Challenges in Developing T Cell Engagers

Ian Chan, CEO of Abpro, discusses the advantages of their DiversImmune and MultiMab platforms for antibody discovery and engineering. Abpro's platform can create novel antibodies at industry-leading speeds, which are then reassembled into custom configurations for therapeutic purposes. They have developed bispecific antibodies, particularly T cell engagers for oncology, which are effective against solid tumors. Abpro's lead oncology program for breast cancer, in partnership with Celltrion, is advancing through clinical phases. Additionally, they have an eye care molecule targeting AMD and DME. The recent NASDAQ listing will aid in accelerating R&D and commercialization efforts. Collaborations, like the one with Celltrion, have been instrumental in the company's success.

What are the key challenges in developing T cell engagers, and how does Abpro's technology address these challenges?

For T cell engagers, they've been around for probably 10 years now. So as with everything else in the biotech industry, it takes multiple generations to really reach prime time, if you will, kind of like any other technology, if you think about it, in other industries as well. So, the first ones were, they were effective. They're very, very potent, mostly used for liquid tumors. I'm thinking Cyto, so, CD19, CD3. It got approved, and it proved that biospecifics actually work, especially when you engage human and immune cells on one arm in the format was, I would say, a first-generation format — meaning that even though it worked, the durability or the half-life was really short — meaning that the soon as the drug was administered, it would really leave the human body very quickly, so within a day, so actually within several hours. Patients had to wear a continuous IV pump while this medication was being administered; very inconvenient and difficult to manage from that perspective. But that was a really interesting window into how well T cell engagers could work.

Then the next generations were spent improving that with longer half-life being the molecule would stay in circulation longer, and those generally worked. You engineer it so the molecule is actually bigger. It looks like a regular Y shaped antibody. But what was missing there was the therapeutic window, so you had the better dosing, but it wasn't fine-tuned or engineered enough so that the molecule could be safe while the dosing was being increased to destroy tumor cells. To kill tumor cells. So, you generally want to be safe first, but then you want to have a dose that's going to kill tumor cells. So that window turned out to be too short for most T cell engagers, so a lot of them got stuck in phase ones during the dose escalation. It would just take many years. The FDA was very aware of the fact that these molecules needed to be escalated very slowly for safety reasons. So that generation, while there were improvements, really didn't lead to a quantum leap forward. So, we, when we set out to create our own TSL engagers, we realized that they had to have strong durability and a long half-life, and at the same time a very, very wide therapeutic window. So that way, you can modulate dosing for patients, increase it as needed, enough to kill tumors else, but while being safe the whole time and also be convenient for patients without having to wear a continuous IV pump. So that's what we've actually incorporated into our platform, all three of those features, so that it could be extremely effective against solid tumors, which is a very, very new kind of occurrence as well, and yet, having the long dosing half-life to make it convenient for patients. So that's where we're different, and this is, I would say, generation three in the industry overall. So that's usually, that's how biotech usually evolves. It's generation two or three that becomes widely acceptable in mainstream.