Delving into the Latest Updates on TUTI-16 with Synapse

Overview

Basic Info

Drug Type

Therapeutic vaccine

Synonyms

Target

HIV-1 tat

Mechanism

Tat (HIV) inhibitors(Human Immunodeficiency Virus tat Gene Products inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

HIV Infections

Originator Organization

Thymon, LLC

Active Organization-

Inactive Organization

Thymon, LLC

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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This protocol represents the first in human study of TUTI-16, and is being conducted to establish the safety and human immunogenicity (anti-HIV-1 Tat titers) of subcutaneously administered TUTI-16. Activity of TUTI-16 will also be determined in minimizing HIV-1 viral loads and sustaining CD4+ T-cell levels.

Start Date01 Feb 2009

Sponsor / Collaborator

Thymon, LLC

100 Clinical Results associated with TUTI-16

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100 Translational Medicine associated with TUTI-16

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100 Patents (Medical) associated with TUTI-16

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3

Literatures (Medical) associated with TUTI-16

16 Oct 2012·Human Vaccines & ImmunotherapeuticsQ3 · MEDICINE

HIV rebound with current ART appears to be due to infection with new endogenous founder virus and not to resurgence of pre-existing Tat-dependent viremia

Q3 · MEDICINE

Article

Author: Mardik Donikyan ; Eve Damiano ; Erik Beckwith ; John Chicca ; Malika Pasha ; Gideon Goldstein

CD4 T cell activation, essential for productive HIV infection, is provided initially in acute HIV infection by innate immune system secretion of activating cytokines. This cytokine response wanes with time and long-term activation of CD4 cells is maintained by HIV Tat protein secreted by HIV infected cells. Structured treatment interruption (STI) in well-controlled antiretroviral-treated (ART) subjects was explored a decade ago with a consensus finding that, in most subjects, HIV levels rebounded within four weeks to pre-ART levels. Based on these observations we initiated a randomized placebo-controlled study of a universal anti-Tat epitope vaccine, TUTI-16, to determine if immunological blockade of Tat would prevent HIV rebound after ART cessation. TUTI-16 immunization was safe, with predominantly mild local and systemic injection-related adverse reactions. TUTI-16 was also immunogenic, with high levels of anti-Tat antibodies compared with levels previously shown to reduce HIV replication in vivo. Of 21 subjects analyzed, 13 (62%) had HIV rebounds vs. 8 (38%) that remained aviremia, but this distribution was not vaccine-related (p = 0.61 log-rank (Mantel-Cox) test), nullifying our hypothesis that anti-Tat antibodies would block rebound of Tat-dependent set-point HIV viremia after ART cessation. Our present findings are consistent with recent molecular findings that rebounding virus following STI is homogeneous and unrelated to previous circulating HIV, suggesting that rebounding HIV represents new founder virus, akin to the original acute HIV infection. We propose, therefore, that STI may have potential as a practical and economical approach to testing the safety and efficacy of candidate prophylactic HIV vaccines.

16 Apr 2012·Human Vaccines & ImmunotherapeuticsQ3 · MEDICINE

Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naïve and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects

Q3 · MEDICINE

Article

Author: Gideon Goldstein ; John J Chicca

TUTI-16 is a synthetic universal HIV-1 Tat epitope vaccine, designed to induce anti-Tat antibodies that block the function of circulating Tat, an HIV encoded protein secreted by HIV-1 infected cells. Circulating Tat activates CD4 T cells, permitting HIV replication and sustained viremia. Safety, immunogenicity and antiretroviral potential of TUTI-16 were explored in a randomized double-blind dose-escalating study in asymptomatic treatment-naïve HIV-1 infected subjects. TUTI-16 was safe, with mild local and systemic injection-related adverse reactions, but the antibody response was barely detectable. Surprisingly, a highly statistically significant reduction of HIV-1 viral load was found in the lowest 30 μg vaccine dose group (p < 0.01) but not at the higher doses. We posited that an anti-Tat antibody response below the limit of detection inhibited HIV viral load at this dose, an effect nullified at higher vaccine doses by activating cytokines induced by adjuvant components in TUTI-16. To clarify this immunogenicity/activation conundrum open label immunogenicity studies were performed in healthy HIV uninfected and aviremic ART-controlled HIV-infected subjects. These established that (1) healthy HIV negative subjects had robust antibody responses, maximal with 1 mg TUTI-16, (2) ART-controlled aviremic HIV infected subjects had similarly robust antibody responses, and (3) adjuvant-induced increases of HIV viral load did not occur in the presence of ART. These studies provided us a basis for the design of a protocol to explore the therapeutic potential of TUTI-16 vaccination to provide drug free control of HIV-1 viremia.

01 Jan 2010·VaccineQ3 · MEDICINE

A universal anti-HIV-1 Tat epitope vaccine that is fully synthetic and self-adjuvanting

Q3 · MEDICINE

Article

Author: John J. Chicca ; Gideon Goldstein

Circulating HIV-1 Tat protein is essential for maintenance of the chronic HIV replication that predicates both HIV transmission and clinical progression to AIDS/death. A synthetic anti-Tat epitope vaccine (TUTI-16) was designed to induce neutralizing antibodies to Tat and, hopefully, provide immunological control of HIV replication. TUTI-16 is composed of (1) a conserved Tat B cell epitope (Tat 4-12), rendered universal by introducing known variant amino acids at variable positions 7, 9 and 12 during solid phase synthesis, (2) a promiscuous T helper sequence and (3) a lipopeptide toll-like receptor 2 (TLR2) agonist. TUTI-16 induced high titer antibodies against all 8 known variants of the Tat epitope.

100 Deals associated with TUTI-16

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 3	US	Thymon, LLC	01 Feb 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01335191 (THYMON-11001, CTgov)	Phase 1/2	HIV Infections	27	TUTI-16 (1.0 mg) (TUTI-16 (1.0 mg))	ihkthsmcqn(igougjaavh) = auwxypyvmf gwiqdfkhmy (pvyweoyetk, ighuaohght - sjqdhcezxo) View more	-	15 Feb 2013
				Placebo (Placebo)	ihkthsmcqn(igougjaavh) = ugyizcxryd gwiqdfkhmy (pvyweoyetk, zpymghekch - gvunjypggl) View more
NCT01144026 (THYMON-10001, CTgov)	Phase 1/2	HIV Infections	15	TUTI-16 (0.2mg) (TUTI-16 (0.2mg))	norfwoptlt(fifiekgkji) = nhpcrspszl tykedexozh (ysurgytiin, ijrxvpcvho - ptfemxkfsx) View more	-	15 Jan 2013
				TUTI-16 (1.0 mg) (TUTI-16 (1.0 mg))	norfwoptlt(fifiekgkji) = xmdkmcqxes tykedexozh (ysurgytiin, fskfcplzzb - gqrbczaouw) View more