Q&A with Pulmocide CEO Garth Rapeport – Why Pulmocide is developing targeted lung therapy.


Pulmocide CEO Garth Rapeport has a long history in biotech research. Heading a team that’s developing inhaled medications for viral and fungal infections, Garth Rapeport’s team is at the cutting edge of targeted lung therapy. In this Q&A he discusses his company’s work to date, his passion for improving quality of life in patients with infections, and plans for the future.

Q: Pulmocide is developing a range of first-in-class anti-infectives for treating life-threatening lung infections. Why did you co-found Pulmocide and focus on these treatments? 

A: I’ve spent most of my working life in researching and discovering treatments for serious lung diseases. After many years working on discovering new treatments for asthma, cystic fibrosis and Chronic Obstructive Pulmonary Disease (COPD), it became apparent to me that pulmonary bacterial, fungal and viral infections were the important drivers of disease in these patients. 

There are currently very few options for safe and effective inhaled antiviral and antifungal therapies. I felt strongly about it and decided that this would be an important opportunity for Pulmocide.

Q: Tell us briefly about the two treatments in Pulmocide’s pipeline – PC786 and PC945

GR: It’s quite technical, here goes. PC945 is a potent anti-fungal azole with broad spectrum activity across a range of disease-causing yeasts and mould infections. After inhalation, lung tissue levels of PC945 are 7,000 fold greater than plasma levels. PC945 can therefore be safely used for preventing or treating fungal lung diseases across a wide range of indications and actually has the potential to alter current treatment paradigm. 

In Phase 1 and early Phase 2 studies, PC945 demonstrates excellent toleration, with minimal systemic exposure and is safety demonstrated on dosing up to 3 months. Initial efficacy is demonstrated in lung transplant patients with severe invasive Aspergillus infections.

PC786 is a potent RSV antiviral with superior potency to competitor polymerase inhibitors with earlier clearance of viral load and reduced inflammation in preclinical test systems. Lung tissue concentrations are 10-14,000 greater than plasma levels. Excellent PK and safety profile over a wide dose range in Phase 1 testing. Currently generating further clinical data in mild asthmatics and in an RSV challenge. RSV treatment study in adult stem cell transplant patients started in Q4 2018. 

Q: Which specific respiratory infections and diseases will these treat?

A: Pulmonary aspergillosis is a life-threatening infection which frequently occurs in immuno-compromised patients undergoing transplantation or those undergoing cancer treatment. Aspergillosis also presents a significant problem in patients with asthma and cystic fibrosis, who develop allergic responses to the presence of the organism. 

Our second program is for an inhaled RSV antiviral agent PC786. RSV is a common winter-time respiratory virus, which is the major cause of serious lower respiratory tract in children and the elderly.

In immunocompromised patients, RSV results in significant morbidity and mortality (patients undergoing bone marrow transplant, graft vs host disease, solid organ transplant especially lung transplant).

There are no effective antivirals for the treatment of RSV and it is unlikely that an RSV vaccine will be introduced for very young infants (0-6months), who are most liable to severe RSV infection.

Q: Why are these respiratory infections so difficult to treat? 

A: Few treatments are currently available for lung delivery for RSV and fungal lung infections – these are unsatisfactory as they use oral treatments which do not reach high concentrations in the bronchial epithelium where the organisms replicate. In addition, existing treatments are limited by serious adverse effects. Potent and specific new treatments are urgently required.

RSV unmet need:

  • Commonest cause of bronchiolitis and pneumonia in children <2 years
  • 3x higher incidence of asthma after hospitalization
  • Hospitalises those with pneumonia, heart failure, COPD and asthma
  • ~14,000 deaths per year in USA.

Q: What is the breakthrough in Pulmocide’s treatments? 

A: Both RSV and Aspergillus replicate in the bronchial epithelium. This tissue is difficult to access with oral treatments. Only inhaled treatments can reach high concentrations to eliminate the pathogen, while avoiding systemic adverse effects.

PC786 is a novel therapy for Respiratory Syncytial Virus (RSV) infection. It’s a first in class non-nucleoside RSV L polymerase inhibitor for inhaled administration. It’s also a potent inhibitor of RSV A and B strains, unlike competitor oral small molecule polymerase inhibitors. It’s administered at a low dose, with minimal systemic exposure and demonstrated safety in human studies.              

PC945 is a novel therapy for respiratory diseases driven by Aspergillus – first in class azole for inhaled delivery. It’s a potent inhibitor of Aspergillus and 100 times more potent than itranonazole). Initial phase 2 clinical studies have started in severe asthmatics, cystic fibrosis and lung transplant populations. There’s a large unmet need in treatment of severe asthmatics with fungal sensitisation

Q: Which stage of funding is Pulmocide at? 

B: Series B financing. This is the second round of funding for businesses backed by venture capitalists and private equity investors. The third and final round is Series C. 

Q: Who are your backers, and what advice would you give for bio pharm companies just starting out? 

A: Pulmocide’s backers are IP Group, F Prime, SRone, SV Health Partners, JJDC and Longwood Partners.

My advice to anyone thinking about starting a new bio-pharm company is to answer several important questions:  

  • Does the idea justify starting a new company?
  • Will investors want to invest?
  • How much will it cost to develop the product?
  • How attractive is the market?
  • What is the competition?
  • Will patent protection be required? 
  • Will it be possible to attract the right individuals to the company?

Remember, investors bet on the jockey, not the horse!

Q: What led to your clinical interest in this area? 

A: A long-standing interest in treating life-threatening lung diseases to improve outcomes for people. 

Q: Tell us about Respivert and the treatments developed there before it was acquired by Johnson&Johnson?

A: RespiVert was a small molecule drug discovery company, based at Imperial College in London. I was the original co-founder together with Professor Peter Barnes (National Heart and Lung Institute), Dr’s Kaz Ito, Peter Strong and John Murray.

At Respivert we focussed on identifying new breakthrough treatments for patients with COPD, Cystic Fibrosis and severe asthma. The more severe forms of these diseases are not very responsive to existing therapies, such as inhaled corticosteroids.

Respivert discovered two new classes of compounds intended for inhaled delivery, which were progressed through pre-clinical development – Narrow Spectrum Kinase Inhibitors (NSKI) and Pi3 kinase gamma/ delta isoform inhibitors. The NSKI inhibitors are unique in that they’re also potent inhibitors of inflammation induced by respiratory virus infection. Therefore they have potential in management of disease exacerbations. In 2010, Respivert was acquired by Centocor – Ortho Biotech (a division of Johnson and Johnson. 

The company became a fully operating division of Janssen Pharmaceuticals (J&J) and is now responsible for a range of small molecule drug discovery activities for COPD and severe asthma indications. In July 2010, Respivert’s lead compound RV568 entered Phase 1 development for COPD and asthma indications. Large scale Phase 2 multi centre studies in COPD are started mid-2013. The first in human studies were initiated in March 2013 in the UK for RV1729, a first in class inhaled inhibitor of Pi3 kinase for treatment of severe asthma and COPD.

Q: What stage are the clinical trials at? 

A: Both PC945 and PC786 are in Phase 2 development studies.

Q: What are your plans for Pulmocide – when do you envisage getting these treatments to market? 

A: Our plan is to target regulatory approval for PC945 in 2021 for treating Aspergillus lung infections in lung transplant patients.

Garth Rapeport is CEO of Pulmocide Ltd, a drug discovery company working on identifying new treatments for Invasive Aspergillosis and RSV and visiting Professor at the National Heart & Lung Institute, Imperial College School of Medicine in London.