Coming out of the IPO gate strong was Lausanne, Switzerland-based ADC Therapeutics SA, which priced about 12 million shares at $19 each, for gross proceeds of about $232.7 million in an upsized deal. Shares (NYSE:ADCT) ended the day at $29.65, up $10.65, or 56%.

The offering is expected to close officially on May 19. As its name suggests, the firm develops antibody-drug conjugates (ADCs) with particular focus in hematological malignancies and solid tumors. Underwriters were granted a 30-day option to purchase up to about 1.8 million more shares. Morgan Stanley, Bofa Securities and Cowen are acting as joint book-running managers for the deal.

Proceeds, along with existing cash and cash equivalents – at the end of 2019, about $115.5 million – will help advance loncastuximab tesirine (ADCT-402), also known as Lonca, through the finish of the ongoing, pivotal phase II study for relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and the ongoing phase I/II experiment in combination with ibrutinib (Imbruvica, Pharmacyclics LLC/Johnson & Johnson) for r/r DLBCL and mantle cell lymphoma. The firm also plans to commence a confirmatory trial of Lonca when paired with rituximab (Rituxan, Roche Holding AG/Biogen Inc.) for r/r DLBCL. Also in the works is a pivotal phase II effort for r/r follicular lymphoma and – if the ibrutinib pairing pays off – a confirmatory bid in DLBCL with the duo. Lonca is directed at CD19.

Lonca’s 145-patient pivotal phase II trial in DLBCL turned up a 45.5% interim overall response rate (ORR) as of October 2019, which “exceeded our target primary endpoint and the 41.4% ORR observed for DLBCL patients in our 183-patient phase I clinical trial,” treated at the initial dose used in the pivotal phase II, ADC noted in SEC paperwork related to the IPO. The company intends to submit a BLA to the FDA in the second half of 2020 for Lonca in DLBCL.

The company also aims to push CD25-targeting camidanlumab tesirine (ADCT-301), also known as Cami, to the end of a continuing phase II trial for r/r Hodgkin lymphoma (HL) and the ongoing phase Ib experiment for advanced solid tumors. As of April 15, the study had enrolled 47 patients. The firm has completed enrollment of a 133-patient phase I bid with Cami for r/r HL and non-Hodgkin lymphoma (NHL) that has shown an 86.5% ORR in patients with HL at the initial dose for the pivotal phase II effort and a 44% ORR in a subset of NHL patients with T-cell lymphomas as of April 2019. The HL study, if successful, could support a BLA submission, ADC said.

ADCT-602, which targets CD22, will be ushered through an ongoing phase I/II effort in r/r acute lymphocytic leukemia. Clinical work with AXL-targeting ADCT-601, at an earlier stage for solid tumors, will continue, the firm said. The latter was licensed from Bergenbio ASA, of Bergen, Norway.

So far, the FDA has cleared seven ADC treatments, three of which were approved in 2019. ADC Therapeutics deploys next-generation pyrrolobenzodiazepine (PBD) technology for its candidates. The mechanism of action differs from other ADC “warheads” by creating cross-links in the cancer cells’ DNA that do not distort the DNA helix, potentially evading the cells’ natural DNA repair mechanisms. They have been shown preclinically to be about 100 times more potent than warheads used in currently marketed ADCs, the company said. The PBD approach is meant to yield less hydrophobic therapies, too, causing them to be easier to conjugate and, based on preclinical data, show less off-target toxicity than first-generation PBD players.

The ADC field has been hot lately, with the likes of Waltham, Mass.-based Immunogen Inc. reporting promising data. Immunogen has mirvetuximab soravtansine, a folate receptor alpha-targeting therapy, which was tested in combination with bevacizumab (Avastin, Roche Holding AG) against platinum-agnostic ovarian cancer (OC). Treatment gained a 43% ORR, or 26/60 in the overall cohort, with what Wainwright analyst Debjit Chattopadhyay called an “impressive” 61% ORR in the subset of patients with high folate receptor alpha expression: 20/33 with ≥75% of cells with PS2+ staining intensity. ORR was ≥50% in both platinum-resistant and sensitive patients. At a median follow-up of 5.5 months, and duration of response and progression-free survival had not been reached.

Chattopadhyay maintained his buy rating on Immunogen and $9 price target in a May 14 report. “Our model is implicitly predicated on mirvetuximab commercialization during the first half of 2022 (pulled forward from 2023),” he wrote. The patient population eligible for therapy with the compound “represents about 40% of the OC patients according to PS2+ testing, and our model reflects about 40% market share for mirvetuximab in patients, i.e., about 15% of the overall commercial opportunity in the platinum-resistant setting,” he wrote. Shares (NASDAQ:IMGN) closed at $4.43, up 30 cents.

Immunogen is expected to provide an update at the virtual American Society of Clinical Oncology meeting at the end of this month. Also presenting there is Mersana Therapeutics Inc., of Cambridge, Mass. The firm has XMT-1536, an NaPi2b-targeting ADC, and will offer phase I expansion cohort findings with a cutoff date of May 1, including 20 evaluable OC patients and four evaluable non-small-cell lung cancer patients, treated with 36 mg/m2 and 43 mg/m2 (about half the patients from each dose). SVB Leerink analyst Jonathan Chang likes the drug’s prospects, while acknowledging the early stage of research. “NaPi2b represents a potentially significant commercial opportunity, with expression levels of about 60% in large oncology indications such as lung [cancer] and OC,” he pointed out in a May 8 report.

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