Unum Therapeutics Inc. followed up last year's series A financing round with a series B that almost triples the amount, hauling down $65 million and adding seven fresh investors to its roster behind New Leaf Venture Partners, the debut backer that led the round. "We've followed the broad space as many have for some time, and this is the one we jumped in on," Liam Ratcliffe, managing director at New Leaf, told BioWorld Today.

CEO Charles Wilson said that "a huge amount has happened for the company" in less than a year. When the series A round closed, "we had just executed the license agreement for the core technology. We still had some very important patents to file. We hadn't gotten regulatory approval to start clinical testing, and we didn't have any partnerships. All of that has changed between then and yesterday."

Proceeds of the series B will be used to advance the firm's Antibody-Coupled T-cell Receptor (ACTR) technology platform and to support pipeline expansion. ACTR is a chimeric protein that combines components from receptors normally found on two immune cell types – natural killer cells and T cells – to create another type of cancer cell-killing activity. T cells bearing the ACTR receptor can be directed to attack tumor cells by providing a monoclonal antibody that binds to antigens on the cancer cell surface, and then acts as a bridge to the ACTR T cell.

Unlike methods that take aim at just one target to treat a narrow set of tumors, Wilson said, Unum's approach is not restricted by antigen. It's the next generation of chimeric antigen receptor (CAR) T-cell therapy. "There are many parallels between what we're doing and what the CAR T's do," he said, though Unum has "essentially a universal approach. We can use the same construct, the same manufacturing process, the same registered product over and over again in many different indications."

Unum's success with the latest fundraising is "multifactorial," said New Leaf's Ratcliffe, who joins the Unum board. "The field of CAR T has moved on and continued to show tremendous efficacy in a range of hematological settings, but also I'd say it's going to show promise in solid tumors as well," he said, with a nod to Oxford, UK-based Adaptimmune Ltd., which recently has turned up encouraging results in advanced synovial sarcoma. Unum's $12 million series A took place last October. "The company wasn't around much longer before that, and it's moved incredibly quickly," he said. (See BioWorld Today, Oct. 17, 2014, and Oct. 22, 2014.)

Evidence today with CAR T-cell therapy is mainly "in leukemias but also, increasingly, in lymphomas," Ratcliffe pointed out. "The solid tumor story will continue to grow and evolve and broaden the potential for CAR T. As the target space opens up, Unum has a very strong competitive advantage." More upside exists in "how you tune the dose of the antibody together with the dose of cells," he said, which makes for the possibility of calibrating dosing regimens more precisely for improved safety. "That obviously still has to be proven out in the clinic, but at least in vitro and in vivo, that tune-ability has advantages on efficacy as well as safety parameters," he said.

MIXED DEALS AHEAD

"Unum has a unique platform, and finding a platform in this space is challenging," Ratcliffe said, and the firm is "extremely well positioned to exploit that." In December, Unum began a phase I trial with its lead program, which pairs the ACTR technology with the CD20-targeting monoclonal antibody Rituxan (rituximab, Biogen Inc./Roche AG). The study is testing the feasibility, safety and potential efficacy of infusing what Unum has dubbed the Attck20 combination therapy in patients with B-cell malignancies and persistent disease following standard therapy.

Rituxan was chosen because it's "so well understood, serves a large patient population, and is well tolerated," CEO Wilson told BioWorld Today. "Those features made it an obvious choice, plus the fact that we can simply go to the pharmacy and buy it without having to wait to put a partnership in place. At the same time, there are many patients who ultimately succumb to their disease despite Rituxan," and maybe pairing the drug with Unum's approach would let patients and doctors "think about cure as opposed to treatment."

The deal between Unum, of Cambridge, Mass., and Bothell, Wash.-based Seattle Genetics Inc. (Sgen) was driven by the latter's expertise in antibody-drug conjugates, which has let the firm assemble a substantial portfolio of cancer targets and tumor-specific monoclonal antibodies from which programs will be selected for the collaboration. Sgen paid $25 million up front and agreed to the equity investment in the series B round.

Tying up with Sgen "puts us in a different place," Wilson said, and "opens up the opportunity with proprietary antibodies that aren't yet on the market." Unum hopes to gain "both depth and breadth" from the series B take, he said. "The real intent with the financing is to give us the firepower to go out, acquire antibodies that we think would make appropriate combination partners, and be in a position to drive those antibodies through proof-of-concept testing" over the next one to three years in varied programs, he said. "In many ways [the Sgen deal] complements and adds on to what we're doing with the financing," and "going forward we expect to see a mix" of antibody acquisition and partnering deals.

Along with New Leaf, new investors in the series B include Brace Pharma Capital, Cowen Private Investments, Jennison Associates (on behalf of certain clients), Novo A/S, Sabby Management LLC, Sectoral Asset Management and Wellington Management Co. LLP. Unum's existing investors – Fidelity Biosciences, Atlas Venture and Sanofi-Genzyme Bioventures – also participated in the oversubscribed round.