Phase Ia Results
In the Phase Ia study which involved 42 healthy volunteers, there were three key findings. The drug was found to be safe and well tolerated at single doses as high as 20mg/kg, with three moderate adverse events. It was found to engage its target, as well as sustaining high levels of receptor occupancy, which means the compound can now be explored for less frequent dosing which will have obvious appeal for patients. The half life of the drug in the body was found to be 44 hours.
There were no clinical symptoms indicating an immune response, with no significant cytokine activity. Eleven of the 31 volunteers who received AD-214 experienced a low titre immune antibody response to AD-214.
With respect to how long AD-214 stays bound to the target receptor CXCR4, there was a surprising, positive finding. Preclinical studies showed that at a 10-20mg/kg dose, receptor occupancy was over 50% at four days. However, in this study, although the half-life was found to be 44 hours, the compound was bound to 75% of the CXCR4 receptors at seven days at a 5mg/kg dose, and over 80% at seven days at the 10mg/kg dose. And at 20mg/kg, the drug bound to 100% of receptors (on the white blood cells) after one week, and still bound to more than 60% of receptors at two weeks.
Findings Shape Next Trial (MAD Study)
The head of Adalta's product development, Claudia Gregorio-King, said that as a result of these findings, which includes the 'excellent safety profile' and the longer than expected binding to targets, the Phase Ia multiple ascending dose study (Part B) will not include the lowest dose of 1mg/kg or the highest dose of 20mg/kg, and the drug candidate will be dosed every two weeks rather than every week.
The Phase Ib study in patients with fibrotic lung disease will be run at the same time as Part B of the Phase Ia study above. It is expected to start in Q3 this year and will involve two parts. A radiolabelled version of AD-214 (which is still under development) will be given to 12 patients with fibrotic diseases, including about half with lung diseases. This may show target engagement in patients with other diseases in which the receptor CXCR4 is involved.
Positive preclinical data in mice has been achieved with radiolabelled AD-214. Further preclinical studies are to be conducted with Adalta CEO Tim Oldham confident the radiolabelled drug candidate will be ready for Q3 studies this year.
The second arm will explore multiple doses of AD-214 in six patients with fibrotic lung disease (ILD), given up to six doses over 18 weeks. This may give initial evidence of efficacy, although Oldham cautioned that with the small patient number this will be difficult to achieve.
Adalta expects to complete its Phase Ib program this year, which will allow the company to move into Phase II studies in any indication where the receptor CXCR4 is involved, following an IND submission to the FDA. The market for the treatment of Idiopathic Pulmonary Fibrosis is currently poorly served by existing therapies (pirfenidone and nintedanib) which generate US$3 billion a year in revenue.
Oldham said that these results provide initial validation of the i-body platform that underpins the company, which is a single domain antibody that is based on the shape of shark antibodies. (This allows the antibodies to reach difficult targets that previously only small molecules could bind to, but with the specificity of an antibody.)
By the end of 2023, the company intends to have nine programs underway, from discovery through to Phase II, with two programs being added this year. The company also expects to sign a co-development program with a partner by mid year.
The company's business model, which is not new for antibody library companies, is to develop its own programs to the Phase II stage and then transact a licensing deal, as well as finding i-bodies to bind to specific targets selected by partners.
Summary
As discussed previously with another antibody company in the sector, Patrys, the ability to progress biologics into the clinic involves substantially more work in the early stages than for small molecule drugs. However, the upside is that antibody drugs have a higher chance of delivering clinical success because of their specific binding nature to targets and therefore less off-target effects.
Biologic drugs need to be injected, so developing a drug with extended activity in the body has significant commercial benefits.
Adalta's Phase Ia trial result has been important not just for the intended application in the treatment of fibrotic lung diseases, but it also validates the company's i-body platform. That the lead compound AD-214 is showing extended activity in the body is an important positive finding. As has confirmation of receptor binding in a dose-dependent response.
Milestones to monitor this year will be completion of the radiolabelled version of AD-214, binding of AD-214 to diseased tissue in patients with not just fibrotic lung disease but in other patient subgroups, and potentially evidence of efficacy in patients in the open label Phase Ib studies.
Adalta is capitalised at $43 million and held $8 million in cash at the end of last year.
Bioshares recommendation: Speculative Buy Class A
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