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Lentigen, Case Western Partner to Create Lentiviral-Based Stem-Cell Cancer Therapy

Lentigen last week said that it has exclusively licensed from Case Western Reserve University a DNA damage-repair gene that Lentigen will pair with its proprietary lentivirus delivery vectors to develop stem-cell therapies for glioblastoma, a form of brain cancer.
As part of the agreement, University Hospitals Case Medical Center, CWRU’s primary hospital affiliate, has the right to lead the first in vivo clinical trials of the therapy later this year. Should the therapy graduate Phase I clinical trials, Lentigen will be responsible for its further clinical development and commercialization, the company said.
“This is a fairly path-finding technology, and having created the technology, it’s clearly important for the [University Hospitals Case Medical] Center to undertake the first clinical trial,” Lentigen CEO Tim Ravenscroft told BTW this week.
Lentigen’s drug technology is based on the methylguanine-DNA methyltransferase, or MGMT gene, which was discovered by Anthony Pegg, a professor of cellular and molecular physiology and pharmacology at Penn State University; and Stan Gerson, director of the UHCMC’s Ireland Cancer Center.
The MGMT gene has been shown to repair damaged DNA, and Lentigen plans to use a specially designed lentivirus vector to deliver the gene to bone marrow stem cells that have been damaged by drugs commonly used to treat cancer, Lentigen said.
The first clinical trial will evaluate the potential of the lentiviral-MGMT technology to enhance current treatments for glioblastoma by repairing or preventing the damage they typically cause to bone marrow stem cells.
Gerson, who is also the director at CRWU’s Case Comprehensive Cancer Center and National Center for Regenerative Medicine, primarily developed the specific anti-cancer therapy applications of the gene. As a result, CWRU will manage the underlying IP, according to Boro Dropulic, founder, president, and CSO of Lentigen.
“Anthony Pegg was the original molecular biologist who first discovered the gene, and Stan is the guy that has really been involved in the clinical translation,” Dropulic said. “So they’ve sort of been working together.”
Specific financial details of the licensing agreement were not disclosed. However, Ravenscroft said that the deal “follows fairly conventional licensing terms.”
Calls to CRWU’s technology-transfer office were not returned in time for this publication.
This week, CWRU’s Gerson told BTW that although he could not share specific terms of the licensing agreement, it incorporated “the appropriate encompassing technology, milestones, and ability for us to continue to work together to develop new applications. I think it was pretty expansive, and I think it will continue to grow for both of our organizations,” Gerson said.
Another aspect of the licensing agreement ensures that the UHCMC’s Ireland Cancer Center would be the site of the Phase I clinical trials, said Gerson.
“CRWU handles the tech transfer, with the hospital an interested onlooker, because it would like to conduct the clinical trials,” Gerson said.
“There is a joint effort in tech transfer between UHCMC and CWRU,” he added. “The faculty members go through the university tech-transfer office, and the medical center is not a licensee. But the agreement allows the hospital to conduct the early-stage clinical trials.”
Gerson added that although he is “scientifically interested” in the outcome of the trials, he will not be involved in their administration.
Delivery to Drug Development
For Lentigen, the deal represents the first in a series of soon-to-be-disclosed collaborations with various non-profit research institutions, as well as the company’s first foray into using its lentiviral vectors in therapeutic applications, Ravenscroft told BTW.
Lentigen has traditionally sold its lentiviral delivery technology as research kits to companies and academic labs that use it to deliver molecules such as siRNAs into cells in vitro. However, Ravenscroft said that in recent years the company has decided to develop the vectors for therapeutic uses as well.

“Once you start to get animal data for a gene therapy, and you’re showing proof of concept in a large animal model, I get very excited about that.”

“Pairing our lentiviral vectors with promising gene targets is a critical part of our business model,” Ravnescroft said.
At first, the company plans to pursue this avenue by forging multiple collaborations, including with universities, Ravenscroft said. “But as we go forward, we intend to develop capabilities to develop therapeutics ourselves,” he added.
He said a recent example of this strategy is the opening of its new GMP-manufacturing facility in Gaithersburg, Md., where Lentigen will likely continue to clinically develop the MGMT treatment after CWRU finishes its Phase I trials of the drug.
Lentigen’s Dropulic told BTW that the company decided on CRWU and Gerson’s lab for its first collaboration because of Dropulic’s ongoing professional relationship with Gerson, and because of recent studies in dog and monkey models that showed a bone-marrow stem cell-enrichment effect when MGMT therapy was combined with temozolomide, a commonly administered drug for brain tumors.
“Once you start to get animal data for a gene therapy, and you’re showing proof of concept in a large animal model, I get very excited about that,” Dropulic said. “The next phase is proving it in humans, but having real animal data showing that you can protect stem cells from the effects of temozolomide is very exciting.”
Dropulic added that the MGMT gene-therapy technology has been in clinical development using a murine onco-retroviral vector, “but not a lentivral vector, and it hasn’t proven as effective a lentiviral vector potentially would be,” he said. “That’s why we’re excited to apply the efficient transducing properties of lentiviruses with the MGMT technology.”
According to Gerson, lentivirus delivery vectors are poised to become the “dominant player” in gene transfer in humans.
Lentivirus delivery vectors “have shown to be safer than retroviruses; more efficient than any other vector we have; stable; they don’t seem to cause insertional mutations at the rate of other vectors; and they’re more predictable,” Gerson said. “All of this hints that, going forward, this will be a better tool than most any other gene-transfer technology that is now available.”
As such, Gerson said that he expects his lab to continue working with Lentigen on other gene targets that would be appropriate for lentiviral-bases therapeutics, although he declined to say whether the partners have drawn up an official sponsored research agreement.
“There is a lot of inventory right now that they and we are developing, and there are going to be, over time, numerous other partners that will want to come and play in this space with the vector backbone from Lentigen and the gene that we’re providing,” Gerson said.

“As one can imagine the variety of modifications of the lentivirus to optimize gene transfer, combined with a whole second generation of genes that would be piggy-backed into this system, that would provide more clinical applications – and the sky’s the limit on what those genes might be,” he added.

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