AstraZeneca helps ADCT to $200M megaround to push anticancer ADCs to pivotal data 

ADC Therapeutics has raised $200 million (€170 million), bringing its total haul up to $455 million. The antibody-drug conjugate (ADC) specialist will use the money to take its two lead hematological cancer assets through registrational trials. 

Lausanne, Switzerland-based ADCT is developing ADCs that combine monoclonal antibodies with pyrrolobenzodiazepine (PBD)-based warheads. It is these PBD dimer toxins that have established ADCT as one of the best-financed private players in biotech. 

Having been delivered into a cancer cell by the antibody-targeting mechanism, PBD binds in the minor groove of DNA and forms DNA interstrand cross-links. These cross-links prevent cell division and kill the cell. PBD does this without distorting the DNA structure. And, as such, repair processes that would help the cancer fight back remain dormant.

ADCT has generated enough data to back up this mechanism to commit to registrational trials and persuade investors to bankroll its plans. The clinical data come from ADCT-301 and ADCT-402, the assets ADCT will move into registrational trials early next year. ADCT has enough cash in the bank to deliver data for the primary endpoints of the registrational studies. 

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AstraZeneca, Auven Therapeutics, Redmile, the Wild Family Office and other new and existing investors put up the money. ADCT said two years ago it sees an IPO in its future and keeps an up-to-date prospectus so it is ready to file for a Nasdaq listing at any time. But the willingness of deep-pocketed private financiers to put up the money means the prospectus is staying in the drawer for now.  

“We looked at public markets,” ADCT CEO Chris Martin said. “We really had a high level of interest from our existing investors and were approached by some other large private financing investors, so we … really didn't need to go to the public markets at this stage. The transaction costs [of the private financing] were considerably lower. The organizational demands were considerably lower. We have so much operationally to do it just made more sense.” 

ADCT-402 is at the top of that to-do list. The CD19-targeting ADC is advancing into a registrational trial on the back of data linking it to a 61% overall response rate in patients with relapsed or refractory non-Hodgkin’s lymphoma. More than 40% of patients had a complete response. ADCT achieved those responses in 62 evaluable patients who had undergone a median of three prior therapies.

The data on CD25-targeting drug ADCT-301 are more preliminary. At the last data drop, five of the 13 Hodgkin lymphoma patients treated with ADCT-301 had experienced a complete or partial response. ADCT will present more data on the drugs at ASH in December. 

As in the ADCT-402 trial, the ADCT-301 study enrolled heavily pretreated patients. ADCT will target the same patient populations in the registrational trials. 

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If ADCT can replicate its early-phase results, it will tee itself up to bring ADCT-301 and ADCT-402 to market as options for patients who have been failed by existing drugs. But the biotech also wants to muscle in on the earlier lines of therapy. To do so, ADCT plans to use some of the $200 million to run combination trials, one of which will feature a checkpoint inhibitor. 

“There's strong preclinical data showing a synergy between PBD-ADCs and checkpoint inhibitors, with the ability to … turn cold tumors into hot tumors,” Martin said.

If the clinical data follows suit, ADCT could move its drugs into earlier lines of therapy by showing they improve on standard of care.

The combination studies are part of a clutch of clinical trials ADCT plans to initiate and expand now it has more money. Development of ADCT’s third internal clinical candidate, solid-tumor drug ADC-502, is set to expand to cover other HER2-positive diseases. And a CD22-targeting program and secretive solid-tumor asset will follow it into the clinic within the next six months.  

ADCT will add to its 66-strong team, which works across four locations in the U.S. and Europe, to support these activities.