The antibody-drug conjugate (ADC) field is witnessing an expansion in the variety of conjugation techniques, linker chemistry, and payloads being used, moving beyond traditional tubulin inhibitors to include novel mechanisms of action. Investments in ADC research continue to grow, with significant funding rounds and acquisitions. For example, Novo Holdings’ $105 million investment in Alentis Therapeutics showcases the ongoing efforts to enhance ADC development platforms. Additionally, the market’s geographical expansion, particularly in China, reflects a global push towards innovative cancer therapies, as evidenced by multiple collaborations and licensing agreements aiming to bring novel ADCs to the clinic. Here are some of the key biotech companies in the ADC landscape.
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Abbvie/ImmunoGen
AbbVie’s strategic move to acquire ImmunoGen for $10.1 billion strengthens the company’s presence in the ADC cancer field, particularly in solid tumor oncology. This acquisition, highlighted by the inclusion of ImmunoGen’s flagship cancer therapy ELAHERE (mirvetuximab soravtansine-gynx) for platinum-resistant ovarian cancer, signifies AbbVie’s ambition to expand its oncology pipeline with potentially transformative programs across a variety of solid tumors and hematologic malignancies. ImmunoGen’s portfolio, including its next-generation ADCs like IMGN-151 for ovarian cancer and pivekimab sunirine for rare blood cancer, enhances AbbVie’s research capabilities and product offerings in oncology.
The acquisition not only accelerates AbbVie’s entry into the ADC market but also represents a pivotal step in its strategy to establish a significant footprint in the treatment of solid tumors. ImmunoGen’s success with ELAHERE, the first medicine to show an overall survival benefit in platinum-resistant ovarian cancer, alongside its promising pipeline, offers AbbVie a unique opportunity to lead in the ADC space and further develop innovative cancer treatments.
This move also reflects AbbVie’s ongoing efforts to rejuvenate its ADC portfolio, learning from past experiences with ADCs and aiming to leverage ImmunoGen’s decades of expertise in the field. By integrating ImmunoGen’s ADC technologies and candidates, AbbVie is poised to enhance its oncology pipeline, potentially speeding up the development and expansion of effective cancer therapies.
Beyond its acquisition of ImmunoGen, AbbVie’s ADC pipeline includes early-stage development projects such as ABBV-400, a c-Met (mesenchymal epithelial transition factor) ADC for solid tumors, and two anti-SEZ6 (Seizure Related 6 Homolog) ADCs, ABBV-011 and ABBV-706, aimed at addressing various cancer indications.
Adcendo
Adcendo was established in 2017 as a spin-out from The University of Copenhagen and Rigshospitalet. Based in Copenhagen, this biotech company harnesses the uPARAP receptor, a novel target identified by its scientific founders, to develop ADCs that aim to improve cancer treatment outcomes.
The uPARAP receptor, also known as Endo180, is a key player in the body’s management of the extracellular matrix, particularly in collagen remodeling. It is crucial for tissue repair and maintenance but also plays a significant role in cancer progression, as it is overexpressed in several cancer types.
Adcendo has partnered with GlyTherix, an Australian immuno-oncology company, to advance the development of an ADC targeting GPC-1, a protein associated with multiple solid tumor types. This collaboration aims to leverage GlyTherix’s Miltuximab, a leading anti-GPC-1 monoclonal antibody, furthering Adcendo’s mission to bring innovative treatment options to the market.
In a recent development, Adcendo has entered into an option license agreement with Duality Biologics. This agreement is part of Adcendo’s strategy to further develop its ADC pipeline, which focuses on creating therapies for various types of cancer. The collaboration aims to utilize Duality Biologics’ capabilities to potentially enhance Adcendo’s existing ADC technologies. This partnership reflects Adcendo’s ongoing efforts to explore new avenues in ADC development, aiming to expand the range and effectiveness of its cancer treatments.
Supported by a series A funding round of $55 million (€51 million) in 2021, which was extended in 2023 with an additional $33 million (€31 million), Adcendo is well-positioned to continue its pioneering work in the ADC space.
AdcentrX Therapeutics
AdcentrX is building an internal pipeline of innovative ADCs to address the current limitations and challenges in the field. Adcentrx has recently raised $38 million in a series A+ financing round. This was then completed by a $13 million additional extension. This financing follows a $50 million Series A round in 2021, and marks a significant step towards clinical development of their ADC oncology pipeline.
ADRX-0706, Adcentrx’s lead candidate, is an ADC that targets Nectin-4, a cell surface adhesion protein overexpressed in multiple human cancers. This targeting strategy is part of Adcentrx’s approach to leverage more stable linker technologies and harness the “bystander effect” to deliver the payload more precisely to the tumor, thereby enhancing efficacy while minimizing side effects. The company plans to advance at least one of its other pipeline programs into clinical testing each year, indicating a robust pipeline in development. ADRX-0706 received FDA Investigational New Drug Application clearance in July 2023.
In addition to ADRX-0706, Adcentrx is working on a second candidate in oncology indications and another candidate aimed at treating conditions in immunology. The company also entered a three-year partnership with AvantGen in February 2022 to co-develop antibodies for use in novel ADCs to expand its pipeline and address the needs of patients with cancer and other serious diseases.
Alentis Therapeutics
Alentis Therapeutics is a clinical-stage biotechnology company that specializes in the development of ADC treatments for organ fibrosis and cancers that are positive for Claudin-1 (CLDN1). The company’s research and development pipeline focuses on anti-Claudin-1 antibodies as a novel therapeutic approach for treating CLDN1-positive tumors and organ fibrosis. Alentis is advancing two lead monoclonal antibodies through clinical development and is also working on next-generation anti-CLDN1 therapies, including ADCs, bispecific antibodies, and T-cell engagers.
Alentis has garnered attention for its innovative work, as evidenced by the completion of a $105 million series C funding round in April 2023. This funding is intended to support phase 2 and phase 1 programs of its lead investigational products ALE.F02 and ALE.C04, respectively, as well as the development of its CLDN1 platform.
Alentis has reported positive topline results from the multiple-ascending dose (MAD) part of its first-in-human phase 1 clinical study of ALE.F02, confirming the drug’s good safety profile, exposure, and target biological activity. Moreover, the company has initiated a Phase 2 trial dosing the first patient with ALE.F02 for ANCA-associated vasculitis with rapidly progressive glomerulonephritis (RPGN). This trial is significant as it investigates the drug’s safety, tolerability, and its potential to preserve kidney function in a condition known for causing rapid kidney failure. Lixudebart targets Claudin-1 (CLDN1) to potentially halt and reverse fibrosis, marking a novel approach to treating severe renal diseases.
Araris Biotech
Araris Biotech AG has been progressing notably in the ADC sector, highlighted by a recent investment from Samsung Ventures. This funding supports the advancement of Araris’ ADC pipeline, which focuses on cancer therapies, employing an innovative linker technology that aims to streamline development and improve drug efficacy.
The company has also successfully raised $24 million to push forward its ADC-linker technology and propel its ADC candidates, such as the promising anti-CD79b, into clinical stages. The anti-CD79b ADC has demonstrated promising results in preclinical studies, showing potential advantages over existing therapies.
At the AACR Annual Meeting 2023, Araris presented preclinical data on two ADCs created with its proprietary linker technology. These ADCs, targeting anti-Nectin-4 and anti-HER2, showed superior anti-tumor activities and stability in comparison to approved ADCs, indicating the potential of Araris’ technology to develop more efficacious and safer ADCs with lower drug loads.
AstraZeneca/Daiichi Sankyo
AstraZeneca and Daiichi Sankyo have a significant collaboration in the ADC field, focusing on the development and commercialization of DS-1062, a TROP2-targeting (trophoblast cell surface antigen 2) ADC. This collaboration highlights the potential of DS-1062 in treating multiple tumor types, including non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC), leveraging Daiichi Sankyo’s proprietary DXd ADC technology. The partnership allows AstraZeneca and Daiichi Sankyo to split development, commercialization costs, and profits, excluding Japan, where Daiichi Sankyo retains exclusive rights.
Moreover, the Lung Cancer Research Foundation (LCRF) announced a new research collaboration with Daiichi Sankyo and AstraZeneca, aiming to fund up to three research grants focused on ADCs to improve outcomes for people with lung cancer. This initiative seeks to explore the potential of ADCs in lung cancer treatment, particularly focusing on HER2-directed and TROP2-directed ADCs, including DS-1062, to study their mechanism of action, biomarkers, and resistance mechanisms.
This strategic partnership follows their initial collaboration on Enhertu, a HER2-directed DXd ADC. Enhertu received FDA approval in 2022 for treating adults with non-small cell lung cancer (NSCLC) harboring specific HER2 mutations. This approval was based on the results of the DESTINY-Lung02 study, which demonstrated that Enhertu significantly shrank tumors in a majority of patients, offering a new treatment option for a specific subset of lung cancer patients.
Daiichi Sankyo’s ADC pipeline is extensive and includes a variety of candidates targeting different antigens and cancers. At the forefront are patritumab deruxtecan (HER3-DXd) for EGFR-mutated (epidermal growth factor receptor) NSCLC and datopotamab deruxtecan (Dato-DXd) for NSCLC without actionable genomic alterations.
Daiichi Sankyo has presented data across its DXd ADC portfolio at significant conferences, including ESMO Asia and SABCS, demonstrating the depth of its oncology portfolio. This includes studies on datopotamab deruxtecan in NSCLC with actionable genomic alterations and ENHERTU in HER2 mutant NSCLC, showcasing Daiichi Sankyo’s ongoing research to advance cancer treatment through ADCs.
Both companies are key players in the ADC space, with AstraZeneca leveraging collaborations to enhance its oncology pipeline and Daiichi Sankyo focusing on its proprietary DXd technology to develop ADCs with the potential for high impact in cancer treatment.
BioNTech/DualityBio
BioNTech, in collaboration with Duality Biologics, has been focusing on developing ADC treatments for cancer and autoimmune diseases. Their notable ADC candidate, BNT323/DB-1303, is currently undergoing a pivotal phase 3 trial for patients with metastatic breast cancer. This trial was initiated based on positive safety and efficacy data from earlier phase 1/2 studies, which demonstrated promising anti-tumor activity, particularly in heavily pretreated patients with HER2-low breast cancer. The objective response rate and disease control rate observed were encouraging, highlighting BNT323/DB-1303’s potential to improve outcomes for patients with advanced solid tumors.
Additionally, BNT323/DB-1303 has gained Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of advanced endometrial cancer.
This partnership is expected to expedite the delivery of these innovative therapies to patients worldwide, with BioNTech holding global commercial rights excluding Mainland China, Hong Kong, and Macau and DualityBio retaining rights within these regions.
Bristol Myers Squibb
Bristol Myers Squibb (BMS) is significantly reinforcing its stance in the ADC market through strategic collaborations aimed at enhancing its oncology portfolio. One notable partnership is with SystImmune, involving the joint development and commercialization of the EGFRxHER3 bispecific ADC, BL-B01D1, in a deal valued at $8.4 billion.
In another strategic move, BMS entered into a $1 billion agreement with Tubulis to develop ADCs targeted at solid tumors, leveraging Tubulis’ proprietary P5 conjugation platform, a novel chemistry for cysteine-selective conjugation, and ‘Tubutecan’ payloads. This collaboration not only involves an upfront payment of $22.75 million to Tubulis but also includes potential development, regulatory, and commercial milestone payments, along with royalty payments on marketed products. The alliance aims to generate uniquely matched ADCs for each antibody target, with BMS taking full responsibility for their subsequent development, manufacturing, and commercialization.
BMS has also expanded its presence in the ADC field through a $100 million deal to acquire a phase 1 blood cancer medication from Orum Therapeutics. The medication in question, ORM-6151, is a first-in-class anti-CD33 (sialic acid binding Ig-like lectin 3) antibody-enabled GSPT1 degrader, targeting acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes, with the potential for $80 million in milestone payments if the program is successful.
These collaborations represent the company’s approach to expanding its ADC pipeline, tapping into innovative technologies to develop therapeutics in cancer treatment.
GSK
GSK has also been actively expanding its oncology portfolio, particularly in the ADC space, through strategic acquisitions and partnerships. A notable recent development is GSK’s $185 million upfront payment to Hansoh Pharma for the rights to HS-20093, an ADC targeting B7-H3, a protein expressed by many different cancers including lung cancer. The ADC has shown early signs of clinical activity in solid tumors, particularly small cell lung cancer and sarcoma, and is set to start phase 1 clinical trials outside China in 2024.
Additionally, the company entered another significant deal involving an ADC targeting B7-H4, known as HS-20089, indicating GSK’s strategic interest in ADCs targeting proteins abundant in various cancers, including ovarian and endometrial cancers. This move pits GSK against major players like Pfizer in the race to develop effective treatments for these cancers.
More recently, the DREAMM-7 phase III trial demonstrated significant improvement in treating relapsed/refractory multiple myeloma with GSK’s Blenrep (belantamab mafodotin) in combination with bortezomib and dexamethasone. This combination nearly tripled the median progression-free survival compared to the standard care combination, showcasing a 59% reduction in disease progression or death risk. The trial also indicated a strong trend towards overall survival benefit, with a 43% reduction in the risk of death. These findings highlight Blenrep’s potential to redefine treatment strategies for multiple myeloma at or after the first relapse.
MBrace therapeutics
The biotech company is actively working in the ADC field, focusing on MBRC-101, which aims at the EphA5 (ephrin type-A receptor 5) receptor tyrosine kinase. The significance of targeting EphA5 comes from its prevalent presence in a variety of solid tumors such as triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC), positioning it as a valuable target for ADC development.
The foundation of MBRC-101 lies in its ability to specifically target EphA5, a membrane-associated tyrosine kinase receptor. This specificity is crucial for the treatment of cancer because EphA5 is differentially expressed in tumor cells compared to normal cells, offering a pathway for selective cancer cell targeting and treatment. MBRC-101 employs a humanized anti-EphA5 IgG1 antibody conjugated to monomethyl auristatin E (MMAE), a potent cytotoxic agent. Upon binding to EphA5 on cancer cells, MBRC-101 is internalized, delivering MMAE directly into the cancer cell to induce cell death.
The preclinical data for MBRC-101 has been compelling, demonstrating significant efficacy in models of breast cancer. It has shown exclusive binding to EphA5, rapid internalization, and cytotoxicity to cells expressing EphA5. In patient-derived xenograft murine models of TNBC, MBRC-101 exhibited dose-dependent, robust, and reproducible anti-tumor activity, providing a strong rationale for its clinical development. Notably, MBRC-101 was well tolerated at various doses in preclinical models, with toxicological findings attributed to the MMAE payload and not to the target itself.
MBrace Therapeutics is currently advancing MBRC-101 through a phase 1/1b clinical trial, aiming to identify the optimal biologically relevant doses and evaluate the safety and preliminary activity of MBRC-101 in TNBC, NSCLC, and other solid tumors.
Financially, MBrace Therapeutics recently raised $85 million in Series B financing to further develop its oncology pipeline.
Oxford Biotherapeutics
One of Oxford Biotherapeutic’s (OBT) leading ADCs, OBT076, targets the CD205 receptor, which is overexpressed in a range of solid and liquid tumors. This innovative approach aims to treat adenoid cystic carcinoma (ACC) of the head and neck, a rare and aggressive cancer type. In collaboration with Groupe d’Oncologie Radiothérapie Tête Et Cou (GORTEC), OBT is conducting a phase 1b trial to investigate OBT076 both as a monotherapy and in combination with balstilimab, a PD-1 (Programmed Cell Death Protein 1) blocking antibody. This trial is notable for its focus on a cancer with limited treatment options.
Additionally, OBT’s collaboration with Boehringer Ingelheim has led to the development of BI 764532, an investigational T-cell engager targeting DLL3 (Delta-like ligand 3), a protein discovered using OBT’s proprietary OGAP platform. This partnership has already achieved significant milestones, including receiving U.S. FDA Fast Track designation for the treatment of advanced or metastatic large-cell neuroendocrine carcinoma of the lung (LCNEC-Lung).
OBT’s ADC development efforts are underpinned by their OGAP platform, their cancer-specific membrane protein library, facilitating the identification of novel, high-specificity antigens for cancer targets. This extensive database supports OBT’s strategy to develop ADC-based therapies.
Pfizer/Seagen
Pfizer’s acquisition of Seagen completed on December 14, 2023, for a value of approximately $43 billion, marks a significant expansion of Pfizer’s oncology capabilities. This strategic move further establishes Pfizer as a leading company in the oncology sector, with the ambition to accelerate the development of next-generation treatments for cancer. The acquisition brings together Seagen’s pioneering ADC technology with Pfizer’s extensive capabilities and expertise.
Seagen’s portfolio at the time of acquisition included four approved cancer therapies with combined sales nearing $2 billion in 2022. The acquisition not only adds significant value to Pfizer’s oncology portfolio, which includes over 25 approved medicines and biosimilars across more than 40 indications but also doubles Pfizer’s oncology pipeline to 60 programs. These programs span a variety of modalities, including ADCs, small molecules, bispecifics, and other immunotherapies, promising a broad impact across multiple cancer types.
One of the most advanced and notable ADCs from Seagen is Tivdak (tisotumab vedotin-tftv), which has received FDA approval for the treatment of recurrent or metastatic cervical cancer that has progressed after chemotherapy. Tivdak represents a significant advancement in the treatment of cervical cancer, marking the first ADC approved for this indication. It is Seagen’s third ADC to receive regulatory approval, demonstrating the company’s leadership and innovation in the ADC space.
In addition to Tivdak, Seagen has been involved in the development of other novel ADCs, including SGN-B7H4V, which is directed against the T cell checkpoint ligand B7-H4, overexpressed in various solid malignancies.
Roche
One of the notable ADCs from Roche is Kadcyla (trastuzumab emtansine), engineered to deliver potent chemotherapy directly to HER2-positive cancer cells. Kadcyla has been approved in over 100 countries, including the U.S. and EU, for the treatment of people with HER2-positive advanced breast cancer who have previously received Herceptin and taxane-based chemotherapy. It’s also approved for adjuvant treatment of HER2-positive early breast cancer with residual invasive disease after neoadjuvant treatment that included Herceptin and taxane-based chemotherapy.
Another important ADC developed by Roche is Polivy (polatuzumab vedotin), an anti-CD79b antibody-drug conjugate approved in combination with bendamustine plus rituximab. It is used for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma who are not candidates for a hematopoietic stem cell transplant.
Roche also advances ADC technology and cancer treatment through strategic partnerships and investments. For example, Roche has entered into a significant collaboration with Moma Therapeutics, dedicating over $2 billion towards the development of precision cancer drugs. This deal underscores Roche’s strategy to leverage external expertise and platforms to identify novel drug targets involved in cancer cell growth and survival, with the aim of developing the next generation of precision medicines.
Another collaboration is with the company MediLink Therapeutics to develop YL211, a next-generation ADC targeting solid tumors. MediLink, brings its proprietary Tumour Microenvironment Activable LINker-payload (TMALIN) ADC technology platform to the partnership, focusing on the c-Mesenchymal epithelial transition factor (c-Met) as a target for this therapy.
Roche will have exclusive international rights to develop, produce, and market YL211, further solidifying its role in the ADC and oncology fields. The agreement includes upfront and near-term milestone payments to MediLink totaling $50 million, with potential development, regulatory, and commercial milestones reaching up to $1 billion, plus royalties on future net product sales.
Takeda Pharmaceuticals
Takeda Pharmaceuticals has been actively involved in the development and commercialization of ADCs.
One notable collaboration is with ImmunoGen, where Takeda licensed exclusive rights to use ImmunoGen’s novel ADC technology, including new DNA-acting IGN payload agents, for up to two undisclosed targets. ImmunoGen received an upfront payment from Takeda, with the potential for milestone payments totaling up to $210 million plus royalties on commercial net sales of any resulting ADC products.
The company has also expanded its partnership with Mersana Therapeutics, aimed at advancing the development of Fleximer ADCs, including XMT-1522, which targets HER2-expressing tumors. This collaboration not only grants Takeda rights to Mersana’s lead product candidate outside the U.S. and Canada but also provides access to Mersana’s Fleximer ADC platform for additional targets.
Moreover, Takeda and Seagen have highlighted the importance of ADCETRIS (brentuximab vedotin) in treating advanced Hodgkin lymphoma. ADCETRIS has received approval in over 70 countries for relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma (sALCL). It’s being evaluated in more than 70 clinical trials, indicating its broad potential in treating CD30-positive malignancies.
More recently, Takeda has also entered into an exclusive licensing agreement with Innate Pharma to develop antibody-drug conjugates (ADCs) targeting celiac disease. Takeda has agreed to pay Innate Pharma $5 million upfront, with the potential for up to $410 million in development, regulatory, and commercial milestones, plus royalties on net sales of any commercial products developed through this partnership.
This deal is part of Takeda’s broader strategy to address celiac disease, marking its fourth initiative since 2019, aimed at developing candidates for this condition. The agreement grants Takeda exclusive worldwide rights to research, develop, manufacture, and commercialize the ADCs using Innate’s antibodies, showcasing a significant move to leverage ADC technology beyond its traditional oncology applications and into autoimmune diseases like celiac disease.
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