Venthera Doses First Patient With Topical Therapy Targeting Genetic Drivers of Rare Vascular Anomalies

BridgeBio Pharma, Inc. and affiliate Venthera recently announced the first subject has been dosed in its Phase 1/2 clinical trial of BBP-681 (also known as VT30 Topical Gel).

This novel investigational therapy is designed to target the genetic drivers of venous (VM), lymphatic (LM), and venolymphatic malformations (VLM) at their source by delivering a potent PI3Kα inhibitor directly to affected tissue. The majority of these cutaneous vascular malformations are driven by somatic mutations in the PIK3CA and TEK genes. These mutations result in overactivation of the PI3K pathway and have been identified as the root cause of the vast majority of VMs, LMs, and VLMs. Because BBP-681 is applied directly to skin lesions, it may minimize complications seen with systemic treatments.

Part 1 of the trial is a 4-week treatment, open-label dose escalation study that will determine the dose and regimen of BBP-681 to be carried into Part 2 of the protocol. Part 2 is a 12-week treatment, randomized, placebo-controlled, double-blind, safety and exploratory efficacy study of topically administered BBP-681.

People living with VMs, LMs, and VLMs have significant unmet medical needs related to pain, functional impairment, and disfigurement. Current treatment options include laser ablation, and invasive procedures such as sclerotherapy and surgical excision.  BBP-681 is the first potential therapy designed specifically to address the needs of people living with cutaneous forms of these lesions. There are 117,000 people estimated to be living with cutaneous VMs, LMs, and VLMs in the US and Europe.

“We are dedicated to giving hope to patients by developing new treatment options and working to improve mobility and alleviate discomfort of people living with cutaneous VMs, LMs, and VLMs. The initiation of this study represents an important milestone for the patient community as we translate cutting-edge science into a clinical-stage investigational therapy designed to target these conditions at their known genetic and tissue-specific source,” said Thomas M. Rossi, PhD, CEO of Venthera.

The Phase 1/2 study is currently enrolling up to 51 patients with venous/lymphatic malformations associated with PIK3CA or TEK gene mutations across multiple centers in the US to evaluate the safety and tolerability of BBP-681. The study will also determine the dose and regimen of BBP-681 to be carried into Part 2 of the protocol. Other aims include documenting plasma drug levels of BBP-681 and its active form VT10 and, on an exploratory basis, examining pharmacologic target engagement and change in potential efficacy readouts. For more information, visit https://clinicaltrials.gov/ct2/show/NCT04409145.

Venthera is dedicated to improving the lives of patients living with rare vascular anomalies by suppressing the underlying pathways that drive vascular anomaly growth. By targeting the genetic root cause of disease(s), Venthera is seeking to address unmet needs and create a new option for treating VMs, LMs, and VLMs with the hope of reducing the need for invasive and systemic treatments. As a member of the BridgeBio family, Venthera’s management team is supported by deep expertise in drug discovery, development, and innovation that advances its mission to bring safe and efficient new treatments to patients living with rare vascular anomalies.

BridgeBio is a team of experienced drug discoverers, developers, and innovators working to create life-altering medicines that target well-characterized genetic diseases at their source. BridgeBio was founded in 2015 to identify and advance transformative medicines to treat patients who suffer from Mendelian diseases, which are diseases that arise from defects in a single gene, and cancers with clear genetic drivers. BridgeBio’s pipeline of over 20 development programs includes product candidates ranging from early discovery to late-stage development. For more information, visit https://bridgebio.com/.