NaPi-2b

A small Swiss drug developer is being scooped up for its pipeline of three antibody-drug conjugates that offer a next-generation approach to the area of oncology R&D that has ballooned in recent years. Otsuka subsidiary Taiho Pharmaceutical said Monday morning it will buy Araris Biotech for $400 million upfront and up to $740 million in additional biobucks. Taiho becomes the latest drugmaker to pounce on the ADC field; nearly every large pharma has either bought and/or licensed ADCs in the past few years. With its technology, the Zurich startup can attach more than one cytotoxic payload onto an antibody to “mimic really conventional chemotherapy,” Araris CEO and co-founder Dragan Grabulovski told Endpoints News in January. Other companies are also working on dual- or multi-payload ADCs . The move comes just two months after the 15-employee biotech said it was teaming up with Roche’s Japanese subsidiary Chugai for an undisclosed amount upfront and up to $780 million in milestones. Araris says its high linker solubility allows it to decrease clumping and let the ADC “properly bind” to cancerous cells. The company says its manufacturing process is also leaner, with the use of off-the-shelf antibodies. At the time, Grabulovski told Endpoints his biotech would seek to raise a Series B in the first half of this year. The startup has raised about $45 million to date from Samsung Ventures, 4BIO, b2venture, Pureos Bioventures, redalpine, Schroders Capital, VI Partners, Wille AG and the Institute for Follicular Lymphoma Innovation. The duo previously inked a research collaboration in November 2023. They expect the deal to close in the first half of this year. Taiho parent Otsuka bought small molecule drug discovery startup Jnana Therapeutics last year. “Since November 2023, Taiho has had the chance to evaluate our technology, to test it with their own antibodies, and throughout this collaboration, we came into discussions early this year about a potential acquisition, which now we have signed the documents today,” Grabulovski told Endpoints on Monday morning. The company still progressed with the Series B fundraising but iced those plans once the Taiho deal talks advanced, he said. The partnership with Chugai will continue, he added. Taiho said Monday that Araris’ three ADCs, for solid tumors and blood cancers, would enter clinical trials between this year and 2026. The biotech’s ADCs target CD79b, Nectin-4 and NaPi2b. “I would also underscore the massive potential synergies with Taiho’s clinical development experience in oncology and their robust salesforce globally as we are going after some of the highest potential, highest profile targets present across multiple solid tumor indications,” said Dima Kuzmin, chair of Araris and managing partner at 4BIO, which seeded Araris in 2020. Also on Monday morning, AstraZeneca said it made a small deal of its own, paying $425 million upfront for a UK cell therapy maker called EsoBiotec .

In order to submit an IND for ZW251 by mid-2025, Zymeworks needs to “reprioritize resources,” with ZW220 taking the hit.\n Zymeworks has pumped the brakes on plans to take one of its antibody-drug conjugates into the clinic so it can prioritize another candidate.The company entered 2025 with a goal of getting two ADCs, dubbed ZW220 and ZW251, into phase 1 trials for solid tumors this year. ZW220 targets human NaPi2b, while ZW251 targets Glypican-3.In its fourth-quarter earnings results, Zymeworks said it is stepping up its plans for ZW251 “based on our encouraging preclinical results and the unique potential opportunity to help hepatocellular carcinoma patients.” The goal is now to submit an IND for the therapy in the coming months. “ZW251 provides a new therapeutic modality option targeting GPC3 for hepatocellular carcinoma and represents an emerging opportunity in oncology that has yet to be fully realized,” Zymeworks Chief Scientific Officer Paul Moore, Ph.D., said in the March 5 release. “With a potential best-in-class design and differentiated mechanism, we believe our pipeline presents meaningful opportunities for both strategic partnerships and value creation, and we look forward to initiating a phase 1 trial for ZW251 this year.”In order to hit this deadline, Zymeworks needs to “reprioritize resources,” with ZW220 taking the hit.“As a result, we have paused preparations for the commencement of phase 1 studies of ZW220 at this time,” the biopharma said. However, Zymeworks still believes ZW220 “remains a highly differentiated, IND-ready ADC with encouraging preclinical data and strong commercial rationale with partnership potential.” “We look forward to providing future updates on the development for ZW220,” Zymeworks added.In November, the company launched another ADC, dubbed ZW191, into a phase 1 trial to assess its potential as a treatment for advanced FR⍺-expressing solid tumors. The same month, Zymeworks’ Jazz Pharmaceuticals-partnered prospect Ziihera secured FDA approval for unresectable or metastatic HER2+ (IHC 3+) biliary tract cancer.

MUNICH--( BUSINESS WIRE )-- Tubulis announced today that its second drug candidate, TUB-030, has entered clinical evaluation with successful dosing of the first patient in the 5-STAR 1-01 Phase I/IIa trial ( NCT06657222 ). The study is evaluating TUB-030, Tubulis’ next-generation antibody-drug conjugate (ADC), in patients with advanced solid tumors. The ADC targets 5T4, an oncofetal antigen expressed in a broad range of solid tumors. The program was developed using Tubulis’ proprietary Tubutecan linker-payload platform, which enables superior biophysical properties for precise and sustained on-tumor payload delivery. “This milestone for TUB-030 demonstrates our ability to execute on our strategy to advance innovative programs into our proprietary pipeline and rapidly bring them into the clinic,” said Dominik Schumacher, PhD, Chief Executive Officer and Co-founder of Tubulis. “As an organization, Tubulis has made a large step forward with two differentiated ADC molecules in clinical evaluation in less than a year. Our goal is to continue being an innovation driver in the field by delivering on the transformative potential of our platforms for patients.” The multicenter, first-in-human, dose escalation and optimization Phase I/IIa study 5-STAR 1-01 aims to investigate the safety, tolerability, pharmacokinetics, and efficacy of TUB-030 as a monotherapy to treat a broad range of solid tumors. The trial will enroll a total of 130 patients and will be conducted at sites across the US and Canada. Phase I comprises dose escalation to determine the safety profile and to identify the maximum tolerated dose and/or the identified dose for optimization in patients with advanced solid tumor indications. Phase IIa will focus on dose optimization, safety, and preliminary efficacy of TUB-030 in selected indications. “Building on our strong preclinical efficacy and safety data, we are expecting that targeting 5T4 with our high-performance ADC technology may offer a new precision therapy option for a variety of solid tumor indications. With our differentiated target, a strong bystander effect and efficient and durable target engagement via the Tubutecan platform, TUB-030 provides the potential to induce robust anti-tumor activity in 5T4-expressing tumors,” stated Günter Fingerle-Rowson, MD, PhD, Chief Medical Officer at Tubulis. TUB-030 consists of a humanized, Fc-silenced IgG1 antibody targeting 5T4 equipped with Tubulis’ proprietary Tubutecan technology, which is based on P5 conjugation chemistry and the topoisomerase-1 inhibitor exatecan. Tubulis previously presented a comprehensive preclinical data set at AACR demonstrating TUB-030’s stability and minimal loss of linker-payload conjugation. In a range of preclinical models, TUB-030 produced high and long-lasting anti-tumor responses, including responses at relatively low 5T4 expression levels, while maintaining an excellent safety and tolerability profile. A single treatment with TUB-030 eliminated tumors in a triple-negative breast cancer mouse model, further underlining its potential efficacy. Preclinical analysis including safety, efficacy and pharmacokinetics demonstrated that TUB-030 has a therapeutic window in a large variety of solid tumors. About TUB-030 and the Tubutecan Technology Tubulis’ second antibody-drug conjugate (ADC) TUB-030 is directed against 5T4, an oncofetal antigen, expressed in a broad range of solid tumor types. It consists of an IgG1 antibody targeting 5T4 connected to the Topoisomerase I inhibitor exatecan through a cleavable linker system based on the company’s proprietary P5 conjugation technology with a homogeneous DAR of 8. P5 conjugation is a novel chemistry for cysteine-selective conjugation that enables ADC generation with unprecedented linker stability and biophysical properties. The candidate is currently being investigated in a multicenter Phase I/IIa study (5-STAR 1-01, NCT06657222 ) that aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-030 as a monotherapy in advanced solid tumors. About Tubulis Tubulis generates uniquely matched antibody-drug conjugates with superior biophysical properties that have demonstrated durable on-tumor delivery and long-lasting anti-tumor activity in preclinical models. The two lead programs from our growing pipeline, TUB-040, targeting NaPi2b, and TUB-030, directed against 5T4, are being evaluated in the clinic in high-need solid tumor indications, including ovarian, lung and head and neck cancers. We will solidify our leadership position by continuing to innovate on all aspects of ADC design leveraging our proprietary platform technologies. Our goal is to expand the therapeutic potential of this drug class for our pipeline, our partners and for patients. Visit www.tubulis.com or follow us on LinkedIn .