Multivir Inc., a Houston-based gene therapy company taking a second swing at two adenovirus-based cancer therapies – one of which drove Introgen Therapeutics Inc. to bankruptcy – has filed to raise up to $70 million in a proposed IPO that will support the first part of phase I/II trials of both candidates.

The company plans a Nasdaq listing under the symbol MVIR, but has yet to price the offering or say how many shares it will offer. RBC Capital Markets LLC is acting as its book­-running manager, while Nomura Securities International Inc. is acting as lead manager and Cantor Fitzgerald & Co. is acting as co-­manager for offering.

Founded in 2009 and orginially named P53 Inc., Multivir is developing as its first lead candidate Ad-p53, a genetically modified adenovirus designed to deliver the normal p53 tumor suppressor gene under development for the treatment of liver metastases from colorectal cancer. According to National Cancer Institute Surveillance, Epidemiology and End Results (SEER) data highlighted by Multivir, colorectal cancer is the second most common cause of cancer death in the U.S., with more than 136,000 estimated new cases and 50,000 deaths in 2014.

Known during its Introgen days as Advexin, the therapy failed in a phase III trial to demonstrate improved efficacy compared to standard treatment in head and neck cancer and was ultimately rejected by the FDA and withdrawn from consideration by the EMA. But while Wall Street reaction to the failure was swift and punishing, Introgen held out hope at the time that a biomarker test might identify patients most likely to benefit from the treatment. It never got the chance to find out. But Robert Sobol, Introgen's former senior vice president of medical and scientific affairs and now Multivir's CEO, clearly carried that hope, leading Multivir to identify just such a test as a key element of the Ad-p53 development strategy, according to the company's S-1 filing. (See BioWorld Today, May 29, 2008, and Dec. 2, 2008.)

To find a workable test that would help it select patients with a favorable tumor p53 biomarker profile, the company plans to first assess a nonvalidated companion diagnostic during the phase I/II study and then develop a validated companion diagnostic to gate enrollment in the randomized, controlled phase II part of the study.

Multivir's second lead candidate is Ad-IL24, a genetically engineered adenovirus modified to deliver the tumor suppressor gene interleukin-24 (IL-24). Known during its Introgen days as INGN 241, Ad-IL24 is now in development for the treatment of squamous cell carcinoma of the head and neck, or SCCHN. About 55,000 people in the U.S. were diagnosed with oral cavity, pharyngeal and laryngeal cancers in 2014, with about 12,000 dying from the disease, according to SEER data noted by Multivir. Preclinical and early stage clinical data indicate the potential for Ad-IL24 to treat a number of different malignancies, including SCCHN, the company said. To build on that, the company will test the therapy in combination with chemotherapy in patients with recurrent, unresectable SCCHN.

Multivir's plan for the trials of both drugs is to run the phase II portions with adaptive designs that permit increasing the number of patients treated during the trial based on interim results. The design will allow the company, it said, to adjust the trial size to increase the statistical power such that the results may support product registration, should sufficient safety and efficacy be demonstrated. Nonetheless, the FDA or other regulatory authorities may require it to conduct additional clinical trials, including phase III studies to obtain marketing approvals, it said.

In addition to Ad-p53 and Ad-IL24, Multivir is working to develop a pipeline of other candidates composed of additional viruses and therapeutic genes. It has Ad-VirRx 007, a therapy engineered to overexpress the adenoviral death protein. Virrx Inc., a company half-owned by Multivir and also headed by Sobol, acquired the program from St. Louis University. Multivir also has an option to license HSV-Rb-p450 from Massachusetts General Hospital, a therapy designed to selectively kill tumors with retinoblastoma, or p16/Rb, tumor suppressor pathway abnormalities. Both candidates have begun phase I testing. A vaccinia virus candidate, VV-IL12, is still in preclinical development.

To date, the company has financed all its activities through equity and debt financing received from Pope Investments II LLC, which currently owns 96.8 percent of the company's 15,7 million shares. As of Dec. 31, it had $500,000 in cash and R&D expenses of $700,000 and $1.7 million for the years ended Dec. 31, 2013, and 2014, respectively. Net proceeds from its proposed offering, together with existing cash and an existing $10 million credit facility, should be sufficient to fund its planned operations for at least the next 12 months, the company said, although it plans to raise additional capital in the future to fund the phase II portion of its phase I/II trials for Ad-p53 and Ad-IL24.

Should any of the programs succeed, Multivir could owe tiered milestone payments of up to $30 million to Introgen, but that's a ways off.