Development of NH101: A Simple and Efficient Outpatient Dry Powder Amphotericin B-DryNeb(dry powder nebulizer) for Treatment of Susceptible and Multidrug Resistant Aspergillus/ Fungal Infections - The overall objective of this project is to progress NH01, a pure (neat) dry powder of amphotericin
B (AMB) combined with our novel, simple to use, DryNeb™, dry powder nebulizer, through proof
of principle pulmonary delivery, efficacy, pharmacokinetics (PK), and device-formulation
characterization. The results of this program will be a decision gate for follow-on Investigational
New Drug (IND)-enabling toxicology and device refinement funded through Phase II SBIR and
other sources. NH101 (AMB-DryNeb™) satisfies an unmet medical need by targeting common
and triazole (antifungal classes, e.g., itraconazole) multidrug resistant (MDR) strains of
pulmonary-infecting fungi (including aspergillus species) at the site of lung infection. NH101 will
initially focus on cystic fibrosis (CF) and asthma-associated allergic bronchopulmonary
aspergillosis (ABPA), a rare, orphan, and severe subset of aspergillosis that causes severe
allergic exacerbations and bronchiectasis. ABPA is associated with an estimated 2.5% of
asthmatics (~5 million) and 15% (~20,000) of CF patients. Exciting proof of principle results have
been generated in many “off label” studies of aerosolized IV formulations of AMB targeted at
fungal lung disease including ABPA. However, there are currently no regulatory-approved aerosol
therapies indicated for fungal infections/ diseases in the lung. For this project AMB will be
formulated as a simple, neat, micronized/milled dry powder using standard techniques (i.e. jet
mills, ball mills, etc.) with our established partners at Lonza. The latter avoids the need for
blending, non-traditional excipients, and advanced technical expertise associated with carrier-
based and spray-dried dry powder formulations. AMB will be delivered clinically by the DryNeb™
(US 9078985) developed by Dr. Hugh D. Smyth (Project Consultant) and exclusively licensed to
Nob Hill Therapeutics (NHT). The DryNeb combines the high-dose capacity and easy tidal
breathing of an on-demand nebulizer with the portability and stability characteristics of a dry
powder inhaler. The AMB-DryNeb will be tested with our collaborator Dr. Pavin Mutilli at the
University of New Mexico (UNM). NHT facilities are located on the Lovelace Respiratory Research
Institute (LRRI) campus in Albuquerque, NM. NHT will utilize this unique location and LRRI’s
scientific expertise to perform proof of principle efficacy and safety studies in guinea pigs. **We
have further recruited clinical and regulatory expertise, Drs. Betty Change and Don
Burstyn, to ensure we have considered “next steps” as the project progresses toward the
clinical and a Phase II SBIR submission.** At project’s end NH101 will be ready to proceed to
IND-enabling toxicology studies funded through a Phase II SBIR or alternate sources.
