On January 31, 2024 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported that management will participate in the following investor conferences (Press release, Protara Therapeutics, JAN 31, 2024, View Source [SID1234639749]):

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Guggenheim Healthcare Talks 6th Annual Biotechnology Conference. A fireside chat will take place on Wednesday, February 7, 2024 at 10:30 am ET in New York.
Oppenheimer 34th Annual Healthcare Life Sciences Conference. A fireside chat will take place virtually on Wednesday, February 14, 2024 at 8:40 am ET0

A live webcast of the events can be accessed by visiting the Events and Presentations section of the Company’s website: View Source The webcasts will be archived for a limited time following the presentations.

On January 31, 2024, Protagonist Therapeutics, Inc. (the "Company") reported to have entered into a License and Collaboration Agreement (the "Collaboration Agreement") with Takeda Pharmaceuticals USA, Inc. ("Takeda") for the development, manufacture and commercialization of the Company’s rusfertide product candidate ("Rusfertide") and other specified second-generation injectable hepcidin mimetic compounds (the "Licensed Products") (Filing, 8-K, Protagonist, JAN 31, 2024, View Source [SID1234639748]). The Collaboration Agreement will become effective (the "Effective Date") upon the receipt of clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976.

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Collaboration and Licenses. The Company and Takeda have agreed that the parties will, as further described below, jointly develop and commercialize the Licensed Products in the United States (the "Profit-Share Territory") and that Takeda solely and exclusively will develop and commercialize the Licensed Products in all other countries (the "Takeda Territory"). Each of the Company and Takeda is obligated to use commercially reasonable efforts to develop and commercialize at least one Licensed Product in the Profit-Share Territory, and Takeda is also obligated to use commercially reasonable efforts to develop and commercialize at least one Licensed Product in major regions of the Takeda Territory.

The Company and Takeda have agreed to share costs of the development, manufacture and commercialization activities for the Licensed Products under the Collaboration Agreement in the Profit-Share Territory, provided that (i) the Company will lead, and will be responsible for its costs associated with, completion of the ongoing Phase 3 VERIFY program evaluating Rusfertide for the treatment of Polycythemia Vera (the "VERIFY Program"); (ii) Takeda will lead, and will be responsible for its costs associated with, pre-commercialization activities related to Rusfertide in the Profit-Share Territory, and (iii) Takeda will lead commercialization of rusfertide globally, with Protagonist holding an option to co-detail in the U.S. Takeda is solely responsible for all costs for the development, manufacture and commercialization activities under the Collaboration Agreement in the Takeda Territory, and will have sole responsibility and decision-making authority with respect to such activities in the Takeda Territory.

The Company has agreed to grant to Takeda a non-transferable, sublicensable, except for certain specified exceptions, license to certain intellectual property of the Company as needed to perform the activities under the Collaboration Agreement. Such license is co-exclusive with the Company in the Profit-Share Territory and exclusive, even as to the Company, in the Takeda Territory, subject to certain retained rights to allow the Company to exercise its rights and perform its obligations under the Collaboration Agreement.

Financial Terms; Opt-out Rights.

Upfront Payment; Profit Share; Booking of Revenues. Under the terms of the Collaboration Agreement, Takeda has agreed to pay the Company an upfront payment of $300 million within 30 days after the Effective Date. For so long as a Licensed Product is being sold in the Profit-Share Territory, the Company and Takeda will share in all operating profits and losses arising from such Licensed Product in the Profit-Share Territory (50 percent to the Company and 50 percent to Takeda) as further defined in the Collaboration Agreement. The Collaboration Agreement provides that Takeda will book sales of Licensed Products globally.

Royalties. Takeda has agreed to pay the Company tiered royalties of 10% – 17% on net sales of Licensed Products in the Takeda Territory. If the Company has exercised an Opt-out Right (as defined below), Takeda has agreed to pay the Company royalties of 14% – 29% on worldwide net sales of Licensed Products with respect to which the Company has exercised an Opt-out Right. Royalty payments may be reduced in certain specified circumstances.

Milestone Payments; Opt-out Payment. The Collaboration Agreement provides for aggregate development, regulatory and commercial milestone payments from Takeda to the Company for Licensed Products of (i) up to $330 million if the Company does not exercise an Opt-out Right and remains in the 50:50 profit- and loss-sharing arrangement in the Profit-Share Territory; and (ii) up to $975 million if the Company exercises the Full Opt-out Right (as defined below). Milestone payments as to Licensed Products other than Rusfertide may be reduced in certain specified circumstances.

In addition to the milestone payments described above, in the event the Company exercises the Full Opt-out Right during the Initial Opt-out Period (as defined below), the Company will receive: (a) a $200 million payment following its exercise of the Full Opt-out Right, and (b) an additional $200 million payment following FDA approval of the New Drug Application for Rusfertide for polycythemia vera (together, the "Opt-out Payment").

Opt-out Rights. The Company will have the right to opt-out entirely of profit- and loss-sharing in the Profit-Share Territory as to all Licensed Products (the "Full Opt-out Right") during the 90-day period beginning 120 days after filing of a New Drug Application with the United States Food and Drug Administration for Rusfertide for Polycythemia Vera (the "Initial Opt-out Period"); and (ii) for convenience without receipt of the Opt-out Payment (generally following the Initial Opt-out Period). In addition, if the Company does not exercise the Full Opt-out Right, the Company may opt-out of profit- and loss-sharing in the Profit-Share Territory as to Licensed Products other than Rusfertide on a Licensed Product-by-Licensed Product basis (each, a "Partial Opt-out Right" and either the Full Opt-out Right or a Partial Opt-out right being an "Opt-out Right"). Following the Company’s exercise of an Opt-out Right, the Company has agreed to transition to Takeda applicable development and commercial activities, and Takeda has agreed to assume sole operational and financial responsibility for such activities.

Governance. The activities of the parties for the Profit-Share Territory are to be conducted pursuant to joint development plans and joint commercialization plans, on a Licensed Product-by-Licensed Product basis, and overseen by a joint steering committee (the "JSC") and various subcommittees, including a Joint Commercialization Committee and a Joint Development Committee. The JSC shall be composed of an equal number of representatives from each of the Company and Takeda.

Exclusivity; Right of First Negotiation. During the term of the Collaboration Agreement, neither party nor any of its respective affiliates is permitted outside of the Collaboration Agreement to directly or indirectly develop, manufacture, or commercialize injectable hepcidin mimetic products beyond agreed-upon stages of development (pre-clinical in vitro research activities in the case of the Company, and up to Phase 2b clinical development in the case of Takeda, respectively are permitted). In addition, the Company has granted to Takeda a 120-day right of first negotiation with respect to other Company products in the hepcidin pathway.

Termination. Unless earlier terminated, the Collaboration Agreement expires on a Licensed Product-by-Licensed Product and country-by-country basis on the later of (a) in the Takeda Territory, the expiration of the royalty term for such Licensed Product in such country or (b) in the Profit-Share Territory, until the parties agree to permanently stop commercializing such Licensed Product. Takeda may terminate the Collaboration Agreement for convenience in its entirety or as to a major region by providing advance written notice following the earliest of (i) the receipt of Phase 3 data with respect to the VERIFY Program, (ii) the third anniversary of the Effective Date or (iii) upon the occurrence of certain specified adverse events related to the clinical development of Rusfertide. Either party may terminate the Collaboration Agreement in its entirety (A) in the event of a material breach by the other party, subject to a cure period and (B) in the event of the insolvency of the other party, in each case subject to specified conditions.

The foregoing description of the terms of the Collaboration Agreement is qualified in its entirety by reference to the full text of the Collaboration Agreement, a copy of which the Company intends to file with the U.S. Securities and Exchange Commission as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ending March 31, 2024.

On January 31, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that management will participate in the following investor conferences in February (Press release, ORIC Pharmaceuticals, JAN 31, 2024, View Source [SID1234639747]):

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6th Annual Guggenheim Biotechnology Conference – Participating in a fireside chat on Wednesday, February 7, 2024, at 10:00 a.m. ET.

Oppenheimer 34th Annual Healthcare Life Sciences Conference – Participating in a virtual fireside chat on Wednesday, February 14, 2024, at 12:00 p.m. ET.

Webcasts of the discussions will be available through the investor section of the company’s website at www.oricpharma.com. Replays of the webcasts will be available for 30 days following each event.

On January 31, 2024 Vas Narasimhan, CEO of Novartis, reported: "Novartis completed its strategic transformation into a pure-play innovative medicines company and continued its relentless pursuit of sustainable shareholder value creation (Press release, Novartis, JAN 31, 2024, View Source [SID1234639746]). Our robust operational performance continues, with strong double-digit top and bottom-line growth, for the quarter and full year. We delivered ten positive Ph3 readouts on assets with significant sales potential, over the past year. The very strong performance of our key growth drivers and pipeline underscores the confidence in our growth (5% cc CAGR 2023-2028) and margin (40%+ by 2027) mid-term guidance."

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Key figures1
Continuing operations
Q4 2023 Q4 2022 % change FY 2023 FY 2022 % change
USD m USD m USD cc USD m USD m USD cc
Net sales 11 423 10 576 8 10 45 440 42 206 8 10
Operating income 2 582 1 755 47 68 9 769 7 946 23 39
Net income 2 638 1 315 101 130 8 572 6 049 42 62
EPS (USD) 1.29 0.62 108 140 4.13 2.77 49 70
Free cash flow 2 141 3 462 -38 13 160 12 123 9
Core operating income 3 821 3 645 5 13 16 372 14 794 11 18
Core net income 3 126 2 963 6 11 13 446 11 946 13 19
Core EPS (USD) 1.53 1.39 10 16 6.47 5.48 18 25
Strategy Update
Our focus
During 2023, Novartis completed our transformation into a "pure-play" innovative medicines business. We have a clear focus on four core therapeutic areas (cardiovascular-renal-metabolic, immunology, neuroscience and oncology), with multiple significant in-market and pipeline assets in each of these areas, that address high disease 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.

Our priorities
Accelerate growth: Renewed attention to deliver high-value medicines (NMEs) and focus on launch excellence, with a rich pipeline across our core therapeutic areas.
Deliver returns: Continuing to embed operational excellence and deliver improved financials. Novartis remains disciplined and shareholder-focused in our approach to capital allocation, with substantial cash generation and a strong capital structure supporting continued flexibility.
Strengthening foundations: Unleashing the power of our people, scaling data science and technology and continuing to build trust with society.
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 business 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.

Following the spin-off of the Sandoz business, Novartis operates as a single global operating segment 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
Fourth quarter

Net sales were USD 11.4 billion (+8%, +10% cc) in the fourth quarter driven by volume growth of 13 percentage points. Generic competition had a negative impact of 3 percentage points and pricing had no impact.

Operating income was USD 2.6 billion (+47%, +68% cc), mainly driven by higher net sales and lower restructuring charges, partly offset by higher SG&A and R&D investments.

Net income was USD 2.6 billion (+101%, +130% cc), mainly driven by higher operating income and non-recurring favorable tax impacts. EPS was USD 1.29 (+108%, +140% cc), benefiting from lower weighted average number of shares outstanding.

Core operating income was USD 3.8 billion (+5%, +13% cc), mainly driven by higher net sales, partly offset by higher SG&A and R&D investments. Core operating income growth in USD was impacted by negative 2 percentage points from the effect of mid-December currency devaluation in Argentina1. Core operating income margin was 33.5% of net sales, decreasing 1.0 percentage point (+1.0 percentage point cc).

Core net income was USD 3.1 billion (+6%, +11% cc), mainly due to higher core operating income. Core EPS was USD 1.53 (+10%, +16% cc), benefiting from lower weighted average number of shares outstanding.

Free cash flow from continuing operations amounted to USD 2.1 billion (-38% USD), compared with USD 3.5 billion in the prior year quarter driven by lower net cash flows from operating activities.

1 IFRS Accounting Standards requires for our Argentina subsidiary, as it operates in a hyperinflation economy, to translate for consolidation purposes their full year income statement to our USD presentation currency using the ARS closing rate, and not using the average exchange rate for the period. This results in the 9-months and the Q4 devaluation impact being recognized in Q4.

Full year

Net sales were USD 45.4 billion (+8%, +10% cc) in the full year, driven by volume growth of 16 percentage points, partly offset by price erosion of 2 percentage points and the negative impact from generic competition of 4 percentage points.

Operating income was USD 9.8 billion (+23%, +39% cc), mainly driven by higher net sales, lower restructuring charges, and income from legal matters, partly offset by higher impairments and higher SG&A and R&D investments.

Net income was USD 8.6 billion (+42%, +62% cc), mainly driven by higher operating income and non-recurring favorable tax impacts. EPS was USD 4.13 (+49%, +70% cc).

Core operating income was USD 16.4 billion (11%, +18% cc), mainly driven by higher net sales, partly offset by higher SG&A and R&D investments. Core operating income margin was 36.0% of net sales, increasing 0.9 percentage points (+2.4 percentage points cc).

Core net income was USD 13.4 billion (+13%, +19% cc), mainly due to higher core operating income. Core EPS was USD 6.47 (+18%, +25% cc), benefiting from lower weighted average number of shares outstanding.

Free cash flow from continuing operations amounted to USD 13.2 billion (+9% USD), compared with USD 12.1 billion in 2022 driven by higher net cash flows from operating activities.

Discontinued operations
Discontinued operations include the Sandoz generic pharmaceuticals and biosimilars division, certain corporate activities attributable to Sandoz prior to the spin-off up to the distribution date of October 3, 2023, and certain other expenses related to the spin-off. Included in 2023 is also the IFRS Accounting Standards non-cash, non-taxable net gain on the distribution of Sandoz Group AG to Novartis AG shareholders of USD 5.9 billion, representing mainly the excess amount of the IFRS Accounting Standards 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. There were no operating results for the fourth quarter 2023 following the distribution date. The prior year includes the results for the full period.

Fourth quarter

Net income from discontinued operations amounted to USD 5.8 billion, driven by the IFRS Accounting Standards non-cash, non-taxable, net gain on distribution of Sandoz Group AG to Novartis AG shareholders of USD 5.9 billion, compared to USD 151 million in prior year.

Full year

Discontinued operations net sales in 2023 were USD 7.4 billion, compared to USD 9.4 billion in 2022 and operating income amounted to USD 265 million compared to USD 1.3 billion in 2022.

Net income from discontinued operations in 2023 amounted to USD 6.3 billion, compared to USD 906 million in 2022, driven by the IFRS Accounting Standards non-cash, non-taxable, net gain on distribution of Sandoz Group AG to Novartis AG shareholders, which amounted to USD 5.9 billion.

Total Company
Fourth quarter

Total Company net income was USD 8.5 billion in 2023, compared to USD 1.5 billion in 2022 and basic EPS was USD 4.14 compared to USD 0.69 in prior year, driven by the IFRS Accounting Standards non-cash, non-taxable, net gain on distribution of Sandoz Group AG to Novartis AG shareholders of USD 5.9 billion. Net cash flows from operating activities for total Company amounted to USD 2.5 billion and free cash flow amounted to USD 2.1 billion.

Full year

Total Company, net income amounted to USD 14.9 billion in 2023, compared to USD 7.0 billion in 2022, and basic earnings per share was USD 7.15 compared to USD 3.19 in prior year, driven by the IFRS Accounting Standards non-cash, non-taxable, net gain on distribution of Sandoz Group AG to Novartis AG shareholders of USD 5.9 billion. Net cash flows from operating activities for the total company amounted to USD 14.5 billion, and free cash flow amounted to USD 13.2 billion.

Q4 key growth drivers
Underpinning our financial results in the quarter is a continued focus on key growth drivers (ranked in order of contribution to Q4 growth) including:

Entresto (USD 1 635 million, +26% cc) sustained robust demand-led growth, with increased patient share across all geographies
Kisqali (USD 610 million, +76% cc) sales grew strongly across all regions, based on increasing recognition of consistently reported overall survival in HR+/HER2- advanced breast cancer
Kesimpta (USD 641 million, +73% cc) sales grew across all regions driven by increased demand and strong access
Cosentyx (USD 1 303 million, +21% cc) US sales grew (+17%) and ex-US sales (+26% cc), benefitting from lower prior year base (including revenue deduction adjustments in the US)
Pluvicto (USD 273 million, +53% cc) continued sales growth in the US. Supply now unconstrained, focusing on initiating new patients
Ilaris (USD 376 million, +29% cc) sales grew across all regions
Leqvio (USD 123 million, +190% cc) launch is ongoing, with focus on patient on-boarding, removing access hurdles and enhancing medical education
Scemblix (USD 125 million, +143% cc) continued its strong launch uptake demonstrating the high unmet need in CML
Jakavi (USD 444 million, +14% cc) sales grew in emerging growth markets, Europe and Japan, driven by strong demand in both myelofibrosis and polycythemia vera indications
Xolair (USD 378 million, +16% cc) sales grew across all regions
Tafinlar + Mekinist (USD 486 million, +7% cc) sales grew mainly in the US and emerging growth markets, partly offset by decline in Europe
Promacta/Revolade (USD 563 million, +4% cc) sales grew mainly in the US driven by increased use in chronic ITP and severe aplastic anemia
Piqray (USD 131 million, +18% cc) sales grew mainly in the US
Lutathera (USD 147 million, +13% cc) sales grew across all regions due to increased demand
Emerging Growth Markets* Grew +18% (cc) overall. China grew (+38% cc) to USD 0.8 billion, due to lower prior year base. For the full year, China grew +17% (cc)
*All markets except the US, Canada, Western Europe, Japan, Australia, and New Zealand
Net sales of the top 20 brands in 2023
Q4 2023 % change FY 2023 % change
USD m USD cc USD m USD cc
Entresto 1 635 27 26 6 035 30 31
Cosentyx 1 303 21 21 4 980 4 5
Promacta/Revolade 563 4 4 2 269 9 10
Kesimpta 641 74 73 2 171 99 99
Kisqali 610 71 76 2 080 69 75
Tafinlar + Mekinist 486 5 7 1 922 9 11
Tasigna 446 -6 - 6 1 848 -4 -3
Jakavi 444 14 14 1 720 10 12
Lucentis 301 -24 - 25 1 475 -21 -20
Xolair 378 17 16 1 463 7 9
Ilaris 376 25 29 1 355 20 22
Sandostatin 316 4 5 1 314 6 8
Zolgensma 286 -7 - 4 1 214 -11 -9
Pluvicto 273 53 53 980 262 261
Gilenya 154 -55 - 55 925 -54 -54
Exforge Group 156 -2 - 1 713 -4 -1
Galvus Group 153 -27 - 17 692 -19 -11
Diovan Group 147 4 6 613 -6 -1
Lutathera 147 15 13 605 28 28
Gleevec/Glivec 128 -27 - 25 561 -25 -22
Top 20 brands total 8 943 13 14 34 935 10 12
R&D update – key developments from the fourth quarter
New approvals
Fabhalta
(iptacopan) Approved in the US as the first oral monotherapy for the treatment of adults (both previously treated and treatment-naïve patients) with paroxysmal nocturnal hemoglobinuria (PNH)
Cosentyx Approved in the US as the first new biologic therapy for the treatment of moderate to severe hidradenitis suppurativa (HS) in adults in nearly a decade

Approved in the US as an intravenous formulation in three indications: psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial SpA
Results from ongoing trials and other highlights
Scemblix
(asciminib) Ph3 ASC4FIRST study met both primary endpoints (major molecular response rate vs. imatinib or investigator-selected tyrosine kinase inhibitors) with clinically meaningful and statistically significant results in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Additionally, Scemblix showed a favorable safety and tolerability profile. Data will be presented at an upcoming medical conference and submitted to regulatory authorities in 2024

Ph3 ASCEMBL study, median follow-up of almost 4 years, in patients with Ph+ CML-CP continue to support the efficacy, safety and tolerability profile compared with bosutinib in 3L+ setting. Data presented at ASH (Free ASH Whitepaper) 2023
Fabhalta
(iptacopan) 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

Ph3 APPEAR-C3G study met its primary endpoint, demonstrating superiority of iptacopan vs placebo in proteinuria reduction at six-month analysis and provided clinically meaningful and statistically significant proteinuria reduction in patients with C3G on top of background therapy. Iptacopan’s safety profile was consistent with previously reported data. Data to be presented at an upcoming medical meeting. Study continues with all patients receiving active therapy for six-months

Ph3 APPLY-PNH extension data showed sustained efficacy and long-term safety of Fabhalta in adults with paroxysmal nocturnal hemoglobinuria (PNH). Data showed sustained clinically meaningful hemoglobin-level increases to near-normal (≥12 g/dL), blood transfusion avoidance, and improved patient-reported fatigue in the majority of patients. Comparable benefits were seen in those patients switching from anti-C5 therapy to Fabhalta. Safety profile at 48 weeks was similar to 24 week data. Data presented at ASH (Free ASH Whitepaper) 2023
atrasentan

Ph3 ALIGN study met its primary endpoint, demonstrating superiority of atrasentan vs placebo in proteinuria reduction at 36-week interim analysis with clinically meaningful and highly statistically significant reduction in proteinuria in IgAN patients receiving supportive care. Safety profile of atrasentan was consistent with previously reported data. Data to be presented at an upcoming medical meeting. Study continues with final readout expected in 2026
remibrutinib Ph3 REMIX-1 and REMIX-2 trials showed clinically meaningful and statistically significant reduction in weekly urticaria activity (UAS7), itch (ISS7) and hives (HSS7) at Week 12 vs placebo in patients with CSU. Significant improvement in symptom control was seen as early as Week 2 and sustained up to Week 12. Remibrutinib was well-tolerated and demonstrated a favorable safety profile with rates of overall adverse events comparable to placebo and balanced liver function tests across both studies. Studies are ongoing with final (52-week) readout and regulatory submissions in 2024. Data presented at AAAI 2023
Kisqali

(ribociclib) Final protocol-specified iDFS analysis of Ph3 NATALEE trial (with a median follow-up of 33.3 months and 78.3% of patients having completed ribociclib) reinforces 25% reduction in risk of recurrence across broad population of patients with HR+/HER2- early breast cancer and continues to support regulatory submissions. iDFS benefit remains consistent across key patient subgroups, with stability in secondary endpoints including overall survival (OS). Among patients with stage II and stage III tumors, ribociclib lowered risk of disease recurrence by 30% and 24.5%, respectively. Safety profile was in line with previously reported results. Data presented at SABCS 2023. NATALEE data submitted to the FDA in December 2023
Early-stage business development in core therapeutic areas and technologies Cardiovascular-Renal-Metabolic:

Chong Kun Dang (LMW, lead asset CKD-510 for diseases in which the enzyme HDAC6 is thought to play a role, including some cardiovascular diseases)
SanReno (LMW and mAb, securing worldwide rights for Atrasentan/Zigakibart)
Argo Biopharma (xRNA, undisclosed targets)
Neuroscience:

Voyager Therapeutics (Gene therapy, strategic collaboration and capsid license agreement for potential Huntington’s Disease and spinal muscular atrophy therapies)
Immunology:

Calypso (Biotherapeutics, lead asset CALY-002 a promising anti-IL-15 mAB, to be investigated in a range of autoimmune indications)
Oncology:

Legend Biotech (Cell Therapy, targeting DLL3, a ligand highly expressed in several cancers)
Isomorphic Labs – Leveraging AI including next generation AlphaFold model, to discover novel small molecule therapeutics against undisclosed targets
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.

In 2023, Novartis repurchased a total of 87.5 million shares for USD 8.4 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 23.0 million shares (USD 2.3 billion) under the new up-to USD 15 billion share buyback announced in July 2023 (which is continuing as planned, with up-to USD 12.7 billion remaining). In addition, 11.7 million shares (USD 1.2 billion) were repurchased to mitigate dilution related to participation plans of associates. Furthermore, 1.6 million shares (for an equity value of USD 0.1 billion) were repurchased from associates. In the same period, 13.5 million shares (for an equity value of USD 1.1 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 75.6 million versus December 31, 2022. These treasury share transactions resulted in an equity decrease of USD 7.4 billion and a net cash outflow of USD 8.6 billion.

As of December 31, 2023, net debt increased to USD 10.2 billion compared to USD 7.2 billion 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 8.6 billion and net cash outflow for M&A / intangible assets transactions of USD 3.3 billion. This increase in net debt was partially offset by USD 13.2 billion free cash flow and a USD 3.0 billion reduction in the net debt position of Novartis related to the Sandoz spin-off.

As of Q4 2023, the long-term credit rating for the Company is A1 with Moody’s Investors Service and AA- with S&P Global Ratings.

2024 outlook
Barring unforeseen events; growth vs prior year in cc

Net sales Expected to grow mid single digit
Core operating income Expected to grow high single digit
Key assumptions:

Our guidance assumes that no Entresto generics launch in the US in 2024
Foreign exchange impact
If late-January exchange rates prevail for the remainder of 2024, the foreign exchange impact for the year would be negative 1 percentage point on net sales and negative 3 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website.

Annual General Meeting
Dividend proposal
The Novartis Board of Directors proposes a dividend payment of CHF 3.30 per share for 2023, up 3.1% from CHF 3.20 per share in the prior year, representing the 27th consecutive dividend increase since the creation of Novartis in December 1996. Shareholders will vote on this proposal at the Annual General Meeting on March 5, 2024.

Reduction of share Capital
The Novartis Board of Directors proposes to cancel 87 547 255 shares (repurchased under the authorization of March 4, 2022) and to reduce the share capital accordingly by CHF 42.9 million, from CHF 1 115 964 098.48 to CHF 1 073 065 943.53.

Elections of the Board Chair and the members of the Board of Directors
The Board of Directors proposes the re-election of all current members of the Board of Directors (including the Board Chair).

Key figures1

Continuing operations2 Q4 2023 Q4 2022 % change FY 2023 FY 2022 % change
USD m USD m USD cc USD m USD m USD cc
Net sales 11 423 10 576 8 10 Net sales 45 440 42 206 8 10
Operating income 2 582 1 755 47 68 Operating income 9 769 7 946 23 39
As a % of sales 22.6 16.6 As a % of sales 21.5 18.8
Net income 2 638 1 315 101 130 Net income 8 572 6 049 42 62
EPS (USD) 1.29 0.62 108 140 EPS (USD) 4.13 2.77 49 70
Cash flows from
operating activities 2 547 3 768 -32 Cash flows from
operating activities 14 220 13 039 9
Non-IFRS measures Non-IFRS measures
Free cash flow 2 141 3 462 -38 Free cash flow 13 160 12 123 9
Core operating income 3 821 3 645 5 13 Core operating income 16 372 14 794 11 18
As a % of sales 33.5 34.5 As a % of sales 36.0 35.1
Core net income 3 126 2 963 6 11 Core net income 13 446 11 946 13 19
Core EPS (USD) 1.53 1.39 10 16 Core EPS (USD) 6.47 5.48 18 25


Discontinued operations2 Q4 2023 Q4 2022 % change FY 2023 FY 2022 % change
USD m USD m USD cc USD m USD m USD cc
Net sales 2 374 nm nm Net sales 7 428 9 372 nm nm
Operating income 194 nm nm Operating income 265 1 251 nm nm
As a % of sales 8.2 As a % of sales 3.6 13.3
Net income 5 842 151 nm nm Net income 6 282 906 nm nm
Non-IFRS measures Non-IFRS measures
Core operating income 385 nm nm Core operating income 1 185 1 871 nm nm
As a % of sales 16.2 As a % of sales 16.0 20.0




Total Company Q4 2023 Q4 2022 % change FY 2023 FY 2022 % change
USD m USD m USD cc USD m USD m USD cc
Net income 8 480 1 466 nm nm Net income 14 854 6 955 nm nm
EPS (USD) 4.14 0.69 nm nm EPS (USD) 7.15 3.19 nm nm
Cash flows from
operating activities 2 547 4 111 nm nm Cash flows from
operating activities 14 458 14 236 nm nm
Non-IFRS measures Non-IFRS measures
Free cash flow 2 141 3 713 nm nm Free cash flow 13 179 13 038 nm nm
Core net income 3 127 3 251 nm nm Core net income 14 336 13 352 nm nm
Core EPS (USD) 1.53 1.52 nm nm Core EPS (USD) 6.90 6.12 nm nm

nm= not meaningful
1Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 49 of the Condensed Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.
2As defined on page 37 of the Condensed Financial Report, Continuing operations include the retained business activities of Novartis, comprising the innovative medicines business and the continuing Corporate activities and Discontinued operations include operational results from the Sandoz business.

On January 31, 2024 Halia Therapeutics, a clinical-stage biopharmaceutical company pioneering a novel class of small molecule medications designed to combat inflammation, reported the completion of a $30 million Series C financing (Press release, Halia Therapeutics, JAN 31, 2024, View Source [SID1234639744]). The financing was led by Todd Pedersen, with continued participation from existing investors.

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Proceeds from the financing will be used to support the advancement of Halia’s lead asset, HT-6184, a selective and orally bioavailable first-in-class inhibitor of NLRP3/NEK7 inflammasome in Phase II clinical trials. Halia Therapeutics recently initiated a Phase IIa trial in India to treat patients with lower-risk myelodysplastic syndromes (LR-MDS). LR-MDS are a group of cancers in which the bone marrow produces underdeveloped cells that are abnormal in size, shape, or appearance and are therefore "dysplastic." The company also plans to evaluate HT-6184 in Phase II trials in the U.S. for the treatment of post-procedure inflammatory pain response, as well as begin a Phase I trial in Alzheimer’s patients. Funding will also support IND-enabling studies for Halia’s alternative programs that are developing Leucine-rich repeat kinase 2 (LRRK2) inhibitors to treat neurological diseases such as Parkinson’s and Alzheimer’s disease, in addition to building out clinical and regulatory teams further to support the global development of the company’s pipeline.

"We are grateful for the trust investors have in our therapeutic approach. Their confidence is the driving force behind our efforts in developing innovative therapies targeting chronic inflammation," said Dr. David Bearss, CEO of Halia Therapeutics. "This financing will help us to advance significantly our lead drug candidate, HT-6184, in ongoing global Phase II trials and will support the trajectory of our additional programs targeting neuroinflammation into the clinic, bringing us even closer to breakthrough treatments for inflammatory-related diseases."

"We believe that Halia’s unique approach of targeting the NLP3 inflammasome holds significant potential for addressing a wide range of inflammatory diseases, along with hematologic conditions and other malignancies," said Todd Pedersen. "The company’s expertise and patient-focused mindset will be invaluable for advancing these anti-inflammatory therapeutics and revolutionizing the approach for targeting chronic inflammation in patients."

About NLRP3

NLRP3, an innate immune sensor, is activated in response to various pathogenic and sterile stimuli. Activation of NLRP3 triggers the release of the pro-inflammatory cytokines IL-1β and IL-18 and induces a lytic cell death process called pyroptosis. These processes lead to systemic chronic inflammation. Halia’s therapeutic inhibition of NLRP3 prevents the formation of the NLRP3 inflammasome and promotes its disassembly once formed, thereby inhibiting the production and release of IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome is thought to drive the onset and progression of many conditions, including fibrotic, dermatological, and auto-inflammatory diseases. Significant neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are also driven by NLRP3 activation.

About HT-6184

HT-6184 represents an innovative approach as it is the first drug candidate to target the protein NEK7 through an allosteric mechanism. NEK7 is an essential component of the NLRP3 inflammasome and is critical for its assembly and the maintenance of NLRP3 activity. In preclinical models, Halia has shown that inhibiting the ability of NEK7 to bind to NLRP3 leads to a disruption in the formation of the NLRP3 inflammasome complex, thereby inhibiting the signaling from the inflammasome and reducing the inflammatory response. Preclinical models also showed that in addition to disrupting the formation of the NLRP3 inflammasome, HT-6184 promotes the disassembly of the inflammasome once activated.