5T4

The concept of an antibody drug conjugate, or ADC, is straightforward: a cancer-killing drug is chemically linked to an antibody that targets the delivery of the therapy to a tumor. This drug class has made progress with several approved products and many more on their heels in clinical development. But there’s still plenty of room to improve on this type of targeted cancer therapy, contends Dominik Schumacher, CEO of Tubulis. When an ADC releases its drug payload too early, it hits healthy tissue and sparks toxic effects, Schumacher said. Also, current ADC designs are restricted in their ability to match the biology of cancer targets. Tubulis has a pipeline of ADCs designed with technologies intended to overcome those limitations. The startup is moving closer to the clinic and this week it announced the closing of €128 million (about $139 million) to support its research. There is no single linker or drug payload that makes sense for all ADCs, Schumacher told MedCity News in a January interview following the J.P. Morgan Health Care Conference. Tubulis’s technologies give the startup multiple ways to add things to an antibody using linkers that improve an ADC’s stability—a stable ADC is less likely to release its drug payload prematurely. The technologies also enable the company to develop ADCs with more potent drug payloads. “We believe that our platform is one of the most flexible ones in the industry,” Schumacher said. Tubulis has two lead programs, both in preclinical development but perhaps not for long. TUB-030 is an ADC that targets 5T4, a protein expressed by many solid tumors. The second lead program, TUB-040, targets Napi2b, a protein found in ovarian and lung cancers. Tubulis says it has optimized both ADCs for long-lasting and durable tumor engagement as well as minimal off-target toxicity. Preclinical proof-of-concept data for both are set to be presented in April during the annual meeting of the American Association for Cancer Research in San Diego. The company also said it expects to start its first Phase 1/2a clinical trial this year. Tubulis’s technologies are based on research from the Leibniz Research Institute in Berlin and the Ludwig Maximilians University in Munich. These technologies have already caught the eye of Bristol Myers Squibb, which last year paid $22.75 million to gain access to the German company’s ADC payloads and its ADC conjugation platform. BMS will use the Tubulis linker technology to develop more stable ADCs. Schumacher said BMS’s research will be guided by Tubulis’s support and expertise. He added that while Tubulis is open to additional partnerships, such deals are not a core part of the startup’s business, which remains focused on developing its internal drug pipeline. Tubulis last raised money in 2022, a Series B round that was announced as €60 million. Tubulis describes its new round as a Series B2 financing, adding in an email that it is not an extension of the Series B round. However, the new €128 million financing includes the undrawn last tranche of the prior Series B round. In total, the company says it has raised €187.1 million, which includes non-dilutive funding received in 2019. In addition to supporting ongoing development of the Tubulis pipeline, the new capital will also fund a new a U.S. subsidiary. Potential sites are still being evaluated. The latest round of investment was co-led by EQT Life Sciences and Nextech Invest. New investors that joined the round are Frazier Life Sciences and Deep Track Capital. All earlier investors also participated, including Andera Partners, BioMedPartners, Fund+, Bayern Kapital (with ScaleUp-Fonds Bayern), Evotec, Coparion, Seventure Partners, Occident, and High-Tech Gründerfonds. Illustration: Getty Images

All of Tubulis’ existing investors from a 60 million euros series B round in 2022 returned. The antibody-drug conjugate (ADC) craze shows no signs of slowing down any time soon, judging by Tubulis’ latest financing. The German biotech raked in 128 million euros ($138.8 million) in an upsized series B2 financing, which will be used to work towards entering clinical trials. At the front of Tubulis’ mind are two lead ADC candidates: TUB-040 and TUB-030. TUB-040 focuses on the tumor-antigen Napi2b, a well-known area of interest for ovarian and lung cancer that is also the target of Mersana and GSK’s ADC UpRi. UpRi was released in November 2023 from a clinical hold implemented by the FDA related to a patient death. Tubulis’ other lead ADC is TUB-030, which targets the protein 5T4, an antigen often overexpressed in solid tumors. Gilead signed a $300 million upfront pact with Dragonfly Therapeutics in 2022 centered on the biotech’s immunotherapy program targeting the same protein. Tubulis is preparing to present preclinical proof-of-concept data for the two ADCs at the Annual Meeting of the American Association for Cancer Research (AACR) next month. Money from today’s funding round will be used to launch one of these candidates into a phase 1/2a clinical trial this year. But the significant sum accrued means the biotech can go further than that, increasing the company’s presence in the U.S. via a new subsidiary as well as expanding its “suite of technology platforms to unlock novel payloads for the development of versatile and customizable ADCs.” The funding round was led by EQT Life Sciences and Nextech Invest, joined by U.S.-based funds Frazier Life Sciences and Deep Track Capital. All existing investors from Tubulis’ $63 million series B round in 2022 also returned, namely Andera Partners, BioMedPartners, Fund+, Bayern Kapital, Evotec, coparion, Seventure Partners, OCCIDENT and High-Tech Gründerfonds. “This substantial financing from a syndicate of global specialist biotech investors recognizes Tubulis’ unique position in the ADC space,” CEO Dominik Schumacher, Ph.D., said in the release. “Our goal is to establish Tubulis as a global ADC leader as we transition into a clinical-stage company and harness the full power of ADCs to bring their therapeutic value to patients with solid tumors.” Tubulis has talked up the potential for the combination of its Tubutecan payloads and P5 conjugation platform to reduce toxicity to stand out in the competitive ADC space. By minimizing premature loss of payload and stopping aggregation in circulation, Tubulis thinks it can limit target-independent toxicity and make better ADCs. The investors aren’t the only ones to have spied potential in Tubulis’ ADC ambitions. A year ago, Bristol Myers Squibb paid $22.8 million upfront to the Munich-based biotech to gain exclusive access to Tubulis’ technology for “a selected number of highly differentiated ADCs to treat solid tumors.” Once BMS selected antibody targets, the plan was for Tubulis to provide its linker-payload to create an ADC and then leave the Big Pharma partner to handle development, manufacturing and commercialization. BMS returned to the ADC gold rush toward the end of last year, paying China’s SystImmune $800 million and Orum Therapeutics $100 million.

As the antibody-drug conjugate (ADC) craze continues, Tubulis raised a €128 million ($138.8 million) series B2 round to start a clinical trial this year for one of its programmes, which are designed to have better durability than currently approved products.Tubulis’ ADC platform has already attracted interest from large pharma, which went on a dealmaking spree last year for the modality. Bristol Myers Squibb partnered with the German biotech last year to develop ADCs in a deal potentially worth over $1 billion in biobucks (see: Vital Signs: AbbVie zooms past Pfizer into top ADC spot).The round, which brings Tubulis’ total funding to €187 million, was co-led by EQT Life Sciences and Nextech Invest Ltd. New investors also Frazier Life Sciences and Deep Track Capital also participated, as did existing investors including Andera Partners, BioMedPartners, Fund+, Bayern Kapital (with ScaleUp Fonds Bayern), Evotec, coparion, Seventure Partners, OCCIDENT and High-Tech Gründerfonds.ADC flexibilityCEO Dominik Schumacher told FirstWord that since the first ADC was approved two decades ago, there’s been a substantial effort to iterate on the modality’s three components of antibody, linker, and payload to make treatments safer and more effective – and he thinks there’s still plenty of room to push the developmental envelope on ADCs so they eventually become a first-line treatment option. “I'm really excited about the momentum that we have in the ADC space. It clearly underpins the relevance of this format and how important it will also be in the future for the treatment of patients in need,” he said. “We have been from the very first day, making a lot of effort to innovate on all aspects of the ADC: antibodies, linkers, and also payloads. And this, I think, puts us into a very unique position to have a lot of flexibility, but also to continue to push the boundaries of this format.”Tubulis’ two lead candidates were developed based on a deep knowledge of their targets, Schumacher said. TUB-030 is directed against solid tumour antigen 5T4, and TUB-040 homes in on Napi2b, a well-characterised target often present in ovarian and lung cancers.“When you design an ADC, you need to really look at the indication and the biology of a target and get educated by that to really understand what the individual need is from a clinical perspective when it comes to resistance mechanisms,” he explained. “At Tubulis, we have been investing heavily into having flexibility to really tailor-make an ADC and thus come with biophysical properties that are optimised for tumour engagement and the delivery of the payload into the tumour microenvironment to really ensure that we get as long as possible durability.” Both programmes deliver a topoisomerase-I inhibitor payload developed with the company’s Tubetecan platform, but Schumacher highlighted payload innovation as one area of investment with Thursday’s fundraising.It’s important to have payload choice and flexibility, he said, in part to reduce target independent toxicities. “Our platform has the capability to unlock completely novel payloads,” he added. According to Schumacher, preclinical studies have shown long durability for both programmes – “now we want to translate that into clinical proof-of-concept,” he added. Tubulis will be presenting some of the preclinical data at the upcoming American Association for Cancer Research annual meeting in April. The company plans to start a Phase I/IIa trial this year, but hasn’t yet selected which candidate will begin in-human studies first. Additionally, Tubulis will allot some of its new funds to open a US subsidiary.