NASDAQ: VTVT

A Phase 1 mechanistic study of cadisegliatin in patients with T1D showed no increased risk of ketoacidosis with cadisegliatin during acute insulin withdrawal in patients. Additionally, a Phase 1 study in healthy male subjects to investigate the absorption, metabolism, and excretion of[14C]-cadisegliatin following single dose oral administration (the "ADME study") was conducted. The ADME study results were consistent with expectations from prior research but also included a radiochromatographic signal that, at the time, could not be further characterized, which led the FDA to impose a clinical hold on the cadisegliatin development program in July 2024. Based upon extensive testing by two independent laboratories, the Company determined that the radiochromatographic signal was an experimental artifact (duplicate peak) of a known metabolite. As a result, the FDA lifted the clinical hold in March 2025, allowing the Company to resume its clinical development plan for cadisegliatin.

In 2025, we completed a food effect study in healthy volunteers that investigated the effect of fasting, low fat, and high fat meals on the absorption of cadisegliatin. The results of the food effect study confirmed the current recommendation in the CATT1 trial that cadisegliatin be taken with food to maximize its absorption.

In December 2025, together with our partner G42 Investments AI Holding RSC Ltd. (“G42 Investments”), we initiated a double-blind, randomized, controlled Phase 2 trial in the Middle East region in people with type 2 diabetes ("T2D"). The Company is the sponsor of this study that will be fully funded by G42 Investments. The study will randomize 300 patients to assess the potential of cadisegliatin as an adjunct therapy to insulin in people with T2D, and is expected to start screening in 2026.

We continue to work on the design of additional international registrational studies for cadisegliatin in T1D.

In addition to our clinical development program for cadisegliatin, we continue to advance the research and development of our other pipeline candidates through collaborations with academic partners and license agreements.

Our Pipeline

The following table summarizes our current drug candidates and their respective stages of development:

Our Strategy

Our primary goal is to advance the development of our lead program cadisegliatin, a novel, oral, liver-selective glucokinase activator. In September 2025, we closed (the “Closing”) a private placement (the “2025 Private Placement”) of our Class A common stock and pre-funded warrants, pursuant to which we received aggregate gross proceeds of approximately $80.0 million, before deducting offering expenses payable by us. Investors in the 2025 Private Placement also received warrants to purchase our Class A common stock at a 50% premium to the stock price on the day of Closing, bringing total potential gross proceeds from the 2025 Private Placement to $200.0 million. The 2025 Private Placement allowed us to continue to advance our lead program for cadisegliatin (TTP399) and, together with cash on hand and the upfront payment received from the recent amendment to the license agreement covering our PDE4 inhibitor (HPP737), we expect it to provide funding well past topline data from the CATT1 clinical trial.

The key components of our business strategy are:

•Continuing to advance cadisegliatin (TTP399) as a potential treatment for diabetes. In 2021 Cadisegliatin received Breakthrough Therapy designation as an adjunctive therapy to insulin for the treatment of T1D based upon the positive results from the Phase 2 SimpliciT-1 Study, a multi-center, randomized, double-blind, adaptive study assessing the safety and efficacy of cadisegliatin as an adjunct to insulin therapy in adults with T1D. In May 2025, we resumed our CATT1 Phase 3 clinical trial investigating cadisegliatin as an adjunctive therapy to insulin in people living with T1D. The CATT1 trial continues to enroll patients and we expect to complete enrollment in the third quarter of 2026. We also continue to work on the design and execution of additional supportive trials in human volunteers, including studies to examine the effects of food on cadisegliatin's pharmacology and the potential effects of cadisegliatin on cardiac function (thorough QT study) as required by FDA.

In December 2025, together with our partner, G42 Investments, we initiated a double-blind randomized controlled Phase 2 trial in the Middle East region in 300 insulin-dependent people with T2D. The study is expected to start screening patients in 2026.

•Seeking additional strategic collaborations and additional funding to support the continued development and commercialization of our pipeline development programs. We continue to seek additional funding to support the development of our pipeline drug candidates as current internal resources are focused mainly on the development of cadisegliatin. We recently amended our license agreement with our partner, Newsoara BioPharma Co., Ltd. ("Newsoara"), to make it a global license to our PDE4 inhibitor (HPP737), which included a $20.0 million upfront payment. Under the amendment, we are conditionally entitled to receive milestone payments totaling up to $115.0 million and royalties in the mid single digits on sales.

We also continue to seek strategic collaborations with other pharmaceutical companies, such as our partnerships with Cantex and Newsoara, or academic or other research organizations for the development of our pipeline assets which have not been partnered.

Our Type 1 Diabetes Program – Cadisegliatin (TTP399)

Diabetes Overview

Type 1 diabetes is an autoimmune disease in which a person’s pancreas stops producing insulin. T1D results when the body’s immune system attacks and destroys the insulin-producing cells in the pancreas called beta cells. While the causes of T1D are not yet entirely understood, scientists believe that both genetic factors and environmental triggers are involved. The onset of T1D is not believed to be affected by diet or lifestyle. According to the T1D Index, an estimated 1.5 million individuals live with T1D in the U.S. as of 2026, a number which is expected to grow to 2.0 million by 2040. Globally, an estimated 9.9 million individuals live with T1D as of 2026.

Current Treatments for T1D and Their Limitations

Patients with T1D have difficulty achieving and maintaining glycemic control, defined as HbA1c <7% as recommended by the American Diabetes Association ("ADA"). To maintain appropriate glycemic control, patients with T1D are required to constantly monitor their blood glucose levels, closely manage their diet, and administer insulin via injection or an insulin pump at meal times and in response to changing blood glucose levels. While technology such as continuous glucose monitors, insulin pumps, and automated insulin delivery systems has advanced to help people with T1D manage this burden, approximately 75% of Americans living with T1D do not achieve the ADA’s recommended HbA1c level <7. Failure to maintain glycemic control can raise a patient’s risk of serious and life-threatening long-term complications, such as cardiovascular disease, blindness, kidney failure, and nerve damage. Blood sugar management for individuals living with T1D is a balancing act between reducing hyperglycemia while avoiding hypoglycemia. In fact, the ADA Standard of Care 2026 states that hypoglycemia is often the major limiting factor in the glycemic management of T1D and T2D.

Given the lack of adjunctive treatments for T1D, several existing treatment options for T2D have been investigated in T1D with limited success. SGLT-1/2 and SGLT-2 inhibitors were temporarily approved in Europe and are approved in Japan for certain sub-groups of people with T1D; however, they have not been approved in the U.S. for T1D primarily due to safety risks related to increased risk of diabetic ketoacidosis (“DKA”).

In 2022, the FDA approved teplizumab (Tzield®), a humanized anti-CD3 monoclonal antibody for the treatment of patients with two or more diabetes-related auto-antibodies to delay onset of Stage 3 T1D, and donislecel (Lantidra™), an allogeneic (donor) pancreatic islet cellular therapy for the treatment of patients with T1D who are in poor glycemic control because of recurrent severe hypoglycemia. Teplizumab does not address the unmet need of existing patients with diagnosed T1D or those that will eventually develop T1D, and donislecel requires long-term concurrent immunosuppressive therapy and is restricted to T1D patients with recurrent severe hypoglycemic episodes.

Despite the availability of these therapies, serious unmet medical need remains for people with T1D which could be addressed by a safe oral treatment option that reduces the incidence of hypoglycemia and improves glycemic control (HbA1c) without the risk of DKA or other serious adverse effects.

The Role of Glucokinase Activation in Diabetes

Glucokinase (“GK”) is a key regulator of glucose homeostasis and acts as the physiological glucose sensor, changing its conformation, activity, and/or intracellular location commensurate with changes in blood glucose concentrations. GK has two distinctive characteristics that make it a good therapeutic target for improving blood glucose control. First, its expression is mostly limited to glucose-sensing tissues (mainly liver cells and pancreatic β-cells), allowing for a focused therapeutic effect. Second, GK acts as a biological sensor for changes in serum glucose levels, modulating changes in the liver's uptake or release of glucose and changes in insulin secretion by β-cells. Activation of GK as a potential treatment of T1D is attractive because it could improve overall blood glucose control and specifically reduce the frequency and severity of low

blood glucose (hypoglycemic) episodes through a mechanism of action that is entirely distinct from currently marketed oral anti-diabetic drugs.

Cadisegliatin (TTP399)

Cadisegliatin (TTP399), is a novel, small-molecule, liver-selective glucokinase activator (GKA) currently being evaluated in a Phase 3 clinical trial as a potential oral adjunctive therapy to insulin for the treatment of T1D. Cadisegliatin has a novel mechanism of action: liver-selective activation of GK that could improve glycemic control and reduce the risk of L2 and L3 hypoglycemia. To date, our trials for cadisegliatin suggest a liver-selective approach to GK activation has the potential to avoid the negative properties associated with other nonselective GKAs including: hypoglycemia, increased lipids, tachyphylaxis, and liver toxicity. Based on data from Phase 1 and 2 trials to date, we believe that cadisegliatin, if approved, has the potential to be a first-in-class oral anti-diabetic drug due to its liver-selectivity and novel mechanism of action. We have completed eleven Phase 1 and three Phase 2 clinical trials of cadisegliatin totaling more than 500 patients with type 1 and type 2 diabetes. In these trials, cadisegliatin was well tolerated with significant reductions of patient-reported symptomatic hypoglycemic events and glycosylated hemoglobin (HbA1c) compared to insulin alone in a Phase 2 study in T1D.

Positive Phase 2 Simplici-T1 Study

In February 2020, we announced positive results from the Simplici-T1 Study, an adaptive Phase 2 clinical trial of cadisegliatin, assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of cadisegliatin in adult patients with T1D over a 12-week period. The Simplici-T1 Study achieved its primary objective by demonstrating statistically significant improvements in HbA1c for cadisegliatin compared to placebo. Moreover, a clinically meaningful decrease (40%) in the number of severe and symptomatic hypoglycemia was observed in patients receiving cadisegliatin when compared to those receiving placebo.

Mechanistic study

We have conducted a study to evaluate the impact of liver-selective GK activation on the safety and tolerability of cadisegliatin. In October 2021, we announced positive results from the mechanistic study indicating no increased risk of ketoacidosis with cadisegliatin during acute insulin withdrawal in patients with T1D. Consistent with previous clinical studies of cadisegliatin, the drug was well tolerated with fewer subjects reporting treatment-emergent adverse events in the group taking cadisegliatin than in the placebo group. Importantly, patients taking cadisegliatin reported no events of hypoglycemia, while four events of hypoglycemia were reported in the placebo group.

ADME study

In August 2023, we completed an Open-Label Phase 1 Study in Healthy Male Subjects to Investigate the Absorption, Metabolism, and Excretion of [14C]-cadisegliatin (TTP399) Following Single Dose Oral Administration. Ten participants were dosed, and cadisegliatin was well tolerated. Initial results indicated the presence of an unexpected radiochromatographic signal which could not be further characterized at the time and led FDA to issue a clinical hold for the cadisegliatin program in July 2024. Based upon extensive testing by two independent laboratories, the Company determined that the radiochromatographic signal was an experimental artifact (duplicate peak) of a known metabolite. As a result, the FDA lifted the clinical hold in March 2025, allowing the Company to resume its clinical development plan for cadisegliatin.

Food Effect Study

In December 2025, we completed a double-blind randomized food effect study in male and female healthy volunteers to investigate the absorption of cadisegliatin following single dose oral administration of cadisegliatin when fasting or when consuming a low or high fat meal concurrently. The study showed significantly higher cadisegliatin exposure observed in the low-fat and high-fat fed groups as compared to the fasted group. The results confirm the currently recommended dosing of cadisegliatin with food to maximize its absorption.

Clinical Development Plan

Based upon the positive results of our Phase 2 Simplici-T1 Study, we requested Breakthrough Therapy designation (BTD) from the FDA which was granted in April 2021.

Carcinogenicity, long-term toxicology studies, development and reproductive toxicology studies, have been completed with no untoward findings. No treatment-related increase in tumor incidence was observed, no carcinogenic signal identified at clinically relevant exposures, and findings were not considered biologically relevant to humans.

In the second quarter of 2025 we resumed our Phase 3 CATT1 trial. The CATT1 trial is a double-blind, randomized trial to assess the effect of cadisegliatin on reducing the frequency of Level 2 hypoglycemia (blood glucose levels are less

than 54 mg/dL or 3 mmol/L, regardless of symptoms) and Level 3 hypoglycemia ("severe" hypoglycemia e.g., requiring assistance of another person). The CATT1 trial will randomize 150 patients with T1D on a 1:1:1 basis (i.e., 50 patients for each study arm) to receive 800 mg cadisegliatin daily, 800 mg cadisegliatin twice daily, or placebo. A key secondary endpoint is reduction in glycated hemoglobin (HbA1c), a traditional efficacy endpoint in diabetes trials, to assess the potential of cadisegliatin to reduce hyperglycemia.

During 2025, we also continued working on the design and execution of supportive trials for cadisegliatin, including a thorough QT study and a Phase 2 study in patients with T1D using hybrid closed loop insulin infusion systems, which we expect to start in 2026. We continue to plan for additional registrational studies for cadisegliatin in T1D following the completion of the current CATT1 study.

In December 2025, we and our partner, G42 Investments, initiated a double-blind randomized controlled Phase 2 trial in the Middle East region in 300 insulin-dependent people with T2D. The study is expected to start screening patients in 2026.

Collaboration Agreements

G42 Transaction

The Company and G42 Investments, entered into a Common Stock Purchase Agreement (the “G42 Purchase Agreement”) on May 31, 2022, pursuant to which the Company sold to G42 Investments 259,657 shares of the Company’s Class A common stock, for an aggregate purchase price of $25.0 million, which was paid (i) $12.5 million in cash at the closing and (ii) $12.5 million in the form of a promissory note.

G42 Investments has agreed to certain transfer restrictions (including restrictions on short sales or similar transactions) and restrictions on further acquisitions of shares, in each case subject to specified exceptions. As part of the transaction the Company has granted to G42 Investments certain shelf and piggyback registration rights with respect to those shares of Class A common stock issued to G42 Investments pursuant to the G42 Purchase Agreement, including the ability to conduct an underwritten offering to resell such shares under certain circumstances. The registration rights include customary cooperation, cut-back, expense reimbursement, and indemnification provisions.

Contemporaneously with the G42 Purchase Agreement, effective on May 31, 2022, the Company entered into a collaboration and license agreement (the “Cogna Agreement”) with Cogna Technology Solutions LLC, an affiliate of G42 Investments (“Cogna”), which requires Cogna to work with the Company in performing clinical trials for the Company’s compound cadisegliatin (the “Licensed Product”) as well as jointly creating a global development plan to develop, market, and commercialize cadisegliatin in certain countries in the Middle East, Africa, and Central Asia (the “Partner Territory”). Under the terms of the Cogna Agreement, Cogna will obtain a license under certain intellectual property controlled by the Company to enable it to fulfill its obligations and exercise its rights under the Cogna Agreement, including to develop and commercialize the Licensed Product in the Partner Territory, but will not have access to the various intellectual property related to the license and cadisegliatin. Specifically, the Company will share various protocols with Cogna related to conducting the clinical trials and will provide the patient dosages and placebo of cadisegliatin needed to conduct the trials.

Under the Cogna Agreement, Cogna has the right to develop and commercialize the Licensed Product in the Partner Territory at its own cost once restrictions on the use of the IP have been lifted by the Company. The Cogna Agreement determined which specific countries in the Partner Territory that Cogna may pursue development and commercialization and provides the Company with the ability to determine when Cogna can benefit from this IP through the powers granted to the Company to approve the global development plan. Further, the Company may supply at cost, or Cogna may manufacture, cadisegliatin for commercial sale under terms to be agreed upon by the parties at a later date.

Separately, the Company will conduct its clinical trials for cadisegliatin outside of the Partner Territory, at its own cost. The results of each party’s clinical trials may be combined by the Company to seek FDA approval in the United States for cadisegliatin. On December 21, 2022, G42 Healthcare Technology Solutions LLC (formerly known as Cogna Technology Solutions LLC) novated its rights and obligations under the Cogna Agreement to G42 Healthcare Research Technology Projects LLC ("G42 Healthcare"), an affiliate of G42 Investments. As a result of the novation, all references to Cogna herein shall be deemed to refer to G42 Healthcare.

The G42 Purchase Agreement also provides for, following the receipt of the FDA Approval of the Licensed Product, at the option of G42 Investments, either (a) the issuance of the Company’s Class A common stock (the “Milestone Shares”) having an aggregate value equal to $30.0 million or (b) the payment by the Company of $30.0 million in cash (the “Milestone Cash Payment”). The issuance of the Milestone Shares or the payment of the Milestone Cash Payment, as applicable, are conditioned upon receipt of the FDA Approval and subject to certain limitations and conditions set forth in the G42 Purchase Agreement. There can be no assurance that the FDA Approval will be granted or as to the timing thereof.

Once commercialization takes place in the Partner Territory, the Company will receive royalties in the single digits from Cogna on the net sales of the Licensed Product for a period of at least ten years after the first commercial sale of the Licensed Product in the Partner Territory.

On February 28, 2023, the Company and G42 Investments amended the G42 Purchase Agreement and modified the G42 Promissory Note to accelerate the payment due under the note. Pursuant to the amendment, on February 28, 2023, the Company received $12.0 million, which reflected the original amount due under the G42 Promissory Note less a 3.75% discount, in full satisfaction of the note. On February 27, 2024, the Company and G42 Investments further amended the G42 Purchase Agreement in connection with the 2024 Private Placement (as defined below).

CinPax and CinRx Transaction

On July 22, 2022, the Company entered into a Common Stock and Warrant Purchase Agreement (as amended, the "CinRx Purchase Agreement") with CinPax, LLC (“CinPax”), a subsidiary of CinRx Pharma, LLC (“CinRx”), pursuant to which the Company sold to CinPax 103,864 shares of the Company’s Class A common stock, for an aggregate purchase price of $10.0 million, which was paid (i) $6.0 million in cash at the closing of the transaction and (ii) $4.0 million in the form of a non-interest-bearing promissory note with CinPax and was paid to the Company on November 22, 2022. The Company, CinPax and CinRx subsequently amended the CinRx Purchase Agreement on February 27, 2024, in connection with the Private Placement which removed the right of CinPax to designate a board observer.

The CinRx Purchase Agreement also provided CinRx warrants to purchase up to 30,000 shares of Class A common stock at an initial exercise of price of approximately $28.80 per share (the “CinRx Warrants”). The CinRx Warrants will become exercisable by CinRx only if (i) the Company receives FDA approval to market and distribute the pharmaceutical product containing the Company’s proprietary candidate, cadisegliatin, or (ii) the Company is acquired by a third party, sells all or substantially all of its assets related to cadisegliatin to a third party or grants a third party an exclusive license to develop, commercialize and manufacture cadisegliatin in the United States. If neither of these events happen within five years of the date of the issuance of the CinRx Warrants, the CinRx Warrants will expire and will not be exercisable by CinRx. The exercise price of the CinRx Warrants and the number of shares issuable upon exercise of the CinRx Warrants are subject to adjustments in accordance with the terms of the CinRx Warrants.

Additionally, in conjunction with the CinRx Purchase Agreement the Company and CinRx entered into a Master Service Agreement whereby CinRx provides the Company with consulting, preclinical and clinical trial services, as enumerated in project proposals negotiated between the Company and CinRx from time to time.

Our Pipeline Programs

TTP273 - Oral Small-Molecule GLP-1 Receptor Agonist

Overview

Glucagon-like peptide-1 (“GLP-1”) is an endogenous incretin hormone that binds the GLP-1 receptor (“GLP-1R”) and plays a role in glucose-dependent insulin secretion, glucagon suppression, gastric emptying, and satiety. GLP-1 receptor agonists (“GLP-1RAs”) are established therapies for T2D and, in certain agents, have demonstrated benefits in weight reduction and cardiovascular risk reduction. TTP273 is an orally administered, small-molecule GLP-1RA that has demonstrated reductions in postprandial glucose excursions in response to oral glucose tolerance testing and mixed-meal tolerance testing in preclinical studies and clinical trials.

GLP-1RA Therapeutic Landscape

GLP-1RA products (and related incretin therapies) have received FDA approvals across multiple indications, including T2D and chronic weight management. For example, semaglutide (Wegovy®) is indicated for chronic weight management and to reduce the risk of major adverse cardiovascular events (“MACE”) in adults with established cardiovascular disease and obesity1. Tirzepatide (Zepbound®), a dual GIP/GLP-1 receptor agonist, is approved for chronic weight management, and since December 20, 2024, for treatment of moderate to severe obstructive sleep apnea in adults with obesity (with diet and exercise).2 GLP-1RA labeling for certain T2D products also includes cardiovascular risk-reduction claims in defined populations (e.g., dulaglutide).

Tolerability - particularly gastrointestinal (“GI”) adverse effects such as nausea and vomiting - may limit use in certain patient populations and in indications where weight loss is not desired or may be contraindicated. We believe that an orally administered GLP-1RA with a favorable tolerability profile could have utility in select settings.

1 Wegovy® is trademarked by Novo Nordisk A/S.

2 Zepbound® is trademarked by Eli Lilly and Company.

TTP273 Program Rationale and Mechanism

TTP273 is an orally administered, small-molecule GLP-1RA. In nonclinical assays, TTP273 demonstrated activation of cyclic adenosine monophosphate (“cAMP”) signaling and limited activation of the extracellular signal-regulated kinase (“ERK”)/β-arrestin pathway at clinically relevant concentrations. We believe this signaling profile may be relevant to balancing efficacy and tolerability of GLP-1 receptor agonists, although the clinical significance of these observations has not been fully established.

We have evaluated TTP273 for the potential treatment of post-meal hyperglycemia in cystic fibrosis-related diabetes (“CFRD”) and in cystic fibrosis (“CF”) patients with abnormal postprandial glucose excursions. CFRD is associated with impaired insulin secretion and abnormal incretin responses, and patients may have clinical considerations that make GI tolerability and unintended weight loss particularly important.

Development Status

We have completed two Phase 1 clinical trials and one Phase 2 clinical trial evaluating TTP273. Across these trials, TTP273 was generally well tolerated. In our clinical experience to date, the incidence of certain GI adverse events, including nausea and vomiting, was low.

In a randomized, double-blind Phase 2 trial in patients with type 2 diabetes (T2D) on background metformin therapy, TTP273 demonstrated statistically significant reductions in glycated hemoglobin (“HbA1c”) after three months of treatment. HbA1c is the standard regulatory and clinical benchmark for assessing long-term glycemic control, reflecting average blood glucose over approximately three months, and reductions in HbA1c are associated with a lower risk of diabetes-related complications. In this study, TTP273 also demonstrated reductions in systolic blood pressure, an important cardiometabolic risk factor commonly elevated in patients with T2D. Additional clinical studies will be required to further characterize the efficacy, safety, dose response, and tolerability of TTP273 in intended target populations.

Receptor for Advanced Glycation End-products (“RAGE”) Antagonist Program - TTP-RA (Preclinical)

Overview

RAGE is a cell-surface pattern-recognition receptor involved in inflammatory signaling. RAGE is expressed on multiple immune cell types, and engagement of RAGE by endogenous ligands released during cellular stress and tissue injury has been associated with activation and shaping of adaptive immune responses, including effects on T-cell activation and differentiation.

Given the central role of immune-mediated β-cell injury in T1D, we believe RAGE antagonism may represent a potential therapeutic approach to modulate pathogenic immune responses relevant to disease initiation and progression.

Scientific Rationale

In published nonclinical research, blockade or genetic absence of RAGE has been associated with altered T-cell responses and attenuation of immune-mediated islet injury and graft rejection in experimental models, supporting a potential role for RAGE signaling in autoimmune and inflammatory settings.

TTP-RA Program

TTP-RA is an orally administered, small-molecule RAGE antagonist in preclinical development being evaluated as a potential approach to prevent or delay the onset of T1D. We have supported and collaborated on investigator-sponsored research evaluating RAGE antagonism in this setting, including work involving academic collaborators and funded research initiatives.

In preclinical studies, TTP-RA has been evaluated for its ability to inhibit interactions between RAGE and a range of RAGE ligands in vitro and to modulate immune activity associated with T1D. In disease-relevant mouse models, TTP-RA has been reported to delay the development of diabetes. Co-administered with an anti-CD3 antibody, TTP-RA prevented autoimmune diabetes development in the PD-L1 accelerated model of disease when compared to the anti-CD3 antibody alone.

Peroxisome Proliferator-Activated Receptor Delta (“PPAR-δ”) Agonist Program - HPP593 (mavodelpar/REN001)

Overview

Peroxisome proliferator-activated receptors (“PPARs”) are nuclear transcription factors involved in regulating lipid metabolism and energy homeostasis. PPAR-δ has been associated with regulation of fatty acid oxidation, including in skeletal

muscle, and has been explored as a potential target in disorders characterized by dysregulated lipid metabolism and muscle function.

Peroxisome Proliferator-Activated Receptor Delta (“PPAR-δ”) Therapeutic Landscape

In August 2024, the FDA granted accelerated approval to seladelpar (Livdelzi®), a PPAR-δ agonist, for primary biliary cholangitis (PBC) (with or without UDCA), based on biochemical response (ALP reduction), with continued approval contingent on confirmatory benefit.3

Scientific Rationale

PPAR-δ activation may influence transcription of genes involved in lipid utilization and mitochondrial function, and has been evaluated for potential effects on lipid parameters and skeletal muscle metabolism. While these biological effects support continued interest in the pathway, clinical relevance is dependent on demonstration of safety and efficacy in controlled clinical studies and may vary by indication and patient population.

HPP593 (mavodelpar/REN001) Program

HPP593 (also known as REN001, mavodelpar) is a PPAR-δ agonist that has been evaluated in clinical studies, including studies assessing lipid parameters and muscle-related endpoints.

Nrf2/Bach1 Program - Non-Electrophilic Modulators of Oxidative Stress and Inflammation

Overview

Nuclear factor erythroid 2-related factor 2 (“Nrf2”) is a transcription factor that regulates antioxidant response element (“ARE”) genes involved in cellular defense against oxidative stress. BTB and CNC homology 1 (“Bach1”) is an ARE transcriptional repressor that can limit Nrf2 pathway activity. We have identified multiple classes of novel, non-electrophilic small molecules designed to modulate the Nrf2/Bach1 axis, resulting in activation of the Nrf2 pathway. We believe activation of the Nrf2 pathway may have therapeutic relevance in diseases characterized by oxidative stress and inflammation.

Scientific Rationale

In many inflammatory and chronic disease settings, oxidative stress and dysregulated inflammatory signaling may contribute to tissue injury and impaired organ function. Activation of Nrf2 can increase expression of antioxidant and cytoprotective genes and may modulate inflammatory responses.

Historically, certain approaches to Nrf2 activation have relied on reactive, electrophilic mechanisms, which may be associated with safety and tolerability considerations. Non-electrophilic activation of the Nrf2 pathway through modulation of Bach1 provides an alternative approach to increasing Nrf2 pathway activity.

Nrf2 Therapeutic Landscape

To date, clinical validation of Nrf2-pathway modulation includes marketed products that are understood to activate or influence Nrf2 signaling. Dimethyl fumarate (Tecfidera®) is an oral therapy approved for relapsing forms of multiple sclerosis and has been described as activating the Nrf2 pathway. In addition, omaveloxolone (Skyclarys®) was approved in the U.S. for Friedreich’s ataxia; while its precise therapeutic mechanism is described as not fully established in labeling, it has been characterized as activating the Nrf2 pathway.4

Preclinical Activity

In preclinical pharmacology studies, our Nrf2/Bach1 modulators have demonstrated pharmacodynamic activity, including induction of Nrf2/Bach1 target genes in multiple organs and across diverse cell types. Efficacy and proof of concept have been observed in multiple disease-relevant animal models including metabolic dysfunction-associated steatohepatitis liver (MASH), neurodegenerative disorders (e.g., Parkinson’s disease, traumatic brain injury, Alzheimer’s disease), bone loss (e.g., osteoarthritis), Sickle Cell Disease (SCD) and other conditions.

Development Status

We have advanced select molecules from this program into clinical development. For example, HPP971 was evaluated in Phase 1 single-ascending dose and multiple-ascending dose studies in healthy participants and was generally

3 Livdelzi® is trademarked by Gilead.

4 Tecfidera® and Skyclarys® are trademarked by Biogen.

well tolerated in those studies. We continue to evaluate additional Nrf2/Bach1 program molecules in preclinical studies to further characterize their pharmacology and identify potential development paths.

Partnered Development Programs

HPP737 - Oral, Non-CNS Penetrant PDE4 Inhibitor

Overview

Phosphodiesterase-4 (“PDE4”) is an intracellular enzyme expressed in a range of inflammatory and immune cells that degrades cyclic adenosine monophosphate (“cAMP”), a signaling molecule involved in regulating inflammatory pathways. Increased PDE4 activity reduces intracellular cAMP and may contribute to increased production of pro-inflammatory mediators, including tumor necrosis factor alpha (“TNF-α”) and interleukins such as IL-17 and IL-23. PDE4 inhibition increases intracellular cAMP and can downregulate inflammatory responses, including effects on T cells and myeloid cell activation. As a result, PDE4 has been clinically validated as a target in multiple immune-mediated inflammatory diseases, including dermatologic and rheumatologic conditions.

PDE4 Therapeutic Landscape

PDE4 inhibition is an established therapeutic approach in certain inflammatory diseases. For example, apremilast (Otezla®)5, an oral PDE4 inhibitor, is approved for indications including psoriasis and psoriatic arthritis, and crisaborole (Eucrisa®)6, a topical PDE4 inhibitor, is approved for atopic dermatitis. PDE4 and cAMP signaling have also been implicated in inflammatory bowel disease (“IBD”), where immune activation and cytokine production contribute to intestinal inflammation and epithelial barrier dysfunction; Notwithstanding the utility of this mechanism, the tolerability of systemic PDE4 inhibition may be limited in some patients by adverse events that commonly include GI effects such as nausea, vomiting, and diarrhea, which can affect persistence on therapy.

HPP737 Program Rationale and Properties

HPP737 is an orally administered, potent and selective PDE4 inhibitor designed to have limited central nervous system (“CNS”) penetration. We believe that reduced CNS penetration may be relevant to improving tolerability for certain adverse events historically associated with systemic PDE4 inhibition, although the relationship between CNS exposure and tolerability outcomes may vary and has not been fully established for HPP737.

In nonclinical studies, HPP737 has demonstrated inhibition of cytokine production, including IL-17A and TNF-α, in vitro, and activity in multiple animal models of inflammation. A

HPP737 and Newsoara Biopharma

On May 31, 2018, we entered into a license agreement with Newsoara (the “Newsoara License Agreement”), under which Newsoara obtained an exclusive and sublicensable license to develop and commercialize our PDE4 program, including the compound HPP737, in China and other Pacific Rim territories (collectively, the “Newsoara License Territory”). In January 2026, the parties entered into the Second Amendment to License Agreement (the "Second Amendment") to provide Newsoara with global rights to HPP737. In exchange for the global rights, Newsoara paid the Company an upfront amount of $20.0 million and agreed to modify the sales and development milestones and royalty on future sales. Under the Second Amendment, the Company is eligible to receive development, regulatory and sales-based milestone payments totaling up to $115.0 million as well as royalties on sales in the mid to upper single digits based on tiers of annual net sales of licensed products. Such royalties will be payable on a licensed product-by-licensed product and country-by-country basis until the latest of expiration of the licensed patents covering a licensed product in a country, expiration of data exclusivity rights for a licensed product in a country or a specified number of years after the first commercial sale of a licensed product in a country.

Under the terms of the Newsoara License Agreement, Newsoara will be responsible for the development and commercialization of the licensed products at its cost, and is required to use commercially reasonable efforts with respect to such development and commercialization efforts.

The Newsoara License Agreement, unless terminated earlier, will continue until expiration of all royalty obligations of Newsoara to us. Either party may terminate the Newsoara License Agreement for the other party’s uncured material breach.

5 Otezla® is trademarked by Amgen.

6 Eucrisa® is trademarked by Pfizer.

Newsoara may terminate the Newsoara License Agreement at will upon prior written notice. Upon expiration (but not earlier termination) of the Newsoara License Agreement the licenses granted to Newsoara will survive on a royalty-free basis in perpetuity.

Azeliragon and Cantex Pharmaceuticals, Inc.

On June 22, 2021, vTv Therapeutics Inc. and Cantex Pharmaceuticals, Inc. (“Cantex”) entered into a licensing agreement under which Cantex obtained exclusive worldwide rights to develop and commercialize azeliragon, vTv’s novel antagonist of RAGE (the receptor for advanced glycation end products). Under the terms of the agreement, Cantex will be responsible for the development and commercialization of azeliragon, and the companies will allocate downstream profits under a tiered arrangement.

On January 9, 2023, Cantex announced that the FDA has granted Orphan Drug Designation to azeliragon for the treatment of glioblastoma. In addition, a Phase 2 trial of azeliragon is in progress in women receiving “neoadjuvant chemotherapy” of breast cancer, which is chemotherapy to prevent cancer from returning after initial potentially curative treatment. In February 2022, Cantex secured a global license from Harvard University to further develop azeliragon as a treatment for inflammatory lung diseases, including COVID-19.

On May 20, 2024, Cantex announced that the FDA granted Orphan Drug Designation to azeliragon, a well-tolerated once-a-day pill, for the treatment of pancreatic cancer. Cantex has completed a clinical trial studying the safety and efficacy of azeliragon in patients refractory to first-line treatment of metastatic pancreatic cancer.

On December 9, 2024, Cantex announced that the FDA granted Orphan Drug Designation to Cantex’s azeliragon for the treatment of brain metastasis from breast cancer.

In February 2025, a Phase 1B clinical trial was initiated by Dr. Jonathan Yang at New York University Langone to assess safety of concurrent azeliragon with craniospinal irradiation in patients with leptomeningeal metastasis from solid tumor malignancies or high-grade gliomas.

A Phase 2 trial of azeliragon is in progress in women receiving “neoadjuvant chemotherapy” of breast cancer, which is chemotherapy to prevent cancer from returning after initial potentially curative treatment. Furthermore, a phase I/II study to assess safety and preliminary evidence of a therapeutic effect of azeliragon combined with stereotactic radiation therapy in patients with brain metastases is ongoing at Miami University.

A randomized, double-blind, placebo-controlled Phase 2/3 Study to determine the safety and effectiveness of azeliragon in the treatment of patients hospitalized for coronavirus disease 2019 (COVID-19) or pneumonia is in progress.

Inbound Partnerships

Novo Nordisk

In February 2007, we entered into an Agreement Concerning Glucokinase Activator Project with Novo Nordisk A/S (the “Novo License Agreement”) whereby we obtained an exclusive, worldwide, sublicensable license under certain Novo Nordisk intellectual property rights to discover, develop, manufacture, have manufactured, use, and commercialize products for the prevention, treatment, control, mitigation, or palliation of human or animal diseases or conditions. As part of this license grant, we obtained certain worldwide rights to Novo Nordisk’s GKA program, including rights to preclinical and clinical compounds such as cadisegliatin. This agreement was amended in May 2019 to create milestone payments applicable to certain specific and non-specific areas of therapeutic use. Under the terms of the Novo License Agreement, the Company has additional potential developmental and regulatory milestone payments totaling up to $6.0 million for approval of a product for the treatment of type 1 diabetes, $50.5 million for approval of a product for the treatment of type 2 diabetes, or $115.0 million for approval of a product in any other indication. The Company may also be obligated to pay an additional $75.0 million in potential sales-based milestones, as well as royalty payments, at mid-single digit royalty rates, based on tiered sales of commercialized licensed products.

Third-Party Suppliers and Manufacturers

We do not own or operate, and currently have no plans to establish, any manufacturing facilities. We currently rely, and expect to continue to rely, on third parties to manufacture clinical supplies of our drug candidates and for our other research and discovery programs. We do not have multiple sources of supply for the components used in our drug candidates.

Intellectual Property

Patents

We actively protect our commercially important proprietary technology by, among other methods, obtaining, maintaining, and defending our patent rights. We have filed numerous patent applications covering our current drug candidates and our other research and discovery programs in the U.S. and in jurisdictions outside of the U.S., resulting in multiple issued patents. We pursue patent protection for all inventions and improvements throughout development, including, when possible, compositions of matter, crystal forms (polymorphs), methods of use, dosage regimens, formulations, combination therapies, and manufacturing processes.

Issued patents can provide protection for varying periods of time, depending upon the date of filing of the patent application, the date of patent issuance and the legal term of patents in the countries in which they are obtained. In general, patents issued for applications filed in the U.S. can provide exclusionary rights for 20 years from the earliest effective non-provisional filing date. In addition, in certain instances, the term of an issued U.S. patent that covers or claims an FDA approved product, or its use in treating an approved indication, can be extended to recapture a portion of the term effectively lost as a result of the FDA regulatory review period, which is called patent term extension. The period of patent term extension in the United States cannot be longer than five years and the total patent term, including the extension period, must not exceed 14 years following FDA approval. The term of patents outside of the U.S. varies in accordance with the laws of the foreign jurisdiction, but typically is also 20 years from the earliest effective non-provisional filing date. However, the actual protection afforded by a patent varies on a product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent. Some countries also provide mechanisms to recapture a portion of the patent term lost during regulatory review, similar to patent term extension in the U.S. The amount of patent term that can be recaptured depends on the laws of the relevant jurisdictions.

The patent portfolio for cadisegliatin includes multiple patent families directed to crystal forms, salt forms, formulations, combinations, and methods of use for treating diabetes, among other things, that are filed in the U.S. and abroad. For example, the patent portfolio for cadisegliatin includes a patent family directed to methods of treating patients with type 1 diabetes using cadisegliatin in combination with insulin. The issued U.S. patents, as well as U.S. and foreign patents issuing from pending patent applications, in this patent family would be expected to expire in 2039, absent any patent term adjustments or extensions. The patent portfolio for cadisegliatin also includes three patent families directed to crystal forms, crystalline salt forms, and solid formulations of cadisegliatin, among other things. The issued patents and patents issuing from pending patent applications in these patent families are projected to expire between 2034 and 2041, absent any patent term adjustments or extensions in the U.S. and ex-U.S. jurisdictions. The patent portfolio for cadisegliatin further includes patent families directed to combinations of cadisegliatin with metformin, DPP-4 inhibitors, or GLP-1r agonists, and their use in methods of treatment. The issued patents and patents issuing from pending patent applications in these additional patent families are projected expected to expire between 2031 and 2033, absent any patent term adjustments or extensions in the U.S. and ex-U.S. jurisdictions.

The patent portfolio for HPP737 includes issued patents in the U.S. generically covering HPP737 as a composition of matter and methods of use to treat various indications. The issued U.S. patent generically covering HPP737 as a composition of matter will expire no earlier than 2029, absent any patent term adjustments or extensions. The patent portfolio for HPP737 also includes a patent family specifically covering HPP737 and another patent family directed to a crystalline form of HPP737. Any patents issuing from the pending patent applications in these two patent families will expire in 2040, absent any patent term adjustments or extensions in the U.S. and ex-U.S. jurisdictions.

The patent portfolio for the GLP-1r program includes multiple patent families covering TTP273 directed to composition of matter, crystal forms, non-crystal forms, salt forms, formulations, combinations, and methods of use for treating various indications, among other things. The GLP-1r IP portfolio includes a patent family directed to TTP273 as a composition of matter. The issued patents covering TTP273 as a composition of matter will expire no earlier than 2030, absent any patent term adjustments or extensions in the U.S. and ex-U.S. jurisdictions. The patent portfolio for TTP273 also includes patent families directed to crystalline, non-crystalline, and crystalline salt forms, and formulations of TTP273, synthetic precursors to, and methods of manufacture of TTP273, as well as combinations of TTP273 and metformin, and their use in methods of treatment, and dosage regimens of TTP273. Patents issuing from pending patent applications in these additional patent families would be expected to expire between 2034 and 2045, absent any patent term adjustments or extensions in the U.S. and ex-U.S. jurisdictions.

The patent portfolio for the Nrf2/Bach1 program includes a patent family directed to HPP971 and HPP3033 as compositions of matter, among other things. The issued patents in this patent family will expire no earlier than 2031, absent any patent term adjustments or extensions in the U.S. and ex-U.S. jurisdictions. The patent portfolio for the Nrf2/Bach1

program also includes patent families directed to methods of use in combination with other Nrf2 activator compounds such as dimethyl fumarate and bardoxolone, and methods to treat sickle cell diseases, osteoporosis, and refractive ocular disorders. The issued patents and patents issuing from pending patent applications in these additional patent families are projected to expire between 2035 and 2041, absent any patent term adjustments or extensions in the U.S. and ex-U.S. jurisdictions.

The patent portfolio for azeliragon also includes patent families covering polymorphs, salt forms, metabolites, degradation products and a synthetic precursor of azeliragon, methods of treatment using select dosage regimens of azeliragon, and methods of treating select patient populations, among other things. The issued patents and patents issuing from pending patent applications in these patent families, are projected to expire between 2028 and 2039, absent any patent term adjustments or extensions in the U.S. and ex-U.S. jurisdictions.

Trade Secrets

In addition to patents, we rely on trade secrets and know-how to develop and maintain our competitive position. We seek to protect our proprietary technology and processes, in part, by entering into confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors and commercial partners. These agreements are designed to protect our proprietary information and, in the case of the invention assignment agreements, to grant us ownership of technologies that are developed by employees or through a relationship with a third party. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems. While we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become publicly known or be independently discovered by competitors. To the extent that our contractors use or incorporate intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions.

Competition

We believe the key competitive factors that will affect the development and commercial success of our drug candidates are efficacy, safety and tolerability profile, mechanism of action, control and predictability, convenience of dosing, price and reimbursement, and availability of comparable alternative therapies.

Many of the companies against which we may compete have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical, biotechnology and medical devices industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. The key competitive factors affecting the success of all our programs are likely to be their efficacy, safety, convenience, and availability of reimbursement.

Potential Competing Products – Type 1 Diabetes

If approved, cadisegliatin for T1D would compete with a broad range of therapies and technologies, including oral and injectable non-insulin agents used adjunctively with insulin, novel insulin formulations, medical devices, and investigational disease-modifying or cell-based approaches intended to reduce hypoglycemia risk, improve glycemic control, or address underlying disease biology.

Adjunctive non-insulin pharmacotherapies and hypoglycemia-focused approaches. Multiple companies are developing agents intended to improve glycemic control and/or reduce hypoglycemia in people with T1D. For example, Zucara Therapeutics is developing ZT-01, an investigational somatostatin receptor 2 (SSTR2) antagonist intended to prevent insulin-induced hypoglycemia, with an initial development focus on nocturnal hypoglycemia. Diasome Pharmaceuticals has reported completion of enrollment in a Phase 2b trial evaluating a hepatocyte-directed vesicle (“HDV”)-enabled insulin lispro formulation intended to more closely replicate physiologic portal delivery and potentially reduce hypoglycemia while improving post-prandial control. In addition, incretin-based approaches are being evaluated in adults with T1D and overweight/obesity, including tirzepatide (a dual GLP-1/GIP receptor agonist) and other dual incretin candidates. REMD

Biotherapeutics has evaluated its glucagon receptor antagonism in T1D (volagidemab/REMD-477), a mechanism intended to reduce hyperglycemia and exogenous insulin requirements.In late 2024, the U.S. Food and Drug Administration ("FDA") declined to approve Lexicon Pharmaceuticals' sotagliflozin (Zynquista), a dual SGLT-1/SGLT-2 inhibitor, for use in T1D; however, Lexicon continues to pursue regulatory approval for this indication. Separately, ultra-rapid prandial insulin formulations such as Adocia’s BioChaperone® Lispro are being developed to improve post-prandial glucose control. None of these therapies are currently approved globally specifically for the treatment of T1D as an adjunct to insulin or as a novel insulin for T1D.

Disease-modifying, immune, and beta-cell replacement approaches. Other development programs focus on delaying progression to stage 3 T1D or preserving, regenerating, or replacing beta cells after diagnosis. Teplizumab (Tzield®), an anti-CD3 monoclonal antibody, was the first FDA-approved therapy to delay progression to stage 3 T1D in at-risk individuals; Sanofi has also reported FDA acceptance for expedited review of a supplemental application in recently diagnosed stage 3 T1D. Lantidra™ (donislecel), an allogeneic pancreatic islet cellular therapy, is FDA-approved for certain adults with T1D who cannot achieve adequate glycemic control due to repeated episodes of severe hypoglycemia despite intensive management. Vertex Pharmaceuticals is developing zimislecel (VX-880), an investigational stem cell-derived islet cell therapy administered via portal vein infusion and currently studied with concomitant immunosuppression. Multiple groups are also pursuing next-generation beta-cell replacement strategies which would not required the concomitant administration of immunosuppressive drugs. Eli Lilly has also announced Phase 3 programs of baricitinib (a JAK inhibitor) intended to evaluate (i) delay of stage 3 T1D in at-risk individuals and (ii) preservation of beta-cell function in newly diagnosed T1D. Additional early-stage disease-modifying approaches include. without being limited to, TXNIP inhibition (e.g., TIXiMED’s oral candidate TIX100, which has completed a Phase 1 study).

Medical devices and digital diabetes management. Devices such as continuous glucose monitors (“CGMs”), connected insulin pens, and automated insulin delivery systems that integrate insulin pumps with CGMs and control algorithms are widely adopted in T1D and continue to evolve. These systems have demonstrated improved glycemic outcomes and reduced hypoglycemia risk in many patients, and next-generation innovation in development includes fully closed-loop systems designed to reduce user burden (including approaches intended to operate without carbohydrate counting or meal boluses) and bi-hormonal systems combining insulin and glucagon. A first fully closed loop algorithm (CamDiab) received EU medical device Regulation approval in early 2026.

Collaboration Revenue and Customers

Most of our collaboration revenue for the years ended December 31, 2025, 2024 and 2023 is related to our licenses of certain compounds in the preclinical stage or clinical stage, including the Huadong License Agreement, which was terminated effective September 1, 2024, and the Newsoara License Agreement. Revenue recognized in these periods relates to the achievement of development milestones.

Government Regulation and Product Approvals

Government authorities in the United States, at the federal, state and local level, and in other countries and jurisdictions, including the European Union (“EU”), extensively regulate, among other things, the research, development, testing, manufacture, pricing, reimbursement, sales, quality control, approval, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and import and export of biopharmaceutical products. The processes for obtaining marketing approvals in the United States and in foreign countries and jurisdictions, along with compliance with applicable statutes and regulations and other regulatory authorities, require the expenditure of substantial time and financial resources.

Approval and Regulation of Drugs in the United States

In the United States, drug products are regulated under the Federal Food, Drug and Cosmetic Act (“FDCA”), and applicable implementing regulations and guidance. The failure of an applicant to comply with the applicable regulatory requirements at any time during the product development process, including non-clinical testing, clinical testing, the approval process or post-approval process, may result in delays to the conduct of a study, regulatory review and approval and/or administrative or judicial sanctions. These sanctions may include, but are not limited to, the FDA’s refusal to allow an applicant to proceed with clinical trials, refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, warning letters, adverse publicity, product recalls, product seizures, total or partial suspension of production

or distribution, injunctions, fines and civil or criminal investigations and penalties brought by the FDA or Department of Justice (“DOJ”), or other government entities, including state agencies.

An applicant seeking approval to market and distribute a new drug in the United States generally must satisfactorily complete each of the following steps before the product candidate will be licensed by the FDA:

•preclinical testing including laboratory tests, animal studies and formulation studies, which must be performed in accordance with the FDA’s good laboratory practice (“GLP”), regulations and standards;

•submission to the FDA of an Investigational New Drug Application (“IND”) for human clinical testing, which must become effective before human clinical trials may begin;

•approval by an independent institutional review board (“IRB”), representing each clinical site before each clinical trial may be initiated;

•performance of adequate and well-controlled human clinical trials to establish the safety, potency and efficacy of the product candidate for each proposed indication, in accordance with current good clinical practices (“GCP”);

•preparation and submission to the FDA of a new drug application (“NDA”), for a drug product which includes not only the results of the clinical trials, but also, detailed information on the chemistry, manufacture and quality controls for the product candidate and proposed labelling for one or more proposed indication(s);

•review of the product candidate by an FDA advisory committee, where appropriate or if applicable;

•satisfactory completion of an FDA inspection of the manufacturing facility or facilities, including those of third parties, at which the product candidate or components thereof are manufactured to assess compliance with current good manufacturing practice (“cGMP”) requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;

•satisfactory completion of any FDA audits of the non-clinical and clinical trial sites to assure compliance with GCP and the integrity of clinical data in support of the NDA;

•payment of user fees and securing FDA approval of the NDA to allow marketing of the new drug product; and

•compliance with any post-approval requirements, including the potential requirement to implement a risk evaluation and mitigation strategy (“REMS”) and the potential requirement to conduct any post-approval studies required by the FDA.

Preclinical Studies

Before an applicant begins testing a product candidate with potential therapeutic value in humans, the product candidate enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, formulation and stability, as well as other studies to evaluate, among other things, the toxicity of the product candidate. The conduct of the preclinical tests and formulation of the compounds for testing must comply with federal regulations and requirements, including GLP regulations and standards. The results of the preclinical tests, together with manufacturing information and analytical data, are submitted to the FDA as part of an IND. Some long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, and long-term toxicity studies, may continue after the IND is submitted.

The IND and IRB Processes

An IND is an exemption from the FDCA that allows an unapproved product candidate to be shipped in interstate commerce for use in an investigational clinical trial and a request for FDA authorization to administer such investigational product to humans. Such authorization must be secured prior to interstate shipment and administration of any product candidate that is not the subject of an approved NDA. In support of a request for an IND, applicants must submit a protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND. In addition, the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and plans for clinical trials, among other things, must be submitted to the FDA as part of an IND. The FDA requires a 30-day waiting period after the filing of each IND before clinical trials may begin. This waiting period is designed to allow the FDA to review the IND to determine whether human research subjects will be exposed to unreasonable health risks. At any time during this 30-day period, or thereafter, the FDA may raise concerns or questions about the conduct of the trials as outlined in the IND and impose a clinical hold or partial clinical hold. In this case, the IND sponsor and the FDA must resolve any outstanding concerns before clinical trials can begin.

Following commencement of a clinical trial under an IND, the FDA may also place a clinical hold or partial clinical hold on that trial. In July 2024, the FDA placed the cadisegliatin program on clinical hold based upon a radiochromatographic signal that could not be fully characterized at that time. The FDA subsequently lifted the clinical hold in March 2025, following the Company’s submission of a complete response that demonstrated that the uncharacterized signal was an experimental artifact

A sponsor may choose, but is not required, to conduct a foreign clinical study under an IND. When a foreign clinical study is conducted under an IND, all FDA IND requirements must be met unless waived. When a foreign clinical study is not conducted under an IND, the sponsor must ensure that the study complies with certain regulatory requirements of the FDA in order to use the study as support for an IND or application for marketing approval. Specifically, such studies must be conducted in accordance with GCP, including review and approval by an independent ethics committee (“IEC”), and informed consent from subjects. The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well as the quality and integrity of the resulting data. They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies.

In addition to the foregoing IND requirements, an IRB representing each institution participating in the clinical trial must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review and reapprove the study at least annually. The IRB must review and approve, among other things, the study protocol and informed consent information to be provided to study subjects. An IRB must operate in compliance with FDA regulations. An IRB can suspend or terminate approval of a clinical trial at its institution, or an institution it represents, if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the product candidate has been associated with unexpected serious harm to patients.

Additionally, some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee (“DSMB”). This group provides authorization as to whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the study. Suspension or termination of development during any phase of clinical trials can occur if it is determined that the participants or patients are being exposed to an unacceptable health risk. Other reasons for suspension or termination may be made by us based on evolving business objectives and/or competitive climate.

Information about clinical trials must be submitted within specific timeframes to the National Institutes of Health (“NIH”), for public dissemination on its ClinicalTrials.gov website.

Human Clinical Trials in Support of an NDA

Clinical trials involve the administration of the investigational product candidate to human subjects under the supervision of a qualified investigator in accordance with GCP requirements which include, among other things, the requirement that all research subjects provide their informed consent in writing before their participation in any clinical trial. Clinical trials are conducted under written clinical trial protocols detailing, among other things, the objectives of the study, inclusion and exclusion criteria, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

Human clinical trials are typically conducted in three sequential phases, but the phases may overlap or be combined. Additional studies may also be required after approval.

Phase 1 clinical trials are initially conducted in a limited population to test the product candidate for safety, including adverse effects, dose tolerance, absorption, metabolism, distribution, excretion and pharmacodynamics in healthy humans or in patients. During Phase 1 clinical trials, information about the investigational drug product’s pharmacokinetics and pharmacological effects may be obtained to permit the design of well-controlled and scientifically valid Phase 2 clinical trials.

Phase 2 clinical trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the efficacy of the product candidate for specific targeted indications and determine dose tolerance and optimal dosage. Multiple Phase 2 clinical trials may be conducted by the sponsor to obtain information prior to beginning larger and more costly Phase 3 clinical trials. Phase 2 clinical trials are well controlled, closely monitored and conducted in a limited patient population.

Phase 3 clinical trials proceed if the Phase 2 clinical trials demonstrate that a dose range of the product candidate is potentially effective and has an acceptable safety profile. Phase 3 clinical trials are undertaken within an expanded patient population to further evaluate dosage, provide substantial evidence of clinical efficacy and further test for safety in an expanded and diverse patient population at multiple, geographically dispersed clinical trial sites. A well-controlled, statistically robust Phase 3 clinical trial may be designed to deliver the data that regulatory authorities will use to decide

whether or not to approve, and, if approved, how to appropriately label a drug: such Phase 3 studies are referred to as “pivotal.”

In some cases, the FDA may approve an NDA for a product candidate but require the sponsor to conduct additional clinical trials to further assess the product candidate’s safety and effectiveness after approval. Such post-approval trials are typically referred to as Phase 4 clinical trials. These studies are used to gain additional experience from the treatment of a larger number of patients in the intended treatment group and to further document a clinical benefit in the case of drugs approved under accelerated approval regulations. Failure to exhibit due diligence with regard to conducting Phase 4 clinical trials could result in withdrawal of approval for products.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if serious adverse events occur. In addition, IND safety reports must be submitted to the FDA for any of the following: serious and unexpected suspected adverse reactions; findings from other studies or animal or in vitro testing that suggest a significant risk in humans exposed to the product; and any clinically important increase in the case of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, or at all. Furthermore, the FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution, or an institution it represents, if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the product has been associated with unexpected serious harm to patients. The FDA will typically inspect one or more clinical sites to assure compliance with GCP and the integrity of the clinical data submitted.

Review and Approval of an NDA

In order to obtain approval to market a drug product in the United States, a marketing application must be submitted to the FDA that provides sufficient data establishing the safety, purity and potency of the proposed drug product for its intended indication. The application includes all relevant data available from pertinent preclinical and clinical trials, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls and proposed labeling, among other things. Data can come from company-sponsored clinical trials intended to test the safety and effectiveness of a use of a product, or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety, purity and potency of the drug product to the satisfaction of the FDA.

The NDA is a vehicle through which applicants formally propose that the FDA approve a new product for marketing and sale in the United States for one or more indications. Every new drug product candidate must be the subject of an approved NDA before it may be commercialized in the United States. Under federal law, the submission of most NDAs is subject to an application user fee and the sponsor of an approved NDA is also subject to an annual program fee. Certain exceptions and waivers are available for some of these fees, such as an exception from the application fee for products with orphan designation and a waiver for certain small businesses.

Following submission of an NDA, the FDA conducts a preliminary review of the application generally within 60 calendar days of its receipt and strives to inform the sponsor by the 74th day after the FDA’s receipt of the submission whether the application is sufficiently complete to permit substantive review. The FDA may request additional information rather than accept the application for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA has agreed to specified performance goals in the review process of NDAs. Under that agreement, 90% of applications seeking approval of New Molecular Entities (“NMEs”), are meant to be reviewed within ten months from the date on which the FDA accepts the application for filing, and 90% of applications for NMEs that have been designated for “priority review” are meant to be reviewed within six months of the filing date. For applications seeking approval of products that are not NMEs, the ten-month and six-month review periods run from the date that the FDA receives the application. The review process and the Prescription Drug User Fee Act goal date may be extended by the FDA for three additional months to consider new information or clarification provided by the applicant to address an outstanding deficiency identified by the FDA following the original submission.

Before approving an application, the FDA typically will inspect the facility or facilities where the product is or will be manufactured. These pre-approval inspections may cover all facilities associated with an NDA submission, including component manufacturing, finished product manufacturing and control testing laboratories. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP.

In addition, as a condition of approval, the FDA may require an applicant to develop a REMS. REMS use risk minimization strategies beyond the professional labeling to ensure that the benefits of the product outweigh the potential risks. To determine whether a REMS is needed, the FDA will consider the size of the population likely to use the product, seriousness of the disease, expected benefit of the product, expected duration of treatment, seriousness of known or potential adverse events and whether the product is a new molecular entity.

The FDA may refer an application for a novel product to an advisory committee or explain why such referral was not made. Typically, an advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Special Expedited Review and Approval Programs

The FDA is authorized to designate certain products for expedited review if they are intended to address an unmet medical need in the treatment of a serious or life‑threatening disease or condition. Two such programs are breakthrough therapy designation and priority review designation, regenerative advanced therapy designation and accelerated approval.

Specifically, the FDA may designate a product as a Breakthrough Therapy if it is intended, either alone or in combination with one or more other products, to treat a serious or life‑threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The FDA may take certain actions with respect to Breakthrough Therapies, including holding meetings with the sponsor throughout the development process; providing timely advice to the product sponsor regarding development and approval; involving more senior staff in the review process; assigning a cross‑disciplinary project lead for the review team; and taking other steps to design the clinical trials in an efficient manner. Cadisegliatin received Breakthrough Therapy designation from FDA in 2021.

The FDA may designate a product for priority review if it is a product that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness. The FDA determines, on a case‑by‑case basis, whether the proposed product represents a significant improvement when compared with other available therapies. Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment‑limiting product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety and effectiveness in a new subpopulation. A priority designation is intended to direct overall attention and resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on a marketing application from ten months to six months.

The FDA’s Decision on an NDA

On the basis of the FDA’s evaluation of the application and accompanying information, including the results of the inspection of the manufacturing facilities, the FDA may issue an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

If the FDA approves a new product, it may limit the approved indications for use of the product. The agency may also require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms, including REMS, to help ensure that the benefits of the product outweigh the potential risks. REMS can include medication guides, communication plans for health care professionals, and elements to assure safe use (“ETASU”). ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring and the use of patent registries. The FDA may prevent or limit further marketing of a product based on the results of post-market studies or surveillance programs. After approval, many types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Post-Approval Regulation

If regulatory approval for marketing of a product or new indication for an existing product is obtained, the sponsor will be required to comply with all regular post-approval regulatory requirements as well as any post-approval requirements that the FDA may have imposed as part of the approval process. The sponsor will be required to report, among other things, certain adverse reactions and manufacturing problems to the FDA, provide updated safety and efficacy information and comply with requirements concerning advertising and promotional labeling requirements. Manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP regulations, which impose certain procedural and documentation requirements upon manufacturers. Accordingly, the sponsor and its third-party manufacturers must continue to expend time, money and effort in the areas of production and quality control to maintain compliance with cGMP regulations and other regulatory requirements.

A product may also be subject to official lot release, meaning that the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution. If the product is subject to official lot release, the manufacturer must submit samples of each lot, together with a release protocol showing a summary of the history of manufacture of the lot and the results of all of the manufacturer’s tests performed on the lot, to the FDA. The FDA may in addition perform certain confirmatory tests on lots of some products before releasing the lots for distribution. Finally, the FDA will conduct laboratory research related to the safety, purity, potency and effectiveness of pharmaceutical products.

Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess safety risks; or imposition of distribution or other restrictions under a REMS program. Other potential consequences include, among other things:

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

•fines, warning letters or holds on post-approval clinical trials;

•refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals;

•product seizure or detention, or refusal to permit the import or export of products; or

•injunctions or the imposition of civil or criminal penalties.

The FDA strictly regulates the marketing, labeling, advertising and promotion of prescription drug products placed on the market. This regulation includes, among other things, standards and regulations for direct-to-consumer advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities, and promotional activities involving the Internet and social media. Promotional claims about a drug’s safety or effectiveness are prohibited before the drug is approved. After approval, a drug product generally may not be promoted for uses that are not approved by the FDA, as reflected in the product’s prescribing information. In the United States, health care professionals are generally permitted to prescribe drugs for such uses not described in the drug’s labeling, known as off-label uses, because the FDA does not regulate the practice of medicine. However, FDA regulations impose rigorous restrictions on manufacturers’ communications, prohibiting the promotion of off-label uses. It may be permissible, under very specific, narrow conditions, for a manufacturer to engage in nonpromotional, non-misleading communication regarding off-label information, such as distributing scientific or medical journal information.

If a company is found to have promoted off-label uses, it may become subject to adverse public relations and administrative and judicial enforcement by the FDA, the DOJ, or the Office of the Inspector General of the Department of Health and Human Services, as well as state authorities. This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products. The federal government has levied large civil and criminal fines against companies for alleged improper promotion, and has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.

In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, or PDMA, and its implementing regulations, as well as the Drug Supply Chain Security Act (“DSCA”), which regulate the distribution and tracing of prescription drug samples at the federal level and set minimum standards for the regulation of

distributors by the states. The PDMA, its implementing regulations and state laws limit the distribution of prescription pharmaceutical product samples, and the DSCA imposes requirements to ensure accountability in distribution and to identify and remove counterfeit and other illegitimate products from the market.

Human Capital

As of December 31, 2025 we had twenty-six employees and none of our employees are represented by a labor union, and we consider our employee relations to be good.

Our Corporate Information

We were incorporated under the laws of the State of Delaware in 2015. Our principal executive offices are located at 3980 Premier Drive, Suite 110, High Point, NC 27265, and our telephone number is (336) 841-0300. We also maintain a corporate website, www.vtvtherapeutics.com, where stockholders and other interested persons may review, without charge, among other things, corporate governance materials and certain Securities Exchange Commission (SEC) filings, which are generally available on the same business day as the filing date with the SEC on the SEC’s website http://www.sec.gov. The contents of our website are not made a part of this Annual Report on Form 10-K.