Can virus-like particles unleash a new wave of CRISPR treatments?; Fosun Pharma and Insilico team up in AI discovery deal
The biggest challenges in genome editing today have a lot less to do with how to build tools that can cut, paste or rewrite DNA and a lot more to do with how to get the tools we have to the right parts of the body.
One method is to employ the viral vectors commonly used in gene therapy, but CRISPR-Cas9 systems are often too large and cumbersome to fit inside these viruses, which also come with their own safety issues. Viral vectors also leave the genome-editing tool permanently expressed inside cells, even after it’s made the required edit, potentially leading to unwanted changes and other types of cell damage.
Another is to use the lipid-nanoparticles, or LNPs, made famous in mRNA Covid-19 vaccines. One company, Intellia, has already done so effectively, but it’s still difficult to target these particles anywhere but the liver.
In the last couple of years, though, researchers from leading CRISPR labs have zeroed in on another approach: Virus-like particles, or VLPs. Originally — and still — used as a vaccine platform, VLPs are particles that look like a virus and can, when engineered a certain way, enter a wide variety of cells as viruses do but don’t actually contain any genetic material.
As a Texas Tech lab showed in 2016, you can engineer HIV-like particles that deliver Cas9 into T cells with minimal off-target effects. Jennifer Doudna’s group and others have since demonstrated the same, largely with an eye toward making CAR-T cancer therapies or a sickle cell gene therapy that can be given by simple infusion, instead of through a costly and intensive procedure.
Largely, though, these VLPs have been inefficient, editing only a small number of the targeted cells. But on Tuesday in Cell, David Liu’s lab at the Broad Institute showed they engineered VLPs that can deliver base editors with significantly improved efficiency.
Although the work remains quite early, they showed they could knock down a key gene in liver cells in mice at similar levels to what Verve Therapeutics showed with an experimental LNP-delivered heart disease treatment. Potentially more impactfully, they were able to show editing in the central nervous system and eye, neither of which can be treated with the current generation LNPs.
“These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine advantages of both viral and non-viral delivery,” Liu said in an email. — Jason Mast
Fosun Pharma and Insilico team up in AI discovery deal
Two Asian biotechs announced a partnership this morning — focusing on four biological targets.
Insilico will receive $13 million upfront from Fosun Pharma for the R&D collaboration projects as part of the deal, which includes co-development of Insilico’s QPCTL program, potential milestone-based payments, and sharing commercialization profits from the QPCTL program. In addition, Fosun will make an equity investment of an undisclosed amount into Insilico.
The collaboration takes shape on two “tracks:” One, Insilico will take responsibility for delivering a preclinical candidate for the QPCTL program and advancing it to the IND stage. After which, Fosun Pharma will take the candidates, conduct clinical trials and co-develop the candidate globally.
On the second track, Fosun will nominate four therapeutic targets to be assessed by Insilico’s AI platform and R&D team, who are responsible for advancing drug candidates to the IND stage.
As part of the collaboration, Fosun will secure access to Insilico’s platforms in order to advance their own internal AI-powered discovery and development efforts. — Paul Schloesser
Allogene strikes cell therapy deal with Swiss biotech Antion Biosciences
Days after the FDA lifted its hold on Allogene’s off-the-shelf CAR-Ts, the company has more good news to share in the cell therapy space.
Allogene has inked a deal with Swiss biotech Antion Biosciences for its microRNA (miRNA) technology to advance multiplex gene silencing as an additional tool for making next-gen allogeneic CAR-Ts, the partners announced on Tuesday.
The South San Francisco-based company is putting down an undisclosed amount of cash upfront, plus an equity investment, milestones, and a single-digit royalty on sales. In return, Antion will collaborate with Allogene on oncology products for “a defined period,” and Allogene gets the global commercialization rights to any products developed using Antion’s technology.
Antion says the platform, dubbed miCAR, was shown in preclinical studies to silence multiple gene targets in a single step and has the potential for broad application across cell and gene engineering.
“We are excited to be working with Antion to explore how their miCAR technology may advance and accelerate Allogene’s research efforts aimed at creating best in class allogeneic cell therapies,” Rafael Amado, Allogene’s CMO and executive VP of R&D, said in a statement.
Late last week, the FDA agreed to lift the hold it had placed on Allogene’s full set of off-the-shelf CAR-Ts after evidence of chromosomal changes in one of the patients triggered a safety alert. CEO David Chang said in an interview that the company worked through the last 3 months with regulators to zero in on the exact trigger of the chromosomal mutations, and determined that the drug wasn’t involved. — Nicole DeFeudis
Less than a month after a PhIII flop, Aldeyra releases new PhII data backing its dry eye candidate
Aldeyra took a big hit at the end of last year when its dry eye candidate reproxalap missed the primary endpoint in a topline Phase III readout. Now, the company’s back with separate Phase II data that suggest the solution can contend with Novartis’ currently approved Xiidra.
Patient-reported ocular discomfort and itching were statistically lower in the reproxalap group than the Xiidra group, Aldeyra announced on Tuesday. While the company didn’t release any hard numbers, it did say discomfort and itching reached p-values of 0.002 and 0.01, respectively.
“The combination of rapid activity and improved tolerability evidenced by reproxalap in clinical testing has the potential to address significant compliance issues with currently available therapy, the median discontinuation rates of which are approximately one month,” CEO Todd Brady said in a statement.
While reproxalap met the primary endpoint of ocular redness in a different Phase II trial, the endpoint didn’t reach statistical significance in the Phase III TRANQUILITY readout, Aldeyra announced at the end of December. It did, however, meet the secondary endpoint for dry eye disease based on the Schirmer test, which determines whether a patient’s eye produces enough tears.
The Schirmer test has been accepted by the FDA as part of the basis for approval of other dry eye products, Aldeyra said. The Lexington, MA-based company is going forth with another Phase III study, dubbed TRANQUILITY-2, but it’s modifying the trial so that the primary endpoint will be met if statistical significance is achieved in either ocular redness or the Schirmer test. — Nicole DeFeudis
Oncology diagnostics biotech gets major Roche investment — to the tune of $290 million
Multiomics biotech Freenome announced a substantial investment from Roche this morning, sending their total capital raised over the $1 billion mark.
Roche invested $290 million into the California biotech, bringing Freenome’s total funding to more than $1.1 billion since the company was founded in 2014. This cash infusion follows Freenome’s recent Series D financing of $300 million last month.
The company was extending its multiomics platform from the raise last month — adding biomarkers for other cancer types currently embedded to develop tests in new indications and recently presented promising data in the detection of pancreatic cancer.
Next month, Freenome will expand and launch additional multi-cancer clinical studies focused on more tailored baskets of screening tests, based on an individual’s risk.
“With Roche’s investment and expertise, we’ll be able to further accelerate and augment the development of our platform to test for additional cancers, and expand our real-world data programs,” said Freenome’s CEO Mike Nolan in a statement. — Paul Schloesser