Updated: New Apple Tree biotech emerges with antibodies that might pair with Amgen, Mirati’s KRAS drugs

Apple Tree Partners is out Monday with a new biotech from the labs of NYU Langone Health that aims to tackle drug resistance in cancer.

Aethon Therapeutics will get $25 million from the VC firm, and another $5 million from New York University and other investors, the New York-based biotech said Monday.

The fledgling startup is working off a so-called HapImmune immunotherapy platform from the labs of Shohei Koide and Benjamin Neel at NYU’s Perlmutter Cancer Center. The two researchers began pondering the idea about three and a half years ago, Neel told Endpoints News, and they came to Apple Tree’s head of oncology Raj Chopra about a year ago to form the company.

In a statement, Chopra, the acting CEO, said Apple Tree was struck by the work out of Koide and Neel’s labs: “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. Aethon has discovered customized antibodies that home in on that beacon, making the cancer cells vulnerable to attack.”

Shohei Koide

“One day, we were thinking about how remarkable it was that all of a sudden RAS was becoming druggable and particularly that KRAS G12C was being drugged with covalent inhibitors,” Neel said about his conversations with Koide a few years ago. But the responses aren’t that durable as resistance builds up, he said.

So, Aethon is making antibodies using its HapImmune platform to drum up the T cells to specifically thwart tumor cells. The antibodies are reformatted into custom bispecific T cell engagers. The goal is to test combinations with RAS and EGFR inhibitors, like Tagrisso, Neel said.

The biotech will likely start by testing the drug in combination with approved KRAS G12C inhibitors, of which there are two: Amgen’s Lumakras and Mirati Therapeutics’ Krazati, which was greenlit in December 2022.

The scientist who kicked off the race toward a KRAS drug, Kevan Shokat at UCSF, is also on the hunt to make them more powerful by creating bispecific T cell engagers bound by the KRAS G12C inhibitors. He and colleagues are also going after haptens, small molecules that hopefully spark an immune response when attached to a larger protein, and their biotech is aptly named Hap10 Bio.

“The fact that a distinguished team from UCSF has also come to the same broad scientific conclusions as us, is validating of this novel approach,” Chopra told Endpoints in a follow-up email.

“Our antibody only binds to the sotorasib[Lumakras]–KRAS G12C protein complex on the cell surface when it is part of another specialized complex, known as a major histocompatibility complex, or MHC,” Chopra said.

Those complexes help inform the immune system that what is being displayed is bad and that the danger needs to be removed. Hap10 and Aethon are both going after the hapten-MHC complex.

Chopra told Endpoints that Aethon expects to enter the clinic in 2025. It has recruited a chief technology officer who will begin in March. The CEO said another executive is coming from BioNTech but declined to name the new hire. Also in the C-suite is acting CSO Paul Da Silva Jardine, an Apple Tree venture partner, a 25-year Pfizer veteran who left in 2015 after ending his stint as VP of cardiovascular and metabolic research. He’s also the co-founder of Staten Biotechnology.

The biotech is in “ongoing discussions” about potential partnerships, Chopra said. Prior to joining Apple Tree, he was a corporate VP of translational research at Celgene.

Aethon comes from Greek mythology. The biotech is named after one of the horses that helped transport the chariot of Helios, god of the sun, Chopra said. There’s also Aethonan, a breed of winged horse, which the CEO analogized to the hybrid platform his company is developing.

Neel’s daughter is a classics professor. “I get free advice from her,” he said.

Editor’s note: This story was updated to clarify ATP and NYU are not the sole investors in the $30 million Series A, and that Hap10 Bio is also going after the hapten-MHC complex. 

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