance,” “expected,” “momentum,” “continue,” “drivers,” “confident,” “outlook,” “remain,” “committed,” “prioritized,” “prioritizing,” “continued,” “growing,” “growth,” “plans,” “on-track,” “continuing,” “anticipated,” “to follow,” “will,” “outlook,” “may,” “upcoming,” “ongoing,” “focus,” “pipeline,” “potential,” “estimated,” “launch,” “to deliver,” “transformation,” “transformative,” “address,” “planned,” “focusing,” “accelerated,” “long-term,” “innovation,” “priority,” “can,” “awaiting,” or similar expressions, or by express or implied discussions regarding potential new products, potential new indications for existing products, potential product launches, or regarding potential future revenues from any such products; or regarding potential future, pending or announced transactions; or regarding potential future sales or earnings of Novartis; or regarding discussions of strategy, priorities, plans, expectations or intentions, including our transformation into a “pure-play” innovative medicines business; or regarding our liquidity or cash flow positions and our ability to meet our ongoing financial obligations and operational needs; or regarding our USD 15 billion share buyback; or regarding our appeal of the negative decision of the US District Court for the District of Delaware on the validity of our patent covering Entresto and combinations of sacubitril and valsartan. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. You should not place undue reliance on these statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. Neither can there be any guarantee expected benefits or synergies from the transactions described in this press release will be achieved in the expected timeframe, or at all. In particular, our expectations could be affected by, among other things: liquidity or cash flow disruptions affecting our ability to meet our ongoing financial obligations and to support our ongoing business activities; the impact of a partial or complete failure of the return to normal global healthcare systems including prescription dynamics; global trends toward healthcare cost containment, including ongoing government, payer and general public pricing and reimbursement pressures and requirements for increased pricing transparency; uncertainties regarding potential significant breaches of data security or data privacy, or disruptions of our information technology systems; regulatory actions or delays or government regulation generally, including potential regulatory actions or delays with respect to the development of the products described in this press release; the potential that the benefits and opportunities expected from our planned spin-off of Sandoz may not be realized or may be more difficult or take longer to realize than expected; the uncertainties in the research and development of new healthcare products, including clinical trial results and additional analysis of existing clinical data; our ability to obtain or maintain proprietary intellectual property protection, including the ultimate extent of the impact on Novartis of the loss of patent protection and exclusivity on key products; safety, quality, data integrity, or manufacturing issues; uncertainties involved in the development or adoption of potentially transformational technologies and business models; uncertainties regarding actual or potential legal proceedings, investigations or disputes; our performance on environmental, social and governance measures; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; uncertainties regarding future global exchange rates; uncertainties regarding future demand for our products; and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise. All product names appearing in italics are trademarks owned by or licensed to Novartis AG and its subsidiaries. BAUSCH + LOMB is a registered trademark of Bausch & Lomb Incorporated. About Novartis Novartis is a focused innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. Novartis will conduct a conference call with investors to discuss this news release today at 14:00 Central European time and 8:00 Eastern Time. A simultaneous webcast of the call for investors and other interested parties may be accessed by visiting the Novartis website. A replay will be available after the live webcast by visiting https://www.novartis.com/investors/event-calendar. Detailed financial results accompanying this press release are included in the condensed interim financial report at the link below. Additional information is provided on Novartis divisions and pipeline of selected compounds in late stage development and a copy of today's earnings call presentation can be found at https://www.novartis.com/investors/event-calendar. Important dates November 13, 2023 Impact and Health Equity Annual Event November 28, 2023 R&D Day Please find full media release in English attached and on the following link: Media release (PDF) German version is available through the following link: Medienmitteilung (PDF) French version is available through the following link: Communiqué aux médias (PDF)