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Item 1. Business

2025-02-26 compared with 2024-02-28 · 310 added, 506 removed, 839 unchanged (49% of the section changed)

We are a late-stage biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where currently approved therapies have not been adequate or well tolerated.

We are a late-stage biopharmaceutical company whose mission is to improve patient care in populations with cardiometabolic diseases where currently approved therapies have not been adequate or well tolerated.

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

In multiple phase 3 studies, we are investigating obicetrapib, an oral, low-dose and once-daily 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 or Type 2 diabetes.

CVD is a leading cause of death worldwide and the top cause of death in the United States.

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.

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.

In each of our Phase 3 clinical trials, BROADWAY and BROOKLYN, evaluating obicetrapib as an adjunct to high-intensity statin therapy, obicetrapib met its primary and secondary endpoints, with statistically significant reductions in LDL-C observed.

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”).

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.

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

Lowering of LDL-C, has been associated with major adverse cardiovascular events (“MACE”) benefit in trials of LDL-C lowering drugs, including the REVEAL trial with the CETP inhibitor, anacetrapib.

In our Phase 3 BROADWAY clinical trial, we observed a 21% reduction in the exploratory MACE endpoint (coronary heart disease death, non-fatal myocardial infarction, non-fatal stroke and coronary revascularization) and we are performing a Phase 3 cardiovascular outcomes trial (“CVOT”), PREVAIL, to reconfirm this relationship.

Obicetrapib has shown to not only reduce LDL-C but also several additional biomarkers associated with MACE.

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.

CVD is a leading cause of death worldwide.

Atherosclerotic cardiovascular disease (“ASCVD”) is primarily caused by atherosclerosis, which involves the build-up of fatty material within the inner walls of the arteries.

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We estimate that in the United States there are approximately 30 million patients that are not at their risk-based LDL-C goals despite treatment with lipid lowering therapy, including approximately 13 million with ASCVD.

Existing non-statin treatment options have been largely unable to address the needs of patients with high cholesterol due to limited efficacy, an inconvenient injectable administration route and market access restrictions.

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

Our product candidate, obicetrapib, is a next-generation, oral, low-dose CETP inhibitor that we are developing to potentially overcome the limitations of current LDL-C lowering treatments.

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

In our Phase 2 ROSE2 clinical trial evaluating obicetrapib in combination with ezetimibe as an adjunct to high-intensity statin therapy, obicetrapib met its primary and secondary endpoints, with statistically significant reductions in LDL-C and apolipoprotein B (“ApoB”) 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 with respect to muscle related side effects, and drug-related treatment-emergent serious adverse events (“TESAEs”).

We have observed a favorable tolerability profile for obicetrapib in an aggregate of over 800 patients with low or moderately elevated LDL-C levels (“dyslipidemia”) in our clinical trials to date.

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

We are developing a fixed dose combination of obicetrapib 10 mg and ezetimibe 10 mg, which has been observed to demonstrate even greater LDL-C reduction in our Phase 2b ROSE2 clinical trial.

Lowering of LDL-C, has been associated with major adverse cardiovascular events ("MACE") benefit in trials of LDL-C lowering drugs, including the REVEAL trial with the CETP inhibitor, anacetrapib.

We are performing a cardiovascular outcomes trial (“CVOT”) to reconfirm this relationship.

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.

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 A.

Menarini International Licensing S.A., part of Menarini Group (“Menarini”), providing them with the exclusive rights to commercialize 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, in the majority of European countries, if approved.

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.

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

We are conducting 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.

We completed enrollment for BROOKLYN in April 2023 and for BROADWAY in July 2023.

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

We currently expect to report top-line data from BROOKLYN in the third quarter of 2024 and from BROADWAY in the fourth quarter of 2024.

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.

We announced topline results for BROOKLYN in July 2024 and for BROADWAY in December 2024, both of which met the primary endpoint for the study with safety and tolerability comparable to placebo.

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 expect to complete enrollment in PREVAIL in the first quarter of 2024 and report top-line data in 2026.

On June 5, 2023, we reported top-line results from our Phase 2b dose-finding trial of obicetrapib as an adjunct to stable statin therapy in patients with dyslipidemia in Japan, and on September 21, 2023, reported initial data from our Phase 2a clinical trial evaluating obicetrapib in patients with early Alzheimer’s disease.

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 2 ROSE2 trial, we evaluated the efficacy and safety of obicetrapib plus ezetimibe compared to obicetrapib and placebo alone.

On June 3, 2023, we reported data from the Phase 2 ROSE2 trial, which met its primary and secondary endpoints.

In parallel with the ROSE2 trial, we formulated two prototype fixed dose combination 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 we anticipate initiating 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.

We anticipate enrolling approximately 400 patients in our TANDEM trial and releasing topline data in the first quarter of 2025.

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.

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.

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

We are executing multiple Phase 3 trials simultaneously, including our Phase 3 BROADWAY trial and PREVAIL CVOT, which both launched in the first quarter of 2022, with clinical plans that incorporate feedback from the FDA, the EMA, the Japan Pharmaceuticals and Medical Devices Agency in Japan (“PMDA”) and the China National Medical Products Administration in China (“NMPA”).

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”).

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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For example, rodents lack the CETP gene and are resistant to Alzheimer’s disease.

In early preclinical studies, when the human CETP gene is

knocked into a mouse, the cholesterol content of the mouse brain was observed to increase by 25%;

In early preclinical studies, when the human CETP gene is knocked into a mouse, the cholesterol content of the mouse brain was observed to increase by 25%;

when combined with the gene for the amyloid precursor protein, hypothesized to be a driver of Alzheimer’s disease, the risk of developing disease analogous to Alzheimer’s disease was observed to greatly increase in the double transgenic mice.

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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.

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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.

In the Phase 3 BROADWAY trial, we observed a statistically significant improvement in these prespecified AEs of special interest after one year of treatment that we hope to reconfirm in the PREVAIL CVOT trial.

Our Management Team and Investors

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Ian Somaiya, our Chief Financial Officer, has nearly three decades of experience in senior leadership roles in the biopharmaceutical industry.

Somaiya most recently served as CFO and Chief Business Officer of Elucida Oncology and, before that, as CFO of TCR 2 Therapeutics, where he guided the company through its initial public offering and two subsequent follow-on offerings, as well as led the company’s finance, reporting, business development and investor relations functions.

Somaiya, our Chief Financial Officer, most recently served as CFO and Chief Business Officer of Elucida Oncology and, before that, as CFO of TCR 2 Therapeutics, where he guided the company through its initial public offering and two subsequent follow-on offerings, as well as led the company’s finance, reporting, business development and investor relations functions.

Prior to joining TCR 2 Therapeutics, Mr.

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He also served as a Managing Director and equity analyst at Nomura Securities, Piper Jaffray and Thomas Weisel Partners.

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.

Earlier in his career, Mr.

Jones held leadership roles of increasing responsibility at Takeda Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim and NitroMed, during which time he supported mass market product launches for notable brands including Excedrin Migraine®, Farxiga®, Pradaxa®, BiDil®, and Abilify®.

In addition, we are backed by leading life sciences investors, including Frazier Life Sciences, Bain Capital, Forbion, RA Capital and Viking Global.

Prospective investors should not rely on the past investment decisions of our investors, as our investors may have different risk tolerances and may have received their shares in prior offerings at a significant discount to the market price.

Prospective investors should not rely on the past investment decisions of our investors, as our investors may have different risk tolerances and may have received their securities in prior offerings at a significant discount to the market price.

Cardiovascular Disease and Hyperlipidemia

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The Cholesterol Treatment Trialists Collaboration (“CTT”) showed that lowering of LDL cholesterol by about 40 mg/dL with standard statin regimens safely reduced the 5-year incidence of major coronary events, revascularizations, and ischemic strokes by 22% .

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.

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.

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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Because PCSK9 inhibitors are injectable, they pose a less attractive option for patients who broadly prefer oral medications, and they have not received the expected utilization by clinicians or patients.

The two non-statin oral LDL-C-lowering therapies, ezetimibe and bempedoic acid, often do not provide the efficacy required for many patients, including high-risk ASCVD patients, that have more aggressive LDL-C goals.

Therefore, there remains a significant unmet medical need for therapies to reduce LDL-C levels and residual cardiovascular risk in a convenient dosage form, and with a more favorable tolerability and safety profile to encourage long-term use and patient compliance We believe that a potent, convenient, safe and well-tolerated low-dose oral medication to reduce LDL-C could fulfill this unmet need.

We believe that a potent, convenient, safe and well-tolerated low-dose oral medication to reduce LDL-C could fulfill this unmet need.

Our Solution:

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We believe that CETP inhibition with obicetrapib has the potential, if approved, to provide patients and physicians with a new oral therapy option to robustly reduce LDL-C.

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

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.

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We have observed a favorable tolerability profile for obicetrapib in an aggregate of over 3,500 patients with dyslipidemia from Phase 1 through Phase 3 clinical trials.

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

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

We completed enrollment for BROADWAY in July 2023 and for BROOKLYN in April 2023.

Over 2,500 patients have been randomized in the BROADWAY trial and over 350 patients have been

randomized in the BROOKLYN trial.

We currently expect to report top-line data from BROOKLYN in the third quarter of 2024 and from BROADWAY in the fourth quarter of 2024.

We currently expect to complete enrollment in PREVAIL in the first quarter of 2024 and report topline data in 2026.

We also conducted a Phase 2b dose-finding trial of obicetrapib as an adjunct to stable statin therapy in patients with dyslipidemia in Japan and announced topline results on June 5, 2023.

We also continue investigating obicetrapib as a fixed dose combination with ezetimibe following the announcement of data from our Phase 2 ROSE2 trial.

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.

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 we anticipate initiating 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.

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.

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 previously conducted clinical trials in patients with moderately high LDL-C levels with or without prior statin therapy, obicetrapib has been observed to lower LDL-C both as a monotherapy and a combination therapy with ezetimibe (an approved LDL-C-lowering medication).

In our Phase 2b ROSE clinical trial, we observed a median LDL-C reduction capability of 51% in patients treated with 10 mg obicetrapib on top of high-intensity statins.

In our Phase 2 ROSE2 clinical trial, we observed a median LDL-C reduction of 63.4% in patients treated with a combination of 10 mg obicetrapib and 10 mg of ezetimibe as an adjunct to high-intensity statins.

In our Phase 3 BROADWAY and BROOKLYN clinical trials, we observed a mean LDL-C reduction capability of 33% and 36%, respectively, compared to placebo in patients treated with 10 mg obicetrapib on top of high-intensity statins.

In our Phase 3 TANDEM clinical trial, we observed a mean LDL-C reduction of 52% in patients treated with a combination of 10 mg obicetrapib and 10 mg of ezetimibe as an adjunct to high-intensity statins, when compared to placebo.

• Promising tolerability profile.

Patients are often non-compliant with existing cholesterol-lowering therapies, particularly statin therapy, due to their side effect profiles, which could result in suboptimal treatment outcomes and disease progression.

In 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, that, if seen in obicetrapib, could make it a potentially attractive adjunct for patients who are concerned about the risks of diabetes associated with statin therapy.

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.

• Convenience.

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• Effect on other predictors of disease risk.

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 clinical trials, obicetrapib also decreases the presence of lipoprotein(a) (“Lp(a)”), an important biomarker for CVD risk reduction.

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.

Lowering LDL-C Through CETP Inhibition

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

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.

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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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.

Small dense LDL particles (“sdLDL-P”) are also believed to be an important predictor of CVD risk, with lower levels of sdLDL-P having been observed to correlate closely to lower cardiovascular risk.

sdLDL-P are also believed to be an important predictor of CVD risk, with lower levels of sdLDL-P having been observed to correlate closely to lower cardiovascular risk.

The measurement of using LDL particle (“LDL-P”) size and particles numbers is an alternative approach to determining CVD risk assessment and research suggest that LDL-P size, density and numbers may be more closely correlated to CVD risk than LDL-C.

Increased levels of LDL-P suggest an increased presence of sdLDL-P which may have a greater potential to develop into arterial plaque due to their increased time in circulation compared to larger LDL-P and greater ability to become

trapped in the arterial wall.

Research has suggested that treatments lowering LDL-C alone may trigger a disconnect between LDL-C and LDL-P, which, given the observed strong connection between LDL-P and CVD risk, suggests there is a need for a drug which lowers both.

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In the Phase 3 REVEAL CVOT investigating the efficacy of anacetrapib in approximately 30,000 patients with ASCVD receiving intensive atorvastatin therapy, there was an observed correlation between MACE benefits for anacetrapib and the magnitude of the LDL-C reduction, suggesting that CETP inhibitors work according to the same principle as statin therapy in reducing MACE.

The REVEAL trial began

enrollment in August 2011 and completed its long-term follow-up in April 2019.

A median four-year follow-up of the REVEAL trial 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.

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.

The REVEAL trial began enrollment in August 2011 and completed its long-term follow-up in April 2019.

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.

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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Obicetrapib has intrinsic properties, such as ionizable features and substantially reduced lipophilicity, that we believe give it more favorable physical, pharmacokinetic and biopharmaceutical properties as a drug candidate compared to other CETP inhibitors.

Our goal is to develop and commercialize potentially transformative oral therapies for patients suffering from cardiometabolic diseases rooted in abnormal cholesterol metabolism for which existing therapies are unsuccessful or not well-tolerated.

The core elements of our strategy to achieve our goal are the following:

• Advance the clinical development of obicetrapib as a next-generation oral, low-dose, once-daily LDL-C lowering treatment as a monotherapy and a fixed dose combination therapy with ezetimibe .

We are conducting three Phase 3 pivotal trials with obicetrapib as a monotherapy, two of which have completed enrollment:

BROADWAY, which has randomized over 2,500 patients, and BROOKLYN, which has randomized over 350 patients, to evaluate obicetrapib as a monotherapy used as an adjunct to maximally tolerated lipid-lowering therapies to potentially enhance LDL-C lowering for ASCVD and/or HeFH patients with elevated LDL-C levels despite being treated with currently available optimal lipid lowering therapy who are at very high risk to experience a future cardiovascular event.

In March 2022, we also commenced our Phase 3 PREVAIL CVOT, which is designed to assess obicetrapib’s potential to reduce occurrences of MACE, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and non-elective coronary revascularization.

We expect to report data from our Phase 3 BROOKLYN trial in the third quarter of 2024 and our Phase 3 BROADWAY trial in the fourth quarter of 2024.

We expect to report data from our Phase 3 PREVAIL CVOT in 2026.

We also anticipate initiating our TANDEM Phase 3 trial using the obicetrapib 10 mg and ezetimibe 10 mg FDC tablet in the first half of 2024.

The TANDEM study is 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 and/or ASCVD.

We anticipate enrolling approximately 400 patients in our TANDEM trial and releasing topline data in the first quarter of 2025.

• Obtain marketing approval from regulatory agencies .

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

We are executing multiple Phase 3 trials simultaneously, with clinical plans that incorporate feedback from the FDA, EMA, PMDA and NMPA.

We have also completed a Phase 2 trial specifically in Japan and are including a significant number of patients in Japan to support approval in those markets on the same timelines as the U.S.

• Commercialize obicetrapib for the treatment of cardiometabolic disease .

We are currently developing capabilities and infrastructure to commercialize obicetrapib in the United States, if approved.

We are additionally focused on selecting optimal partners in targeted geographies at the right time in obicetrapib’s development and commercialization process.

We have partnered with Menarini to exclusively 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.

• Continue evaluating the role of obicetrapib for the treatment of Alzheimer’s disease .

Evidence observed in our preclinical studies suggests that cholesterol accumulation in the brain may be a precursor to Alzheimer’s disease.

For example, rodents lack the CETP gene and are resistant to Alzheimer’s disease.

In early preclinical studies, when the human CETP gene was knocked into a mouse, the cholesterol content of the mouse brain was observed to increase by 25%.

When the CETP gene knock-in is combined with the knock-in gene for the amyloid precursor protein, hypothesized to be a driver of Alzheimer’s disease, the risk of developing a mouse analog of Alzheimer’s disease may greatly increase.

In a preclinical study, we observed that CETP inhibition promoted cholesterol removal from the brain and improved cognition.

We commenced a Phase 2a open-label and single-arm clinical trial in early 2022 in patients with early Alzheimer’s disease and the ApoE4 mutation to evaluate the pharmacodynamic and pharmacokinetic effects, safety and tolerability of obicetrapib.

A total of 13 patients were given 10 mg obicetrapib per day and followed for 24 weeks.

In September 2023, we announced initial data from this trial.

We observed reductions in the levels of 24-hydroxycholesterol and 27-hydroxycholesterol of 11% and 12%, respectively, in the CSF, compared to baseline.

In addition, an increase of 8% compared to baseline in the Aβ42/40

ratio in patient’s plasma was observed and pTau181 levels were observed to be stable.

Increases in 24-hydroxycholesterol and 27-hydroxycholesterol over time have been observed by others to lead to a rise in cognitive and related functional impairment.

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.

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.

We plan to evaluate these markers in our BROADWAY trial, taking advantage of the long term follow up of this study in a patient population of whom, approximately one-third of patients are APoE4 carriers.

• Explore the potential of CETP inhibitors for use in other indications .

We believe that CETP inhibition, by markedly increasing HDL-C and lowering LDL-C, may also have a role to play in other indications by potentially mitigating the risk of developing diseases such as diabetes, which led to an estimated 1,500,000 deaths globally in 2019, in addition to CVD and Alzheimer’s disease.

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 statins.

We are planning preclinical studies examining the potential of obicetrapib for patients suffering from diabetes and have included the onset of diabetes as an endpoint in our CVOT.

Clinical Development Plan

We are conducting two Phase 3 pivotal trials – our BROADWAY and BROOKLYN trials – designed to measure obicetrapib’s ability to reduce LDL-C as a monotherapy administered as an adjunct to maximally tolerated lipid-modifying therapy.

We conducted two Phase 3 pivotal trials – our BROADWAY and BROOKLYN trials – designed to measure obicetrapib’s ability to reduce LDL-C as a monotherapy administered as an adjunct to maximally tolerated lipid-modifying therapy.

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.

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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.

On June 5, 2023, we reported topline results from our Phase 2b dose-finding trial of obicetrapib as an adjunct to stable statin therapy in patients with dyslipidemia in Japan.

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.

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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.

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We believe the REVEAL results provide clinical support for the hypothesis 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.

Specifically, the decrease in MACE observed in the REVEAL trial of anacetrapib is consistent with the findings of the CTT Collaboration, illustrated in the

graphic below.

Specifically, the decrease in MACE observed in the REVEAL trial of anacetrapib is consistent with the findings of the CTT Collaboration, illustrated in the graphic below.

The CTT collaboration conducted a meta-analysis of 26 statin clinical trials and showed that there is a consistent, linear decrease in MACE for every absolute unit of non-HDL (which is primarily composed of LDL-C) cholesterol reduction.

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With these learnings in mind, we are executing a phase 3 clinical development plan for obicetrapib focused on patients with elevated baseline LDL-C and that is designed to support a broad CVD label, if successful.

To date, we have completed seven Phase 1 trials and five Phase 2 trials of obicetrapib.

We are currently conducting two Phase 3 lipid trials as well as a Phase 3 CVOT.

We anticipate initiating our TANDEM Phase 3 trial of obicetrapib 10 mg and ezetimibe 10 mg FDC in the first half of 2024.

In TANDEM, we plan to enroll patients with HeFH, ASCVD or ASCVD risk equivalents 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 compared to placebo, ezetimibe and obicetrapib monotherapy.

To date, we have completed seven Phase 1 trials, five Phase 2 trials and three Phase 3 trials of obicetrapib, and we are currently conducting a Phase 3 PREVAIL CVOT trial.

Planned and Ongoing Clinical Trials for Cardiovascular Disease

Phase 3 TANDEM Fixed Dose Combination Trial

We anticipate initiating 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.

We anticipate enrolling approximately 400 patients in the United States who have a baseline LDL-C of ≥ 70 mg/dL.

Following a 14-day screening period, patients will be 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 primary endpoints include percent change from baseline in LDL-C of obicetrapib 10 mg and ezetimibe 10 mg FDC compared to placebo, ezetimibe 10 mg monotherapy and obicetrapib 10 mg monotherapy on day 84.

Secondary endpoints include percent changes from baseline of obicetrapib 10 mg and ezetimibe 10 mg FDC compared to placebo, ezetimibe 10 mg monotherapy and obicetrapib 10 mg monotherapy on day 84 in ApoB and non-HDL-C.

We also expect to evaluate the safety and tolerability profile of the fixed dose combination.

Phase 3 BROADWAY and BROOKLYN Lipid Trials

We are conducting two Phase 3 pivotal trials designed to measure obicetrapib’s LDL-C lowering capability and plan to enroll patients across both trials who require additional LDL-lowering on top of their maximum tolerated lipid-modifying therapies.

BROADWAY, which completed enrollment in July 2023, randomized approximately 2,500 patients in the United States, Europe and Asia with HeFH (individuals genetically predisposed to very high cholesterol) or established ASCVD, and who have baseline LDL-C of at least 55 mg/dL, and an additional risk enhancer in participants with an LDL-C level below 100 mg/dL (including other abnormal biometrics, a recent myocardial infarction or Type 2 diabetes).

BROOKLYN, which completed enrollment in April 2023, enrolled HeFH patients in the United States, Canada, Europe and

Africa who have baseline LDL-C of at least 70 mg/dL.

Obicetrapib will be 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.

Such lipid-modifying therapies include 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).

The primary endpoint of both trials is percent change from baseline in LDL-C of obicetrapib 10 mg compared to placebo after 12 weeks.

Secondary endpoints will also include percent changes from baseline of obicetrapib 10 mg compared to placebo after 12 weeks in Lp(a), ApoB, HDL-C, non-HDL-C (representing total cholesterol minus HDL-C), LDL-C from baseline to placebo after 180 days and 52 weeks, and, for BROADWAY, total cholesterol and triglycerides and MACE from baseline to 30 days after the last dose.

We also expect to evaluate the safety and tolerability profile of obicetrapib in a broadly representative population 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 as well as to evaluate the effects of obicetrapib on blood pressure.

Phase 3 PREVAIL Cardiovascular Outcomes Trial

We have also initiated our PREVAIL trial (TA-8995-304), our Phase 3 CVOT, to evaluate the effects of 10 mg obicetrapib in participants with ASCVD on MACE (cardiovascular death, myocardial infarction, stroke and non-elective coronary revascularization).

We expect to enroll at least 9,000 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 therefore are not adequately controlled despite maximally tolerated lipid-modifying therapies.

We have initiated our PREVAIL trial (TA-8995-304), our Phase 3 CVOT, to evaluate the effects of 10 mg obicetrapib in participants with ASCVD on MACE, including cardiovascular death, myocardial infarction, stroke and non-elective coronary revascularization.

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.

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

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.

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We believe that the inclusion of a patient population with established ASCVD who are at very high risk to experience a future cardiovascular event given their elevated LDL-C levels despite being treated with maximum lipid lowering therapy and who have other additional risk enhancers increases the likelihood that the trial will accrue sufficient primary endpoint events over time and potentially result in a strong relative risk reduction in the treatment arm.

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.

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.

Phase 2 VINCENT Trial

VINCENT is a Phase 2 clinical study to evaluate the effects of obicetrapib alone and in combination with evolocumab on Lp(a) in patients with mild dyslipidemia.

The single arm study will treat patients with obicetrapib 10 mg daily for 8 weeks followed by obicetrapib 10 mg daily plus evolocumab 140 mg/dL every other week for 8 weeks.

There will be two cohorts in the study.

The first cohort will include 39 participants with Lp(a) levels greater than 50 mg/dL or 125 nmol/L, and the second cohort will include 30 participants with Lp(a) levels greater than 20 mg/dL or 50 nmol/L but less than 50 mg/dL or 125 nmol/L.

Completed Phase 3 Clinical Trials

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.

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 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.

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.

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.

While obicetrapib is designed to promote the expression of LDL receptors in the liver, there is evidence that CETP inhibition also promotes cholesterol excretion into the intestines, where ezetimibe is designed to block cholesterol reabsorption into the body.

Therefore, the combined mechanism is expected to synergistically enhance fecal sterol removal of cholesterol.

We believe that LDL-C lowering effects of ezetimibe can be enhanced by introducing obicetrapib to help facilitate this synergistic mechanism of action.

LDL-C percentage change:

Obicetrapib (n=102)

Obicetrapib and Ezetimibe FDC

Day 84 – from placebo

Comparison to pbo

Comparison to eze 10 mg

Comparison to obi 10 mg

Phase 3 BROADWAY and BROOKLYN Lipid Trials

We conducted two Phase 3 pivotal trials designed to measure obicetrapib’s LDL-C lowering capability and enrolled patients across both trials who require additional LDL-lowering on top of their maximum tolerated lipid-modifying therapies.

BROADWAY, which completed enrollment in July 2023 and for which topline results were announced in December 2024, randomized approximately 2,500 patients in the United States, Europe and Asia with HeFH (individuals genetically predisposed to very high cholesterol) or established ASCVD, and who have baseline LDL-C of at least 55 mg/dL, and an additional risk enhancer in participants with an LDL-C level below 100 mg/dL (including other abnormal biometrics, a recent myocardial infarction or Type 2 diabetes).

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.

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).

The primary endpoint of both trials was percent change from baseline in LDL-C of obicetrapib 10 mg compared to placebo after 84 days.

Secondary endpoints also included percent changes from baseline of obicetrapib 10 mg compared to placebo after 84 days in Lp(a), ApoB, HDL-C and non-HDL-C (representing total cholesterol minus HDL-C), and for BROADWAY, LDL-C levels at days 180 and 365, total cholesterol and triglycerides.

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.

The tables below summarize data from each study:

LDL-C LS mean percentage change in BROOKLYN trial:

% Change from Baseline

Obicetrapib % Change

Placebo (n=118)

Obicetrapib (n=236)

Compared to Placebo

LDL-C percentage change at day 84 in BROADWAY trial:

Obicetrapib 10 mg

LS mean (with imputation)

While BROADWAY was not designed or powered to measure MACE benefit, MACE was evaluated as an exploratory endpoint and as part of our safety analysis.

Despite the limitations of the trial design, we observed a 21% reduction in MACE favoring obicetrapib after one year.

MACE from BROADWAY:

Obicetrapib 10 mg

All-cause mortality – no.

Coronary heart death – no.

First 4-point MACE – no.

4-point MACE:

CHD death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization.

MACE was not a primary or secondary endpoint of the BROADWAY trial.

Pooled MACE from BROADWAY and BROOKLYN:

Obicetrapib 10 mg

All-cause mortality – no.

Coronary heart death – no.

First 4-point MACE – no.

4-point MACE:

CHD death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization.

MACE was not a primary or secondary endpoint of the BROADWAY or BROOKLYN trials.

Neither the BROADWAY nor BROOKLYN trials were designed to assess MACE as the primary or secondary endpoints and as a result there are limitations on the results presented above.

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.

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.

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

Obicetrapib 10 mg

1,007 ( 59.8)

Any TEAEs by maximum severity

Any trial drug related TEAEs

Any trial drug-related TEAEs by maximum severity

Any TEAEs leading to discontinuation of trial drug

Any treatment-emergent non-serious AEs

Any trial drug-related TESAEs

Any TEAEs leading to death

Completed Phase 2 Clinical Trials

We have completed five Phase 2 trials of obicetrapib for the treatment of cardiometabolic disease.

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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 treatment-emergent adverse events (“TEAEs”) were mild or moderate in severity and there were no drug-related, treatment-emergent serious AEs.

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.

Phase 2b ROSE Trial

In our Phase 2b ROSE trial, we observed that obicetrapib has robust LDL-C lowering capability as an adjunct to high-intensity statins at both 5 mg and 10 mg dosages.

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Based on observations from our Phase 2b OCEAN trial, we believe that obicetrapib is at least additive for LDL lowering as a combination therapy with ezetimibe.

The table below summarizes the trial designs of the first three Phase 2 trials we have completed.

Randomized, double-blind placebo-controlled trial to evaluate the percent changes in LDL-C and HDL-C levels

364 patients with mild dyslipidemia not on lipid-altering therapy at screening

1, 2.5, 5 or 10 mg alone

and as a combination

therapy with statins

(TA-8995-201)

Randomized, double-blind placebo-controlled trial to evaluate LDL-C reduction

114 patients with mild dyslipidemia already receiving high-intensity statin therapy

5 mg or 10 mg

(TA-8995-303)

Randomized, double-blind placebo-controlled trial to evaluate LDL-C reduction

112 patients with mild dyslipidemia

5 mg alone and as a

combination therapy

with 10 mg ezetimibe

Phase 2a TULIP Trial

A Phase 2a TULIP trial of obicetrapib, which was completed in 2014, was a randomized, double-blind placebo-controlled trial among 364 patients with mild dyslipidemia and not on lipid-altering therapy at screening and involved once-daily oral dosing of obicetrapib up to 10 mg or a placebo alone and as a combination therapy with statins.

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In patients treated with 10 mg obicetrapib plus statin therapy (20 mg atorvastatin or 10 mg rosuvastatin), LDL-C levels were approximately 50% lower and HDL-C levels were approximately 140% higher, respectively, than those observed in patients receiving statin therapy alone.

Key secondary endpoints included percent changes in ApoB and apolipoprotein A1 (“ApoA1”).

In patients treated with 5 mg obicetrapib, ApoB was reduced by 33.8%, while ApoA1 levels increased by 58.3%.

A daily dose of 10 mg obicetrapib on top of statin therapy resulted in an ApoB reduction of 30% and an ApoA1 increase of 54.1% than those observed in patients receiving statin therapy alone.

Other secondary endpoints included percent change in apolipoprotein E (“ApoE”), nascent HDL levels and ABCA-1 efflux.

A summary of certain of these results follows:

A total of 284 (78.2%) patients experienced at least one TEAE, of which 95 (26.2%) experienced a suspected trial drug-related TEAE.

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

Phase 2b ROSE Trial

Our Phase 2b ROSE trial, which was completed in August 2021, was a randomized, double-blind placebo-controlled trial among 120 patients with mild dyslipidemia who were already receiving high-intensity statin therapy.

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at the 10 mg dose level, that percentage nearly doubled.

A summary of these statistically significant results is as follows:

Median (min, max) LDL-C levels (mg/dL) at baseline and EoT

Baseline Median

% Change from Baseline (median)

(-53.9, 31.6)

(-71.2, 62.3)

(-76.9, 15.6)

% Change from Baseline

LS mean (95% Cl) P-value

(-11.74, 2.22)

(-44.80, -31.17)

(-50.95, -37.35)

We also observed median percent reductions in ApoB of 24.4% and 29.8%;

decreases in non-HDL-C of 38.9% and 44.4%;

increases in HDL-C of 135.4% and 165.0%;

and decreases in Lp(a) of 33.8% and 56.5%, in each case at the 5 mg and 10 mg doses, respectively.

These statistically significant results are summarized as follows:

Percent Change from Baseline to 8 Weeks in Lipid Biomarkers

Median (min, max)

Percent Change:

Median (min, max)

LS Mean (SE) 1

87.0 (66, 136)

88.0 (53, 171)

82.0 (49, 161)

-22.62 (21.9)

-27.19 (15.3)

-2.60 (-50.0, 28.4)

-24.40 (-58.5, 47.4)

-29.75 (-58.4, 13.0)

Median (min, max)

Percent Change:

Median (min, max)

LS Mean (SE) 1

115.0 (87, 227)

118.5 (69, 276)

113.0 (53, 242)

-34.28 (25.6)

-39.25 (17.6)

-3.50 (-50.3, 48.4)

-38.90 (-65.6, 66.3)

-44.40 (-70.2, 22.5)

Median (min, max)

Percent Change:

Median (min, max)

LS Mean (SE) 1

44.5 (19, 99)

46.5 (24, 79)

44.0 (25, 138)

123.92 (57.7)

156.41 (52.2)

-4.90 (-30.3, 28.6)

135.40 (-26.4, 212.9)

164.95 (55.1, 286.3)

Median (min, max)

Percent Change:

Median (min, max)

LS Mean (SE) 1

108.2 (123.3)

117.1 (115.3)

45.3 (2.9, 410)

89.4 (2.8, 354)

29.9 (2.8, 435)

4.00 (-29.6, 45.5)

-33.8 (-84.6, 93.8)

-56.5 (-85.7, 18.3)

Least squares (LS) means and p-values (two-sided) are from a mixed model for repeated measures (MMRM) model with treatment, visit and treatment-by-visit as factors and baseline LDL-C as a covariate.

p-values from comparison to placebo.

For percent change values, n=39 for placebo and obicetrapib 5 mg groups for all, except n=38 for LDL-C and Lp(a) for obicetrapib 5 mg.

Overall, obicetrapib as an adjunct to high-intensity statin therapy at both doses was observed to be well-tolerated compared to placebo.

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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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Based on our ROSE trial and the enhanced LDL-C reduction capability of a 10 mg dose compared with 5 mg and the safety profile we observed, we selected a 10 mg dose for our Phase 3 lipid trials and CVOT.

Phase 2b OCEAN Trial

Our Phase 2b OCEAN trial, which we completed in June 2021, evaluated the effect of obicetrapib as a combination therapy with ezetimibe on LDL-C levels.

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We observed that obicetrapib 5 mg, ezetimibe 10 mg and their combination each significantly reduced LDL-C from baseline and compared with placebo, with statistically significant reductions compared to baseline measured at 34.4%, 14.8% and 52.0%, respectively, compared to a 1.4% reduction in the placebo group.

The results are summarized as follows:

Median (min, max) LDL-C levels (mg/dL) at baseline and EOT

Baseline Median

% change from Baseline median

(-24.5, 35.9)

(-46.8, 46.9)

(-56.7, 19.1)

% change from Baseline LS Mean (95%CI) p-value

(-6.03, 8.84)

(-20.29, -5.42)

(-38.21, -23.19)

(-48.73, -33.16)

We also observed median ApoB reductions of 23.5%, 8.9% and 34.8% for obicetrapib 5 mg, ezetimibe 10 mg and their combination, respectively, compared to 0.9% reduction in the placebo group.

Median (min, max) ApoB levels (mg/dL) at baseline and EOT

Obi 5mg + Eze

Baseline Median

% change from Baseline Median

(-19.8, 25.4)

(-45.4, 32.3)

(-39.3, 21.2)

Obicetrapib 5 mg alone and as a combination therapy with ezetimibe 10 mg taken once daily for eight weeks displayed a favorable tolerability profile.

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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.

A summary of key observations from the ROSE2 trial is set forth below:

Topline Results

The p-value for the LS mean for each endpoint presented in the table below compared to placebo was <0.0001.

The table below shows the median percent change from baseline in patients receiving the combination of obicetrapib and ezetimibe, obicetrapib monotherapy and placebo.

Median Percent Change from Baseline

10 mg + Ezetimibe 10

Friedewald-calculated LDL-C

In addition, we observed median reduction in Lp(a) of 47.2% and 40.2% in the monotherapy and combination arms, respectively.

Percent Change from Baseline to 12 Weeks in Lipid Biomarkers

Obicetrapib 10 mg

Obicetrapib 10 mg /

Ezetimibe 10 mg

Median (min, max)

Percent Change:

Median (min, max)

LS Mean (SE) 1

95.5 (60, 211)

100.0 (35, 189)

87.0 (62, 152)

-6.4 (-36.4, 96.7)

-43.5 (-78.4, 22.6)

-63.4 (-83.7, 29.7)

-39.20 (4.13)

Median (min, max)

Percent Change:

Median (min, max)

LS Mean (SE) 1

89.0 (52, 146)

85.0 (33, 130)

85.0 (56, 130)

-2.1 (-30.9, 76.9)

-24.2 (-44.8, 27.1)

-34.4 (-54.3, 14.7)

Median (min, max)

Percent Change:

Median (min, max)

LS Mean (SE) 1

p-value vs placebo

42.5 (31, 68)

47.0 (28, 111)

46.0 (28, 76)

0.75 (-33.3, 45.0)

142 (34.9, 311)

136 (46.5, 261)

Median (min, max)

Percent Change:

Median (min, max)

LS Mean (SE) 1

p-value vs placebo

126 (73, 227)

122 (57, 209)

116 (77, 189)

-5.6 (-34.9, 83.6)

-37.5 (-59.2, 20.0)

-55.6 (-76.2, -30.8)

In addition, the combination of obicetrapib plus ezetimibe resulted in significantly more patients achieving LDL-C levels of less than 100 mg/dL, 70 mg/dL and 55 mg/dL than the placebo group (100%, 93.5% and 87.1% compared to 66.7%, 16.7% and 0.0%, respectively) (p<0.05 compared to placebo for combination therapy).

These results are presented in further detail below:

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).

Therefore, the combined mechanism is expected to synergistically enhance fecal sterol removal of cholesterol, as shown in the figure below.

As suggested by the calculations below, we believe that LDL-C lowering effects of ezetimibe can be enhanced by introducing obicetrapib to help facilitate this synergistic mechanism of action.

The calculations above are not based on a head-to-head comparison or clinical trial and are hypothetical calculations.

These calculations are based on the findings in our ROSE2 trial with respect to the figures on the bottom right and the findings of source noted above with respect to the figures on the bottom left, and assume one patient was treated with each drug independently.

In parallel with the ROSE2 trial, we formulated two prototype fixed-dose combination 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.

Our goal is to submit an NDA for the combination shortly after submitting an NDA for obicetrapib as a monotherapy.

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.

Japan Phase 2b Clinical Trial

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The trial was conducted at hospitals and clinics across Japan.

The primary endpoint was the percent change from baseline to end of treatment (day 56) in LDL-C for each obicetrapib group compared

The primary endpoint was the percent change from baseline to end of treatment (day 56) in LDL-C for each obicetrapib group compared to placebo.

The trial enrolled 102 adult participants, who were randomized 1:1:1:1 to receive obicetrapib 2.5 mg, 5 mg, 10 mg or placebo for the 56-day treatment period.

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Overall, no drug-related TESAEs were observed, and there were no TEAEs leading to death.

Phase 1 Clinical Trials

We have completed seven Phase 1 clinical trials of obicetrapib in healthy patients to date, which are summarized in the below table.

Phase 1 Trial

Single ascending dose study in healthy Caucasian and Japanese subjects

Randomized, double-blind, single-dose, placebo-controlled trial in healthy men and women.

12 groups of 8 subjects.

2 to 6 randomized to placebo or active treatment.

Single oral dose of 5, 10, 25, 50, 100 and 150 mg obicetrapib capsules, or

Single oral dose of placebo

Dose-dependent and sustained inhibition of CETP activity accompanied by a decrease in LDL-C and ApoB and increases in CETP, HDL-C, ApoA1 and ApoE.

Pharmacokinetics and pharmacodynamics generally consistent across ethnicity, age and gender.

Multiple ascending dose study in healthy subjects

Randomized double-blind, placebo-controlled, sequential, multiple ascending-dose design.

5 groups of 12 subjects randomized to placebo or active treatment.

Duration of treatment:

28 days of dosing for group 1, 21 days for groups 2-5.

Multiple oral dosages of 5, 10, 2.5, 1, and 25 mg obicetrapib capsules, or

Multiple oral dosages of placebo

No safety or tolerability issues observed.

Single and multiple doses of up to 25 mg of obicetrapib did not yield adverse effects on vital signs or ECG changes, nor did clinical laboratory assessments and physical examinations reveal any safety issues.

The maximum percent reduction in CETP activity from baseline following the 5 mg and 10 mg doses were 90.9% and 97.6%, respectively.

Study to assess the mass balance recovery, pharmacokinetics, metabolism and excretion of 14 C-TA-8995 in healthy male subjects

Open label, single oral dose study in 6 subjects.

10 mL 14 C-obicetrapib oral suspension, containing 10 mg and 100 µCi of 14 C-obicetrapib

Obicetrapib was steadily absorbed with a median of 4.5 hours to maximum absorption levels.

Median half-life was 161 hours.

A mean of 63.8% radioactivity was recovered in the feces and 15.4% in the urine, Overall total recovery of radioactivity in excreta approximately 78% of the administered dose.

Phase 1 Trial

Study of the electrocardiographic effects of TA-8995 in healthy male and female subjects

135 subjects randomized to one of 3 study treatments.

Single oral dose of 150 mg obicetrapib capsules, or Single oral dose of placebo, or Single open-label oral dose of 400 mg moxifloxacin

No clinically meaningful effects on any ECG parameter were observed.

A Phase 1, open label study to assess the effects of TA-8995 on the pharmacokinetics of midazolam and digoxin in healthy male subjects

Open label, crossover, fixed sequence study in 16 healthy male

Duration of treatment up to 15 days.

Digoxin 0.25 mg oral tablet on the morning of Days 1 and 13

Midazolam 5 mg oral solution on the morning of Days 2 and 14 obicetrapib 25 mg (2 x 10 mg and 1 x 5 mg) oral capsules on the morning of Day 8 and 10 mg oral capsule on the morning of Days 9 to 15.

No significant effect on digoxin was observed, with a statistically significant decrease in midazolam plasma.

Absorption rates of digoxin and midazolam were unaffected by the presence of multiple doses of obicetrapib.

Bioequivalence study of capsule and tablet formulations of TA-8995 in healthy male subjects

Open-label, randomized, 2 treatment period (3 days), cross-over study in 26 subjects

5 mg obicetrapib orally, either as a capsule or as a tablet in the first treatment period, and vice versa in the second treatment period.

Obicetrapib formulated as a tablet was bioequivalent to obicetrapib formulated as a capsule in terms of overall concentration over time but not in terms of the maximum observed concentration, which varied among study subjects.

A Phase 1 study of the effects of TA-8995 on Lp(a) in male and female subjects with elevated Lp(a)

Single-center, randomized, double-blind, placebo- controlled, parallel-group

TA-8995 10 mg once daily, TA-8995 2.5 mg once daily, or matching placebo once daily.

There were statistically significant reductions in Lp(a) in both the TA-8995 2.5 mg and 10 mg groups, compared with placebo, at week 12 (primary endpoint) and at week 4 (secondary endpoint).

There were statistically significant increases in HDL-C,

Phase 1 Trial

ApoA1, and ApoE levels and decreases in LDL-C and ApoB levels, at week 12, for both the TA-8995 2.5 mg and 10 mg groups, compared with placebo.

TA-8995 2.5 mg and 10 mg once daily for 12 weeks was generally well tolerated in subjects with elevated Lp(a) levels.

A randomized, open-label, two-sequence, two-period, two-treatment crossover study to evaluate the effect of food on the bioavailability of obicetrapib tablets in healthy adult subjects

Open-label, single-dose, randomized, 2-sequence, 2-period, 2-treatment crossover study in 30 subjects

10 mg obicetrapib tablets orally administered either after an overnight fast of at least 10 hours (Treatment T1, fasted) or at 30 minutes after the start of a completed standardized high-fat, high-calorie breakfast that was preceded by an overnight fast of at least 10 hours (Treatment T2, fed)

Based on the plasma concentration data for obicetrapib, the peak and overall systemic exposure were 55-59% greater under fed conditions compared to that of fasted conditions.

The least-squares geometric mean of fed versus fasted ratios were 154.87%, 155.42% and 158.53% for AUC0-t, AUC0-∞ and C max , respectively.

Obicetrapib for Other Therapeutic Areas

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Alzheimer’s disease is the most prevalent form of dementia, resulting in the generalized degeneration of the brain.

In a healthy brain, excess cholesterol levels in the neurons and amyloid-beta (“Ab”) peptide removal from brain parenchyma are regulated properly.

In a healthy brain, excess cholesterol levels in the neurons and amyloid-beta (“Aβ”) peptide removal from brain parenchyma are regulated properly.

The brain is the most cholesterol-rich organ in the body;

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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.

Overall, obicetrapib was observed to be well-tolerated.

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Manufacturing and Supply

We currently have no manufacturing facilities and a small but experienced group of personnel managing manufacturing activities.

We rely on several contract manufacturers to produce both drug substances and drug products required for our clinical trials.

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 Italy.

We currently have no manufacturing facilities and instead rely on several contract manufacturers to produce drug substance and drug products.

The production is overseen by an experienced group of personnel.

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

Marketing and Sales

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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 an exclusive license agreement, dated June 23, 2022, with Menarini (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 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.

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.

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Menarini has also committed to providing €27.5 million in funding for our research and development activities over several years, together with bearing 50% of any development costs incurred in respect of the pediatric population in the Menarini Territory.

We are also eligible to receive up to an additional €863 million upon the achievement of various clinical, regulatory and commercial milestones.

We are also eligible to receive up to an additional €863 million upon the achievement of various clinical, regulatory and commercial milestones, of which a total of €30 million has been received to date.

If obicetrapib is approved and successfully commercialized by Menarini, we will be entitled to tiered royalties ranging from the low double digits to the mid-twenties as a percentage of net sales in the Menarini Territory, with royalty step-downs in the event of generic entrance or in respect of required third-party intellectual property payments.

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

Through December 31, 2023, we received one milestone payment from Menarini under the Menarini License upon the achievement of a clinical milestone.

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.

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.

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, 2023, we owned eight issued U.S.

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

patents and 17 pending U.S.

patent applications.

We also owned 100 granted European patents and four pending European patent applications, two granted Chinese patents and seven pending Chinese 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.

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

or remain in force for only a short period following commercial launch, thereby limiting the protection such patent would afford the applicable product and any competitive advantage such patent may provide.

In addition, because of the extensive time required for clinical development and regulatory review of a product candidate we may develop, it is possible that, before our product candidate can be commercialized successfully, any related patents may expire or remain in force for only a short period following commercial launch, thereby limiting the protection such patent would afford the applicable product and any competitive advantage such patent may provide.

For any individual patent, the term depends on the applicable law in the country in which the patent is issued.

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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 have one granted patent in India.

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.

Patent applications are pending in Argentina and Thailand.

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

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.

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.

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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 three granted patents in the United States.

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

We have 39 granted patents in Europe.

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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, Venezuela and the United States.

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 Europe and other foreign jurisdictions, methods of use in which obicetrapib and a statin are separately administered.

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.

We have a pending application, but no granted patents, in Europe.

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

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.

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

Patents, and patent applications if granted, are expected to expire between February 2034 and 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 the synthetic process we intend to use commercially, as well as processes to make that intermediate.

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 Taiwan and one granted patent in India.

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 Argentina, Europe, Republic of Korea and Venezuela.

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

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 pending US, PCT, Argentina, Taiwan, Pakistan and Lebanon applications covering the solid salt form of obicetrapib that we intend to commercialize and the process for its commercial synthesis.

Patents if granted are expected to expire in July 2043, without taking potential patent term adjustment or extensions into account.

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.

Two of these families are directed to combinations with ezetimibe, one of which is for use in certain subpopulations of patients and one of which is directed to improved formulation of obicetrapib in fixed dose combinations with ezetimibe.

Patents if granted are expected to expire in February 2042 and August 2043, without taking potential patent term adjustment or extensions into account.

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.

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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 currently consists of patent applications pending in the United States, Europe, China and other jurisdictions.

If granted, these patents 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.

Any patents that grant from this second family will expire in September 2043, without taking potential patent term adjustments or patent term extensions into account.

Finally, we have one patent family, consisting of pending patent applications, drawn to treatment of another clinical indication.

Patents if granted from this family will expire in November 2044, without taking potential patent term adjustments or patent term extensions into account.

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.

Trade Secrets

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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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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, and the FDA is able to validate the data through an onsite inspection, if deemed necessary.

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

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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.

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.

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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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.

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.

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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.

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.

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

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

The FDA does, however, restrict manufacturer’s 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 labelling.

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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federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil FCA.

In addition, the civil monetary penalties statute, subject to certain exceptions, prohibits, among other things, the offer or transfer of remuneration, including waivers of copayments and deductible amounts (or any part thereof), to a Medicare or state healthcare program beneficiary if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner or supplier of services reimbursable by Medicare or a state healthcare program.

In addition, the civil monetary penalties statute, subject to certain exceptions, prohibits, among other things, the offer or transfer of remuneration to a Medicare or state healthcare program beneficiary if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner or supplier of services reimbursable by Medicare or a state healthcare program.

The federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) created additional federal criminal statutes that prohibit, among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

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federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and their respective implementing regulations, which impose 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 certain 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.

Effective January 1, 2022, these reporting obligations extend to include transfers of value made to certain non-physician providers (physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists and anesthesiologist assistants, and certified-nurse midwives).

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.

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.

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Healthcare Reform

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.

In the United States, by way of example, in March 2010, the Patient Protection and Affordable Care Act and the Health Care and Education Affordability Reconciliation Act of 2010 (collectively, the “ACA”) was signed into law, which substantially changed the way healthcare is financed by both governmental and private insurers in the United States and significantly affected the pharmaceutical industry.

The ACA, among other things, increased the minimum level of Medicaid rebates payable by manufacturers of brand name drugs;

required collection of rebates for drugs paid by Medicaid managed care organizations;

required manufacturers to participate in a coverage gap discount program, under which they must agree to offer point-of-sale discounts (increased to 70%, effective as of January 1, 2019) off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D;

imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell certain “branded prescription drugs” to specified federal government programs;

implemented a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected expanded the types of entities eligible for the 340B drug discount program;

expanded eligibility criteria for Medicaid programs;

created a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research;

and established a Center for Medicare Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.

Since its enactment, there have been judicial, administrative, executive and Congressional legislative challenges to certain aspects of the ACA.

While Congress has not passed comprehensive repeal legislation, several bills affecting the implementation of certain taxes under the ACA have been signed into law.

In December 2017, Congress repealed the tax penalty, effective January 1, 2019, for an individual’s failure to maintain ACA-mandated health insurance as part of the Tax Act.

President Biden issued an executive order that instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

It is possible that the ACA will be subject to judicial or Congressional challenges in the future.

Further, there have been a number of health reform initiatives by the Biden administration that have impacted the ACA.

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.

Among other actions, the IRA permits the U.S.

Department of Health and Human Services (“HHS”) to engage in price-capped negotiation to set the price of certain drugs and biologics reimbursed under Medicare Part B and Part D.

The IRA contains statutory exclusions to the negotiation program, including for certain orphan designated drugs for which the only approved indication (or indications) is for the orphan disease or condition.

Should our product candidates be approved and covered by Medicare Part B or Part D, and fail to fall within a statutory exclusion, such as that for an orphan drug, those products could, after a period of time, be selected for negotiation and become subject to prices representing a significant discount from average prices to wholesalers and direct purchasers.

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.

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

These provisions began to take effect in 2023, although several significant challenges concerning the provisions for Medicare price negotiations are currently pending before federal appeals courts.

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.

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 cost 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 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.

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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The IRA is anticipated to have significant effects on the pharmaceutical industry and may reduce the prices we can charge and reimbursement we can receive for our products, among other effects.

It is unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA.

In addition, other federal health reform measures have been proposed and adopted in the United States since the ACA was enacted.

For example, as a result of the Budget Control Act of 2011, providers are subject to Medicare payment reductions of 2% per fiscal year, which went into effect on April 1, 2013.

These provisions of the IRA may heighten the risk that we would not be able to achieve the expected return on our drug products or full value of our patents protecting our products.

In addition as a result of the Budget Control Act of 2011, health care providers are subject to Medicare payment reductions of 2% per fiscal year.

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 providers and increased the statute of limitations period for the government to recover overpayments from providers from three to five years.

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.

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

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.

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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 eliminates the statutory Medicaid drug rebate price cap, currently set at 100% of the a drug’s average manufacturer price for single source and innovator multiple source products, beginning on January 1, 2024.

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.

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

Additionally, the IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under 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.

These provisions will take effect progressively starting in fiscal year 2023, although they may be subject to legal challenges.

It is currently unclear how the IRA will be effectuated but is likely to have a significant impact on the pharmaceutical industry.

Specifically, 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 and 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 Part 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 9 years and biologics that have been licensed for 13 years, but it does not apply to drugs and biologics that have been approved for a single rare disease or condition.

Nonetheless, since CMS may establish a maximum price for these products in price negotiations, we would be fully at risk of government action if our products are the subject of Medicare price negotiations.

Moreover, given the risk that could be the case, these provisions of the IRA may also further heighten the risk that we would not be able to achieve the expected return on our drug products or full value of our patents protecting our products if prices are set after such products have been on the market for nine years.

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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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.

The process governing the marketing authorization (“MA”) of medicinal products in the EU entails 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 before the product can be marketed and sold in the EU.

The aforementioned EU rules are generally 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, MA 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.

Medicinal products in 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.

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.

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These GLP standards reflect the Organization for Economic Co-operation and Development requirements.

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 in the EU.

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.

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, trials may 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.

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.

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a streamlined application procedure 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;

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

and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts.

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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 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 EU, it must appoint an EU entity to act as its legal representative.

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 EU member states in which the clinical trial is to be conducted.

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.

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EU Marketing Authorizations

To obtain an MA for a product in the EU, an applicant must submit an MAA either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the EU member states (decentralized procedure, national procedure, or mutual recognition procedure).

An MA may be granted only to an applicant established in the EU.

The centralized procedure comprises a single application, evaluation and authorization and provides for the grant of a single MA by the European Commission that is valid for all EU member states.

To obtain an MA for a product in the EU, an applicant must submit an MAA either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the EEA member states (decentralized procedure, national procedure, or mutual recognition procedure).

An MA may be granted only to an applicant established in the EEA.

The centralized procedure comprises a single application, evaluation and authorization and provides for the grant of a single MA by the European Commission that is valid for all EU member states, and by extension also in the three EEA states.

Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for (i) medicinal products derived from biotechnological processes, (ii) products designated as orphan medicinal products, (iii) advanced therapy medicinal products and (iv) products with a new active substance indicated for the treatment of HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto-immune and other immune dysfunctions and viral diseases.

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Under the centralized procedure in the EU, the maximum timeframe for the evaluation of an MAA is 210 days, excluding clock stops when additional information or written or oral explanation is to be provided by the applicant in response to questions of the CHMP.

Accelerated assessment may be granted by the CHMP in exceptional cases, when a medicinal product targeting an unmet medical need is expected to be of major interest from the point of view of public health and in particular from the viewpoint of therapeutic innovation.

Accelerated assessment may be granted by the CHMP in exceptional cases, when a medicinal product is expected to be of major interest from the point of view of public health and in particular from the viewpoint of therapeutic innovation.

If the CHMP accepts a request for accelerated assessment, the time limit of 210 days will be reduced to 150 days (not including clock stops).

The CHMP can, however, revert to the standard time limit for the centralized procedure if it considers that it is no longer appropriate to conduct an accelerated assessment.

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.

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.

This application is identical to the application that would be submitted to the EMA for authorization through the centralized procedure.

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

The resulting assessment report is 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 for review.

If such referral is decided by majority vote, the subsequent decision of the European Commission is binding on all EU member states.

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 CMDh seeks to resolve the issue by achieving a negotiated consensus amongst participating member states.

If that is not possible, the issue may be referred to the CHMP.

The CHMP will allow submissions from the applicant and, having considered the relevant issues and data, will issue an opinion by majority vote.

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.

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The holder of a national MA may submit an application to the competent authority of an EU member state requesting that this authority recognize the MA delivered by the competent authority of another EU member state.

In principle, an MA has an initial validity of five years.

In principle, any EU MA has an initial validity of five years.

The MA may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent authority of the EU member state in which the original MA was granted.

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Any authorization that is not followed by the actual placing of the medicinal product on the EU market (in case of centralized procedure) or on the market of the authorizing EU member state within three years after authorization ceases to be valid (the so-called sunset clause).

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.

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

In the EU, a “conditional” MA may be granted in cases where all the required safety and efficacy data are not yet available.

In the EU, a “conditional” MA may be granted to meet the unmet medical needs of patients for medicinal products intended for the treatment, prevention or medical diagnosis of seriously debilitating or life-threatening diseases in cases where all the required safety and efficacy data are not yet available.

The conditional MA is subject to conditions to be fulfilled for generating the missing data or ensuring increased safety measures.

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Once the specific obligations under the conditional MA are fulfilled (such as the completion of certain ongoing or new trials) and the complete data confirm that the medicinal product’s benefits continue to outweigh its risks, the conditional MA can be converted into a standard MA.

However, if the specific obligations are not fulfilled within the timeframe set by the EMA, the MA will cease to be renewed.

However, if the specific obligations are not fulfilled within the timeframe set by the EMA, the conditional MA may cease to be renewed.

An MA may also be granted “under exceptional circumstances” where the applicant can show that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced.

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

Manufacture of medicinal products in the EU requires a manufacturing authorization, and import of medicinal products into the EU requires a manufacturing authorization allowing for import.

Manufacture of medicinal products in the EEA requires a manufacturing authorization, and import of medicinal products into the EEA requires a manufacturing authorization allowing for import.

The manufacturing authorization holder must comply with various requirements set out in the applicable EU laws, regulations and guidance.

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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.

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

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.

EU Data and Market Exclusivity

The EU provides opportunities for data and market exclusivity related to MAs.

Upon receiving an MA, innovative medicinal products are generally 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 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.

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.

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.

The overall ten-year period may, occasionally, be extended for a further year to a maximum of 11 years if, during the first eight years of those ten years, the MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical entity, and products may not qualify for data exclusivity.

However, there is no guarantee that an innovative medicinal product will be considered by the EU’s regulatory authorities to be a new active substance eligible for data and market exclusivity.

These periods of data and market exclusivity may also be granted for a new MA for an existing active substance if the applicant is unrelated to the original MA holder and the MAA comprises a full free-standing dossier with relevant preclinical and clinical data

In the EU, there is a special regime for biosimilars products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product.

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.

The proposed reforms must be reviewed and approval by the EU Parliament and Council, and in light of their controversial nature it is unclear whether they will be adopted as proposed or further revised.

EU Post-Approval Requirements

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In the EU, the advertising and the promotion of medicinal products are subject to both EU and EU member states’ laws governing promotion of medicinal products, interactions with physicians and other healthcare professionals or organizations, misleading and comparative advertising and unfair commercial practices.

Although these general requirements for the advertising and the promotion of medicinal products are established under EU directives, the details are governed by regulations in each member state and can differ from one country to another.

For example, applicable laws 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.

Although the general requirements for the advertising and the promotion of medicinal products are established under EU directives, the details are governed by laws and regulations in each member state and can differ from one country to another.

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.

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Proposals to amend EU pharmaceutical laws

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

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 proposals need to be debated and approved by the EU Parliament and Council before any changes to the current regime will come into effect, if at all.

Depending on the progress of the EU parliament, legislative changes are not expected to come into force until 2025 or 2026 at the earliest.

It is also expected that there will further transition periods for the new rules once the necessary legislation becomes effective.

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.

Japanese Drug Regulation

Japan is a member of the ICH, and has pharmaceutical law and regulations that are similar in many respects those of the United States and the EU.

Those requirements are embodied in the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and

Medical Devices (also known as the Pharmaceuticals and Medical Devices Act) and related cabinet orders, Ministerial ordinances, and guidelines.

Those requirements are embodied in the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (also known as the Pharmaceuticals and Medical Devices Act) and related cabinet orders, Ministerial ordinances, and guidelines.

Clinical trials of medicinal products in Japan must be conducted in accordance with Japanese regulations and the ICH GCP guidelines.

1 unchanged sentence

The sponsor must hold a clinical trial insurance policy, and in accordance with industry practice, should establish a compensation policy for the injuries from the trial.

Prior to the commencement of human drug clinical trial, the sponsor must complete a pre-clinical safety evaluation of the investigative product and submit a clinical trial notification, including the clinical trial protocol, to the Ministry of Health Labor and Welfare’s PMDA.

Prior to the commencement of human drug clinical trial, the sponsor must complete a preclinical safety evaluation of the investigative product and submit a clinical trial notification, including the clinical trial protocol, to the Ministry of Health Labor and Welfare’s PMDA.

This notification must be submitted after obtaining agreement of the IRB in relevant clinical trial institution(s).

37 unchanged sentences

For domestic laboratories, NMPA oversees an accreditation program pursuant to China’s GLP.

If the pre-clinical research is conducted outside of China, then the applicant must sign and submit a certification with its CTA and marketing application stating that such research was conducted in accordance with applicable good laboratory practice rules.

If the preclinical research is conducted outside of China, then the applicant must sign and submit a certification with its CTA and marketing application stating that such research was conducted in accordance with applicable good laboratory practice rules.

PRC Clinical Trials and Regulatory Approval

23 unchanged sentences

A marketing authorization must be renewed every five years.

As the marketing authorization holder (“MAH”), a drug company is responsible for the life cycle of the product, including development, production and distribution, post-market trials, routine annual reporting, and safety monitoring and reporting of adverse drug reactions, among

other obligations.

The MAH may engage third parties to fulfill some of these obligations, such as appropriately-qualified manufacturers and distributors.

40 unchanged sentences

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

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

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”).

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”):

10 unchanged sentences

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 of the Closing Date.

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

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.

8 unchanged sentences

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