T Cells Attacking Cancer Cell
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The biotech company Aethon Therapeutics has launched in New York to develop antibody immunotherapies for tumors that have developed resistance to current cancer drugs. The company is funding its work with a $30 million Series A round.

Aethon is the result of an alliance between the life sciences venture capital firm ATP and a research team from the Perlmutter Cancer Center at NYU Langone Health. The researchers, led by Shohei Koide and Benjamin G. Neel, published promising preclinical data from their antibody technology HapImmune in December 2022.

Some cancer drugs can covalently bind to therapeutic targets inside cancer cells. One example is sotorasib, which is approved to treat non-small-cell lung cancer by blocking a mutated form of the protein KRAS. However, cancer cells can evolve to resist covalent blockers when they bind to their targets, leading the cancer to recur.

To solve this problem, Aethon looks to the major histocompatibility complex (MHC), a molecule on the cell surface that can betray signs of cancer or infection to nearby immune cells. In the case of sotorasib-resistant tumor cells, drug-bound fragments of mutant KRAS can get displayed on a cancer cell’s MHCs.

Aethon is using the HapImmune platform to develop antibodies that can recognize fragments of drug-bound cancer targets on the cancer cell’s MHCs, and avoid forms of the target that aren’t bound by a drug molecule. It then engineers them into bispecific antibodies that recruit immune T cells when they detect drug-resistant cancer cells, triggering the destruction of the tumor cell.

“ATP worked with Koide and Neel to establish Aethon because we were struck by the  novelty of their original observation: That when covalent inhibitors bind to their target proteins inside cancer cells, they produce a peptide conjugate ‘beacon’ that is delivered only to the surface of cancer cells, not to healthy cells,” said Raj Chopra, head of Oncology at ATP and Aethon’s acting CEO, in a public statement. “Aethon has discovered customized antibodies that home in on that beacon, making the cancer cells vulnerable to attack.”

Aethon is developing drug programs to tackle malignancies that become resistant to covalent blockers of mutated KRAS and another cancer target called EGFR, with the first clinical trials expected in 2025. The firm will initially focus on pairing its antibody drugs with existing covalent blockers of these cancer targets, but eventually plans to develop its own covalent compounds against other targets.

“Immuno-oncology therapy can be curative, but it is not applicable to most tumors or  intracellular proteins because many cancers lack neoantigens recognizable by the immune  system,” stated Koide. “By uniting immunotherapy and targeted therapy in this way, we hope to amplify the power of both.”

It is theoretically possible that the cancer cells also become resistant to Aethon’s HapImmune candidates if mutations prevent binding of the covalent blocker to its cancer target. However, Chopra explained in an email to Inside Precision Medicine that this scenario is relatively uncommon.

Aethon’s $30 million Series A round includes $25 million from ATP. NYU Langone Health also participated in the funding round, and has licensed the HapImmune intellectual property to Aethon.

One of the closest competitors to Aethon is Hap10 Bio, a startup that was recently founded by a group at the University of California San Francisco. Chopra said that the Hap10 Bio founding team arrived at a very similar approach to Aethon’s independently, giving this strategy more weight. He also sees Aethon’s technology as having several advantages over that of Hap10 Bio, with one being that Aethon focuses on more cancer targets at the moment.

“We would say that Aethon has a structural advantage in that we engineer antibodies that are not competed out by free drug—that is, the targeted drug will not compete with one of our antibodies,” added Chopra.

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