• Findings shared in article co-authored by Aethon Therapeutics scientists and NYU researchers support the hypothesis that combining covalent inhibitors and T cell engagers can overcome drug resistance in KRAS-mutated cancers

    New York, New York — December 19, 2025 — Aethon Therapeutics today announced the publication of a new study, “Engineered antibodies that stabilize drug-modified KRASG12C neoantigens enable selective and potent cross-HLA immunotherapy,” in Nature Communications. The work described in the publication was performed by Aethon scientists in collaboration with researchers at New York University (NYU).

    KRASG12C inhibitors such as sotorasib, adagrasib, and divarasib generate synthetic neoantigens are drug-modified peptides (p*) that are presented on cancer cells by major histocompatibility complex (MHC) molecules as p*MHCs. Although these antigens exist at extremely low copy number, they present a uniquely tumor-specific signature.

    Using targeted immunopeptidomics, the study authors directly identify and quantify these KRASG12C haptenated peptides for the first time. Through further detailed characterization—including their abundance, HLA allele coverage, and intrinsic instability—the Aethon team generated key insights that guided a tailored antibody engineering strategy.

    The resulting bispecific T cell engagers, AETX-R114 (sotorasib companion) and AETX-R302 (divarasib companion), bind drug-modified KRASG12C p*MHCs with high specificity and affinity across multiple HLA supertypes. This binding increases the stability, and thus the effective surface density of these ultra-low-abundance antigens, enabling potent and selective T-cell–mediated killing of KRASG12C inhibitor–resistant cancer cells in vitro and in vivo.

    Overall, the study highlights how high-affinity, high-specificity antibodies targeting hapten-modified KRASG12C peptides can bypass historic limitations of pMHC-directed therapeutics—particularly low antigen density and HLA restriction. The findings advance Aethon’s HapImmune™ platform and support ongoing work through its strategic collaboration with Revolution Medicines. The full article is available open access in Nature Communications.

    Link: https://www.nature.com/articles/s41467-025-66132-w

  • New York, April 21, 2025 — Aethon Therapeutics, Inc., a biotechnology company discovering and developing novel antibody therapeutics designed to attack cancer cells in tandem with targeted covalent inhibitor cancer therapies, will present updates on its programs in oral and poster presentations at the American Association of Cancer Research (AACR) Annual Meeting taking place April 26-30, 2025, in Chicago, Illinois.

    Aethon will also participate in a showcase session at the pre-conference Oncology Industry Partnering event on April 24 at the McCormick Place Convention Center in Chicago, featuring research highlights across programs and an overview of the company’s pipeline.

    Details of Aethon’s AACR Annual Meeting 2025 presentations are as follows:

    Oral Presentation

    Mini symposium session: Antigens, Antibodies, BiTEs, and Vaccines

    Date and time: 4/28/2025 2:30-4:30PM

    Location: Room S102 – McCormick Place South

    Title: Cross-HLA targeting of synthetic neoepitopes with T cell engagers to eradicate sotorasib-resistant, KRAS-G12C mutant cancer

    Presenter: Lauren Stopfer, Ph.D., Executive Director of Proteomics & Innovation, Aethon Therapeutics

    Poster Presentation

    Session: PO.ET01.01 – Antireceptors and Other Biological Therapeutic Agents

    Date and time: 4/27/25 2:00-5:00PM

    Location: Poster Session, Section 15, 310

    Title: Deciphering the molecular basis for pan-HLA recognition of divarasib-modified pMHCs by newly discovered hit-to-lead antibody AETX-R302

    Presenter: Lorenzo Maso, Ph.D., Principal Scientist, Aethon Therapeutics

    AACR Oncology Industry Partnering Event

    Location: McCormick Place Convention Center West Building, W196

    Date and time: 4/24/25 4:30-5:35 PM

    Showcase Session 1: Aethon Therapeutics

    Presenter: Sean Toenjes, Ph.D., Executive Director of Chemistry & Innovation, Aethon Therapeutics

     

    About Aethon Therapeutics
    Aethon Therapeutics creates neoantigens by design, to transform cancer treatments into cures. Aethon’s novel anti-drug-peptide conjugate/MHC antibodies are designed to be used in combination with targeted covalent inhibitors of KRAS, EGFR, and other oncogenic driver mutations to mount immune attacks to selectively kill residual cancer cells, including drug-resistant “persister” cells. Co-founded in 2022 by venture capital firm Apple Tree Partners with New York University cancer researchers Shohei Koide, Ph.D. and Benjamin G. Neel, M.D., Ph.D., Aethon unites immunotherapy and targeted therapy to expand the power and promise of both approaches for people living with cancer. For more information, visit aethontx.com

  • Aethon will apply its proprietary HapImmune™ platform to create novel antibodies that home in on cancer neoantigens generated by treatment with RAS inhibitors

    Collaboration focuses on key Revolution Medicines pipeline programs

    NEW YORK, April 4, 2024 /PR Newswire/ — Aethon Therapeutics, Inc., a biotechnology company discovering and developing novel antibody therapeutics designed to attack cancer cells in tandem with targeted covalent inhibitor cancer therapies, today announced that it has entered into a collaboration agreement with Revolution Medicines, Inc., a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers. Under the terms of the agreement, Aethon will use its HapImmune™ platform to discover novel bispecific antibodies to mount an immune attack directed towards cancer cells hit by Revolution Medicines’ RAS(ON) inhibitors, with the goal of fueling tumor clearance and helping to establish immune memory.

    The terms of the agreement provide for a multi-year collaboration under which Aethon is responsible for conducting preclinical work, with full reimbursement by Revolution Medicines. Revolution Medicines has an option to conduct any clinical development of products that may arise from the collaboration. The arrangement provides for both upfront and potential downstream payments covering future development and commercialization activities should Revolution Medicines exercise its option.

    “Aethon has proprietary expertise in creating and developing novel, cancer-specific drug-target peptide conjugates that seek out and bind to neoantigens created by different classes of covalent inhibitor anti-cancer therapies. This collaboration with Revolution Medicines represents an important validation of Aethon’s HapImmune platform and an exciting opportunity to potentially enhance RAS targeting by combining the power of highly selective immune cell attack with Revolution Medicines’ novel RAS(ON) inhibitors,” said Raj Chopra, M.D., Ph.D., CEO of Aethon Therapeutics and Head of Oncology and Venture Partner at Apple Tree Partners.

    “We are delighted to have the opportunity to work with Aethon and exploit their novel and innovative platform,” said Steve Kelsey, M.D., President, Research and Development at Revolution Medicines. “Through our own publications, and those of other leaders in the field, we have become increasingly aware of the interaction between oncogenic RAS activation and anti-tumor immunity. This collaboration represents an important component of our long-term vision to optimize treatments for patients with RAS-driven cancers.”

    Beyond the programs being advanced in partnership with Revolution Medicines, Aethon has additional programs targeting validated covalent small molecules that inhibit RAS, EGFR, and BTK. “Aethon is discovering its own proprietary covalent inhibitors that target known oncogenes and tumor suppressors to create cancer-specific neoantigens as targets for engaging the immune system. This includes CD3+T cells and T cell subsets. Our significant progress on this front is very encouraging,” Dr. Chopra said.

    About Aethon Therapeutics

    Aethon Therapeutics creates neoantigens by design, to transform cancer treatments into cures. Aethon’s novel anti-drug-peptide conjugate/MHC antibodies are designed to be used in combination with targeted covalent inhibitors of RAS, EGFR, and other oncogenic driver mutations (including intracellular targets) to mount immune attacks to selectively kill residual cancer cells, including drug-resistant “persister” cells. Co-founded by venture capital firm Apple Tree Partners with New York University cancer researchers Shohei Koide, Ph.D. and Benjamin G. Neel, M.D., Ph.D., Aethon unites immunotherapy and targeted therapy to expand the power and promise of both approaches for people living with cancer. For more information, visit aethontx.com.

    Media contact:
    Sally Jacob / sjacob@appletreepartners.com

  • Aethon’s HapImmune™ platform, described in a recent publication in the journal Cancer Discovery, unites immunotherapy and targeted therapy

    $30M in Series A funding, with $25M from Apple Tree Partners (ATP) and participation by NYU Langone Health

    NEW YORK, January 9, 2023 – New therapies targeting oncogenic mutations in proteins such as RAS and EGFR hold great promise for people fighting cancer. However, their efficacy is limited by tumor cells’ ability to develop resistance to these drugs, which can lead to disease recurrence.

    Today, Aethon Therapeutics launches to create novel antibodies designed to eliminate drug resistance by enabling the immune system to find and kill persistent cancer cells. Apple Tree Partners (ATP), a leader in life sciences venture capital, co-founded Aethon with researchers from NYU Langone Health’s Perlmutter Cancer Center – Shohei Koide, Ph.D. and Benjamin G. Neel, M.D., Ph.D. – inventors of the HapImmune™ immunotherapy platform that is Aethon’s drug discovery engine. Aethon is funded with $30 million in Series A financing, $25 million of which comes from ATP. NYU Langone Health also participated in this funding round and holds equity in Aethon.

    Raj Chopra, FRCP, FRCPath, FRSB, Ph.D., Head of Oncology for ATP, and a Venture Partner at the firm, is acting Chief Executive Officer for Aethon, and Paul Da Silva Jardine, Ph.D., an ATP Venture Partner, is acting Chief Scientific Officer for the new company, which is based in New York City. Seth Harrison, M.D., ATP founder and managing partner, chairs Aethon’s Board of Directors. Drs. Koide and Neel are scientific advisors to Aethon.

    “ATP worked with Drs. 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. Aethon has discovered customized antibodies that home in on that beacon, making the cancer cells vulnerable to attack,” Dr. Chopra said. “Aethon is moving quickly to advance programs focused on combinations with KRAS and EGFR inhibitors, and over the mid to long term we plan to develop other bespoke drug-antibody combinations.”

    Aethon’s proprietary HapImmune™ platform is a mechanism to increase the antigenicity of any cancer-specific protein that can be targeted with any covalent drug and presented by the major histocompatibility complex (MHC), an essential component of the adaptive immune system. The antibodies produced via the HapImmune platform are designed to activate T cells that will specifically kill tumor cells. HapImmune uses NYU Langone Health’s proprietary repertoire of 100 billion synthetic antibody sequences to find antibodies that recognize drug-peptide complexes (haptens) presented by MHC molecules while avoiding binding to wild-type (e.g., drug-free) peptides on the same MHCs or to the free drug.

    The chosen antibodies are then reformatted into custom bi-specific T cell engagers, with one recognition arm directed toward the drug-peptide:MHC and the other toward T cell surface proteins, to recruit T cells to attack the tumor cells. In vitro studies have shown that such engineered antibodies can selectively kill drug-treated resistant tumor cells. The HapImmune platform is described in an article published online recently in Cancer Discovery, a journal of the American Association for Cancer Research.[1]

    “Immuno-oncology therapy can be curative, but it is not applicable to most tumors or intracellular proteins because many cancers lack neo-antigens recognizable by the immune system,” said Dr. Koide. “We are excited to be part of new efforts in the field to improve and extend the effects of targeted therapy and prevent resistance and relapse. By uniting immunotherapy and targeted therapy in this way, we hope to amplify the power of both.”

    “This is an amazing opportunity, and we are grateful to everyone who has been a part of this research over the years,” Dr. Neel said. “’We are excited to deploy the HapImmune platform to advance new therapeutic approaches that we believe will ultimately help many people to not only fight cancer—but to fight cancer and win.”

    NYU Langone Health and its Technology Opportunities & Ventures arm has exclusively licensed to Aethon pending patent applications and expertise covering the HapImmune™ platform. NYU Langone Health is the owner of the technology exclusively licensed to Aethon and has equity and other financial interests in Aethon. Drs. Koide and Neel also have equity in Aethon, and Aethon is also sponsoring research conducted by Dr. Koide and Dr. Neel at NYU Langone Health. These interests are being disclosed and managed in accordance with NYU Langone Health policies.

    [1] T. Hattori T, Maso L, Araki K, Koide A, Hayman J, Akkapedi P, Bang I, Neel B, Koide S. Creating MHC-Restricted Neoantigens with Covalent Inhibitors That Can Be Targeted by Immune Therapy. Cancer Discovery, January 2023 print edition, first published October 2022. https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-22-1074/711560/Creating-MHC-Restricted-Neoantigens-with-Covalent. Accessed on January 7, 2023.

    ###

    About Aethon Therapeutics

    Aethon Therapeutics, an ATP company, creates neoantigens by design, to transform cancer treatments into cures. Aethon’s novel anti-drug-peptide conjugate/MHC antibodies, engineered using the company’s proprietary HapImmune™ platform, are designed to be used in combination with targeted covalent inhibitors (TCI) of RAS, EGFR, and other oncogenic driver mutations, to mount immune attacks to selectively kill residual cancer cells, including drug-resistant “persister” cells. Aethon unites immunotherapy and targeted therapy to expand the power and promise of both approaches for people living with cancer. For more information, visit www.aethontx.com.

    About ATP

    Founded in 1999, ATP is a leader in life sciences venture capital, with $2.65 billion in committed capital and offices in New York, London, San Francisco, and Cambridge, MA. ATP creates companies starting at various stages, from pre-IP ideas to asset spinouts, investing in them from seed stage through IPO and beyond. The core of ATP’s strategy is providing flexible capital and access to a world-class team of venture partners and EIRs, to build sustainable, research-driven enterprises that deliver therapeutics to improve human lives. For more information, visit www.appletreepartners.com.

    Media Contact

    Sally Jacob, ATP
    +1 212-468-5800
    sjacob@appletreepartners.com

  • Some of the deadliest cancers have mutations in a gene called KRAS. The recent development of drugs that can kill cancer cells with these mutations has been heralded as a major breakthrough. But in nearly all patients, tumors eventually become resistant to these drugs, and they stop working.

    Two research teams have now developed a way to overcome this resistance that may enable KRAS-targeted drugs—and perhaps drugs that target other mutant cancer-causing proteins in cancer cells—to pull double duty as an immunotherapy.

    View full article

  • NEW YORK, Oct. 17, 2022 /PRNewswire/ — Targeted therapies specifically attach to and hinder cancer-causing proteins, but cancer cells can quickly evolve to thwart their action. A second drug class, immunotherapies, harnesses the immune system to attack cancer cells, but these agents often cannot “see” the disease-causing changes happening inside cancer cells, which look normal from the outside.

    Now, a new study led by researchers from the Perlmutter Cancer Center at NYU Langone Health describes a strategy to overcome these limitations based on several insights. First, the research team recognized that certain targeted drugs called “covalent inhibitors” form stable attachments with the disease-related proteins they target inside cancer cells. They also knew that proteins once inside cells are naturally broken down and presented as small pieces (peptides) on cell surfaces by major histocompatibility complex (MHC) molecules. Once bound to MHC, peptides are recognized as foreign by the immune “surveillance” system if they are sufficiently different from the body’s naturally occurring proteins.

    View full release

New Publication in Nature Communications Demonstrates the Therapeutic Utility of Targeting Synthetic Neoantigens Generated by KRASG12C Inhibitors

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