Oxford spinout Theolytics launches with oncolytic virus tech

Theolytics debuts with a library of viral variants that could yield more selective oncolytic viruses than redesigning an existing virus

Theolytics emerged from stealth mode Wednesday with £2.5 million in seed financing from Oxford Sciences Innovation and a library of viral variants, against which it applies Darwinian theory to produce more selective oncolytic viruses, faster than humans can design them.

The company was spun out of Len Seymour's lab at the University of Oxford in 2017 with the idea of applying external pressures to viruses to force the emergence of a variant with a set of desired characteristics.

"It's the survival of the fittest phenomenon -- the best viruses out-compete the others," Theolytics Ltd. CEO Charlotte Casebourne told BioCentury.

She said traditional approaches to oncolytic virus design of optimizing a single virus variant can take 5-10 years, while Theolytics can isolate a new candidate in 6-12 months.

The main difference between other oncolytic virus companies and Theolytics, Casebourne said, is its in-house library of thousands of viral variants upon which it draws for its candidates, akin to phage display libraries used for antibody development.

"We're the first people in this field to do that," she said. "This is completely different than groups working with a virus that may originally have been a repurposed vaccine or lab virus, and then trying to arm it with various qualities."

Theolytics used three main technologies to develop its library, and will apply them to continue expanding the diversity of its library: bioinformatics, long-read sequencing and genetic engineering.

Casebourne said the company is continuously building viral DNA sequencing data sets, which allows it to measure and maximize the sequence of viruses and look at how the virus is infecting the cell. Because virus genomes are so diverse -- the homology between two variants can be less than 20% -- a combination of short and long read sequencing enables Theolytics to interrogate the genome and characterize the viruses. And with genetic engineering, Theolytics can transfer therapeutic genetic characteristics between viruses, further diversifying the library.

Theolytics then runs the library through its bioselection models, which are reverse-engineered to apply selection pressures to garner candidates with specific characteristics. While Casebourne declined to disclose what the pressures are or how they're applied within the model, she said Theoloytics can select viruses for selectivity, potency, immunogenicity and lytic potential. Different characteristics vary by indication.

The models can also select candidates for their ability to be systemically delivered via IV. Casebourne said many oncolytic viruses in development, as well as Amgen Inc.'s approved virus Imlygic talimogene laherparepvec, can only be delivered intratumorally.

Chairman Ken Powell added that the models themselves, which use patient-derived tumor tissue, are more clinically relevant than the cell culture models with which most other oncolytic virus companies develop and test their candidates.

This year, Theolytics will select its lead virus and which cancers it will initially focus on. Casebourne declined to disclose the number of Theolytics' preclinical programs or any potential indications.

Casebourne said the company plans to raise an undisclosed amount in its series A over the next year.

COMPANY PROFILE

Theolytics Ltd.

Oxford, U.K.

Technology: Oncolytic viral therapies

Disease focus: Cancer

Clinical status: Preclinical

Founded: December 2017 by Charlotte Casebourne, Margaret Duffy, Kerry Fisher and Len Seymour

University collaborators: University of Oxford

Corporate partners: NA

Number of employees: 11

Funds raised: £2.5 million ($3.2 million)

Investors: Oxford Sciences Innovation plc

CEO: Charlotte Casebourne

Patents: Undisclosed

Companies and Institutions Mentioned

Amgen Inc. (NASDAQ:AMGN), Thousand Oaks, Calif.

Theolytics Ltd., Oxford, U.K.

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