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RXi’s CEO Resigns as Company Looks to Clinic, Industry Partnerships


By Doug Macron

RNAi drug developer RXi Pharmaceuticals announced last week that its founding president and CEO, Tod Woolf, had resigned as the company “looks to advance from the research stage to product development and execution of therapeutic collaborations and partnerships.”

In a filing with the US Securities and Exchange Commission last week, RXi said that Woolf’s departure was part of a “planned succession in leadership,” which included the appointment of Noah Beerman as the company’s new top executive. The company, a spin-off of CytRx, said the resignation was “not a result of any disagreement with the company or its management.”

The change follows a number of false starts RXi has made in regard to its pipeline, as well as the firm’s failure to meet previously stated partnering goals. But RXi is not alone in this respect, and management changeups have been par for the course among RNAi drug shops.

When RXi was spun out of CytRx in early 2007 (see RNAi News, 1/11/2007), the company listed neurodegenerative disease, oncology, type II diabetes, and metabolic disease as its key areas of focus. It also inherited CytRx’s RNAi programs in obesity and amyotrophic lateral sclerosis.

About a year later, Woolf said that RXi aimed to file its first investigational new drug application in 2009, with a second clinical program established the following year (see RNAi News, 3/13/2008). He also said at the time that the company expected to ink at least two corporate partnerships by the end of 2009.

By October of 2008, RXi was tweaking those goals. During an investor meeting, Woolf predicted that Alzheimer’s and inflammatory diseases had been added to the company’s diseases-of-interest roster (see RNAi News, 10/23/2008). He also told RNAi News at the time that RXi would now only pursue cancer with a collaborator.

At that meeting, Pam Pavco, RXi’s vice president of pharmaceutical development, also provided details about a newly acquired oral delivery technology, highlighting the company increasing focus on novel but early-stage technologies, while CFO Stephen DiPalma — who stepped down this summer — said that the company’s first industry alliance would come before the end of 2008. It did not.

In early 2009, RXi announced another pipeline shuffle, stating that an undisclosed program in inflammatory disease had become its lead drug-development effort — a move driven by the firm’s interest in its oral delivery approach — with neurological disease, including its most advanced effort in ALS, falling by the wayside (see RNAi News, 3/26/2009).

In June, Woolf told RNAi News that RXi expected to select its first therapeutic candidate before the end of the year (see RNAi News, 6/25/2009), but suggested that it could be based on yet another nascent technology, the company’s so-called self-delivering rxRNAs (RXi refers to all its proprietary RNAi molecules as rxRNAs).

At the same time, company officials were publicly discussing additional indications under evaluation, most notably an "undisclosed compromised skin indication," which Ramani Varanasi, RXi's vice president of business development, touched on during Cambridge Healthtech Institute's RNA Interference Summit this summer.

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Since that time, RXi has been relatively quiet, making no announcements about a lead drug candidate or its expected partnerships. RXi’s Beerman declined to comment ahead of the release of the company’s third-quarter financial results next week.

Under New Management

Although the CEO changeover at RXi is the most recent, there have been others in the space.

Perhaps the most dramatic occurred during Nastech Pharmaceutical’s transition from a floundering nasal-delivery technology company to a pure-play RNAi drug developer.

Nastech, under the leadership of Chairman, President, and CEO Steven Quay, first dipped its toes in the RNAi waters in early 2006 (see RNAi News, 2/23/2006), and by late 2007 was planning to spin its RNAi assets out into a publicly traded subsidiary: MDNRA (see RNAi News, 11/15/2007).

However, by May 2008, financial troubles and clinical setbacks prompted Nastech to adopt the MDRNA identity itself (see RNAi News, 5/8/2008). Although Quay initially led the new company himself, Sirna Therapeutics alumni Michael French stepped in as MDRNA’s new CEO in June of that year, with Quay remaining as chairman and CSO.

A few months later, Quay handed off the CSO mantle to Sirna’s former CSO Barry Polisky, and resigned his role as chairman of the company’s board. By May of this year, Quay, along with two other Nastech-era board members, left the company.

Also undergoing a management facelift was Arrowhead Research subsidiary Calando Pharmaceuticals. When it was created in 2005, Calando was led by President and CEO John Petrovich, but in late 2007, Arrowhead brought in Larry Stambaugh to take over those roles.

In a bid to contain costs, Arrowhead decided in mid-2008 to combine Calando and another of its subsidiaries, Insert Therapeutics (see RNAi News, 5/1/2008). As part of that restructuring, Stambaugh resigned as CEO and was replaced by Arrowhead executive James Hamilton.

Since then, Arrowhead has continued to struggle financially, and recently said that it would halt all of Calando’s research and development activities except for work on its phase I siRNA-based cancer drug (see RNAi News, 11/5/2009). According to a company official, Hamilton left Calando this summer, and his duties have been picked up by Arrowhead President and CEO Christopher Anzalone.

Big changes also hit Intradigm. An early player in RNAi, the company had been predicting that it was poised to move its long-time lead candidate, the vascular endothelial growth factor-targeting cancer therapy ICS-283, into the clinic in 2004 (see RNAi News, 5/7/2004).

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The company missed that goal, and in 2005 CEO John Spears said that human trials of the drug would begin by the middle of the following year (see RNAi News, 9/16/2005).

Intradigm missed that goal, as well, and in late 2006 Spears had been replaced by President and CEO Mohammad Azab (see RNAi News, 11/22/2006), who came on board as part of a reorganization that included relocating the company’s headquarters to California from Maryland.

Shortly thereafter, Intradigm co-founders Martin Woodle, Patrick Lu, and Puthupparampil Scaria stepped down from their positions as CSO, executive vice president, and vice president, respectively.

As Intradigm continued to focus on ICS-283, early this year the company underwent another management change, with Azab resigning and Phil Haworth coming in as the firm’s new CEO (see RNAi News, 1/8/2009). With the new leadership, Intradigm also dropped ICS-283 because the drug’s target was deemed not commercially promising enough, Haworth told RNAi News.

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