This week Novartis announced the acquisition of Myricx Bio, a privately held UK-based biotechnology company developing a novel class of antibody-drug conjugates (ADCs) featuring N-myristoyltransferase inhibitor (NMTi) payloads. This landmark deal, valued at up to $1.5 billion, with an upfront payment of $1.1 billion and up to $400 million in potential milestones [1,2], positions Novartis at the forefront of ADC innovation and introduces a differentiated payload mechanism designed to address resistance to current ADC payloads, notably topoisomerase I (TOPO-1) inhibitors.
The centerpiece of this acquisition is Myricx’s N-myristoyltransferase inhibitor (NMTi) ADC payload platform. This article explores the scientific underpinnings, preclinical validation, and future potential of NMTi-based ADCs in the context of the Novartis-Myricx deal.
Drawing on recent peer-reviewed literature, what is the scientific rationale for NMTi payloads, the preclinical evidence, and the potential clinical impact, and the implications for the future of targeted cancer therapy?
Antibody-drug conjugates (ADCs) have emerged as a transformative class of targeted cancer therapies, combining the specificity of monoclonal antibodies with the cytotoxic potency of small-molecule payloads. However, most clinically approved ADCs rely on a narrow set of payload classes—primarily tubulin binders, DNA-damaging agents, and TOPO-1 inhibitors. Resistance to these payloads and associated toxicities limit their broader application and effectiveness. Consequently, there is an urgent need for novel payload mechanisms with orthogonal and differentiated modes of action.
N-Myristoyltransferase: A Novel Target in Cancer
Biology and Therapeutic Rationale
N-myristoyltransferase (NMT) is an essential enzyme responsible for the covalent attachment of myristoyl groups (a 14-carbon saturated fatty acid) to the N-terminal glycine of substrate proteins. This modification is crucial for the proper localization and function of over 100 proteins, many of which are implicated in cancer cell signaling, survival, metabolism, vesicle trafficking, and mitochondrial biogenesis [3,4].
Recent insights reveal that NMT activity is particularly vital in cancer cells with deregulated MYC-family oncogenes, rendering them highly sensitive to NMT inhibition [5,6]. Moreover, NMT inhibition induces endoplasmic reticulum (ER) stress, cell cycle arrest, and apoptosis in diverse cancer models [7]. Modulation of NMT activity has also been shown to reprogram tumor-associated macrophages toward an anti-cancer phenotype, suggesting additional benefits for the tumor microenvironment [8].
NMT Inhibition: Preclinical Evidence
Multiple series of potent, selective NMT inhibitors have been developed and characterized in vitro and in vivo [3]. Notably, these NMTis are compatible with established linker chemistries and can be conjugated to antibodies targeting clinically validated cancer antigens [2].
In preclinical cancer models, NMT inhibition demonstrates broad activity across multiple solid tumors, including those with known resistance to TOPO-1 and tubulin inhibitor payloads [2,4]. Studies have shown complete tumor regression in xenograft models, superior efficacy in MYC-deregulated cancer cell lines, and favorable tolerability profiles compared to conventional cytotoxics [5,6].
Myricx Bio’s NMTi-ADC Platform
Platform Overview
Founded in 2019 as a spin-out from Imperial College London and the Francis Crick Institute, Myricx Bio has established a proprietary NMTi payload chemistry platform. [2][9] The platform comprises multiple patent-protected NMTis with varying potencies, enabling compatibility with a broad spectrum of linker–antibody combinations.
Lead Programs and Clinical Potential
Myricx Bio’s pipeline prioritizes two lead NMTi-ADCs directed toward the cancer antigens B7-H3 and HER2, both of which are highly expressed in a variety of solid tumors [2]. Preclinical data indicate that these agents possess orthogonal mechanisms of action compared to existing ADC payloads, offering potential efficacy in tumors resistant to standard therapies. [3][5]
The company’s Series A financing in 2024, totaling $114 million, enabled rapid advancement of its pipeline and scaling of operations, culminating in Novartis’s acquisition in 2026 [9].
Strategic Implications
The acquisition accelerates Novartis’ expansion in next-generation oncology platforms. The NMTi-ADC platform provides Novartis with:
- Two lead ADC assets: B7-H3 and HER2-targeted ADCs in preclinical development
- A novel, differentiated payload platform: Designed to overcome resistance to current ADC payloads
- Potentially broad applications: Across multiple solid tumor indications, including those poorly responsive to existing ADCs
Novartis’ oncology strategy is now poised to diversify beyond conventional payload classes, mirroring the company’s recent investments in radioligand therapies and covalent drug design. [1][2][10]
Scientific Context and Supporting Evidence
MYC Deregulation Sensitizes Cancer to NMTi
Recent studies have established that MYC-deregulated tumors are particularly vulnerable to NMT inhibition [5,6]. Lueg et al. (2025) demonstrated that MYC-driven cancer cells exhibited synthetic lethality to NMT inhibition, underpinning the rationale for targeting NMT in difficult-to-treat solid tumors [5]. Zhang et al. (2023) further elucidated the molecular mechanisms, showing that dysregulation of MYC-family proteins increases cellular dependence on NMT, thereby sensitizing tumors to NMTi-based therapies [6].
Efficacy in Preclinical Models
Carr et al. (2023) reported that NMTi payloads, when conjugated to antibodies, maintained potency and selectivity across a range of cancer cell lines, including those resistant to TOPO-1 and tubulin inhibitors [3]. These findings suggest that NMTi-ADCs could address significant unmet needs in oncology, particularly for patients with limited options due to acquired resistance to conventional ADCs.
Cell Death and Microenvironment Modulation
Thinon et al. (2016) demonstrated that NMT inhibition in cancer cells leads to ER-stress, G1 cell cycle arrest, and apoptosis, mediated by disruption of multiple signaling and metabolic pathways [7]. Kallemeijn et al. (2023) showed that NMT modulation can also reprogram tumor-associated macrophages to support anti-tumor immunity, providing a dual mechanism of action through both direct cytotoxicity and modulation of the immune microenvironment [8].
Platform Versatility and Broader Applications
Myricx’s NMTi payloads are structurally versatile, allowing conjugation with a range of linker technologies and antibody formats [2,3]. Given the essential role of NMT across various tumor types, the platform has potential for use in multiple solid tumor settings, including those with high unmet need due to resistance or poor tolerability to existing payloads.
Clinical Translation and Unmet Medical Needs
Diversification of ADC Payload Mechanisms
Currently, over 90% of ADC payloads in clinical development target three mechanisms: tubulin binding, topoisomerase inhibition, and DNA damage. [2][3] The introduction of NMTi as a payload class represents a significant diversification, addressing the urgent need for orthogonal, non–cross-resistant mechanisms.
Addressing Resistance and Improving Safety
The differentiated mechanism of NMTi payloads may overcome inherent and acquired resistance observed with traditional ADCs. Preclinical studies indicate a wider therapeutic index and improved tolerability, potentially enabling higher dosing and broader patient eligibility [2,3,6].
Enabling Combinatorial and Personalized Approaches
Given the synthetic lethality observed in MYC-deregulated tumors, patient selection based on MYC status or NMT dependency could further enhance clinical outcomes. [5][6] Moreover, the ability of NMTis to modulate the tumor microenvironment opens avenues for combination with immunotherapies and other targeted agents. [8]
The Novartis acquisition of Myricx Bio marks a pivotal advance in ADC innovation, introducing a first-in-class NMTi payload platform with the potential to address limitations of current therapies. Supported by robust preclinical evidence and a clear mechanistic rationale, NMTi-ADCs are poised to become a new frontier in targeted cancer therapy, with broad applications across tumor types and resistance settings. As these agents advance into clinical development, their impact will be closely watched by the oncology and biopharmaceutical communities.
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References
[1] Novartis agrees to acquire Myricx Bio, advancing next-generation antibody-drug conjugate innovation with a novel NMTi payload, expanding options for cancer patients. Novartis Press Release, July 6, 2026.
[2] Myricx Bio to be Acquired by Novartis to Advance Next-Generation ADC Payloads for Oncology with Novel NMTi Platform. Myricx Bio Press Release, July 6, 2026.
[3] Carr RA, Solari R, D’Arcy N, Tate E, Walton J, Orafidiya F. N-Myristolytransferase (NMT) inhibitors as novel potent payloads for antibody drug conjugates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): American Association for Cancer Research; Cancer Res. 2023;83(7 Suppl): Abstract nr 2635.
[4] Demetriadou A, Morales-Sanfrutos J, Nearchou M, Baba O, Kyriacou K, Tate EW, Drousiotou A, Petrou PP. Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology. J Cell Sci. 2017 Mar 1;130(5):903-915. doi: 10.1242/jcs.195263. Epub 2017 Jan 30. PMID: 28137759; PMCID: PMC5358331.
[5] Lueg GA, Zhang J, Faronato M, Gorelik A, Kallemeijn WW, Falciani F, Walton J, Houghton JW, Vannini S, Poon E, Costa BM, Solari R, Carr R, Bell AS, Bartlett EJ, Brzezicha B, Janz M, Chesler L, Calado DP, Tate EW. MYC deregulation sensitizes cancer cells to N-myristoyltransferase inhibition. Cell Rep. 2025 Sep 23;44(9):116180. doi: 10.1016/j.celrep.2025.116180. Epub 2025 Aug 22. PMID: 40849903.
[6] Zhang J, Lueg GA, Faronato M, Poon E, Gorelik A, Grocin AG, Caamano-Gutierrez E, Falciani F, Solari R, Carr R, Bell AS, Bartlett E, Hutton J, Llorian-Sopena M, Chakravarty P, Brzezicha B, Janz M, Garnett MJ, Chesler L, Calado DP, Tate EW. Dysregulation of MYC-family proteins sensitizes cancers to NMT inhibition: identification of NMTi sensitivity and mechanism. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): American Association for Cancer Research; Cancer Res. 2023;83(7 Suppl): Abstract nr 4871.
[7] Thinon E, Morales-Sanfrutos J, Mann DJ, Tate EW. N-Myristoyltransferase Inhibition Induces ER-Stress, Cell Cycle Arrest, and Apoptosis in Cancer Cells. ACS Chem Biol. 2016 Aug 19;11(8):2165-76. doi: 10.1021/acschembio.6b00371. Epub 2016 Jun 7. PMID: 27267252; PMCID: PMC5077176.
[8] Kallemeijn WW, Spear S, Walton J, Bussi C, Soudy C, Flynn HR, Skehel M, Carling D, Solari R, McNeish IA, Tate EW. From foe to friend: In vivo reprogramming of tumor-associated macrophages to an anti-cancer phenotype by modulating N-myristoyltransferase activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): American Association for Cancer Research; Cancer Res. 2023;83(7 Suppl): Abstract nr 439.
[9] Our Biology and Pipeline: Myricx Bio. Online. Last accessed on July 6, 2026
[10] Novartis Oncology: Recent strategic transactions in cancer and molecular glue therapies. Novartis, 2024-2026.
Featured image 2026 © Sunvalley Communication. Used with permission
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