A SUPER-powered WP Engine Atlas Test Site

Joe&#039;s Atlas Experimentation Site

Spanish pharmaceutical company Ferrer will co-develop and market Verge Genomics&#8217; investigational PIKfyve inhibitor VRG50635 for the treatment of <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) in Europe, Central and South America, Southeast Asia, and Japan, under a collaboration agreement announced by the two companies.
<a href="https://www.ferrer.com/en">Ferrer</a> will have exclusive co-development and commercialization rights to VRG50635 for the <a href="https://alsnewstoday.com/forms-of-als/sporadic-als/">sporadic</a> and <a href="https://alsnewstoday.com/forms-of-als/familial-als/">familial</a> forms of ALS in those regions. <a href="https://www.vergegenomics.com/">Verge</a> will retain the rights to using the medication for all indications in the U.S. and other countries not covered by the agreement.
“We&#8217;re thrilled to work with Ferrer to progress VRG50635 through clinical development and towards potential commercialization,&#8221; Alice Zhang, CEO and co-founder of Verge, said in a <a href="https://www.globenewswire.com/news-release/2024/03/25/2851439/0/en/Verge-Genomics-and-Ferrer-Announce-Agreement-to-Co-Develop-Clinical-Stage-ALS-Therapy-VRG50635.html">company press release</a>.
&#8220;Ferrer has extensive experience navigating clinical development and regulatory landscapes across the globe,&#8221; Zhang said. &#8220;They also understand the complex and variable payer and reimbursement environments in the territories in which we will collaborate.&#8221;
VRG50635 is an experimental oral therapy designed to slow ALS progression and potentially extend survival by boosting nerve cells&#8217; ability to clear the toxic protein clumps that accumulate in virtually all ALS cases.
[recommended-reading id=90522]
<h3>PIKfyve inhibitor, lysosome booster</h3>
The therapy, identified through Verge&#8217;s CONVERGE artificial intelligence platform, works by blocking the PIKfyve protein and increasing the number of lysosomes in cells. Lysosomes are cellular organelles that break down faulty or unwanted molecules. They are essential to prevent the accumulation of toxic proteins, and are usually faulty in ALS.
The collaboration is &#8220;important news for people living with ALS, their families, and their caregivers,&#8221; said Mario Rovirosa, CEO of Ferrer. &#8220;In line with our purpose to use business to fight for social justice, we are reinforcing our commitment to bring transformative therapeutic solutions for people living with severe and debilitating diseases.&#8221;
In preclinical studies, VRG50635 showed success in extending the survival of nerve cells from ALS patients and in models of motor neuron degeneration. It also was <a href="https://alsnewstoday.com/news/potential-oral-therapy-vrg50635-found-safe-healthy-adults/">deemed safe</a> at varying doses in healthy volunteers who took part in a <a href="https://www.isrctn.com/ISRCTN14792372">Phase 1 clinical trial (ISRCTN14792372)</a>.
A proof-of-concept <a href="https://clinicaltrials.gov/study/NCT06215755?term=VRG50635&amp;rank=2#study-overview">Phase 1b study (NCT06215755)</a> is now enrolling people with sporadic and familial <a href="https://alsnewstoday.com/forms-of-als/">types of ALS</a> to assess the safety and tolerability of VRG50635 in patients.
The trial, sponsored by Verge, expects to enroll 50 adult participants at sites in Canada and several European countries. Those taking part in the trial will receive multiple, ascending doses of the oral medication, followed by long-term treatment.
While the trial&#8217;s main goal is to determine the treatment&#8217;s safety, researchers will also look at secondary measures including changes in disease progression rates, levels of the nerve damage biomarker neurofilament light chain (NfL), and the treatment&#8217;s pharmacological properties.
Verge will also use its digital technology to objectively evaluate disease-relevant changes, including changes in speech and language, in patients.
“We believe VRG50635 represents a promising new approach to treating this devastating disease, and we look forward to combining our strengths to accelerate the development of this potential treatment, said Oscar Pérez, chief scientific and business development officer at Ferrer.

Ferrer to co-develop, market PIKfyve inhibitor VRG50635

A Phase 1b proof-of-concept clinical trial of the experimental oral therapy VRG50635 in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) is expected to launch in the coming months, according to the therapy&#8217;s developer, <a href="https://www.vergegenomics.com/" rel="nofollow">Verge Genomics</a>.
Verge also announced that the upcoming trial will use <a href="https://modality.ai/" rel="nofollow">Modality.AI</a>, a computer-based tool that performs automated assessments of language and speech patterns.
“Gradually deteriorating vocal communication is one of the major issues many people with ALS experience. It is, therefore, crucial for us to capture objective data to quantify changes in speech during therapeutic trials and explore how this data can be used to better understand the potential benefits of VRG50635,” Diego Cadavid, MD, Verge&#8217;s chief medical officer, said in a <a href="https://www.globenewswire.com/news-release/2023/11/29/2787605/0/en/Verge-Genomics-Will-Use-Modality-AI-in-Its-ALS-Phase-1b-Clinical-Trial-of-Its-Lead-Drug-Candidate-VRG50635.html">company press release</a>.
[recommended-reading id=88361]
<h3>ALS weakens muscles of mouth and throat, affecting speech</h3>
Clinical trials are the gold standard for testing <a href="https://alsnewstoday.com/experimental-treatments-for-als/">potential disease treatments</a>. One of the most important aspects to consider when designing these studies is determining their endpoints — that is, what measurements will be used to determine whether or not the experimental treatment is working.
&#8220;Endpoints used in ALS trials are often subjective, biased, and only limited objective biomarkers of neurological function are available,&#8221; said Anil Tarachandani, PhD, vice president and head of translational medicine at Verge.
ALS is characterized by the progressive death and dysfunction of motor neurons, the nerve cells that control voluntary movements. Degeneration of motor neurons impairs communication with muscles, leading to muscle weakness and atrophy (shrinkage). When muscles in the mouth and throat are affected, patients typically experience <a href="https://alsnewstoday.com/symptoms-of-als/#Speech_problems">problems with speech</a>, among the common <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms of ALS</a>.
Modality.AI uses a multimodal platform where a computer analyzes what patients say and how they say it. The platform doesn&#8217;t require a doctor or specialized equipment; it can be done using home devices like smartphones and laptops.
To analyze vocal recordings, Modality.AI uses machine learning, a branch of artificial intelligence, in which a computer is given a set of mathematical rules, called algorithms, alongside a heap of data. The computer uses the algorithms to &#8220;learn&#8221; from these data by detecting patterns, and patterns then be can applied to build models that help in understanding new data.
&#8220;There are several publications already on the ability of Modality’s platform to measure vocal communication in ALS. Using speech as an objective endpoint in ALS trials can provide evidence of the efficacy of potential therapeutic interventions, such as VRG50635,&#8221; Tarachandani said.
The platform &#8220;has been extensively used by the broader ALS community and can provide insights into ALS disease progression,&#8221; he added.
<h3>Trial in healthy adults supports VRG50635 tolerability and safety</h3>
VRG50635 is designed to block the activity of a protein called PIKfyve, which Verge identified as a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112156/">potential treatment target in ALS</a> using a machine learning analysis of biological data.
“At the core of both Verge Genomics and Modality.AI is the use of machine learning in combination with proprietary data sets to optimize drug development,” said David Suendermann-Oeft, PhD, founder and CEO of Modality.AI.
&#8220;While the Verge platform is designed to predict new drugs with a higher probability of clinical success, Modality.AI’s multimodal platform reduces inefficiencies in clinical trials of these new drugs, increasing the success probability … by delivering more accurate and comprehensive insights into how these drugs may benefit people with ALS,&#8221; he added.
Verge reported top-line data from a <a href="https://www.isrctn.com/ISRCTN14792372">Phase 1 trial (ISRCTN14792372)</a> of VRG50635 in healthy adults earlier this year. Results showed that the experimental <a href="https://alsnewstoday.com/news/potential-oral-therapy-vrg50635-found-safe-healthy-adults/">treatment was generally well tolerated</a> at varying doses and may be given once daily.
In addition to working with Modality.AI, Verge previously <a href="https://www.businesswire.com/news/home/20230523005354/en/Verge-Genomics-to-Incorporate-Emerald-Digital-Health-Technology-into-its-ALS-Phase-1b-Proof-of-Concept-Clinical-Trial" rel="nofollow">announced a collaboration</a> with <a href="https://emeraldinno.com/" rel="nofollow">Emerald Innovations</a> for the upcoming trial of VRG50635 in ALS patients.
Under this earlier collaboration, the trial will incorporate digital sensors made by Emerald in study participants&#8217; homes, allowing continuous monitoring of breathing, sleeping, walking, and other aspects of daily life that are impacted by ALS.

Changes in speech with ALS to be monitored in planned Phase 1b trial

VRG50635, an experimental oral therapy being developed by <a href="https://www.vergegenomics.com">Verge Genomics</a> for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), was found to be safe and well-tolerated in healthy volunteers, new Phase 1 trial data show.
Top-line data from the <a href="https://www.isrctn.com/ISRCTN14792372">trial (ISRCTN14792372)</a> also showed a promising tolerability and pharmacological profile supporting once-daily dosing.
The company is now planning to advance the treatment into a proof-of-concept study in people with <a href="https://alsnewstoday.com/sporadic-als/">sporadic</a> and <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial ALS</a> that’s expected to start in the final months of 2023.
“We are extremely encouraged by these initial results which highlight the favorable safety and tolerability profile of VRG50635,” Diego Cadavid, MD, chief medical officer of Verge, said in a <a href="https://www.businesswire.com/news/home/20230615018038/en/Verge-Genomics-Announces-Positive-Safety-and-Tolerability-Data-from-the-Phase-1-Clinical-Trial-of-VRG50635-a-Potential-Best-in-Class-Therapeutic-for-All-Forms-of-ALS">company press release</a>.
[recommended-reading id=21684]
<h3>VRG50635 works to block PIKfyve, identified by AI as therapeutic target</h3>
VRG50635 is a small molecule designed to block the PIKfyve protein, a potential therapeutic target in ALS. PIKfyve was identified by the company’s artificial intelligence (AI) platform after sorting a large amount of biological data stemming from brain and spinal cord samples of ALS patients.
The protein is thought to play a role in the endolysosomal pathway, a kind of recycling system inside cells that helps break down faulty or unneeded molecules to keep the cells clean and functioning properly.
In ALS patients, this recycling system is usually not working as needed, leading to the buildup of toxic protein clumps — a hallmark of the disease known to contribute to the death of motor neurons and the progression of <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a>. Motor neurons are the nerve cells that control muscle movement and are progressively lost in ALS.
VRG50635 <a href="https://alsnewstoday.com/news/verge-starts-first-human-trial-pikfyve-inhibitor-als/">advanced from discovery</a> to a first-in-human trial in four years. In the lab, it extended survival of nerve cells from ALS patients and models of motor neuron degeneration.
“The lack of predictive animal models is one of the greatest challenges to developing effective ALS therapies today,” said Alice Zhang, CEO and co-founder of Verge. “This is why we’re excited to advance VRG50635, a drug derived directly from human data, into trials in people with ALS.”
The Phase 1 trial tested VRG50635 versus a placebo in 80 healthy adult volunteers. The therapy was given at different doses once or multiple times over one week, starting with a low dose of 60 mg and gradually increasing it up to 1,800 mg in subsequent groups.
There were no serious side effects, and VRG50635 was considered safe. The therapy was also deemed well-tolerated at the highest planned dose.
Data also showed the maximum concentration of VRG50635 in the body and the total exposure to the drug increased in proportion to the dose. Its active metabolite had a half-life (the time taken for its concentration to reduce by half) of about 37 hours, suggesting that VRG50635 may be taken by mouth once daily.
[recommended-reading id=84924]
<h3>Data to be presented at upcoming European conference in Barcelona</h3>
More detailed data will be presented at the upcoming European Network to Cure ALS (ENCALS) 2023 meeting, which will be held July 12-14 in Barcelona, Spain.
“We look forward to sharing additional information at the ENCALS meeting in Barcelona next month and anticipate progressing to a proof-of-concept study in patients with sporadic and familial ALS later this year,” Cadavid said.
According to Zhang, the study is “designed to overcome historical challenges in ALS clinical trials by using state of the art technology, such as digital at-home devices and blood-based biomarkers, that can capture richer, higher-fidelity patient data and have the potential to detect efficacy with greater sensitivity.”

Tag: Verge Genomics

Ferrer to co-develop, market PIKfyve inhibitor VRG50635

Changes in speech with ALS to be monitored in planned Phase 1b trial

Potential ALS therapy, VRG50635, found to be safe in healthy adults