Oncology & Clinical Context — Glossary¶

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The biology, modalities, mechanisms, and indication terms that come up in oncology drug development conversations — particularly in the antibody / immunotherapy / ADC space that dominates Adagene-style portfolios.

Terms covered:

SAFEbody / NEObody / POWERbody
Masked antibody / conditional activation
Tumour microenvironment (TME)
T-cell engager (TCE)
Antibody-drug conjugate (ADC)
CTLA-4 / PD-1 / PD-L1 / CD137 / CD20
Treg depletion
Common cancer indications (HCC, CRC, NHL, NSCLC)
Neoadjuvant vs adjuvant vs metastatic settings
Combination therapy

SAFEbody / NEObody / POWERbody¶

Definition. Adagene's proprietary antibody discovery platforms:

NEObody — antibodies discovered against unique or under-explored epitopes on validated targets, intended to provide differentiation versus existing antibodies against the same target
SAFEbody — masked antibodies that are inactive in healthy tissue and become active only in the tumour microenvironment, intended to widen the therapeutic window
POWERbody — multi-functional antibodies (e.g., bispecific T-cell engagers built on the NEObody / SAFEbody scaffolds)

In practice. Adagene's pipeline programs are categorised by which platform produced them:

ADG126 (muzastotug, anti-CTLA-4) — SAFEbody
ADG116 (anti-CTLA-4, unique epitope) — NEObody
ADG138 (anti-HER2 T-cell engager) — SAFEbody POWERbody
ADG152 (anti-CD20 T-cell engager) — SAFEbody POWERbody
ADG106 (anti-CD137, deprioritised)

Why it matters. The SAFEbody platform is Adagene's primary differentiator and the basis of their major partnerships (Sanofi, Exelixis, Third Arc Bio, ConjugateBio). Understanding the platform helps frame why these partnerships exist.

Masked antibody / conditional activation¶

Definition. A class of antibody therapeutics designed to be inactive in normal tissue and become active only in a specific tumour-relevant context — typically by being "unmasked" in the tumour microenvironment by tumour-specific proteases or other localised conditions.

In practice. The mechanism typically involves:

The antibody binding site is sterically blocked ("masked") by a peptide tether
The tether contains a cleavage sequence specific to proteases enriched in the tumour microenvironment
In healthy tissue, the protease activity is too low to cleave the tether — the antibody stays inert
In the tumour microenvironment, the protease activity is high enough to cleave the tether — the antibody becomes active locally

The result is a wider therapeutic window — a higher dose can be tolerated systemically because off-target activity is minimised.

Why it matters. Conditional activation is one of the most active areas of antibody engineering because it addresses a fundamental constraint of immuno-oncology: the most active mechanisms (CTLA-4 blockade, T-cell engagement) are also the most toxic. Conditional activation widens the dose-response window and may unlock combinations that would otherwise be intolerable.

Tumour microenvironment (TME)¶

Definition. The cellular and molecular environment surrounding a tumour — including immune cells (T cells, regulatory T cells, macrophages, etc.), stromal cells, blood vessels, extracellular matrix, and the molecular signals exchanged between them. The TME is increasingly understood as a critical determinant of tumour behaviour and therapy response.

In practice. Key TME features that matter for oncology drug development:

Immune infiltration — "hot" tumours have substantial immune cell infiltration; "cold" tumours don't (and respond poorly to immunotherapy)
Treg presence — regulatory T cells suppress local immune responses; depleting them is a key therapeutic strategy
Hypoxia / acidic pH — distinct from healthy tissue; targeted by some conditional-activation strategies
Tumour-specific proteases — used as activation triggers for masked antibodies
Immune checkpoint expression — PD-L1 expression on tumour cells is a marker of immunotherapy response

Why it matters. Many modern oncology drugs are designed to act in or on the TME — masked antibodies, T-cell engagers, ADCs all leverage TME features. Understanding the TME context is essential to understanding why a particular asset works (or doesn't).

T-cell engager (TCE)¶

Definition. A class of antibody-based therapeutic that recruits T cells to attack tumour cells. Typically a bispecific antibody with one arm binding a tumour-associated antigen and the other arm binding CD3 on T cells, forcing physical proximity and activating the T cell to attack.

In practice. Major T-cell engager classes:

BiTE (Bispecific T-cell Engager) — Amgen's pioneering format; blinatumomab (Blincyto) is the prototype
CD3 × tumour-antigen bispecifics — many configurations; growing clinical pipeline (e.g., Roche's mosunetuzumab/glofitamab against CD20, Janssen's teclistamab against BCMA)
TriTACs / DARTs / similar formats — various structural variations

A typical T-cell engager mechanism:

The bispecific binds tumour antigen on one side, CD3 on a T cell on the other
The T cell is activated (CD3 cross-linking)
The activated T cell releases perforin and granzymes, killing the bound tumour cell

Why it matters. T-cell engagers have produced striking efficacy in haematological malignancies (B-cell lymphomas, multiple myeloma) and are now expanding into solid tumours. The major challenge is cytokine release syndrome (CRS) — overzealous T cell activation causing systemic inflammation. Conditional activation strategies (masked T-cell engagers like Adagene's ADG138 and ADG152) are designed to mitigate CRS.

Antibody-drug conjugate (ADC)¶

Definition. A class of therapeutic that combines an antibody (for tumour targeting) with a cytotoxic small-molecule "payload" (for tumour killing) connected by a chemical "linker." The antibody binds the tumour cell, gets internalised, and releases the payload inside the cell where the toxic agent kills it.

In practice. ADC development has accelerated dramatically over the past decade. Notable approved ADCs include:

Trastuzumab deruxtecan (Enhertu) — anti-HER2 + topoisomerase inhibitor; transformative for HER2+ breast cancer
Sacituzumab govitecan (Trodelvy) — anti-Trop2 + topoisomerase inhibitor; effective in triple-negative breast cancer
Brentuximab vedotin (Adcetris) — anti-CD30 + microtubule inhibitor; Hodgkin lymphoma
Enfortumab vedotin (Padcev) — anti-Nectin-4 + microtubule inhibitor; bladder cancer

Adagene's collaboration with Exelixis is developing masked ADCs — combining the SAFEbody conditional-activation approach with ADC payload delivery, intended to widen the therapeutic window of cytotoxic ADCs.

Why it matters. ADCs are among the most commercially significant new oncology modalities, and conditional-activation ADCs (Adagene-Exelixis, others) represent one of the next frontiers in the space.

CTLA-4 / PD-1 / PD-L1 / CD137 / CD20¶

Definition. Major immune-related cell surface targets relevant to current oncology drug development:

CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) — immune checkpoint; blocking it amplifies T cell activation. Approved drug: ipilimumab (Yervoy)
PD-1 (programmed cell death protein 1) — immune checkpoint on T cells; blocking it reactivates exhausted T cells. Approved drugs: pembrolizumab (Keytruda), nivolumab (Opdivo)
PD-L1 (programmed death-ligand 1) — the ligand for PD-1, expressed on tumours and immune cells; blocking it reactivates T cells. Approved drugs: atezolizumab (Tecentriq), durvalumab (Imfinzi)
CD137 (4-1BB) — costimulatory receptor on T cells; engaging it activates T cells. Multiple agents in development
CD20 — B-cell surface marker; target of rituximab and many B-cell-malignancy therapeutics

In practice. Each of these targets has driven a generation of oncology therapeutics. Adagene's pipeline plays in this space:

ADG126 (muzastotug) — anti-CTLA-4 SAFEbody
ADG116 — anti-CTLA-4 (unique epitope)
ADG106 — anti-CD137 (deprioritised)
ADG152 — anti-CD20 T-cell engager

Why it matters. Understanding which target a drug hits, and what the existing therapeutic landscape against that target is, is essential for understanding the asset's commercial and clinical positioning. The CTLA-4 space is particularly relevant for Adagene because the existing CTLA-4 inhibitor (ipilimumab) has well-known toxicity issues that SAFEbody-masked CTLA-4 inhibitors aim to mitigate.

Related: Treg depletion · Combination therapy

Treg depletion¶

Definition. A therapeutic strategy that selectively eliminates regulatory T cells (Tregs) — a subset of T cells that suppress immune responses and protect tumours from immune attack. Some anti-CTLA-4 antibodies (including Adagene's muzastotug) work primarily through Treg depletion in the tumour microenvironment, in addition to or instead of the historical "checkpoint blockade" mechanism.

In practice. The mechanism typically requires:

Anti-CTLA-4 binding to CTLA-4 on Tregs (which express CTLA-4 at higher levels than effector T cells)
Antibody-dependent cellular cytotoxicity (ADCC) — natural killer cells or macrophages eliminate the antibody-bound Tregs
The result is enhanced effector T cell activity in the tumour microenvironment because the suppressive Treg population is reduced

Why it matters. Treg depletion as a primary mechanism (versus pure checkpoint blockade) is increasingly understood as a driver of CTLA-4 inhibitor efficacy. Designing antibodies to maximise Treg depletion while minimising systemic toxicity is a key area of development — exactly where Adagene's masked-CTLA-4 approach plays.

Related: CTLA-4 · Tumour microenvironment (TME)

Common cancer indications (HCC, CRC, NHL, NSCLC)¶

Definition. Common cancer-type abbreviations that come up in oncology trial portfolios:

HCC (Hepatocellular Carcinoma) — primary liver cancer; major unmet need especially in APAC
CRC (Colorectal Cancer) — third most common cancer globally; subdivided by molecular features (MSS vs MSI-H, KRAS status, etc.)
NHL (Non-Hodgkin Lymphoma) — B-cell or T-cell lymphomas; major target for CD20 / CD3 bispecifics
NSCLC (Non-Small Cell Lung Cancer) — most common lung cancer; major immunotherapy and targeted-therapy battleground
TNBC (Triple-Negative Breast Cancer) — breast cancer lacking ER, PR, HER2; high unmet need
HNSCC (Head and Neck Squamous Cell Carcinoma)
RCC (Renal Cell Carcinoma) — kidney cancer
MM (Multiple Myeloma) — plasma cell malignancy
AML (Acute Myeloid Leukaemia)
ALL (Acute Lymphoblastic Leukaemia)

In practice. Adagene's active or upcoming indications include MSS-CRC (lead, muzastotug + pembrolizumab), HCC (per recent disclosures), and broader solid tumours. The choice of indication shapes trial design, comparator selection, regulatory strategy, and commercial positioning.

Why it matters. Indication selection is one of the most consequential strategic decisions in early-stage oncology development. High unmet need + favourable competitive landscape + tractable trial design = preferred indication.

Related: MSS vs MSI-H · Combination therapy

Neoadjuvant vs adjuvant vs metastatic settings¶

Definition. The three principal disease settings in which oncology therapeutics are tested:

Neoadjuvant — given before primary treatment (typically surgery), with the goal of shrinking the tumour and improving surgical outcomes. Increasingly important for immunotherapy because the intact tumour antigen-presenting context appears to enhance response.
Adjuvant — given after primary treatment to reduce recurrence risk. The dominant historical paradigm for post-surgical cancer therapy.
Metastatic — given to patients with advanced disease that has spread beyond the primary site. Most early oncology development happens here because patient need is highest and the regulatory pathway is most established.

In practice. The Adagene NUH Singapore IIT (NCT06846268) is a neoadjuvant CRC trial — testing muzastotug ahead of surgical resection. This is meaningful because neoadjuvant immunotherapy is an emerging area where Adagene's SAFEbody conditional activation may produce particular benefit.

Why it matters. The disease setting determines patient population characteristics, trial design, regulatory pathway, and commercial opportunity. Moving an asset from metastatic into adjuvant or neoadjuvant settings (as muzastotug appears to be doing via the IIT) is a major value-creation step if successful.

Related: Common cancer indications · IIT

Combination therapy¶

Definition. A therapeutic regimen combining two or more drugs intended to produce synergistic efficacy beyond what either drug provides alone. Combinations are pervasive in modern oncology because most novel mechanisms work better in combination than as monotherapy.

In practice. Common combination patterns:

Checkpoint + checkpoint — anti-PD-1 + anti-CTLA-4 (e.g., ipilimumab + nivolumab in melanoma)
Checkpoint + targeted therapy — anti-PD-1 + tyrosine kinase inhibitor (e.g., pembrolizumab + lenvatinib in HCC)
Checkpoint + ADC — emerging area; trastuzumab deruxtecan + checkpoint inhibitor in HER2+ disease
Novel + checkpoint — most early-stage immunotherapy assets are tested in combination with anti-PD-1 because the combination shows benefit where monotherapy doesn't

The Adagene–Merck collaboration (muzastotug + pembrolizumab) is a textbook example — Adagene's SAFEbody anti-CTLA-4 combined with Merck's Keytruda (pembrolizumab) anti-PD-1 in MSS-CRC, where neither monotherapy is effective.

Why it matters. Combination trials are operationally more complex than monotherapy trials — they require partner agreements (drug supply, data sharing), more complex safety monitoring, and harder benefit-attribution analysis. Understanding the combination context is essential for understanding the trial economics and partnership dynamics.

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