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Read Sarina’s Story

Targeting Cutaneous Venous and Lymphatic Malformations at Their Source.

Read Sarina’s Story

Targeting cutaneous venous and lymphatic malformations at their source.

PATIENTS

Venous and lymphatic malformations (VM and LM respectively) are types of congenital vascular anomalies, which are present at birth. These malformations can cause a number of clinical complications including pain, bleeding and impairment of the function of the affected area. Many people living with either VMs or LMs have disfigurement, which can have a meaningful psychological and social impact.

Cutaneous VMs are characterized by overgrown, disorganized veins near the skin, and they may look like a blue discoloration of the skin.

Cutaneous LMs are fluid-filled sacs that do not drain properly due to abnormalities in the lymphatic system, and they tend to become infected and may require repeated antibiotic treatments. Cutaneous LMs often lie just under the skin or involve other tissues close to the skin.

Both VM and LM channels have little to no flow and are susceptible to the formation of clots, also known as coagulopathy.

Current treatment options are limited to surgery, sclerotherapy, laser treatments, and compressive garments. There are no pharmacological therapies currently approved for people with cutaneous VM and LM.

CLINICAL TRIALS

Venthera is developing VT30 topical gel intended to treat VMs, LMs and VLMs. Venthera has initiated a first in human phase 1/2 trial of topical VT30 in patients with VMs, LMs or VLMs.

For more information, please visit clinicaltrials.gov or fill out the contact form.

Clinical Trial News

Clinical Trials Contact

SCIENCE

The majority of VMs and LMs are caused by somatic mutations in either the TEK or PIK3CA gene. These genes encode the proteins Tie2 and PI3Kα respectively, both of which are key proteins in the PI3Kα/AKT signaling pathway. This signaling pathway plays a central role in the development and maintenance of healthy venous and lymphatic channels. TEK and PIK3CA mutations result in the abnormal activation of the PI3Kα/AKT signaling pathway, which in turn drives increased growth and survival of the endothelial cells that line venous and lymphatic channels. The increased signaling results in overgrown and malformed venous and lymphatic channels.

VM or LM are often considered “mosaic” because only a fraction of cells in a person contain the mutation. The number of the cells that contain the mutation determines the extent of the VM or LM, which can sometimes be associated with overgrowth. Because the mutation arises during fetal development, it is only present in subsequently dividing cells, and these cells ultimately comprise the VM or LM.

OUR APPROACH

Our approach to treating VMs and LMs focuses on getting the right medicine to the right tissue.

PIK3CA mutationTEK mutation
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Right drug: PI3K inhibition targets VM and LM at their genetic source

No Mutation
PIK3CA Mutation
Treated with PI3K Inhibitor

Activation of the Tie2 receptor stimulates the PI3K pathway, leading to healthy cell proliferation.

Increased activation of the PI3K pathway leads to the underlying cellular changes in VM and LM.

VT10 reduces PI3K signaling.

Right drug: PI3K inhibition targets VM and LM at their genetic source

No Mutation
TEK Mutation
Treated with PI3K Inhibitor

Activation of the Tie2 receptor stimulates the PI3K pathway, leading to healthy cell proliferation.

Increased activation of the PI3K pathway leads to the underlying cellular changes in VM and LM.

VT10 reduces PI3K signaling.

Targeting the PI3K pathway emerged as a promising clinical approach in a 2016 paper from Castel, et al., that demonstrated activating mutations of the PIK3CA gene in mice gives rise to venous malformations and that treating those mice with topical PI3K inhibitors achieved a rapid and sustained regression of skin lesions.1 Human data from a compassionate use study (Venot, 2018) has demonstrated that oral administration of a PI3K inhibitor quickly and markedly improves VMs and LMs in PIK3CA-related overgrowth spectrum (PROS) patients – indicating that PI3K inhibition is a potentially effective therapeutic approach.2 Based on these encouraging earlier results, we believe that delivering a PI3K inhibitor to the skin and structures close beneath has the potential to be an effective way of managing VMs/LMs.

VT10 targets VMs and LMs at their genetic source, suppressing the PI3K signaling pathway that drives growth of these lesions. Our in vitro and in vivo experiments have shown that VT10 can suppress PI3K signaling and reduce the viability of VM cells.

References
1. Castel, P., et al. “Somatic PIK3CA mutations as a driver of sporadic venous malformations.” Sci Transl Med. (2016).
2. Venot, Q., et al. “Targeted therapy in patients with PIK3CA-related overgrowth syndrome.” Nature. (2018).

Right tissue: VT30 topical gel is designed for direct delivery to cutaneous lesions

Our lead product, VT30 topical gel, is designed to target the right tissue – the network of malformed vasculature lying just underneath the skin. It is a gel formulation optimized for skin permeation. Once VT30 crosses the skin, it is cleaved by naturally occurring enzymes to produce VT10, a potent inhibitor of PI3Kα. Our local transdermal approach is designed to deliver the drug directly to the cutaneous lesion, bypassing the need for systemic administration.

ABOUT US

Venthera, an affiliate of BridgeBio Pharma, is a biotechnology company focused on developing therapeutics for the treatment of venous and lymphatic malformations, congenital conditions that are driven by activating mutations of the PI3K signaling pathway. We aim to develop a safe and effective treatment for these painful disorders as quickly and safely as possible.

LEADERSHIP

Thomas Rossi, PhD

Chief Executive Officer

Ken Truitt, MD

Chief Medical Officer

Kahlil D’Souza

VP of Business Development and Operations

Lisa Pugliese

VP of Clinical Operations

CLINICAL ADVISORY BOARD

Dra. Eulalia Baselga (Co-founder)

SJD Barcelona Children’s Hospital

Dr. Ilona Frieden

University of California, San Francisco

Dr. Laurence Boon

Cliniques Universitaires Saint-Luc

Dr. Beth Drolet

University of Wisconsin Madison

Dr. Denise Adams

Boston Children’s Hospital

Dr. Guillaume Canaud

Necker Hospital, Paris

Our work continues in memory of our co-founder, Dr. José Baselga. A pioneer in targeted oncology and beyond, his work has impacted countless patients.

SCIENTIFIC ADVISORY BOARD

Pau Castel, PhD (Co-founder)

University of California, San Francisco

Kevan Shokat, PhD

University of California, San Francisco

Miikka Vikkula, MD, PhD

Université Catholique de Louvain

Bart Vanhaesenbroeck, PhD

University College London

VENTHERA IS A MEMBER OF
THE BRIDGEBIO FAMILY

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.

www.BridgeBio.com

SCIENTIFIC PUBLICATIONS

Targeted Therapy in Patients with Pik3ca-Related Overgrowth Syndrome
Venot Q & Canaud G. Nature. 2018 Jun;558(7711):540-546. doi: 10.1038/s41586-018-0217-9. Epub 2018 Jun 13.

Somatic PIK3CA Mutations as a Driver of Sporadic Venous Malformations
Castel P & Baselga J. Sci Transl Med. 2016 Mar 30;8(332):332ra42. doi: 10.1126/scitranslmed.aaf1164.

NEWS

BridgeBio Pharma And Affiliate Venthera Announce Dosing Of First Patient In Phase 1/2 Clinical Trial Of BBP-681 For Venous, Lymphatic, And Venolymphatic Malformations

CONTACT

421 Kipling Street
Palo Alto, California 94301

To receive updates or get in touch, contact us at:
info@venthera.com

© Venthera 2023
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