FDA Approves TrueBinding's Parkinson’s Phase 2A Trial

On November 18, 2024, TrueBinding, Inc., a company in the clinical stage of biotherapeutics, announced it has received FDA clearance for an Investigational New Drug (IND) application for TB006, a Biologic IgG4 antibody aimed at neutralizing Galectin-3. This promising treatment is aimed at potentially modifying the course of Parkinson’s Disease, an area with unmet medical needs.

Alan K. Jacobs, M.D., FAAN, the Chief Medical Officer of TrueBinding, highlighted the significance of this milestone, stating that the FDA's IND approval for TB006 represents a monumental step forward in treating Parkinson’s Disease on a global scale. TB006 is a pioneering therapeutic approach utilizing antibody selectivity to target the Galectin-3 protein, presenting a new hope for patients lacking disease-modifying options.

TB006, administered via monthly intravenous infusions, targets and neutralizes Galectin-3. This mechanism may facilitate the dissolution of neurotoxic oligomers, including alpha-synuclein, mitigate pro-inflammatory microglial activation, reduce cytokine release, and provide reparative benefits to intracellular lysosomes. With the IND application approved, TrueBinding is set to begin clinical trials for Parkinson’s in the U.S.

The clinical study will be a multi-center, placebo-controlled Phase 2A trial designed to evaluate the safety and efficacy of TB006 in treating early to mild Parkinson’s Disease. The study will include patients aged 50 to 80 years with Hoehn and Yahr grade 1 or 2 Parkinson’s Disease, diagnosed in the last five years, and either not on Parkinson’s medications or only on immediate-release Levodopa. The trial aims to enroll 62 patients, with an anticipated primary completion date in the first quarter of 2026.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, impacting dopamine-producing neurons. Around 70% of individuals with PD experience tremors. The symptoms of PD fluctuate throughout the day and can worsen with anxiety, fatigue, or the wearing off of medication. Regular exercise is beneficial in managing symptoms and enhancing life quality. Currently, Carbidopa/levodopa (Sinemet) remains the primary medication for PD, though treatment adjustments are often needed as symptoms evolve.

PD hinders dopamine production, essential for neurotransmission, affecting movement and non-motor functions like mood and motivation. Besides dopamine, PD alters other brain chemicals. Nearly one million people in the U.S. and 10 million globally live with PD, with 90,000 new American cases annually. It is the second most prevalent neurodegenerative disease after Alzheimer’s, with numbers expected to rise due to an aging population.

Visible PD symptoms include tremors, slow movements, stiffness, and balance issues. Non-motor symptoms affecting mood and life quality, such as anxiety and sleep disturbances, also develop. Early signs are often mild and mistaken for normal aging. PD is typically diagnosed after age 60, but young-onset Parkinson’s Disease (YOPD) affects about 4% of those diagnosed, with men 1.5 times more likely to develop PD.

Researchers attribute PD to a mix of genetic, environmental, and other factors. A genetic link is present in 10-15% of cases. Diagnosis is based on symptoms, medical history, and physical exams, sometimes supplemented by lab tests and imaging to rule out similar conditions. PD diagnosis requires bradykinesia plus one or more of the following: resting tremor, limb stiffness, or balance issues.

Diagnosing PD can be time-consuming. Symptoms often lead individuals to consult a family doctor, who may refer them to a neurologist. Movement disorder specialists, neurologists with additional training in PD, can provide more refined diagnoses and treatments. While PD varies among individuals, most patients require medications to manage symptoms, enhancing dopamine function. Regular exercise significantly benefits both movement and non-movement symptoms, improving overall life quality. In some cases, surgical options might be viable. Given the complexity of PD, a multidisciplinary healthcare team, including physical, occupational, and speech therapists, as well as mental health and other specialists, is crucial for comprehensive care.

TB006 is a humanized monoclonal antibody with potential benefits for cognition and functioning in Alzheimer’s and Parkinson’s patients. Pre-clinical studies showed that Galectin-3 promotes aggregation of Aβ and pTau proteins. TB006 demonstrated reductions in Aβ/Tau protein aggregation and neuroinflammation, along with cognitive improvements in Alzheimer’s models. A Phase 1b/2 trial in Alzheimer’s patients showed positive trends in cognitive improvements. TB006 has also been evaluated in a Phase 2 open-label extension trial for Alzheimer’s and received FDA conditional use approval through an Expanded Access Program, demonstrating a favorable safety profile.

TrueBinding, Inc. is dedicated to developing innovative monoclonal antibodies for difficult-to-treat neurodegenerative diseases, including Alzheimer's and Parkinson's. The company is advancing TB006, aiming to make significant strides in treating these challenging conditions.