Biologics drug development company Adalta (1AD: $0.09) has announced that its lead drug candidate, AD-214, will now be developed as an inhaled drug rather than a systemically delivered injected therapy.
The key reason for the change is that preclinical imaging studies with a radiolabelled version of AD-214 showed high accumulation levels (more than half the administered dose) in the liver. The reasons for strong binding affinity in the liver are unknown at this point, but it is not related to the i-body platform with the rapid distribution to the liver seen only with this drug candidate.
CEO Tim Oldham expects the company to have the first inhalation formulations of AD-214 to be ready for preclinical testing in the next three to four months. Adalta is currently in discussions with drug reformulation groups that have expertise in developing inhaled biologic drug candidates.
Currently there are two inhaled biologics on the market, one being inhaled insulin and the second being Pulmozyme for the treatment of cystic fibrosis. There are a further 19 inhaled biologics that are in clinical trials.
One of the challenges in delivering a biologic through inhalation is ensuring that the drug is not degraded from the shear forces resulting from inhalation. That there are only two approved biologics also highlights the technical challenges.
However direct delivery of AD-214 to the lungs for the treatment of lung diseases (including idiopathic pulmonary fibrosis) is a more appropriate approach and one that is likely to maintain a beneficial safety profile. AD-214 has now been tested through IV delivery at doses as high as 5mg/kg, dosed three times per patient.
There were some mild-moderate side effects linked to the formulation but not to AD-214, with the side effects commonly seen in the placebo and active arms in the healthy volunteer study. It's likely that an inhaled version will require lower doses than an IV delivered therapy. With the drug already tested at multiple doses of 5mg/kg and a lower level likely required for inhalation, Oldham believes that safety will not be a concern. (Also important to note is that binding in the liver was not to the hepatocytes involved with metabolic liver function.)
Another favourable aspect with AD-214 for inhaled delivery is its relatively small size as a biologic, being 73 kDa, with most inhaled biologics in development ranging between 15 kDa - 80 kDa in size according to the company. Some feasibility work on an inhaled version of AD-214 was conducted two years ago.
Adalta will seek to develop the inhaled version of AD-214 delivered in a nebulized form. Specific selection of the nebulizer can allow for specific delivery to sections of the lungs suitable for the disease being treated. At this point the company expects minimal changes to the formulation.
The radiolabelled version of AD-214, that has helped the company understand distribution of the drug following delivery, will be utilised as a tool in the inhaled drug trial.
Timing for Phase II Study
Adalta had anticipated conducting Phase Ib studies now and moving into Phase IIa efficacy studies around mid 2023. The timing of the efficacy studies will remain unchanged according to the company with the limiting factor for Phase II studies being supply of AD-214, which will take around two years due to current global supply restraints.
Adalta expects to release animal lung distribution data in Q1 next year, animal efficacy data by mid next year, and to start a Phase Ib/IIa efficacy study around mid 2023.
Other Programs
Whilst the development of AD-214 has taken another detour, following earlier redevelopment of a longer half-life version of the drug, the clinical data has provided important safety data around AD-214, around the i-body drug platform, and has confirmed binding to the CXCR4 target, notwithstanding a higher than expected loading in the liver.
The company has a continuing program with GE Healthcare and still plans to begin two new internal programs on new targets this year. The company finished March with $6 million in funds.
Bioshares recommendation: Speculative Buy Class B
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