DUBLIN – Memo Therapeutics AG raised CHF13.8 million (US$15.3 million) in a first close of a series B round to take forward a patient-derived monoclonal antibody therapy for COVID-19, MTX-Covab, which will move into a phase I/II trial in Germany in the new year.
The Schlieren, Switzerland-based firm aims to secure CHF25 million in total over the coming months. “We had to do a really quick first close, because the costs for production ramp up quickly,” CEO Karsten Fischer told BioWorld. Memo has entered a process development and manufacturing agreement with Northway Biotechpharma UAB, of Vilnius, Lithuania, and will receive clinical trial material at the end of this month.
The company has spent several years developing a single-cell-based antibody discovery platform, which combines microfluidics technology with molecular cloning to capture the entire B-cell repertoire of individuals. “We use a monoclonal which is untouched, so to speak. It comes directly from the human system, and we don’t modify it,” Fischer said.
At present, the platform can capture a large majority of a patient’s B cells, which enables it to screen for rare but potent antibodies that have exceptional target binding affinities and neutralization activity. “In most runs we’re getting 80%. It depends a bit on the input material,” the firm’s chief scientific officer and co-founder, Christoph Esslinger, told BioWorld.
In its COVID-19 antibody discovery campaign, Memo interrogated B cells from about 100 convalescent patients, which, combined with the platform’s efficiency, gave it what Fischer claimed is an unequalled level of antibody diversity in the resulting library. In benchmarking in vitro experiments, MTX-Covab is, he said, on a par with or superior to clinical-stage antibodies that are currently in development against COVID-19. Because the molecule is derived from a patient, safety issues are unlikely to arise.
At the same time, delivering high doses of a single, patient-derived antibody does not recapitulate the actual clinical experience of the patient who originally produced the said molecule. Any potent antibody that is produced following an infection acts as part of the patient’s polyclonal response.
Nevertheless, clinical validation for that general approach has started to emerge. Most pertinently, ansuvimab (formerly mAb-114), an effective Ebola treatment currently undergoing regulatory review at the FDA, was isolated from the blood of an Ebola survivor in the Democratic Republic of the Congo. Miami-based Ridgeback Biotherapeutics LP (which has a small-molecule alliance in COVID-19 with Merck & Co. Inc.) licensed the antibody from the U.S. National Institute of Allergy and Infectious Diseases.
Memo’s Essinger has long experience of working with patient-derived antibodies, including stints at CT Atlantic AG, a cancer-focused antibody discovery firm where he was chief technology officer, and, before that, at Schlieren-based Neurimmune AG, where he served as director of antibody discovery. Neurimmune famously discovered aducanumab by screening elderly individuals who did not develop Alzheimer’s for protective antibodies – and the underlying thesis could soon receive a major boost if it passes regulatory muster.
Memo’s upcoming trial, meanwhile, will test MTX-Covab in high-risk patients during early stage infection. The protocol has not been finalized as yet, so it has not defined the precise cohort, but COVID-19 patients with either cardiovascular disease, diabetes or kidney dysfunction represent the most likely candidates. The study has a target enrollment of 200 patients, but it will stop at 100 if clear-cut evidence of efficacy emerges. It expects to report efficacy data next summer.
At that point, vaccines may already be shipping, but multiple uncertainties are still attached to their rollout. It is not yet clear how effective they will be, particularly in vulnerable populations, nor how quickly the production ramp-up and mass distribution can happen. Nor is it clear what the level of take-up will be – vaccine hesitancy appears to be growing in some countries to the point where it could derail any prospect of attaining herd immunity. “I doubt that a vaccine will really be the solution, even if it is working quite well,” Fischer said. For that reason, antibody therapies for those with active infection, are likely to be part of the picture. Antibody production has its own scaling issues, of course. “We, for sure, will not solve the entire problem here,” Fischer said.
Memo is also planning to move an antibody directed against BK virus into clinical trials late next year. BK virus, a polyomavirus, is widely distributed in the population and remains dormant in most people. However, it can re-emerge in immunosuppressed individuals and is a particular problem in kidney transplant recipients – and can result in nephropathy and graft loss. San Diego-based Amplyx Pharmaceuticals Inc. is in phase II in that indication with MAU-868, an antibody in-licensed from Basel, Switzerland-based Novartis AG.