Based in Lexington, MA Pulmatrix is a clinical-stage pharmaceutical company developing a broad new class of inhaled therapies for the treatment and prevention of infectious and progressive respiratory diseases via a fundamentally new way approach through potentially simple and safe therapies that harness the airway and lungs own natural biophysical properties and host defense mechanisms.

Rather than a one-bug:one-drug tactic Pulmatrix’s technology is pathogen-independent so it has broad potential to treat a wide range of respiratory diseases, including respiratory infections such as influenza, ventilator acquired pneumonia and respiratory syncytial virus, as well as progressive respiratory diseases such as COPD, asthma, and cystic fibrosis.

The Pulmatrix drugs are potentially able to deliver this benefit through a dual mechanism of action which enhances and stimulites the inherent biophysical and biochemical properties of the airway:

• Biological: The drugs stimulate host defense mechanisms that prevent infection and enhance the clearance of pathogens and,
• Biophysical: The drugs activate the assembly of endogenous proteins into three dimensional matrices, resulting in enhanced barrier function in the lung and reducing the penetration of pathogens into the lung tissue.

This unique approach of enhancing the biophysical capabilities of the airway while augmenting host defense mechanisms potentially offers a novel approach to treat and prevent infectious and progressive respiratory diseases.

PRODUCTS IN DEVELOPMENT

PUR003 (Phase Ib/IIa initiated 3Q09) is the lead drug candidate and is designed to treat, prevent, and reduce transmission of a broad spectrum of airborne pathogens that pose community and public health risks. PUR003 is intended to demonstrate utility in the treatment, prevention, and control of respiratory infections including influenza and in the reduction of acute exacerbations of progressive respiratory diseases, including asthma, and COPD. In a 2008 Phase I double-blind, placebo-controlled, randomized study designed to evaluate the safety and tolerability of single ascending doses of inhaled PUR003, the drug was found to be well tolerated at all doses with no serious adverse events reported. In preclinical studies, PUR003 demonstrated significant efficacy in the treatment and prophylaxis of influenza across multiple strains and in multiple species, including swine.

INDICATIONS & MARKETS PURSUED

• The worldwide influenza market is estimated at $7.1 billion in 2010, up from $1.5 billion is 2004, with average annual growth estimate now at 19.8%. Annually, more than 3.5 million people die of influenza. The outbreak of H1N1 (swine flu) highlighted the public health importance of improved vaccines and testing techniques creating new market opportunities.

The two classes of antiviral drugs used against influenza are neuraminidase inhibitors and M2 protein inhibitors. Neuraminidase inhibitors are currently preferred for flu virus infections since they are less toxic and more effective. The CDC recommended against using M2 inhibitors during the 2005–06 influenza season due to high levels of drug resistance. As pregnant women seem to be more severely affected than the general population by the 2009 H1N1 influenza virus, prompt treatment with anti-influenza drugs has been recommended.

Neuraminidase inhibitors: Antiviral drugs such as oseltamivir (Tamiflu) by Roche (VTX: ROG.VX) and zanamivir (Relenza) by GlaxoSmithKline (NYSE: GSK) are neuraminidase inhibitors that are designed to halt the spread of the virus in the body. These drugs are often effective against both influenza A and B. Different strains of influenza viruses have differing degrees of resistance against these antivirals, and it is impossible to predict what degree of resistance a future pandemic strain might have.

M2 inhibitors: The antiviral drugs amantadine and rimantadine block a viral ion channel (M2 protein) and prevent the virus from infecting cells. These drugs are sometimes effective against influenza A if given early in the infection but are always ineffective against influenza B because B viruses do not possess M2 molecules. Measured resistance to amantadine and rimantadine in American isolates of H3N2 has increased to 91% in 2005. This high level of resistance may be due to the easy availability of amantadines as part of over-the-counter cold remedies in countries such as China and Russia and their use to prevent outbreaks of influenza in farmed poultry.

FINANCING (to date ~$43M)

It appears as though Pulmatrix may have got going back in 2004 with an $850K seed round followed by their first institutional financing in 2007 of $8M which an additional $4M was added to shortly thereafter. Participants in this Series A included Polaris Venture Partners and 5AM Ventures. In 2008 it looks like a $3.5M debt offering was put in place. The most recent Series B financing, announced in November, totals $30.2M with $15.4M of it closed as a B-1, and includes new investors ARCH Venture Partners and Novartis Venture Fund with participation from previous investors. In addition, a non-dilutive $2.2M grant from the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health was received for the advancement of novel influenza therapeutics for the treatment of seasonal and pandemic influenza.

Intended use-of-proceeds from this new financing are to enhance Pulmatrix’s R&D capabilities and enhance the product pipeline, as well as the ongoing clinical program of PUR003.