What changed in this filing

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Item 1. Business

2026-02-18 compared with 2025-02-26 · 301 added, 298 removed, 851 unchanged (41% of the section changed)

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We seek to fill a significant unmet need for a safe, well tolerated and convenient low-density lipoprotein cholesterol (“LDL-C”) lowering therapy.

In multiple Phase 3 trials, we have investigated obicetrapib, an oral, low-dose, once-daily, highly selective cholesterol ester transfer protein (“CETP”) inhibitor, alone or as a fixed-dose combination with ezetimibe, as preferred LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of cardiovascular disease (“CVD”) with elevated LDL-C, for whom existing therapies are not sufficiently effective or well tolerated.

We believe that CETP inhibition may also play a role in other indications by potentially mitigating the risk of developing diseases such as Alzheimer’s disease.

In multiple Phase 3 trials, we have investigated obicetrapib, an oral, low-dose, once-daily, highly selective cholesteryl ester transfer protein (“CETP”) inhibitor, alone or as a fixed-dose combination (“FDC”) with ezetimibe, as preferred LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of cardiovascular disease (“CVD”) with elevated LDL-C, for whom existing therapies are not sufficiently effective or well tolerated.

Additionally, we believe that CETP inhibition may also play a role in other indications by potentially mitigating the risk of developing diseases such as Alzheimer’s disease.

Obicetrapib is a next-generation, oral, low-dose, highly selective CETP inhibitor that we are developing to potentially overcome the limitations of current LDL-C lowering treatments.

In addition to LDL-C, obicetrapib has shown significant reductions in lipoprotein(a) ("Lp(a)") and small LDL particles, all with safety comparable to placebo.

We believe that obicetrapib has the potential to be a once-daily oral CETP inhibitor for lowering LDL-C, if approved.

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In our Phase 3 TANDEM clinical trial, evaluating obicetrapib in combination with ezetimibe as an adjunct to high-intensity statin therapy, obicetrapib in combination with ezetimibe met its primary and secondary endpoints, with statistically significant reductions in LDL-C observed.

In five of our Phase 2 clinical trials, TULIP, ROSE, OCEAN, ROSE2 and our Japan Phase 2b clinical trial, evaluating obicetrapib as a monotherapy or a combination therapy with ezetimibe 10 mg, we observed statistically significant LDL-C lowering with side effects similar in frequency and severity to placebo including muscle-related side effects and drug-related treatment-emergent serious adverse events (“TESAEs”).

In each of these trials, side effects were similar in frequency and severity to placebo including muscle-related side effects and drug-related treatment-emergent serious adverse events (“TESAEs”).

We have observed obicetrapib to be well tolerated in an aggregate of over 3,500 patients with low or moderately elevated LDL-C levels (“dyslipidemia”) in our clinical trials to date.

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To date, obicetrapib has shown reductions in non-HDL-C, apolipoprotein B (“ApoB”), and small dense lipoprotein particles (“sdLDL-P”).

In our clinical trials, we have also observed reductions in Lp(a), which is believed to be an independent MACE risk factor, along with reductions in total lipoprotein (“LDL”) particles and more specifically small LDL particles, which are believed to be more atherogenic particles.

In our clinical trials, we have also observed reductions in lipoprotein(a) (“Lp(a)”), which is believed to be an independent MACE risk factor, along with reductions in total lipoprotein (“LDL”) particles and more specifically small LDL particles, which are believed to be more atherogenic particles.

CVD is a leading cause of death worldwide.

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It is estimated that over 75% of ASCVD and heterozygous familial hypercholesterolemia (“HeFH”) outpatients prefer oral drugs to injectable therapies.

Our goal is to develop and commercialize an LDL-C lowering monotherapy and a fixed-dose combination therapy, which offers the advantage of a single, low dose, once-daily oral pill, and fulfills the significant unmet need for an effective and convenient LDL-C lowering therapy.

Our goal is to develop and commercialize an LDL-C lowering monotherapy and an FDC therapy, which offers the advantage of a single, low dose, once-daily oral pill, and fulfills the significant unmet need for an effective and convenient LDL-C lowering therapy.

If we obtain marketing approval, we intend to commercialize obicetrapib for patients with ASCVD and/or HeFH and elevated levels of LDL-C despite being treated with currently available optimal lipid lowering therapy.

We have partnered with Menarini, providing them with the exclusive rights to commercialize obicetrapib 10 mg, either as a sole active ingredient product or in a fixed-dose combination with ezetimibe, in the majority of European countries, if approved.

Subject to receipt of marketing approval, our current plan is to pursue development and commercialization of obicetrapib in the United States ourselves, and to consider additional partners for jurisdictions outside of the United States and the European Union (the “EU”), including in Japan and China.

We have partnered with Menarini, providing them with the exclusive rights to commercialize obicetrapib 10 mg, either as a sole active ingredient product or in an FDC with ezetimibe, in the majority of European countries (the "Menarini Territory"), if approved.

In August 2025, the EMA accepted for review the Marketing Authorization Applications ("MAAs") submitted by Menarini for obicetrapib 10 mg monotherapy and the FDC of 10 mg obicetrapib plus 10 mg ezetimibe for the treatment of primary hypercholesterolemia, including heterozygous familial and non-familial or mixed dyslipidemia.

Subsequently, MAAs were also submitted to regulators in the United Kingdom ("UK") and Switzerland and accepted for review.

The submissions are supported by data from the BROADWAY, BROOKLYN, and TANDEM pivotal Phase 3 trials.

We anticipate that Menarini will receive decisions on the MAAs from each of the regulators in the second half of 2026.

MAAs are approved by the regulators, Menarini will be required to use commercially reasonable efforts to commercialize obicetrapib in the Menarini Territory.

Our current plan is to pursue development and, subject to the receipt of marketing approval, commercialization of obicetrapib in the United States ourselves, and to consider additional partners for jurisdictions outside of the United States and Europe, including in Japan and China.

We conducted multiple Phase 3 trials simultaneously, with clinical plans that incorporate feedback from the FDA, the EMA, the Japan Pharmaceuticals and Medical Devices Agency (“PMDA”) and the China National Medical Products Administration (“NMPA”).

In addition to our partnership with Menarini, we may in the future utilize a variety of types of collaboration, license, monetization, distribution and other arrangements with other third parties relating to the development or commercialization, once approved, of obicetrapib or future product candidates or indications.

We are also continually evaluating the potential acquisition or license of new product candidates.

We are also regularly evaluating the potential acquisition or license of new product candidates.

The following table summarizes our current clinical programs:

* Other than as noted, the pipeline represents trials that are currently ongoing.

* PREVAIL will continue until the last participant has been followed up for a minimum of 2.5 years and the target number of MACE events have occurred.

As a result, the earliest the trial could conclude based on the minimum follow-up period is the end of 2026.

However, we will continue the trial until the target number of MACE events occur, which could likely require the trial to continue beyond this point.

Other than as noted, this graphic represents trials that are currently ongoing.

Projections are subject to inherent limitations.

Actual results may differ from expectations.

The timing of regulatory submissions is subject to additional discussions with regulators.

Other than as noted, the timing of regulatory submissions is subject to additional discussions with regulators.

We conducted two Phase 3 pivotal clinical trials, BROADWAY and BROOKLYN, to evaluate obicetrapib as a monotherapy used as an adjunct to maximally tolerated lipid-lowering therapies to potentially enhance LDL-C lowering in patients with ASCVD and/or HeFH.

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Over 2,500 patients were randomized in the BROADWAY trial and over 350 patients were randomized in the BROOKLYN trial.

We currently expect to report additional data from each study over the course of 2025.

In March 2022, we commenced our Phase 3 PREVAIL CVOT, which is designed to assess the potential of obicetrapib to reduce occurrences of MACE, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and non-elective coronary revascularization in at least 9,000 patients.

We completed enrollment in PREVAIL in April 2024 and expect to complete the study by the end of 2026.

We are also investigating obicetrapib as a fixed-dose combination with ezetimibe, an oral cholesterol absorption inhibitor and LDL-C lowering therapy, and plan to seek approval for this fixed-dose combination in parallel with obicetrapib monotherapy.

In our Phase 3 TANDEM trial, we evaluated the efficacy and safety of 10 mg obicetrapib and 10 mg ezetimibe as a fixed-dose combination used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-lowering in patients with HeFH, ASCVD or ASCVD risk equivalents.

We completed enrollment in PREVAIL in April 2024.

PREVAIL will continue until the last participant has been followed for a minimum of 2.5 years and the target number of MACE events have occurred.

As a result, the earliest the trial could conclude based on the minimum follow-up period is the end of 2026.

However, we will continue the trial until the target number of MACE events occur, which could likely require the trial to continue beyond this point.

We are also investigating obicetrapib as an FDC with ezetimibe, an oral cholesterol absorption inhibitor and LDL-C lowering therapy, and plan to seek approval for this FDC in parallel with obicetrapib monotherapy.

In our Phase 3 TANDEM trial, we evaluated the efficacy and safety of 10 mg obicetrapib and 10 mg ezetimibe as an FDC used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-lowering in patients with HeFH, ASCVD or ASCVD risk equivalents.

In November 2024, we reported data from the Phase 3 TANDEM trial, which met its primary and secondary endpoints, with safety and tolerability comparable to placebo.

Our goal is to submit a New Drug Application (“NDA”) for the fixed-dose combination shortly after submitting an NDA for obicetrapib as a monotherapy.

We expect that efficacy and safety data from BROADWAY and BROOKLYN will be described in the fixed-dose combination product label, if approved.

We plan to seek approval of obicetrapib in the United States, the EU, Japan, China and the United Kingdom.

Our goal is to submit a New Drug Application (“NDA”) in the U.S.

for the FDC shortly after submitting an NDA for obicetrapib as a monotherapy.

We expect that efficacy and safety data from BROADWAY and BROOKLYN will be described in the FDC product label, if approved.

We believe that CETP inhibition may also play a role in other indications by potentially mitigating the risk of developing diseases such as Alzheimer’s disease or diabetes.

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We observed reductions in the levels of 24-hydroxycholesterol and 27-hydroxycholestrol of 11% and 12%, respectively, in the cerebrospinal fluid (“CSF”) compared to baseline.

In addition, an increase of 8% compared to baseline in the

Aβ42/40 ratio in patients’ plasma was observed and pTau181 levels were observed to be stable.

In addition, an increase of 8% compared to baseline in the Aβ42/40 ratio in patients’ plasma was observed and pTau181 levels were observed to be stable.

Overall, obicetrapib was observed to be well-tolerated.

No serious adverse events (“AEs”) were reported, nor were any AEs considered to be related to the trial drug.

Clinically demonstrated anti-diabetic benefits have been observed with CETP inhibition in Phase 3 CVOTs that, if seen in obicetrapib, would differentiate it from current treatment alternatives, especially statin therapy.

Additionally, in July 2025, we announced data from the prespecified Alzheimer’s disease biomarker analysis in our BROADWAY clinical trial.

This analysis evaluated the effect of obicetrapib on plasma biomarkers of Alzheimer’s disease in 1,727 patients with established ASCVD and/or HeFH whose apolipoprotein E (“ApoE”) status was able to be determined based on phenotypic testing, including 367 ApoE4 carriers.

Safety in this population was not evaluated independently from the overall BROADWAY study population, where obicetrapib was observed to be well-tolerated, with safety results comparable to placebo.

Because this analysis was based on a subset of patients from BROADWAY, it was not controlled for baseline differences between the treatment and placebo population.

In this analysis, treatment with obicetrapib 10 mg daily for 12 months resulted in statistically significant lower absolute changes in plasma p-tau217, a key biomarker of Alzheimer’s disease pathology, in both the analysis set of patients with baseline and end of study datapoints above the lower limit of quantification (p=0.0019;

n=1,515) and in ApoE4 carriers (p=0.0215;

Favorable trends were also observed across additional biomarkers, including neurofilament light chain (“NFL”), glial fibrillary acidic protein (“GFAP”), p-tau181, and the Aβ42/40 ratio, in the full analysis set and in ApoE4 carriers, with the greatest effect generally observed in carriers of two E4 proteins.

Based on these results, we expect to initiate a new clinical trial evaluating obicetrapib in patients with early Alzheimer’s disease in 2026.

Clinically demonstrated anti-diabetic benefits have also been observed with CETP inhibition in Phase 3 CVOTs that, if seen in obicetrapib, would differentiate it from current treatment alternatives, especially statin therapy.

We are planning preclinical studies to examine the potential of obicetrapib for patients suffering from diabetes and have included new onset of Type 2 diabetes as an endpoint in our PREVAIL CVOT, as measured by AEs indicating Type 2 diabetes, initiation of anti-diabetes medication after confirmed diabetes diagnosis or high levels of hemoglobin A1c and fasting plasma glucose.

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BJ Jones, our Chief Commercial Officer, has three decades of commercial and launch experience in both large pharmaceutical and small biotech companies.

Most recently, he served as CCO, Migraine & Common Diseases at Biohaven Pharmaceuticals, and led the commercial enterprise that launched Biohaven’s Nurtec® ODT.

Most recently, he served as CCO, Migraine & Common Diseases at Biohaven Pharmaceuticals, and led the commercial enterprise that launched Biohaven’s

Earlier in his career, Mr.

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Market Overview and Unmet Medical Need

According to the World Health Organization, CVD is a leading cause of death globally and was responsible for approximately 19 million deaths, or approximately 32% of all global deaths, in 2020.

According to the World Health Organization, CVD is the leading cause of death globally and was responsible for approximately 20 million deaths, or approximately 32% of all global deaths, in 2022.

Hyperlipidemia, more commonly known as high cholesterol, has been observed to nearly double the risk of developing CVD compared to those with normal total cholesterol levels.

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They also noted that a more pronounced absolute reduction of LDL-C may lead to substantially greater relative reduction in cardiovascular events.

Furthermore, as seen in the Heart Protection

Study and the CTT collaboration, benefit was seen in each tertile of baseline LDL-C.

Furthermore, as seen in the Heart Protection Study and the CTT collaboration, benefit was seen in each tertile of baseline LDL-C.

Similar relationships have also been documented in non-statin CVOTs for ezetimibe, two PCSK9 inhibitors, evolocumab and alirocumab, and the CETP inhibitor, anacetrapib.

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Obicetrapib is designed to be a next-generation, oral, low-dose, highly selective CETP inhibitor with powerful LDL-C lowering capability.

We are developing obicetrapib as both a monotherapy and a fixed-dose combination therapy with ezetimibe and have structured our obicetrapib program to overcome the safety, potency, trial design and commercial viability limitations of prior CETP inhibitors.

We are developing obicetrapib as both a monotherapy and an FDC with ezetimibe and have structured our obicetrapib program to overcome the safety, potency, trial design and commercial viability limitations of prior CETP inhibitors.

Further, we believe that obicetrapib’s oral delivery, demonstrated activity in low doses, chemical properties and potential tolerability make it well-suited for combination approaches.

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Over 2,500 patients were randomized in the BROADWAY trial and over 350 patients were randomized in the BROOKLYN trial.

We reported top-line data from BROOKLYN in July 2024 and from BROADWAY in December 2024, and currently expect to report additional data from each study over the course of 2025.

In March 2022, we commenced our Phase 3 PREVAIL CVOT, which is designed to assess the potential of obicetrapib to reduce occurrences of MACE, including cardiovascular death, non-fatal myocardial

infarction, non-fatal stroke and non-elective coronary revascularization.

We completed enrollment in PREVAIL in April 2024 and expect to complete the trial by the end of 2026.

We also continue investigating obicetrapib as a fixed-dose combination with ezetimibe following the announcement of data from our Phase 3 TANDEM trial.

In parallel with the ROSE2 trial, we formulated two prototype fixed-dose combination tablets of obicetrapib and ezetimibe.

We reported top-line data from BROOKLYN in July 2024 and from BROADWAY in December 2024.

We completed enrollment in PREVAIL in April 2024.

PREVAIL will continue until the last participant has been followed for a minimum of 2.5 years and the target number of MACE events have occurred.

As a result, the earliest the trial could conclude based on the minimum follow-up period is the end of 2026.

However, we will continue the trial until the target number of MACE events occur, which could likely require the trial to continue beyond this point.

We also continue investigating obicetrapib as an FDC with ezetimibe following the announcement of data from our Phase 3 TANDEM trial.

In parallel with the ROSE2 trial, we formulated two prototype FDC tablets of obicetrapib and ezetimibe.

These formulations were compared to the co-administration of obicetrapib and ezetimibe in a pilot bioequivalence trial, which was completed in the first half of 2023.

Based on the results of this pilot bioequivalence trial and the data and learnings from our ROSE2 trial, we selected a formulation for a fixed-dose combination tablet of obicetrapib and ezetimibe and initiated TANDEM, a Phase 3 pivotal trial, to evaluate 10 mg obicetrapib and 10 mg ezetimibe as a fixed-dose combination used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-C lowering in patients with HeFH, ASCVD or ASCVD risk equivalents, in the first quarter of 2024 and announced topline data in November 2024.

Based on the results of this pilot bioequivalence trial and the data and learnings from our ROSE2 trial, we selected a formulation for an FDC tablet of obicetrapib and ezetimibe and initiated TANDEM, a Phase 3 pivotal trial, to evaluate 10 mg obicetrapib and 10 mg ezetimibe as an FDC used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-C lowering in patients with HeFH, ASCVD or ASCVD risk equivalents, in the first quarter of 2024 and announced topline data in November 2024.

We believe that obicetrapib has the potential to significantly impact the existing treatment paradigm for patients with ASCVD and/or HeFH and elevated levels of LDL-C, and that the key differentiating attributes of our product candidate include the following:

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In three of our Phase 3 and five of our Phase 2 clinical trials of obicetrapib, we observed statistically significant LDL-lowering activity combined with a similar incidence of generally moderate side effects compared to placebo and no drug-related, treatment-emergent serious AEs.

In addition, CETP inhibitors previously under development were observed to produce anti-diabetic benefits in Phase 3 CVOTs, which was also shown in obicetrapib, and could make it a potentially attractive adjunct for patients who are concerned about the risks of diabetes associated with statin therapy.

In addition, CETP inhibitors previously under development were observed to produce anti-diabetic benefits in Phase 3 CVOTs, which has also been observed with obicetrapib, and could make it a potentially attractive adjunct for patients who are concerned about the risks of diabetes associated with statin therapy.

• Convenience.

We believe that obicetrapib’s simple once-daily, low-dose oral formulation can improve patient adherence, thereby amplifying its cholesterol-lowering impact.

Additionally, unlike injectable PCSK9 inhibitors, obicetrapib, an oral small molecule, is better suited for combination with other oral treatments as oral fixed-dose combination products.

Additionally, unlike injectable PCSK9 inhibitors, obicetrapib, an oral small molecule, is better suited for combination with other oral treatments as oral FDC products.

• Patient access.

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Like other types of LDL-C lowering therapies, i.e., statins and PCSK9 inhibitors, CETP inhibition enhances the removal of ApoB, a protein found in lipoprotein particles that contributes to atherosclerosis.

However, unlike statins, based on observations from our Phase 2 and Phase 3 clinical trials, obicetrapib also decreases the presence of Lp(a), an important biomarker for CVD risk reduction.

However, unlike statins, based on observations from our Phase 2 and Phase 3 clinical trials, obicetrapib also decreased the presence of Lp(a), an important biomarker for CVD risk reduction.

Lowering LDL-C Through CETP Inhibition

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in addition, statins upregulate the LDL receptor, resulting in lower blood cholesterol.

inhibitors, another LDL-C-lowering treatment, also increase the presence of LDL receptors by inhibiting PCSK9, an enzyme involved in the degradation of LDL receptors.

PCSK9 inhibitors, another LDL-C-lowering treatment, also increase the presence of LDL receptors by inhibiting PCSK9, an enzyme involved in the degradation of LDL receptors.

Two other LDL-C lowering therapies, ezetimibe and Nexletol/Nexlizet, also work by upregulating LDL receptors.

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As shown in the figure below, the primary effect of CETP inhibition is a reduced rate of transfer of cholesteryl esters from HDL into triglyceride-rich lipoproteins, including LDL, which in turn leads to an increased concentration of cholesteryl esters in HDL particles and the formation of larger HDL particles.

Consequently, we have observed an increase in the excretion of cholesterol via the liver into digestive tract and an upregulation of LDL receptors on the liver, resulting in an enhanced clearances of LDL or ApoB-containing lipoproteins from the body.

Consequently, we have observed an increase in

the excretion of cholesterol via the liver into digestive tract and an upregulation of LDL receptors on the liver, resulting in enhanced clearances of LDL or ApoB-containing lipoproteins from the body.

In addition, there is evidence that CETP inhibition also promotes cholesterol excretion into the intestines directly contributing to the reduced cholesterol levels in the liver thus maintaining upregulation of LDL receptors.

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Although these drugs are administered at a low dose, which contributes to their safety and tolerability, and are generic and broadly available, they have been shown to only moderately reduce LDL-C.

Ezetimibe as monotherapy or when given in combination with statin therapy has been observed to reduce LDL-C by approximately 13% to 20%.

Ezetimibe as monotherapy or when given in combination with statin therapy has been observed to reduce LDL-C by approximately 13% to 20% and reduce MACE by 7%.

Despite its modest efficacy, ezetimibe is the most prescribed non-statin lipid lowering therapy with approximately 11% market share.

• Nexletol/Nexlizet.

The other currently available oral non-statin therapy, Nexletol/Nexlizet, which inhibits the enzyme ATP citrate lyase, an enzyme involved in cholesterol synthesis, shows only relatively modest improvement in lowering LDL-C.

The other currently available oral non-statin therapy, Nexletol/Nexlizet (Esperion Therapeutics), which inhibits the enzyme ATP citrate lyase, an enzyme involved in cholesterol synthesis, shows only relatively modest improvement in lowering LDL-C by approximately 17% as a monotherapy and a MACE reduction of 13%.

Along with its relatively modest efficacy, Nexletol/Nexlizet’s label contains safety warnings that include tendon rupture and gout.

Given that Nexletol/Nexlizet’s efficacy profile is comparable to generic ezetimibe, payors are reluctant to cover it, thus limiting its access and slowing uptake.

We believe Nexletol/Nexlizet’s access and uptake have been limited because its efficacy profile is comparable to generic ezetimibe.

• PCSK9 Inhibitors.

The PCSK9 inhibitors on the market are injectable monoclonal antibodies and small interfering RNA that have been observed to reduce LDL-C levels by approximately 50% compared to baseline.

The PCSK9 inhibitors on the market, such as Repatha (Amgen Inc.), Praluent (Regeneron Pharmaceuticals, Inc.) and Leqvio (Novartis International AG), are injectable monoclonal antibodies and small interfering RNA that have been observed to reduce LDL-C levels by approximately 50% compared to baseline and MACE by 15%.

While PCSK9 inhibitors have demonstrated their effectiveness at reducing LDL-C when used alone and as an adjunct to statin therapy, we believe their injectable route of administration makes them inconvenient for patients, and their access is further limited by their associated high cost and low rates of prescription approval by payors.

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A median four-year follow-up of the REVEAL trial showed that CETP inhibition resulted in a 9% reduction in MACE (first major coronary event, a composite of coronary death, myocardial infarction or coronary revascularization) compared to placebo.

We believe the REVEAL results provide clinical support showing that the absolute reduction

in LDL-C over time by CETP inhibition confers a predictable benefit in the prevalence of adverse cardiovascular outcomes, as measured by MACE.

We believe the REVEAL results provide clinical support showing that the absolute reduction in LDL-C over time by CETP inhibition confers a predictable benefit in the prevalence of adverse cardiovascular outcomes, as measured by MACE.

However, due to a very low baseline level of LDL-C (61 mg/dl), the trial showed only a modest absolute LDL-C lowering of 11 mg/dl (17%).

In addition, anacetrapib’s commercial viability was limited by its lipophilicity, which caused it to accumulate in fat tissue over time.

In addition, anacetrapib’s potential commercial viability was limited by its lipophilicity, which caused it to accumulate in fat tissue over time.

We selected obicetrapib 10 mg for our Phase 3 development program given its observed LDL-C-lowering activity and safety profile and designed our CVOT to avoid the shortcomings of prior CETP inhibitor programs and to ultimately fulfill the unmet need of ASCVD or HeFH patients with elevated LDL-C levels despite being treated with currently available optimal lipid lowering therapy.

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Following our end of Phase 2 meeting with the FDA in the fourth quarter of 2021, we also commenced our Phase 3 PREVAIL CVOT for obicetrapib as a monotherapy administered as an adjunct to maximally tolerated lipid-modifying therapy in early 2022.

In our Phase 2 ROSE2 trial, we evaluated the effect of a fixed-dose combination of obicetrapib 10 mg with ezetimibe 10 mg on top of high-intensity statin therapy on reduction in LDL-C.

In parallel with the ROSE2 trial, we formulated two prototype fixed-dose combination tablets of obicetrapib and ezetimibe.

In our Phase 2 ROSE2 trial, we evaluated the effect of an FDC of obicetrapib 10 mg with ezetimibe 10 mg on top of high-intensity statin therapy on reduction in LDL-C.

In parallel with the ROSE2 trial, we formulated two prototype FDC tablets of obicetrapib and ezetimibe.

These formulations were compared to the co-administration of obicetrapib and ezetimibe in a pilot bioequivalence trial, which was completed in the first half of 2023.

Based on the results of this pilot bioequivalence trial and the data and learnings from our ROSE2 trial, we selected a formulation for a fixed-dose combination tablet of obicetrapib and ezetimibe.

We initiated TANDEM, a Phase 3 pivotal trial, to evaluate 10 mg obicetrapib and 10 mg ezetimibe as a fixed-dose combination used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-lowering in patients with HeFH, ASCVD or ASCVD risk equivalents, in the first quarter of 2024 and released topline data in November 2024.

Based on the lipid-modifying effects of CETP inhibition we have observed in our clinical trials for obicetrapib to date, we have conducted preclinical assessments of obicetrapib to test its potential for the prevention and treatment of Alzheimer’s disease.

Following a Type B meeting in June 2021, the FDA confirmed that our preclinical data are sufficient to support a proposed clinical trial of obicetrapib for this indication, and we commenced a Phase 2a clinical trial in early 2022 in patients with early Alzheimer’s disease to evaluate the pharmacodynamic and pharmacokinetic effects, safety and tolerability of obicetrapib.

We announced initial data from this trial in September 2023.

We have set forth below our current obicetrapib clinical development pipeline.

*Other than as noted, the pipeline represents trials that are currently ongoing.

Based on the results of this pilot bioequivalence trial and the data and learnings from our ROSE2 trial, we selected a formulation for an FDC tablet of obicetrapib and ezetimibe.

We initiated TANDEM, a Phase 3 pivotal trial, to evaluate 10 mg obicetrapib and 10 mg ezetimibe as an FDC used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-lowering in patients with HeFH, ASCVD or ASCVD risk equivalents, in the first quarter of 2024 and released topline data in November 2024.

We have set forth below our current obicetrapib clinical development programs.

* PREVAIL will continue until the last participant has been followed up for a minimum of 2.5 years and the target number of MACE events have occurred.

As a result, the earliest the trial could conclude based on the minimum follow-up period is the end of 2026.

However, we will continue the trial until the target number of MACE events occur, which could likely require the trial to continue beyond this point.

Other than as noted, this graphic represents trials that are currently ongoing.

Projections are subject to inherent limitations.

Actual results may differ from expectations.

The timing of regulatory submissions is subject to additional discussions with regulators.

Other than as noted, the timing of regulatory submissions is subject to additional discussions with regulators.

Additionally, based on the lipid-modifying effects of CETP inhibition we have observed in our clinical trials for obicetrapib to date, we have conducted preclinical and early clinical assessments of obicetrapib to test its potential for the prevention and treatment of Alzheimer’s disease.

We announced initial data from this trial in September 2023.

In July 2025, we announced data from a prespecified analysis in BROADWAY that evaluated the effects of longer duration of therapy (12 months) on certain biomarkers associated with Alzheimer's disease with a prespecified population of ApoE3/4 or 4/4 carriers, based on phenotypic analysis.

Based on these results, we expect to initiate a new clinical trial evaluating obicetrapib in patients with early Alzheimer’s disease in 2026.

Obicetrapib for Cardiovascular Disease

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A study published in the Journal of the American Medicine in 2017 found that genetic variants related to lower LDL-C levels were significantly associated with a lower risk of CVD.

Specifically, the study concluded that the quantum of reduced genetic risk for CVD associated with CETP mutations was almost identical to the genetic risk of CVD

observed in patients with genetically reduced levels of the proteins targeted by statins, PCSK9 inhibitors and ezetimibe.

Specifically, the study concluded that the quantum of reduced genetic risk for CVD associated with CETP mutations was almost identical to the genetic risk of CVD observed in patients with genetically reduced levels of the proteins targeted by statins, PCSK9 inhibitors and ezetimibe.

We believe the consistency of benefit across genotypes observed in all target genes is predictive of the clinical efficacy of CETP-induced LDL-C lowering on CVD.

The direct correlation between LDL-C reduction and decrease in atherosclerotic cardiovascular events has been documented for both statin, as well as non-statin, therapies in CVOTs for ezetimibe, the PCSK9 inhibitors evolocumab and alirocumab, and for the CETP inhibitor anacetrapib.

Most notably, a median four-year follow-up of the REVEAL Phase 3 trial of anacetrapib showed that CETP inhibition resulted in a nine percent reduction in MACE (first major coronary event, a composite of coronary death, myocardial infarction or coronary revascularization) compared to placebo.

Most notably, a median four-year follow-up of the REVEAL Phase 3 trial of anacetrapib showed that CETP inhibition resulted in a 9% reduction in MACE (first major coronary event, a composite of coronary death, myocardial infarction or coronary revascularization) compared to placebo.

However, due to a very low baseline level of LDL-C (61 mg/dl), the trial showed only a modest absolute LDL-C lowering of 11 mg/dl (17%).

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We enrolled over 9,500 participants at sites in the United States, Canada, Europe, Asia, and Australia with established ASCVD and an LDL-C level of at least 55 mg/dL, and an additional risk enhancer in participants with an LDL-C level below 100 mg/dL, whose LDL-C levels are not adequately controlled despite maximally tolerated lipid-modifying therapies.

The planned median trial follow-up is expected to be approximately 42 months, and the treatment period will continue until the last participant has been followed for a minimum of 2.5 years after the last patient has been randomized or until the target number of primary endpoint events (i.e., cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or non-elective coronary revascularization) have occurred, whichever is later.

The planned median trial follow-up is expected to be approximately 42

months, and the treatment period will continue until the last participant has been followed for a minimum of 2.5 years after the last patient has been randomized or until the target number of primary endpoint events (i.e., coronary heart disease death, non-fatal myocardial infarction, fatal or non-fatal ischemic stroke, or coronary revascularization) have occurred, whichever is later.

We designed our PREVAIL trial based on insights gained from analyzing failures of prior CVOTs for other CETP inhibitors.

Our trial design targets patients above their LDL-C risk-based goal, despite treatment with maximally tolerated lipid modifying therapies, which we believe creates potential for greater observed absolute LDL-C reduction, particularly given the observed median LDL-lowering activity of 51% in our Phase 2b ROSE clinical trial.

We are focused on patients with elevated LDL-C levels and who have at least one other risk enhancer (including recent myocardial infarction, Type 2 diabetes, high triglyceride levels or low HDL-C), compared to prior CVOTs for CETP inhibitors that enrolled patients with low baseline LDL-C.

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Phase 3 REMBRANDT Imaging Trial

We have initiated REMBRANDT, a Phase 3 cardiovascular computed tomography angiography imaging trial to evaluate the effect of obicetrapib and ezetimibe in fixed-dose combination ("FDC") on coronary plaque.

We have initiated REMBRANDT, a Phase 3 cardiovascular computed tomography angiography imaging trial to evaluate the effect of obicetrapib and ezetimibe in FDC on coronary plaque.

The placebo-controlled, double-blind, randomized, Phase 3 study is being conducted in adult participants with high-risk ASCVD who are not adequately controlled by their maximally tolerated lipid-modifying therapy, to assess the impact of the obicetrapib 10 mg and ezetimibe 10 mg FDC daily on coronary plaque and inflammation characteristics.

The study is expected to enroll 300 patients.

The study is expected to complete enrollment of approximately 300 patients in 2026.

Phase 3 RUBENS Trial

RUBENS is a placebo-controlled, double-blind, randomized, 12-week study conducted in adult participants with Type 2 diabetes and/or Metabolic Syndrome on stable, guideline- recommended lipid lowering therapy to evaluate the LDL-C lowering of obicetrapib alone, or obicetrapib and ezetimibe in FDC.

Participants completing the 12-week double-blind treatment will enter a 9-month open label extension with obicetrapib and ezetimibe in FDC.

The study is expected to enroll approximately 300 patients, with topline data expected by the end of 2026.

Phase 2 VINCENT Trial

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We have completed three Phase 3 clinical trials of obicetrapib for the treatment of cardiometabolic disease.

TANDEM evaluated 10 mg obicetrapib and 10 mg ezetimibe as a fixed-dose combination, while BROADWAY and BROOKLYN were designed to measure the effect of obicetrapib 10 mg as monotherapy on top of maximally tolerated lipid-modifying therapy.

TANDEM evaluated 10 mg obicetrapib and 10 mg ezetimibe as an FDC, while BROADWAY and BROOKLYN were designed to measure the effect of obicetrapib 10 mg as monotherapy on top of maximally tolerated lipid-modifying therapy.

Phase 3 TANDEM Fixed-Dose Combination Trial

We completed TANDEM, a Phase 3 pivotal trial, to evaluate 10 mg obicetrapib and 10 mg ezetimibe as a fixed-dose combination used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-lowering in patients with HeFH, ASCVD or ASCVD risk equivalents in November 2024.

We completed TANDEM, a Phase 3 pivotal trial, to evaluate 10 mg obicetrapib and 10 mg ezetimibe as an FDC used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-lowering in patients with HeFH, ASCVD or ASCVD risk equivalents in November 2024.

We enrolled approximately 400 patients in the United States that had a baseline LDL-C of ≥ 70 mg/dL.

Following a 14-day screening period, patients were randomized 1:1:1:1 to obicetrapib 10 mg and ezetimibe 10 mg FDC, obicetrapib 10 mg monotherapy, ezetimibe 10 mg monotherapy or placebo for an 84-day treatment period.

TANDEM’s co-primary endpoints were percent change from baseline in LDL-C of the fixed-dose combination compared to each monotherapy arm after 84 days and obicetrapib 10 mg compared to placebo after day 84.

TANDEM’s co-primary endpoints were percent change from baseline in LDL-C of the FDC compared to each monotherapy arm after 84 days and obicetrapib 10 mg compared to placebo after day 84.

Secondary endpoints incorporated percent changes from baseline in other biomarkers, including Lp(a), non-HDL-C and ApoB.

The TANDEM trial met all co-primary endpoints.

The safety and tolerability profile of the fixed-dose combination was observed to be comparable to placebo in the trial.

Overall, the FDC was observed to be well-tolerated compared to placebo in this trial.

For all treatment groups, the most common treatment-emergent adverse events (“TEAEs”) were hypertension (4.4%), arthralgia (4.2%), upper respiratory tract infection (3.4%), diarrhea (2.5%), and fatigue (2.5%).

We believe that the stronger observed LDL-C lowering among patients receiving the combination therapy as compared with those receiving ezetimibe in combination with statin therapy is potentially due to the synergistic mechanisms of action for each of obicetrapib and ezetimibe.

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BROOKLYN, which completed enrollment in April 2023 and for which topline results were announced in July 2024, enrolled HeFH patients in the United States, Canada, Europe and Africa who had baseline LDL-C of at least 70 mg/dL.

Obicetrapib was administered in a once-daily 10 mg dose as an adjunct to diet (for regulatory purposes in the EU) and maximally tolerated lipid-modifying therapy, for a 52-week treatment period.

Obicetrapib was administered in a once-daily 10 mg dose as an adjunct to diet (for regulatory purposes in the European Union) and maximally tolerated lipid-modifying therapy, for a 52-week treatment period.

Such lipid-modifying therapies included statins or, for statin-intolerant patients, ezetimibe, Nexletol/Nexlizet, PCSK9 inhibitors, or fibrates (a class of drugs which increase HDL-C without significantly reducing LDL-C).

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For BROADWAY, other exploratory outcome measures included time from randomization until first confirmed occurrence of MACE in the obicetrapib arm compared to placebo.

The safety and tolerability profile of obicetrapib was comparable to placebo in both trials (which included a broad representation of adult males and females of all ages, including elderly and very elderly participants), assessed by AEs, vital signs, clinical laboratory values and electrocardiogram (“ECG”) measurements.

In addition, we evaluated obicetrapib’s effects on blood pressure and no difference from placebo was shown.

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We are conducting PREVAIL, our Phase 3 cardiovascular outcomes trial designed to assess the MACE benefit of obicetrapib, to provide support for obicetrapib’s potential MACE benefit.

Overall, obicetrapib was observed to be well-tolerated compared to placebo.

Treatment-emergent adverse events (“TEAEs”) were reported by 1,007 (59.8%) patients in the obicetrapib 10 mg group compared to 513 (60.9%) patients in the placebo group.

Overall, obicetrapib was observed to be well-tolerated compared to placebo in the BROADWAY trial.

TEAEs in BROADWAY were reported by 1,007 (59.8%) patients in the obicetrapib 10 mg group compared to 513 (60.9%) patients in the placebo group.

Most TEAEs were mild or moderate.

Treatment-emergent serious adverse events (“TESAEs”) were observed in 13.9% of the placebo group and in 12.5% of the obicetrapib group.

TESAEs were observed in 13.9% of the placebo group and in 12.5% of the obicetrapib group.

For all treatment groups, the most common TEAEs were COVID-19 (5.1%), hypertension (4.5%), upper respiratory tract infection (3.2%), hyperglycemia (2.8%), and nasopharyngitis (2.6%).

The following table summarizes the safety results from the BROADWAY trial:

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Any TEAEs leading to death

Overall, obicetrapib was also observed to be well-tolerated compared to placebo in the BROOKLYN trial.

TEAEs were reported by 149 (63.7%) patients in BROOKLYN in the obicetrapib 10 mg group compared to 83 (70.3%) patients in the placebo group.

Most TEAEs were mild or moderate.

TESAEs were observed in 6.8% of the placebo group and in 5.6% of the obicetrapib group.

For all treatment groups, the most common TEAEs were influenza (8.0%), COVID-19 (6.5%), hypertension (6.3%), nasopharyngitis (5.7%), and diarrhea (4.8%).

The following table summarizes the safety results from the BROOKLYN trial:

Obicetrapib 10 mg

Any trial drug related TEAEs

Any TEAEs leading to discontinuation of trial drug

Completed Phase 2 Clinical Trials

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Obicetrapib was also observed to be well-tolerated compared to placebo, in both the 5 mg and 10 mg doses and as a combination therapy with ezetimibe.

The majority of TEAEs were mild or moderate in severity and there were no drug-related, treatment-emergent serious AEs.

The graphs below summarize the results of our Phase 1 MAD and Phase 2 trials, with 10 mg of obicetrapib.

The majority of TEAEs were mild or moderate in severity and there were no drug-related, TESAEs.

The graphs below summarize the results of our Phase 1 multiple ascending dose and Phase 2 trials, with 10 mg of obicetrapib.

Phase 2b ROSE Trial

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Most TEAEs were mild or moderate in severity with only 13 (3.6%) patients experiencing a severe TEAE, two of which were suspected to be related to the trial drug (one subject in the placebo group and one subject in the atorvastatin 20 mg and obicetrapib 10 mg combination).

Prevalence, incidence and severity of TEAEs were similar across all treatment groups.

Prevalence, incidence

and severity of TEAEs were similar across all treatment groups.

There were eight patients with a TESAE, none of which were trial drug related, and no deaths occurred during the trial.

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All other TEAEs were experienced by only one or no subjects in each treatment group.

TEAEs that were considered by the investigator

to be related to trial treatment were reported by three subjects (two subjects in the 5 mg group and one subject in the 10 mg group), compared with four subjects in the placebo group.

TEAEs that were considered by the investigator to be related to trial treatment were reported by three subjects (two subjects in the 5 mg group and one subject in the 10 mg group), compared with four subjects in the placebo group.

There were no TEAEs leading to death.

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ROSE2 Clinical Trial

On June 3, 2023, we announced full results from our Phase 2 ROSE2 trial, our clinical trial evaluating obicetrapib in combination with ezetimibe as an adjunct to high-intensity statin therapy.

In June 2023, we announced full results from our Phase 2 ROSE2 trial, our clinical trial evaluating obicetrapib in combination with ezetimibe as an adjunct to high-intensity statin therapy.

ROSE2 met its primary and secondary endpoints, with statistically significant reductions in LDL-C and ApoB observed.

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Secondary efficacy endpoints included the percent changes from baseline to week 12 in LDL-C for obicetrapib monotherapy compared with placebo and in ApoB for the obicetrapib plus ezetimibe combination compared with placebo and the obicetrapib monotherapy compared with placebo.

Exploratory endpoints included the percent changes from baseline to week 12 in lipoprotein(a), non-HDL-C, HDL-C, total and small LDL-P assessed by NMR, and the proportion of patients at the end of treatment who achieved LDL-C levels below 100 mg/dL, 70 mg/dL and 55 mg/dL for the obicetrapib plus ezetimibe combination and obicetrapib monotherapy groups compared with placebo.

Exploratory endpoints included the percent changes from baseline to week 12 in lipoprotein(a), non-HDL-C, HDL-C, total and small LDL-P assessed by nuclear magnetic resonance (NMR), and the proportion of patients at the end of treatment who achieved LDL-C levels below 100 mg/dL, 70 mg/dL and 55 mg/dL for the obicetrapib plus ezetimibe combination and obicetrapib monotherapy groups compared with placebo.

Overall, obicetrapib alone and in combination with ezetimibe was observed to be well-tolerated compared to placebo.

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There were two severe TEAEs in the placebo group (both nervous system disorders) and one in the monotherapy group (a cardiac disorder).

In parallel with the ROSE2 trial, we formulated two prototype fixed-dose combination tablets of obicetrapib and ezetimibe.

In parallel with the ROSE2 trial, we formulated two prototype FDC tablets of obicetrapib and ezetimibe.

These formulations were compared to the co-administration of obicetrapib and ezetimibe in a pilot bioequivalence trial, which was completed in the first half of 2023.

Based on the results of this pilot bioequivalence trial and the data and learnings from our ROSE2 trial, we have selected a

formulation for a fixed-dose combination tablet of obicetrapib and ezetimibe and initiated TANDEM, a Phase 3 pivotal trial, to evaluate 10 mg obicetrapib and 10 mg ezetimibe as a fixed-dose combination used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-lowering in patients with HeFH, ASCVD or ASCVD risk equivalent patients, in the first quarter of 2024 and released topline data in November 2024.

Based on the results of this pilot bioequivalence trial and the data and learnings from our ROSE2 trial, we have selected a formulation for an FDC tablet of obicetrapib and ezetimibe and initiated TANDEM, a Phase 3 pivotal trial, to evaluate 10 mg obicetrapib and 10 mg ezetimibe as an FDC used as an adjunct to diet and maximally tolerated lipid-lowering therapies to potentially enhance LDL-lowering in patients with HeFH, ASCVD or ASCVD risk equivalent patients, in the first quarter of 2024 and released topline data in November 2024.

Japan Phase 2b Clinical Trial

On June 5, 2023, we announced topline results from our Phase 2b Japan trial evaluating the effects of three doses of obicetrapib (2.5 mg, 5 mg, and 10 mg) on LDL-C levels.

In June 2023, we announced topline results from our Phase 2b Japan trial evaluating the effects of three doses of obicetrapib (2.5 mg, 5 mg, and 10 mg) on LDL-C levels.

This was a randomized, double-blind, placebo controlled trial designed to evaluate the efficacy, safety and tolerability of obicetrapib as an adjunct to stable statin therapy in Japanese patients.

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Importantly, certain forms of ApoE (in particular, ApoE4) are worse at Ab transport than others, such as ApoE2, and are known to be associated with an increased risk of Alzheimer’s disease.

Further, CETP activity has been detected in astrocytes, the cells where ApoE bind with cholesterol, indicating the potential for a CETP inhibitor to function in the brain similarly to its lipid-modifying effects in the cardiovascular system.

Further, CETP activity has been detected in astrocytes, the cells where ApoE bind with cholesterol,

indicating the potential for a CETP inhibitor to function in the brain similarly to its lipid-modifying effects in the cardiovascular system.

Genetic studies have shown that CETP loss of function mutations mitigate the risk of Alzheimer’s disease in patients with the ApoE4 genotype.

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We believe reductions of these oxysterols in the CSF may indicate improved cholesterol metabolism in the brain and may lead to improved cognitive function.

In addition, this trial assessed the Aβ42/40 ratio and plasma pTau181, also believed to be biomarkers of Alzheimer’s disease, with lower levels of Aβ42/40 and increased

levels of pTau181 having been associated with a greater risk of Alzheimer’s disease.

In addition, this trial assessed the Aβ42/40 ratio and plasma pTau181, also believed to be biomarkers of Alzheimer’s disease, with lower levels of Aβ42/40 and increased levels of pTau181 having been associated with a greater risk of Alzheimer’s disease.

Overall, obicetrapib was observed to be well-tolerated.

No serious AEs were reported, nor were any AEs considered to be related to the trial drug.

In BROADWAY, a pre-specified Alzheimer's disease analysis was designed to assess plasma Alzheimer's disease biomarkers in patients enrolled in the BROADWAY trial and evaluated the effects of longer duration of therapy (12 months) with a prespecified population of ApoE3/4 or 4/4 carriers, based on phenotypic analysis.

The analysis included 1,515 patients, including 367 ApoE4 carriers, whose ApoE status was able to be determined.

Because this analysis was based on a subset of patients from BROADWAY (which was designed to evaluate LDL-C reductions in an ASCVD and/or HeFH population), the Alzheimer's disease analysis was not controlled for baseline differences between the treatment and placebo population.

The primary outcome measure was p-tau217 absolute and percent change over 12 months, among patients with baseline and end of study datapoints above the lower limit of quantitation.

Additional outcome measures included NFL, GFAP, p-tau181, and Aβ42/40 ratio absolute and percent change over 12 months.

We observed statistically significant lower absolute changes in p-tau217 compared to placebo over 12 months in both the full analysis set (p=0.0019;

n=1,515) and in ApoE4 carriers (p=0.0215;

Although a safety analysis was not performed in the Alzheimer's disease study population, in BROADWAY obicetrapib was observed to be well-tolerated, with safety results comparable to placebo.

Based on these results, we expect to initiate a new clinical trial evaluating obicetrapib in patients with early Alzheimer’s disease in 2026.

Manufacturing and Supply

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The production is overseen by an experienced group of personnel.

Obicetrapib and obicetrapib and ezetimibe FDC tablets are manufactured and tested in accordance with current good manufacturing practices (“cGMPs”) at facilities in the United States, Canada and Austria.

In preparation for commercial supply, we are in the process of expanding our supply network to support a commercial launch of obicetrapib, if approved.

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We may also opportunistically seek strategic collaborations to maximize the commercial opportunities for our future product candidates inside and outside the United States.

We entered into the Menarini License, pursuant to which Menarini has been granted the exclusive rights to commercialize obicetrapib 10 mg either as a sole active ingredient product or in a fixed-dose combination with ezetimibe in the majority of European countries, if approved.

We entered into the Menarini License, pursuant to which we granted Menarini the exclusive rights to commercialize obicetrapib 10 mg either as a sole active ingredient product or in an FDC with ezetimibe in the majority of European countries, if approved.

As any future product candidates near regulatory approval and potential commercial launch, we plan to assess our options for commercializing each respective product candidate and may choose to commercialize themselves ourselves or with a partner.

Menarini License

We entered into the Menarini License, pursuant to which we granted Menarini an exclusive, royalty-bearing, sublicensable license under certain of our intellectual property and our regulatory documentation to undertake post approval development activities and commercialize multiple brands of obicetrapib in a single unit dose of 10 mg or less, either as a sole active ingredient product or in a fixed-dose combination with ezetimibe (the “Licensed Products”), for any use in the majority of European countries (the “Menarini Territory”).

We entered into the Menarini License, pursuant to which we granted Menarini an exclusive, royalty-bearing, sublicensable license under certain of our intellectual property and our regulatory documentation to undertake post approval development activities and commercialize multiple brands of obicetrapib in a single unit dose of 10 mg or less, either as a sole active ingredient product or in an FDC with ezetimibe (the “Licensed Products”), for any use in the Menarini Territory.

We retained all rights to obicetrapib in all other territories and in other dosages.

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Menarini may conduct market access studies, medical affairs activities, non-registration studies and Phase IV clinical trials in the Menarini Territory.

Menarini will be responsible for submitting and obtaining the required regulatory approvals to commercialize obicetrapib (at the licensed dosage) in the Menarini Territory and will own the regulatory approvals, if received.

Menarini will also be solely responsible for commercializing obicetrapib (at the licensed dosage), if approved, and will be required to use commercially reasonable efforts to commercialize obicetrapib in the Menarini Territory.

Menarini is responsible for submitting and obtaining the required regulatory approvals to commercialize obicetrapib (at the licensed dosage) in the

Menarini Territory and will own the regulatory approvals, if received.

In August 2025, the EMA accepted for review the MAAs submitted by Menarini for obicetrapib 10 mg monotherapy and the FDC of 10 mg obicetrapib plus 10 mg ezetimibe for the treatment of primary hypercholesterolemia, including heterozygous familial and non-familial or mixed dyslipidemia.

If the MAAs are approved by the EMA, Menarini will also be solely responsible for commercializing obicetrapib monotherapy and the FDC of obicetrapib plus ezetimibe (at the licensed dosage) and will be required to use commercially reasonable efforts to commercialize obicetrapib in the Menarini Territory.

Pursuant to the Menarini License, Menarini made an upfront payment to us of €115.0 million.

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The Menarini License will expire on the last to expire royalty term, which is determined on a Licensed Product-by-Licensed Product and country-by-country basis, and is the later of (i) the expiration of the last to expire licensed patent that includes a valid claim in the country, (ii) expiration of regulatory exclusivity granted by the prevailing governmental authority for the Licensed Product in the country or (iii) 12 years from the first commercial sale of the Licensed Product in the country.

In addition, Menarini is expected to purchase obicetrapib and obicetrapib and ezetimibe FDC tablets from us in accordance with a supply agreement to be entered into by Menarini and us (the “Supply Agreement”).

We will supply all required quantities of products for the Menarini Territory as set forth in the Supply Agreement.

In the year ended December 31, 2024, we received one milestone payment from Menarini under the Menarini License upon the achievement of a clinical milestone.

In addition, we have entered into a supply agreement with Menarini pursuant to which we will supply Menarini with obicetrapib monotherapy and with the FDC of obicetrapib plus ezetimibe finished product in bulk tablet form (the “Drug Products”).

We will initially be Menarini’s exclusive supplier of the Drug Products and fulfill purchase orders based on periodic volume forecasts that Menarini is required to provide, a portion of which will be binding.

The price to be paid by Menarini will be based on a specified mark-up to our “cost of goods sold” for the supplied Drug Products (as determined in accordance with the supply agreement), subject to periodic adjustments.

The term of the supply agreement continues for the duration of the term of the Menarini License unless terminated earlier.

We may terminate the supply agreement for convenience upon advance 120 days’ written notice to Menarini, provided that the effective date of such a termination must follow the earlier of (i) completion of a process to transfer manufacturing of the Drug Products to Menarini or a designated third-party contract manufacturer, and (ii) two years after the initiation of such transfer.

Either party may terminate the supply agreement for uncured material breaches of the supply agreement, if the other party becomes insolvent, or if a force majeure event continues for six months or longer.

Intellectual Property

Our future commercial success depends, in part, on our ability to obtain and maintain patent and other proprietary protection for commercially important inventions, to obtain and maintain know-how related to our business, including our product candidates, to defend and enforce our intellectual property rights, in particular our patent rights, to preserve the confidentiality of our trade secrets, and to operate without

infringing, misappropriating, or violating the valid and enforceable patents and other intellectual property rights of third parties.

Our ability to preclude or restrict third parties from making, using, selling, offering to sell, or importing competing molecules to our products may depend on the extent to which we have rights under valid and enforceable patents and trade secrets that cover these activities.

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All of the issued patents and pending patent applications in our patent portfolio are owned by our subsidiary, NewAmsterdam Pharma B.V., Dutch Chamber of Commerce registry number 55971946.

As of December 31, 2024, we owned 10 issued U.S.

As of December 31, 2025, we owned:

• 10 issued U.S.

patents and 25 pending U.S.

patent applications,

We also owned 132 granted European patents and five pending European patent applications, two granted Chinese patents and 12 pending Chinese patent applications.

In addition, we owned 77 granted patents and 70 pending patent applications in other foreign jurisdictions, including international applications under the PCT.

• 114 granted European patents and 10 pending European patent applications,

• 1 granted Chinese patent and 14 pending Chinese patent applications,

• 5 granted Japanese patents and 6 pending Japanese patent applications, and

• 54 granted patents and about 139 pending patent applications in other foreign jurisdictions, including international applications under the Patent Cooperation Treaty (“PCT”).

The patent positions of pharmaceutical companies are generally uncertain and can involve complex legal, scientific, and factual issues.

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In addition, the coverage claimed in a patent application may be significantly reduced before a patent is granted, and its scope can be reinterpreted and even challenged after issuance.

As a result, we cannot guarantee that any of our products will be protected or remain protectable by enforceable patents.

As a result, we cannot

guarantee that any of our products will be protected or remain protectable by enforceable patents.

Moreover, any patents that we license or may own in the future may be challenged, circumvented, or invalidated by third parties.

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The issued patents and pending patent applications for obicetrapib as of December 31, 2025 are detailed below.

We have segregated these patents into three groups for ease of reference:

First Generation Patents, Second Generation Patents and Third Generation Patents based on the patent application filing dates and subject matter.

Obicetrapib First Generation Patents

The patent portfolio for obicetrapib composition of matter includes a first generation patent family directed generally to compounds, pharmaceutical compositions comprising the compounds, and methods of treatment using the compounds and pharmaceutical compositions.

We have two granted patents in the United States covering a genus of compounds that includes obicetrapib and claims that more narrowly cover the obicetrapib compound, pharmaceutical compositions, and methods of treatment.

In Europe, we have 17 granted patents.

In Asia, we have one granted patent in China, two granted patents in Japan, one granted patent in the Republic of Korea, one granted patent in Taiwan and one granted patent in Singapore.

We also have one granted patent in India.

In North America outside of the United States, we have one granted patent in Canada and one granted patent in Mexico.

In addition, we have 13 granted patents in other foreign jurisdictions.

Patents are expected to expire between April 2025 and August 2027, without taking potential patent term extensions into account.

The first generation portfolio also includes a patent family covering a method of synthesizing obicetrapib.

We have one patent in the United States, five patents in Europe

including the United Kingdom, and one patent in Japan in this latter patent family.

Patents in this family are expected to expire between March 29, 2027 and March 31, 2029, not including patent term extensions.

Our first generation obicetrapib patent portfolio includes:

• a patent family directed generally to compounds, pharmaceutical compositions comprising the compounds, and methods of treatment using the compounds and pharmaceutical compositions.

We have 1 granted patent in the United States in this patent family covering a genus of compounds that includes obicetrapib and claims that more narrowly cover the obicetrapib compound and pharmaceutical compositions thereof.

This United States patent is expected to expire in August 2027, without taking potential patent term extension into account.

• a patent family covering a method of synthesizing obicetrapib.

In this patent family, we have 1 granted patent in the United States, 5 granted patents in Europe including the United Kingdom, and 1 granted patent in Japan.

Patents in this family are expected to expire between March 29, 2027 and March 31, 2029, not including potential patent term extensions.

Obicetrapib Second Generation Patents

Our second generation obicetrapib patent portfolio includes a patent family directed to solid oral dosage forms containing 5 to 10 mg of obicetrapib, including tablet forms, and methods of treatment comprising administration of 1 to 25 mg of obicetrapib daily.

We have four granted patents in the United States and a pending application.

We have 39 granted patents in Europe.

In Asia, we have no granted patents in China, one granted patent in the Republic of Korea, one granted patent in Japan, one granted patent in Taiwan, one granted patent in Singapore and one granted patent in Hong Kong.

We have one granted patent in India.

In North America outside of the United States, we have one granted patent in Mexico and one granted patent in Canada.

In addition, we have 15 granted patents in other foreign jurisdictions.

Patent applications are pending in Argentina, Brazil, China, Hong Kong, Colombia, Costa Rica, Egypt, Libya, Peru, Thailand and Venezuela.

Patents, and patent applications, if granted, are expected to expire in February 2034, without taking potential patent term extensions or patent term adjustment into account.

We also have a patent family directed to compositions that contain obicetrapib and a statin, methods of treating with compositions that contain obicetrapib and a statin, and in various foreign jurisdictions, methods of use in which obicetrapib and a statin are separately administered.

We have one granted patent in the United States.

This patent is expected to expire in February 2034.

We have no granted patents in Europe.

In Asia, we have no granted patents in China, two granted patents in Japan, one granted patent in the Republic of Korea and two granted patents in Taiwan.

In North America outside of the United States, we have one granted patent in Mexico and one granted patent in Canada.

In addition, we have two granted patents in other foreign jurisdictions.

Patent applications are pending in China, Hong Kong, Thailand and Venezuela.

Our second generation obicetrapib patent portfolio includes:

• a patent family directed to solid oral dosage forms containing 5 to 10 mg of obicetrapib, including tablet forms, and methods of treatment comprising administration of 1 to 25 mg of obicetrapib daily which includes 4 granted patents and 2 pending patent applications in the United States, 39 granted patents in Europe, 1 granted patent in Japan, 6 pending patent applications in China, and 22 granted patents and 13 pending patent applications in other foreign jurisdictions.

These patents, and patent applications if granted, are expected to expire in February 2034, without taking potential patent term extensions or patent term adjustment into account.

• a patent family directed to compositions that contain obicetrapib and a statin, methods of treating with compositions that contain obicetrapib and a statin, and in various foreign jurisdictions, methods of use in which obicetrapib and a statin are separately administered which include 1 granted patent in the United States (expected to expire in February 2034), 2 granted patents in Japan, 2 pending patent applications in China, and 7 granted patents and 3 pending patent applications in other foreign jurisdictions.

Outside the United States, patents, and patent applications if granted, are expected to expire in August 2035, without taking potential patent term extensions or patent term adjustment into account.

In addition, we have a patent family that claims a synthetic intermediate used in a synthetic process we intend to use commercially, as well as processes to make that intermediate.

We have one issued US patent and 39 granted patents in Europe.

In Asia, we have one granted patent in China, one granted patent in Hong Kong, one granted patent in Japan, one granted patent in Singapore, one granted patent in Republic of Korea and one granted patent in Taiwan.

We also have one granted patent in India.

In North America outside of the United States, we have one granted patent in Mexico and one granted patent in Canada.

In addition, we have 15 granted patents in other foreign jurisdictions.

Patent applications are pending in Europe, Hong Kong and Venezuela.

• a patent family that claims a synthetic intermediate used in a synthetic process we intend to use commercially, as well as processes to make that intermediate, which includes 1 granted patent in the United States, 39 granted patents and 1 pending patent application in Europe, 1 granted patent in China, 1 granted patent in Japan, and 22 granted patents and 2 pending patent applications in other foreign jurisdictions.

Patents, and patent applications if granted, are expected to expire in July 2035, without taking potential patent term extensions or patent term adjustment into account.

Obicetrapib Third Generation Patents

We have a third generation patent family covering the solid salt form of obicetrapib that we intend to commercialize, a process for its commercial synthesis and a novel intermediate used in that synthetic process.

In the United States, we have an issued patent with claims covering the solid salt form of obicetrapib, and a pending application.

Patent applications are pending worldwide in over 40 jurisdictions.

patent, and patents if granted on the pending applications, are expected to expire in July 2043, without taking potential patent term adjustment or extensions into account.

We also have patent families directed to various compositions and methods of use of obicetrapib as a combination therapy.

These families all consist of pending applications.

Seven of these families are directed to combinations with ezetimibe, several of which cover the formulation of our intended commercial fixed-dose combination product.

Two of these families further include the commercial formulation of our intended obicetrapib single active product.

Patents if granted are expected to expire between February 2042 and November 2045, without taking potential patent term adjustment or extensions into account.

Another family is directed to a combination with statins, for use in certain subpopulations.

Patents if granted are expected to expire in July 2042, without taking potential patent term adjustment or extensions into account.

We also have two families directed to combinations with SGLT2 inhibitors.

If granted, these patents are expected to expire in December 2042 and April 2044, without taking potential patent term adjustment or extensions into account.

We have an additional patent family directed to a new process for synthesis of an intermediate in the manufacture of obicetrapib.

This family currently consists of a U.S.

provisional application.

Any patents, if granted, are expected to expire about November 2045.

We have two patent families respectively covering treatment of the patient populations enrolled in our BROOKLYN and BROADWAY trials.

These families currently consist of pending applications.

Patents if granted on these applications are expected to expire approximately in September 2044 and September 2045.

We also have a patent family directed to reductions in atherosclerotic plaque which currently consists of a pending PCT application.

Patents if granted in this family are expected to expire in December 2044.

In addition, we have two patent families covering methods of using obicetrapib to treat neurodegenerative diseases.

The first of these families includes 31 granted patents in Europe, one granted patent in Hong Kong and one granted patent in Israel.

We also have patent applications pending in this family in the United States, Europe, China and other jurisdictions.

The granted patents, and patent applications if granted, are expected to expire in March 2042, without taking potential patent term adjustment or extensions into account.

The second family consists of a PCT application and a pending U.S.

provisional application.

Any patents that grant from this second family are expected to expire in September 2044, without taking potential patent term adjustments or patent term extensions into account.

Finally, we have three patent families drawn to treatment of other clinical indications.

Patents if granted from these families will expire in about October 2044, without taking potential patent term adjustments or patent term extensions into account.

Our third generation obicetrapib patent portfolio includes:

• a patent family covering the solid salt form of obicetrapib that we intend to commercialize, a process for its commercial synthesis, and a novel intermediate used in that synthetic process.

In the United States, we have 2 granted patents including a granted patent with claims covering the solid salt form of obicetrapib, and 2 pending applications.

Patent applications are pending in Europe, China, Japan, and in over 40 other foreign jurisdictions.

Our United States patents, and patents if granted on the pending applications worldwide, are expected to expire in July 2043, without taking potential patent term adjustment or extensions into account.

• patent families directed to the combination of obicetrapib with ezetimibe, including patent families covering methods of treatment, fixed dose combinations, and the formulation of our intended FDC product.

Certain patent families directed to formulations also include the commercial formulation of our intended single-active product.

Patents in these families, if granted, are expected to expire from February 2042 to November 2045, without taking potential patent term adjustment or extensions into account.

• patent families directed to the combination of obicetrapib with statins for use in certain subpopulations, the combination of obicetrapib with SGLT2 inhibitors, and the combination of obicetrapib with PCSK9 inhibitors.

Patents in these families, if granted, are expected to expire from July 2042 to April 2046, without taking potential patent term adjustment or extensions into account.

• patent families directed to methods of using obicetrapib to treat neurodegenerative diseases.

Granted patents in these families, and patent applications if granted, are expected to expire from March 2042 to September 2045, without taking potential patent term adjustment or extensions into account.

• patent families directed to treatment of patient populations enrolled in our Phase 3 clinical trials, or directed to other clinical indications.

Patents in these families, if granted, are expected to expire from September 2044 to September 2045, without taking potential patent term adjustment or extensions into account.

• patent families directed to other aspects of obicetrapib and related molecules, such as synthesis processes, solid forms and formulations, and methods of preparation and use thereof.

Patents in these families, if granted, are expected to expire from November 2045 to November 2046, without taking potential patent term adjustment or extensions into account.

Trade Secrets

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Government Regulation and Product Approval

Government authorities in the United States, at the federal, state and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing, and export and import of drug products.

Government authorities in the United States, at the federal, state and local level, and in other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing, and export and import of drug products.

We, along with any third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies, clinical trials or seek approval of our products and product candidates.

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• completion of preclinical laboratory tests, animal studies, and formulation studies in accordance with FDA’s Good Laboratory Practice (“GLP”) requirements and other applicable regulations;

• submission to the FDA of an Investigational New Drug (“IND”) application, which must become effective before human clinical trials may begin and must be updated annually and when certain changes are made;

• submission to the FDA of an Investigational New Drug application (“IND”), which must become effective before human clinical trials may begin and must be updated annually and when certain changes are made;

• approval by an independent investigational review board (“IRB”) or independent ethics committee (“EC”) at each clinical site before each trial may be initiated;

• performance of adequate and well-controlled human clinical trials in accordance with good clinical practice (“GCP”) regulations, to establish the safety and efficacy of the proposed drug for its intended use;

• performance of adequate and well-controlled human clinical trials in accordance with good clinical practice (“GCP”) requirements, to establish the safety and efficacy of the proposed drug for its intended use;

• preparation of and submission to the FDA of an NDA after completion of pivotal trials;

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The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical trials.

The IND also includes results of animal and in vitro

studies assessing the toxicology, pharmacokinetics, pharmacology and pharmacodynamic characteristics of the product;

The IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology and pharmacodynamic characteristics of the product;

chemistry, manufacturing and controls information;

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Furthermore, an independent IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site and must monitor the trial until completed.

Some trials also include oversight by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board, which provides authorization for whether or not a trial may move forward at designated check points based on access to certain data from the trial and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

Depending on its charter, this group may determine whether a trial may move forward at designated check points based on access to certain data from the trial.

Some trials also include oversight by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or data monitoring committee, which provides authorization for whether or not a trial may move forward at designated check points based on access to certain data from the trial and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives.

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If a foreign clinical trial is not conducted under an IND, the sponsor must ensure that the clinical trial complies with regulatory requirements if the data is to be used in support of NDA approval.

The FDA will accept a well-designed and well-conducted foreign clinical trial not conducted under an IND if the trial was conducted in accordance with GCP requirements, and the FDA is able to validate the data through an onsite inspection, if deemed necessary.

The FDA will accept a well-designed and well-conducted foreign clinical trial not conducted under an IND if the trial was conducted in accordance with GCP requirements, the FDA is able to validate the data through an onsite inspection, if deemed necessary, and the FDA determines that the data is applicable to the U.S.

patient population.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

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These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval and labeling.

Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of an NDA.

Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of an NDA, although this may vary and in some instances hybrid trials may be conducted that meet the criteria for multiple phases under one trial design.

In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product.

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In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.

While the IND is active and before approval, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected AEs, findings from other trials suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.

In addition, during the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points.

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The FDA conducts a preliminary review of all NDAs within the first 60 days after submission, before accepting them for filing, to determine whether they are sufficiently complete to permit substantive review.

The FDA may request additional information rather than accept an NDA for filing.

The FDA may refuse to file the application if the application is not sufficiently complete to permit substantive review and request additional information rather than accept an NDA for filing.

In this event, the NDA must be resubmitted with the additional information.

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An advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates, and provides a recommendation as to whether the application should be approved and under what conditions.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

The FDA is not bound by the recommendations of an advisory committee, but it has considered such recommendations carefully when making decisions.

Before approving an NDA, the FDA will typically inspect the facility or facilities where the product is manufactured.

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Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications.

After the FDA evaluates an NDA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter, a tentative approval letter (in the case of, for example, certain types of NDAs referred to as 505(b)(2) NDAs that rely in whole or in part on other company’s approvals), or a Complete Response Letter (“CRL”).

An approval letter authorizes commercial marketing of the product with specific prescribing information for specific conditions of use, including specific indications.

A tentative approval letter is notification that an NDA otherwise meets the requirements for approval but cannot be approved because of exclusivity or patent reasons.

A drug product that is granted tentative approval is not an approved drug and will not be approved until FDA issues an approval letter after any necessary additional review of the NDA.

A CRL indicates that the review cycle of the application is complete and the application is not ready for approval.

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In issuing the CRL, the FDA may recommend actions that the applicant might take to place the NDA in condition for approval, including requests for additional information or clarification.

The FDA may delay or refuse approval of an NDA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed.

The FDA will refuse approval of an NDA if applicable statutory and regulatory criteria are not satisfied and may require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

If regulatory approval of a product is granted, such approval will be granted for particular conditions of use, including particular indications, and may entail limitations on the indicated uses for which such product may be marketed.

For example, the FDA may approve the NDA with a Risk Evaluation and Mitigation Strategy (“REMS”), to ensure the benefits of the product outweigh its risks.

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The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current, or fails to submit a request for approval of a pediatric formulation.

In addition, failure to fulfill the requirement to submit a pediatric study plan with an application may be grounds for refusal to file an application.

Expedited Development and Review Programs

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For example, the Fast Track program is intended to expedite or facilitate the process for reviewing new products that are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition.

Fast Track designation applies to the combination of the product and the specific indication for which it is being studied.

Fast Track designation applies to a particular product for the specific qualifying disease or condition.

The sponsor of a Fast Track designated product has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an NDA is submitted, the product candidate may be eligible for priority review.

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Rolling review may occur if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.

FDA may also only commence its review upon submission of the final section of the NDA.

A product candidate intended to treat a serious or life-threatening disease or condition may also be eligible for Breakthrough Therapy designation to expedite its development and review.

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Even if a product candidate qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Marketing Exclusivity

Market exclusivity provisions under the FDCA can delay the submission or the approval of certain marketing applications.

Marketing and Data Exclusivity

Market and data exclusivity provisions under the FDCA can delay the submission or the approval of certain marketing applications.

The FDA provides periods of non-patent regulatory exclusivity, which provides the holder of an approved NDA limited protection from new competition in the marketplace.

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An NCE is a drug that contains no active moiety that has been approved by the FDA in any other NDA.

An active moiety is the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt, including a salt with hydrogen or coordination bonds, or other noncovalent, or not involving

the sharing of electron pairs between atoms, derivatives, such as a complex (i.e., formed by the chemical interaction of two compounds), chelate (i.e., a chemical compound), or clathrate (i.e., a polymer framework that traps molecules), of the molecule, responsible for the physiological or pharmacological activity of the drug substance.

During the exclusivity period, the FDA may not accept for review or approve an abbreviated new drug application (“ANDA”), or a 505(b)(2) NDA submitted by another company that contains the same active moiety.

An active moiety is the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological activity of the drug substance.

During the exclusivity period, an abbreviated new drug application (“ANDA”) or a 505(b)(2) NDA that contains the same active moiety may not be submitted.

An ANDA or 505(b)(2) application, however, may be submitted one year before NCE exclusivity expires if a Paragraph IV certification of patent invalidity, unenforceability, or non-infringement is filed.

The FDCA alternatively provides three years of marketing exclusivity for an NDA, or supplement to an existing NDA, if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications, dosages or strengths of an existing drug.

This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations and does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the active ingredient for the original indication or condition of use.

The FDCA alternatively provides three years of marketing exclusivity for an NDA, or supplement to an existing NDA, containing a previously approved active moiety, if FDA determines that it contains reports of new clinical investigations (other than bioavailability studies) essential to the approval of the application and conducted or sponsored by the applicant.

New indications, dosages or strengths of an existing active moiety may be eligible for three-year exclusivity.

If eligible, FDA may not approve an ANDA or 505(b)(2) application containing the same active moieties (or combination of active moieties) for the same conditions of approval protected by the exclusivity for three years after approval of the eligible NDA or supplement.

This three-year exclusivity protects only the modification for which the drug received approval on the basis of the new clinical investigations and often can be “carved out” of the labeling of the ANDA or 505(b)(2) application to permit approval.

This exclusivity does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the active moiety (or combination of active moieties) for previously approved, unprotected conditions of use.

Five-year and three-year exclusivity will not delay the submission or approval of a 505(b)(1) NDA.

however, an applicant submitting a 505(b)(1) NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and efficacy.

Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs intended to treat rare diseases or conditions affecting fewer than 200,000 individuals in the United States.

If a product with orphan drug designation receives FDA approval for an indication within the designated disease, the FDA generally may not approve another marketing application for the same drug for the same approved indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiority by a subsequent product or if the holder of the orphan drug exclusivity is unable to assure sufficient quantities of the product to meet patient needs.

The FDA may also grant pediatric exclusivity, which provides a six-month extension to existing regulatory or patent exclusivity.

To be eligible for pediatric exclusivity, the FDA must issue a Written Request detailing the trials to be performed and the timeframe for their completion.

If an applicant agrees to perform the trials as outlined in the Written Request, the applicant must submit trial reports at least nine months prior to the expiry of the exclusivity that is to be extended.

The trial reports must demonstrate that the applicant has met the conditions of the Written Request.

To be eligible for pediatric exclusivity, the FDA must issue a Written Request detailing the studies to be performed and the timeframe for their completion.

If an applicant agrees to perform the studies as outlined in the Written Request, the applicant must submit study reports at least fifteen months prior to the expiry of the exclusivity that is to be extended.

To be eligible for pediatric exclusivity, FDA must determine that the studies fairly respond to the Written Request, have been conducted in accordance with commonly accepted scientific principles and protocols, and have been reported in accordance with the requirements for filing.

Post-approval Requirements

Drug products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product, which include restrictions on promoting products for unapproved uses or patient populations (known as “off-label use”) and limitations on industry-sponsored scientific and educational activities.

In rare cases, pre-approval of promotional materials may be required.

After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval.

Further, for certain modifications to the drug, including changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain prior FDA approval of a new NDA or NDA supplement, which may require the development and submission of additional data.

After approval, for certain modifications to the drug or the labeling of the drug, including changes in indications, other prescribing information or manufacturing processes or facilities, the applicant may be required to submit and obtain prior FDA approval of a new NDA or NDA supplement, which may require the development and submission of additional data.

A limited category of changes made be made 30 days after submission of an NDA supplement or at the same time as an NDA supplement is submitted.

These are known as “changes being effected” supplements.

There also are continuing, annual program fees for any marketed products.

Drug manufacturers and their subcontractors involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP, which impose certain procedural and documentation requirements upon us and our third-party manufacturers.

Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented.

FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting requirements in the event of a deviation.

FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting requirements in the event of a deviation involving distributed product.

Manufacturers and other parties involved in the drug supply chain for prescription drug products must also comply with product tracking and other tracking requirements and must notify the FDA of counterfeit, diverted, stolen and intentionally adulterated products or products that are otherwise unfit for distribution in the United States.

Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.

Accordingly, manufacturers must continue to expend time, money, and effort in the area of production, quality and distribution control to maintain compliance with cGMP and other aspects of regulatory compliance.

The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.

Later discovery of previously unknown problems with a product, including AEs of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information;

imposition of post-market trials or clinical trials to assess new safety risks;

or imposition of distribution restrictions or other restrictions under a REMS program.

Other potential consequences include, among other things:

If new or increased safety risks are identified, there may be required revisions to the approved labeling, imposition of post-market trials or clinical trials, or imposition of distribution restrictions or other restrictions under a REMS program.

A failure to meet applicable regulatory requirements can result in potential consequences to include, among other things:

• restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

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The FDA closely regulates the marketing, labeling, advertising, and promotion of drug products.

A company can make only those claims relating to safety and efficacy, purity, and potency that are approved by the FDA and in accordance with the provisions of the approved label.

The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses.

A company can make only those claims relating to safety and efficacy, purity, and potency that are approved by the FDA and in accordance with the provisions of the approved labeling.

The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and other advertising and promotion requirements.

Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising, and potential civil and criminal penalties.

Physicians may prescribe, in their independent professional medical judgment, legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA.

Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances.

The FDA does not regulate the behavior of physicians in their choice of treatments.

The FDA does, however, restrict manufacturer’s promotional communications on the subject of off-label use of their products.

However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA-approved labeling.

Other Healthcare Laws

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Actions under the civil FCA may be brought by the U.S.

Attorney General or as a qui tam action by a private individual in the name of the government.

Department of Justice or as a qui tam action by a private individual in the name of the government.

Moreover, a claim including items or services resulting from a violation of the U.S.

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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and their respective implementing regulations, imposes obligations on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” and their respective subcontractors that create, receive, maintain, or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security, and transmission of individually identifiable health information.

The federal Physician Payments Sunshine Act requires applicable manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services (“CMS”), information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), certain other healthcare professionals including physician assistants and nurse practitioners, and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate family members.

The federal Physician Payments Sunshine Act requires applicable manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to the Centers for Medicare & Medicaid Services (“CMS”) information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), certain other healthcare professionals including physician assistants and nurse practitioners, and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate family members.

There are federal price reporting laws, which require manufacturers to calculate and report complex pricing metrics to government programs, and such reported prices may be used in the calculation of reimbursement and/or discounts on approved products.

Similar state and local laws and regulations may also restrict business practices in the pharmaceutical industry, such as state anti-kickback and false claims laws, which may apply to business practices, including but not limited to, research, distribution, sales, and marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, or by patients themselves;

state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources;

state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s otherwise voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources;

state laws and regulations that require drug manufacturers to file reports relating to pricing information and marketing expenditures or which require tracking gifts and other remuneration and items of value provided to physicians, other healthcare providers and entities;

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Coverage and Reimbursement

Sales of any pharmaceutical product depend, in part, on the extent to which such product will be covered by third-party payors, such as federal, state and foreign government healthcare programs, commercial insurance and managed healthcare organizations, and the level of reimbursement for such product by third-party payors.

reimbursement for such product by third-party payors.

In the United States, no uniform policy exists for coverage and reimbursement for pharmaceutical products among third-party payors.

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Additionally, a third-party payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved.

Moreover, as a condition of participating in, and having products covered under, certain federal healthcare programs, such as Medicare and Medicaid, we are subject to federal laws and regulations that require pharmaceutical manufacturers to calculate and report certain price reporting metrics to the government, such as Medicaid Average Manufacturer Price (“AMP”), and Best Price, Medicare Average Sales Price, the 340B Ceiling Price and Non-Federal AMP reported to the Department of Veteran Affairs, and with respect to Medicaid, pay statutory rebates on utilization of manufacturers’ products by Medicaid beneficiaries.

Moreover, as a condition of participating in, and having products covered under, certain federal healthcare programs, such as Medicare and Medicaid, we will be subject to federal laws and regulations that require pharmaceutical manufacturers to calculate and report certain price reporting metrics to the government, such as Medicaid Average Manufacturer Price (“AMP”), and Best Price, Medicare Average Sales Price, the 340B Ceiling Price and Non-Federal AMP reported to the Department of Veteran Affairs, and with respect to Medicaid, pay statutory rebates on utilization of manufacturers’ products by Medicaid beneficiaries.

Compliance with such laws and regulations require significant resources and any findings of non-compliance may have a material adverse effect on our revenues.

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In the United States and certain foreign jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system and the reimbursement of drug products.

For example, on August 16, 2022, President Biden signed the Inflation Reduction Act (the "IRA") into law which sets forth meaningful changes to drug product reimbursement by Medicare.

The IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered Medicare and subjects drug manufacturers to civil monetary penalties and a potential excise tax for offering a price that is not equal to or less than the negotiated "maximum fair price" under the law, and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

For example, the Inflation Reduction Act of 2022 (the “IRA”) sets forth meaningful changes to drug product reimbursement by Medicare.

The IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered by Medicare and subjects drug manufacturers to civil monetary penalties and a potential excise tax for offering a price that is not equal to or less than the negotiated "maximum fair price" under the law, and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

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With respect to price negotiations, Congress authorized Medicare to negotiate lower prices for certain costly single-source drug and biologic products that do not have competing generics or biosimilars and are reimbursed under Medicare Part B or Part D.

CMS may negotiate prices for ten high-cost drugs paid for by Medicare Part D starting in 2026, followed by 15 Part D drugs in 2027, 15 Part B or D drugs in 2028 and 20 Part B or Part D drugs in 2029 and beyond.

This provision applies to drug products that have been approved for at least 7 years and biologics that have been licensed for 11 years, but it does not apply to drugs and biologics that have been approved for a single rare disease or condition.

CMS may establish a maximum price for these products in price negotiations.

CMS negotiated prices for ten high-cost drugs paid for by Medicare Part D effective in 2026 and 15 Part D drugs effective in 2027.

CMS will negotiate prices for 15 Part B or D drugs effective in 2028 and 20 Part B or Part D drugs effective in 2029 and each year thereafter.

The IRA also establishes a rebate obligation for drug manufacturers that increase prices of Medicare Part B and Part D covered drugs at a rate greater than the rate of inflation.

The inflation rebates may require us to pay rebates if we increased the price of a covered Medicare Part B or Part D approved product faster than the rate of inflation.

In addition, the law eliminates the “donut hole” under Medicare Part D beginning in

2025 by significantly lowering the beneficiary maximum out-of-pocket cost and requiring manufacturers to subsidize, through a newly established manufacturer discount program, 10% of Part D enrollees’ prescription costs for brand drugs below the out-of-pocket maximum and 20% once the out-of-pocket maximum has been reached.

The inflation rebates may require us to pay rebates if we increase the price of a covered Medicare Part B or Part D approved product faster than the rate of inflation.

In addition, the law eliminates the “donut hole” under Medicare Part D as of 2025, significantly lowers the beneficiary maximum out-of-pocket cost, and requires manufacturers to subsidize, through a newly established manufacturer discount program, 10% of Part D enrollees’ prescription costs for brand drugs below the out-of-pocket maximum and 20% once the out-of-pocket maximum has been reached.

Our cost-sharing responsibility for any approved product covered by Medicare Part D could be significantly greater under the newly designed Part D benefit structure compared to the pre-IRA benefit design.

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This 2% reductions was temporarily suspended during the COVID-19 pandemic, but has since been reinstated and, unless Congress and/or the Executive Branch take additional action, will begin to increase gradually starting in April 2030, reaching 4% in April 2031, until sequestration ends in October 2031.

Further, the American Taxpayer Relief Act of 2012 reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments from providers from three to five years.

The Medicare Access and CHIP Reauthorization Act of 2015 also introduced a quality payment program under which certain individual Medicare providers will be subject to certain incentives or penalties based on new program quality standards.

In November 2019, CMS issued a final rule finalizing the changes to the Medicare Quality Payment Program.

There has been heightened governmental scrutiny in the United States of pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics.

Such scrutiny has resulted in several recent Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for products.

At the federal level, the first Trump administration used several means to propose or implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives.

For example, on July 24, 2020 and September 13, 2020, the Trump administration announced several executive orders related to prescription drug pricing that attempt to implement several of the administration’s proposals.

The FDA also released a final rule, effective November 30, 2020, implementing a portion of the importation executive order providing guidance for states to build and submit importation plans for drugs from Canada.

At the federal level, the Trump Administration (the “Administration”) has issued Executive Orders relating to prescription drug pricing and letters to pharmaceutical

manufacturers that direct drug manufacturers to, among other things, offer most favored nation (“MFN”) pricing in Medicaid, offer MFN pricing for all newly launched drugs;

repatriate increased revenue from abroad to lower drug prices in the United States, and implement direct-to-consumer and direct-to-business distribution of their products at MFN pricing.

The Administration has warned that manufacturers that fail to make “significant progress” toward MFN pricing will face enumerated regulatory and enforcement consequences.

In September 2025, the Administration began announcing deals with specific manufacturers to address the Administration’s MFN goals.

Further, on November 30, 2020, HHS, finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

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the implementation of these provisions has also been delayed by the IRA until January 1, 2032.

In addition, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminated the statutory Medicaid drug rebate price cap as of January 1, 2024.

Further, in July 2021, the Biden administration released an executive order that included multiple provisions aimed at prescription drugs.

In response to Biden’s executive order, on September 9, 2021, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug price reform.

The plan sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions by HHS.

No legislative or administrative actions have been finalized to implement these principles.

In addition, Congress is considering drug pricing as part of the budget reconciliation process.

Individual states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures and, in some cases, mechanisms to encourage importation from other countries and bulk purchasing.

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laws, such as the California Consumer Privacy Act, the California Privacy Rights Act and the European General Data Protection Regulation 2016/679 (“GDPR”), govern the privacy and security of personal information, including health-related information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

Privacy and security laws, regulations and other obligations are

constantly evolving, and these may conflict with each other which makes compliance efforts more challenging.

Privacy and security laws, regulations and other obligations are constantly evolving, and these may conflict with each other which makes compliance efforts more challenging.

Failure to comply with these laws, where applicable, can result in (i) the imposition of significant civil claims;

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and (vi) negative publicity, reputational harm and a potential loss of business and goodwill.

Regulation and Procedures Governing Approval of Medicinal Products in the EU

Regulation and Procedures Governing Approval of Medicinal Products in the European Union

In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales, manufacturing and distribution of our product candidates to the extent we choose to sell any of our product candidates outside of the United States.

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As in the United States, post-approval regulatory requirements, such as those regarding product manufacture, marketing, or distribution would apply to any product that is approved outside the United States.

Medicinal products in the EU must be granted a marketing authorization (“MA”) before they can be marketed and sold in any EU member state.

Medicinal products in the European Union (the “EU”) must be granted a marketing authorization (“MA”) before they can be marketed and sold in any EU member state.

The process to obtain an MA requires the satisfactory completion of preclinical studies and adequate and well-controlled clinical trials to establish the safety, quality and efficacy of the medicinal product for each proposed therapeutic indication.

It also requires the submission to the relevant competent authorities of an EU marketing authorization application (“MAA”) and granting of an MA by these authorities.

It also requires the submission to the relevant competent authorities of an EU MAA and granting of an MA by these authorities.

The aforementioned EU rules are applicable in the European Economic Area (“EEA”), which consists of the 27 EU member states, as well as Norway, Liechtenstein and Iceland.

Failure to comply with EU and member state laws that apply to the conduct of clinical trials, manufacturing approval, the authorization of medicinal products and marketing of such products, both before and after grant of the MA, or with other applicable regulatory requirements may result in administrative, civil, or criminal penalties.

These penalties could include delays or refusal to authorize the conduct of clinical trials, or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal, or variation of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties.

suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties.

EU Non-Clinical Studies and Clinical Trials

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Research involving animals conducted within the EEA must comply with relevant national implementations of Directive 2010/63/EU, requiring that such testing is carried out in licensed facilities with appropriate staff and in compliance with animal welfare standards.

Until recently, the Clinical Trials Directive 2001/20/EC, the Directive 2005/28/EC on GCP, the Directive 2003/94/EC on GMP and the related national implementing provisions of the individual EU member states governed the system for the approval of clinical trials and the investigational medicinal product supply chain in the EU.

As of January 31, 2022, the new Clinical Trials Regulation (EU) No 536/2014 took effect and replaced the Clinical Trials Directive 2001/20/EC.

Commission Implementing Regulation (EU) 2017/556 replaces the GCP Directive 2005/28/EC, and Commission Delegated Regulation (EU) 2017/1569 replaces the GMP Directive 2003/94/EC with respect to investigational medicinal products.

Pursuant to transitional provisions under the Regulation, qualifying trials could continue to be governed by the national implementations of the Directives until January 31, 2025 if (i) a request for approval was submitted prior to January 31, 2022 or (ii) a request for approval was submitted prior to January 31, 2023 and the sponsor elected to follow the national implementations of the Directives instead of the Regulation.

All ongoing clinical trials in the EU will be subject to the requirements of the Regulation after January 31, 2025.

The new Clinical Trials Regulation aims to simplify and streamline the approval of clinical trials in the EU.

The main characteristics of the regulation include:

a streamlined application procedure via a single-entry point, the Clinical Trials Information System;

The Clinical Trials Regulation (EU) No 536/2014 (which replaced the previous Clinical Trials Directive 2001/20/EC) governs the system for the approval of clinical trials and the investigational medicinal product supply chain in the EU.

The main characteristics of the Clinical Trials Regulation include:

a streamlined application procedure for clinical trial authorization via a single-entry point, the Clinical Trials Information System;

a single set of documents to be prepared and submitted for the application, as well as simplified reporting procedures for clinical trial sponsors;

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Part I is jointly assessed by the competent authorities of all EU member states in which an application for authorization of a clinical trial has been submitted (member states concerned).

Part II is assessed separately by each member state concerned.

Part II is assessed separately by each member state concerned, and applicant may only start a clinical trial at a specific trial site after the competent ethics committee has issued a related favorable opinion.

Strict deadlines have been established for the assessment of clinical trial applications.

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However, overall related timelines are defined by the Clinical Trials Regulation.

Under either the Clinical Trials Directive or the Clinical Trials Regulation, clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and, if intended for regulatory submissions, the International Conference on Harmonization (“ICH”), guidelines on GCP, as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

If the sponsor of the clinical trial is not established within the EEA, it must appoint an entity within the EEA to act as its legal representative.

Under the Clinical Trials Directive, the sponsor was obliged to take out a clinical trial insurance policy and/or maintain an appropriate indemnity or compensation scheme for clinical trial subjects, and in most EU member states, the sponsor was liable to provide ‘no fault’ compensation to any study subject injured in the clinical trial.

Similarly, the Clinical Trials Regulation prescribes that member states must implement a scheme providing for compensation for damage caused by participation in clinical trials within their territory in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk.

Under the applicable regulatory system, an applicant must obtain prior approval from the competent national authority of the EEA member states in which the clinical trial is to be conducted.

Furthermore, the applicant may only start a clinical trial at a specific trial site after the competent ethics committee has issued a related favorable opinion.

The application for authorization of a clinical trial must be accompanied by, among other documents, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation as prescribed by the Clinical Trials Regulation (EU) No 536/2014 and the Implementing Regulation (EU) 2017/556, as applicable, and further detailed in applicable guidance documents.

Any substantial changes to the trial protocol or to other information submitted with the clinical trial application must be notified to or approved by the relevant competent national authorities and ethics committees.

The application for authorization of a clinical trial must be accompanied by, among other documents, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation as prescribed by the Clinical Trials Regulation, and further detailed in applicable guidance documents.

Medicinal products used in clinical trials must be manufactured in accordance with GMP, including in accordance with Commission Delegated Regulation (EU) 2017/1569.

EU clinical trials must be conducted in accordance with EU and national regulations and, if intended for regulatory submissions, the International Conference on Harmonization (“ICH”) guidelines on GCP, as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

If the sponsor of the clinical trial is not established within the EEA, it must appoint an entity within the EEA to act as its legal representative.

The Clinical Trials Regulation additionally prescribes that member states must implement a scheme providing for compensation for damage caused by participation in clinical trials within their territory in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk.

EU Marketing Authorizations

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Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the Priority Medicines ("PRIME") scheme, which provides incentives similar to the breakthrough therapy designation in the United States.

PRIME is a voluntary scheme aimed at enhancing the EMA's support for the development of medicinal products that show the potential to target unmet medical needs.

It permits increased interaction and early dialogue with companies developing promising medicinal products, to optimize their product development plans and speed up their evaluation to help the product reach patients as early as possible.

PRIME is a voluntary scheme aimed at enhancing the EMA's support for the development of medicinal products that are not authorized in the EU and show the potential to target unmet medical needs.

It permits increased interaction and early dialogue with companies developing promising medicinal products, to optimize their product development plans and speed up their evaluation under the centralized procedure to help the product reach patients as early as possible.

Product developers that benefit from PRIME designation are potentially eligible for accelerated assessment of their MAA although this is not guaranteed.

Benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and potentially accelerated MAA assessment once a dossier has been submitted.

Unlike the centralized authorization procedure, the decentralized MA procedure requires a separate application to, and leads to separate approval by, the competent authorities of each EU member state in which the product is to be marketed.

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The reference EU member state prepares a draft assessment report and drafts of the related materials within 120 days after receipt of a valid application.

The resulting assessment report

and related materials are submitted to the concerned EU member states who, within 90 days of receipt, must decide whether to approve the assessment report and related materials.

The resulting assessment report and related materials are submitted to the concerned EU member states who, within 90 days of receipt, must decide whether to approve the assessment report and related materials.

If a concerned EU member state cannot approve the assessment report and related materials due to concerns relating to a potentially serious risk to public health, disputed elements may be referred to the Heads of Medicines Agencies’ Coordination Group for Mutual Recognition and Decentralised Procedures—Human ("CMDh") for review.

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The Committee will then send the opinion to the European Commission, which will adopt a decision that is binding on the applicant and all EU relevant member states.

The mutual recognition procedure allows companies that have a medicinal product already authorized in one EU member state to apply for this authorization to be recognized by the competent authorities in other EU member states.

The mutual recognition procedure allows companies that have a medicinal product already authorized in one EU member state under national procedures to apply for this authorization to be recognized by the competent authorities in other EU member states.

Like the decentralized procedure, the mutual recognition procedure is based on the acceptance by the competent authorities of the EU member states of the MA of a medicinal product by the competent authorities of other EU member states.

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Like a conditional MA, an MA granted in exceptional circumstances is reserved for medicinal products intended to be authorized for the treatment of rare diseases or unmet medical needs for which the applicant does not hold a complete data set that is required for the grant of a standard MA.

While an MA under exceptional circumstances may be subject to an obligation to conduct post-approval studies, unlike the conditional MA, an applicant for authorization in exceptional circumstances is not required to provide the missing data on the medicinal product’s efficacy and safety necessary to convert the conditional MA into a standard MA.

Subject to renewal after five years (as with all standard MAs), the MA “under exceptional circumstances” is granted definitively, but the risk-benefit balance of the medicinal product is reviewed annually and the MA is withdrawn in case the risk-benefit ratio is no longer favorable.

the medicinal product’s efficacy and safety necessary to convert the conditional MA into a standard MA.

Subject to renewal after five years (as with all standard MAs), the MA “under exceptional circumstances” is granted definitively, but the risk-benefit balance of the medicinal product is reviewed annually and the MA can be withdrawn if the risk-benefit ratio is no longer favorable.

In addition to an MA, various other requirements apply to the manufacturing and placing on the EU market of medicinal products.

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These requirements include compliance with EU GMP standards when manufacturing medicinal products and active pharmaceutical ingredients (“API”), including the manufacture of APIs outside of the EU with the intention to import the APIs into the EU.

Similarly, the distribution of medicinal products within the EU is subject to compliance with the applicable EU laws, regulations and guidelines, including good distribution practice (“GDP”) standards and the requirement to hold appropriate authorizations for distribution granted by the competent authorities of the EU member states.

Similarly, the distribution of medicinal products within the EU is subject to compliance with the applicable EU laws, regulations and guidelines, including good distribution practice standards and the requirement to hold appropriate authorizations for distribution granted by the competent authorities of the EU member states.

MA holders, manufacturing and import authorization (“MIA”) holders or distribution authorization holders may be subject to civil, criminal or administrative sanctions, including suspension of the MA, MIA or distribution authorization, in case of non-compliance with the EU or EU member states’ requirements applicable to the manufacturing, import and distribution of medicinal products.

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Upon receiving an initial MA, innovative medicinal products that comprise a new active substance are entitled to eight years of data exclusivity and ten years of market exclusivity.

Data exclusivity, if granted, prevents generic or biosimilar product manufacturers from referencing the innovator’s preclinical and clinical data in

generic or biosimilar MAAs for eight years from the date of authorization of the innovative product, after which a generic or biosimilar MAA can be submitted, and the innovator’s data may be referenced.

Data exclusivity, if granted, prevents generic or biosimilar product manufacturers from referencing the innovator’s preclinical and clinical data in generic or biosimilar MAAs for eight years from the date of authorization of the innovative product, after which a generic or biosimilar MAA can be submitted, and the innovator’s data may be referenced.

The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU until ten years have elapsed from the initial MA of the reference product in the EU.

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For such products, the results of appropriate preclinical or clinical trials regarding biosimilarity must be provided in support of an MAA.

In April 2023, the European Commission proposed widespread changes to the existing pharmaceutical legislation that would, among other things, alter the data exclusivity periods available to MA holders if adopted into EU law.

In December 2025, the European Parliament and the Council of the European Union reached a provisional agreement to amend existing EU pharmaceutical legislation that will, among other things, alter the conditions and periods for data exclusivity available to MA holders when adopted into EU law.

The final text of the new legislation is due to be released in early 2026 and expected transitional provisions mean that it will most likely apply from mid-2028.

EU Post-Approval Requirements

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For example, applicable laws prohibit pre-authorization and misleading advertising and require that promotional materials and advertising in relation to medicinal products comply with the product’s Summary of Product Characteristics (“SmPC”), as approved by the competent authorities in connection with an MA.

The SmPC is the document that provides information to physicians concerning the safe and effective use of the product.

The SmPC is the document that provides information to physicians concerning the safe and

effective use of the product.

Promotional activity that does not comply with the SmPC is considered off-label and is prohibited in the EU.

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Proposals to amend EU pharmaceutical laws

In April 2023, the European Commission released proposals to amend the current EU pharmaceutical regulatory framework.

The proposals seek to achieve a balance between supporting innovation and increasing the affordability and geographic availability of medicines.

The potential reforms include shortening and modulating the periods of regulatory and/or marketing protections available for innovative products, requiring applicants to include environmental impact assessments in MAAs, increasing transparency and disclosure requirements, and restructuring the EMA’s scientific committees.

The European Parliament adopted its position on the proposals on April 10, 2024 and the European Council is expected to adopt its position in 2025.

Further trialogue negotiations between the European Commission, European Parliament and the European Council will then begin before the proposed reforms can enter into force under EU legislative procedures.

Depending on the progress of these negotiations, legislative changes, if any, are not expected to come into force until 2026 at the earliest.

It is also expected that there will further transition periods for most, if not all, of the new rules once the necessary legislation becomes effective.

In December 2025, the European Parliament and the Council of the European Union reached a provisional agreement on legislation to amend the current EU pharmaceutical regulatory framework.

The legislative reforms are intended to achieve a balance between supporting innovation and increasing the affordability and geographic availability of medicines.

The text of the new legislation is due to be released in early 2026.

Such legislation is likely to include altering the conditions and periods of marketing protections available for innovative products, requiring applicants to include environmental impact assessments in MAAs, increasing transparency and disclosure requirements, and restructuring the EMA’s scientific committees.

Legislative changes are not expected to come into force until early 2026 and the expected transitional provisions mean that such changes will most likely apply from mid-2028.

Japanese Drug Regulation

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For purposes of the below description of drug regulation in China, Hong Kong, Macao and Taiwan, which are governed by separate drug laws, are excluded.

The regulatory requirements applicable depend, in part, on whether the drug is made and finished in China, which is referred to as a domestically manufactured drug, or made abroad and imported into China in finished form, which is referred to as an imported drug, as well as the approval or “registration” category of the drug.

or “registration” category of the drug.

For both imported and domestically manufactured drugs, China requires regulatory approval for a clinical trial application (“CTA”) to conduct clinical trials in China and submit China clinical trial data, prior to submitting an application for marketing approval.

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Trials must also be conducted at sites that have received credentials from the NHC and NMPA.

China is a member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (“ICH”), so its GCP resemble the ICH GCP in a great many respects.

China is a member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (“International Council for Harmonisation”), so its GCP resemble the International Council for Harmonisation GCP in a great many respects.

However, there are some differences.

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If approved, obicetrapib would compete with approved non-statin treatments such as ezetimibe, Nexletol/Nexlizet and PCSK9 inhibitors such as Repatha, Praluent and Leqvio.

There are also a number of product candidates in clinical development by third parties, such as Amryt Pharma, Arrowhead Pharmaceuticals, AstraZeneca, CVI Pharmaceuticals, Innovent Biologics, Ionis Pharmaceuticals, Matinas BioPharma, Merck, Novartis, Novo Nordisk, Regeneron Pharmaceuticals, Verve Therapeutics and others, that are intended to treat CVD.

We are also aware of two orally administered small molecule product candidates that target the PCSK9 protein as a mechanism to lower LDL-C and reduce the risk of ASCVD in various stages of clinical development.

These consist of MK-0616 (Enlicitide) from Merck & Co., Inc, for which Merck released data from completed Phase 3 trials of adult patients with hypercholesterolemia in November 2025 and, if approved, has the potential to enter the U.S.

market in 2026, and AZD0780 from AstraZeneca, which is being evaluated in an ongoing Phase 3 clinical trial.

There are also a number of other product candidates in clinical development by third parties, such as Arrowhead Pharmaceuticals, CVI Pharmaceuticals, Innovent Biologics, Ionis Pharmaceuticals, Lib Therapeutics, Novartis, Novo Nordisk, Regeneron Pharmaceuticals, Verve Therapeutics and others, that are intended to treat ASCVD by lowering LDL-C and/or Lp(a).

Employees and Human Capital Resources

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These independent contractors provide a diverse array of services, which includes assisting with our clinical development, manufacturing activities and regulatory obligations.

No Works Council or other employee representative body ( personeelsvertegenwoordiging ) is established within the Company, NewAmsterdam Pharma Holding B.V.

or NewAmsterdam Pharma B.V.

No Works Council or other employee representative body ( personeelsvertegenwoordiging ) is established within the Company or its subsidiaries.

We recognize that our continued ability to attract, retain and motivate exceptional employees is vital to ensuring our long-term competitive advantage.

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Our legal and commercial name is NewAmsterdam Pharma Company N.V.

We were incorporated as a private company with limited liability ( besloten vennootschap met beperkte aansprakelijkheid ) under the laws of the Netherlands on June 10, 2022, solely for the purpose of effectuating the Business Combination.

As part of the Business Combination, we converted our legal form to a public limited liability company ( naamloze vennootschap ) under the laws of the Netherlands on November 21, 2022.

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The address of our registered office is Gooimeer 2-35 1411 DC Naarden, the Netherlands, and the telephone number of the Company is +31 (0) 35 206 2971.

Our agent in the United States is our subsidiary, NewAmsterdam Pharma Corporation.

Our agent in the United States is our subsidiary, NewAmsterdam Pharma Corporation, a corporation organized under the laws of the State of Delaware.

NewAmsterdam Pharma Corporation’s address is 20803 Biscayne Blvd, Suite #105, Aventura, Florida.

Corporation, a Cayman Islands exempted company (“FLAC”), NewAmsterdam Pharma, and NewAmsterdam Pharma Investment Corporation, a Cayman Islands exempted company and wholly owned subsidiary of the Company (“Merger Sub”).

On November 22, 2022 (the “Closing Date”), we consummated a business combination pursuant to the Business Combination Agreement, dated as of July 25, 2022 (the “Business Combination Agreement”), by and among the Company, Frazier Lifesciences Acquisition Corporation, a Cayman Islands exempted company (“FLAC”), NewAmsterdam Pharma Holding B.V., and NewAmsterdam Pharma Investment Corporation, a Cayman Islands exempted company and wholly owned subsidiary of the Company (“Merger Sub”).

Beginning on the day immediately prior to the Closing Date and finishing on the day immediately after the Closing Date, the following transactions occurred pursuant to the terms of the Business Combination Agreement (collectively, the “Business Combination”):

• The shareholders of NewAmsterdam Pharma (“Participating Shareholders”) contributed all outstanding shares in the capital of NewAmsterdam Pharma to the Company in exchange for the issuance of ordinary shares, nominal value €0.12 per share (the “Ordinary Shares”), in the share capital of the Company (the “Exchange”);

• The shareholders of NewAmsterdam Pharma Holding B.V.

(“Participating Shareholders”) contributed all outstanding shares in the capital of NewAmsterdam Pharma Holding B.V.

to the Company in exchange for the issuance of ordinary shares, nominal value €0.12 per share (the “Ordinary Shares”), in the share capital of the Company (the “Exchange”);

• Immediately after giving effect to the Exchange, the Company’s legal form was converted from a Dutch private company with limited liability ( besloten vennootschap met beperkte aansprakelijkheid ) to a Dutch public limited liability company ( naamloze vennootschap );

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• Immediately following the Merger, each outstanding warrant to purchase a Class A ordinary share, par value $0.0001 per share, of FLAC became a warrant to purchase one Ordinary Share, on the same contractual terms;

• Each NewAmsterdam Pharma option that was outstanding and unexercised (“NewAmsterdam Pharma Options”) remained outstanding, and to the extent unvested, such option will continue to vest in accordance with its applicable terms, and at the time of the Exchange, such NewAmsterdam Pharma Options became options to purchase, and will when exercised be settled in Ordinary Shares;

• Each NewAmsterdam Pharma Holding B.V.

option that was outstanding and unexercised (“NewAmsterdam Pharma Options”) remained outstanding, and to the extent unvested, such option will continue to vest in accordance with its applicable terms, and at the time of the Exchange, such NewAmsterdam Pharma Options became options to purchase, and will when exercised be settled in Ordinary Shares;

• On the day following the Closing Date, FLAC changed its jurisdiction of incorporation by deregistering as a Cayman Islands exempted company and domesticated as a corporation incorporated under the laws of the State of Delaware (the “Domestication”).

Upon the achievement of a certain clinical development milestone, we will issue to the Participating Shareholders (including Saga Investments Coöperatief U.A.

(“Amgen”), an affiliate of Amgen, Inc., and Mitsubishi Tanabe Pharma Corporation (“MTPC”) for this purpose) and holders of NewAmsterdam Pharma Options prior to the closing of the Business Combination, who were directors, officers, employees or consultants of NewAmsterdam Pharma as of the date of the Business Combination Agreement and who are at the time of achievement of such milestone providing services to the Company or its subsidiaries (the “Participating Optionholders”), 1,886,137 additional Ordinary Shares (the “Earnout Shares”), which in the case of the Participating Optionholders will take the form of awards of restricted stock units under the LTIP.

As of December 31, 2024, 1,743,135 Earnout Shares and 143,002 Earnout Shares were allocated to Participating Shareholders and Participating Optionholders, respectively.

The development milestone consists of the achievement and public announcement of Positive Phase 3 Data (as defined in the Business Combination Agreement) for each of NewAmsterdam Pharma’s BROADWAY clinical trial and BROOKLYN clinical trial at any time during the period beginning on the date immediately prior to the Closing Date and ending on the date that is five years after the date immediately after the Closing Date, or November 23, 2027.

As a result, no Earnout Shares will be issuable if the applicable milestone is not achieved within five years of the Closing Date.

Upon the achievement of a certain clinical development milestone, pursuant to the Business Combination Agreement, in March 2025 we issued to the Participating Shareholders (including Saga Investments Coöperatief U.A.

as of the date of the Business Combination Agreement and who were at the time of achievement of such milestone providing services to the Company or its subsidiaries (the

“Participating Optionholders”), 1,886,137 additional Ordinary Shares (the “Earnout Shares”), which in the case of the Participating Optionholders took the form of awards of 143,001 restricted stock units (the “Earnout RSUs”) in the aggregate under the LTIP.

Prior to the Business Combination, we did not conduct any material activities other than those incident to our formation and certain matters related to the Business Combination, such as the making of certain required securities law filings.

Upon the closing of the Business Combination, NewAmsterdam Pharma became our direct, wholly owned subsidiary, and holds all of our material assets and conducts all of our business activities and operations.

Upon the closing of the Business Combination, NewAmsterdam Pharma Holding B.V.

became our direct, wholly owned subsidiary, and holds all of our material assets and conducts all of our business activities and operations.

Available Information

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business