What changed in this filing

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Item 1. Business

2026-03-10 compared with 2025-03-20 · 226 added, 193 removed, 319 unchanged (57% of the section changed)

We are a clinical stage biopharmaceutical company focused on the development of orally administered treatments for metabolic and inflammatory diseases to minimize their long-term complications and improve the lives of patients.

Our lead product candidate, cadisegliatin (TTP399) , is an orally administered, small molecule, liver-selective glucokinase activator (“GKA”) that is a potential adjunctive therapy to insulin for the treatment of type 1 diabetes ("T1D").

On March 14, 2025, based upon the Company's submission of a complete response letter, the U.S.

Food and Drug Administration ("FDA") lifted the clinical hold that had been placed on the cadisegliatin development program in July 2024.

We plan to resume our Phase 3 trial ("the CATT1 trial") in the second quarter of 2025.

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 or twice daily or to receive 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.

Although we had planned to conduct the primary assessment of efficacy after 6 months and then continue to retain patients in the CATT1 trial for another 6 months to collect safety data, we plan to amend the protocol of the CATT1 trial to remove the second 6-month period, which will allow us to obtain topline data from the trial sooner and expedite the start of the required pivotal trials.

The FDA granted Breakthrough Therapy designation for cadisegliatin as an adjunctive therapy to insulin for the treatment of T1D in 2021.

The Breakthrough Therapy designation provides a sponsor with added support and the potential to expedite development and review timelines for a promising new investigational medicine.

We are a late-stage biopharmaceutical company focused on developing orally administered therapies for metabolic and inflammatory diseases with the goal of improving patient outcomes.

Our lead product candidate, 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 type 1 diabetes (T1D).

The Cadisegliatin as Adjunctive Therapy to Insulin in Participants with Type 1 Diabetes ("CATT1") Phase 3 clinical trial is a randomized, double-blind, placebo-controlled trial designed to evaluate the effect of cadisegliatin on hypoglycemia outcomes in patients with T1D.

The primary endpoint is the reduction in the frequency of Level 2 hypoglycemia (blood glucose <54 mg/dL) and Level 3 (severe) hypoglycemia over a six-month treatment period.

A key secondary endpoint is change in hemoglobin A1c (HbA1c), a standard measure of glycemic control, to assess cadisegliatin’s potential to reduce hyperglycemia.

The CATT1 trial will randomize 150 patients with T1D on a 1:1:1 basis (50 patients per study arm) to receive 800 mg cadisegliatin daily, 800 mg cadisegliatin twice daily, or placebo.

In 2021, the FDA granted Breakthrough Therapy designation for cadisegliatin as an adjunctive therapy to insulin for the treatment of T1D.

Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

The Breakthrough Therapy designation for cadisegliatin in T1D was supported by 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 this trial, treatment with cadisegliatin resulted in a clinically meaningful decrease (40%) in the frequency of sever and symptomatic hypoglycemia and in a statistically significant improvement in HbA1c relative to placebo.

In this trial, treatment with cadisegliatin resulted in a clinically meaningful decrease (40%) in the frequency of severe and symptomatic hypoglycemia and in a statistically significant improvement in HbA1c relative to placebo.

Cadisegliatin demonstrated a favorable safety profile, in which abnormal levels of serum or urine ketones were detected less frequently in patients taking cadisegliatin than those taking placebo.

Moreover, a Phase 1 mechanistic study of cadisegliatin in patients with T1D conducted to determine the impact of cadisegliatin on ketone body formation showed no increased risk of ketoacidosis with cadisegliatin during acute insulin withdrawal in patients with T1D.

We also completed a Phase 1 study in healthy male subjects to investigate the absorption, metabolism, and excretion of [ 14 C]- cadisegliatin following single dose oral administration (the "ADME study").

The ADME study results 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.

Based upon extensive testing by two independent laboratories, the Company determined that the radiochromatographic signal identified in the ADME study was an experimental artifact and submitted the results of the investigation to the FDA as part of its complete response.

As previously noted, the FDA lifted the clinical hold on March 14, 2025, allowing the Company to resume its clinical development plan for cadisegliatin .

We continue to work with our partner, G42 Investments AI Holding RSC Ltd.

(“G42 Investments”), to initiate a double-blind, randomized, controlled Phase 2 trial in the Middle East region in patients with type 2 diabetes ("T2D").

The study will randomize 450 patients to assess the potential of cadisegliatin as an adjunct therapy to insulin in patients with T2D.

We expect that trial to begin in 2025.

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

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

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[ 14 C]- 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 20 25, 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.

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

Our primary goal is to advance the development of our lead program cadisegliatin , a novel, oral, liver-selective glucokinase activator.

In February 2024, we closed (the “Closing”) a private placement (the “Private Placement”) of our Class A common stock and pre-funded warrants, pursuant to which we received aggregate gross proceeds of approximately $51.0 million, before deducting offering expenses payable by us.

The securities purchase agreement for the Private Placement, among other things, grants the investors the right to purchase up to an additional $30.0 million of Class A common stock on or before August 27, 2025.

The Private Placement will allow us to continue to advance our lead program for cadisegliatin ( TTP399 ).

We are also actively seeking licensing deals for our pipeline assets that are not currently partnered.

As key components of our strategy, we are focused on:

• Continuing to advance cadisegliatin (TTP399) as a potential treatment for type 1 diabetes .

The FDA granted Breakthrough Therapy designation for cadisegliatin as an adjunctive therapy to insulin for the treatment of T1D in 2021 which was supported by 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.

Now that the FDA has lifted the clinical hold imposed in July 2024, we plan to reinitiate the CATT1 trial in the second quarter of 2025.

• During 2025, we also will be working on the design and execution of two supportive trials in human volunteers 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 guidance.

We will also start preparing plans for additional international registrational studies for cadisegliatin in T1D.

In addition, we continue to work with our partner, G42 Investments, to initiate a double-blind randomized controlled Phase 2 trial in the Middle East region in 450 insulin-dependent patients with T2D.

We expect that trial to begin in 2025.

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 further development of our drug candidates because internal resources are solely focused on the development of cadisegliatin .

Support may come from additional strategic collaborations with other pharmaceutical companies, like our partnerships with Cantex and Newsoara or academic or other research organizations.

We continue to seek financing, partnering and licensing transactions for the further development of the pipeline assets which have not been partnered.

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)

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The onset of T1D is not believed to be affected by diet or lifestyle.

An estimated 1.6 million individuals live with T1D in the U.S.

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.

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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 including continuous glucose monitors, insulin pumps and automated insulin delivery systems has advanced to help people with T1D manage this burden, approximately 80% of people with T1D still do not achieve the ADA’s recommended HbA1c levels.

Failure to maintain glycemic control results in dangerous excursions into hyperglycemia or hypoglycemia that are potentially fatal.

In addition, the accumulated impact of these glycemic excursions can raise a patient’s risk of potentially serious and life-threatening long-term complications, such as cardiovascular disease, blindness, kidney failure, and nerve damage.

Facing a lack of adjunctive treatments for T1D, several existing treatment options for T2D have been investigated in T1D without success.

SGLT-1/2 and SGLT-2 inhibitors were temporarily approved in Europe and Japan for certain sub-groups of people with T1D;

however, they never received regulatory approval in the U.S.

for T1D and were withdrawn from the European market due to safety risks primarily relating to increased risk of diabetic ketoacidosis (“DKA”).

Pramlintide (Symlin), an amylin peptide analog approved for mealtime injections, was approved for use in both T1D and T2D in 2005 but has not been adopted widely.

While technology such as continuous glucose monitors, insulin pumps, and automated insulin delivery systems has advanced to help people with T1D manage this burden, approximat ely 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.

However, teplizumab does not address the unmet need of existing patients with T1D or those that will eventually develop T1D following any therapeutic delay in disease onset.

The use of donislecel is restricted to patients with T1D and recurrent severe hypoglycemic episodes, and requires long-term concurrent immunosuppressive therapy.

Thus, there is a serious unmet medical need to provide people with T1D additional, especially oral, treatment options that can help them to reduce the incidence of hypoglycemia and improve glycemic control (HbA1c) without the risk of DKA or other serious adverse effects.

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 choice for a therapeutic target for improving blood glucose control.

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 is attractive as a potential therapy for the treatment of T1D because it may 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 (“OAD”).

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 is an orally administered, small molecule, liver-selective GKA in development as an adjunctive therapy to insulin for the treatment of T1D.

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.

C adisegliatin has a novel mechanism of action:

liver-selective activation of GK that seeks to provide improved glycemic control and a reduction in the risk of hypoglycemia.

Our trials for cadisegliatin to date also suggest that our liver-selective approach to GK activation has the potential to avoid the tolerability issues associated with other GKAs, such as stimulation of insulin secretion independent of ambient blood glucose causing hypoglycemia, increased

lipids, 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 OAD due to its liver-selectivity and novel mechanism of action.

We have completed ten Phase 1 and three Phase 2 clinical trials of cadisegliatin in patients with type 1 and type 2 diabetes , one of which was six months in duration.

In these trials, cadisegliatin was well tolerated with a significant reduction or hypoglycemia observed in the Phase 2 study in T1D and a negligible incidence of hypoglycemia in the T2D studies .

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

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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 frequency of severe and symptomatic hypoglycemia was observed in patients taking cadisegliatin when compared to those taking 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 previously conducted a study to evaluate the impact of liver-selective GK activation on the safety and tolerability of cadisegliatin .

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.

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In August 2023, we completed an Open-Label Phase 1 Study in Healthy Male Subjects to Investigate the Absorption, Metabolism, and Excretion of [ 14 C]- cadisegliatin (TTP399) Following Single Dose Oral Administration.

Ten participants were dosed.

The original 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.

vTv initiated a series of studies conducted by two independent laboratories to characterize this signal.

The results from these additional investigations concluded that this signal was an experimental artifact, which resulted in the FDA lifting the clinical hold.

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 treatment designation (BTD) from th e FDA which was granted in April 2021.

• Based upon the lifting of the clinical hold imposed in July 2024, we plan to resume our Phase 3 CATT1 trial in the second quarter of 2025.

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 or twice daily or to receive placebo.

Based upon the positive results of our Phase 2 Simplici-T1 Study, we requested Breakthrough Therapy designation (BTD) from th e 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 will be working on the design and execution of two supportive trials in human volunteers to examine the effects of food on cadisegliatin's pharmacokinetics and the potential effects of cadisegliatin on cardiac function (thorough QT study) as required by FDA guidance.

We will also start preparing plans for additional international registrational studies for cadisegliatin in T1D.

We also will continue to work with our partner, G42 Investments to initiate a double-blind, randomized, controlled Phase 2 trial in the Middle East region in patients with T2D.

We expect that trial to begin in 2025.

Preclinical Development

Long-term toxicology studies, development and reproductive toxicology studies, have been completed.

Carcinogenicity studies have been completed in 2024 with no untoward findings.

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

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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.

Following the expiration of a lock up period, from the period May 31, 2022 until December 31, 2024, or if earlier, the date of receipt of FDA approval in the United States for cadisegliatin (the “FDA Approval”), 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.

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.

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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 Private Placement.

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

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.

The CinRx Purchase Agreement provides CinPax the right for two years following the Closing to designate a board observer, which has been subsequently approved by the Company’s board.

The CinRx Purchase Agreement also provides 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”).

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.

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Our Pipeline Programs

TTP273 - GLP-1r Agonist

Glucagon-like peptide (GLP-1) is a naturally occurring hormone ligand for the GLP-1 receptor (GLP-1R) that has been associated with improved metabolism and decreased inflammation, as well as cardio and neuroprotective effects.

Glucagon-like peptide 1 receptor agonists (GLP-1RA) are effective therapies in lowering glycosylated hemoglobin (HbA1c), providing cardio protective benefits and lowering weight.

TTP273 is an orally available, small molecule GLP-1RA which has been demonstrated to reduce postprandial glucose excursion in response to an oral glucose test or mixed meal tolerance test in both preclinical and clinical studies.

Therapeutic use of GLP1-RAs overview

GLP-1 RAs were initially developed to treat T2D but have demonstrated effectiveness in promoting weight loss.

The success of GLP-1 RAs in treating obesity has been noteworthy and has positioned GLP-1 RAs as a promising pharmacological intervention for weight management, contributing to improved overall health outcomes for individuals with obesity.

The number of indications for GLP-1 RAs also continues to grow steadily.

Currently, GLP-1RAs have been approved by the FDA for five indications:

T2D, obesity, cardiovascular disease, chronic kidney disease, and sleep apnea.

Additionally, GLP-1 RAs are being investigated in clinical trials for a range of other conditions, including diabetes prevention, heart failure, non-alcoholic steatohepatitis (NASH), and osteoarthritis and recent research has highlighted the potential for GLP-1 RAs to be of benefit in over 100 health outcomes, including in addiction, psychotic disorders, neurocognitive illnesses, and cardiovascular events like myocardial infarction and stroke.

Additionally, in cystic fibrosis related diabetes (“CFRD”) which presents with abnormally low postprandial stimulation of incretin hormones like GLP-1, an improvement in postprandial hyperglycemia has been demonstrated following prandial administration of GLP-1 agonists.

As the indications for GLP-1 RAs expand, the gastrointestinal (GI) side effects associated with many GLP-1 RAs may pose increasing challenges, particularly for those individuals with pre-existing GI conditions or who do not require weight loss (e.g.

Therefore, GLP-1 RAs like TTP273, which in studies has shown to be well tolerated, would be particularly useful for indications where GI issues or excessive weight loss are undesirable or even contraindicated.

TTP273 is an orally available, small molecule GLP-1RA, which has been demonstrated to reduce postprandial glucose excursion in response to an oral glucose test or mixed meal tolerance test in both preclinical and clinical studies.

Unlike some other GLP-1RAs, TTP273 exhibits biased increase of cyclic adenosine monophosphate ("cAMP") signaling but does not activate the extracellular signal-regulated kinase ("ERK")/β-arrestin pathway significantly at clinically relevant concentrations which may improve efficacy and tolerability.

We believe that TTP273 could be used to treat postprandial hyperglycemia in CFRD patients and CF patients with abnormal postprandial glucose excursions without inducing hypoglycemia or GI side effects.

We have completed two Phase 1 clinical trials and one Phase 2 clinical trial of TTP273 .

In these trials, TTP273 has been demonstrated to be well-tolerated with lower incidences of GI side effects, such as nausea and vomiting, than placebo with minimal weight loss, especially in nonobese patients.

In a randomized, double-blind Phase 2 trial in patients with T2D treated with metformin only, TTP273 showed clinically relevant reductions of glycated hemoglobin (HbA1c) and systolic blood pressure after 3 months of treatment.

HPP3033 - Nrf2/Bach1 Modulator

Our candidate, HPP3033 , represents a novel, non-electrophilic therapeutic approach to activating the nuclear factor erythroid 2–related factor 2 ("Nrf2") pathway that has the potential to be used in the treatment of chronic diseases associated with oxidative stress.

The Role of Nrf2/Bach1 Modulators

Chronic, unresolved inflammation, oxidative stress, and resulting fibrosis are key features of many diseases.

Inflammation is an integral component of the normal immune response that occurs when cells encounter harmful stimuli, such as invading pathogens, damaged cells, or irritants.

During inflammation, cells activate inflammatory processes and complexes that increase the production of cytokines, which are proteins that recruit and activate immune cells.

Inflammation and mitochondrial metabolism are closely associated.

The mitochondria are often called the “powerhouses” of the cell as they produce the energy that the cell needs to function.

This energy is produced by converting fatty acids and glucose into adenosine triphosphate (ATP) by a process called oxidative phosphorylation.

During inflammation, mitochondrial metabolism is temporarily reprogrammed to suppress oxidative phosphorylation.

Instead of primarily making ATP, the mitochondria divert fatty acids and glucose to increase the production of proinflammatory mediators.

During this reprogramming, the mitochondria release chemically reactive molecules called reactive oxygen species (ROS) that can directly attack pathogens and amplify the production of cytokines.

In a normal immune response, the resolution of inflammation begins after the harmful stimuli have been eliminated.

Nrf2 is a protein that plays a key role in the resolution of inflammation by regulating the expression of specific genes involved in mitochondrial metabolism, redox balance, and cytokine production.

When activated, Nrf2 promotes the resolution of inflammation by normalizing mitochondrial metabolism, restoring redox balance, and suppressing cytokine production.

In many chronic and genetic diseases, Nrf2 activity is suppressed, and the resolution of inflammation fails to occur or is inadequate, leading to persistent mitochondrial dysfunction, excess production of ROS, and production of cytokines.

These processes cause chronic inflammation, which can ultimately lead to tissue damage and loss of organ function.

To date, FDA-approved Nrf2 activators, Tecfidera and Skyclarys for patients with multiple sclerosis and Friedreich's ataxia, respectively, are nonspecific alkylating agents relying on reactive, electrophilic biological targets that present safety and tolerability issues.

Non-electrophilic activation of the Nrf2 pathway via targeting the transcription factor BTB and CNC homology 1 ("Bach1") transcriptional repressor provides an alternative mechanism by which to increase the activation of Nrf2 to reduce the oxidative stress and inflammation associated with many acute and chronic diseases.

Bach1 is a transcriptional repressor that controls the expression of certain genes involved in the body’s antioxidant response processes.

Genetic knock-out models of Bach1 have shown increased expression of multiple antioxidant proteins such as heme oxygenase-1 (HMOX1), leading to a significant level of cellular, tissue and organ protection in a wide variety of mouse models.

Hemin and the hemin mimetic cobalt protoporphyrin IX (“CoPP”) are Bach1 ligands that have served as useful tool compounds to investigate the role of Bach1 inhibition in a variety of disease settings.

Both molecules have been shown to have beneficial effects on oxidative stress and inflammatory-mediated pathologies in several animal models.

Further, the ubiquity of the response suggests that the observed tissue protective effects are not related to the underlying causes of a particular disease, but instead are an intrinsic outcome of Bach1 modulation along with Nrf2 activation.

Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD).

In a model of Parkinson's disease, oral administration of HPP3033 attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ("MPTP") neurotoxicity in pre- and post-treatment paradigms.

Bach1 inhibitor-induced neuroprotection was associated with the up regulation of Bach1 targeted pathways in concurrence with the results from Bach knock-out ("KO") mice.

Nrf2 activators are known to exert protection in the pre-treatment paradigm, but the benefits of pharmacological Nrf2 activation are rarely observed in post-treatment models.

Therefore, the results obtained with HPP3033 in this study hold promise for the future development of this compound.

HPP737 - PDE4 Inhibitor

Psoriasis Overview

Psoriasis is a chronic autoimmune inflammatory disease in which the growth cycle of skin is accelerated due to an imbalance in proinflammatory and anti-inflammatory cytokines.

This results in the proliferation of skin cells and the development of raised, red, silvery scale plaques (i.e., plaque psoriasis, psoriasis vulgaris) that have not only medical implications but an impact on a patient’s quality of life.

While the specific inciting events for this proinflammatory process are unknown, psoriasis may be caused by autoimmunity and genetic predisposition.

Events such as trauma to the skin, stress, illness, or infection that triggers the immune systems, obesity, and weather have been identified as triggers for flare ups.

Current Treatment for Psoriasis and Their Limitations

Topical therapies, including glucocorticoids and vitamin D analogs, are the mainstay of treatment for mild psoriasis.

The continuous long-term use of glucocorticoids is limited by the risk of skin thinning and/or atrophy and the potential for systemic absorption.

Vitamin D analogs are often added to glucocorticoids to improve glucocorticoid efficacy while allowing for reduction in glucocorticoid dose.

Moderate to severe disease is treated with systemic therapies including oral phosphodiesterase-4 ("PDE4") inhibition, immunosuppressants, retinoids, and biologics (e.g., anti-tumor necrosis factor ("anti-TNF") agents, interleukin-17 ("IL-17") inhibitors, and interleukin-23 ("IL-23") inhibitors).

Biologics, while realizing high efficacy rates in treating psoriasis, are associated with administration by injection, high cost, need for laboratory monitoring and increased risk of infection.

Inhibitors of PDE4 act by increasing intracellular concentrations of cyclic adenosine monophosphate (“cAMP”), which has a broad range of anti-inflammatory effects.

PDE4 activity is increased in the skin of patients with psoriasis leading to up-regulation of immune modulatory, proinflammatory genes and cytokines, including IL-17, IL-23, and tumor necrosis factor-alpha (TNF-α).

Treatments for psoriasis are aimed at reducing proinflammatory cytokine activity.

The therapeutic potential of oral PDE4 inhibitors has been limited by dose limiting adverse events such as nausea, vomiting, diarrhea, and headache.

HPP737 is an orally administered, potent and selective, non-central nervous system ("non-CNS") penetrant PDE4 inhibitor that addresses inflammatory diseases and offers the potential for an improved tolerability profile and efficacy over commercially available PDE4 inhibitors.

HPP737 has shown potent inhibition of IL-17a and TNF-α production in in vitro studies and activity in several animal models of inflammation.

HPP737 has completed Phase 1 single-ascending dose and initial multiple-ascending dose studies, in which it was well tolerated at all doses tested in healthy volunteers.

Clinical data generated to date supports achieving target engagement (reduction in ex vivo lipopolysaccharide ("LPS") stimulated TNF-α) at HPP737 plasma concentrations predicted to be efficacious from preclinical models.

In September 2021, we announced the results of a multiple ascending dose Phase 1 study of HPP737 to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of HPP737 in healthy volunteers as part of our psoriasis development program.

The trial enrolled 12 subjects in each of two dose cohorts, 15mg and 20mg, randomized to receive HPP737 or placebo (3:1) orally once daily for 14 days.

Dose escalation up to 20mg once per day demonstrated dose proportional increases in exposure, while maintaining a favorable safety and tolerability profile with no dose limiting safety or tolerability findings observed.

There were no serious adverse events and no discontinuations due to treatment emergent adverse events.

TTP273 - Oral Small-Molecule GLP-1 Receptor Agonist

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 obesity 1 .

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)

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)

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.

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

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.

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

PDE4 and Newsoara Biopharma

HPP737 - Oral, Non-CNS Penetrant PDE4 Inhibitor

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.

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”).

Additionally, under the Newsoara License Agreement, we obtained a non-exclusive, sublicensable, royalty-free license to develop and commercialize certain Newsoara patent rights and know-how related to our PDE4 program for therapeutic uses in humans outside of the Newsoara License Territory.

Under the terms of the Newsoara License Agreement, as amended, Newsoara paid us an upfront cash payment of $2.0 million.

We are eligible to receive additional potential development, regulatory and sales-based milestone payments totaling up to $76.5 million.

In addition, Newsoara is obligated to pay the Company royalty payments at mid to upper single digit rates, 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 in the Newsoara License Territory, at its cost, and is required to use commercially reasonable efforts with respect to such development and commercialization efforts.

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.

In June 2024, the parties entered into the Second Amendment to License Agreement, which provided that upon Newsoara's payment of the upfront fee of $20.0 million, the Newsoara License Agreement would be expanded to a global license.

The Second Amendment also requires Newsoara to pay vTv LLC up to $41.5 million in development milestones, $35.0 million in sales-related milestones and royalties in the mid to upper single digits depending upon sales volumes.

To date, Newsoara has not paid the upfront fee to expand the license.

Azeliragon and Cantex Pharmaceuticals, Inc.

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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 an ongoing clinical trial studying the safety and efficacy of azeliragon in patients refractory to first-line treatment of metastatic 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

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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.

The issued patents in this patent family will expire no earlier than 2031, absent any patent term adjustments or extensions in the 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 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.

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Potential Competing Products – Type 1 Diabetes

If approved, we expect that our type 1 diabetes investigational drug candidate will compete with oral or injectable non-insulin agents, new insulin formulations or medical devices that are currently marketed or being developed.

An injectable somatostatin type 2 receptor blocker is being developed by Zucara Therapeutics to treat nocturnal hypoglycemia.

In addition, in 2024 Diasome Pharmaceuticals began a Phase 2b study to assess the effects of their hepatic directed vesicle (HDV)-based insulin lispro formulation on the incidence of nocturnal hypoglycemia in patients with T1D.

In 2023, Carmot Therapeutics has started a phase 2 study of an injectable GLP-1/GIP agonist in overweight or obese patients with T1D to assess its effects on A1c, body weight and continuous glucose monitory ("CGM") metrics including time in hypoglycemia.

REMD Biotherapeutics is developing an injectable glucagon receptor monoclonal antibody, volagedimab, which may help address hyperglycemia in T1D, while Adocia is developing an ultra-rapid insulin with the aim to confer glycemic control benefits by reducing post-prandial hyperglycemia.

None of these therapies are currently approved or marketed for the treatment of type 1 diabetes.

Other therapies in development focus on either delaying the onset of stage 3 T1D or to preserve, regenerate or replace B cells post stage 3 T1D diagnosis.

For example, Teplizumab is an injectable CD-3 targeting immune therapy that was the first disease modifying therapy approved by FDA to delay onset of stage 3 T1D in adults and children while Lantidra is an FDA approved islet cell therapy for patients with T1D who cannot achieve adequate glycemic control because of frequent hypoglycemia.

Because islet cell therapy like Lantidra requires adjunctive immunosuppressive therapy, several companies are developing similar therapies that may not require adjunctive immunosuppressive therapy.

The company Biomea is currently in stage 2 development of an oral covalent menin inhibitor which aims to improve B cell function post stage 3 T1D diagnosis to improve overall glycemic control.

The company TIXiMED recently initiated a phase 1 study of its drug candidate that targets thioredoxin-interacting protein (TXNIP), a detrimental protein that is elevated in diabetes and leads to beta cell death and dysfunction.

Finally, medical devices such as continuous glucose monitors (CGMs), connected smart insulin pens and automated insulin delivery systems, which tie insulin pumps with CGMs through control algorithm software and allow to constantly adjust insulin delivery in response to changing blood glucose levels, continue to evolve and have already shown to improve glucose control and reduce the risk for hypoglycemia.

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.

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

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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.

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:

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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.

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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:

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.”

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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.

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.

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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.

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, 2024, we had twenty-three employees (eight of whom work in North Carolina), of which at least thirteen hold graduate degrees (including ten doctorate degrees).

None of our employees are represented by a labor union, and we consider our employee relations to be good.

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

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

What changed 10-K

Item 1. Business