Fourteen Biotech Companies Spearheading the Antibody-Drug Conjugate (ADC) Industry File IPO Prospectus

The field of Antibody-Drug Conjugates (ADCs) is witnessing an expansion in various conjugation technologies, linker chemistries, and payloads used, moving beyond traditional tubulin inhibitors to include new mechanisms of action. With significant financing and acquisitions underway, investment in ADC research continues to grow. For instance, Novo Holdings' $105 million investment in Alentis Therapeutics demonstrates its ongoing efforts to enhance the ADC development platform. Additionally, geographic market expansion, particularly in China, reflects a global push for innovative oncology therapies, evidenced by numerous collaborations and licensing agreements aimed at advancing novel ADCs into clinical trials. Below are some of the key biotechnology companies in the ADC space.

Abbvie/ImmunoGen

AbbVie Enhances ADC Oncology Portfolio with $10.1 Billion Acquisition of ImmunoGenAbbVie's strategic move to acquire ImmunoGen for $10.1 billion strengthens its position in the ADC oncology treatment space, particularly within solid tumors. The acquisition highlights the inclusion of ImmunoGen’s flagship oncology therapy, ELAHERE (mirvetuximab soravtansine-gynx), designed for platinum-resistant ovarian cancer, signifying AbbVie’s ambition to expand its oncology portfolio through potentially transformative programs targeting various solid tumors and hematologic malignancies. ImmunoGen’s pipeline, featuring next-generation ADCs such as IMGN-151 for ovarian cancer and pivekimab sunirine for rare blood cancers, bolsters AbbVie’s research capabilities and therapeutic offerings in oncology.

This acquisition not only accelerates AbbVie's entry into the ADC market but also represents a key strategic step in establishing a significant presence in the field of solid tumor treatments. ImmunoGen’s ELAHERE is the first drug to demonstrate overall survival benefits in platinum-resistant ovarian cancer, and its success, along with its promising pipeline, provides AbbVie with a unique opportunity to lead in the ADC space and further develop innovative oncology therapies.

This move also reflects AbbVie's efforts to revitalize its ADC portfolio, drawing on past ADC experiences and aiming to leverage ImmunoGen's decades of expertise in the field. By integrating ImmunoGen's ADC technology and drug candidates, AbbVie is poised to strengthen its oncology treatment pipeline, potentially accelerating the development and expansion of effective cancer therapies.

In addition to the acquisition of ImmunoGen, AbbVie's ADC pipeline also 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 treating various oncology indications.

Adcendo

ADCendo, founded in 2017, is a spin-off company from the University of Copenhagen and Rigshospitalet. Headquartered in Copenhagen, this biotechnology company leverages a novel target, the uPARAP receptor, identified by its scientific founders to develop ADCs aimed at improving cancer treatment outcomes.

uPARAP Receptor, Also Known as Endo180, Plays a Key Role in the Human Extracellular Matrix, Particularly in Collagen Remodeling. It Is Crucial for Tissue Repair and Maintenance and Also Plays a Significant Role in Tumor Progression Due to Its Overexpression in Various Types of Cancer.

Adcendo Collaborates with Australian Immuno-Oncology Company GlyTherix to Advance the Development of ADC Targeting GPC-1 (a Protein Associated with Various Solid Tumor Types). This collaboration aims to leverage GlyTherix’s Miltuximab (a leading anti-GPC-1 monoclonal antibody) to further Adcendo's mission of bringing innovative therapeutic options to the market.

In Recent Developments, Adcendo Has Signed an Option Licensing Agreement with Duality Biologics. This agreement is part of Adcendo's strategy to further develop its ADC pipeline, focusing on creating therapies for various types of cancer. The collaboration aims to leverage Duality Biologics' capabilities to potentially enhance Adcendo’s existing ADC technology. This partnership reflects Adcendo's continued efforts to explore new avenues in ADC development, aiming to expand the scope and effectiveness of its oncology treatments.

Backed by a $55 million (€51 million) Series A financing in 2021, Adcendo added a $33 million (€31 million) financing in 2023, positioning itself favorably to continue its pioneering work in the ADC field.

AdcentrX Therapeutics

Adcentrx Therapeutics is building an internal pipeline of innovative ADCs to address current limitations and challenges in the field. Adcentrx recently raised $38 million in an A+ round of financing, followed by an additional $13 million. This financing follows the $50 million Series A round in 2021 and marks a significant step forward in the clinical development of its ADC oncology pipeline.

Adcentrx's lead candidate drug, ADRX-0706, is an ADC targeting Nectin-4, a cell surface adhesion protein that is overexpressed in various human tumors. This targeted strategy is part of Adcentrx’s approach to leverage more stable linker technology and utilize the "bystander effect" to deliver payloads more precisely to tumors, thereby enhancing efficacy while minimizing side effects. The company plans to advance at least one other pipeline project into clinical testing each year, indicating a robust development pipeline. ADRX-0706 received FDA approval for an Investigational New Drug (IND) application in July 2023.

In addition to ADRX-0706, Adcentrx is also studying another candidate drug for oncology indications and a candidate drug aimed at treating immune disorders. In February 2022, the company established a three-year partnership with AvantGen to co-develop antibodies for novel ADCs, expanding its pipeline to meet the needs of patients with cancer and other serious diseases.

Alentis Therapeutics

Alentis Therapeutics is a clinical-stage biotechnology company specializing in the development of ADC therapies targeting Claudin-1 (CLDN1)-positive organ fibrosis and tumors. The company’s R&D pipeline focuses on anti-Claudin-1 antibodies as a novel treatment approach for CLDN1-positive tumors and organ fibrosis. Alentis is advancing two leading monoclonal antibodies through clinical development and is committed to next-generation anti-CLDN1 therapies, including ADCs, bispecific antibodies, and T-cell engagers.

Alentis Therapeutics Gains Attention for Its Innovative Work, as Evidenced by the $105 Million Series C Financing Completed in April 2023. This Funding Aims to Support Phase 2 and Phase 1 Programs for Its Lead Research Products, ALE.F02 and ALE.C04, as Well as the Development of Its CLDN1 Platform.

Alentis Reports Positive Results from Multiple Ascending Dose (MAD) Portion of First-in-Human Phase 1 Clinical Study of ALE.F02, Confirming the Drug’s Favorable Safety, Exposure, and Target Biological Activity. Additionally, the Company Has Initiated a Phase 2 Trial, Treating 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 conditions known to cause rapid renal failure. Lixudebart, targeting Claudin-1 (CLDN1), has the potential to halt and reverse fibrosis, marking a novel approach to treating severe kidney diseases.

Araris Biotech

Araris Biotech AG has made significant progress in the ADC field, highlighted by a recent investment from Samsung Ventures. This funding supports the development of Araris' ADC pipeline, which focuses on oncology treatments and employs innovative linker technology aimed at streamlining development and enhancing drug efficacy.

The company also successfully raised $24 million to advance its ADC linker technology and propel its ADC candidates, such as the promising anti-CD79b ADC, into clinical stages. The anti-CD79b ADC demonstrated encouraging results in preclinical studies, showing potential advantages over existing therapies.

At the AACR 2023 Annual Meeting, Araris presented preclinical data for two ADCs created using its proprietary linker technology. Compared to approved ADCs, these anti-Nectin-4 and anti-HER2 ADCs demonstrated superior antitumor activity and stability, indicating the potential of Araris's technology to develop more effective, 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, an ADC targeting TROP2 (trophoblast cell surface antigen 2). This collaboration highlights the potential of DS-1062 to leverage Daiichi Sankyo's proprietary DXd ADC technology for treating various tumor types, including non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC). The partnership allows AstraZeneca and Daiichi Sankyo to share development, commercialization costs, and profits, except in Japan, where Daiichi Sankyo retains exclusive rights.

In addition, the Lung Cancer Research Foundation (LCRF) announced a new research collaboration with Daiichi Sankyo and AstraZeneca to fund up to three studies focused on ADCs aimed at improving treatment outcomes for lung cancer patients. The initiative aims to explore the potential of ADCs in lung cancer therapy, with particular attention on HER2-targeted and TROP2-targeted ADCs, including DS-1062, to investigate their mechanisms of action, biomarkers, and resistance mechanisms.

This strategic partnership follows an initial collaboration between the two parties on Enhertu (a HER2-targeted DXd ADC). Enhertu received FDA approval in 2022 for the treatment of adult patients with non-small cell lung cancer (NSCLC) carrying specific HER2 mutations. This approval was based on the results of the DESTINY-Lung02 study, which demonstrated that Enhertu significantly reduced tumor size in most patients, offering a new treatment option for a specific subgroup of lung cancer patients.

Daiichi Sankyo's ADC pipeline is very broad, including a variety of candidate drugs targeting different antigens and tumors. Leading the way are patritumab deruxtecan (HER3-DXd) for the treatment of EGFR-mutated (epidermal growth factor receptor) NSCLC and datopotamab deruxtecan (Dato-DXd) for the treatment of NSCLC without actionable genomic alterations.

Daiichi Sankyo showcased data from its DXd ADC portfolio at major conferences such as ESMO Asia and SABCS, demonstrating the depth of its oncology treatment offerings. This included research on datopotamab deruxtecan targeting NSCLC with actionable genomic alterations, as well as ENHERTU targeting HER2-mutated NSCLC, highlighting Daiichi Sankyo's ongoing efforts to advance cancer therapy through ADCs.

Both companies are key players in the ADC field, with AstraZeneca leveraging collaborations to enhance its oncology portfolio, while Daiichi Sankyo focuses on its proprietary DXd technology to develop ADCs with significant potential impact on cancer treatment.

BioNTech/DualityBio

BioNTech Collaborates with Duality Biologics (Duality Bio) to Focus on Developing ADC Therapies Targeting 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. The Trial Was Initiated Based on Positive Safety and Efficacy Data from Earlier Phase 1/2 Studies, Demonstrating Promising Antitumor Activity, Particularly in Heavily Pretreated HER2-Low Breast Cancer Patients. The Observed Objective Response Rate and Disease Control Rate Were Encouraging, Highlighting the Potential of BNT323/DB-1303 to Improve Outcomes for Patients with Advanced Solid Tumors.

In addition, BNT323/DB-1303 has also received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of advanced endometrial cancer.

This collaboration is expected to accelerate the delivery of these innovative therapies to patients worldwide, with BioNTech holding global commercial rights excluding mainland China, Hong Kong, and Macao, while DualityBio retains the rights in these regions.

Bristol Myers Squibb

Bristol Myers Squibb (BMS) has significantly strengthened its position in the ADC market through strategic collaborations aimed at enhancing its oncology portfolio. A notable partnership is with SystImmune (Baili Tianheng), involving the co-development and commercialization of the EGFRxHER3 bispecific ADC BL-B01D1, in a deal valued at $8.4 billion.

In another strategic move, BMS struck a $1 billion deal with Tubulis to develop ADCs targeting solid tumors, leveraging Tubulis' proprietary P5 conjugation platform, a novel chemistry for cysteine-selective conjugation, and the "Tubutecan" payload. The collaboration involves an upfront payment of $22.75 million to Tubulis, along with potential development, regulatory, and commercial milestone payments, as well as royalties on marketed products. The alliance aims to generate uniquely matched ADCs for each antibody target, with BMS taking full responsibility for subsequent development, manufacturing, and commercialization.

BMS also expanded its influence in the ADC field by acquiring a Phase 1 blood cancer drug from Orum Therapeutics through a $100 million deal. The drug in question, ORM-6151, is a first-in-class anti-CD33 (Sialic Acid-Binding Ig-Like Lectin 3) antibody GSPT1 degrader, targeting acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome, with potential milestone payments of $80 million if the project succeeds.

These collaborations represent the company's approach to expanding its ADC pipeline and leveraging innovative technologies to develop oncology treatments.

GSK

GSK (GlaxoSmithKline) is also actively expanding its oncology portfolio, particularly in the ADC field, through strategic acquisitions and partnerships. A recent notable development is GSK’s upfront payment of $185 million to Hansoh Pharma for the rights to HS-20093, an ADC targeting B7-H3, a protein expressed by many different tumors, including lung cancer. The ADC has shown early signs of clinical activity in solid tumors, especially small cell lung cancer and sarcoma, with plans to initiate Phase 1 clinical trials outside of China in 2024.

In addition, the company has reached another major deal involving an ADC targeting B7-H4 (called HS-20089), indicating GSK's strategic interest in ADCs targeting proteins abundant in various tumors, including ovarian and endometrial cancers. This move positions GSK to compete with key players like Pfizer in the race to develop effective treatments targeting these tumors.

Recently, the DREAMM-7 Phase III trial demonstrated significant improvement with GSK's Blenrep (belantamab mafodotin) in combination with bortezomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. Compared to the standard treatment regimen, this combination nearly doubled the median progression-free survival and reduced the risk of disease progression or death by 59%. The trial also showed a strong trend toward overall survival benefit, reducing the risk of death by 43%. These findings highlight Blenrep's potential to redefine treatment strategies for multiple myeloma at or after first relapse.

MBrace Therapeutics

The biotech company is actively advancing in the ADC field, with a primary focus on MBRC-101, a product targeting EphA5 (ephrin type-A receptor 5) receptor tyrosine kinase. The significance of targeting EphA5 lies in its widespread presence across various solid tumors, such as triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC), making it 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 cancer treatment because the expression of EphA5 differs between tumor cells and normal cells, offering a pathway for selective tumor cell targeting and therapy. MBRC-101 utilizes a humanized anti-EphA5 IgG1 antibody conjugated with monomethyl auristatin E (MMAE), a potent cytotoxic agent. After binding to EphA5 on tumor cells, MBRC-101 is internalized, delivering MMAE directly into the tumor cells and inducing cell death.

The preclinical data for MBRC-101 is compelling, demonstrating significant efficacy in breast cancer models. It exhibits exclusive binding to EphA5, rapid internalization, and cytotoxicity against cells expressing EphA5. In patient-derived TNBC xenograft mouse models, MBRC-101 displayed 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 toxicology findings attributed to the MMAE payload rather than the target itself.

MBrace Therapeutics is currently advancing MBRC-101 through a Phase 1/1b clinical trial aimed at determining the optimal biologically relevant dose and evaluating the safety and preliminary activity of MBRC-101 in TNBC, NSCLC, and other solid tumors.

Financially, MBrace Therapeutics recently completed an $85 million Series B financing to further develop its oncology therapeutic pipeline.

Oxford Biotherapeutics

One of Oxford BioTherapeutics' (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 tumor type. OBT, in collaboration with Groupe d’Oncologie Radiothérapie Tête Et Cou (GORTEC), is conducting a Phase 1b trial to investigate OBT076 as a monotherapy and in combination with balstilimab, a PD-1 (programmed cell death protein 1) blocking antibody. The trial stands out for its focus on tumors with limited treatment options.

In addition, the collaboration between OBT and Boehringer Ingelheim has also developed 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 Fast Track designation from the U.S. FDA for the treatment of advanced or metastatic large cell neuroendocrine carcinoma of the lung (LCNEC-Lung).

OBT's ADC development work, based on the OGAP platform and a library of tumor-specific membrane proteins, helps identify novel high-specificity antigens for tumor targets. This extensive database supports OBT's strategy for developing ADC-based therapies.

Pfizer/Seagen

Pfizer completed the acquisition of Seagen on December 14, 2023, for approximately $43 billion, marking a significant expansion of Pfizer's oncology treatment capabilities. This strategic move further establishes Pfizer as a leading company in the field of cancer therapy, committed to accelerating the development of next-generation oncology treatments. The acquisition combines Seagen’s groundbreaking ADC technology with Pfizer’s extensive capabilities and expertise.

Seagen’s portfolio at the time of acquisition included four approved oncology therapies, with total sales approaching $2 billion by 2022. This acquisition not only added significant value to Pfizer's oncology portfolio—which includes more than 25 approved drugs and biosimilars covering over 40 indications—but also doubled Pfizer’s revenue. The number of oncology treatment programs has reached 60. These programs encompass multiple modalities, including ADCs, small molecules, bispecific drugs, and other immunotherapies, with the potential to have a broad impact on various types of cancer.

One of Seagen's most advanced and notable ADCs 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 cervical cancer treatment, marking the first ADC approved for this indication. This is the third ADC to gain regulatory approval for Seagen, showcasing the company’s leadership and innovation in the ADC field.

In addition to Tivdak, Seagen is also involved in the development of other novel ADCs, including SGN-B7H4V, which targets the T-cell checkpoint ligand B7-H4, overexpressed in various solid malignancies.

Roche

One of Roche's well-known ADCs is Kadcyla (trastuzumab emtansine), designed to deliver potent chemotherapy directly to HER2-positive tumor cells. Kadcyla has been approved in more than 100 countries, including the United States and the European Union, for the treatment of patients with HER2-positive advanced breast cancer who have previously received Herceptin and taxane-based chemotherapy. It is also approved as an adjuvant treatment for HER2-positive early breast cancer with residual invasive disease following neoadjuvant treatment, including Herceptin and taxane-based chemotherapy.

Another significant ADC developed by Roche is Polivy (polatuzumab vedotin), an anti-CD79b antibody-drug conjugate, which has been approved for use in combination with bendamustine and rituximab. It is used to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma who are not candidates for hematopoietic stem cell transplantation.

Roche also advances ADC technology and cancer therapies through strategic partnerships and investments. For instance, Roche entered into a significant collaboration with Moma Therapeutics, investing over $2 billion in the development of precision oncology drugs. This deal highlights Roche's strategy of leveraging external expertise and platforms to identify new drug targets associated with cancer cell growth and survival, aiming to develop the next generation of precision medicines.

Another collaboration is with MediLink Therapeutics to develop YL211, a next-generation ADC targeting solid tumors. MediLink incorporates its proprietary Tumor Microenvironment Activatable LINker payload (TMALIN) ADC technology platform into the partnership, focusing on c-Mesenchymal Epithelial Transition Factor (c-Met) as the target for this therapy.

Roche will have the exclusive international rights to develop, manufacture, and sell YL211, further solidifying its position in the ADC and oncology treatment fields. The agreement includes an upfront payment and near-term milestone payments totaling $50 million to MediLink, potential development, regulatory, and commercial milestones of up to $1 billion, as well as royalties on future net sales of the product.

Takeda Pharmaceuticals

Takeda Pharmaceuticals has been actively involved in the development and commercialization of ADCs. One notable collaboration is with ImmunoGen, where Takeda obtained 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 potential milestone payments totaling up to $210 million, plus royalties on net commercial sales of any resulting ADC products.

The company also expanded its partnership with Mersana Therapeutics to advance the development of Fleximer ADC, including XMT-1522 targeting HER2-expressing tumors. This collaboration not only grants Takeda rights to Mersana’s lead candidate outside the U.S. and Canada but also provides access to Mersana's Fleximer ADC platform targeting other antigens.

Moreover, Takeda and Seagen highlighted the significance of ADCETRIS (brentuximab vedotin) in treating advanced Hodgkin lymphoma. ADCETRIS has been approved in over 70 countries for the treatment of relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma (sALCL). More than 70 clinical trials are currently evaluating it, demonstrating its broad potential in treating CD30-positive malignancies.

Recently, Takeda 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 an upfront fee of $5 million, with potential development, regulatory, and commercial milestone payments of up to $410 million, plus royalties on net sales of any commercial products developed through this collaboration.

This deal is part of Takeda's broader strategy to address celiac disease, marking the company's fourth initiative since 2019 aimed at developing candidate drugs to treat this condition. The agreement grants Takeda global exclusive rights to utilize Innate's antibody research, development, manufacturing, and commercialization of ADC, showcasing a significant move to leverage ADC technology beyond its traditional oncology applications into autoimmune diseases like celiac disease.

J.Adam, Fourteen Biotech Companies Spearheading the Antibody Drug Conjugate Industry. Labiotech, 2024.