China’s productivity nearly matches the output of the US and places Europe in a distant third.
A couple of weeks ago, Bloomberg also summarized deal data showing how the share of global licensing by Chinese biotech companies has jumped over the past two years.
Licenses involving Chinese biotechs, as shown by share of upfront cash in licensing deals involving at least one foreign buyer. Data as of June 18, 2025. Calculation includes companies with headquarters in mainland China and Hong Kong. Source: Bloomberg/Dealforma
Judging by a report listing 16 ‘high-value’ currently unlicensed assets from China being hawked by longtime Phalanx Investment Partners analyst David Maris, there is more licensing to come.
In this context, we read with interest a recent Science Immunology paper describing a monoclonal antibody (mAb) program targeting a novel phagocytic checkpoint under development at yet another Chinese biotech: MedimScience, founded in Hangzhou City in 2021. MedimScience is one of a growing cadre of companies, including LTZ Therapeutics, Dren Bio, Chengdu Kanghong, Antengene and ImmuneOnco, looking to develop novel myeloid cell engagers/phagocytic checkpoint inhibitors.
Phagocytic checkpoint inhibitors are drugs that circumvent the molecular cloaks that tumors throw around themselves to avoid uptake and destruction by myeloid cells, such as macrophages, monocytes, and neutrophils. The strategy first came to the fore through pioneering work on the ‘don’t eat me’ signal CD47, work carried out by Ravi Majeti and Irv Weissman at Stanford. Results from their preclinical studies spurred the launch of startup Forty Seven (subsequently acquired in 2020 by Gilead) and the first-in-class anti-CD47 IgG4 magrolimabprogram.Phase 1b trial results of magrolimab combined with azacitidine in acute myeloid leukemia (AML) patients were so impressive that, by 2022, more than 20 different companies had anti-CD47 programs in clinical development. This blew up spectacularly when early trials failed to be reproduced in larger efficacy trials of combinations — failure that was largely attributed to intolerability/anemia issues related to the target, slow action/early disease progression, and a failure to account for patient heterogeneity with regard to P53 mutation status. But the strategy is compelling and the hunt for new phagocytic checkpoints has continued with new antibody formats seeking to avoid these pitfalls.
Now, Cheng Zhong and his colleagues at MedimScience report the identification of a new evasion actor — PSGL-1 — that suppresses macrophage-mediated phagocytosis in a variety of hematological malignancies. PSGL-1, which was previously known largely for its role in cell adhesion, is highly expressed in various hematologic cancers, including AML, T-acute lymphoblastic leukemia (T-ALL) and multiple myeloma (MM).
PSGL-1 transcript expression in various cancers. Source: Human Protein Atlas
Moreover, high PSGL-1 expression has been found to correlate with poor patient survival in AML, T-ALL and MM.
PSGL-1 expression and patient survival. (A) Correlation analysis of PSGL-1 expression with survival of patients with AML (n = 957); (B) Correlation analysis of PSGL-1 expression with survival of patients with MM (n = 559). (C) PSGL-1 expression quantified by flow cytometry among patients with B cell acute lymphoblastic leukemia (B-ALL; n = 33), AML (n = 41), T-ALL (n = 32), and MM (n = 29). Source:Science Immunology
Using several mouse models, the researchers found that tumors lacking PSGL-1 show slower progression, increased macrophage infiltration, and higher rates of phagocytosis by macrophages, effects that were independent of T cells or dendritic cells.
Mechanistically, the team found that PSGL-1 disrupts the interaction between the cell-adhesion molecule ICAM-1 on tumor cells and the integrin LFA-1 (CD11a/CD18) on macrophages. And when they tested Novartis’ lifitegrast, an inhibitor of ICAM-1/LFA-1 binding, they found this largely abrogates the phagocytosis of PSGL-1 knockout tumor cells, confirming PSGL1’s role in impairing prophagocytic signaling and cytoskeletal reorganization required for effective tumor-cell engulfment.
The authors went on to develop a humanized mAb against PSGL-1 and show its ability to induce phagocytosis of human tumor cells in vitro and to reduce tumor burden in mouse models of AML, T-ALL, and MM. The antibody showed a good safety profile in non-human primates with no significant toxicity at high doses. Additionally, PSGL-1 blockade synergized with chemotherapy (doxorubicin) and antibody-based therapies (anti-CD47 and anti-CD38), further underscoring the translational potential of this strategy, particularly in treatment-resistant settings.
Molecular glue degraders (MGDs) are currently having a bit of a moment. In the first half of 2025, the number of papers describing such compounds has doubled.
Molecular glue uptick in the literature —a doubling of output since the start of the year. (Search based on number of papers indexed in PubMed with search term “molecular glue” in title or abstract. As of June 30, a total of 28 preprints describing molecular glue drugs had been published on BioRxiv/MedRxiv.)
2025 has also witnessed a whole raft of MGD startups publish research related to their programs:
Startup (location)
Scientific founders (location)
2025 paper
Ambagon Therapeutics (Eindhoven, The Netherlands)
Michelle Arkin (UCSF, San Francisco, CA), Luc Brunsveld and Christian Ottman (Eindhoven University of Technology)
Rajesh Chopra and Ian Collins (The Institute of Cancer Research and Cancer Research UK); Nicolas Thomä (Friedrich Miescher Institute, Basel, Switzerland)
Héctor G. Palmer, Esther Riambau, Isabel Puig, Josep Tabernero, Xavier Barril, and Carles Galdeano (Vall d’Hebron Institute of Oncology, University of Barcelona and ICREA)
On the commercial front, the march of startups receiving funding shows no sign of slowing down, with Trimtech Therapeutics and Booster Therapeutics raising substantive rounds. The first few months of the year have also seen the continuation of last year’s pharma MGD scramble to license programs from Triana Biomedicines and Neomorph, with deals based around molecular glues from Abbvie and Merck targeting Neomorph and Springworks, respectively.
Unlike their more recent cousins, the PROTACs (proteolysis targeting chimeras), MGDs have a long history. The archetypal MGD, thalidomide, was discovered back in the 1950s. From the late 1990s, a new generation of immunomodulatory imide drug (IMiD) derivatives of thalidomide were synthesized, culminating with the approvals of lenalidomide and pomalidomide for myeloma (which formed the basis for the Celgene (now BMS) franchise).
Unlike PROTACs, which use two ligands with a linker and tend to be rather unwieldy, MGDs are small, single compounds that induce conformational changes in E3 ubiquitin ligases and target proteins, reshaping both to enable binding. The vast majority of MGDs bind Cereblon (CRBN), leading to ubiquitination of the protein of interest and degradation in the 26S proteasome, although work is progressing to broaden MGD action to some of the other 600 or so E3 ubiquitin ligases (e.g., DCAF11,15 or 16, DDB1, SIAH, KEAP1, VHL, β-TrCP, Nedd1 and, just last week, TRIM21).
A key challenge in finding new MGDs has been a lack of understanding of the structural rules whereby MGDs turn their target proteins into CRBN ‘neosubstrates’, which has meant MGD ‘hit-finding’ is much more challenging, with fewer degrees of freedom than PROTACs.
What drug hunters have established is that many protein targets of glues contain a β-hairpin structural motif known as the ‘G-loop’. When a MGD brings a target together with CRBN, one end of the MGD interacts with a binding pocket in the C-terminal domain of CRBN, while the other end protrudes from the pocket and interacts with the G-loop (part of the so-called ‘degron’) in the neosubstrate. But how many proteins possess the β-hairpin G-loop or whether the loop is strictly necessary for MGD action have remained open questions. A recent study by Monte Rosa Therapeutics’ scientists starts to tackle these issues, disclosing a large cadre of potential new substrates for CRBN, some of which depart from the canonical β-hairpin G-loop, radically expanding MGD target space.
To map the full range of proteins potentially recruitable by CRBN through MGDs, the team led by John Castle and Sharon Townson developed computational algorithms to search for β-hairpin G-loop motifs in protein structures from two databases: Protein Data Bank and AlphaFold2. This approach resulted in 1424 candidate proteins, some of which were experimentally validated in MGD assays. The list included previously known neosubstrates, but also new proteins such as NEK7—a protein of interest as an autoimmunity target.
The researchers then wondered if the full β-hairpin structure of the G-loop is required for CRBN recognition and rescreened the structure databases looking for a minimal, structurally defined helical G-loop motif. This resulted in the identification of 184 additional potential neosubstrates, including mTOR, a well-established therapeutic target for drugs like rapamycin and sirolimus. Crystallographic data showed that the binding of this helical G-loop to CRBN is similar to that of the canonical β-hairpin G-loops.
As these protein–protein interactions have been well characterized, the team then tried to identify an even wider set of potential neosubstrates, looking now for proteins with sequences that might result in surfaces with electrostatic properties similar to known CRBN interactors, independently of secondary structure and the existence of G-loops. Using surface-matching algorithms, they identified and validated VAV1 (another autoimmune disease target) as a CRBN neosubstrate, providing compelling evidence that G-loops are not strictly necessary for the action of MGDs.
These findings show that CRBN recruitment through MGDs can be driven by a broader set of structural features than previously thought. The identification of a large number of neosubstrates potentially opens up a whole new set of previously ‘undruggable’ targets to MGDs (>1,600 proteins from many target classes, according to the Monte Rosa team).
An expanding protein target universe for MGD drugs. Source: Science
The big questions, though, are still ahead. How will drug developers mitigate the risks of ‘off-tissue’ toxicity as this swathe of novel MGD compounds and new targets make their way into the clinic?One answer to the toxicity concern is molecular glue antibody conjugates (MACs), which can better localize glues to the tissue of interest. But that’s a subject for a whole other future Haystack Chat!
The firm is focused on therapeutics companies and does not invest in medical devices, diagnostics, or digital health. The firm is open to considering assets of very early stages, even those as early as lead optimization phase. The firm considers various modalities, including antibodies, small molecules, and cell therapy. Currently, the firm is not interested in gene therapy. Indication-wise, the firm is most interested in oncology and autoimmune diseases but has recently looked at fibrotic diseases and certain rare diseases as well.
The firm is opportunistic across all subsectors of healthcare. Within MedTech, the firm is most interested in medical devices, artificial intelligence, robotics, and mobile health. The firm is seeking post-prototype innovations that are FDA cleared or are close to receiving clearance. Within therapeutics, the firm is interested in therapeutics for large disease markets such as oncology, neurology, and metabolic diseases. The firm is open to all modalities with a special interest in immunotherapy and cell therapy.
A strategic investment firm of a large global pharmaceutical makes investments ranging from $5 million to $30 million, acting either as a sole investor or within a syndicate. The firm is open to considering therapeutic opportunities globally, but only if the company is pursuing a market opportunity in the USA and is in dialogue with the US FDA.
The firm is currently looking for new investment opportunities in enterprise software, medical devices, and the healthcare IT space. The firm will invest in 510k devices and healthcare IT companies, and it is very opportunistic in terms of indications. In the past, the firm was active in medical device companies developing dental devices, endovascular innovation devices, and women’s health devices.
A venture capital firm founded in 2005 has multiple offices throughout Asia, New York, and San Diego. The firm has closed its fifth fund in 2017 and is currently raising a sixth fund, which the firm is targeting to be the largest fund to date. The firm continues to actively seek investment opportunities across a […]
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