What changed in this filing

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Item 1. Business

2024-03-13 compared with 2023-03-06 · 226 added, 213 removed, 176 unchanged (71% of the section changed)

We are a clinical stage biopharmaceutical company focused on the development of orally administered treatments for diabetes.

We are focused on treating metabolic and inflammatory diseases to minimize their long-term complications and improve the lives of patients.

We have an innovative pipeline of first-in-class small molecule clinical and preclinical drug candidates.

Our lead program is TTP399 , 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.

On April 13, 2021, we announced that the U.S.

Food and Drug Administration (FDA) granted Breakthrough Therapy designation for TTP399 as an adjunctive therapy to insulin for the treatment of type 1 diabetes.

Breakthrough Therapy designation is based on FDA’s determination that preliminary clinical evidence indicates that an investigational therapy may demonstrate substantial improvement on one or more significant endpoints relative to available therapies for a serious or life-threatening condition.

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

The Breakthrough Therapy designation for TTP399 in type 1 diabetes 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 TTP399 as an adjunct to insulin therapy in adults with type 1 diabetes.

In this trial, treatment with TTP399 resulted in a statistically significant improvement in HbA1c relative to placebo and a clinically meaningful decrease (40%) in the frequency of severe and symptomatic hypoglycemia.

TTP399 demonstrated a favorable safety profile, in which abnormal levels of serum or urine ketones were detected less frequently in patients taking TTP399 than those taking placebo.

Moreover, a Phase 1 mechanistic study of TTP399 in patients with type 1 diabetes to determine the impact of TTP399 on ketone body formation showed no increased risk of ketoacidosis with TTP399 during acute insulin withdrawal in patients with type 1 diabetes.

We have completed the study conduct for An Open-Label Phase 1 Study in Healthy Male Subjects to Investigate the Absorption, Metabolism, and Excretion of [14C]- TTP399 Following Single Dose Oral Administration.

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.

On February 27, 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 18 months following the Closing.

We anticipate that the financing will enable us to conduct a Phase 3 clinical trial for our lead product candidate, cadisegliatin (TTP399) , 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.

Food and Drug Administration ("FDA") granted Breakthrough Therapy designation in 2021 for cadisegliatin as an adjunctive therapy to insulin for the treatment of type 1 diabetes ("T1D").

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.

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 statistically significant improvement in HbA1c relative to placebo and a clinically meaningful decrease (40%) in the frequency of severe and symptomatic hypoglycemia.

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 have 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.

Ten participants have been dosed and analysis is ongoing.

We are working on the design for pivotal and registrational studies for TTP399 , with input from the FDA, which we expect to launch in 2023.

We are currently in active discussions with respect to financing, partnering and/or licensing transactions for the further development of TTP399 .

We also conducted a multiple ascending dose Phase 1 study of HPP737 , an orally administered phosphodiesterase type 4 (“PDE4”) inhibitor, to assess the pharmacokinetics, pharmacodynamics, safety, and tolerability of HPP737 in healthy volunteers as part of our psoriasis program.

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

Given the strategic focus of vTv announced on November 9, 2021, development activities in the United States on HPP737 have remained paused while evaluating strategic options for this program, including potential licensing arrangements.

In addition to our internal development programs, we are continuing to further the development of five partnered programs:

a small molecule GLP-1r agonist, TTP273 (in certain Asian territories excluding Japan), the PDE4 inhibitor, HPP737 (in certain Asian territories excluding Japan), a PPAR-δ agonist, HPP593 , an Nrf2 activator, HPP971 and the RAGE antagonist, azeliragon , through collaborations with pharmaceutical partners via licensing arrangements.

Impact of COVID-19

We have been actively monitoring the COVID-19 global health crisis and its impact on our business, employees, patients, partners, suppliers, and vendors.

Our financial results for the twelve months ended December 31, 2022, were not significantly impacted by COVID-19.

Though our financial results were not significantly impacted, COVID-19 precautions directly and indirectly impacted the timelines for the clinical trials conducted during 2022 and may impact the timelines of the trials currently in process with our partners and being planned.

vTv has continued to make adjustments that allow us to maintain our business operations despite current circumstances, including establishing remote working options for all employees.

Given the current scope of the pandemic, we cannot predict the impact of the progression of the COVID-19 outbreak on future clinical trials and financial results due to a variety of factors, including the continued good health of our employees, the ability of our third-party suppliers, vendors, manufacturers and partners to continue to operate and provide services, the ability of our clinical trial sites to continue or resume operations, any further government and/or public actions taken in response to the pandemic and the ultimate duration of the COVID-19 pandemic.

Table of Con tents

In May of 2023, the FDA issued new draft guidance on "Diabetes Mellitus:

Efficacy Endpoints for Clinical Trials Investigating Antidiabetic Drugs and Biological Products" which, for the first time, permitted the use of hypoglycemia as an endpoint to support a label claim.

Consistent with this guidance and with input from the FDA, we have initiated a Phase 3 double-blind, controlled 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) in 150 patients with T1D.

Participants in the trial will be randomized to two doses of cadisegliatin or placebo.

Reduction in glycated hemoglobin (HbA1c), a traditional efficacy endpoint in diabetes trials, is a key secondary endpoint to assess the potential of cadisegliatin to reduce hyperglycemia, Following the initial assessment of efficacy after six months of treatment, participants will remain on trial for another six months to assess the durability of potential beneficial effects and safety.

The study protocol was submitted to the FDA on February 29, 2024.

The trial will be conducted in the U.S.

only and is expected to complete enrollment by the fourth quarter in 2024 providing top line 1-year data by the first quarter in 2026.

Concurrently, we will be working on the design for two international registrational studies for cadisegliatin in T1D, which we expect to start in 2026.

In addition, 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 450 insulin-using patients with type 2 diabetes ("T2D").

We expect that trial to begin in 2024.

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.

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

Our goal is to advance the development of our differentiated pipeline of orally administered, small molecule drug candidates to treat metabolic and inflammatory diseases to minimize their long-term complications and to improve the lives of patients.

In December 2021, the Company announced a strategic decision to prioritize the development of its lead program TTP399 , a novel, oral, liver-selective glucokinase activator.

This decision included a reduction in the Company’s workforce affecting approximately 65% of its employees.

In December 2021, the Company announced a strategic decision to prioritize the development of its lead program cadisegliatin , a novel, oral, liver-selective glucokinase activator.

The recent successful closing of the Private Placement will allow us to further advance our lead program for cadisegliatin ( TTP399 ).

We are also actively seeking licensing deals for our other assets.

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

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

On April 13, 2021, we announced that the U.S.

Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for TTP399 as an adjunctive therapy to insulin for the treatment of type 1 diabetes.

The Breakthrough Therapy designation for TTP399 in type 1 diabetes 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 TTP399 as an adjunct to insulin therapy in adults with type 1 diabetes.

In addition the mechanistic study in patients with type 1 diabetes to determine the impact of TTP399 on ketone body formation during a period of acute insulin withdrawal indicated no increased risk of ketoacidosis with TTP399 during acute insulin withdrawal in patients with type 1 diabetes.

These results are important since the FDA has declined to approve SGLT2 inhibitors as an adjunctive therapy in Type 1 Diabetes ("T1D"), with concerns over the potential increased risks of diabetic ketoacidosis (DKA) in focus.

The Company is planning two pivotal, placebo-controlled clinical trials of TTP399 in patients with type 1 diabetes and is engaged with the FDA on the optimal clinical trial designs for these studies.

The Company expects to begin these pivotal studies in 2023.

• 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 type 1 diabetes ("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.

Consistent with the May 2023 FDA guidance on efficacy endpoints in clinical trials investigating antidiabetic drugs, and with input from the FDA, we now have initiated a Phase 3 double-blind, controlled 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) in 150 patients with T1D.

Participants in the trial will be randomized to two doses of cadisegliatin or placebo.

Reduction in glycated hemoglobin (HbA1c), a traditional efficacy endpoint in diabetes trials, is a key secondary endpoint to assess the potential of cadisegliatin in reducing hyperglycemia.

Following the initial assessment of efficacy after six months of treatment, participants will remain on trial for another six months to assess durability of potential beneficial effects and safety.

The study protocol was submitted to the FDA on February 29, 2024.

The trial will be conducted in the U.S.

only and is expected to complete enrollment by the fourth quarter in 2024 providing top line 1-year data by the first quarter in 2026.

Concurrently, we will be working on the design for two international registrational studies for cadisegliatin in T1D, which we expect to start in 2026.

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-using patients with type 2 diabetes ("T2D").

We expect that trial to begin in 2024.

• Seeking additional strategic collaborations and additional funding to support the continued development and commercialization of our development programs .

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Such support may come from strategic collaborations with non-profit research funding organizations, such as JDRF International, or from collaboration agreements with other pharmaceutical companies.

We are currently in active discussions with respect to financing, partnering and licensing transactions for the further development of TTP399 .

Table of Con tents

• Continuing to monitor and support existing partnerships for pipeline programs .

Our partners developing our GLP-1r, PPAR-δ, PDE4, and Nrf2 programs continue to advance these assets in their respective licensed territories.

We continue to support and monitor these partnerships.

Our Type 1 Diabetes Program – TTP399

We are currently in active discussions with respect to financing, partnering and licensing transactions for the further development of cadisegliatin .

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 (a hormone that enables people to get energy from food).

Type 1 diabetes results when the body’s immune system attacks and destroys the insulin-producing cells in the pancreas called beta cells.

While the causes of type 1 diabetes are not yet entirely understood, scientists believe that both genetic factors and environmental triggers are involved.

The onset of type 1 diabetes is not believed to be affected by diet or lifestyle.

Current Treatments for Type 1 Diabetes and Their Limitations

Patients with type 1 diabetes have difficulty achieving and maintaining consistent glycemic control, defined as HbA1c < 7% as recommended by the American Diabetes Association (ADA).

In order to maintain appropriate glycemic control, patients with type 1 diabetes are required to constantly monitor their blood glucose levels, closely manage their diet, and administer insulin via injection in response.

While technology has advanced to help people with type 1 diabetes manage the burden of this monitoring and insulin administration process, including continuous glucose monitors and insulin pumps, patient outcomes have not improved:

approximately 80% of people with type 1 diabetes fail to achieve the ADA’s recommended HbA1c levels.

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 TID 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.

Current Treatments for T1D and Their Limitations

Patients with T1D have difficulty achieving and maintaining consistent glycemic control, defined as HbA1c < 7% as recommended by the American Diabetes Association ("ADA").

In order 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 in response.

While technology has advanced to help people with T1D manage the burden of this monitoring and insulin administration process, including continuous glucose monitors and insulin pumps, patient outcomes have not improved:

approximately 80% of people with T1D fail to 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.

Several existing treatment options for type 2 diabetes have been investigated to treat type 1 diabetes, generally without success.

While a pair of SGLT-1/2 and SGLT-2 inhibitors were approved in recent years in Europe and Japan with label restrictions to certain sub-groups of people with type 1 diabetes, these therapies have not been approved in the U.S.

due to safety risks primarily relating to diabetic ketoacidosis (“DKA”).

Alternative therapeutic modalities, including monoclonal antibodies, are under clinical investigation and have demonstrated evidence of the potential to delay the onset of type 1 diabetes.

Such alternatives have not completed clinical development or received regulatory approval, nor do they address the unmet need of existing patients with type 1 diabetes or those that eventually become patients with type 1 diabetes following any therapeutic delay in disease onset.

With insulin and pramlintide injection as the only treatment options approved in the United States for type 1 diabetes, there is a serious unmet medical need to provide people with type 1 diabetes additional, especially oral, treatment options that can help them to reduce HbA1c, or the incidence of hypoglycemia (blood glucose levels below normal) or DKA.

Several existing treatment options for T2D have been investigated to treat T1D, generally without success.

While SGLT-1/2 and SGLT-2 inhibitors were initially approved in Europe and Japan with label restrictions to certain sub-groups of people with T1D, and continue to be approved for patients with T2D, these therapies have since been withdrawn from the European market and never received regulatory approval in the U.S.

for T1D due to safety risks primarily relating to the risk of diabetic ketoacidosis (“DKA”).

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

Alternative therapeutic modalities, including monoclonal antibodies, are under clinical investigation and have demonstrated evidence of the potential to delay the onset of T1D.

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 full-blown disease, 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 are eventually at risk to become patients with T1D following any therapeutic delay in disease onset.

The use of Donislecel, on the other hand, 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 HbA1c and the incidence of hypoglycemia (blood glucose levels below normal) or DKA.

The Role of Glucokinase Activation in Diabetes

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GK has two distinctive characteristics that make it a good choice for blood glucose control.

First, its expression is mostly limited to tissues that require glucose-sensing (mainly liver and pancreatic β-cells).

Second, GK acts as a biological sensor for changes in serum glucose levels and modulates changes in liver glucose metabolism that in turn regulates the balance between hepatic glucose production and glucose consumption and modulates changes in insulin secretion by the β-cells.

GK activation is attractive as a potential therapy for the treatment of type 1 diabetes and has a mechanism of action entirely distinct from currently marketed oral anti-diabetic drugs (“OAD”).

TTP399 is an orally administered, small molecule, liver-selective glucokinase activator (“GKA”) in development as an adjunctive therapy to insulin for the treatment of type 1 diabetes.

TTP399 has a novel mechanism of action:

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

Our trials for TTP399 to date suggest that our liver-selective approach to GK activation has the potential to avoid the tolerability issues associated with other GKAs, such as activation of GK in the pancreas, stimulation of insulin secretion independent of glucose, hypoglycemia, increased lipids, and liver toxicity.

Based on data from Phase 1 and 2 trials to date, we believe that TTP399 , 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 TTP399 , one of which was six months in duration.

Table of Con tents

Phase 1 and 2 clinical trials, TTP399 was well tolerated with negligible incidence of hypoglycemia in the type 2 diabetes studies and a significant reduction of hypoglycemia observed in the Phase 2 study in type 1 diabetes.

First, its expression is mostly limited to tissues that require glucose-sensing (mainly liver cells and pancreatic β-cells).

Second, GK acts as a biological sensor for changes in serum glucose levels and modulates changes in the liver's uptake or release of glucose and changes in insulin secretion by the β-cells.

GK activation is attractive as a potential therapy for the treatment of T1D because it may improve

overall 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”).

Cadisegliatin (TTP399)

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

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 negligible incidence of hypoglycemia in the T2D studies and a significant reduction of hypoglycemia observed in the Phase 2 study in TID.

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 TTP399 , assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of TTP399 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 TTP399 compared to placebo.

Moreover, a clinically meaningful decrease (40%) in the frequency of severe and symptomatic hypoglycemia was observed in patients taking TTP399 when compared to those taking placebo.

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 TID 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 frequency of severe and symptomatic hypoglycemia was observed in patients taking cadisegliatin when compared to those taking placebo.

Mechanistic study

In October 2021, we announced positive results from the mechanistic study indicating no increased risk of ketoacidosis with TTP399 during acute insulin withdrawal in patients with type 1 diabetes.

Consistent with previous clinical studies of TTP399 , the drug was well tolerated with fewer subjects reporting treatment-emergent adverse events in the group taking TTP399 than in the placebo group.

Importantly, patients taking TTP399 reported no events of hypoglycemia, while four events of hypoglycemia were reported in the placebo group.

Clinical Development Plan

Based upon the positive results of our Simplici-T1 Study, we requested breakthrough treatment designation (BTD) with the FDA which was granted in April 2021.We have completed the study conduct for An Open-Label Phase 1 Study in Healthy Male Subjects to Investigate the Absorption, Metabolism, and Excretion of [14C]- TTP399 Following Single Dose Oral Administration.

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.

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 have been dosed, and analysis is ongoing.

The Company is planning two pivotal, placebo-controlled clinical trials of TTP399 in subjects with type 1 diabetes and is engaged with the FDA on the optimal clinical trial designs for these studies.

The Company expects to begin these pivotal studies in the second half of 2023.

The FDA confirmed that the effect size of TTP399 on events of hypoglycemia as demonstrated in the Phase 2 SimpliciT-1 Study are clinically meaningful and that a reduction in events of hypoglycemia would be an acceptable clinical endpoint for evaluation of an adjunctive therapy for the treatment of type 1 diabetes.

Clinical Development Plan

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

Consistent with the new 2023 FDA guidance on efficacy endpoints for anti-diabetic drugs, the Company is planning one supportive small and two larger pivotal, placebo-controlled Phase 3 clinical trials of cadisegliatin in patients with T1D and is engaged with the FDA on the optimal clinical trial designs for these studies.

The FDA confirmed that the effect size of cadisegliatin on events of hypoglycemia as demonstrated in the Phase 2 SimpliciT-1 Study are clinically meaningful and that a reduction in events of hypoglycemia would be an acceptable clinical endpoint for evaluation of an adjunctive therapy for the treatment of T1D.

We now have initiated a Phase 3 double-blind, controlled 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 of hypoglycemia) and Level 3 hypoglycemia ("severe" hypoglycemia e.g., requiring assistance of another person) in 150 patients with T1D.

Participants in the trial will be randomized to two doses of cadisegliatin or placebo.

Reduction in glycated hemoglobin (HbA1c), a traditional efficacy endpoint in diabetes trials, is a key secondary endpoint to assess the potential of cadisegliatin in reducing hyperglycemia.

Following the initial assessment of efficacy after six months of treatment, participants will remain on trial for another six months to assess durability of potential beneficial effects and safety.

The study protocol was submitted to the FDA on February 29, 2024.

The trial will be conducted in the U.S.

only and is expected to complete enrollment by the fourth quarter in 2024 providing top line 1-year data by the first quarter in 2026.

Concurrently, we will be working on the design for two international registrational studies for cadisegliatin in T1D, which we expect to start in 2026.

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-using patients with T2D.

We expect that trial to begin in 2024.

Preclinical Development Plan

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

Carcinogenecity studies are ongoing and expected to be completed by the second quarter of 2024.

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

Carcinogenicity studies are ongoing and expected to be completed by the second quarter of 2024.

Collaboration Agreements

G42 Transaction

On May 31, 2022, the Company and G42 Investments AI Holding RSC Ltd, a private limited company (“G42 Investments”), entered into a Common Stock Purchase Agreement (the “G42 Purchase Agreement”), pursuant to which the Company sold to G42 Investments 10,386,274 shares of the Company’s Class A common stock at a price per share of approximately $2.41, 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 of G42 Investments to be paid on May 31, 2023 (the "G42 Promissory Note").

As part of the G42 Purchase Agreement, G42 Investments nominated a director as appointee and the Company’s board of directors approved appointing the new director to the Company’s board.

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 at a price per share of approximately $96.40, 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.

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 TTP399 (the “FDA Approval”) of TTP399 ), 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.

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.

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 TTP399 compound (the “Licensed Product”) as well as jointly creating a global development plan to develop, market, and commercialize TTP399 in certain countries in the Middle East, Africa, and Central Asia (the “Partner Territory”).

Table of Con tents

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 TTP399 .

Specifically, the Company will share various protocols with Cogna related to conducting the clinical trials and will provide the patient dosages and placebo of TTP399 needed to conduct the trials.

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, TTP399 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 TTP399 outside of the Partner Territory, at its own cost.

The results of each party’s clinical trials will be combined by the Company to seek FDA approval in the United States for TTP399 .

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 will 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 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 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.

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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.

CinPax and CinRx Transaction

On July 22, 2022, the Company entered into the CinRx Purchase Agreement with CinPax, LLC (“CinPax”), a subsidiary of CinRx Pharma, LLC (“CinRx”), pursuant to which the Company agreed to sell to CinPax 4,154,549 shares of the Company’s Class A common stock at a price per share of approximately $2.41, 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 CinRx Purchase Agreement provides CinPax the right to nominate a director to be approved on vTv’s Board of Directors and a board observer, which was subsequently approved by the Company’s board.

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 at a price per share of approximately $96.40, 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”).

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, TTP399 , or (ii) the Company is acquired by a third party, sells all or substantially all of its assets related to TTP399 to a third party or grants a third party an exclusive license to develop, commercialize and manufacture TTP399 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 not be exercisable by CinRx.

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.

Table of Con tents

Our Psoriasis Program – 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 pro-inflammatory 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 has not only medical implications but an impact on a patient’s quality of life.

While the specific inciting events for this pro-inflammatory 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 / 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 PDE4 inhibition, immunosuppressants, retinoids, and biologics (ex:

anti-TNF agents, IL-17 inhibitors, 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, pro-inflammatory genes and cytokines including interleukin-17 (IL-17), interleukin-23 (IL-23), and tumor necrosis factor-alpha (TNF-α).

Treatments for psoriasis are aimed at reducing pro-inflammatory cytokine activity.

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

HPP737 is an orally administered, potent and selective, 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 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 , an orally administered phosphodiesterase type 4 (“PDE4”) inhibitor, 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.

Business Plan

Given the new strategic focus of vTv announced on November 9, 2021, development activities in the United States on HPP737 were paused while evaluating strategic options for this program, including potential licensing arrangements.

Our Cystic Fibrosis Related Diabetes Program – TTP273 - GLP-1r Agonist

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.

We are currently exploring options to study the therapeutic potential of TTP273 in patients with cystic fibrosis related diabetes ("CFRD").

Cystic Fibrosis Related Diabetes Overview

Cystic fibrosis related diabetes (“CFRD”) shares some features with both type 1 and type 2 diabetes but is distinct, and is likewise categorized as diabetes due to other causes, specifically a disease of the exocrine pancreas by the American Diabetes Association.

Cystic fibrosis related diabetes (“CFRD”) shares some features with both type 1 and type 2 diabetes but is distinct, and is categorized as diabetes due to other causes, specifically a disease of the exocrine pancreas, by the American Diabetes Association.

In people with cystic fibrosis (“CF”), the thick, sticky mucus that is characteristic of the disease causes scarring of the pancreas.

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The damaged pancreas also responds to insulin signaling in a delayed manner.

The delay and blunting of the insulin response in patients with CFRD results in post-prandial hyperglycemia.

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The delay and blunting of the insulin response in patients with CFRD results in postprandial hyperglycemia.

The Role of GLP-1r Activation in Cystic Fibrosis Related Diabetes

GLP-1, an incretin hormone that is released by the gut in response to nutrients, lowers postprandial glucose by promoting insulin secretion.

Abnormally low postprandial stimulation of incretins has been described in CF patients and improvement in postprandial hyperglycemia has been demonstrated following prandial administration of GLP-1 agonists or DPP-4 inhibitors.

Nevertheless, the use of existing GLP-1 mimetics that are available for the treatment of type 2 diabetes to treat CFRD is limited by the GI side effects and undesired weight loss associated with these agents.

TTP273 is an orally available, small molecule GLP-1 receptor agonist 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.

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

GLP-1 is released by the gut in response to nutrients and lowers postprandial glucose by promoting insulin secretion.

Abnormally low postprandial stimulation of incretin hormones like GLP-1 has been described in CF patients and improvement in postprandial hyperglycemia has been demonstrated following prandial administration of GLP-1 agonists or dipeptidyl peptidase-4.

Although existing GLP-1 mimetics are available for the treatment of CFRD, their use is limited by the gastrointestinal ("GI") side effects and undesired weight loss associated with these agents.

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.

An oral therapy such as TTP273 is needed because the current method of treatment of CFRD is injected insulin, which comes with associated risks of hypoglycemia and poses additional burdens on patients.

Other available oral therapies for type 2 diabetes are not recommended for the treatment of CFRD due to side effects such as hypoglycemia, weight loss, or nausea.

In particular, the GLP-1 mimetics currently in the market have been demonstrated to result in increased GI side effects and undesired weight loss, both of which are major drawbacks for patients with CFRD.

Other available oral therapies for type 2 diabetes ("T2D") are not recommended for the treatment of CFRD due to side effects, such as hypoglycemia, weight loss, or nausea.

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

Additionally, we have completed nine Phase 1 clinical trials and one Phase 2 clinical trial of TTP054 , a predecessor orally administered GLP-1r agonist.

In our Phase 1 and Phase 2 clinical 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 non-obese patients.

We are currently planning an adaptive Phase 1b/2 clinical trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of TTP273 , but the final design may be adjusted based on the feedback received, if any, from the FDA and the conduct of this clinical trial is dependent upon securing a funding partner.

Our Nrf2/Bach1 Modulator Program

Additionally, we have completed nine Phase 1 clinical trials and one Phase 2 clinical trial of TTP054 , a predecessor orally administered GLP-1RA.

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

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

To date, therapeutic agents seeking to active Nrf2, such as such as Bardoxolone or Tecfidera, have relied on reactive, electrophilic biological targets that may present safety and tolerability issues.

Non-electrophilic activation of the Nrf2 pathway via targeting the 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.

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

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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.

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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.

Our candidate, HPP3033 , represents a novel, non-electrophilic therapeutic approach to activating the Nrf2 pathway that has the potential to be used in the treatment of chronic diseases associated with oxidative stress.

We are currently evaluating HPP3033 and other Nrf2 activator compounds in various preclinical studies.

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.

Partnered Development Programs

PDE4 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 $58.5 million.

In addition, Newsoara is obligated to pay us royalty payments at high-single to low-double 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.

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.

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.

PPAR-δ and Reneo Pharmaceuticals, Inc.

On December 21, 2017, we entered into a License Agreement with Reneo Pharmaceuticals, Inc.

(“Reneo”) (the “Reneo License Agreement”), under which Reneo obtained an exclusive, worldwide, sublicensable license to develop and commercialize our peroxisome proliferation activated receptor delta (PPAR-δ) agonist program, including the compound HPP593 (REN001), for therapeutic, prophylactic, or diagnostic application in humans.

(“Reneo”) (the “Reneo License Agreement”), under which Reneo obtained an exclusive, worldwide, sublicensable license to develop and commercialize our peroxisome proliferation activated receptor delta (PPAR-δ) agonist program, including the compound HPP593 (REN001, mavodelpar ), for therapeutic, prophylactic, or diagnostic application in humans.

Under the terms of the Reneo License Agreement, Reneo paid us an initial license fee of $3.0 million.

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Upon expiration (but not earlier termination) of the Reneo License Agreement, the licenses granted to Reneo will survive on a royalty-free basis in perpetuity.

Reneo has continued to progress the development of REN001 for primary mitochondrial myopathy (PMM) and long-chain fatty acid oxidation disorders (LC-FAOD).

The Phase 2 study of REN001 for glycogen storage disorder type V (McArdle Disease) showed only modest benefits, and Reneo does not plan to proceed further for this indication.

GLP-1r and Huadong

Reneo has continued to progress the development of mavodelpar for primary mitochondrial myopathy (PMM) and long-chain fatty acid oxidation disorders (LC-FAOD).

The Phase 2 study of mavodelpar for glycogen storage disorder type V (McArdle Disease) showed only modest benefits, and Reneo does not plan to proceed further for this indication.

Reneo announced on December 14th, 2023, that its pivotal STRIDE study (NCT04535609) of mavodelpar in adult patients with PMM did not meet its primary efficacy or secondary efficacy endpoint.

The primary efficacy endpoint of the trial was the change from baseline in the distance walked during the 12-minute walk test (12MWT) at week 24.

The secondary efficacy endpoint was the change from baseline in the PROMIS® Short Form Fatigue 13a score.

GLP-1r and Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

On December 21, 2017, we entered into a License Agreement with Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

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Under the original Huadong License Agreement, we had the obligation to conduct a Phase 2 multi-region clinical trial (the “Phase 2 MRCT”), should Huadong require us to do so.

We were also responsible for contributing up to $3.0 million in

Table of Con tents

connection with the Phase 2 MRCT, if it occurs.

We were also responsible for contributing up to $3.0 million in connection with the Phase 2 MRCT, if it occurs.

However, the Huadong License Agreement was amended in January 2021 to remove these obligations.

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Either party may terminate the Huadong License Agreement for the other party’s uncured material breach.

PDE4 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 phosphodiesterase type 4 inhibitors (“PDE4”) program, including the compound HPP737 , in China and other Pacific Rim territories (collectively, 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 $58.5 million.

In addition, Newsoara is obligated to pay us royalty payments at high-single to low-double digit rates, based on tiers of annual net sales of licensed products.

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.

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.

Nrf2 and Anteris Bio

On December 18, 2023, Huadong notified us of its intent to terminate the Huadong License Agreement.

The termination will not be effective until after both parties negotiate and finalize a termination agreement, which is expected to occur in the first half of 2024.

Nrf2 and Anteris Bio, Inc.

On December 11, 2020, we entered into a license agreement with Anteris Bio, Inc.

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Either party may terminate the Anteris License Agreement for the other party’s uncured material breach.

Table of Con tents

Anteris may terminate the Anteris License Agreement at will upon prior written notice.

Either party may terminate the Anteris License Agreement for the other party’s insolvency.

Azeliragon and Cantex Pharmaceuticals

On June 22 2021, vTv Therapeutics Inc.

and Cantex Pharmaceuticals, Inc.

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 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 September 25, 2023, Anteris notified the Company that it was terminating the Anteris License Agreement.

The termination became effective on December 24, 2023, and Anteris has since liquidated its assets and ceased doing business.

Inbound Partnerships

JDRF Agreement

In August 2017, we entered into a research and collaboration agreement with JDRF International (the “JDRF Agreement”) to support the funding of the Simplici-T1 Study, a Phase 2 study to explore the effects of TTP399 in patients with type 1 diabetes.

The JDRF Agreement was amended in June 2021 to provide additional funding for the Company’s mechanistic study exploring the effects of TTP399 on ketone body formation during a period of insulin withdrawal in people with type 1 diabetes.

The JDRF Agreement was amended in June 2021 to provide additional funding for the Company’s mechanistic study exploring the effects of cadisegliatin on ketone body formation during a period of insulin withdrawal in people with type 1 diabetes.

According to the terms of the JDRF Agreement, as amended, JDRF provided research funding of $3.4 million based on the achievement of research and development milestones.

Additionally, the Company has the obligation to make certain milestone payments to JDRF upon the commercialization, licensing, sale or transfer of TTP399 as a treatment for type 1 diabetes.

Additionally, the Company has the obligation to make certain milestone payments to JDRF upon the commercialization, licensing, sale or transfer of cadisegliatin as a treatment for type 1 diabetes.

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 TTP399 .

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.

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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.

During the year ended December 31, 2021, the Company made a payment of $2.0 million related to the satisfaction of the milestone to complete the phase 2 trials for TTP399 under this agreement.

During the year ended December 31, 2021, the Company made a payment of $2.0 million related to the satisfaction of the milestone to complete the Phase 2 trials for cadisegliatin under this agreement.

Third-Party Suppliers and Manufacturers

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Intellectual Property

The IP portfolio for TTP399 includes issued patents in approximately 35 countries and territories, including the U.S., Europe, Japan, Canada, Australia, and China, directed to TTP399 as a composition of matter.

The IP portfolio for cadisegliatin (TTP399) includes issued patents in approximately 35 jurisdictions, including the U.S., over 10 European countries, Japan, Canada, Australia, and China, directed to cadisegliatin as a composition of matter, among other things.

The issued U.S.

patent covering TTP399 as a composition of matter will expire no earlier than 2025, absent any patent term adjustments or extensions, but may expire as late as 2030 if, after approval by the U.S.

FDA, we apply for and obtain the maximum possible PTE that is available under the Hatch-Waxman Act.

Patents covering TTP399 as a composition of matter outside the United States will expire no earlier than 2025, absent any patent term adjustments or extensions.

patent covering cadisegliatin as a composition of matter will expire no earlier than 2025,

absent any patent term adjustments or extensions, but may expire as late as 2030 if, after approval by the U.S.

Food and Drug Administration (FDA), we apply for and obtain the maximum possible patent term extension (PTE) that is available under the Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman Act”).

Only one U.S.

patent applicable to an approved drug may be extended and only those claims covering the approved drug, a method of using it, or a method for manufacturing it may be extended.

Patents covering cadisegliatin as a composition of matter outside the United States will expire no earlier than 2025, absent any patent term adjustments or extensions.

Provisions that are similar to the U.S.

PTE under the Hatch-Waxman Act are available in Europe and some other foreign jurisdictions to extend the term of the patent

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covering TTP399 as a composition of matter.

The IP portfolio for TTP399 also includes patent families covering crystal forms, salt forms, and solid formulations of TTP399 as well as combinations of TTP399 with metformin, DPP-4 inhibitors, or GLP-1r agonists, and their use in methods of treatment.

The IP portfolio also includes a patent family covering methods of treating type 1 diabetics using TTP399 in combination with insulin.

The patent applications in these additional patent families, if issued, would be expected to expire between 2031 and 2040, absent any patent term adjustments or extensions.

PTE under the Hatch-Waxman Act are available in Europe and some other foreign jurisdictions to extend the term of the patent covering cadisegliatin as a composition of matter.

The IP portfolio for cadisegliatin also includes patent families covering crystal forms, salt forms, and solid formulations of cadisegliatin , among other things.

The issued patents and patent applications, if issued, in these additional patent families would be expected to expire between 2034 and 2041, absent any patent term adjustments or extensions.

The IP portfolio for cadisegliatin further includes additional patent families covering combinations of cadisegliatin with metformin, DPP-4 inhibitors, or GLP-1r agonists, and their use in methods of treatment.

The issued patents and patent applications, if issued, in these additional patent families would be expected to expire between 2031 and 2033, absent any patent term adjustments or extensions.

In addition, the IP portfolio also includes a patent family covering methods of treating patients with type 1 diabetes using cadisegliatin in combination with insulin.

The issued patents and patent applications, if issued in this additional patent family, if issued, would be expected to expire in 2039, absent any patent term adjustments or extensions.

The IP portfolio for HPP737 includes issued patents in the U.S.

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Any patents issuing from these two patent families will expire in 2040, absent any patent term adjustments or extensions.

The IP portfolio for the GLP-1r program includes issued patents in over 25 countries and regions, including the U.S., Europe, Japan, Canada, Australia, and China, directed to TTP273 as a composition of matter.

The IP portfolio for the GLP-1r program includes issued patents in over 25 countries and regions, including the U.S., over 10 European countries, Japan, Canada, Australia, and China, directed to TTP273 as a composition of matter.

The issued U.S.

4 unchanged sentences

PTE under the Hatch-Waxman Act are available in Europe and some other foreign jurisdictions to extend the term of the patent covering TTP273 as a composition of matter.

The IP portfolio for TTP273 also includes patent families covering crystalline, non-crystalline, and salt forms 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 .

The IP portfolio for TTP273 also includes patent families covering crystalline, non-crystalline, and 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 .

The patent applications in these additional patent families, if issued, would be expected to expire between 2034 and 2042, absent any patent term adjustments or extensions.

The IP portfolio for the Nrf2/Bach1 program includes issued patents in approximately 25 countries and regions, including the U.S., Europe, Japan, Canada, Australia, and China, directed to HPP971 and HPP3033 as compositions of matter.

The issued U.S.

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The patent applications in these additional patent families, if issued, would be expected to expire between 2035 and 2041, absent any patent term adjustments or extensions.

The IP portfolio for azeliragon includes issued patents in the U.S.

directed to azeliragon as a composition of matter and methods of use to treat various indications.

The issued U.S.

patent covering azeliragon as a composition of matter will expire no earlier than 2023, absent and patent term adjustments and extensions.

However, this issued patent may expire as late as 2029 if, after approval by the U.S.

The IP 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.

The patent applications in these additional patent families, if issued, would be expected to expire between 2028 and 2039.

The issued patents and patent applications, if issued in these additional patent families, if issued, would be expected to expire between 2028 and 2039.

The issued U.S.

patent covering the polymorph of azeliragon used in clinical development will expire no earlier than 2028, absent any patent term adjustments or extensions, but may expire as late as 2033 if after approval by the U.S.

patent covering the polymorph of azeliragon used in clinical development will expire no earlier than 2028, absent any patent term

adjustments or extensions, but may expire as late as 2033 if after approval by the U.S.

FDA we decide to apply for and obtain the maximum PTE under the Hatch-Waxman Act for the U.S.

3 unchanged sentences

Similar provisions available in Europe and some other foreign jurisdictions to extend the term of a patent that covers an approved drug.

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Trade Secrets

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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 non-insulin agents that are currently being developed or which have limited approval in certain jurisdictions.

These include SGLT-1/2 inhibitors, such as sotagliflozin, being developed by Lexicon and SGLT-2 inhibitors such as AstraZeneca’s dapagliflozin, both of which are approved for limited use in the European Union and Japan as well as Eli Lilly/Boehringer Ingelheim’s empagliflozin, which is not currently approved for the treatment of type 1 diabetes.

None of these treatments are approved for treatment of type 1 diabetes in the United States.

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

These include the SGLT-1/2 inhibitor sotagliflozin, being developed by Lexicon, and the oral somatostatin type 2 receptor blocker ZT-01 by Zucara Therapeutics.

In addition, Diasome Pharmaceuticals has started a new Phase 2 study in February 2024 to assess the effects of their Hepatic Directed Vesicle (HDV)-based insulin lispro formulation ("HDV Insulin lispro") on the incidence of nocturnal hypoglycemia in patients with T1D.

However, none of these treatments are currently approved or marketed for the treatment of type 1 diabetes.

Collaboration Revenue and Customers

Most of our collaboration revenue for the years ended December 31, 2022, 2021 and 2020 is related to our licenses of certain compounds in the preclinical stage or clinical stage, including the Cantex License Agreement, Anteris License Agreement, Huadong License Agreement, the Reneo License Agreement, and the Newsoara License Agreement.

Most of our collaboration revenue for the years ended December 31, 2023, 2022 and 2021 is related to our licenses of certain compounds in the preclinical stage or clinical stage, including the Huadong License Agreement, the Reneo License Agreement, and the Newsoara License Agreement.

Revenue recognized in these periods relates to initial consideration received in the form of upfront payments and equity interests, research activities performed by our personnel, and the achievement of development milestones.

1 unchanged sentence

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

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expenditure of substantial time and financial resources.

For a full discussion of the regulatory framework for the approval and regulation of investigational drug candidates, and applicable domestic and foreign healthcare law, please see “Part 1 – Item 1 – Business - Government Regulation and Product Approvals” in our Annual Report on Form 10-K filed on February 21, 2020.

Human Capital

As of December 31, 2022, we had thirteen employees (all but four of whom work in North Carolina), of which at least eight hold graduate degrees (including six doctorate degrees) and six are engaged in full-time research and development activities.

As of December 31, 2023, we had sixteen employees (all but seven of whom work in North Carolina), of which at least ten hold graduate degrees (including eight doctorate degrees) and seven are engaged in full-time research and development activities.

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

4 unchanged sentences

The contents of our website are not made a part of this Annual Report on Form 10-K.

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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