March 31, 2021
Precision Oncology News | March 19, 2021 | Caroline Hopkins | NEW YORK – After spending nearly two decades building out a multi-omics database rich with uniformlycollected samples from cancer patients around the world, Indivumed this week said it will use that data todevelop precision oncology drugs.
The Hamburg, Germany-based precision oncology company has teamed up with biopharma investing firmXlife Sciences to launch Ix Therapeutics. The drug development joint venture, according to Indivumed'sCEO Harmut Juhl, will have a close working relationship with Indivumed and use its resources to identifycandidates against a variety of molecularly defined tumor types, starting with colorectal and lung cancer.Juhl is now also the managing director of Ix Therapeutics.
Indeed, Ix Therapeutics would not be possible without Indivumed's IndivuType multi-omics database andits AI Advanced Analytics Platform. Indivumed has used its analytics platform to process and aggregate themulti-omics data and tissue samples in its biobank and distill from this information the specific targets itintends to go after with drugs developed by Ix Therapeutics.
"What Indivumed has developed is this unique multi-omics database with comprehensive biological cancerinformation linked with clinical information," Juhl said. "This allows us to look for targets … with our AIplatform, and to select those targets with a very high probability of being useful for drug development."
An example of this type of target, Juhl said, would be surface proteins that are differentially expressed ontumor cells. The multi-omics nature of the database, he pointed out, allows Indivumed "not only to definehow [the targets] are behaving in tumor and normal tissue, but also to put them in the full biologicalcontext, which means we can understand how the target is related to pathways [and] to certain biologicalco-events."
But as much as Indivumed brings to Ix Therapeutics on the target discovery and validation side, thecompany does not, on its own, have the necessary technologies to efficiently screen and select thetherapeutic antibodies it will use to develop treatments against these targets. That expertise will come fromanother player in the new joint venture: the functional antibody and antibody-drug conjugate developmentcompany Veraxa Biotech.
Xlife Sciences is a shareholder in both Veraxa Biotech and Ix Therapeutics and typically doesn't activelyinvolve itself much in the business operations of these firms beyond financing. In partnering with Indivumedto launch Ix Therapeutics, though, Xlife Sciences is helping Indivumed join its target identificationcapabilities with Veraxa's antibody screening capabilities, setting the stage for efficient drug development.
Veraxa uses its proprietary, high-throughput droplet microfluidic technology to screen millions of B cells forfunctional antibodies. After identifying the hits, Veraxa performs single-cell sequencing of these B cells anddelivers the antibody sequences to a drug development partner — in this case Indivumed by way of Ix Therapeutics — for target selection. Veraxa performs this work via licensing deals; companies come toVeraxa with cell lines overexpressing a particular target, and Veraxa screens up to 250,000 B cells in aneight-hour period to identify the possible functional antibodies. The company also has the technology totake these antibodies and build them into payload-delivering antibody-drug conjugates.
"The key [contribution] that Veraxa brings to the table is techniques to take a huge number of potentialantibodies available after the immunization step, then to select those antibodies that are most suitable andmost promising," Juhl said. He further highlighted as an advantage the speed with which Veraxa'smicrofluidic technology, originally developed by the European Molecular Biology Laboratory (EMBL)Institute in Europe, screens the B cells that produce these antibodies for functionality.
Given the speed of the screening platform, Juhl anticipates it won't be long before Ix Therapeutics hasearly-stage treatment candidates primed for validation. "This is a several-week process that goes veryfast," he said. "We are expecting to have first therapeutics within less than a year, depending of course onwhat we find."
After selecting the antibody candidates through Veraxa's technologies, Juhl explained that the next stepwill be to validate the candidates, a process that will again draw on Indivumed's multi-omics database andbiobank.
Juhl also sees Indivumed growing as a player in the diagnostics space, since the company intends tosimultaneously develop companion diagnostic assays for selecting patients for its future therapies. "Whenwe identify the target, we also identify the biological signatures around it, which means we can [develop]the companion diagnostic for the future use of this target and therapeutic," he said, adding that thecompany will develop such companion tests in parallel with the drugs.
Then, down the line, as the selected therapeutic candidates progress toward the clinic, Ix Therapeutics willeither look for pharmaceutical partners interested in in-licensing the candidates, or build out its ownresources to run preclinical trials on the therapies.
"When we validate these antibodies as targetable and functional, there is still the need to [perform] toxicityassays [and] look into animal experiments to test them in these models," Juhl said. "That is a process wewill either do ourselves or, if a pharma company is interested, we'll sell it at that stage and participate in thedownstream development."
These decisions will become clearer in the months to come. "It depends on what we find and how we canmove forward," Juhl explained, adding that Ix Therapeutics will likely need additional funding to advance itsdrug development ambitions.
Ix Therapeutics will first focus on advancing drugs for colorectal and lung cancer, not only because of thehigh incidence and mortality rates associated with these tumor types, but also because Indivumed has hadsome success in target identification in these cancers, according to Juhl. Ideally, he is hoping that IxTherapeutics will be able to develop treatments in a variety of tumor types that harbor these same targets.
It is also possible that the therapeutic antibodies that Veraxa identifies could work with other targetsidentified within Indivumed's database. "We have more than one hundred potential targets alreadyidentified, and we will check them for the particular application of the therapeutic antibodies," Juhlexplained.
As Ix Therapeutics works to advance these precision oncology drugs, Indivumed will continue to focus ongrowing the reach of its database and the utility of its platform. The global reach of IndivuType, and thenetwork of clinicians that contribute to it, will be key when it comes to ensuring these drugs can benefitpatients from disparate backgrounds, Juhl emphasized.
"Indivumed itself is a platform company," Juhl said. "We have this clinical network with which we work toobtain our samples … and our samples, because of their quality, give us the capacity to build thistremendous database into a tool that you can apply in many ways. One natural step now is to apply it forearly-stage drug development."