A Multi-Center, Randomized, Double-Blind, Parallel-Group, Multiple-Dose, Adaptive Study Assessing the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of TTP399 in With Adult Patients Type 1 Diabetes Mellitus

The purpose of this study is to evaluate the safety and efficacy of TTP399 in Type 1 diabetics. This study will be in 2 phases: phase 1 will evaluate the safety of different TTP399 dosage regimens over 1 week of daily dosing. Phase 2 will evaluate the safety and efficacy of a TTP399 dosing regimen over 12 weeks of daily dosing.

Start Date25 Oct 2017

Sponsor / Collaborator

vTv Therapeutics, Inc.

[+1]

NCT02405260 / CompletedPhase 2

A Multi-Center, Adaptive Phase 2, Randomized, Double-Blind, Placebo- and Active-Controlled (Sitagliptin), Parallel Group Study to Evaluate the Safety and Efficacy of TTP399 Following 6 Months Administration in Subjects With Type 2 Diabetes Mellitus on A Stable Dose of Metformin

This trial is a multi-center, adaptive, randomized, double-blind, placebo- and active- controlled, parallel group, Phase 2 study in subjects with T2DM to evaluate the effect of TTP399 on HbA1c following administration for 6 months.

Start Date01 Mar 2015

Sponsor / Collaborator

vTv Therapeutics, Inc.

100 Clinical Results associated with Cadisegliatin

100 Translational Medicine associated with Cadisegliatin

100 Patents (Medical) associated with Cadisegliatin

Literatures (Medical) associated with Cadisegliatin

01 Oct 2024·Microbial Pathogenesis

Identification of small molecule glucokinase activators for the treatment of diabetes based on plants from the traditional Chinese medicine: In silico analysis

Article

Author: Saih, Asmae ; Moussamih, Samya ; Kettani, Anass ; Safi, Amal ; Regragui, Anas ; Khamlich, Jihane ; Douiyeh, Imane

Mutations in glucokinase (GCK) can either enhance or inhibit insulin secretion, leading to different forms of diabetes, including gestational diabetes. While many glucokinase activators (GKAs) have been explored as treatments, their long-term effectiveness has often been unsatisfactory. However, recent interest has surged with the introduction of dorzagliatin and TTP399. This study investigates the efficacy of four previously studied compounds (Swertiamarin, Apigenin, Mangiferin, and Tatanan A) in activating GCK using computational methods. Initial molecular docking revealed binding affinities ranging from -6.7 to -8.6 kcal/mol. The compounds were then evaluated for drug-likeness and pharmacokinetic properties. Re-docking studies were performed for validation. Based on their favorable binding affinities and compliance with Lipinski's rule and ADMET criteria, three compounds (Swertiamarin, Apigenin, and Tatanan A) were selected for molecular dynamics (MD) simulations. MD simulations demonstrated that Swertiamarin showed excellent stability, as indicated by analyses of RMSD, RMSF, radius of gyration (Rg), hydrogen bonding, and principal component analysis (PCA). These results suggest that Swertiamarin holds promise for further investigation in in vivo and clinical settings to evaluate its potential in enhancing GCK activity and treating diabetes. This study assessed the potential of four compounds as GCK activators using molecular docking, pharmacokinetic profiling, and MD simulations. Swertiamarin, in particular, showed significant stability and adherence to drug-likeness criteria, making it a promising candidate for further research in combating diabetes.

01 Aug 2022·Diabetes, Obesity and Metabolism

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes

Article

Author: Valcarce, Carmen ; Klein, Klara R. ; Boeder, Schafer C. ; Madduri, Supradeep ; Dvergsten, Chris ; Freeman, Jennifer L. R. ; Pettus, Jeremy H. ; Giovannetti, Erin R. ; Dunn, Imogene ; Buse, John B.

AbstractAimsTo determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D).Materials and methodsTwenty‐three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n = 12) or placebo (n = 11) for 7 to 10 days. After the treatment period, an insulin withdrawal test (IWT) was performed, during which insulin pumps were removed to induce ketogenesis. The IWT was stopped after 10 hours or if blood glucose reached >399 mg/dL [22.1 mmol/L], if beta‐hydroxybutyrate (BHB) was >3.0 mmol/L, or for patient discomfort. The primary endpoint was the proportion of participants who reached BHB concentrations of 1 mmol/L or greater.ResultsDuring the 7‐ to 10‐day treatment period, mean fasting plasma glucose was significantly reduced ( −27.6 vs. −4.4 mg/dL [−1.5 vs. −0.2 mmol/L]; P = 0.03) and there were fewer adverse events, including hypoglycaemia, in the TTP399‐treated arm. During the IWT, no differences were observed between TTP399 and placebo in mean serum BHB concentration, mean duration of IWT, or BHB at termination of IWT. However, serum bicarbonate was numerically higher and urine acetoacetate was quantitatively lower in the TTP399‐treated participants. As a result of higher bicarbonate values, none of the TTP399‐treated participants met the prespecified criteria for diabetic ketoacidosis (DKA), defined as BHB >3 mmol/L and serum bicarbonate <18 mEq/L, compared to 42% of placebo‐treated participants.ConclusionsWhen used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA.

01 Jun 2022·Journal of Diabetes & Metabolic Disorders

Targeting human Glucokinase for the treatment of type 2 diabetes: an overview of allosteric Glucokinase activators

Review

Author: Sharma, Prateek ; Sharma, Neelam ; Grewal, Ajmer Singh ; Singla, Deepak ; Guarve, Kumar ; Singh, Sukhbir

Diabetes mellitus is a worldwide impacting disorder and the ratio through which the number of diabetic patients had increased worldwide, puts medical professionals to serious stress for its effective management. Due to its polygenic origin and involvement of multiple genes to its pathophysiology, leads to understanding of this ailment more complex. It seems that current interventions, such as dietary changes, life style changes and drug therapy such as oral hypoglycaemics and insulin, are unable to halt the trend. There are various novel and emerging targets on which the researchers are paying attention to combat with this ailment successfully. Human glucokinase (GK) enzyme is one of these novel and emerging targets for management of diabetes. Its availability in the pancreas and liver cells makes this target more lucrative. GK's presence in the pancreatic and hepatic cells plays a very important function for the management of glucose homoeostasis. Small molecules that activate GK allosterically provide an alternative strategy for restoring/improving glycaemic regulation, especially in type 2 diabetic patients. Although after enduring many setbacks in the development of the GK activators, interest has been renewed especially due to introduction of novel dual acting GK activator dorzagliatin, and a novel hepato-selective GK activator, TTP399. This review article has been formulated to discuss importance of GK in glucose homeostasis, recent updates on small molecules of GK activators, clinical status of GK activators and challenges in development of GK activators.

News (Medical) associated with Cadisegliatin

12 Nov 2024

·www.globenewswire.com

vTv Therapeutics Announces 2024 Third Quarter Financial Results and Provides Corporate Update

HIGH POINT, N.C., Nov. 12, 2024 (GLOBE NEWSWIRE) -- vTv Therapeutics Inc. (Nasdaq: VTVT), a clinical stage biopharmaceutical company with a portfolio of novel small molecules and a lead program in diabetes, today reported financial results for the third quarter ended September 30, 2024, and provided an update on recent corporate developments. "Our cadisegliatin program continues to show promise as a new oral adjunct therapy being investigated for improvement in glycemic control and reduction of hypoglycemia in patients with type 1 diabetes. During the quarter, our team made progress addressing the basis for the clinical hold placed on our clinical program by the Food and Drug Administration in July,” said Paul Sekhri, Chairman, President and Chief Executive Officer of vTv Therapeutics. "We look forward to continuing our discussion with the FDA regarding the clinical hold and our clinical program for cadisegliatin." Third Quarter 2024 Financial Results Cash Position: The Company’s cash position as of September 30, 2024, was $41.6 million compared to $9.4 million as of December 31, 2023. This increase is largely due to proceeds from the private placement financing on February 27, 2024, and additional funds from the ATM Offering during the quarter ended September 30, 2024.Research & Development (R&D) Expenses: R&D expenses were $3.2 million and $2.8 million in each of the three months ended September 30, 2024, and 2023, respectively. The increase reflects higher indirect costs and other project-related expenses. This was partially offset by lower spending on cadisegliatin, primarily due to reduced costs in toxicity studies and drug manufacturing, countered by increased clinical trial start-up costs.General & Administrative (G&A) Expenses: G&A expenses were $3.3 million and $2.5 million for each of the three months ended September 30, 2024, and 2023, respectively. The increase was primarily due to increases in share-based expense, legal expense and higher payroll costs.Other Income (Expense), Net: Other income for the three months ended September 30, 2024, was $0.2 million and was driven by gains related to the change in the fair value of the warrants to purchase shares of our own stock. Other expense for the three months ended September 30, 2023, was $3.3 million and was driven by an impairment charge on a cost-method investment. This was partially offset by an unrealized gain from the Company’s investment in OnKure and gains from changes in the fair value of warrants to purchase shares of our own stock issued to related parties.Net Loss: Net loss attributable to vTv shareholders for the three months ended September 30, 2024, was $4.8 million or $0.88 per basic share. Net loss attributable to vTv shareholders for the comparable period a year ago was $6.7 million or $3.19 per basic share. vTv Therapeutics Inc.Condensed Consolidated Balance Sheets(in thousands) September 30,2024 December 31,2023 (Unaudited) Assets Current assets: Cash and cash equivalents$41,571 $9,446 Accounts receivable 242 102 Prepaid expenses and other current assets 1,060 1,044 Current deposits 85 65 Total current assets 42,958 10,657 Property and equipment, net 50 117 Operating lease right-of-use assets 156 244 Total assets$43,164 $11,018 Liabilities, Redeemable Noncontrolling Interest and Stockholders’ Equity (Deficit) Current liabilities: Accounts payable and accrued expenses$6,226 $10,242 Current portion of operating lease liabilities 181 169 Current portion of contract liabilities 17 17 Current portion of notes payable — 191 Total current liabilities 6,424 10,619 Contract liabilities, net of current portion 18,669 18,669 Operating lease liabilities, net of current portion 32 169 Warrant liability, related party 82 110 Warrant liability 44 — Total liabilities 25,251 29,567 Commitments and contingencies Redeemable noncontrolling interest — 6,131 Stockholders’ equity (deficit): Class A Common Stock 26 21 Class B Common Stock 6 6 Additional paid-in capital 311,060 256,335 Accumulated deficit (296,084) (281,042)Total stockholders’ equity (deficit) attributable to vTv Therapeutics Inc. 15,008 (24,680)Noncontrolling interest 2,905 — Total stockholders’ equity (deficit) 17,913 (24,680)Total liabilities, redeemable noncontrolling interest and stockholders’ equity (deficit)$43,164 $11,018 vTv Therapeutics Inc.Condensed Consolidated Statements of Operations(in thousands, except per share data) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2024 2023(*) 2024 2023(*) (Unaudited) (Unaudited)Revenue$— $— $1,000 $— Operating expenses: Research and development 3,224 2,824 9,312 11,457 General and administrative 3,282 2,544 10,976 9,338 Total operating expenses 6,506 5,368 20,288 20,795 Operating loss (6,506) (5,368) (19,288) (20,795)Interest income 504 131 1,136 384 Interest expense — (4) — (6)Other income (expense), net 162 (3,299) (16) (1,108)Loss before income taxes and noncontrolling interest (5,840) (8,540) (18,168) (21,525)Income tax provision — — 100 — Net loss before noncontrolling interest (5,840) (8,540) (18,268) (21,525)Less: net loss attributable to noncontrolling interest (1,057) (1,886) (3,440) (4,753)Net loss attributable to vTv Therapeutics Inc.$(4,783) $(6,654) $(14,828) $(16,772)Net loss attributable to vTv Therapeutics Inc. common shareholders$(4,783) $(6,654) $(14,828) $(16,772)Net loss per share of vTv Therapeutics Inc. Class A common stock, basic and diluted$(0.88) $(3.19) $(2.70) $(8.04)Weighted average number of vTv Therapeutics Inc. Class A common stock, basic and diluted 5,456,307 2,084,973 5,498,479 2,084,973 (*) Adjusted retroactively for reverse stock split About vTv Therapeutics vTv Therapeutics Inc. is a late-stage biopharmaceutical company focused on developing oral, small molecule drug candidates. vTv's clinical pipeline is led by cadisegliatin, a potential adjunctive therapy to insulin for the treatment of type 1 diabetes. vTv and its development partners are investigating additional indications including type 2 diabetes and other chronic conditions. Forward-Looking Statement This release contains forward-looking statements, which involve risks and uncertainties. These forward-looking statements can be identified by the use of forward-looking terminology, including the terms “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and, in each case, their negative or other various or comparable terminology. All statements other than statements of historical facts contained in this release, including statements regarding the timing of our clinical trials, our strategy, future operations, future financial position, future revenue, projected costs, prospects, plans, objectives of management and expected market growth are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Important factors that could cause our results to vary from expectations include those described under the heading “Risk Factors” in our Annual Report on Form 10-K and our other filings with the SEC. These forward-looking statements reflect our views with respect to future events as of the date of this release and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. These forward-looking statements represent our estimates and assumptions only as of the date of this release and, except as required by law, we undertake no obligation to update or review publicly any forward-looking statements, whether a result of new information, future events or otherwise after the date of this release. We anticipate that subsequent events and developments will cause our views to change. Our forward-looking statements do not reflect the potential impact of any future acquisitions, merger, dispositions, joint ventures, or investments we may undertake. We qualify all our forward-looking statements by these cautionary statements. ContactAshley RobinsonLifeSci Advisors, LLCarr@lifesciadvisors.com

Financial Statement

09 Sep 2024

·www.pharmaceutical-technology.com

Epsilogen secures additional funds in Series B for cancer treatment

The funds will support the trial of MOv18 IgE to potentially treat platinum-resistant ovarian cancer. Credit: Jo Panuwat D/Shutterstock. Epsilogen has completed a Series B expansion financing round, raising £12.5m ($16.4m) to progress the development of its immunoglobulin E (IgE) antibodies for cancer treatment. The investment was sourced entirely from existing backers British Patient Capital, the Novartis Venture Fund, Epidarex Capital, the 3B Future Health Fund and ALSA Ventures. The latest funding takes the total raised in the Series B financing round to £43.25m. The funds will primarily support the clinical proof of concept for MOv18 IgE, the company’s leading asset, in a Phase Ib trial targeting platinum-resistant ovarian cancer. MOv18 IgE, a therapeutic IgE antibody, is designed to target the folate receptor alpha (FRα) which is prevalent in various cancers. See Also: LACTIN-V by Osel for Human Papillomavirus Infections: Likelihood of Approval Cadisegliatin by VTv Therapeutics for Type 1 Diabetes (Juvenile Diabetes): Likelihood of Approval The Phase Ib trial of MOv18 IgE will have dose escalation and expansion parts, enrolling patients with FRα-positive PROC who have undergone up to four previous treatments. The trial follows a Phase I study where MOv18 IgE showed safety, tolerability and initial signs of clinical activity. MOv18 IgE’s unique mechanism of action is different from that of other clinical agents, due to its high-affinity binding to FcεR1 that promotes immunosurveillance and robust tumour cell destruction by myeloid cells. IgE antibodies have the potential to alter the tumour immune microenvironment, making it more pro-inflammatory, which results in higher levels of activated T cells and macrophages within the tumour, enhancing its destruction. Established in 2017, Epsilogen is a spin-out from King’s College London, UK. Its CEO Tim Wilson stated: “We are delighted to have received strong continued support from our existing investors, and we thank them. “The promise of IgE to treat cancer is based upon its unique mechanism of action and MOv18 IgE is the first ever to be tested in man. Everything is ready for phase Ib initiation which will occur shortly and we look forward to reporting progress from the trial.”

Phase 1INDPhase 2Immunotherapy

09 Sep 2024

·www.pharmaceutical-technology.com

Sun Pharma and Moebius gain FDA fast track for osteoarthritis drug

In Phase IIb trial, the product provided substantial pain relief in osteoarthritis knee pain patients. Credit: VPLAB/Shutterstock. Sun Pharmaceutical Industries (Sun Pharma) and Moebius Medical have received fast track designation (FTD) from the US Food and Drug Administration (FDA) for MM-II (Large Liposomes of DPPC [dipalmitoylphosphatidylcholine] and DMPC [1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine]), a non-opioid treatment for osteoarthritis knee pain. Osteoarthritis is a common chronic joint disease marked by the deterioration of joint cartilage. The FTD aims to expedite the development and review of treatments for serious conditions with unmet medical needs. This programme will accelerate the availability of new medicines that could significantly improve patient outcomes. Sun Pharma and Moebius will benefit from more frequent communication with the FDA and the possibility of an expedited approval process. See Also: LACTIN-V by Osel for Human Papillomavirus Infections: Likelihood of Approval Cadisegliatin by VTv Therapeutics for Type 1 Diabetes (Juvenile Diabetes): Likelihood of Approval Moebius Medical CEO Moshe Weinstein stated: “This fast track designation, which will enable the FDA to review MM-II in an expedited manner, is an important milestone in the development of MM-II and follows our recently released Phase IIb data, which showed MM-II’s potential to provide effective and durable treatment for patients with knee pain of osteoarthritis.” MM-II is based on a technology involving large liposomes composed of DPPC and DMPC, designed to reduce joint friction and wear, thereby alleviating pain. The potential of MM-II was demonstrated in a Phase IIb clinical trial (NCT04506463), where a single 3ml intra-articular injection provided substantial pain relief compared to a placebo for up to 26 weeks. The companies are now preparing for confirmatory Phase III clinical trials to further evaluate the efficacy and safety of MM-II. Sun Pharma Global Development head and senior vice-president Marek Honczarenko stated: “As we enter Phase III development, we are very encouraged by the FDA’s decision to grant fast track designation to MM-II and recognise its potential to fill an unmet medical need for patients suffering from osteoarthritis.”

Phase 2Fast TrackClinical ResultPhase 3

100 Deals associated with Cadisegliatin

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 1	Phase 3	US	vTv Therapeutics, Inc.	14 Jun 2024
Diabetes Mellitus, Type 2	Phase 3	US	vTv Therapeutics, Inc.	01 Mar 2015

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03335371 (Simplici-T1 \| The Simplici-T1 Trial \| SimpliciT1, CTgov)	Phase 1/2	Diabetes Mellitus, Type 1	115	Placebo (Part 1 Placebo)	nzhtcbhehb(nbodobvszh) = eclkgskpng mbgecltkgu (npsycoayir, zensemkpke - rjjnrnhwjg) View more	-	03 Jul 2023
				TTP399 (Part 1 TTP399 800 mg)	nzhtcbhehb(nbodobvszh) = judxakdgto mbgecltkgu (npsycoayir, wiyzcwqsmp - qdozfolxgv) View more
ADA2022	Not Applicable	Diabetes Mellitus, Type 1	23	TTP399	yipbxyfrmu(aiwgcecgbo) = No patients on TTP399 met prespecified criteria for DKA while 43% of subjects on placebo did cslekzxozu (yvfbavasdd ) View more	-	01 Jun 2022
				Placebo
NCT03335371 (SimpliciT1, Pubmed \| Diabetes Care)	Phase 1/2	Diabetes Mellitus, Type 1	115	TTP399 800 mg	(grioqylxfs) = rnyleawptu xnuymyobbi (bhfjoptjpm, -1.3, - 0.07)	Positive	23 Feb 2021
NCT03335371 (Simplici-T1, EASD2020)	Phase 1/2	Diabetes Mellitus, Type 1	-	TTP399 800mg	(sxemrpwvvu) = jaxucrcbbz aklcfskxbp (sbboymitzi, -0.5 to -0.01) View more	Positive	22 Sep 2020
NCT03335371 (Simplici-T1, EASD2020)	Phase 1/2	Diabetes Mellitus, Type 1	-	TTP399 800mg	(fpsddgjqtt) = mxiyqpypdo yzqtbvikdd (dygqulmszi ) View more	Positive	22 Sep 2020
				Placebo	(kqipgnezwb) = ueygisdncu saxopgmrzs (nbjcfgvgku )
NCT03335371 (The Simplici-T1 Trial, ADA2020)	Phase 1/2	Diabetes Mellitus, Type 1	85	TTP399 800 mg	(umzdrdztdz) = gpbnxwnoff msvitdzdvc (udlsbfvwpq, -0.50, - 0.13) View more	Positive	01 Jun 2020
				Placebo	(umzdrdztdz) = dxsjkiusgp msvitdzdvc (udlsbfvwpq, -0.38, - 0.02) View more
NCT02405260 (Pubmed \| Sci Transl Med) Manual	Phase 2	Diabetes Mellitus	190	TTP399	(xgpznjwbom) = TTP399 (800 mg/day) was associated with a clinically significant and sustained reduction in glycated hemoglobin, with a placebo-subtracted least squares mean HbA1c change from baseline of -0.9% mwzofodfjv (tvunoxpukx ) View more	Positive	16 Jan 2019
				Placebo

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