Written Q&A

Small-Format Antibody Drug Conjugates for the Treatment of Solid Tumours

By Tom Cohen |
06 December 2021
Could 'Small' Antibody Drug Conjugates Bring Big Advances in Solid Tumour Treatment?

An interview with Dr. Gokhan Yahioglu, Director of Medicinal Chemistry, Antikor Biopharma Ltd.

After a successful keynote address at Biologics UK 2021, Oxford Global sat down with the keynote speaker, Dr. Gokhan Yahioglu, Director of Medicinal Chemistry at Antikor Biopharma. His address discussed how Antikor is leading the charge on new research into Antibody Drug Conjugate (ADC) technology. As a relatively new treatment in the world of oncology, developers are now quietly optimistic after seeing six ADC approvals since 2019 but recognising that there are still many hurdles ahead especially for solid tumours. ADC developers have mainly focused on ‘lower hanging fruit’ like blood cancers or targets that are highly expressed and ‘clean’. Now, Antikor’s novel small-format ADC model shows exciting potential in delivering cytotoxic payloads to solid cancer cells.

The renewal of antibody drug conjugates for the treatment of solid tumours

“Until recently the majority of approvals were for ADCs against blood ‘liquid’ cancers with many failures for ADCs against solid tumours”, Dr Yahioglu explained. He noted that this is because blood cancers are ‘relatively’ easier to treat as solid tumours present a significant barrier for drug delivery with a pressure gradient that tries to push out the cytotoxic drugs that attempt to enter and kill it. ADCs, being large biological molecules, find it hard to come out of blood vessels and enter the tumour which is why there are not many ADCs approved for treating difficult solid tumours, “they don’t usually work and are too toxic”. “Our ADCs are different” he said, explaining that they have a smaller format that allows them to enter the tumour quicker and easier, carrying more drugs and therefore doing more damage to the cancer before clearing, so called ‘hit hard and leave and quickly’.

Dr. Yahioglu went on to comment further on the possibilities smaller format ADCs can offer for the treatment of cancers, “We’re also looking at combining our format with the really hot areas of immunotherapy. Immunogenic cell death is needed for T-cell priming and because our drugs are small, they can get in and do damage to the tumour very quickly.” According to Dr. Yahioglu, this rapid tumour cell death “leads to faster priming of the immune system”. The cancer cells burst open, alerting the immune system that something is going on. The sooner you can prime the immune system, the faster and more effective the immune response is. “The other advantage our smaller format is that unlike whole antibodies they do not cross-react with Fc-receptors thus do not damage bone marrow or immune cells” he said.

The challenges facing small-format antibody drug conjugates

“We’re going against the grain.” Dr. Yahioglu explains, “Most ADCs, well over 100 in pre-clinical and clinical development, carry a low number of drugs with a large antibody. We do the opposite; we’ve gone for a small antibody carrying lots of drugs. The problem with that is that people are more sceptical, they think it’s too far outside the mainstream. Therefore, the bar is set higher in terms of convincing people to invest in our technology.”

Dr. Yahioglu remarked on the way these challenges translate into Antikor’s developmental priorities: “Our key priorities going forward is to close our funding round.”, explaining that this will allow Antikor to take their lead drug ANT-045 into IND filing, which means they can begin phase one clinical trials. “This should be an 18-month period. That will turn us from a preclinical small biotech company into a company with clinical assets. I think that’s one of our key priorities, to take our lead ANT-045 into the clinic.”

Despite the challenge of securing funding, Dr. Yahioglu remains excited about what the future could hold for small ADCs, “We’re starting to see clinical and manufacturing translations of non-standard ADC formats such as Bicycle Drug Conjugates. The ‘one size fits all’ approach of using large, whole antibodies is slowly changing and people are now looking at different formats and frameworks as the potential carriers of drugs, and I think that’s the next big thing that’s coming.”

Looking forward to collaborations and further research, he further added: “I think a stream purely dedicated to small format ADCs would bring like-minded people together.  Often, what we find is, we stand on our own because everyone’s doing full size ADCs and we’re doing a small ADC. To have more people in our field would be great.”

Although the ADC market is currently dominated by traditional, large ADCs, Antikor’s progress in developing smaller antibodies with a higher drug loading could be revolutionary in the treatment of solid tumours, that have hitherto been very difficult to treat. It seems that the largest obstacle, Dr. Yahioglu believes, is the scepticism of investors. However, Dr. Yahioglu hopes that Antikor’s current work and positive results could reverse the doubt around ADCs, along with collaboration with other developers.

To track more ground-breaking developments in Biologics, please consider coming along to Oxford Global’s Biologics UK 2022 conference starting 21 March 2022.

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