Hyperlipidemia, a cardiovascular disease risk factor, is characterized by a rise in low-density lipoprotein (LDL), triglycerides and total cholesterol, and a decrease in high-density lipoprotein (HDL). Cholesteryl ester transfer protein (CETP) enables the transfer of cholesteryl ester from HDL to LDL and very low-density lipoprotein.

Objective::

CETP inhibition is a promising approach to prevent and treat cardiovascular diseases. By inhibiting lipid transport activity, it increases HDL levels and decreases LDL levels.

Materials and Method::

Herein, diaryl sulfonamides 6a-6g and 7a-7g were prepared, and the structure of these compounds was fully determined using different spectroscopic techniques.

Results::

These compounds underwent biological evaluation in vitro and showed different inhibitory activities against CETP; 100% inhibitory activity was observed for compounds 7a-7g, while activities of compounds 6a-6g ranged up to 42.6% at 10 μM concentration. Pharmacophore mapping agreed with the bioassay results where the four aromatic ring compounds 7a-7g possessed higher fit values against Hypo4/8 and the shape-complemented Hypo4/8 in comparison to compounds 6a-6g.

Conclusion::

Docking of the synthesized compounds using libdock and ligandfit engines revealed that compounds 7a-7g formed п-п stacking and hydrophobic interactions with the binding pocket, while compounds 6a-6g missed these hydrophobic interactions with amino acids Leu206, Phe265, and Phe263.

2024-12-01·Pharmacology Research & Perspectives

Obicetrapib exhibits favorable physiochemical and pharmacokinetic properties compared to previous cholesteryl ester transfer protein inhibitors: An integrated summary of results from non‐human primate studies and clinical trials

Review

作者: Hsieh, Andrew ; Curcio, Danielle ; Kastelein, John J. P. ; Nelson, Adam J. ; Ditmarsch, Marc ; Kling, Douglas ; Nicholls, Stephen J. ; Davidson, Michael H. ; Kirkpatrick, Carol F. ; Johnson, Judith

Abstract:

Anacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor previously under development, exhibited an usually extended terminal half‐life and large food effect and accumulated in adipose tissue. Other CETP inhibitors have not shown such effects. Obicetrapib, a potent selective CETP inhibitor, is undergoing Phase III clinical development. Dedicated assessments were conducted in pre‐clinical and Phase I and II clinical studies of obicetrapib to examine the pharmacokinetic issues observed with anacetrapib. After 9 months of dosing up to 50 mg/kg/day in cynomolgus monkeys, obicetrapib was completely eliminated from systemic circulation and not detected in adipose tissue after a 13‐week recovery period. In healthy humans receiving 1–25 mg of obicetrapib, the mean terminal half‐life of obicetrapib was 148, 131, and 121 h at 5, 10, and 25 mg, respectively, and food increased plasma levels by ~1.6‐fold with a 10 mg dose. At the end of treatment in Phase II trials, mean plasma levels of obicetrapib ranged from 194.5 ng/mL with 2.5 mg to 506.3 ng/mL with 10 mg. Plasma levels of obicetrapib decreased by 92.2% and 98.5% at four and 15 weeks post‐treatment, respectively. Obicetrapib shows no clinically relevant accumulation, is minimally affected by food, and has a mean terminal half‐life of 131 h for the 10 mg dose. These data support once daily, chronic dosing of obicetrapib in Phase III trials for dyslipidemia management.

2024-10-01·Current computer-aided drug design

Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors

Article

作者: Abu Khalaf, Reema ; Albadawi, Ghadeer ; Sabbah, Dima ; Abusaad, Amani ; Al-Nawaiseh, Bara'a

Background::

Hyperlipidemia is considered a major risk factor for the progress of atherosclerosis.

Objective::

Cholesteryl ester transfer protein (CETP) facilitates the relocation of cholesterol esters from HDL to LDL. CETP inhibition produces higher HDL and lower LDL levels.

Methods::

Synthesis of nine benzylamino benzamides 8a-8f and 9a-9c was performed.

Results::

In vitro biological study displayed potential CETP inhibitory activity, where compound 9c had the best activity with an IC50 of 1.03 µM. Induced-fit docking demonstrated that 8a-8f and 9a-9c accommodated the CETP active site and hydrophobic interaction predominated ligand/ CETP complex formation.

Conclusion::

Pharmacophore mapping showed that this scaffold endorsed CETP inhibitors features and consequently elaborated the high CETP binding affinity.

项与 CETP inhibitors(Bristol-Myers Squibb/ Simcere) 相关的新闻（医药）

2024-10-22

·BioSpace

Gilead to Present Latest Research Across Key Liver Disease Indication at the American Association for the Study of Liver Disease (AASLD) Meeting 2024

- Key Insights from Viral Hepatitis, PBC, and MASH/Fibrosis Studies Highlight Gilead’s Ongoing Commitment to Advancing Life-Changing Liver Disease Research - FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced new research to be presented at The Liver Meeting ® 2024, hosted by the American Association for the Study of Liver Diseases (AASLD) from November 15-19 in San Diego, Calif. More than 40 abstracts will be presented with key data, including 11 abstracts reporting new data on primary biliary cholangitis (PBC). The data will include findings from the RESPONSE trial that demonstrate the efficacy and safety pro Livdelzi ® (seladelpar) in people living with PBC and compensated cirrhosis. Additionally, data will be presented on the effects of Livdelzi on pruritus (chronic itching), a symptom that has significant impact on the quality of life of people living with PBC, along with interim long-term efficacy and safety results from the ongoing ASSURE study. Beyond PBC, Gilead will be presenting an interim analysis of the Phase 3 MYR301 study, which is evaluating people living with hepatitis Delta virus (HDV) who received bulevirtide monotherapy (2 mg for 144 weeks; 10 mg for 144 weeks; or 10 mg for 96 weeks) for chronic HDV and have been off treatment for 48 weeks. The study is evaluating whether or not patients treated with bulevirtide monotherapy for 2-3 years maintained virological and biochemical responses one year after stopping treatment. An additional 144-week analysis of patient-reported outcomes for individuals treated with bulevirtide 2 mg will also be presented, adding to the wealth of long-term data for the treatment for chronic HDV. “We’re excited to share our latest research at The Liver Meeting, as we push the boundaries of what’s possible in liver disease treatment. The breadth of this research reflects Gilead’s unwavering dedication to advancing life-changing science and shaping healthier futures for people living with liver disease,” said Anu Osinusi, Vice President of Clinical Development for Hepatitis, Respiratory and Emerging Viruses, Gilead Sciences. “The depth and range of our data, spanning both viral and inflammatory liver diseases, underscores our commitment to making a meaningful impact at every stage of a person’s journey in liver disease. Our goals go far beyond treatment alone—our work spans awareness, education, screening, diagnosis, and long-term care, all intending to address unmet needs and enhance treatment outcomes.” Gilead will also present hepatitis C virus (HCV) data which will include safety and tolerability outcomes for Epclusa ® (velpatasvir/sofosbuvir) in pregnant individuals with chronic HCV (the STORC study). As a special population that is often excluded from clinical research, these results may help clinicians better support pregnant people living with HCV, which in turn may reduce the risk of transmission to infants. Furthermore, real-world findings from the SVR10K study on HCV will be showcased, demonstrating the effects of direct-acting antivirals against all HCV genotypes across diverse regions. Late-breaking data from a Phase 2a open-label study assessing the safety and efficacy of novel combination therapies for chronic hepatitis B virus (HBV) will also be presented by Gilead. Key Abstracts at AASLD 2024: ID Abstract Title PBC 164 Efficacy and Safety of Seladelpar in Patients with PBC and Compensated Cirrhosis in the Phase 3 Placebo-controlled RESPONSE Trial 167 Attenuation, Near Resolution, and Prevention of Pruritis in Patients with PBC Treated with Seladelpar: A Secondary Analysis of Patterns of Pruritis Change in the RESPONSE Trial 4339 Alkaline Phosphatase Changes with Seladelpar Across Subgroups of Primary Biliary Cholangitis Patients in the RESPONSE Trial 4342 Seladelpar and Reductions in Lipids in Patients with Primary Biliary Cholangitis with and without Statin use in the Phase 3 Placebo-controlled RESPONSE Study 4341 Long-term Safety of Seladelpar 10 mg with up to 5 Years of Treatment in Patients with Primary Biliary Cholangitis Primary sclerosing cholangitis (PSC) 151 Associations Between Biomarkers and Magnetic Resonance Imaging-derived ANALI Score in Patients with Primary Sclerosing Cholangitis: Analysis from the Phase 3 PRIMIS Study HDV 1147 Efficacy and Safety of BLV Monotherapy for Chronic Hepatitis Delta: Post Treatment Results through 48 Weeks after the End of Treatment from an Interim Analysis of a Randomized Phase 3 Study MYR301 1193 Patient-reported Outcomes among Patients with Chronic Hepatitis Delta Treated with Bulevirtide 2 mg: A Long-term Analysis of the Phase 3 MYR301 Trial at 144 Weeks 139 Long-term Bulevirtide Monotherapy in Patients with HDV-related Compensated Cirrhosis: Effectiveness, Safety and Clinical Outcomes from the Retrospective Multicenter European Study (SAVE-D) HCV 222 Safety, Tolerability, and Outcomes of Velpatasvir/Sofosbuvir in Treatment of Chronic Hepatitis C Virus during Pregnancy (STORC) 1455 The SVR10K Study: A Real-world Data with Pangenotypic Direct-acting Antivirals across Multiple Diverse Regions 1476 Hepatitis C Treatment Uptake Differs by Gender among a Commercially Insured Population in the United States HBV 1380 Results from a Phase 2a, Open-label Study to Evaluate the Safety and Efficacy of Novel Combination Therapies Containing VIR-2218, Selgantolimod, and Nivolumab for the Treatment of Chronic Hepatitis B 1252 Effectiveness and Safety of Tenofovir Alafenamide in Chronic Hepatitis B Patients with Suboptimal Response to Antiviral Therapy 1337 Characterization of Changes in Noninvasive Fibrosis Markers over 8 Years of Tenofovir-based Treatment in Chronic Hepatitis B Patients Enrolled in Two Phase 3 Trials Nonalcoholic steatohepatitis (NASH)/Fibrosis 1520 Prospective Validation of the Mediterranean Diet Adherence Screener (MEDAS) for Point-of-care Assessment of Diet Quality in Patients with Metabolic Dysfunction-associated Steatotic Liver Disease For more information, including a complete list of abstract titles being presented at the meeting, please visit the AASLD website . In July 2023, the European Commission (EC) granted full Marketing Authorization (MA) for bulevirtide 2 mg for the treatment of adults with chronic HDV and compensated liver disease. Bulevirtide’s conditional MA license in Great Britain was converted to a full MA in August 2023 and a full MA was granted in Switzerland and Australia in 2024. In regions where it is not approved, including the U.S., bulevirtide 2 mg is an investigational product. In these regions, health authorities have not established the safety and efficacy of bulevirtide. Bulevirtide 10 mg is an investigational product and has not been approved anywhere. Cilofexor and selgantolimod are investigational compounds and are not approved by the FDA or any other regulatory authority; their safety and efficacy have not been established. Please see below for the U.S. Indications and Important Safety Information, including BOXED WARNINGS, for Epclusa and Livdelzi. U.S. Important Safety Information And Indication for EPCLUSA BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. Contraindications If EPCLUSA is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information. Warnings and Precautions Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with EPCLUSA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. Risk of Reduced Therapeutic Effect Due to Use with P-gp Inducers and/or Moderate to Strong Inducers of CYP2B6, CYP2C8 or CYP3A4 : Rifampin, St. John’s wort and carbamazepine are not recommended for use with EPCLUSA as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations. Adverse Reactions The most common adverse reactions (≥10%, all grades) with EPCLUSA in adults and pediatric patients 6 years of age and older were headache and fatigue; and when used with RBV in adults with decompensated cirrhosis were fatigue, anemia, nausea, headache, insomnia and diarrhea. The most common adverse reactions (≥10%, grade 1 or 2) in pediatric patients less than 6 years of age were vomiting and spitting up the drug. Drug Interactions Coadministration of EPCLUSA is not recommended with topotecan due to increased concentrations of topotecan. Coadministration of EPCLUSA is not recommended with proton-pump inhibitors, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir. Consult the full Prescribing Information for EPCLUSA for more information on potentially significant drug interactions, including clinical comments. Indication EPCLUSA is indicated for the treatment of adult and pediatric patients 3 years of age and older with chronic hepatitis C virus genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis. U.S. Important Safety Information for LIVDELZI Warnings and Precautions Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care. Liver Test Abnormalities: LIVDELZI has been associated with dose-related increases in serum transaminase (AST and ALT) levels > 3 x ULN in patients receiving 50 mg and 200 mg once daily (5x and 20x higher than the recommended dosage of 10 mg once daily). Perform baseline clinical and laboratory testing when starting LIVDELZI and monitor thereafter according to routine patient management. Interrupt treatment if the liver tests (ALT, AST, total bilirubin, and/or ALP) worsen, or if the patient develops signs and symptoms of clinical hepatitis (eg, jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI. Biliary Obstruction: Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated. Adverse Reactions The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%). Drug Interactions OAT3 Inhibitors and Strong CYP2C9 Inhibitors: Avoid coadministration with LIVDELZI due to increased LIVDELZI exposure. Rifampin: Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment. Coadministration may result in delayed or suboptimal biochemical response of LIVDELZI. Dual Moderate CYP2C9 and Moderate-to-Strong CYP3A4 Inhibitors and BCRP Inhibitors (eg, cyclosporine): Monitor closely for adverse effects. Concomitant administration with LIVDELZI may increase LIVDELZI exposure. CYP2C9 Poor Metabolizers Using Moderate-to-Strong CYP3A4 Inhibitors: Monitor more frequently for adverse reactions as concomitant use of a moderate-to-strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers may increase LIVDELZI exposure and risk of LIVDELZI adverse reactions. Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible. Pregnancy and Lactation Pregnancy: There are insufficient data from human pregnancies exposed to LIVDELZI to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at 1-800-445-3235. Lactation: There are no data on the presence of LIVDELZI in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LIVDELZI and any potential adverse effects on the breastfed infant from LIVDELZI. Indication LIVDELZI is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Limitations of Use: Use of Livdelzi is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy). About HDV HDV is considered the most aggressive or severe form of viral hepatitis, associated with more rapid progression towards liver-related death and liver cancer in people with HBV. On average, HDV progresses to cirrhosis within 5 years and to liver cancer within 10 years. Nearly 5% of people who have a chronic infection with HBV are estimated to have HDV, equating to 12-15 million people worldwide. The prevalence of HDV infection is largely underestimated due to lack of universal testing of HBV-positive individuals for HDV. About PBC PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the U.S.). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of alkaline phosphatase (ALP), alanine transaminase (ALT) and gamma-glutamyl transferase (GGT), enzymes found primarily in the liver, as well as total bilirubin. The most common symptoms of PBC are pruritus and fatigue, which can be debilitating for some people. Progression of PBC is associated with an increased risk of liver-related mortality. About Gilead Sciences in Liver Disease For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. We have helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For people living with hepatitis B or D, our focus on advancing our medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, we’re working to deliver advanced treatments for people living with PBC. But our commitment doesn’t stop there. Through our ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. We are committed to a future without liver disease. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials or studies, including those involving Epclusa, Hepcludex (bulevirtide), Livdelzi (seladelpar), cilofexor and selgantolimod (such as the ASSURE, RESPONSE, MYR301, STORC and SVR10K studies); uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the FDA and other regulatory authorities may not approve bulevirtide for the treatment of HDV, and the risk that any such approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; the possibility that Gilead may make a strategic decision to discontinue development of investigational programs for indications that are currently under evaluation and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. Epclusa, Hepcludex, Livdelzi, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Contacts Meaghan Smith, Media public_affairs@gilead.com Jacquie Ross, Investors investor_relations@gilead.com

临床2期临床结果上市批准临床3期

2024-05-21

·GlobeNewswire-Health Care

NewAmsterdam Pharma to Present New Clinical and Preclinical Data Highlighting Obicetrapib’s Impact on Key Risk Factors for Cardiovascular Disease at Upcoming Medical Meetings

-- Presentations include new data from OCEAN, ROSE, and ROSE2 Phase 2 clinical trials, demonstrating obicetrapib’s impact on key lipid and lipoprotein biomarkers -- -- On track to report topline data from Phase 3 BROOKLYN trial in HeFH in 3Q 2024 and Phase 3 BROADWAY trial in ASCVD in 4Q 2024 -- NAARDEN, the Netherlands and MIAMI, May 21, 2024 (GLOBE NEWSWIRE) -- NewAmsterdam Pharma Company N.V. (Nasdaq: NAMS or “NewAmsterdam” or the “Company”), a late-stage, clinical biopharmaceutical company developing oral, non-statin medicines for patients at risk of cardiovascular disease (“CVD”) with elevated low-density lipoprotein cholesterol (“LDL-C”), for whom existing therapies are not sufficiently effective or well-tolerated, today announced that it will present new clinical and preclinical data highlighting the potential for obicetrapib as a novel, oral, low-dose therapy for hypercholesterolemia, at the European Atherosclerosis Society (EAS) 92nd Congress and the National Lipid Association (NLA) 2024 Scientific Sessions, taking place on May 26 – 29 in Lyon, France and May 30 – June 2 in Las Vegas, Nevada, respectively. Presentation details are as follows: EAS 92nd Congress, Lyon, France, May 26-29, 2024 Title: Obicetrapib Treatment Increases Pre-Beta1 HDL and Lipophilic Antioxidants in the OCEAN and ROSE2 Studies Session Name: 0390 - SaaG Session: New tricks of HDL Oral Presentation Session Date and Time: Monday, May 27, 2024, 2:42 PM- 2:49 PM CET (8:42 AM-8:49 AM ET)Location: Station 7 Title: Obicetrapib Demonstrates Significant Reductions of Lp(a) on Top of High-Intensity Statins Session Name: 0601 - SaaG Session: Late-breaking lipids Oral Presentation Session Date and Time: Tuesday, May 28, 2024, 2:12 PM- 2:19 PM CET (8:12 AM-8:19 AM ET)Location: Station 8 Title: Obicetrapib Alone and in Combination with Ezetimibe Reduces Non-HDL-Cholesterol by Enhanced LDL-Receptor-Mediated VLDL Clearance and Increased Net Fecal Sterol Excretion in APOE*3-Leiden.CETP Mice Session Name: 0660- SaaG Session: Breaking updates in lipid-lowering treatmentsOral Presentation Session Date and Time: Tuesday, May 28, 2024, 3:17-3:24 CET (9:17 AM-9:24 AM ET)Location: Station 3 Title: Obicetrapib Alone and in Combination with Ezetimibe Reduces Atherosclerotic Lesion Size and Severity in APOE*3-Leiden.CETP Mice Session Name: 0660- SaaG Session: Breaking updates in lipid-lowering treatmentsOral Presentation Session Date and Time: Tuesday, May 28, 2024, 3:24-3:31 CET (9:24 AM-9:31 AM ET)Location: Station 3 Title: Obicetrapib does not Accumulate in Adipose Tissue: Results from Studies in Man and Non-Human Primates Flatboard Presentation Date: Monday, May 27 and Tuesday, May 28, 2024 NLA 2024 Scientific Sessions, Las Vegas, Nevada, May 30-June 2, 2024 Title: Obicetrapib Demonstrates Significant Reductions Of Lp(a) On Top Of High-intensity StatinsAbstract/Poster #: 128Date and Time: Friday, May 31, 2024, 2:30 PM- 2:55 PM PT (5:30 PM-5:55 PM ET)Location: Poster Hall Monitor # 30 Title: Synergistic Effect of Obicetrapib and Ezetimibe on Circulating LDL Particles Abstract/Poster #: 138Date and Time: Friday, May 31, 2024, 2:30 PM- 2:55 PM PT (5:30 PM-5:55 PM ET)Location: Poster Hall Monitor # 22 Title: Obicetrapib Does Not Accumulate in Adipose Tissue: Results from Studies in Man and Non-human Primates Abstract/Poster #: 127Date and Time: Friday, May 31, 2024, 2:30 PM- 2:55 PM PT (5:30 PM-5:55 PM ET)Location: Poster Hall Monitor # 18 Title: Obicetrapib Treatment Increases Pre-Beta1 HDL and Lipophilic Antioxidants in the OCEAN and ROSE2 Studies Abstract/Poster #: 140Date and Time: Friday, May 31, 2024, 2:30 PM- 2:55 PM PT (5:30 PM-5:55 PM ET)Location: Poster Hall Monitor # 15 Title: Assessment of Unmet Clinical Needs and Healthcare Resource Use Among Statin-Treated Patients with or at Risk of Developing ASCVD Abstract/Poster #: 139Date and Time: Friday, May 31, 2024, 2:30 PM- 2:55 PM PT (5:30 PM-5:55 PM ET)Location: Poster Hall Monitor # 12 Presentation Title: Obicetrapib Alone and with Ezetimibe Reduces Non-HDL-C by Enhanced LDL-Receptor-Mediated VLDL Clearance and Increased Net Fecal Sterol Excretion Abstract/Poster #: 141Oral Presentation Session: Session V Date and Time: Saturday, June 1, 2024, 11:05 AM- 11:55 AM PT (2:05-2:55 PM ET) About ObicetrapibObicetrapib is a novel, oral, low-dose CETP inhibitor that NewAmsterdam is developing to overcome the limitations of current LDL-lowering treatments. In each of the Company’s Phase 2 trials, ROSE2, TULIP, ROSE, and OCEAN, evaluating obicetrapib as monotherapy or combination therapy, the Company observed statistically significant LDL-lowering combined with a side effect profile similar to that of placebo. The Company is conducting two Phase 3 pivotal trials, BROADWAY and BROOKLYN, to evaluate obicetrapib as a monotherapy used as an adjunct to maximally tolerated lipid-lowering therapies to provide additional LDL-lowering for CVD patients and TANDEM, to evaluate obicetrapib and ezetimibe as a fixed-dose combination. The Company began enrolling patients in BROADWAY in January 2022, in BROOKLYN in July 2022, and in TANDEM in March 2024; completing enrollment of BROOKLYN in April 2023 and BROADWAY in July 2023. The Company also commenced the Phase 3 PREVAIL cardiovascular outcomes trial in March 2022, which is designed to assess the potential of obicetrapib to reduce occurrences of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and non-elective coronary revascularization. NewAmsterdam completed enrollment of PREVAIL in April 2024 and randomized over 9,500 patients. About NewAmsterdamNewAmsterdam Pharma (Nasdaq: NAMS) is a late-stage biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where currently approved therapies have not been adequate or well tolerated. We seek to fill a significant unmet need for a safe, well-tolerated and convenient LDL-lowering therapy. In multiple phase 3 studies, NewAmsterdam is investigating obicetrapib, an oral, low-dose and once-daily CETP inhibitor, alone or as a fixed-dose combination with ezetimibe, as LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of CVD with elevated LDL-C, for whom existing therapies are not sufficiently effective or well tolerated. Forward-Looking StatementsCertain statements included in this document that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the Company’s business and strategic plans, the Company’s commercial opportunity, the therapeutic and curative potential of the Company’s product candidate, the Company’s clinical trials and the timing for enrolling patients, the timing and forums for announcing data, the achievement and timing of regulatory approvals, and plans for commercialization. These statements are based on various assumptions, whether or not identified in this document, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to the approval of the Company’s product candidate and the timing of expected regulatory and business milestones, including potential commercialization; ability to negotiate definitive contractual arrangements with potential customers; the impact of competitive product candidates; ability to obtain sufficient supply of materials; global economic and political conditions, including the Russia-Ukraine and Israel-Hamas conflict; the effects of competition on the Company’s future business; and those factors described in the Company’s public filings with the Securities Exchange Commission. Additional risks related to the Company’s business include, but are not limited to: uncertainty regarding outcomes of the Company’s ongoing clinical trials, particularly as they relate to regulatory review and potential approval for its product candidate; risks associated with the Company’s efforts to commercialize a product candidate; the Company’s ability to negotiate and enter into definitive agreements on favorable terms, if at all; the impact of competing product candidates on the Company’s business; intellectual property related claims; the Company’s ability to attract and retain qualified personnel; ability to continue to source the raw materials for its product candidate. If any of these risks materialize or the Company’s assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. There may be additional risks that the Company does not presently know or that the Company currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. In addition, forward-looking statements reflect the Company’s expectations, plans, or forecasts of future events and views as of the date of this document and are qualified in their entirety by reference to the cautionary statements herein. The Company anticipates that subsequent events and developments may cause the Company’s assessments to change. These forward-looking statements should not be relied upon as representing the Company’s assessment as of any date subsequent to the date of this communication. Accordingly, undue reliance should not be placed upon the forward-looking statements. Neither the Company nor any of its affiliates undertakes any obligation to update these forward-looking statements, except as may be required by law. Company ContactMatthew PhilippeP: 1-917-882-7512matthew.philippe@newamsterdampharma.com Media ContactSpectrum Science on behalf of NewAmsterdamJenn GordonP: 1-202-957-7795jgordon@spectrumscience.com Investor ContactStern Investor Relations on behalf of NewAmsterdamHannah DeresiewiczP: 1-212-362-1200hannah.deresiewicz@sternir.com

临床3期临床2期AHA会议临床结果

2024-05-09

·GlobeNewswire-Health Care

NewAmsterdam Pharma Provides Corporate Update and Reports First Quarter Financial Results

-- Enrolled over 9,500 patients in Phase 3 PREVAIL global CVOT-- -- On-track to report topline data from Phase 3 BROOKLYN trial in HeFH in 3Q 2024 and Phase 3 BROADWAY trial in ASCVD in 4Q 2024 -- -- Dosed first patients in TANDEM, pivotal Phase 3 trial evaluating fixed-dose combination of obicetrapib and ezetimibe; topline data expected in 1Q 2025 -- -- Company to host R&D event on May 16, 2024, beginning at 9:00 a.m. ET in New York City – -- Strong financial position; ending the quarter with $481.1 million in cash -- NAARDEN, the Netherlands and MIAMI, May 09, 2024 (GLOBE NEWSWIRE) -- NewAmsterdam Pharma Company N.V. (Nasdaq: NAMS or “NewAmsterdam” or the “Company”), a late-stage, clinical biopharmaceutical company developing oral, non-statin medicines for patients at risk of cardiovascular disease (“CVD”) with elevated low-density lipoprotein cholesterol (“LDL-C”), for whom existing therapies are not sufficiently effective or well-tolerated, today announced corporate updates and financial results for the quarter ended March 31, 2024. “Recent months were marked by important milestones across our organization as we execute our multi-pronged clinical development strategy for obicetrapib and begin to prepare for a global launch,” said Michael Davidson, M.D., Chief Executive Officer of NewAmsterdam. “We recently completed enrollment in PREVAIL, our cardiovascular outcomes trial ("CVOT”), and initiated TANDEM, a pivotal Phase 3 trial evaluating a fixed-dose combination of obicetrapib and ezetimibe. These trials, alongside BROOKLYN and BROADWAY, are expected to provide important insights into obicetrapib’s ability to potentially improve upon the existing standard of care, by helping patients achieve their target LDL-C goals and, ultimately, avoid catastrophic outcomes. We are grateful to patients and physicians globally for their partnership, and we look forward to reporting pivotal data, beginning with topline results from BROOKLYN and BROADWAY in the third and fourth quarters of this year, respectively.” Dr. Davidson continued, “In parallel, we are working diligently to lay the foundation for a future global launch of obicetrapib, if approved. We believe that the market opportunity for obicetrapib is substantial; millions of people are living with hypercholesterolemia and many of those with atherosclerotic cardiovascular disease (“ASCVD”) or heterozygous familial hypercholesterolemia (“HeFH”) are not achieving LDL-C targets, despite the availability of statin therapies and PCSK9 inhibitors. We look forward to sharing additional details on our pre-launch activities and commercial strategy at our R&D Day on May 16th and, if our Phase 3 program is successful and regulatory approval is received, to delivering obicetrapib to improve health outcomes for CVD patients worldwide.” Clinical Development Updates: NewAmsterdam is developing obicetrapib, an oral, low-dose and once-daily cholesteryl ester transfer protein (“CETP”) inhibitor, as the preferred LDL-C lowering therapy to be used in patients at risk of CVD for whom existing therapies are not sufficiently effective or well-tolerated. In March 2024, NewAmsterdam announced the initiation of, and the dosing of the first patient in, TANDEM, a pivotal Phase 3 clinical trial to evaluate a fixed-dose combination of obicetrapib and ezetimibe in adult patients with HeFH and/or ASCVD or multiple risk factors for ASCVD, whose LDL-C is not adequately controlled despite being on maximally tolerated lipid-modifying therapies.In April 2024, NewAmsterdam announced that it has met the enrollment target for the pivotal Phase 3 PREVAIL CVOT evaluating obicetrapib in adult patients with a history of ASCVD, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy. Driven by strong patient and physician interest globally, NewAmsterdam extended enrollment to the end of April and randomized over 9,500 patients.Also in April 2024, at the 2024 American College of Cardiology Congress, NewAmsterdam presented additional data from the Phase 2 ROSE2 clinical trial, which evaluated the impact of obicetrapib in combination with ezetimibe as an adjunct to high-intensity statin therapy on multiple lipid biomarkers, including LDL particle number and small dense LDL-C. Corporate Updates In January 2024, NewAmsterdam appointed William H. Lewis, J.D., M.B.A as Chair of its Board of Directors. Mr. Lewis has more than 30 years of executive experience in the pharmaceutical and finance industries both in the U.S. and internationally and has been widely recognized for his commitment to a patient-first approach to drug discovery, development, and commercialization.In February 2024, NewAmsterdam completed an upsized public offering of 5,871,909 ordinary shares and 4,736,841 pre-funded warrants, generating net proceeds of $190.0 million after deducting underwriting discounts and commissions and offering expenses payable by the Company. NewAmsterdam intends to use the additional capital to support the continued development and ongoing commercial readiness of obicetrapib. The offering attracted several new and existing investors.In April 2024, NewAmsterdam appointed Juliette Audet as Chief Business Officer. Simultaneous with this announcement, Ms. Audet resigned from the Company’s Board of Directors. Ms. Audet is a seasoned life sciences executive with extensive pharmaceutical business development, finance and operational expertise. In her prior role as a Partner at Forbion, she was part of the team that built NewAmsterdam and she played a key role in out licensing obicetrapib, setting up operations and recruiting NewAmsterdam’s management team. Upcoming Potential Milestones NewAmsterdam currently expects to achieve the following upcoming milestones: Announce topline data from the Phase 3 BROOKLYN trial for obicetrapib monotherapy in the third quarter of 2024. BROOKLYN is evaluating obicetrapib in patients with HeFH, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy.Announce topline data from the Phase 3 BROADWAY trial for obicetrapib monotherapy in the fourth quarter of 2024. BROADWAY is evaluating obicetrapib in adult patients with HeFH and/or established ASCVD, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy.Announce topline data from the Phase 3 TANDEM trial evaluating a fixed-dose combination of obicetrapib and ezetimibe in first quarter of 2025. Upcoming Investor Events NewAmsterdam management will participate in a fireside chat at the RBC Capital Markets Global Healthcare Conference on Tuesday, May 14 at 4:35 p.m. ET in New York City. Additionally, NewAmsterdam will host an R&D Day event on Thursday, May 16, 2024, beginning at 9:00 a.m. ET in New York City. The event will feature a panel discussion and presentations from management to discuss obicetrapib’s clinical development path, the Company’s commercial readiness and strategy, and the cardiovascular disease landscape and opportunities for innovative new products. Live webcasts of both events will be available through the investor relations section of the NewAmsterdam website at ir.newamsterdampharma.com. Following the live webcasts, archived replays will be available on the Company’s website. First Quarter Financial Results Cash Position: As of March 31, 2024, NewAmsterdam recorded cash of $481.1 million, compared to $340.5 million as of December 31, 2023. The increase in cash is primarily driven by the proceeds of the follow-on offering and warrant exercises partially offset by cash outflows related to research and development costs as the Company continues development of obicetrapib and increased spending on selling, general and administrative expenses to support the Company’s growing organization.Revenue: NewAmsterdam recognized $1.4 million in revenue for the quarter ended March 31, 2024, compared to $8.6 million in the same period in 2023. This decrease was primarily due to the recognition of license revenue related to a clinical development milestone in the quarter ended March 31, 2023 while no clinical development milestones were achieved in the same period in 2024.Research and Development (“R&D”) Expenses: R&D expenses were $42.4 million in the quarter ended March 31, 2024, compared to $40.4 million for the same period in 2023. This increase was primarily due to an increase in clinical expenses related to the Company’s ongoing Phase 3 clinical trials, partially offset by a decrease in manufacturing costs.Selling, General and Administrative (“SG&A”) Expenses: SG&A expenses were $14.5 million in the quarter ended March 31, 2024, compared to $8.1 million for the same period in 2023. This increase was primarily due to an increase in personnel costs related to expansion of the team to support the growth of the organization and investments in capabilities to support the Company’s planned commercial launch of obicetrapib, if approved.Net loss: Net loss for the quarter ended March 31, 2024 was $93.8 million, or $1.06 per diluted share, compared to net loss of $42.0 million, or $0.51 per diluted share, for the same period in 2023. About Obicetrapib Obicetrapib is a novel, oral, low-dose CETP inhibitor that NewAmsterdam is developing to overcome the limitations of current LDL-lowering treatments. In each of the Company’s Phase 2 trials, ROSE2, TULIP, ROSE, and OCEAN, evaluating obicetrapib as monotherapy or combination therapy, the Company observed statistically significant LDL-lowering combined with a side effect profile similar to that of placebo. The Company is conducting two Phase 3 pivotal trials, BROADWAY and BROOKLYN, to evaluate obicetrapib as a monotherapy used as an adjunct to maximally tolerated lipid-lowering therapies to provide additional LDL-lowering for CVD patients and TANDEM, to evaluate obicetrapib and ezetimibe as a fixed-dose combination. The Company began enrolling patients in BROADWAY in January 2022, in BROOKLYN in July 2022, and in TANDEM in March 2024; completing enrollment of BROOKLYN in April 2023 and BROADWAY in July 2023. The Company also commenced the Phase 3 PREVAIL cardiovascular outcomes trial in March 2022, which is designed to assess the potential of obicetrapib to reduce occurrences of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and non-elective coronary revascularization. NewAmsterdam completed enrollment of PREVAIL in April 2024 and randomized over 9,500 patients. About NewAmsterdam NewAmsterdam Pharma (Nasdaq: NAMS) is a late-stage biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where currently approved therapies have not been adequate or well tolerated. We seek to fill a significant unmet need for a safe, well-tolerated and convenient LDL-lowering therapy. In multiple phase 3 studies, NewAmsterdam is investigating obicetrapib, an oral, low-dose and once-daily CETP inhibitor, alone or as a fixed-dose combination with ezetimibe, as LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of CVD with elevated LDL-C, for whom existing therapies are not sufficiently effective or well tolerated. Forward-Looking Statements Certain statements included in this document that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the Company’s business and strategic plans, the Company’s commercial opportunity, the therapeutic and curative potential of the Company’s product candidate, the Company’s clinical trials and the timing for enrolling patients, the timing and forums for announcing data, the achievement and timing of regulatory approvals, and plans for commercialization. These statements are based on various assumptions, whether or not identified in this document, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to the approval of the Company’s product candidate and the timing of expected regulatory and business milestones, including potential commercialization; ability to negotiate definitive contractual arrangements with potential customers; the impact of competitive product candidates; ability to obtain sufficient supply of materials; global economic and political conditions, including the Russia-Ukraine and Israel-Hamas conflict; the effects of competition on the Company’s future business; and those factors described in the Company’s public filings with the Securities Exchange Commission. Additional risks related to the Company’s business include, but are not limited to: uncertainty regarding outcomes of the Company’s ongoing clinical trials, particularly as they relate to regulatory review and potential approval for its product candidate; risks associated with the Company’s efforts to commercialize a product candidate; the Company’s ability to negotiate and enter into definitive agreements on favorable terms, if at all; the impact of competing product candidates on the Company’s business; intellectual property related claims; the Company’s ability to attract and retain qualified personnel; ability to continue to source the raw materials for its product candidate. If any of these risks materialize or the Company’s assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. There may be additional risks that the Company does not presently know or that the Company currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. In addition, forward-looking statements reflect the Company’s expectations, plans, or forecasts of future events and views as of the date of this document and are qualified in their entirety by reference to the cautionary statements herein. The Company anticipates that subsequent events and developments may cause the Company’s assessments to change. These forward-looking statements should not be relied upon as representing the Company’s assessment as of any date subsequent to the date of this communication. Accordingly, undue reliance should not be placed upon the forward-looking statements. Neither the Company nor any of its affiliates undertakes any obligation to update these forward-looking statements, except as may be required by law. Company ContactMatthew PhilippeP: 1-917-882-7512matthew.philippe@newamsterdampharma.com Media ContactSpectrum Science on behalf of NewAmsterdamJen GordonP: 1-202-957-7795jgordon@spectrumscience.com Investor ContactStern Investor Relations on behalf of NewAmsterdamHannah DeresiewiczP: 1-212-362-1200hannah.deresiewicz@sternir.com Financial Tables NewAmsterdam Pharma Company N.V.Condensed Consolidated Balance Sheets(Unaudited) March 31,2024 December 31,2023 (In thousands of USD) Assets Current assets: Cash 481,147 340,450 Prepayments and other receivables 6,675 6,341 Total current assets 487,822 346,791 Property, plant and equipment, net 101 46 Operating right of use asset 38 55 Intangible assets 486 170 Long term prepaid expenses 16 35 Total assets 488,463 347,097 Liabilities and Shareholders' Equity Current liabilities: Accounts payable 8,536 16,923 Accrued expenses and other current liabilities 9,970 11,398 Deferred revenue, current 8,116 8,942 Lease liability, current 43 60 Derivative warrant liabilities 33,061 12,574 Total current liabilities 59,726 49,897 Deferred revenue, net of current portion 444 1,019 Derivative earnout liability 16,490 7,788 Total liabilities 76,660 58,704 Commitments and contingencies (Note 10) Shareholders' Equity (deficit): Ordinary shares, €0.12 par value; 400,000,000 shares authorized; 89,720,836 and 82,469,768 shares issued and outstanding as at March 31, 2024 and December 31, 2023, respectively 11,113 10,173 Additional paid-in capital 807,008 590,771 Accumulated loss (410,740) (316,973)Accumulated other comprehensive income (loss) 4,422 4,422 Total shareholders' equity 411,803 288,393 Total liabilities and shareholders' equity (deficit) 488,463 347,097 NewAmsterdam Pharma Company N.V.Condensed Consolidated Statements of Operations and Comprehensive Income (Loss)(Unaudited) For the three months ended March 31, 2024 2023 (In thousands of USD, except per share amounts) Revenue 1,401 8,629 Operating expenses: Research and development expenses 42,430 40,420 Selling, general and administrative expenses 14,453 8,062 Total operating expenses 56,883 48,482 Operating loss (55,482) (39,853)Other income (expense): Interest income 3,083 943 Fair value change – earnout and warrants (38,950) (6,175)Foreign exchange gains/(losses) (2,418) 3,067 Loss before tax (93,767) (42,018)Income tax expense — — Loss and comprehensive loss for the period (93,767) (42,018)Net loss per ordinary share Basic and diluted$(1.06) $(0.51) NewAmsterdam Pharma Company N.V.Condensed Consolidated Statements of Shareholders' Equity (Deficit)(Unaudited) (In thousands of USD, except share amounts)Shares Amount Additional Paid-In Capital Accumulated Loss Cumulative Translation Adjustments Total Shareholders' Equity Balance at December 31, 2022 81,559,780 10,055 555,625 (140,036) 4,422 430,066 Exercise of warrants 208,032 27 2,671 — — 2,698 Share-based compensation — — 7,663 — — 7,663 Total loss and comprehensive loss for the period — — — (42,018) — (42,018)As at March 31, 2023 81,767,812 10,082 565,959 (182,054) 4,422 398,409 Balance at December 31, 2023 82,469,768 10,173 590,771 (316,973) 4,422 288,393 Issuance of Ordinary Shares and Pre-Funded Warrants, net of issuance costs 5,871,909 759 189,207 — — 189,966 Exercise of warrants 926,698 121 19,674 — — 19,795 Exercise of stock options 452,461 60 (609) — — (549)Share-based compensation — — 7,965 — — 7,965 Total loss and comprehensive loss for the period — — — (93,767) — (93,767)As at March 31, 2024 89,720,836 11,113 807,008 (410,740) 4,422 411,803 NewAmsterdam Pharma Company N.V.Condensed Consolidated Statements of Cash Flows(Unaudited) For the three months ended March 31, 2024 2023 (In thousands of USD) Operating activities: Loss for the period (93,767) (42,018)Non-cash adjustments to reconcile loss before tax to net cash flows: Depreciation and amortization 15 9 Non-cash rent expense 1 2 Fair value change - derivative earnout and warrants 38,950 6,175 Foreign exchange (gains)/losses 2,418 (3,067)Share-based compensation 7,918 7,616 Changes in working capital: Changes in prepayments (current and non-current) and other receivables 956 (1,413)Changes in accounts payable (8,311) (2,920)Changes in accrued expenses and other current liabilities (1,381) 6,997 Changes in deferred revenue (1,401) (3,244)Net cash (used in)/provided by operating activities (54,602) (31,863)Investing activities: Purchase of property, plant and equipment, including internal use software (385) (7)Net cash used in investing activities (385) (7)Financing activities: Proceeds from offering of ordinary shares and pre-funded warrants 190,481 — Transaction costs on issue of Ordinary Shares and Pre-Funded Warrants (515) — Proceeds from exercise of warrants 8,763 2,392 Proceeds from exercise of options 440 — Payment of withholding taxes related to net share settlement of exercised options (989) — Net cash provided by financing activities 198,180 2,392 Net change in cash 143,193 (29,478)Foreign exchange differences (2,496) 3,062 Cash at the beginning of the period 340,450 467,728 Cash at the end of the period 481,147 441,312 Noncash financing and investing activities Receivable related to exercise of warrants 1,271 —

临床3期财报高管变更临床结果临床2期

100 项与 CETP inhibitors(Bristol-Myers Squibb/ Simcere) 相关的药物交易

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