Axplora announced the completion of its first research and development batches of exatecan, a camptothecin-class topoisomerase I inhibitor, to establish an additional European source for antibody-drug conjugate (ADC) developers [1]. The company said exatecan development and manufacture are based at its Farmabios site in Gropello Cairoli, Italy, and linked to payload-linker development and bioconjugation operations at its Novasep CDMO site in Le Mans, France [1]. Validation batches are targeted before the end of 2026, with initial GMP supply targeted for late 2027 [1].
Key Takeaways
- Axplora has completed the first research and development (R&D) batches of exatecan under its Axotecan program, producing gram-scale material to establish an additional European source of this topoisomerase I inhibitor for ADC developers.
- Key milestones include validation batches before the end of 2026 and initial GMP supply in late 2027, each contingent on technical, quality, and regulatory milestones.
- Exatecan (DX-8951) is a camptothecin-class topoisomerase I inhibitor. It is chemically distinct from DXd, the exatecan-derived payload used in Daiichi Sankyo’s deruxtecan ADCs, including trastuzumab deruxtecan and datopotamab deruxtecan-dlnk.
- Exatecan manufacture at the Farmabios site in Gropello Cairoli, Italy, is linked to payload-linker and bioconjugation operations at the Novasep CDMO site in Le Mans, France.
Axplora, a manufacturer of small-molecule APIs and ADCs, announced on September 29, 2026, that it has completed the first R&D batches of exatecan under its Axotecan program [1]. The program aims to create an additional European supply route for exatecan and link its manufacture to the company’s payload-linker and ADC drug substance operations [1].
Program Milestones and Development Timeline
Axplora has produced gram quantities of exatecan in its first R&D batches. Axplora prioritizes the key milestone of initial GMP supply, targeted for late 2027, with each subsequent stage dependent on successful completion of the required technical, quality, and regulatory milestones.
Axplora reports that it is engaging with ADC developers during development to define required specifications, volumes, and integration options ahead of GMP availability [1]. It has not disclosed the specific regulatory filings, jurisdictions, or registration pathway associated with the planned 2027 registration activities [1].
Exatecan: Pharmacology and Role as an ADC Payload Starting Point
Exatecan (DX-8951; DX-8951f as the mesylate salt) is a water-soluble camptothecin analog originally synthesized by investigators at Daiichi Pharmaceutical [2]. Unlike irinotecan (CPT-11), which requires carboxylesterase-mediated conversion to its active metabolite SN-38, exatecan does not depend on enzymatic activation [2]. In the original preclinical characterization across 32 human cancer cell lines, the mean GI50 of DX-8951f was approximately 6-fold lower than that of SN-38 and 28-fold lower than that of topotecan [2]. The compound also retained activity against P-glycoprotein-mediated multidrug resistance [2].
Camptothecins act as DNA topoisomerase I poisons, stabilizing the enzyme-DNA cleavage complex and preventing religation of single-strand breaks [3]. The clinical utility of the class as free drugs has been limited by solubility, lactone stability, toxicity, and acquired resistance, and targeted conjugation has been identified as a route to improve the therapeutic index [3]. Exatecan and DXd are distinct molecules. DXd is an exatecan-derived topoisomerase I inhibitor payload developed by Daiichi Sankyo for its deruxtecan ADC platform [4]. In deruxtecan ADCs, DXd is connected to the antibody through a tetrapeptide-based, enzymatically cleavable linker. Trastuzumab deruxtecan (DS-8201a) combines a humanized anti-HER2 antibody with this linker-payload system [4].
Preclinical studies attributed a bystander killing effect in HER2-heterogeneous tumor models to the high membrane permeability of released DXd [5]. The FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu®) on December 20, 2019; the indication subsequently received regular approval in 2022 [6]. The same DXd-based linker-payload is also used in datopotamab deruxtecan-dlnk (Datroway®), a Trop-2-directed ADC that has received multiple FDA approvals since January 2025 [7][8][9].
Axplora describes exatecan as an important starting point for a growing class of ADC payloads and states that access to material of the required quality, scale, and timing becomes more critical as exatecan-based programs advance [1]. This announcement concerns exatecan itself and does not state that Axotecan material is intended for DXd-based ADC programs [1].
Manufacturing Architecture
The Axotecan program draws on two of Axplora’s three business units: Farmabios for high-potency exatecan synthesis and Novasep CDMO for downstream ADC manufacturing [1]. The third unit, PharmaZell, focuses on complex small-molecule APIs [1].
Exatecan synthesis at Gropello, Cairoli, Italy
Farmabios provides highly potent development, containment, and manufacturing capabilities at Gropello Cairoli [1]. Axplora reports five independent manufacturing lines under an occupational exposure band (OEB) 5 containment strategy, with batch sizes ranging from 0.5 to 300 kilograms [1]. The company reports more than 35 years of experience in high-potency synthesis and purification [1].
In March 2026, Axplora announced a milestone in a $60 million investment program to expand HPAPI development and manufacturing at the Farmabios site in Gropello Cairoli [10]. The current phase includes construction of a new 4,500 m², three-story R&D and laboratory hub intended to support development, scale-up, analytical testing, and high-potency manufacturing [10]. Axplora stated that the site’s existing HPAPI manufacturing capacity is qualified and operational, with initial projects underway, and that the new facility is targeted for completion in February 2027 [10]. This investment is separate from the Axotecan program, which is another initiative at the same site [1][10].
Payload-linker and bioconjugation at Le Mans, France
Novasep CDMO operates Axplora’s ADC center of excellence at Le Mans, where payload-linker development and manufacturing are co-located with bioconjugation [1]. Axplora reports more than 20 years of cGMP ADC development and manufacturing experience and states that its operations are part of the supply chain for six commercial FDA-approved ADCs [1][10]. It did not publicly identify the six products in the materials reviewed for this article.
Axplora’s stated rationale for integration
According to Axplora, linking exatecan manufacture with downstream operations is intended to reduce technical handoffs between suppliers and support technology transfer and scale-up from payload starting material through ADC drug substance [1]. It also states that this model allows evaluation of synthesis and purification decisions alongside their effects on conjugation and the final drug substance [1].
Supply-Chain Context and Network Realignment
Axplora identifies three supply constraints for exatecan-based ADC programs: limited sourcing options, lengthy supplier qualification, and technical handoffs across multiple vendors [1]. It positions Axotecan as an additional European supply route to address these constraints. Still, it has not published comparative data on the size or geographic distribution of the current global exatecan supply base [1].
The program follows a realignment of the Gropello Cairoli site. In June 2026, Axplora announced that ursodeoxycholic acid (UDCA) manufacturing would transfer fully from Gropello Cairoli, within the Farmabios unit, to its Vizag, India facility, within the PharmaZell unit, by the end of 2026 [12][13]. The company said the consolidation allows Farmabios to focus on highly potent API and steroid manufacturing [13].
Axplora announced a €6.5 million investment to expand manufacturing capacity at its Vizag site in August 2025 [14]. In June 2026, the company said this investment supported expanding UDCA manufacturing capacity and developing an integrated production platform spanning bile sourcing through API manufacturing [15]. Axplora reports operating nine API manufacturing sites across Europe and India [1].
Series Cross-Reference
References
[1] Axplora. Axplora launching “Axotecan” to strengthen global ADC supply [press release]. September 29, 2026. Online. Last accessed on September 29, 2026.
[2] Mitsui I, Kumazawa E, Hirota Y, Aonuma M, Sugimori M, Ohsuki S, Uoto K, Ejima A, Terasawa H, Sato K. A new water-soluble camptothecin derivative, DX-8951f, exhibits potent antitumor activity against human tumors in vitro and in vivo. Jpn J Cancer Res. 1995 Aug;86(8):776-82. doi: 10.1111/j.1349-7006.1995.tb02468.x. PMID: 7559102; PMCID: PMC5920901.
[3] Martino E, Della Volpe S, Terribile E, Benetti E, Sakaj M, Centamore A, Sala A, Collina S. The long story of camptothecin: From traditional medicine to drugs. Bioorg Med Chem Lett. 2017 Feb 15;27(4):701-707. doi: 10.1016/j.bmcl.2016.12.085. Epub 2016 Dec 31. PMID: 28073672.
[4] Ogitani Y, Aida T, Hagihara K, Yamaguchi J, Ishii C, Harada N, Soma M, Okamoto H, Oitate M, Arakawa S, Hirai T, Atsumi R, Nakada T, Hayakawa I, Abe Y, Agatsuma T. DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1. Clin Cancer Res. 2016 Oct 15;22(20):5097-5108. doi: 10.1158/1078-0432.CCR-15-2822. Epub 2016 Mar 29. PMID: 27026201.
[5] Ogitani Y, Hagihara K, Oitate M, Naito H, Agatsuma T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016 Jul;107(7):1039-46. doi: 10.1111/cas.12966. Epub 2016 Jun 22. PMID: 27166974; PMCID: PMC4946713.
[6] Narayan P, Osgood CL, Singh H, Chiu HJ, Ricks TK, Chiu Yuen Chow E, Qiu J, Song P, Yu J, Namuswe F, Guiterrez-Lugo M, Hou S, Pierce WF, Goldberg KB, Tang S, Amiri-Kordestani L, Theoret MR, Pazdur R, Beaver JA. FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. Clin Cancer Res. 2021 Aug 15;27(16):4478-4485. doi: 10.1158/1078-0432.CCR-20-4557. Epub 2021 Mar 22. PMID: 33753456; PMCID: PMC8570919.
[7] US Food and Drug Administration. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. January 17, 2025. Online. Last accessed on September 29, 2026.
[8] US Food and Drug Administration. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. June 23, 2025. Online. Last accessed September 29, 2026.
[9] US Food and Drug Administration. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic triple-negative breast cancer. May 22, 2026. Online. Last accessed September 29, 2026.
[10] Axplora. Biopharma’s growing emphasis on highly potent drugs drives Axplora manufacturing expansion [press release]. March 17, 2026. Online. Last accessed September 29, 2026.
[11] Hofland P, Garcia D, Portillo S, Saldana S, Reynolds SC, Rosenthal ET, Hofland EE, Corvalán Urízar M, Adair A. ADC Drug Map – J. ADC. December 2, 2013 DOI: 10.14229/jadc.2013.12.02.001
[12] Contract Pharma. Axplora to consolidate UDCA manufacturing at Vizag, India site by end of 2026. June 10, 2026. Online. Last accessed September 29, 2026.
[13] Pharma Manufacturing. Axplora consolidates UDCA manufacturing at India site to expand integrated API supply. June 2026. Online. Last accessed September 29, 2026.
[14] Axplora. Axplora announces €6.5 million investment at Vizag site and FDA inspection success across Indian operations [press release]. August 5, 2025. Online. Last accessed September 29, 2026.
[15] Axplora. Axplora consolidates UDCA manufacturing at Vizag site to strengthen integrated global supply and support future growth [press release]. June 10, 2026. Online. Last accessed September 29, 2026.
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