EBT-101

[MitchMiller]

After reading about it for a few years, CRISPR is about to be trialed in humans to excise HIV from cells.  The hope is that enough virus (including latent virus) can be removed from the body to accomplish a functional cure.  It has already worked on primates that have SIV. 

https://www.phillymag.com/healthcare-news/2021/03/05/excision-biotherapeutics-temple-hiv-clinical-trial/

[em]

new article on this https://www.popbuzz.com/life/news/hiv-cure-excision-biotherapeutics-ebt-101-trial/ this one is from facebook HIV long term survivors.
 https://www.gaytimes.co.uk/life/functional-cure-for-hiv-approved-for-human-trials/?fbclid=IwAR2HorT37AICI0j6Zyj_lPXee4Z7A8RVEDsrQiDVDntticuIF25PXKbjH6A

human trials ,    any thoughts

[Jim Allen]

human trials ,    any thoughts

The same thoughts I had in 2016 about Dr. Khalili work with CRISPR when they cured a mouse and in 2020 on the primate. Scientifically interesting but no other thoughts at such an early stage.

[CircularNatural]

It's so interesting to follow this kind of novel treatments... one can only be hopeful 

[Da2020]

They have posted it on clinicaltrails.gov in December and recently updated the trail start date as Jan 2022. If only they would start the trail. It is a very interesting approach and trail. They want to start ATI within 3 months which is definitely very interesting

[em]

trial information

https://clinicaltrials.gov/ct2/show/NCT05144386

[Da2020]

They have started the trail in St.Louis, MO

[Da2020]

They have presented a poster demonstrating, no off target cuts . At least we know its not going to create zombies

[geobee]

Another breathless "milestone" -- demonstrated "efficacy" against HIV.

https://www.americangene.com/news-releases/agt-hiv-blood-markers-of-efficacy-more-patients/

[Da2020]

Another breathless "milestone" -- demonstrated "efficacy" against HIV.

https://www.americangene.com/news-releases/agt-hiv-blood-markers-of-efficacy-more-patients/

They have reaped this news in February, there actually is a separate thread tracking them

[Cosmicdancer]

Excision BioTherapeutics Doses First Participant in EBT-101 Phase 1/2 Trial Evaluating EBT-101 as a Potential Cure for HIV

* EBT-101 is an in vivo CRISPR-based therapeutic designed to remove HIV proviral DNA from affected cell reservoirs

* First-in-human study will evaluate the safety and efficacy of EBT-101 in participants who chronically suppress HIV with daily antiretroviral therapy

* EBT-101 has been well tolerated to-date and the trial is proceeding as planned

SAN FRANCISCO, Sept. 15, 2022 (GLOBE NEWSWIRE) -- Excision BioTherapeutics, Inc., a clinical-stage biotechnology company developing CRISPR-based therapies intended to cure viral infectious diseases, today announced that the first participant has been dosed in the Phase 1/2 clinical trial of EBT-101 for human immunodeficiency virus type 1 (HIV-1). The participant was dosed in July 2022, with initial findings indicating EBT-101 has been well tolerated to-date. The participant continues to be monitored for safety and is expected to qualify for analytical treatment interruption (ATI) of their background anti-retroviral therapy (ART) in an evaluation of a potential cure.

“Dosing the first participant with EBT-101 is a landmark event that solidifies Excision’s position as a pioneer in gene editing,” said Daniel Dornbusch, Chief Executive Officer of Excision. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first ever clinical assessment of a multiplexed, in vivo gene editing approach. We were able to reach this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease."

https://www.tmcnet.com//usubmit/2022/09/15/9674271.htm

[Cosmicdancer]

The article is brief, so here it is in its entirety. Given that the first person treated with this CRISPR-Cas9 therapy was reported in September of last year, I assume that it has been found to be safe, although perhaps it's too early to know about its efficacy.


The Food and Drug Administration (FDA) has granted Fast Track designation to EBT-101, an investigational gene therapy, for the treatment of HIV-1.

EBT-101 uses an adeno-associated virus to deliver CRISPR-Cas9 and dual guide RNAs, which target and excise large portions of the HIV genome. The treatment is delivered as a single intravenous infusion and is being sought as the first curative therapy for HIV-1.

A phase 1/2 trial (ClinicaTrials.gov Identifier: NCT05144386) is evaluating the gene therapy in adult patients with HIV-1 (18 to 65 years old) who are on stable antiretroviral therapy (ART) with HIV RNA below the level of detection. The primary endpoint of the study is to assess safety and tolerability; efficacy assessments will also be conducted. At week 12, patients will be assessed for eligibility for an analytical treatment interruption of their background ART.

After 48 weeks post infusion, patients will be eligible to continue in a long-term follow-up study (ClinicalTrials.gov Identifier: NCT05143307) that is expected to last 15 years.

“We are pleased with the FDA’s decision to grant Fast Track designation to EBT-101,” said Daniel Dornbusch, Chief Executive Officer of Excision. “This designation underscores the importance of finding a cure for people living with HIV and bolsters Excision’s efforts to rapidly develop potentially curative therapies for significant unmet medical needs.”

The FDA’s Fast Track designation helps to accelerate the development and review of products for serious and life-threatening conditions where no treatment exists or where the investigational therapy is likely to provide an advantage over currently available treatments.

https://www.empr.com/home/news/drugs-in-the-pipeline/crispr-based-gene-therapy-candidate-fast-tracked-for-hiv-treatment/

[Towel]

That seems hopeful. But even if they did discover a cure, it would beat least another 5 years and further safety testing before it starts to reach the general population, no?

[Cosmicdancer]

I have no idea about the timeline, but I'm sure it would be years before this therapy is approved by the FDA. But given that this clinical trial started 11 months ago, it looks like they may have reached the 48 week post infusion end point for trial participants.  Perhaps some of the participants that began treatment interruption 13 weeks after the infusion are undetectable or have low viral loads. I'm just speculating about why the FDA is fast tracking this. If there's something newsworthy, I'm sure it will be reported at the next International conference on retroviruses (CROI) in the Spring of 2024. Meanwhile, I'm glad we have effective treatments with HAART.

[xxxyyy]

.

[Jim Allen]

@xxxyyy

Please read your thread:

https://forums.poz.com/index.php?topic=77265.msg

[Jim Allen]

General reminder for those living with HIV regarding posting in this Forum section: https://forums.poz.com/index.php?topic=11292.0

[Jim Allen]

POZ.com article in full: https://www.poz.com/article/crispr-gene-editing-removes-virus-cells

In Brief:

A single injection of a novel CRISPR gene-editing therapy known as EBT-100 safely and effectively removed simian immunodeficiency virus (SIV)—a virus related to HIV—from viral reservoirs in monkeys, according to a report in Nature Gene Therapy. The first human trial of the EBT-100 started last year.

“The long timeframe of the study and the use of high doses of the gene-editing construct help confirm the safety of EBT-001,” lead study author Tricia Burdo, PhD, of the Lewis Katz School of Medicine at Temple University, said in a news release. “Our preclinical work in non-human primates was essential for allowing us to establish the criteria for applying EBT-101 in clinical studies and enabling the [Food and Drug Administration] authorization for an HIV-specific gene-editing therapy to move forward.”

Senior investigator Kamel Khalili, PhD, of Temple University, and colleagues have been studying gene therapy to cure HIV for more than a decade. In 2014, they published a groundbreaking study showing that a CRISPR-Cas9 tool could delete a segment of integrated proviral DNA that includes the gene for HIV’s Gag protein, which is necessary for viral replication. A study published in 2019 showed that the technique could cut out integrated HIV genes and clear latent viral reservoirs in humanized mice. The next year, an early study in monkeys showed that the CRISPR tool excised segments of integrated SIV from blood cells and viral reservoir tissues.

“Our study supports safety and demonstrates evidence of in vivo SIV editing of a CRISPR gene-editing technology aimed at the permanent inactivation of virus in a broad range of tissues in a large, preclinical animal model, using a one-time injection of the treatment,” Khalili said. “The outcome of the preclinical model set the stage for the ongoing clinical trial of EBT-101.”

[Jim Allen]

https://www.poz.com/article/crispr-hiv-gene-therapy-looks-safebut-work

EBT-101, a novel CRISPR-based gene-editing therapy from Excision BioTherapeutics, was not associated with any serious adverse events in the first three treated study participants, researchers reported last week at the European Society for Gene & Cell Therapy annual meeting in Brussels. But the presentation was frustratingly short on data about whether the treatment works to control HIV.

According to the company, study participants will be followed for 48 weeks after EBT-101 administration, and all eligible participants will be assessed for sustained viral suppression after stopping antiretrovirals in an analytical treatment interruption starting at week 12. After the initial study, they will be enrolled in a long-term follow-up study (EBT-101-002).


The first participant who received EBT-101 in the summer of 2022 is already well past the 12-week mark when the treatment interruption should have commenced, but Excision has not provided any further information about his status. The company said in its press release that additional data would be presented in 2024.

While these initial results appear promising, it is far too soon to say that a functional cure for HIV is on the horizon.

“Scientists tell me that this is going to be part of a cure some day. And I shrug my shoulders and say, ‘Here we go again,’” long-term survivor and advocate Matt Sharp told the San Jose Mercury News. “Now we just have to get the research done. We’ve got to have hope, because the epidemic isn’t over.”

So, basically, there is no substantial update. I see that some other popular media outlets have been publishing misleading headlines this past week; I suppose it is the same old story: Publish whatever sells papers, gets clicks, improves your stock position or gets you funding, and the truth and damage caused be dammed.

 

[gorka]

not sure about this group but number of groups are gearing up for cell therapy or gene therapy approach using crispr.  it has been very succesful for some cancers so far. hoping it will eventually work for hiv