Of warheads and wellness

Cancer Research Technology and ADC Therapeutics join forces on antibody-drug conjugates

Jeffrey Bouley
LONDON—Cancer Research Technology (CRT), the commercial armof Cancer Research UK, and recent startup ADC Therapeutics Sarl (ADCT) inLausanne, Switzerland, in early July signed agreements to develop antibody-drugconjugates (ADCs) using CRT antibodies and peptides, and ADCT's "warhead" andlinker chemistries, to fight cancer. 
 
The warheads coming out of ADCT—which was recentlyestablished with $50 million from Celtic Therapeutics, a private equity firm,to develop a pipeline of as many as 10 new therapies based on ADCs—are based onproprietary technology around pyrrolobenzodiazepines (PBDs) that was developedby London-based Spirogen Ltd. It was in March of this year that ADCT andSpirogen announced a partnership to develop proprietary ADC products, and thatconnection to Spirogen provides a dual link for ADCT to CRT and Celtic, as someof the technology that went into Spirogen's formation was originally financed by Cancer Research UK academic funding,and Celtic is a major investor in Spirogen, notes Laura Fletcher,associate director of business management at CRT.
 
"Over the years we've had allkinds of dialogue with Spirogen, and a couple years ago, we started looking atwhether CRT had access to targeting agents that might fit well with their ADCtechnology," Fletcher tells ddn."With the founding of ADC Therapeutics, those discussions pretty muchtransferred over to them, but much of the management team is shared betweenADCT and Spirogen, so there's significant overlap and continuity. Many aspectsof the current agreement are extensions of deals we formed a year ago or morewith Spirogen to work on promising targeting agents and the current agreementsare to take the work into the in-vivorealm."
 
 
ADCT will initially fund preclinical studies for the newADCs in a range of cancer models, but other deal terms were not disclosed, norare the cancer targets a matter of public discussion yet.
 
 
However, Fletcher did share that,"The agents we are looking at are against targets that have not yet been testedin the ADC arena, which fits well with CRT's goal to fill gaps and exploreareas that others haven't—that makes this deal fit the box very well for us."
ADCs are a clinically important class of oncology drugsbecause they combine the specificity of antibodies with novel warheadchemistries, note ADCT and CRT. The antibody component selectively targets thecancer cells to deliver tumor-destroying chemicals that are internalized intothe cancer cell while avoiding damage to healthy tissue. Once inside the cancercell, the linker degrades and the active toxin is released, binding to thecell's DNA and killing the cancer cell. ADCT's toxic chemicals interact withDNA without disrupting the double helix structure that avoids triggering DNArepair processes. In part, it is hoped that this will prevent drug resistance. 
 
"ADCs are receiving a lot ofattention at the moment, in part because Seattle Genetics got an ADC productapproved recently, plus there's another product [Roche's Trastuzumab-DM1]showing promise in clinical studies," Fletcher explains. "There is a lot ofattention on the potential for ADCs to strike a therapeutic blow and taketoxins straight to the source to eliminate tumors. It's a field that hasgenerated great excitement, so it's a great time to be involved in this area."
 
 
"We are very excited to see our potent PBD-based warheadscombined with CRT's leading tumor-targeting antibodies and peptides," said Dr.Chris Martin, ADCT's collaboration manager and CEO of Spirogen, echoingFletcher's upbeat attitude in the news release about the deal. "Together, weare committed to faster and more efficient drug development, and have alreadycommenced our preclinical work for these exciting programs. We believe thisprovides a very promising and rapid route to develop novel ADCs for cancertherapy and are very much looking forward to working in partnership with CRT." 
 
Calling the collaboration"unique," Dr. Phil L'Huillier, CRT's director of business management,said in the same news release that the collaboration "marries ADCT's targetedportfolio with CRT's access to world-class cancer research supported by GBP 334million each year. We hope the collaboration will identify a range of ADCs thatcan be taken forward for development into innovative new ways to treat cancerand save lives."
 
 
While the collaboration is an important one, Fletcheremphasizes it isn't the only iron that CRT has in the fire.
 
 
"This is not an exclusiverelationship by any means, but it's great to have an avenue through which toexplore these three agents and maybe similar ones in the future, whether withADC Therapeutics or others," she says. "Also, this collaboration shouldn't betaken to mean that CRT is tied to ADC therapies in general, either. We welcomeand seek other partners and other kinds of agents."
 
 

 
Cancer ResearchTechnology and BioInvent in oncology deal
 
 
LONDON—Cancer Research Technology Ltd. (CRT) also announcedlast month that it has entered into a collaboration with BioInventInternational AB and Queen Mary, University of London, to identify newtherapeutic antibodies in oncology.
 
 
BioInvent and scientists funded by Cancer Research UK atQueen Mary, under the leadership of Dr. Thorsten Hagemann, Senior CancerResearch UK Fellow, will jointly be looking for new therapeutic targets byapplying BioInvent's F.I.R.S.T. technology, a functional approach totherapeutic antibody discovery. Hagemann and his team will provide thecollaboration with biological pathways for the development of new oncologytherapies.
 
 
The F.I.R.S.T. platform, through its biopanning technology,enables identification of functionally superior antibodies across multipletargets overexpressed by target cells. This combined target and drug discoveryplatform utilizes primary cancer patient cells, rather than recombinantproteins, as an antigen source allowing for discovery of novel specificities(receptors and epitopes) and target receptor functions. 

The agreement gives BioInvent the option to enter intolicenses to bring forward drug candidates beyond lead candidate identificationin exchange for milestones and royalties to CRT.
 
"By combining the preclinical expertise in animal modelswithin my laboratory and our access to patient samples with BioInvent'sF.I.R.S.T. technology we hope to speed up the discovery and development of newpossible treatments," said Hagemann in a news release announcing thepartnership. "We will focus primarily on targets which affect the pro-tumorrole of myeloid cells in solid malignancies, an area in which my lab hasdeveloped significant experience. We would anticipate such therapies to be applicableacross a range of tumor types."
 
 
"It is of majorimportance for BioInvent to tap into the vast knowledge base of a multi-prongedorganization such as Cancer Research Technology," added Björn Frendéus,BioInvent's vice president of preclinical development. "One of our first areasof interest will be in the biology of myeloid cells in cancer, which has beenan area of focus for us for many years."
 
 
 

Jeffrey Bouley

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