HAVCR2 hepatitis A virus cellular receptor 2
ENSG00000135077 · protein coding · Open Targets profile
Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand (PubMed:24825777). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556005). In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss of IL-2 secretion. The function may implicate its association with LCK proposed to impair phosphorylation of TCR subunits, and/or LGALS9-dependent recruitment of PTPRC to the immunological synapse (PubMed:24337741, PubMed:26492563). In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (By similarity). Expressed on Treg cells can inhibit Th17 cell responses (PubMed:24838857). Receptor for LGALS9 (PubMed:16286920, PubMed:24337741). Binding to LGALS9 is believed to result in suppression of T-cell responses; the resulting apoptosis of antigen- specific cells may implicate HAVCR2 phosphorylation and disruption of its association with BAG6. Binding to LGALS9 is proposed to be involved in innate immune response to intracellular pathogens. Expressed on Th1 cells interacts with LGALS9 expressed on Mycobacterium tuberculosis- infected macrophages to stimulate antibactericidal activity including IL-1 beta secretion and to restrict intracellular bacterial growth (By similarity). However, the function as receptor for LGALS9 has been challenged (PubMed:23555261). Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (By similarity). Receptor for phosphatidylserine (PtSer); PtSer-binding is calcium-dependent. May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells. Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells. Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll- like receptors promotes secretion of TNF. In tumor-infiltrating DCs suppresses nucleic acid-mediated innate immune repsonse by interaction with HMGB1 and interfering with nucleic acid-sensing and trafficking of nucleid acids to endosomes (By similarity). Expressed on natural killer (NK) cells and acts as a coreceptor to enhance IFN-gamma production in response to LGALS9 (PubMed:22323453). In contrast, shown to suppress NK cell-mediated cytotoxicity (PubMed:22383801). Negatively regulates NK cell function in LPS-induced endotoxic shock (By similarity). {ECO:0000250|UniProtKB:Q8VIM0, ECO:0000269|PubMed:11823861, ECO:0000269|PubMed:14556005, ECO:0000269|PubMed:16286920, ECO:0000269|PubMed:22323453, ECO:0000269|PubMed:23555261, ECO:0000269|PubMed:24838857, ECO:0000269|PubMed:26492563, ECO:0000269|PubMed:30374066, ECO:0000305|PubMed:24825777}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Structure with Ligand, High-Quality Ligand
- Antibody
- Advanced Clinical, UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.5269799828529358 (upper bound 0.8378499746322632). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 25 registry trials, updated in the last three years, of the most advanced drugs against HAVCR2 (sabatolimab, cobolimab, lomvastomig), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Andrew BrunnerMassachusetts General Hospital · 1 of 1 trials Phase 2+
- Courtney DiNardoM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Jared D AcobaUniversity of Hawaii · 1 of 1 trials Phase 2+
- Lawrence KleinbergJohns Hopkins University/Sidney Kimmel Cancer Center · 0 of 1 trials Phase 2+
Registry trials of sabatolimab, cobolimab, lomvastomig updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 7 of 24 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 1 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
13 trials of drugs against HAVCR2 were stopped early
Terminated, withdrawn and suspended interventional trials of sabatolimab, cobolimab, lomvastomig, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 13 most recent of 13.
- terminated · 2026-10-20 · Massachusetts General Hospital · matched by the registry's drug synonyms“The trial closed early due to changes in support for the study drug.”
- terminated · 2026-01-13 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“In December 2023, Novartis decided to terminate the sabatolimab clinical development program early after Phase II (MDS1) and Phase III (MDS2) studies failed to meet their primary objectives. The termination was not due to safety concerns.”
- terminated · 2026-01-13 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Novartis made a decision to early terminate the sabatolimab clinical development program, including the CMBG453C12201 trial, following the negative results from other 2 trials.”
- terminated · 2026-01-13 · Novartis Pharmaceuticals · Sabatolimab“In December 2023, Novartis decided to terminate the sabatolimab clinical development program early after Phase II (MDS1) and Phase III (MDS2) studies failed to meet their primary objectives. The termination was not due to safety concerns.”
- terminated · 2025-10-16 · Novartis Pharmaceuticals · Sabatolimab“Study was stopped following a strategic decision from the Sponsor. It was not based on any safety findings or safety concerns with sabatolimab.”
- terminated · 2025-10-16 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Lack of efficacy in the program as demonstrated in the earlier CMBG453B12301 (STIMULUS MDS-2) study.”
- terminated · 2025-10-10 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Business decision”
- terminated · 2025-10-10 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Business reasons”
- terminated · 2025-10-09 · Novartis Pharmaceuticals · sabatolimab“Study was stopped following a strategic decision from the Sponsor. It was not based on any safety findings or safety concerns with sabatolimab.”
- terminated · 2025-08-07 · Novartis Pharmaceuticals · Sabatolimab“Sponsor Decision”
- withdrawn · 2024-04-11 · Novartis Pharmaceuticals · Sabatolimab“waiting for update from Study Lead”
- terminated · 2023-12-06 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Business reasons”
- withdrawn · 2021-03-04 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“This study was cancelled before enrolling any patients for business related reasons.”
Paediatric incentives and obligations for HAVCR2's drugs
For sabatolimab, cobolimab, lomvastomig: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: yes · HAVCR2 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000246904 (cobolimab, Treatment of all conditions included in the category of malignant neoplasms including lymphoma): PM: decision on the application for modification of an agreed PIP, 12 Sept 2025; EMEA-003273-PIP01-22 (cobolimab, Treatment of lung cancer): W: decision granting a waiver in all age groups for all conditions or indications, 2 Dec 2022; EMEA-002931-PIP01-20 (sabatolimab, Treatment of myelodysplastic syndromes): W: decision granting a waiver in all age groups for all conditions or indications, 14 Apr 2021Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/21/2494 withdrawn 20 Aug 2021: Treatment of myelodysplastic syndromesRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA EU/3/21/2494, 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of sabatolimab, cobolimab, lomvastomigRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of sabatolimab, cobolimab, lomvastomigRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 3 interventional studies of sabatolimab, cobolimab, lomvastomig include patients under 18; 2 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 3 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| SABATOLIMAB | Antibody | approval | neoplasm, myelodysplastic syndrome, chronic myelomonocytic leukemia, acute myeloid leukemia, ovarian cancer, small cell lung carcinoma, non-small cell lung carcinoma, colorectal cancer, +4 more | Open Targets · ChEMBL |
| COBOLIMAB | Antibody | phase 2 3 | non-small cell lung carcinoma, hepatocellular carcinoma, melanoma, cervical cancer, cancer, neoplasm | Open Targets · ChEMBL |
| LOMVASTOMIG | Antibody | phase 2 | esophageal squamous cell carcinoma, neoplasm | Open Targets · ChEMBL |