Excalipoint is betting that the next chapter of T-cell engagers will be written in solid tumours, where the modality is beginning to challenge the boundaries of cancer immunotherapy. Co-Founder, Chairman and CEO/CSO Dr Lei Fang explains how two decades of T-cell research underpin a differentiated pipeline, a China-first global development strategy and a partnership-driven model designed to translate clinical learning into better therapies, with ambitions now extending into autoimmune disease.
What made the Roche Accelerator the right fit for Excalipoint?
When we established Excalipoint, the Roche Accelerator was one of the options we considered because we did not want to invest heavily in laboratories, facilities or equipment. We wanted a ready-to-use environment where we could start our work immediately and focus our investment on advancing our technology and our preclinical and clinical programmes. We are very much an asset-focused and technology-focused biotech, so this model made sense for us. The facilities here are built to the same standards as Roche’s own R&D centres, but rather than making that infrastructure investment ourselves, we can access it through the Accelerator.
There was also an important strategic dimension to our decision. The Roche Accelerator is not simply a laboratory rental space. Companies go through a selection process in which they present their technology, pipeline and development strategy, and Roche considers how closely these align with its research priorities and whether there is potential for future collaboration. Roche has a strong interest in immuno-oncology, and we felt that our work in T-cell engagers was a good strategic fit. Roche also saw our platforms as differentiated and relevant to its research priorities.
For us, it was therefore a combination of efficiency and strategic alignment. We wanted Roche to be one of the major pharmaceutical companies we could potentially collaborate with, and being part of its innovation ecosystem creates opportunities for those discussions. Roche Accelerator is Roche’s first in-house accelerator globally, and Excalipoint was the first T-cell engager company selected to join it.
How did your scientific and entrepreneurial journey lead you to focus on T-cell engagers?
Excalipoint is my third biotech venture, after I-Mab and Lepu Biopharma, but my work with T cells goes back almost 20 years. During my PhD at the Chinese Academy of Sciences, I spent about five years studying T-cell differentiation in autoimmune diseases, particularly multiple sclerosis and rheumatoid arthritis. I then joined GSK R&D China, where I continued working in neuroinflammation, but moved from basic research into drug discovery. Over nearly seven years there, I learned how to translate our understanding of T-cell biology into potential therapies and how to take a molecule towards clinical development.
I later joined my PhD mentor, Dr Jingwu Zang, as part of the founding team at I-Mab. This was around the time that PD-1 checkpoint inhibitors were beginning to transform cancer treatment by showing that reactivating a patient’s own immune response could produce durable tumour control. At I-Mab, we explored other mechanisms through which tumours evade or suppress the immune system, including CD47, CD73 and TIGIT, essentially asking what could come next after PD-1.
That work naturally led me into bispecific antibodies. In 2018, we began collaborating with ABL Bio on several programmes, including 4-1BB-based bispecifics such as givastomig (ABL111), targeting Claudin 18.2 and 4-1BB, and ragistomig (ABL503), targeting PD-L1 and 4-1BB. We were trying to address one of the main limitations of first-generation 4-1BB agonists, namely systemic toxicity, particularly in the liver. By using a second arm to anchor the molecule within the tumour microenvironment, we could make 4-1BB activation more conditional and concentrate T-cell co-stimulation in the tumour. That experience became very relevant to how I later thought about next-generation T-cell engagers.
After I-Mab’s Nasdaq listing in 2020, I joined Lepu Biopharma as Vice President and became General Manager of CtM Bio, its innovative drug-discovery subsidiary, where I built capabilities in target identification, antibody discovery and translational research. My experience with immune checkpoints had convinced me that T cells were central to effective anti-tumour immunity, but I became interested in going beyond releasing inhibitory signals and instead redirecting T cells directly against cancer cells. T-cell engagers had already demonstrated that this biology could work in haematological malignancies, but solid tumours remained a major challenge. That was precisely the opportunity I wanted to pursue, and from 2020 onwards I began building the T-cell engager platform at Lepu that eventually became the foundation for Excalipoint.
What convinced you that the T-cell engager platform should become a standalone company?
The turning point for the field came in 2024 with the approval of Amgen’s tarlatamab in small-cell lung cancer. Until then, we did not really have a clinical model demonstrating what a successful T-cell engager could look like in a major solid tumour. Tarlatamab provided that validation and showed that T-cell engagers could achieve meaningful responses in solid cancer, which gave the field much greater confidence. I had already been working on T-cell engager technologies for solid tumours for almost five years, so for me it reinforced the potential I had seen in the modality.
You could also see a broader shift across the industry. Merck, known as MSD outside the US and Canada, acquired Harpoon Therapeutics for around USD 680 million, while Gilead entered into a major collaboration with Merus around trispecific T-cell engagers. Investors in both the US and China were also beginning to recognise the opportunity. There was still some debate over whether tarlatamab represented an isolated success or the beginning of a broader trend, but Big Pharma interest in next-generation T-cell engagers was clearly growing.
At Lepu, however, the platform was part of a much broader oncology pipeline that included ADCs and other programmes, so the resources available to advance it were naturally limited. Investors began approaching Lepu about creating a NewCo around the T-cell engager platform, and Dr Pu Zhongjie and the leadership eventually suggested that, if I could raise the capital, I should take the programmes forward independently. I believed they would progress faster with dedicated resources, capital and management rather than remaining one part of a larger portfolio.
That was the origin of Excalipoint. Through a transaction with Lepu, we obtained exclusive global rights to two T-cell engager programmes, CTM012 and CTM013, which became EXP011 and EXP012, together with the associated intellectual property from the TOPAbody platform. Lepu retained an economic interest through equity, potential milestones and royalties. The purpose of creating Excalipoint was therefore very focused: to give the T-cell engager platform the resources and attention it needed to move faster and explore its potential in solid tumours.
What is Excalipoint seeking to achieve with its next-generation T-cell engagers in solid tumours and what is the goal of your EXPO11 program?
I have believed in the potential of T-cell engagers in solid tumours since around 2020, although the broader market and investors were not yet convinced. By 2024, that began to change as clinical data and growing industry interest provided stronger validation for the modality. We had also accumulated substantial preclinical data, including in PD-1-refractory tumour models, which gave me confidence that our approach could remain active where checkpoint inhibition had failed.
The opportunity is significant because checkpoint inhibitors such as PD-1 antibodies still benefit only a subset of patients across many solid tumours. T-cell engagers work differently. Rather than removing an inhibitory signal, they directly redirect T cells towards tumour cells, potentially extending T-cell-based immunotherapy to patients who do not respond to, or relapse after, checkpoint inhibition. We are already seeing encouraging activity in difficult settings such as prostate cancer and microsatellite-stable colorectal cancer, where checkpoint inhibitors have generally shown limited efficacy.
At Excalipoint, our aim is not simply to show that T-cell engagers can work in solid tumours, but to develop a better generation of these therapies and broaden their reach. We deliberately chose DLL3 and small-cell lung cancer for EXP011 because the target and disease setting have already been clinically validated by tarlatamab. This allows us to focus on whether our differentiated design, combining DLL3 targeting and CD3 engagement with 4-1BB co-stimulation, can generate stronger and more durable T-cell activity.
EXP011 also helps us de-risk the broader platform. What we learn clinically in this validated setting can inform programmes pursuing less established targets, including EXP012, our CDH17-directed T-cell engager for colorectal and other gastrointestinal cancers. Our broader goal is to extend the potential of T-cell engagers across solid tumours and bring T-cell-based immunotherapy to more patients.
How is Excalipoint building a differentiated T-cell engager platform with global potential, beyond your lead program and how can China speed on reaching faster POC can impact your development?
EXP011 is strategically important to Excalipoint beyond the value of the asset itself because it gives us the opportunity to clinically validate our trispecific design, which combines tumour targeting, CD3-mediated T-cell engagement and 4-1BB co-stimulation in a single molecule. I describe Excalipoint as a “CD3-plus” company. CD3 engagement is at the core of our approach, but we are not limited to 4-1BB, and the clinical learnings from EXP011 should help us understand how CD3 can be combined with different complementary mechanisms across the broader pipeline.
Our ambition is not to build Excalipoint around one or two assets, but to become a specialist platform company for T-cell engagers. In some ways, we want to follow a model similar to DualityBio in ADCs, remaining deeply focused on one modality while exploring different targets, technologies and disease settings. Solid tumours have very different tumour microenvironments and clinical needs, so we do not believe the same molecular architecture should be applied to every cancer. EXP016, for example, targets STEAP2 in prostate cancer using a different approach, while we are developing another T-cell engager technology for non-small cell lung cancer. We start with the clinical need and then select the technology we believe is best suited to the biology of that tumour.
It is important to note, we formally launched Excalipoint only in August 2025 with EXP011 and EXP012, but within roughly a year we had already generated additional programmes internally, including one progressing towards an IND filing and another differentiated programme in autoimmune disease. We have been able to move quickly because we started with technologies developed over many years and a team with deep experience in T-cell biology and multispecific antibodies, including lessons from programmes that did not work as expected.
China is also an important part of that efficiency. We can begin dose escalation here with access to large patient populations and experienced clinical investigators, allowing us to establish safety, pharmacology, the appropriate dose and early efficacy signals before expanding internationally. The unmet needs in oncology are also broadly comparable between China and the US, which means the clinical evidence we generate here can inform a global development strategy. For assets with global potential, we still expect to pursue clinical development in the US, but our approach is to generate and de-risk the initial clinical evidence efficiently in China before taking those programmes into broader global development.
How far would you like bring your programs in correlation with the vision for the company?
Our ambition is to build Excalipoint as a globally focused biotech specialising in T-cell engagers, rather than becoming a fully integrated pharmaceutical company. We want to develop differentiated technologies, advance programmes into the clinic, generate data that de-risk the assets and then pursue business development partnerships where they make sense. Clinical development is also an important feedback loop for the platform, because both positive and negative results help us understand which designs work, where they can be improved and how we should approach the next generation of molecules. We want to create a continuous cycle in which clinical learning strengthens the technology, leads to better programmes and creates further opportunities for global partnerships.
The timing is favourable because pharmaceutical companies are showing much greater interest in T-cell engagers, while much of the specialised technology and development expertise remains within biotech. We believe this creates a natural opportunity for Excalipoint as the clinical potential of T-cell engagers in solid tumours becomes clearer. Our advantage comes from the depth of experience we have accumulated in this field and our ability to explore new designs efficiently, including knowing when to stop a programme that is not working and apply those learnings elsewhere. We want to remain a specialised biotech at the forefront of T-cell engager innovation, while working with global pharmaceutical partners that can take successful programmes through later-stage development and commercialisation.
How do you maintain focus across a broad pipeline while ensuring that each programme has a clear path to the clinic?
This is my third time building a biotech company, so we wanted to do things differently. Although we currently have six programmes, they are all focused on T-cell engagers and are designed to build on one another rather than operate as standalone assets. Every programme adds to our understanding of CD3 engagement, molecular design, target biology, manufacturability, safety and translational biology, allowing us to progressively de-risk and mature the platform. Our first T-cell engager took roughly three years to move from molecular design into clinical development, whereas by our third programme we were able to reach an IND-ready stage in around 12 months. We are not starting from zero with every molecule. We are accumulating knowledge across the pipeline and using it to design T-cell engagers that are smarter, safer and more efficient. We are also working with an artificial intelligence company to explore how our own data and accumulated experience can help us design future molecules more efficiently.
My background also means that I do not look at a molecule only from the laboratory perspective. At I-Mab, I primarily led discovery and R&D, but as part of the founding team I had to think about each programme through the entire development pathway, including indication selection, clinical strategy and the evidence eventually required for registration. That perspective deepened during my five years at Lepu Biopharma, where I gained greater exposure to late-stage development, regulatory interactions and the decisions required to move programmes towards approval. This is important at Excalipoint because, even if our strategy is to partner an asset once we see a strong clinical signal, we still need to develop it with the eventual registration pathway in mind. A partner will not value a programme simply because the early data are interesting. There also needs to be a credible path towards global registration.
How do you see Excalipoint’s T-cell engager capabilities evolving beyond solid tumours?
We see opportunities for T-cell engagers well beyond oncology, and we are already extending our capabilities into autoimmune diseases, where we have two first-in-class programmes based on B-cell depletion. The differentiation we are pursuing is greater precision. Rather than broadly depleting B cells, we want to use T cells to selectively eliminate the pathogenic B-cell populations driving disease. In that sense, I see Excalipoint as a T-cell modulation company. We are using T cells as a therapeutic tool and learning how to control them more precisely, whether the objective is to target tumour cells in solid cancers or pathogenic immune cells in autoimmune disease.
An important part of that strategy is making better use of everything we have learned over many years of developing T-cell engagers, including from molecules that succeeded and those that failed. We are now working with DP Technology to build a proprietary artificial intelligence capability for T-cell engagers and multispecific antibodies, combining our molecular libraries and preclinical data with its AI technology. We want the system to learn from parameters such as binding affinity, valency, molecular geometry and the balance between efficacy and toxicity, so this is not about applying AI as a generic tool. The aim is to capture our accumulated knowledge and use it to design better T-cell engagers more efficiently, while continuing to explore complementary technologies and collaborations that can strengthen the platform.
How are you approaching financing and business development as Excalipoint builds its global strategy?
Since establishing Excalipoint in August 2025, we have raised USD 68.7 million across two financing tranches, beginning with a USD 41 million seed round and followed by a USD 27.7 million extension in March 2026. As a China-based biotech with global ambitions, we can draw on several pools of capital, including domestic renminbi funds, China-focused US-dollar funds and dual-currency investment platforms, so we still see considerable depth in the funding environment despite the constraints around US investment into China.
We had not planned to return to the market so quickly, but the transaction with Lepu Biopharma was publicly disclosed and generated significant inbound investor interest. We were able to raise the extension at a higher valuation, and our philosophy is that you should raise capital when you do not need it, because once you need it, it becomes much harder. The round also brought in Eisai Innovation, the corporate venture arm of Eisai. Its investment was relatively modest, but the strategic significance was greater. Eisai spent around six months conducting due diligence before investing, which was meaningful validation for a young company like ours, and we are now discussing potential research collaborations with them.
We apply the same proactive approach to business development. Over the past six months, we have built an active network of potential partners across the US and Europe and signed around 20 confidentiality agreements, mostly with large pharmaceutical companies. We continue to advance licensing discussions while speaking with investors about future financing because the two reinforce one another. We are only around 25 people, so business development is very much an all-hands effort, with the scientific and corporate teams working together once a potential partner begins evaluating the data and technology.
Our collaboration with Roche illustrates this strategy well. Roche will supply its anti-PD-L1 antibody atezolizumab (Tecentriq) for planned studies combining it with EXP011, while Excalipoint remains responsible for the trial and development of our asset. Since atezolizumab is already part of the established first-line treatment backbone for extensive-stage small-cell lung cancer, the collaboration gives us an opportunity to explore whether EXP011 could eventually move directly into that treatment pathway rather than remain a later-line therapy. This is how we think about development from the outset. Generating an encouraging clinical signal is important, but we also need to anticipate where the standard of care is heading, how our molecule could fit into that future treatment landscape and whether there is a credible path towards global registration and, eventually, the market.
