China's ADC Consortium Scores $1.1B Victory: Nona Biosciences Submits IPO Prospectus Following Landmark Pfizer Deal

On December 15, Harbour BioMed's wholly-owned subsidiary, Harbour BioMed (Suzhou) Co., Ltd, announced that it had entered into an exclusive licensing agreement with Pfizer for the global clinical development and commercialization of the mesothelin (MSLN)-targeted antibody-drug conjugate (ADC) HBM9033.It is reported that the cooperation partner of this transaction is Seagen, and the signing party is Pfizer. This means that Harbour BioMed will not only cooperate with Pfizer, a leading global MNC, but also establish close ties with Seagen, which ranks among the top tier in the ADC sector, thereby receiving maximum support in terms of resources and technology.

According to the agreement, Harbour BioMed (Suzhou) Co., Ltd. will receive a prepayment and near-term payment totaling $53 million, as well as milestone payments of up to $1.05 billion. Additionally, Harbour BioMed is eligible to receive tiered royalties ranging from high single digits to high teens based on net sales.

It is reported that HBM9033 is an antibody-drug conjugate (ADC) specifically targeting human mesothelin (MSLN), a tumor-associated antigen that is upregulated in various solid tumors. The fully human monoclonal antibody in HBM9033 is developed by Harbour Mice.^® The platform exhibits excellent properties, maintaining strong binding and internalization with membrane-bound MSLN while reducing binding with soluble MSLN.

Harbour Mice^®Capable of generating fully human monoclonal antibodies in classic (H2L2) and heavy-chain only (HCAb) formats, working in tandem with a single B-cell cloning platform to optimize antibody discovery efficiency. The unique antibody design demonstrates superior efficacy and safety in preclinical tumor models with varying MSLN expression levels, positioning HBM9033 as a potential best-in-class global therapy.

In addition to this collaboration exceeding $1 billion, just yesterday, Pfizer announced the completion of its acquisition of Seagen, the leader in ADC. This acquisition amounted to approximately $43 billion, marking the largest merger and acquisition case in the ADC sector to date.

Pfizer's aggressive move into the ADC track vividly illustrates the saying, "We had no connection, but I made it happen with my money." These transaction amounts may seem substantial, but for the pharmaceutical giant Pfizer, this is just a drop in the bucket.

According to Pfizer's 2022 financial report, its full-year revenue for 2022 reached a record-breaking $100.3 billion, marking a significant year-over-year increase of 23%. Pfizer has thus become the world’s first pharmaceutical company to surpass $100 billion in annual revenue. Of this, combined sales of Pfizer’s COVID-19 vaccine and antiviral drug Paxlovid amounted to nearly $57 billion last year, accounting for nearly 60% of the company’s total revenue in 2022. Excluding the contributions from the COVID-19 drug Paxlovid and the COVID-19 vaccine, Pfizer’s revenue grew by 2% year-over-year.

The huge revenue brought by the COVID-19 vaccine has enabled Pfizer to acquire Seagen at a 30% premium, but even before this, Pfizer has never been stingy in its investment in the ADC field.

In 2009, Pfizer acquired Wyeth for $68 billion, thereby gaining the world's first ADC drug, Mylotarg, which targets CD33. Pfizer also entered the top tier in the global ADC field as a result.

Mylotarg was approved by the FDA in 2000 for the treatment of acute myeloid leukemia (AML) but was withdrawn from the market in 2010 due to adverse reactions. In June 2010, Pfizer announced the voluntary withdrawal of gemtuzumab ozogamicin from the market and initiated a reevaluation. In 2017, Mylotarg returned to the market, marking a tumultuous approval journey. In the same year, Pfizer also launched another ADC product, Besponsa, which targets CD22 and is used for the treatment of acute lymphoblastic leukemia (ALL).

The market expectations for these two ADC products launched by Pfizer are not optimistic.

In addition to these two unexpected products, Pfizer also successively terminated several ADC pipelines in the following years:In 2018, Pfizer terminated its five-year ADC collaboration with CytomX and licensed the development and commercialization rights of YX-201 and PYX-203 to Pyxis Oncology. Amid a 9% decline in revenue in Q4 2019, Pfizer announced the discontinuation of the development of ADC drug PF-06688992.

A Turn for the Better: The outbreak of the pandemic at the end of 2019 allowed Pfizer to reap substantial rewards in the following years with its COVID-19 vaccine. However, as the pandemic waned, Pfizer's revenue predictably declined.

Pfizer has accumulated sufficient funds due to the pandemic, and indeed needs to seek new growth points before a significant downturn becomes apparent.

ADC is undoubtedly a popular choice at present. Although ADC is popular, it is not overcrowded.

Although many articles compare ADCs to PD-1, believing that the field is highly competitive with little room for differentiation and seemingly reaching the end of its development, this notion of "involution" only scratches the surface. While ADC products may appear crowded in terms of targets, ADCs differ from pure antibody drugs as they do not kill tumor cells by affecting the intrinsic function of a target to achieve therapeutic effects. The target is merely a transit point; the real therapeutic effect comes from the toxin.

In addition, the therapeutic window of existing ADC drugs is still relatively narrow, far from achieving the level of safety expected of a "magic bullet," leaving significant room for improvement. On the other hand, all aspects of ADCs can be optimized and enhanced, including specific antibody binding, the diversity of toxin mechanisms, and specific linker cleavage and release. Moreover, the application of ADCs in non-oncology diseases represents a new direction yet to be explored.

Pfizer, recognizing this potential, has chosen to "double down" on ADCs, successively acquiring Seagen, the leader in ADCs, and introducing Harbour BioMed's ADC pipeline. This persistence represents Pfizer's bet on the future new trends in the pharmaceutical field.

This year's ADC BD deal boom has extended to Harbour BioMed. In this collaboration, Harbour BioMed will not only be able to closely engage with Pfizer but, more importantly, deeply communicate and cooperate with Seagen, a top innovative company in the global ADC field.

The core of being able to reach a cooperative deal with Pfizer lies in the innovative genes of Harbour BioMed's subsidiary, Harbour BioMed (Suzhou) Co., Ltd.

In 2022, to maximize the value of its technology platform, Harbour BioMed split its business into two pillars: one is Harbour BioMed, which focuses on a product pipeline with an emphasis on the research and development of tumor immunotherapy; the other is Nanobio (Suzhou) Co., Ltd., a subsidiary spun off from the technology platform, aiming to become a platform company through continuous innovation, iteration, and the licensing, collaboration, and servicing of technologies.

The gene from which Harbour BioMed (Suzhou) Co., Ltd originated was the Dutch antibody platform company Harbour Antibodies, acquired by Harbour BioMed in 2016.

At the beginning, the business of this platform was relatively单一, only doing technology licensing, without the capability for new drug development. After the establishment of Harbour BioMed, the technology platform kept optimizing and iterating. The emergence of the second-generation, third-generation of Harbour mice greatly improved the R&D efficiency and technical maturity. Currently, it has expanded into Harbour Mice.^®Fully human antibody transgenic mouse platform, and a new generation of independently developed immune cell engager bispecific antibody platform HBICE^®And technical integration platforms like Antibody Plus. The platform's capacity has surpassed merely meeting the internal new drug R&D demands of Harbour BioMed, and it is fully capable of supporting antibody discovery and screening for the entire industry.

Currently, the most core underlying technology of this platform has been continuously validated by the Harbour BioMed team. The company has utilized this technology platform to advance more than 14 projects to the IND and clinical development stages, making it one of the few globally recognized platforms with clinically proven and mature technology.

These antibody technologies, after years of deep沉淀, have enabled Harbour BioMed's layout in the ADC field to not only be innovative but also more forward-looking.For ADC technology, Harbour BioMed (Suzhou) Co., Ltd.'s fully human antibody technology platform can reduce the immunogenicity of many ADC drugs, while also holding its own patented technology in site-specific conjugation.Utilizing the ADC antibody technology platform, Harbour BioMed has carried out a series of expansions. Currently, this antibody technology platform can be applied to directions such as ADC and XDC, with successful preclinical cases in areas like AOC and RDC.

Looking back at the product HBM9033 that achieved cooperation this time, the therapy targets mesothelin (MSLN) and has unique differentiation in the ADC field. The product consists of a fully human monoclonal antibody generated by Harbour BioMed's technology platform and a next-generation payload-linker, demonstrating differentiated advantages in biology, physicochemical properties, and drugability. Not only is it novel in design with unique biological functions, but it is also highly efficient in research and development progress.

In this transaction, there is a noteworthy detail: behind the collaboration between Harbour BioMed and Pfizer lies the support of another Chinese ADC company, Yilian Biotechnology.

It is reported that HBM9033 is developed by Harbour BioMed using Harbour Mice technology.^®The platform generates fully human monoclonal antibodies, then utilizes the latest generation ADC technology platform TMALIN from Yilian Biotechnology.^®Optimize to better bind with membrane-bound MSLN while minimizing interference from free MSLN. At the same time, achieve high DAR value uniformity and stable conjugation, further broaden the therapeutic window of ADC drugs, and enhance the therapeutic effect of ADC drugs in solid tumors.

Based on the strong collaboration between the two platforms,HBM9033's unique antibody and linker-payload design has demonstrated outstanding efficacy and safety in preclinical studies. This ADC utilizes a tumor-specific cleavable linker and a novel topoisomerase inhibitor to enhance stability and activity.Currently, HBM9033 received IND approval in August this year. Its Phase I study aims to evaluate its safety, tolerability, pharmacokinetics, and anti-tumor activity in patients with advanced solid tumors.

Therefore, rather than a win-win situation between Harbour BioMed and Pfizer, it is more of a triple-win among Harbour BioMed, Pfizer, and Yilian Biotechnology. Reviewing this year's overseas licensing deals for Chinese ADCs, this is not the first time that Chinese pharmaceutical companies have ventured abroad in ADC drug research and development collaborations. Previously, in the successful overseas expansion case of Kelun-Biotech's ADC, two out of seven products were developed using fully human antibodies generated from Harbour BioMed’s transgenic mice platform. Currently, Harbour BioMed (Suzhou) Co., Ltd has reached cooperation with many ADC enterprises to support innovative R&D of ADC drugs, including domestic star ADC companies such as DualityBio and QED Therapeutics, as well as hot overseas ADC enterprises like LegoChem Bioscience.

Harbour BioMed is providing the underlying technology engine and support for the research and development of innovative drugs in China, while the collaborative innovation in China's ADC sector has shown the industry more possibilities for domestic Biotech companies to collaborate and expand overseas.