Private equity firm Celtic Therapeutics has placed a big bet on antibody drug conjugates (ADCs), pledging $50m to a Swiss start-up formed around ten proprietary oncology programmes. The eponymous ADC Therapeutics has an ambitious aim - to achieve clinical proof of concept in phase II studies with “several” of the projects within three to five years.
The company has effectively been spun out of UK oncology researcher Spirogen, which developed the linker and cytotoxic agents that will form the ADCs and last year attracted Genentech as a research partner over its conjugate technologies. Christopher Martin, the chief executive of Spirogen who will also sit on the board of the new company, says encouraging data that emerged in the last few years from the Genentech deal and other research projects encouraged the establishment of the new company, to push on independently with several proprietary candidates.
Celtic Therapeutics invested in Spirogen in 2009, specifically to fund the development of its lead drug, SG2000. It will be the majority owner of ADC Therapeutics.
Dr Martin says the $50m is “fully committed” to fund the business plan of the new company. To be headed by Michael Forer, a Celtic partner, ADC will push the first ten programmes through pre-clinical development over the next 12 months, and hopefully move the first projects into the clinic within two years. Partners will be sought after phase II proof of concept.
This is pretty speedy progress but Mr Martin says much of the groundwork has already been done, within Spirogen.
“In many ways the whole concept of forming this company came from the work we’ve been doing in Spirogen and preparing these assets,” he says. “The structure allows Spirogen, which already has research agreements underway, to carry on with that business model.”
As well as Genentech six other deals have been struck although not announced he says, as the company has spent the last few years filing and building its patent estate.
Spirogen’s most advanced candidate is SG2000, a pyrrolobenzodiazepine, a class of drug designed by the company, itself spun out of several institutions, including University College London, more than a decade ago. Phase II data from a trial being conducted in platinum resistant ovarian cancer should emerge later this year or early next, Dr Martin says.
Pyrrolobenzodiazepines or PBDs will form the cytotoxic “warheads” that ADC’s antibodies will deliver. They are DNA minor groove binding agents which bind and cross-link specific sites of DNA of the cancer cell, which block a cancer cell’s division without distorting its DNA helix. This should help prevent drug resistance from emerging, the company believes.
However the PBDs can be dosed as standalone agents or used in conjugates, Dr Martin says.
“The PBDs are by orders of magnitude more potent [than other cytoxic agents being used in ADCs]. However, because of their particular mechanism of action, they don’t recruit the repair machinery which typically leads to resistance in DNA damaging agents. That in turn means they have a therapeutic index – they are significantly more toxic to cancer tissue than healthy tissue.
“They also have a quite a benign side effect profile; you don’t get acute toxicity and myelosuppression which you do with many DNA damaging agents. So that really was why we developed the PBDs in this direction because they are particularly suitable as ADC warheads.”
Picking up the pace
The ten antigen targets that ADC will focus its attention upon have already been chosen by a panel of scientific advisors - well-validated, cancer-specific antigens, they are important in large subsets of many of the most common forms of cancer, the company says.
The antibodies that will be used have been found for seven of the targets, sourced from a variety of companies or academic and research institutions. Further details on the drug and disease targets will be revealed as IP is put in place and progress made.
If ADC meets its target - of generating phase II data in several programmes within three to five years – that will be notable progress. Antibody drug conjugates is a field that has prompted much excitement and interest in recent years, but this has yet to be matched by substantial clinical or commercial success (Therapeutic focus - Antibody drug conjugates still making slow progress, July 15, 2011).
Dr Martin reckons that pace of progress is about to pick up, as the work of the last few years starts to bear fruit.
“There’s been a lot of development on all three aspects of antibody drug conjugates – the antibodies, the linkers and the drugs. Probably more importantly there has been a significant increase in understanding on how one develops an ADC, understanding the pharmacokinetics and pharmacodynamics of the whole construct, and I think all of these things together have de-risked the development path for an ADC,” he says.
With ten declared shots on goal, ADC’s hit rate will be watched with interest.