Despite the success of the first round of COVID-19 vaccines, and particularly in light of the continued emergence of new SARS-CoV-2 variants, there remains a critical need to continue to develop treatments for the infected, particularly those who either haven’t received the vaccine or who do not respond to it. The development of new antibody treatments will be critical to saving lives. One company seeking a leadership position in this race is Abpro, who recently initiated a phase II/III trial for the COVID antibody drug ABP-300. Abpro’s CEO, Ian Chan, met with Pharma’s Almanac Editor in Chief David Alvaro, Ph.D., to discuss the continuing role for new antibody therapeutics in the ongoing fight against COVID-19.
David Alvaro (DA): For most people, COVID-19 vaccines were like the Holy Grail in the fight against the virus. Can you discuss why that might be a bit shortsighted and why the development of new antibody treatments continues to be so critical?
Ian Chan (IC): I think it perhaps makes sense to start with the difference between vaccines and therapies. Vaccines primarily give your human immune system the blueprint to make antibodies to fight COVID-19. The therapies, especially neutralizing antibodies, are actually tools that can be used to fight COVID-19 directly. When the blueprint fails to lead the body to make sufficient antibodies to fight the infection, that’s when you need neutralizing antibodies to directly fight. So while vaccines have been extremely effective to date — we’ve seen some pretty phenomenal numbers, there’s still a lot of logistical challenges to actually getting everybody vaccinated; that’s not an easy task at all, especially when you’re dealing with a global issue.
Secondly, there’s many people who don’t respond very well to vaccines. For many vaccines, over 5% of the individuals who receive it can still have no response at all to the blueprint to create antibodies. So that’s where the neutralizing antibody therapies can play a huge role. These are antibodies created directly by the human immune system, generally from recovered patients, that can be used directly to fight COVID-19 directly.
DA: I’d like to talk a little bit about the science underlying Abpro. Can you explain a little bit about the DiversImmuneTM discovery platform and how it allows you to identify antibodies against targets that have traditionally been challenging?
IC: The DiversImmune platform is something we put together very early in the company. We saw that antibodies were going to continue to grow as a therapeutic modality, yet at the same time, we knew that the ability to create and discover antibodies quickly was going to be a bottleneck in the industry.
DiversImmune offers the ability to create novel therapeutic antibodies against traditionally difficult targets at industry-leading speeds. There are really three components behind that: the first is a way to generate a wide immune response in a large diversity of antibodies on the one hand — and to do so very, very quickly. We have a series of technologies that allow us to do that. And then the second step is the ability to screen those antibodies and pick the antibodies that work against the targets the way you want them in a therapeutic way. Here, we’ve built in a set of technologies that allows us to pick out these antibodies at industry-leading speeds: almost eight million cells in as little as two or three days.
The last step is to take these antibodies, which are your building blocks for the therapies, and fine-tune them for a clinical benefit. For example, you may want an antibody to bind tighter to a certain target; our platform provides the ability to increase the affinities on the backend which will lead to a certain type of clinical outcome.
DA: From there, can you explain how the MultiMab antibody engineering platform allows you to combine those building blocks and create bi- and multi-specific antibody candidates?
IC: I think we can all remember back to basic biochemistry and the cascades that complex molecules really interact with each other in combinations. So that pathway has multiple, multiple antibodies sometimes working together in concert. Right now, it’s all about moving from single antibodies to multiple antibodies working together. The ability to modulate how these antibodies interact, either as cocktails or bispecifics, is another core element of our platform. There are certain features that you’ll want to build into how these interactions occur. For example, in a bispecific antibody, which is part of our immune-oncology pipeline, we have T cell engagers. In that kind of situation, you want to be able to create as wide a therapeutic window as possible. And this can be done on the engineering backend of the platform. There are certain ways to tune these molecules so that you can have a wide therapeutic window: meaning efficacy can take place before toxicity comes in.
DA: It appears that the platform has already borne some fruit. What can you tell us about ABP-300, your late-phase COVID-19 antibody candidate?
IC: ABP-300 is a great neutralizing antibody that’s been isolated directly from recovered patients. It’s a program that went quickly from inception to phase II trials in less than a year. Right now, it's in the middle of finishing a phase II trial. It’s also part of our broader cocktail program, which is meant to be future-proof against new variants that’ll pop up, so that we can get ahead of the variants that are coming up almost every few months.
DA: How do you see that ABP-300 ultimately fitting into the continuum of care with the vaccines and therapies that are already out there? What role will it play in that larger picture?
IC: Vaccines will continue to be rolled out; they’ll always be the first line of defense as a preventative measure. In general, we have embarked on a future-proofed strategy against mutants that are here and yet to come. Our overall program has demonstrated success against Omicron, for example, very recently, against which almost all currently approved monoclonal antibodies have failed. This was a great validation of our strategy. Our therapies can be used as a therapy or for pre-exposure for immunosuppressed individuals who don't generate a response to current vaccines.
DA: Looking beyond COVID, what comes next for Abpro and the rest of your preclinical pipeline?
IC: There’s an exciting set of molecules that we’ve been working on, since before COVID. We’ve always been deep in immuno-oncology. Our pipeline explores the ability to stimulate our own immune system to fight disease or grab immune molecules and bring them to diseased molecules. These are T-cell engagers. We also have a very exciting eyecare molecule, which is a bispecific VEGF and ANG2, which is a synergistic grouping of targets for wet AMD and DME, which are two of the biggest indications in the eyecare space today. This is a molecule that’s shown pretty phenomenal data preclinically to date that will enter the clinic next year.
