Argos passes on IPO and raises $25m Series D to fund personalized cancer immunotherapy
Rather than pursue an initial public offering this year, personalized cancer immunotherapy developer Argos Therapeutics raised $25 million in a Series D financing round to fund its Phase III ADAPT clinical trial for AGS-003 in metastatic renal cell carcinoma (mRCC) through mid-2013 when it will have interim data to support additional venture capital investment, an IPO or a partnership.
Alongside its funding announcement on 24 April, Durham, North Carolina-based Argos said the company obtained fast-track status from the US FDA for AGS-003 in mRCC. The new funding gives Argos enough cash to begin enrolling patients in its 450-subject Phase III clinical trial this summer under a revised special protocol assessment (SPA) with the FDA, which changed the ADAPT study's primary endpoint from progression-free survival (PFS) to overall survival.
Argos filed a registration statement with the US Securities in Exchange Commission (SEC) on 29 July 2011 to announce its intent to pursue an IPO, but withdrew the registration on 6 March 2012 (scripintelligence.com, 3 August 2011).
Argos president and CEO Mr Jeff Abbey said Argos decided not to pursue an IPO, because the public markets did not value it appropriately and its existing investors were willing to continue supporting the private company and its Arcelis immunotherapy platform.
"It was a better decision for the company to move forward privately and get the phase III trial funded to begin this summer as planned. We will need to do additional financing and we will do that either privately or publicly or with a partner," Mr Abbey said.
Forbion Capital led the Series D funding round that included TVM Capital, Lumira Capital, Intersouth Partners, Caisse de depot et placement due Quebec, Morningside Group and Aurora Funds.
When Argos has two-thirds of its patients enrolled in the Phase III ADAPT study and interim data from 40 to 50 subjects in mid-2013, that's when Mr Abbey said the company will seek new venture funding, pursue an IPO or enter into a partnership to complete Phase III.
The ADAPT study is a randomized, open-label clinical trial with 450 newly diagnosed, untreated mRCC patients at 100 clinical sites in North America and Europe. The trial will evaluate AGS-003 in combination with Pfizer's small molecule drug Sutent (sunitinib) versus Sutent in combination with a placebo. In addition to the primary endpoint of overall survival, secondary endpoints include overall response, immune response, PFS and safety.
"By next summer, we will know if it's working as expected," Mr Abbey said.
Argos plans to complete Phase III patient enrollment by the end of 2013, get full immune response data by mid-2014 and have final data on overall survival by the second half of 2015.
The company will get tumor samples needed to create personalized AGS-003 treatments from patients with mRCC when they undergo surgery to remove their tumors immediately following initial diagnosis. The company's Arcelis technology allows Argos to create the eight injections needed for a full one-year course of treatment plus a few years worth of booster shots from one small tumor tissue sample.
Mr Abbey said the US FDA granted fast-track status, which is reserved for new therapies that meet unmet needs for serious or life-threatening conditions, to AGS-003 for a few reasons.
"There is a recognition by the FDA and leaders in the field that patients don't fare very well on current therapy," he said.
First, the standard of care for 75% to 80% of mRCC patients is Sutent and the median overall survival is just 15 months. Second, those patients don't fare well when other therapeutics are given in combination with Sutent, because of overlapping toxicities.
Mr Abbye said that isn't an issue with AGS-003, because Argos' Arcelis technology for personalizing RNA-loaded dendritic cell immunotherapies uses the patient's own dendritic cells to trigger a tumor-specific immune response. Argos loads the autologous dendritic cells with messenger RNA isolated from the tumor to generate an immune response specific to the genetic makeup of the patient's tumor and minimize side effects.
"Because our drug has virtually no toxicity, it's really the perfect therapy to add on to these other therapies in kidney cancer. If you have an anticipated benefit of increased survival on top of the standard of care, that merits review," Mr Abbey said.
Argos presented Phase II data at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco on 4 February that showed median overall survival of 29.3 months in the 21 patients treated with AGS-003 in combination with Sutent – twice the median overall survival period for Sutent alone – in addition to the median progression-free survival (PFS) rate of 11.2 months (scripintelligence.com, 7 February 2012).
The FDA revised the SPA for Phase III to change the primary endpoint from PFS to overall survival based on overall survival data available from Phase II after the SPA was negotiated. The median overall survival rate has increased since January to more than 30 months.
"What's exciting about the switch to the overall survival design is that what that allows us to do is continue dosing through progression. Even though patients are likely to switch their targeted therapy at that point, we'll continue dosing. They'll get at least eight doses, which is the first year of therapy. We hope to have significant overall impact on a large percentage of patients," Mr Abbey said.
Argos already has developed a manufacturing plan for AGS-003 that it is discussing with the FDA. The company has a closed system manufacturing process with costs of goods that are comparable to a biologic.
The Argos process allows four days to obtain a patient's plasma via leukapheresis to incorporate their monocytes into a personalized immunotherapy as opposed to 18 hours for Dendreon's Provenge. Also, the immunotherapy is administered intradermally rather than via infusion.
"Our whole philosophy on treating patients with immunotherapy is quite different, not just from Dendreon and Provenge, because we look at the mutated antigens," Mr Abbey said.
He explained that every other cancer immunotherapy is based on non-mutated antigens, which are overexpressed in certain cancers, but it's the memory T-cells – T-cells that respond to an individual's mutated antigens – that correlate with the survival demonstrated with AGS-003.
Argos also has used the Arcelis technology in AGS-004, an HIV immunotherapy in Phase II development funded by $34 million in grants from the National Institutes of Health. Phase II data is anticipated by the end of 2013.
The company is looking for partners to begin a Phase Ib or Phase II study for AGS-009, its monoclonal antibody to treat lupus, and to move AGS-010 to treat organ transplant rejection, inflammatory and autoimmune diseases into the clinic. Preclinical work on AGS-010 was funded by the Juvenile Diabetes Research Foundation.
Argos will use virtually all of the funding from its Series D funding round for Phase III development of AGS-003.
The company previously raised $35.2 million in a Series C funding round in 2008, $5 million in debt financing in 2007 and $39.5 million in a Series B funding round in 2001 when the company was known as Merix Bioscience.