Why Lung Cancer ?
Lung cancer was the leading cause of cancer death in 2020
Number of cancer deaths in 2020
(both sexes, all ages)
Problem: 40-65% of NSCLC are resistant to immune checkpoint inhibitors (currently used as SOC in stage III and IV NSCLC)
Resistance is caused by poor infiltration, proliferation and activation of T cells in the tumor microenvironment (TME).
Need: local stimulation of TNFα and INF response in the TME can be used as a strategy to increase T cell infiltration and increase tumor inflammation (i.e. converting a "cold" tumor into "hot")
Antonia (2019) Lancet Oncol 20(10):1395 -408.
Memon (2021) bioRvix 2021.07.21.452854 (preprint)
Our innovative solution
Engineered bacteria to increase
NSCLC inflammation and response to ICI
NSCLC recalcitrant to
Inflamed NSCLC responding to immunotherapy
Pulmobiotics proposes to engineer a lung-specific bacteria (Mycoplasma pneumoniae) to stimulate the immune system in a sustained and local manner to increase the efficacy of ICI
Summary and Main
objectives of EIC transition
Pulmobiotics is the first company to design recombinant live biotherapeutic products (LBPs) based on Mycoplasma pneumoniae (a human bacteria naturally present in lung) for the treatment of respiratory diseases. Recombinant LBPs are therapeutic products based on genetically engineered bacteria that contain all the biological machinery necessary to synthesize different proteins simultaneously, opening the possibility of generating new combinatorial and local or site-specific therapies with reduced side effects.
Thanks to this EIC Transition grant Pulmobiotics will develop PB_LC product to treat lung cancer. Lung cancer, with 2.21 million of new cases in 2020 and 1.8 million deaths worldwide, is the leading cause of cancer-related death. Despite notable recent advances in lung cancer treatment, which include targeted and immune therapies, these are still too often ineffective, toxic and/or applicable to only a small subset of patients. Most of the patients either do not respond or develop resistance only after a few months, leading to disease recurrence. Less than 25% of patients survive lung cancer beyond 5 years.
In this EIC transition grant, Pulmobiotics proposes to use M. pneumoniae to stimulate the immune system in a sustained and local manner to increase the efficacy of immune checkpoint inhibitors. Our proprietary attenuated M. pneumoniae strain (PB_Ch3) is able to localize and replicate in tumors and stimulate the production of cytokines in PBMCs cells and in vivo. We have also engineered PB_Ch3-based strains that express interleukins (to stimulate T cell proliferation and the expansion of dendritic cells), providing local production of these agents after inhalation delivery of the bacterial strain. Our solution has the advantage of producing therapeutic proteins in a local and sustained manner, combined with natural pro-inflammatory response to the bacterial strain.
The advantage of our MycoChassis-based product PB_LC is that it stimulates the immune system in a sustained and local manner, taking advantage of the natural ability of M. pneumoniae to locate to lung tumors and induce inflammation in the tumor area to increase T cell inflammation.
1. Validation of PB_LC efficacy and establishing formulation and delivery methods (TRL3 to TRL4): We will demonstrate the ability of our PB_LC strains to rescue the efficacy of anti-PD1 treatment in resistant tumor models in vivo and develop formulation and administration methods (e.g. intranasal, intratracheal or nebulized aerosol from spray dried or lyophilized product formulations) through extensive in vitro and in vivo experimentation.
2. PB_LC preclinical development (TRL4): Characterization of PB_LC activity by determining the maximum tolerable dose and demonstrating its safety, efficacy and mechanism of action, through dose-range assays in pre-clinical lung tumor models resistant to immunotherapy and assessment of off-target effects.
3. Manufacturing of PB_LC (TRL5): Production of a ‘technical batch’ of the PB_LC clinical development candidate strain to be used in IMPD-enabling studies. We will produce a Good Manufacturing Practices (GMP)-like batch (i.e. in the exact same conditions that will be used for the GMP clinical trial batch) of PB_LC, which will then be formulated according to product specifications for delivery using the previously established method.
4. PB_LC IMPD enabling studies (TRL5): One the PB_LC clinical development candidate strain is nominated and manufactured, a preclinical development program will be carried out, designed with input and validation from regulatory agencies, to test the pharmacology, pharmacokinetics/pharmacodynamics, toxicology and safety pharmacology of PB_LC. This objective will allow advancing the development of PB_LC towards clinical studies.