Fresh from a prostate cancer deal with Johnson & Johnson unit Janssen Biotech Inc. and in the midst of ushering an immunotherapy bid against pancreatic cancer through phase IIb trials, Aduro Biotech Inc. nailed down $55 million in a series C round that should see the privately held company into 2016.
The arrangement with Janssen brought the potential for $365 million, if all milestones are reached. "Of course, a lot of that is downstream, but there was a very significant up-front payment," said Stephen Isaacs, CEO of Berkeley, Calif.-based Aduro. The prostate program is preclinical.
"We feel now that we are very well funded and we can be selective about what we do," Isaacs told BioWorld Today. "We don't feel pressure, which is nice for a change, to do any particular deal that we don't like or do a financing that we don't like the terms of."
By the time 2016 arrives, "we see other opportunities for financing the company through traditional and nontraditional channels, and we believe we're going to be able to make the right deal" rather than bow to necessity, Isaacs said. Meanwhile, the pancreatic cancer effort is "our most expensive program" and will "consume a big chunk" of resources, he added.
Proceeds from the series C also will fund clinical development in mesothelioma and glioblastoma, as well as expansion into more indications and advancement of Aduro's small-molecule program targeting the immunomodulatory STING (stimulator of interferon genes) receptor.
Aduro disclosed at the J.P. Morgan Healthcare Conference in January that the phase IIa trial of CRS-207 and Gvax Pancreas in combination against metastatic pancreatic cancer was halted early on the recommendation of the data safety monitoring board and approval by the FDA after the study met the primary efficacy endpoint at a pre-planned interim analysis. (See BioWorld Today, Jan. 15, 2014.)
Details of the immunotherapies' success in the 93-patient study rolled out at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium conference earlier this year. The combo garnered a statistically significant survival benefit vs Gvax Pancreas vaccine alone. The median overall survival of the patients receiving the combination turned out to be 6.1 months compared to 3.9 months for those receiving Gvax monotherapy (HR = 0.59, one-sided p = 0.0172). The results formed the basis for the ongoing, randomized 240-patient phase IIb trial called Eclipse in metastatic pancreatic cancer patients who have progressed after at least one line of therapy.
In February of last year, Aduro acquired all the Gvax assets from Biosante Pharmaceuticals Inc., of Lincolnshire, Ill., including intellectual property and cell lines. The set of vaccines is based on human cancer cell lines that are genetically modified to secrete granulocyte macrophage colony-stimulating factor, and initially were developed by Cell Genesys Inc., which was acquired by Biosante in 2009 following disappointing GVAX data in phase III studies. (See BioWorld Today, July 1, 2009.)
Aduro previously had licensed rights to two Gvax members directed at pancreas and prostate cancers for use in combo with its Listeria-based vaccines. Aduro paid Biosante $1 million up front for the full roster and committed to additional milestone and royalty payments.
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The company's platform of live-attenuated double-deleted (LADD) Listeria monocytogenes strains, which drew Janssen to the table, have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity.
CRS-207 is one of a family of candidates that grew out of the LADD platform. Aduro engineered it to express the tumor-associated antigen mesothelin, overexpressed in many cancers including mesothelioma and pancreatic, non-small-cell lung, ovarian and gastric cancers.
At this month's ASCO meeting, the company presented data from a phase Ib trial of CRS-207 with standard chemotherapy in treatment-naïve patients with unresectable malignant pleural mesothelioma. Of 16 evaluable patients, 69 percent (11/16) had confirmed partial responses and 25 percent (4/16) had stable disease after CRS-207 and chemo, resulting in an overall disease control rate of more than 94 percent.
In glioblastoma, the company has ADU-623, also from the LADD platform. "There we use two antigens that are overexpressed in that indication," Isaacs said, with a dose-escalation study underway. A program in non-small-cell lung cancer (NSCLC) is in the works, too.
Aduro's combos will be tried in pancreatic cancer with checkpoint inhibitors, too, specifically with an anti-PD1 agent, at Johns Hopkins. "There are disease states where they work very well, such as melanoma, renal cell carcinoma and NSCLC, but there are other diseases such as pancreatic cancer where they don't work very well," Isaacs said. "The thought is that there's not really a T-cell population in the first place to 'take the brakes off of,' in the vernacular. So the major pharmaceutical companies Bristol-Myers Squibb Co. [BMS], Roche, Merck, Astrazeneca, and so on are looking for companies that can stimulate that T-cell response, put the army in place, and the checkpoint inhibitors can make sure they continue to have bullets to fight the battle."
The interest in Aduro's combo approach "all flows from the fact that we got efficacy in metastatic pancreatic cancer, which is basically the hardest nut to crack," Isaacs said. "People believe if you can get something there, it's going to be much better in early stage disease. And 94 percent disease control in mesothelioma is beginning to show that the hypothesis has legs."
In pancreatic cancer, the phase IIb trial is "not designed as a registration per se" and the company is making no claims in that regard, "but stranger things have happened," Isaacs said. "We're in the metastatic setting, not in the surgical setting, and about 85 percent of patients who are diagnosed metastatic disease. We almost doubled survival relative to our control vaccine, which was Gvax. If the results hold up, we would hope that would be looked at in the aggregate. We do believe we'll have to do a phase III, but if the data are very good, I'm sure the agency will take note."
A decade or so ago, "you couldn't get anybody to talk to you" about immunotherapy, Isaacs said. "It's like you were untouchable, but now it's completely flipped, and it's in the sunlight. All these companies like BMS that made deals with companies like Medarex, and people thought, 'Oh how you could possibly pay $2.4 billion for that?' Now it's probably worth 10 times that to them. The point is, look what it's doing for patients. This is what we've all been waiting for." New York-based BMS bought Medarex Inc., of Princeton, N.J., in 2009. (See BioWorld Today, Aug. 6, 2009.)
New investor Johnson & Johnson Development Corp. joined the Morningside group and other new and existing investors in Aduro's latest round. Privately held Aduro has raised a total of $84 million from equity financings so far.