Managing Editor

Pulmatrix Inc. topped off its 2009 $30 million Series B with another $14 million to accelerate development of PUR118, its lead iCALM candidate, through Phase IIa studies in chronic obstructive pulmonary disease (COPD) and cystic fibrosis.

The internal B1 round came from all of the firm's existing investors, including Polaris Venture Partners, 5AM Ventures, Arch Venture Partners and Novartis Venture Fund. They "were very pleased with the progress we'd made with the Series B funding," said CEO Robert Connelly. "We hit all the milestones they set for us."

Part of that progress consisted of converting Pulmatrix's iCALM (inhaled cationic airway lining modulator) program from liquid formulations into dry powder, aimed at creating more portable and convenient versions. The lead liquid formulation, PUR003, previously had shown safety and tolerability in patients with asthma and influenza, and, with the latest funding in hand, the firm plans to launch five clinical studies of dry powder candidate PUR118, starting with two Phase Ib trials in COPD.

The studies will be "largely dedicated to expanding the safety and tolerability data, as well as to look at signs of efficacy," as measured by mucociliary clearance and inflammatory markers, Connelly said.

Pulmatrix already has started one of the Phase Ib COPD studies, with the second expected to start recruiting patients this fall. The randomized, ascending multiple-dose studies are expected to enroll patients with COPD, including those with emphysema and chronic bronchitis.

Next year, the Lexington, Mass.-based biotech anticipates moving into a Phase IIa study in COPD, as well as launching a Phase Ib trial and subsequent Phase IIa study in cystic fibrosis.

For Pulmatrix, the move into COPD was an easy decision, given that PUR118's mechanism of action was "perfectly matched" to the disease by targeting infection, which cause most of the COPD exacerbations, while also reducing the chronic inflammation without the use of steroids and enhancing mucociliary clearance. Currently, there is no available COPD treatment that "addresses the infection challenge and addresses the clearance challenge," Connelly told BioWorld Today.

It's a space that is "starving for a new mechanism," he added.

Among drugs in development for COPD are several working on improved formulations and/or combinations of well-known bronchodilators such as LABA (long-acting beta agonist), LAMA (long-acting muscarinic antagonist) or corticosteroids. Partners Theravance Inc. and GlaxoSmithKline plc, for instance, are in Phase III testing with Relovair, a once-daily LABA/corticosteroid combo intended to replace twice-daily Advair (fluticasone/salmeterol). Those firms also have a LABA/LAMA dual bronchodilator in late-stage trials.

Pearl Therapeutics Inc., meanwhile, is in Phase IIb testing with PT003, another dual LABA/LAMA product for COPD.

Because it works via a different mechanism, Pulmatrix's PUR118 could end up working well in combination with existing bronchodilators. In vivo testing has shown efficacy with an iCALM drug combined with either Advair, a LABA/LAMA drug or an inhaled corticosteroid. That fact could prove a draw to big pharma firms when Pulmatrix starts looking for a partner.

In COPD, the company will need some big pharma muscle. Going after an exacerbation claim in COPD will require large and costly late-stage trials, and "is not something we would take on ourselves," Connelly said, adding that the firm is hoping to bring a partner on board before Phase IIb.

Pulmatrix, however, could go it alone in cystic fibrosis, an orphan space that would be manageable for a small biotech.

While a smaller market than COPD, cystic fibrosis also fits well with the iCALM mechanism since it clears mucus and relieves inflammation. And, as in COPD, it aims to address infection, key to helping cystic fibrosis patients who "live in constant fear of getting a cold," Connelly said.

Beyond PUR118, Pulmatrix intends to seek collaborations involving its iSPERSE delivery platform. Essentially created as a byproduct of the firm's switch to dry powder, iSPERSE is based on the use of cationic salt formulations to enable delivery of the dry powder therapeutics.

"We're hoping for individual drug deals rather than platform deals," Connelly said, adding that the firm already has been looking at iSPERSE versions of LABA/LAMA drugs and corticosteroids. That opens the possibility of co-development deals, and Connelly said Pulmatrix already has started discussions.

The Series B1 round brings the firm's total venture funding to date to $60 million It's also pulled in more than $10 million in research funding from the likes of the Defense Advanced Research Projects Agency and the National Institute of Allergy and Infectious Diseases. And over the last year and a half, Pulmatrix has expanded its scientific advisory board to include a number of "top-name players in the respiratory field," Connelly said. "So we've been drawing a lot of support."

In other financings news:

• Embera NeuroTherapeutics Inc., of Shreveport, La., closed a $4.5 million round in a continuation of its Series A financings. Existing investors Louisiana Ventures LP, Louisiana Fund I and Themelios Ventures, as well as private investors, participated in the round. Proceeds from the financing, combined with development grant funding from the National Institute for Drug Abuse, will support ongoing development of EMB-001 through a Phase I study, enabling the company's programs for both smoking cessation and cocaine dependence. (See BioWorld Today, Oct. 8, 2010.)

• Evolva Holding SA, of Reinach, Switzerland, entered a standby equity distribution agreement (SEDA) with YA Global Master SPV Ltd., which has committed to provide up to CHF30 million (US$38. 1 million) in equity financing over a 36-month period in individual advances of up to CHF600,000, with an initial advance of CHF500,000, in exchange for Evolva shares. Any subsequent drawdown of funds will be at Evolva's discretion. The company has previously said it is funded through the end of 2012. If it uses the SEDA in full, that cash runway would be extended by at least one year.

• Lorus Therapeutics Inc., of Toronto, completed its offering of 5.5 million units – each comprising one common share and one common share purchase warrant – priced at C40 cents apiece, for gross proceeds of C$2.2 million (US$2.2 million). About 2.4 million units were acquired by Lorus director Herbert Abramson, who now holds about 44.6 percent of the firm's outstanding shares. Net proceeds are expected to advance LOR-253, a small-molecule metal-responsive transcription factor 1 inhibitor in development for cancer, to the end of Phase I, as well as to support working capital and general corporate purposes. Shares of Lorus (TSX:LOR) fell C6 cents, or 17 percent, to close Monday at C30 cents.