SOPHIA ANTIPOLIS, France – October 24, 2025 │ Hansoh Pharmaceutical has signed a license agreement with Roche to develop HS-20110, a CDH17-targeting antibody-drug conjugate (ADC) utilizing a clinically validated topoisomerase inhibitor payload. Hansoh Pharma gives Roche an exclusive worldwide license (excluding the Chinese Mainland, Hong Kong, Macau and Taiwan) to advance the clinical development and commercialization of HS-20110. Roche will pay $80 million upfront in the deal. According to the Chinese collaborator, they are entitled to development, regulatory, and commercialization milestones, but they did not specify the amount.

Innovating for the future: Hansoh Pharma’s strategic focus on targeted therapies and ADCs

Founded in 1995 and headquartered in China, Hansoh Pharmaceutical Group, also known as Hansoh Pharma, is one of China’s leading innovation-driven pharmaceutical companies. Listed on the Hong Kong Stock Exchange since 2019, the company develops, manufactures, and commercializes both innovative and generic medicines across major therapeutic areas, including oncology, central nervous system disorders, infectious diseases, metabolism, and autoimmune conditions. Hansoh operates as a fully integrated R&D-driven organization, supported by more than 700 patent families and four research centers located in China and the United States.

In the oncology field, Hansoh Pharma has gained recognition for developing targeted therapies and antibody-based biologics. Its flagship product, Aumolertinib (Ameile), a third-generation EGFR inhibitor, is approved in China for the treatment of non-small cell lung cancer and exemplifies the growing strength of domestic clinical innovation. The company is also advancing several immuno-oncology candidates, including monoclonal antibodies and antibody-drug conjugates, aiming to meet global biopharmaceutical standards. Hansoh’s ADC platform, integrating antibody engineering, novel tumor target discovery, and optimized cytotoxic payload design, represents a strategic pillar of its oncology pipeline.

HS-20110: a next-generation ADC targeting cadherin 17 in solid tumors

HS-20110 is an ADC targeting cadherin-17 (CDH17), a cell adhesion molecule that maintains the integrity of tissues. It is a membranous cell adhesion protein predominantly expressed in intestinal epithelial cells. The ADC is linked to topoisomerase inhibitor payload. Topoisomerases are enzymes that can alter DNA topology in eukaryotic cells.

Safety and tolerability of HS-20110 in advanced solid malignant tumors

On December 16, 2024, HS-20110 for injection obtained the Clinical Trial Approval issued by the National Medical Products Administration (NMPA) of China, which is intended to be investigated in clinical trials for advanced solid tumor.

The ongoing first-in-human study NCT06892379 is an open-label, multicenter phase I dose-escalation/expansion trial of HS-20110, in adults with pathologically confirmed advanced solid tumors. Sponsored by Hansoh Biomedical R&D, the trial aims to characterize safety, tolerability, pharmacokinetics, and preliminary antitumor activity, with an estimated enrollment of 475 patients. The study started on February 26, 2025, and is still recruiting. It lists an estimated primary completion in December 2026 and study completion in September 2027. U.S. sites include BRCR Medical Center in Florida and The University of Texas MD Anderson Cancer Center, underscoring the program’s global footprint.

Building a versatile ADC platform: Hansoh’s strategic patents on anti-CDH17 conjugates

Hansoh Pharma owned 780 patent families whose 2 on ADC area (7 documents – Europe, Australia, New Zealand, China, Taiwan, Mexico, Brazil), filed in 2024 (pending applications).

The ADC related in WO2024/199337 patent family is an anti-CDH17 antibody conjugated to a toxin drug by a linker for cancer treatment. In claims, many drugs are described: tubulin inhibitors (e.g., auristatin and maytansine analogues such as MMAE, MMAF, DM1, DM4) and topoisomerases inhibitors (e.g., camptothecin derivatives such as SN-38, exatecan, Dxd). In in vivo studies disclosed in this patent application, it is not the ADC HS-20110, conjugated to topoisomerase inhibitor, which is used but an ADC with MMAE drug. Studies were performed in female BALB/c nude mice, engrafted subcutaneously with AsPC1 cells (pancreatic cancer) or with GP2d cells (colorectal cancer). The mice were treated with ADCs (6 mg/kg) intravenously Q4D x 3. Tumor growth in mice treated with ADC-02, ADC-05, ADC-06, ADC-07, and ADC-10 was inhibited compared to the vehicle/PBS group (figure 1). Among them, the tumor growth of ADC-02, ADC-05, ADC-07, and ADC-10 was inhibited compared to the ADC-11 positive control group. The tumor volumes in ADC-11 group increased after around 30 days.

Figure 1: Tumor-Inhibitory Experiment of ADCs Towards CDH17 Positive Cancer Cell Nude Mouse Subcutaneous Transplantation Tumor Model. a) Anti-CDH17 ADCs inhibit tumor growth in AsPC1 tumor-bearing mice. B) Anti-CDH17 ADCs inhibit tumor growth in GP2d tumor-bearing mice.

The second patent family, WO2025/087264, extends and strengthens Hansoh’s intellectual property protection around its anti-CDH17 ADC. Claims are focused on the ADC formula; no drug is described. In the description, topoisomerase inhibitors and tubulin inhibitors are advanced such as camptothecin derivatives such as SN-38, exatecan, Dxd and auristatin / maytansine analogues such as MMAE, MMAF, DM1, DM4. This strategic continuation demonstrates Hansoh’s intent to protect a versatile ADC platform adaptable to multiple payload classes, ensuring freedom to operate for future developments beyond HS-20110. From a competitive intelligence perspective, this second patent family underlines Hansoh’s effort to build a broad IP perimeter around CDH17 as a therapeutic target in gastrointestinal and other solid tumors, while aligning its claims with the molecule currently in clinical evaluation.

Hansoh and Roche strengthen IP and global ties in the ADC Landscape

Hansoh Pharmaceutical’s recent patent filings on CDH17-targeting ADCs illustrate a clear intent to secure intellectual property around its innovative antibody-drug conjugate platform. By covering both topoisomerase and tubulin inhibitor payload classes, Hansoh aims to establish a broad technological perimeter and reinforce its competitive position in oncology. The deal with Roche builds on this foundation, positioning Hansoh as a key innovator in the ADC field. For Roche, already a major player in ADCs, this collaboration follows its 2024 partnership with MediLink Therapeutics on a c-Met–directed ADC, reinforcing its investment in Chinese innovation. Hansoh’s recent alliances, including with GSK for rezetecan, reflect growing global confidence in China’s biopharma capabilities. In a broader context, Western biopharma firms invested over $48.5 billion in Chinese partnerships in the first half of 2025, underscoring the country’s emergence as a crucial hub for next-generation oncology assets.

Press contact
contact@knowmade.fr
Le Drakkar, 2405 route des Dolines, 06560 Valbonne Sophia Antipolis, France
www.knowmade.com

About the author
Fabienne Massa, PhD., works for KnowMade in the field of Biotechnology and Life Sciences. She holds a PhD in Molecular and Cellular Biology from the IPMC (Sophia Antipolis, France). She also holds a Master of Business Management from IAE (Nice, France) and she previously worked in the pharmaceutical industry.

About KnowMade
KnowMade is a technology intelligence and IP strategy consulting company specialized in analyzing patents and scientific publications. The company helps innovative companies, investors, and R&D organizations to understand competitive landscape, follow technological evolutions, reduce uncertainties, and identify opportunities and risks in terms of technology and intellectual property.
KnowMade’s analysts combine their strong technology expertise and in-depth knowledge of patents with powerful analytics tools and methodologies to turn patent information and scientific literature into actionable insights, providing high added value reports for decision makers working in R&D, innovation strategy, intellectual property, and marketing. Our experts provide prior art search, patent landscape analysis, freedom-to-operate analysis, IP due diligence, and monitoring services.
KnowMade has a solid expertise in Compound Semiconductors, Power Electronics, Batteries, RF Technologies & Wireless Communications, Solid-State Lighting & Display, Photonics, Memories, MEMS & Sensors, Semiconductor Packaging, Medical Devices, Medical Imaging, Microfluidics, Biotechnology, Pharmaceutics, and Agri-Food.

SOPHIA ANTIPOLIS, France – July 10, 2025 │ In July, Regeneron received accelerated approval from the FDA for its bispecific antibody (bsAb) Linvoseltamab (brand name Lynozyfic). It is intended to treat adult patients with relapsed or refractory (R/R) multiple myeloma (MM) who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti‑CD38 monoclonal antibody. According to Regeneron, “Linvoseltamab is the 1^st FDA-approved BCMAxCD3 bsAb that can be dosed every 2 weeks starting at week 14, and every 4 weeks if a very good partial response or better is achieved following completion of at least 24 weeks of therapy”. The company and its patent portfolio have been previously described in a KnowMade article “Regeneron Strengthens Odronextamab Patent Portfolio While Adjusting Approval Strategy”.

Linvoseltamab (REGN5458), a fully human BCMA×CD3 bsAb for R/R multiple myeloma

Linvoseltamab is a fully human BCMAxCD3 bsAb designed to bridge B-cell maturation antigen (BCMA) on MM cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing. It was invented using Regeneron’s VelocImmune^® technology which utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. Lynozyfic is cautioned against cytokine release syndrome and neurotoxicity.

The FDA initially rejected the drug in August 2024 due to manufacturing issues at a third-party fill/finish site. However, on July 2, the FDA granted accelerated approval to Regeneron’s bispecific antibody Linvoseltamab for the treatment of patients with R/R MM. Lynozyfic is also approved in the European Union to treat adults with R/R MM after at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy.

Figure 1: Schematic representation of bsAb from Regeneron. For Linvoseltamab, the tumor-specific target (purple) is BCMA binding sites. MHC, major histocompatibility complex; TCR, T-cell receptor. From “Regeneron Corporate presentation – February 2024”.

Evolution of Linvoseltamab clinical development across 12 myeloma studies

There are 12 studies, identified on ClinicalTrials.gov, describing Linvoseltamab for myeloma treatment (table below). For all of them, Regeneron is the sponsor or the collaborator.

Between January 2019 and mid-2025, twelve Phase 1/2, Phase 2 and Phase 3 trials of Linvoseltamab have launched, reflecting a clear shift from first-in-human dose-escalation studies toward combination regimens and maintenance strategies. Early trials established safety and optimal dosing in relapsed/refractory multiple myeloma, paving the way for studies pairing Linvoseltamab with daratumumab, carfilzomib or lenalidomide and even another bsAb from Regeneron to enhance efficacy. Simultaneously, “window-of-opportunity” and IMMUNOPLANT trials are exploring activity in newly diagnosed, treatment-naïve patients, while a dedicated maintenance study aims to prolong minimal residual disease negative status. Nearly all studies are actively recruiting, underscoring robust interest in this BCMA×CD3 bispecific across diverse lines of therapy and clinical settings.

Table 1: Clinical trials for Myeloma treatment with Linvoseltamab.

Efficacy and adverse-event profile of Linvoseltamab in the LINKER-MM1 R/R MM study

The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial (NCT03761108) is investigating Linvoseltamab in more than 300 enrolled patients with R/R MM. The Phase 1 intravenous dose-escalation portion of the trial assessed safety, tolerability and dose-limiting toxicities (nine dose levels) and explored different administration regimens. A subcutaneous Phase 1 portion and an intravenous dose expansion portion Phase 2 are ongoing.

Linvoseltamab was approved by the FDA based on the results of the pivotal Phase 1/2 LINKER-MM1 trial that investigated it for R/R MM. For 80 patients of the study:

• The objective response rate is 70% and 45% achieve a complete response or better.
• The median time to first response is 0.95 months (range: 0.5 to 6 months).
• The median duration of response (DoR) was not reached. Among responders who had a median follow-up of 13 months, the estimated DoR was 89% at 9 months and 72% at 12 months.
• The most common adverse reactions (≥20%) in the safety population of LINKER-MM1 (n=117) were musculoskeletal pain, CRS, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache and dyspnea.
• The most common Grade 3 or 4 laboratory abnormalities (≥30%) were decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin and decreased white blood cell count.

Two complementary patents: BCMA×CD3 bsAb and its dosage regimen

Regeneron has 49 patent families related to bispecific antibodies for oncology treatment, published between 2010 and 2024 (see KnowMade’s report: Bispecific Antibody & Cancer Patent Landscape Analysis).

The patent family WO2020/018820, published in 2020, includes granted patents in Europe, the USA, Japan, China, and other countries, as well as pending applications in Canada, Australia, Brazil, Korea, and additional jurisdictions. It provides bsAbs that bind to both BCMA and CD3, to treat myeloma. In vitro assays, such as binding assays and cytotoxic activity measurements, confirm that these bispecific antibodies activate T cells and mediate the lysis of BCMA-positive cell lines. In vivo efficacy is demonstrated in mouse xenograft models where single or repeat dosing at 0.04 to 4 mg/kg achieves significant tumor growth inhibition. Anti-BCMA x anti-CD3 bsAbs reduce the size and prevent growth of established BCMA-expressing tumors, in a dose-dependent manner (figure 2). These bispecific antibodies also reduce tumor burdens to background levels in vivo.

Figure 2: therapeutic dose-dependent tumor inhibition in vivo by anti-BCMA x anti-CD3 bsAbs (REGN5458).
Immunodefcient NOD.Cg-PrkdcscidII2rgtm1Wjl/SzJ (NSG) mice were subcutaneously implanted with a mixture of 10×106 BCMA-expressing NCI-H929 human multiple myeloma tumor cells and 0.5×106 human peripheral blood mononuclear cells isolated from a normal, healthy donor. On day 5, the mice (n=7 8 per group) were then administered a PBS vehicle control, a CD3-binding control bispecifcAb (mAb17664D) at a dose of 4 mg/kg, a BCMAxCD3 (REGN5458) bsAb at doses of either 4 mg/kg, 0.4 mg/kg, or 0.04 mg/kg. The mice were administered these Abs twice per week for a total of seven doses, and tumor growth was assessed over 55 days. While BCMA+ NCI-H929 tumors grew similarly in the vehicle and CD3-binding control-treated mice, BCMAxCD3 Abs that were tested shrank established tumors and prevented the growth of tumors in a dose-dependent manner in vivo.

One year later, the patent family WO2021/113701 was published. It now includes granted patents in the USA, Japan, and China, as well as pending applications in Europe, Canada, Australia, South Korea, and other jurisdictions. It describes methods for treating multiple myeloma (R/R) using bsAbs that bind to both BCMA and CD3. The subject received at least three prior therapies for multiple myeloma. The bispecific antibody is administered to the subject in a dosing regimen comprising the administration of a single dose of 5 mg of the bsAb during week one, a single dose of 25 mg during week two and a single dose of 200 mg during week three of the dosing regimen.

In summary, Linvoseltamab represents a landmark advancement in the treatment of heavily pretreated multiple myeloma, combining a bispecific antibody targeting BCMA and CD3 complemented by a convenient administration schedule. Its accelerated FDA approval—supported by robust safety and efficacy data from the pivotal LINKER-MM1 trial—validates the clinical potential of T-cell–redirecting therapies in relapsed/refractory multiple myeloma. Across many ongoing clinical studies, Linvoseltamab continues to demonstrate deep, durable responses with a manageable toxicity profile. Noteworthy, the two complementary patent families afford very specific protection for both the BCMA×CD3 bsAb (structure, optimized VH/VL sequences, preclinical efficacy) and its optimized dosing regimen for the treatment of multiple myeloma (dosages, administration regimens, drug combinations). Together, they provide comprehensive protection from molecular design to clinical applications, and the pending applications in key regions are expected to be granted soon, ensuring a broad, global IP shield. Moreover, according to Sundar Jagannath, M.D., Network Director of the Center of Excellence for Multiple Myeloma at Mount Sinai (New York) “Lynozyfic has a convenient response-adapted dosing regimen, which provides the potential to extend time between doses. This is a significant patient-centric advancement that could help reduce treatment burden.” Together, these developments underscore a new era of targeted immunotherapy for BCMA-expressing malignancies and pave the way for broader exploration of bispecific antibodies in oncology.

Press contact
contact@knowmade.fr
Le Drakkar, 2405 route des Dolines, 06560 Valbonne Sophia Antipolis, France
www.knowmade.com

About the author
Fabienne Massa, PhD., works for KnowMade in the field of Biotechnology and Life Sciences. She holds a PhD in Molecular and Cellular Biology from the IPMC (Sophia Antipolis, France). She also holds a Master of Business Management from IAE (Nice, France) and she previously worked in the pharmaceutical industry.

About KnowMade
KnowMade is a technology intelligence and IP strategy consulting company specialized in analyzing patents and scientific publications. The company helps innovative companies, investors, and R&D organizations to understand competitive landscape, follow technological evolutions, reduce uncertainties, and identify opportunities and risks in terms of technology and intellectual property.
KnowMade’s analysts combine their strong technology expertise and in-depth knowledge of patents with powerful analytics tools and methodologies to turn patent information and scientific literature into actionable insights, providing high added value reports for decision makers working in R&D, innovation strategy, intellectual property, and marketing. Our experts provide prior art search, patent landscape analysis, freedom-to-operate analysis, IP due diligence, and monitoring services.
KnowMade has a solid expertise in Compound Semiconductors, Power Electronics, Batteries, RF Technologies & Wireless Communications, Solid-State Lighting & Display, Photonics, Memories, MEMS & Sensors, Semiconductor Packaging, Medical Devices, Medical Imaging, Microfluidics, Biotechnology, Pharmaceutics, and Agri-Food.

SOPHIA ANTIPOLIS, France – May 30, 2025 │ CytomX Therapeutics announced positive Phase 1 data for its Epithelial Cell Adhesion Molecule (EpCAM) PROBODY® Antibody Drug Conjugate candidate, CX-2051, in advanced Colorectal Cancer (CRC).

CytomX Therapeutics: precision oncology through Probody® innovation

CytomX Therapeutics is based in South San Francisco, California. It was founded in 2008 by Frederick Gluck, Dr. Nancy Stagliano, and Professor Patrick Daugherty of the University of California Santa Barbara (Department of Chemical Engineering). CytomX is a clinical-stage biopharmaceutical company focused on oncology. The Probody® platform was developed by using technology licensed from the university, which enables for drug designs that can selectively activate in the tumor microenvironment while minimizing drug activity in healthy tissue. Its pipeline comprises various oncology therapeutic candidates such as antibody-drug conjugates (ADCs), T-cell engagers, and immune modulators (e.g., cytokines). The company has developed strategic partnerships with leaders in oncology, including Amgen, Astellas, Bristol Myers Squibb, Regeneron and Moderna.

Probody® therapeutics are designed to fight cancer by exploiting conditions of the tumor microenvironment by localizing treatment in the tumor and limiting activity in healthy tissue. The company designs Probody therapeutics to mask target binding regions. These “novel therapeutics take advantage of the high levels of protease activity in the tumor microenvironment”. When Probody therapeutics encounter active proteases near tumor tissue, the mask is designed to be removed so that the unmasked therapeutic can bind to the tumor target (figure 1). According to the company, Probody therapeutics have the potential to “create or widen therapeutic window (the balance between a therapy’s dose that is effective without causing unacceptable toxicity), enable new combinations of drugs previously not possible due to toxicities and expand the universe of viable therapeutic targets by opening “undruggable” target space”.

Figure 1: Probody therapeutic. 1- The pioneering antibody prodrug technology. 2- The “masking” peptide is designed to limit the ability of Probody therapeutics to bind to healthy tissue—thereby helping to minimize toxicities. 3- In the tumor environment, protease enzymes are expected to cleave the substrate, removing the “mask” and activating the Probody therapeutic to bind to its target on cancer cells. From CytomX website.

CX-2051: A Next-Generation ADC Targeting EpCAM in Epithelial Cancers

CX-2051 is a conditionally activated ADC directed toward the epithelial cell adhesion molecule (EpCAM), with potential applicability across multiple EpCAM-expressing epithelial cancers. Four decades ago, EpCAM was found to be a tumor antigen in colorectal carcinomas. Due to its frequent and high expression on carcinomas and metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells. However, EpCAM plays also a role in adhesion of normal cells which explains the lack of therapy for now.

CX-2051 is an investigational, masked, conditionally activated ADC directed toward EpCAM-expressing epithelial cancers, including CRC, and armed with camptothecin, a topoisomerase-1 inhibitor payload (figure 2). It was developed in collaboration with ImmunoGen, now part of AbbVie.

Figure 2: CX-2051 detailed.

First-in-Human study of CX-2051 shows encouraging activity and safety in refractory colorectal cancer

The clinical trial NCT06265688 (CTMX-2051-101) is a Phase 1a open-label study, enrolling patients with advanced solid tumors, with a focus on advanced metastatic colorectal cancer (CRC). The purpose of this first-in-human study is to characterize the safety, tolerability, and antitumor activity of CX-2051 in participants with advanced CRC. The study is comprised of 2 parts. In part 1, there is a dose escalation of CX-2051 to identify the maximum tolerated dose (MTD) of CX-2051. In part 2, safety and tolerability will be further evaluated as well as antitumor activity of CX-2051 in indication-specific expansion cohorts.

The clinical study was initiated in April 2024 with dose escalation proceeding through seven dose levels as of the April 7, 2025 data cutoff. The therapeutic activity of the 2.4 and 4.8 mg/kg doses in single patient dose escalation cohorts was not expected. At the 7.2, 8.6, and 10 mg/kg doses, 23 patients were treated in total, 18 of whom were efficacy evaluable, having had at least one post-baseline tumor assessment as of the data cutoff. CX-2051 was administered on a once every three-week schedule (Q3W). The 25 patients enrolled in the study had previously received a median of 4 prior lines of therapy and all patients had previously been treated with irinotecan. 64% of patients had liver metastases, 64% had KRAS mutations (most commonly occurring hotspot mutations in human cancers and associated with a poor prognosis), and 96% were microsatellite stable. Patients were not preselected based on EpCAM expression levels.

Preliminary data revealed by CytomX:

• Efficacy Results: At the expansion dose levels of 7.2, 8.6 and 10 mg/kg administered every three weeks (Q3W), 18 patients were evaluable for efficacy.
• Overall response rate (ORR): Five of these 18 patients (28 %) achieved confirmed partial Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 responses. ORR for currently approved therapies in 3^rd line or later CRC are in the low to mid-single digit percentages1. Notably, at the 10 mg/kg dose, 3 of 7 evaluable patients (43%) achieved confirmed partial responses. Across all three dose cohorts, the Disease Control Rate was 94%.
• Durability: At the data cutoff, the median progression free survival was 5.8 months and 10 of 18 patients remained on the treatment.
• Safety Results: CX-2051 was well-tolerated with manageable adverse events, with no observed dose limiting toxicity. Most of treatment related adverse events (TRAEs) were Grade 1 or Grade 2 in severity. The most frequently reported TRAEs were diarrhea, nausea, vomiting, fatigue, anemia, hypokalemia, neutrophil count decrease and neutropenia. Five patients experienced serious TRAEs, but there were no Grade 4 or 5 TRAEs observed. No events of pancreatitis, interstitial lung disease or febrile neutropenia were reported at time of data cutoff.

Dose expansions have been initiated at doses of 7.2, 8.6 and 10 mg/kg Q3W. The selection of the recommended phase 2 dose will be informed by enrolling a total of 20 patients at each dose level.

CytomX builds global IP position around activatable EpCAM ADCs with promising preclinical profiles

CytomX Therapeutics owns 84 patent families (960 documents), filed between 2000 and 2024. The company has a strong worldwide IP strategy, with patent applications in Europe, the USA and Asia. About 73% of its patents are currently alive (pending or granted patents), reflecting that its R&D efforts are still on going to improve the current technologies involving cancer therapies. The strength of its patent portfolio may increase in the coming years because 55% of its live patents are pending applications. CytomX has co-filed several patent families with major players in the pharmaceutical industry such as Immunogen (AbbVie), Amgen or BMS.

There are 2 patent families (26 documents) describing ADC against Epithelial Cell Adhesion Molecule (EpCAM). They were filed in 2019 and 2023 by CytomX in collaboration with Immunogen, acquired by AbbVie in 2024. Both patent applications are published worldwide such as Europe, America (the USA, Canada, Mexico, Brazil), Australia and Asia (Japan, China, Korea, Singapore, India, Taiwan). At the end of March 2025, the Examining Division notified its intention to grant a European patent for the invention EP3873512 (WO2020/086665 – 2019). Before, claims and description were amended several times (December 2021, September 2022, May 2023, September 2023, February 2025). The new claims are now more precise (heavy and light chains with specific sequences). Therefore, they have a more limited scope which is less restrictive for competitors.

The ADC described in the patent family WO2020/086665 is an EpCAM antibody coupled to a maytansinoid compound (antimitotic agent). It is not the ADC CX-2051 which is conjugated to camptothecin. However, this patent family describes also an EpCAM activable antibody, linked to a cytotoxic drug, to treat solid cancers. Studies were performed in CB17 SCID mice bearing NCI- H2110 tumors, a human non-small cell lung cancer sub-cutaneous xenograft model. All treatments were well tolerated at the indicated doses, and no body weight loss was observed. Tumor regressions in the 3 µg/kg regimen started at early time points following ADC administration and resulted in multiple partial regressions as early as 7 days post treatment (figure 3). These data show that treatment with huEpCAM23Gv4.2-DGN549 induces a high incidence of tumor regressions in this tumor model and results in potent anti-tumor activity at doses as low as 1.5 µg/kg.

Figure 3: It shows the anti-tumor activity of huEpCAM23Gv4.2-lys-DGN549 in the non-small cell lung cancer xenograft model. The ADC huEpCAM23Gv4.2-DGN549 was highly active at 3 µg/kg, with a tumor growth inhibition value of 1.8%. Furthermore, this group also showed a LCK = 1.77 (log cell kill), qualifying the treatment as active (++), and a 179% increased life span (highly active), demonstrating good tumor growth delay. dpi: days post-inoculation; TV: tumor volume.

The patent family WO2024/015830 relates to an activatable human lgG1 EpCAM antibody. This antibody has eight cysteines covalently bounded to linker-payloads, camptothecin toxin (CPT66). The EpCAM activatable antibodies have relatively low systemic toxicities. In cynomolgus monkeys EpCAM-CPT66 was tolerated up to 60 mg/kg. This was in stark contrast to EpCAM-DM21 , an immunoconjugate comprising the same EpCAM activatable antibody as EpCAM-CPT66 but with the auristatin-based DM21 linker-payload, which was only tolerated up to 6 mg/kg. Tolerability of EpCAM-CPT66 is also favorable when compared to fam-trastuzumab deruxtecan-nxki, where the highest non-severely toxic dose was determined to be 30 mg/kg in cynomolgus monkeys. In another study, unmasked immunoconjugate (EpCAM antibody with conjugated CPT66 linker-payload; EpCAM(-)-CPT66) was also evaluated in a tolerability assay, where it was administered intravenously in cynomolgus monkey at 10 mg/kg at Q2Wx2. The animal made it to scheduled necropsy with mild intervention, mild clinical signs including vomitus and low food consumption. Hematology revealed mild signs of neutropenia and reticulocytosis. At the end of treatment period gross observation was noted in the cecum. Microscopic findings were noted in the lung, Gl tract, and lymphoid tissues. In contrast, there was no test article-related findings at 10 mg/kg dosing of EpCAM-CPT66 (EpCAM activatable antibody) in cynomolgus monkeys.

Figure 4: activatable EpCAM antibody immunoconjugate. The ADC comprises an EpCAM antibody, a cleavable substrate linker, and a mask. In an uncleaved (inactive) state, the mask inhibits the binding of the EpCAM antibody to EpCAM. The cleavable substrate linker is cleavable by a protease. Upon cleavage, the mask is released and the antibody is free to bind to EpCAM. There are 8 conjugated camptothecin-derived (CPT66) linker-payloads (shown as ovals in cartoon). The conjugation of the linkerpayloads to the activatable EpCAM antibody is stochastic, with conjugation occurring at the antibody’s inter-chain cysteines.

Strong foundations for the future of CX-2051

CytomX Therapeutics is advancing precision oncology with CX-2051, a novel EpCAM-targeted Probody® ADC showing encouraging early clinical results in advanced colorectal cancer. The favorable safety and efficacy signals underscore its therapeutic promise. With a robust global IP portfolio (84 patent families) and strong industry partnerships, CytomX is well-positioned for future development. Continued clinical progress and patent protection could unlock new treatment options for hard-to-treat epithelial cancers. CX-2051 may represent a new standard in conditionally activated cancer therapies.

Press contact
contact@knowmade.fr
Le Drakkar, 2405 route des Dolines, 06560 Valbonne Sophia Antipolis, France
www.knowmade.com

About the author
Fabienne Massa, PhD., works for Knowmade in the field of Biotechnology and Life Sciences. She holds a PhD in Molecular and Cellular Biology from the IPMC (Sophia Antipolis, France). She also holds a Master of Business Management from IAE (Nice, France) and she previously worked in the pharmaceutical industry.

About KnowMade
KnowMade is a technology intelligence and IP strategy consulting company specialized in analyzing patents and scientific publications. The company helps innovative companies, investors, and R&D organizations to understand competitive landscape, follow technological evolutions, reduce uncertainties, and identify opportunities and risks in terms of technology and intellectual property.
KnowMade’s analysts combine their strong technology expertise and in-depth knowledge of patents with powerful analytics tools and methodologies to turn patent information and scientific literature into actionable insights, providing high added value reports for decision makers working in R&D, innovation strategy, intellectual property, and marketing. Our experts provide prior art search, patent landscape analysis, freedom-to-operate analysis, IP due diligence, and monitoring services.
KnowMade has a solid expertise in Compound Semiconductors, Power Electronics, Batteries, RF Technologies & Wireless Communications, Solid-State Lighting & Display, Photonics, Memories, MEMS & Sensors, Semiconductor Packaging, Medical Devices, Medical Imaging, Microfluidics, Biotechnology, Pharmaceutics, and Agri-Food.

SOPHIA ANTIPOLIS, France – April 11^th, 2025 │ On March 19^th, 2025, a collaboration was announced between Oxford BioTherapeutics (OBT) and Roche to discover novel potentially first-in-class antibody-based therapeutics for the treatment of cancer. Targets will be identified via the OGAP®-Verify discovery platform of OBT, a proprietary database on membrane protein abundance, with around 7,000 cataloged proteins across cancers and healthy tissues, and will be validated through research collaboration. Any further research, development and commercialization efforts against these targets will be driven by Roche. OBT will receive up to US$36 million upfront payments from Roche and may be eligible to receive milestone payments potentially exceeding US$1 billion, plus product royalties on net sales.

Targeting the toughest tumors: how Oxford BioTherapeutics and Roche are advancing next-gen ADC therapies

Empowering immuno-oncology: Oxford BioTherapeutics develops first-in-class ADCs for difficult-to-treat cancers

Oxford BioTherapeutics was founded in Oxford, UK, in 2004. It is a clinical stage oncology company which develops immuno-oncology (IO) and antibody-drug conjugate (ADC) treatments for cancer.

Its lead clinical program, OBT076, is an ADC in Phase 1b clinical development in patients with advanced or refractory solid tumors, including gastric, bladder, ovarian and lung cancer, where CD205 is overexpressed (NCT04064359, “Safety and Preliminary Efficacy of OBT076 in Recurrent/​Metastatic CD205+ Solid Tumors”, recruiting). OBT076 is composed of an antibody (Ab) that targets the CD205 protein present on immune cells promoting tumor growth, conjugated via a cleavable linker SPDB to the derivative microtubule inhibitor, DM4, which can kill them. By depleting immunosuppressive dendritic cells, OBT076 has the potential to reactivate the immune system and promote the induction and activation of T-cells to enhance the anti-tumor response.

OBT develops multiple strategic partnerships including with Boehringer Ingelheim, ImmunoGen (now part of Abbvie), Zymeworks, Amgen, WuXi, Medarex (BMS), etc.

Roche at the forefront of targeted cancer therapy with approved and emerging ADCs

Roche develops differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. It also provides in vitro diagnostics, tissue-based cancer diagnostics, and diabetes management.

Currently, Roche has 4 ADC in its pipeline, whose 2 are on the market, Polivy and Kadcyla. Polivy (Polatuzumab vedotin, RG7596) is an ADC develops with Seagen that consists of a monoclonal Ab anti-CD79b, conjugated to a potent anti-cancer agent that is selectively delivered to tumor cells. It is currently approved in combination with rituximab, cyclophosphamide, doxorubicin and prednisone in more than 95 countries worldwide, including the US and EU, for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL). Polivy is also approved in combination with bendamustine plus rituximab in more than 100 countries worldwide for the treatment of adults with relapsed or refractory (R/R) DLBCL after one or more prior therapies. Regarding Kadcyla (trastuzumab emtansine, RG3502) is an ADC develops with ImmunoGen (acquired by AbbVie) that combines the therapeutic effect of trastuzumab (the active substance of Herceptin) with intracellular delivery of DM1, a highly potent chemotherapy agent, to specifically target HER2-positive tumors. It is indicated for high-risk patients with adjuvant HER2-positive breast cancer (HER-2+ eBC high-risk). Moreover, Roche has 2 ADC in development. First, YL211 is developed in collaboration with MediLink. It selectively targets cMET expressed on the surface of target cancer cells (solid tumors). Second, IBI3009, in partnership with Innovent, an ADC targeting DLL3 antigen with a Topo1 isomerase payload (Small Cell Lung Cancer).

Roche is exploring the ADC space more deeply through its partnership with OBT.

Transforming ADC discovery: OBT’s OGAP® platform identifies novel targets beyond conventional biomarkers

Figure 1: Workflow of OBT’s target discovery, adapted from a poster of OBT.

OBT’s proprietary Oxford Genome Anatomy Project (OGAP®) target discovery platform is based on a large proprietary cancer membrane proteomic database, with data on over 7,000 cancer cell proteins, providing highly qualified oncology targets. The company leverages its platform – OGAP® to identify first-in-class Ab based therapeutic targets by directly measuring membrane protein abundance in patient tissues using quantitative mass spectrometry.

Few cancer patients are eligible for treatment with existing ADCs because ADC-target expression on patient tumors is a major factor in patient eligibility. Furthermore, most ADCs in development target the same proteins as those already approved. With OGAP®-Verify, OBT can identify first-in-class targets to treat patients who are currently ineligible for existing treatments. The platform is able to detect protein expression levels as low as 50 copies-per-cell, which may reveal targets that were missed by mRNA analysis. Moreover, it provides insights into normal tissue expression which improves target selection and accelerates the drug target discovery process. The likelihood of success in ADC development is increased by OGAP®-Verify evaluation of factors like therapeutic index, protein abundance and benchmarking against known clinical ADC targets during target selection.

The strategic collaboration between Oxford BioTherapeutics and Roche leverages the power of the OGAP®-Verify platform, whose value is largely based on a robust intellectual property portfolio. A comprehensive set of patent families supports the scientific foundations and therapeutic applications of the platform, highlighting the breadth of novel targets and methods identified by OBT.

Identified patent families related to OGAP®-Verify

Oxford Biotherapeutics owns 26 patent families (171 documents) published between 2006 and 2019, including 21 filed between 2006 and 2011 (Table 1). The company follows a global IP strategy, with protections in the USA, Europe, Japan, and additional coverage in Canada, Australia, China, and other countries. OBT holds 11 patent families describing antibody constructs. These antibodies are capable of binding to antigens that have been observed in various types of cancer, such as:

• Lymphocyte antigen 75 (LY75): endocytic receptor to direct captured antigens from the extracellular space to a specialized antigen-processing compartment;
• Bone marrow stromal antigen 1 (BST1): lipid-anchored, bi-functional ectoenzyme that catalyzes ribonucleotide cyclisation and hydrolysis;
• Cadherin-17: calcium dependent cell adhesion proteins, they preferentially interact with themselves in a homophilic manner in connecting cells;
• Immunoglobulin superfamily member 4 (IGSF4): membrane glycoprotein with an extracellular domain homologous to those of immunoglobulin superfamily proteins. It may act as a tumor antigen recognized by activated NK or CD8+ T cells;
• Integrin beta 4: receptor for laminin, plays a critical structural role in the hemidesmosome of epithelial cells;
• Delta-like protein 3 or (DLL3): type I membrane protein, member of the Delta family;
• Matriptase stem: the protein is known to undergo a series of endoproteolytic cleavages followed by activation site autocleavage resulting in a matriptase stem which remains on the cell surface and a catalytic domain of the matriptase protein which is released into the blood;
• Mucin 13: high-molecular-weight transmembrane glycoprotein;
• Ephrin type-A receptor 7: receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

The company also discloses several methods across 17 patent families. Six of these families describe diagnostic methods, while eight focus on cancer treatment approaches. For cancer diagnosis, assays are performed to detect polypeptides in samples from subjects, and the results are correlated with the presence or absence of cancer. These results may also be linked to a therapeutic regimen, the risk of relapse, or prognostic clinical outcomes. To evaluate colorectal cancer marker proteins (CRCMPs) in patient serum, a sandwich ELISA is performed using a biotinylated antibody, followed by a multiplex assay using Luminex Technology (with antibodies conjugated to unique Luminex magnetic microspheres — Mug beads, Luminex Corporation, Austin, TX).

For cancer treatments, a therapeutically effective amount of an antibody is administered, with a diluent or carrier. In an example, toxicity of DM1- and DM4-conjugated anti-LY75 monoclonal Ab was tested in cynomolgus monkeys. LY75_DM4 (cleavable) or LY75_DM1 (non-cleavable) was administered twice by intravenous infusion at 5 mg/kg/dose (LY75_DM4) or 10 mg/kg/dose (LY75_DM1). The treatment was well tolerated in cynomologus monkeys. All treatment-related toxicity findings were reversible following a 4-week recovery period (e.g., anemia, decrease in the blood leukocyte profile or increase in AST, CK, LDH).  Most patent families describe colorectal cancer (9) or lung cancer (5).

Table 1:  patent families owned by Oxford Biotherapeutics and describing OGAP®-Verify.

The collaboration between Oxford BioTherapeutics and Roche represents a significant step forward in the evolution of antibody-drug conjugate development. By harnessing the power of OBT’s OGAP®-Verify platform to uncover novel, first-in-class targets, this partnership aims to expand treatment options for patients with cancers currently underserved by existing therapies. Furthermore, beyond the scientific and technological complementarity of the two companies, this alliance is supported by a solid intellectual property base, with a portfolio of strategic patents protecting the targets, antibodies, and associated methods. This IP dimension not only reinforces the value of the OGAP® platform but also ensures freedom of operation and sustainable differentiation in the ADC market. Together, OBT and Roche are paving the way for more effective and personalized cancer treatments.

Oncology treatment innovation is one of KnowMade’s areas of healthcare expertise that you may need for your IP and R&D projects. For more information, please contact us.

Press contact
contact@knowmade.fr
Le Drakkar, 2405 route des Dolines, 06560 Valbonne Sophia Antipolis, France
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About the author
Fabienne Massa, PhD., works for Knowmade in the field of Biotechnology and Life Sciences. She holds a PhD in Molecular and Cellular Biology from the IPMC (Sophia Antipolis, France). She also holds a Master of Business Management from IAE (Nice, France) and she previously worked in the pharmaceutical industry.

About KnowMade
KnowMade is a technology intelligence and IP strategy consulting company specialized in analyzing patents and scientific publications. The company helps innovative companies, investors, and R&D organizations to understand competitive landscape, follow technological evolutions, reduce uncertainties, and identify opportunities and risks in terms of technology and intellectual property.
KnowMade’s analysts combine their strong technology expertise and in-depth knowledge of patents with powerful analytics tools and methodologies to turn patent information and scientific literature into actionable insights, providing high added value reports for decision makers working in R&D, innovation strategy, intellectual property, and marketing. Our experts provide prior art search, patent landscape analysis, freedom-to-operate analysis, IP due diligence, and monitoring services.
KnowMade has a solid expertise in Compound Semiconductors, Power Electronics, Batteries, RF Technologies & Wireless Communications, Solid-State Lighting & Display, Photonics, Memories, MEMS & Sensors, Semiconductor Packaging, Medical Devices, Medical Imaging, Microfluidics, Biotechnology, Pharmaceutics, and Agri-Food.

SOPHIA ANTIPOLIS, France – April 3^rd, 2025 │ March 11^th, Bristol Myers Squibb (BMS) announced a definitive merger agreement to acquire all of the outstanding shares of 2seventy bio for a total equity value of approximately $286 million. The company 2seventy bio decided to focus exclusively on Abecma which was the first B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) – T cells treatment for relapsed or refractory (R/R) multiple myeloma. Abecma is BMS’ second CAR-T therapy, following in the footsteps of the CD19-targeting Breyanzi, approved in February 2021 for large B-cell lymphoma.

The journey of Abecma: from Bluebird bio and Celgene collaboration to BMS and 2seventy bio partnership

The collaboration for BCMA CAR-T cells therapy began between Bluebird bio and Celgene. In March 2013, Bluebird bio and Celgene entered into a collaboration to develop CAR T cell therapies to target cancer cells. Two years later, the collaboration was amended and restated to focus on developing anti-BCMA CAR T program. At the beginning of 2018, Celgene acquired CAR-T specialist Juno Therapeutics for around $9 billion and in 2019, it is BMS which acquired Celgene. In May 2021, the company 2seventy bio entered the market when it was spun out of Bluebird bio, taking with it the BMS-partnered CAR-T therapy Abecma.

Currently, Abecma is being jointly developed and commercialized in the U.S. as part of a co-development, co-promotion, and profit share agreement between BMS and 2seventy bio. BMS assumes sole responsibility for Abecma drug product manufacturing and commercialization outside of the U.S. The companies’ broad clinical development program for Abecma includes ongoing and planned clinical studies (KarMMa-2, KarMMa-9) for patients with multiple myeloma.

Abecma: personalized CAR T-Cell therapy targeting BCMA in R/R Multiple Myeloma

Idecabtagene vicleucel (brand name Abecma) is a BCMA-directed genetically modified autologous CAR T-cell therapy. Each dose is customized using a patient’s own T-cells, which are collected and genetically modified, and infused back into the patient. BCMA is a protein that is nearly universally expressed on cancer cells in multiple myeloma. The therapy is used for the treatment of adult patients with R/R multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

FDA approves Abecma: first cell-based gene therapy for multiple myeloma

On March 26, 2021, the FDA approved Abecma for the treatment of adult patients with R/R multiple myeloma after several prior lines of therapy. This is the first FDA-approved cell-based gene therapy for multiple myeloma. Approval was based on KarMMa clinical trial (NCT03361748). Patients received a single infusion of idecabtagene vicleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Results of the study are:

• Overall response rate: 72% with stringent complete response (CR) rate of 28%.
• Median duration of response: 11 months in responders (PR or better) and 19 months in patients who achieved stringent CR.
• Serious adverse reactions occurred in 67% of patients evaluated for safety. Grade 3 or higher cytokine release syndrome and neurologic toxicities occurred in 9% and 4%, respectively. Hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred in 4% with 2 fatalities. Prolonged cytopenia requiring hematopoietic rescue occurred in 2% with 2 fatalities.

The European Commission approves Abecma as first CAR-T therapy for earlier lines of R/R multiple myeloma

In March 2024, the European Commission has granted approval to Abecma for the treatment of adult patients with R/R multiple myeloma who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Abecma is the 1^st CAR-T cell immunotherapy approved in the European Union for use in earlier lines of therapy for R/R multiple myeloma. This expanded approval of Abecma covers all EU member states. In the EU, Abecma has maintained its Orphan Designation for the treatment of multiple myeloma.

Identified patent families related to BCMA CAR-T cells

To protect this innovative technology, companies own several patent families covering their developments in BCMA CAR-T cell therapies to fight cancer (see table below). However, there is any patent family co-filled by 2seventy Bio / Bluebird Bio with BMS / Celgene.

2seventy Bio / Bluebird Bio own 8 patent families on BCMA CAR-T cells published between 2015 and 2020. First, the patent portfolio described the CAR construct, a humanized anti-BCMA antibody with a CTLA-4 or PD-1 transmembrane domain that reduces cytokine release syndrome of the CAR. Then, manufacturing methods are detailed to construct the CAR T cells. For example, T cells are activated and stimulated by phosphatidylinositol-3 kinase (PI3K) inhibitor (e.g., ZSTK474), and they are transduced with a viral vector comprising a polynucleotide encoding a CAR. To detect anti-BCMA CAR expression on T cells, an anti-BCMA CAR antibody is produced and described in some patent families. Finally, a composition is realized with immune effectors cells transfected with the CAR construct and a pharmaceutical carrier. In human clinical trials, the therapeutically effective amount of anti- BCMA CAR T cells in patients with R/R multiple myeloma is between 5×10⁷ and 45×10⁷ cells. No dose limiting toxicities, neurotoxicity and Grade 2, 3 or higher cytokine release syndrome have been observed. The composition is formulated for intravenous administration in a single dose.

BMS / Celgene / Juno Therapeutics own 12 patent families on BCMA CAR-T cells published between 2020 and 2024. These patent families mainly describe methods of treatment or methods of predicting treatment response. For example, before administrating immune cells expressing BCMA CAR T cells in subject with multiple myeloma, the level of soluble BCMA is determined. Moreover, previously CAR T treatment, the subject can receive prior cancer therapy such as topoisomerase or proteasome inhibitor therapies. However, the subject was treated with no more than three lines of prior therapy (e.g., dexamethasone, doxorubicin, cisplatin, doxorubicin, etoposide, an anti-CD38 antibody, elotuzumab), and there is evidence of progressive disease within 60 days of the most recent line of prior treatment. The patient can also have an early relapse, an inadequate response, or a suboptimal response to one or more anti-myeloma drugs. For CAR T cells treatment in patients with R/R multiple myeloma, the immune cells can be administered in a dosage between 150 × 10⁶ and 450 × 10⁶ cells. Then, for predicting treatment response, the level of one or more inflammation-related soluble factors in serum is determined. If the level is similar to that in serum from a patient responsive to CAR T cells, a therapeutically effective dose of the CAR T cells is administered. For example, in a study, results identified IgG, sBCMA, and PT-INR test as negative correlates of complete response (CR), and vector copy number in drug product as a positive correlate of CR. As sBCMA is an indicator of tumor burden and can affect therapies targeting BCMA, selecting patients with low tumor burden and controlling tumor burden during manufacturing or bridging therapy may be important in achieving CR.

Table 1: patent families owned by BMS or 2seventy Bio and describing BCMA CAR-T cells.

From autologous to allogeneic CAR-T cells: a necessary evolution?

Autologous CAR-T cells are now an established treatment for patients with R/R B cell lymphomas, B cell acute lymphoblastic leukemia and multiple myeloma. Data on the outcomes of patients shows that remissions induced by anti-BCMA CAR-T cells have generally limited long-term toxicities but are more short-lived.

Moreover, several disadvantages of autologous CAR therapy are widely described, such as an expensive process, manufacturing failure in some patients, and too long manufacturing times. These problems have led some scientists to develop other approaches, such as allogeneic CAR. To produce allogeneic CAR-T cells, a source of third-party healthy T lymphocytes is needed. These T cells are genetically modified to express a CAR. Then, T cells are expanded and selected. Finally, vials are filled with allogeneic CAR T cells, stored, frozen, and shipped to hospitals when needed. These “off-the-shelf” CAR T-cells, from healthy donors, could potentially address major issues of autologous CAR therapy. However, this brings with it new risks such as graft versus host disease (GVHD). To avoid GVHD, many solutions are evaluated by companies and academics in allogeneic CAR area and they are described in our report: Allogeneic CAR – 2023.

Press contact
contact@knowmade.fr
Le Drakkar, 2405 route des Dolines, 06560 Valbonne Sophia Antipolis, France
www.knowmade.com

About the author
Fabienne Massa, PhD., works for Knowmade in the field of Biotechnology and Life Sciences. She holds a PhD in Molecular and Cellular Biology from the IPMC (Sophia Antipolis, France). She also holds a Master of Business Management from IAE (Nice, France) and she previously worked in the pharmaceutical industry.

About KnowMade
KnowMade is a technology intelligence and IP strategy consulting company specialized in analyzing patents and scientific publications. The company helps innovative companies, investors, and R&D organizations to understand competitive landscape, follow technological evolutions, reduce uncertainties, and identify opportunities and risks in terms of technology and intellectual property.
KnowMade’s analysts combine their strong technology expertise and in-depth knowledge of patents with powerful analytics tools and methodologies to turn patent information and scientific literature into actionable insights, providing high added value reports for decision makers working in R&D, innovation strategy, intellectual property, and marketing. Our experts provide prior art search, patent landscape analysis, freedom-to-operate analysis, IP due diligence, and monitoring services.
KnowMade has a solid expertise in Compound Semiconductors, Power Electronics, Batteries, RF Technologies & Wireless Communications, Solid-State Lighting & Display, Photonics, Memories, MEMS & Sensors, Semiconductor Packaging, Medical Devices, Medical Imaging, Microfluidics, Biotechnology, Pharmaceutics, and Agri-Food.

SOPHIA ANTIPOLIS, France – March 7, 2025 │ A few days ago, Regeneron decided to no longer seek accelerated approval of odronextamab, a bispecific antibody (bsAb) CD20 x CD3, for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, the company is continuing to pursue this approval for follicular lymphoma (FL), with an FDA decision expected by July 30, 2025. Regeneron is justifying its withdrawal of accelerated approval for DLBCL by “competitive developments.” The company now plans to seek full approval for odronextamab in DLBCL, but only after the results of ongoing Phase III studies are published.

The company

Regeneron is founded in 1988 by Leonard S. Schleifer, a young neurologist and assistant professor at Cornell University Medical College. Regeneron’s medicines and pipeline are designed to treat patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases and rare diseases. It accelerates drug development using its proprietary technologies, such as VelociSuite®. Regeneron uses its platforms to design minimally engineered, fully human bsAb medicines that resemble naturally occurring antibodies as closely as possible. Veloci-Bi® allows for the generation of full-length bsAb medicines that can be made via standard manufacturing techniques with the goal of having favorable properties similar to natural antibodies. In August 2024, European Commission has approved Ordspono™ (odronextamab) to treat adult patients with R/R follicular lymphoma or R/R diffuse large B-cell lymphoma.

To protect its innovative technologies, Regeneron has built a significant patent portfolio covering its developments in the field of bsAbs, particularly in oncology, where its therapies aim to harness the immune system to fight cancer.

Regeneron’s patent portfolio

Regeneron has 49 patent families identified in bispecific antibody for oncology treatment (see KnowMade’s report: Bispecific Antibody & Cancer Patent Landscape Analysis), published between 2010 and 2024. This patent portfolio (figure 1) represents more than 800 documents with worldwide applications (Europe, USA, Asia). 89 % are alive patent families (pending applications and granted patents). For now, there is no EP opposition or US litigation identified.

Figure 1: Regeneron’s patent portfolio in bsAbs for cancer treatment.

The company is mainly focused on bsAb with an “obligate” mechanism which is the redirection of immune cells to cancer cells to eliminate them. Indeed, it developed bsAb targeting a tumor antigen (TA) in combination with a T cell (CD3 or CD28). By this approach, T cells are physically linked with tumor cells via bsAbs (figure 2). The main bsAbs identified in Regeneron’s patent portfolio are: CD20 x CD3, BSMA x CD3, Muc16 x CD3 or CD28, PSMA x CD3 or CD28 and EGFR x CD28.

Figure 2: Overview of Regeneron’s patented technologies in bsAbs for cancer treatment.

Odronextamab

Odronextamab (REGN1979) is a hinge-stabilized, human CD20 x CD3 IgG4-based bispecific antibody that binds CD20-expressing cells and CD3 on T cells, targeting CD20+ cells via T-cell-mediated cytotoxicity, independent of T-cell receptor-mediated recognition (figure 3).

Figure 3: Schematic representation of the bsAb odronextamab from Regeneron.

Cytokine Release Syndrome (CRS)

Regeneron owns 8 patent families describing CD20 x CD3 bsAbs. The three last patent families, published between 2019 and 2023, are alive and describe a method of treatment against cancer and to reduce cytokine release syndrome. CRS is a systemic inflammatory response that can be triggered by certain drugs. T cell-activating cancer immunotherapies carry a particularly high risk of CRS, which is usually due to on-target effects induced by binding of a bsAb or chimeric antigen receptor (CAR) T cell to its antigen and subsequent activation of bystander immune cells and non-immune cells, such as endothelial cells. Activation of the bystander cells results in the massive release of a range of cytokines. IL-6, IL-10, and interferon (IFN)-y are among the core cytokines that are consistently found to be elevated in the serum of patients with CRS. With T cell-activating therapies directed against tumor cells, CRS is triggered by the massive release of IFN-y by activated T cells, or the tumor cells themselves. Secreted IFN-y induces activation of other immune cells, most importantly macrophages, which in turn produce excessive amounts of IL-6, TNF-α, and IL-10. In some cases, the symptoms associated with CRS are termed infusion-related reaction (IRR) if they occur less than 6h following the start of infusion, and CRS if they occur from 6h onward following the start of infusion. Signs and symptoms of CRS include fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. Most patients have a mild reaction, but sometimes, the reaction may be severe or life threatening. The management of the toxicities of cancer immunotherapy is a challenging clinical problem.

How does Regeneron prevent severe CRS with odronextamab?

The patent family published in 2019 has granted patents in Europe, the USA, Japan, etc. and pending applications in Canada, Australia, China, Korea, etc. The company provides a dosing strategy to mitigate CRS (EP3844189) in patients with CD20+ DLBCL, refractory to CAR-T therapy or that have relapsed following prior CAR-T therapy. The methods employ initial fractional dosing with optional administration of additional agents such as steroids or cytokine antagonists that are discontinued with maximal weekly dosing over the course of the dosing regimen. The cumulative odronextamab safety and pharmacokinetics experience through the dose-limiting toxicities evaluation period of 27 mg  REGN1979 demonstrates that the management algorithm for CRS or IRR reactions (i.e., incremental dose escalation, split dosing during the initial weeks of REGN1979 administration, and premedication with corticosteroid) has proved effective in preventing severe CRS or IRR despite incremental increases in dosing in successive dose cohorts. Split dosing provided a benefit to patient safety in weeks 1 through 4 (the available data), wherein less overall incidents of severe CRS/IRR were observed. Particularly, the dosing strategy discussed herein provided a safer strategy for escalating doses to levels greater than 80 mg, even 160 mg or greater, with less severe events occurring in weeks 3 and 4 when higher doses reached and exceeded the desired serum concentrations discussed above.

In 2021, Regeneron filed a patent application (pending patent applications in Europe, the USA and Asia) disclosing a method to administering anti-CD20/anti-CD3 bsAb before administering to the cancer subject cemiplimab, an Ab that specifically binds programmed death 1 (PD-1) (WO2022/072762). This method inhibits tumor growth and ameliorates CRS in the subject. This disclosure is based, at least in part, on the unexpected discovery that pretreatment of the T-cells with odronextamab and delaying exposure to an anti-PD-1 Ab (cemiplimab) led to a marked decrease in cytokine (e.g., IL-2) release upon exposure to the combination of odronextamab plus cemiplimab, compared to control T-cells that had not undergone odronextamab pretreatment. This reduction in cytokine levels seen after odronextamab pretreatment supports the conclusion that initiating odronextamab before adding cemiplimab can help to significantly mitigate CRS.

Then, in 2023, the company disclosed a dosing regimen for administering odronextamab to treat a B-cell malignancy in patients (pending patent applications in Europe, the USA and Asia – WO2023/164143). The methods employ fractional dosing over several weeks of treatment along with administration of a steroid and an antihistamine. In an example, an intravenous (IV) odronextamab step-up regimen for reducing the risk of high-grade CRS is performed. The step-up dosing regimen consists of 0.7 mg (0.2/0.5 mg split over 2 days) at Week 1, 4 mg (2/2 split) at Week 2, and 20 mg (10/10 split) at Week 3. Early administration of premedication (12-24 hours prior to first split dose and on the day of each split dose vs. only on the day of each split dose) significantly reduced baseline (pre-treatment) cytokine levels. This new regimen has been tested in clinical studies in patients with follicular lymphoma and diffuse large B-cell lymphoma.

As of April 2022, there have been no Gr≥3 CRS in the first 100 patients treated with this regimen. Importantly, although the odronextamab IV step-up dosing regimen showed a lower concentration of odronextamab compared with the original regimen during Weeks 1-3, the concentrations were similar after the first full dose was administered, with similar trough concentrations after Week 4. This indicates that the same therapeutic levels are achieved with both regimens, which is beneficial for the treatment of disease.

To conclude, Regeneron continues to strengthen its position in the field of bsAbs, notably with odronextamab, despite the withdrawal of its accelerated approval application for DLBCL due to competition. The company is now focused on full approval following completion of Phase III studies, while continuing the approval process for follicular lymphoma, with an FDA decision expected by July 2025. Its patent portfolio demonstrates its commitment to developing innovative strategies to maximize the efficacy of bsAbs while limiting side effects, in particular cytokine release syndrome. Through optimized dosing protocols and combination approaches with other antibodies, Regeneron improves the safety and efficacy of its therapies. This strategic approach, combined with strong intellectual property protection, gives the company a key competitive advantage in the field of oncology.

Press contact
contact@knowmade.fr
Le Drakkar, 2405 route des Dolines, 06560 Valbonne Sophia Antipolis, France
www.knowmade.com

About the author
Fabienne Massa, PhD., works for Knowmade in the field of Biotechnology and Life Sciences. She holds a PhD in Molecular and Cellular Biology from the IPMC (Sophia Antipolis, France). She also holds a Master of Business Management from IAE (Nice, France) and she previously worked in the pharmaceutical industry.

About KnowMade
KnowMade is a technology intelligence and IP strategy consulting company specialized in analyzing patents and scientific publications. The company helps innovative companies, investors, and R&D organizations to understand competitive landscape, follow technological evolutions, reduce uncertainties, and identify opportunities and risks in terms of technology and intellectual property.
KnowMade’s analysts combine their strong technology expertise and in-depth knowledge of patents with powerful analytics tools and methodologies to turn patent information and scientific literature into actionable insights, providing high added value reports for decision makers working in R&D, innovation strategy, intellectual property, and marketing. Our experts provide prior art search, patent landscape analysis, freedom-to-operate analysis, IP due diligence, and monitoring services.
KnowMade has a solid expertise in Compound Semiconductors, Power Electronics, Batteries, RF Technologies & Wireless Communications, Solid-State Lighting & Display, Photonics, Memories, MEMS & Sensors, Semiconductor Packaging, Medical Devices, Medical Imaging, Microfluidics, Biotechnology, Pharmaceutics, and Agri-Food.