Table 2.
SARS-CoV-2 neutralizing antibodies in development
| Molecule | Sponsor | Development stage (example NCT)a | Source | Format | Dosing and comments | References |
|---|---|---|---|---|---|---|
|
Bamlanivimab (LY3819253; LY-CoV555) |
Eli Lilly/Abcellera |
US-FDA EUA 11/9/20; revoked 4/16/21 |
BC/CPs | Human IgG1κ | IV dosing; no longer in development as single agent; still used in combination with etesevimab | [203] |
|
Etesevimab (LY3832479; LY-CoV016; JS016; CB6-LALA) |
Eli Lilly/Shanghai Junshi Bioscience |
Phase I/II (studied as single agent) |
BC/CPs | Human IgG1κ | IV dosing | [204] |
|
Bamlanivimab plus Etesevimab |
Eli Lilly/Shanghai Junshi Bioscience |
US-FDA EUA 2/9/21; EMA EUA 5/3/21 |
BC/CPs | See above for each antibody | IV combination cocktail of etesevimab (1400 mg) and bamlanivimab (700 mg) | [203, 204] |
|
REGEN-COV™ (US); Ronapreve™ (UK and EU) (casirivimab plus imdevimab) |
Regeneron |
Approved by Japan 7/22/21, UK 8/26/21, EMA, 11/11/21; FDA EUA 11/20/20; NCT04452318 ANR |
CAS: immunized VLI tg mice; IMD: BC/CPs |
Casirivimab, Human IgG1κ; imdevimab, human IgG1λ | IV or SC dosing; combination cocktail; casirivimab (1200 mg) + imdevimab (1200 mg) and other doses; testing both therapeutic and prophylactic use | [205] |
|
Regkirona™ (regdanvimab) |
Celltrion |
Approved by Korea MFDS, 9/17/21 and EMA, 11/11/21; |
BC/CPs | Humanized IgG1κ | IV dose; recommended dose 40 mg/kg (2.8 g for 70 kg patient) | [206, 207] |
|
Xevudy™ (UK); sotrovimab (GSK4182136; VIR-7831) |
GSK/Vir Biologics |
Approved by UK MHRA 12/2/21; US-FDA EUA 5/26/21; EMA EUA 5/21/21 NCT04545060 ANR |
BC/CPs | Human IgG1κ LS HLE | IV and IM dosing being compared (NCT04913675); Also binds SARS-CoV-1 RBD; Derived from S309, which was isolated from SARS-CoV-1 patient B cells; neutralizes Omicron BA.1 | [208, 209] |
| EvuSheld™ (AZD7442; Tixagevimab [AZD8895, COV2-2196] plus cilgavimab [AZD1061, COV2-2130]) | AstraZeneca/Vanderbilt |
US-FDA EUA 12/8/21 Phase III R |
Both BC/CPs | Both human IgG1κ FE/YTE/S HLE and FCM | IV and IM dosing being compared; Fixed dose combination cocktail of tixagevimab (150 mg) + cilgavimab (150 mg); EUA for pre-exposure prophylaxis in immunocompromised subjects; two IM injections provide protection for up to 6 months; neutralizes Omicron BA.1 | [210, 211] |
| Amubarvimab (BRII-196, P2C-1F11) plus romlusevimab (BRII-198, P2B-1G5) | Brii Biosciences | Approved by China NMPA 12/8/21; Application for US-FDA EUA submitted; Phase III R NCT04518410 | Both BC/CPs | Human IgG1 YTE HLE, minor FCM | IV dose; Fixed dose combination cocktail of BRII-196 (1000 mg) and BRII-198 (1000 mg); testing for ambulatory patients; met Phase III clinical endpoints; EUA application submitted to US-FDA; neutralizes Omicron BA.1 | [212, 213] |
|
Bebtelovimab LY-3853113 (LY-CoV1404) |
Eli Lilly |
US-FDA EUA 2/11/22 Phase II C NCT04634409 |
BC/CPs | Human IgG1 | IV dosing; Newer antibody to address VOI, and VOC variants; neutralizes Omicron BA.1 | [214] |
| Ensovibep (MP0420) | Molecular Partners |
EUA application submitted to US-FDA (2/10/22) Phase II/III R NCT04870164 |
DARPin library | Trimeric DARPins | IV delivery; non-antibody protein-binding scaffold | [215] |
| TY027 | Tychan Pte., Ltd (Singapore) |
Phase III R |
In vitro designed and engineered | Human IgG | IV dose at 1500 mg; Reportedly effective against all VOCs, including Delta | [216] |
|
BMS-986414 (C135-LS) plus BMS-986413 (C144-LS) |
BMS/Rockefeller |
Phase II/III R |
Both BC/CPs | Both human IgG1 LS HLE | SC dosing; two injections of C135-LS 200 mg and two injections of C144-LS 200 mg for each dose | [217, 218] |
| ADG-20 (ADG-2 HLE) | Adagio Therapeutics |
Phase II/III R |
BC/CPs - YDAF | Human IgG; reported HLE | IV dosing; Affinity-matured in vitro; Testing therapeutic vs prophylactic (isolated from SARS-CoV-1 patient); Fc activities ADCP, ADCC present | [219, 220] |
| MAD0004J08 | Toscana Life Sciences Sviluppo |
Phase II/III R |
BC/CPs | Human IgG1κ LALAPG/LS FCM, HLE | IV dosing; Human IgG Fc modified to reduce effector function | [221] |
|
Meplazumab (Ketantin®) |
Jiangsu Pacific Meinuoke Bio- pharmaceutical |
Phase III (NYR) |
NA | Humanized IgG2 | Anti-malaria antibody clinical candidate that targets CD147 (EMMPRIN), a proposed alternative receptor for SARS-CoV-2 entry | [222] |
|
(COV2-2130-YTE-LALA and COV2-2381-YTE-LALA) |
Ology Bioservices |
Phase II/III NYR |
NA | Cocktail of 2 human IgGs with FCM, HLE | IM dosing; 1:1 mixture of two human IgG1-YTE-LALA non-competitive binding antibodies targeting SARS-CoV-2 | [223] |
|
ABP-300 (MW05 LALA, MW33) |
Abpro Biotech/Mabwell Biosciences |
Phase II R |
BC/CPs | Human IgG1κ LALA FCM | IV dosing; LALA mutation inserted to eliminate ADE activity observed in preclinical studies | [224, 225] |
| STI-2020 (COVI-AMGTM) | Sorrento |
Phase II R |
GMNDAL | Human IgG | IV dosing; affinity-matured version of STI-1499 | NP |
| STI-2099 (COVI-DROPS) | Sorrento |
Phase II NYR |
GMNDAL | Human IgG | IN delivered; affinity-matured version of STI-1499 | [226] |
|
BI 767551 (DZIF-10c) |
Boehringer Ingelheim |
Phase II/III W,T |
BC/CPs | Human IgG1 | Inhaled vs IV dosing (tested IN preclinically, as well); tested therapeutic vs prophylactic; Development recently discontinued (7/26/21) | [227] |
| VIR-7832 | GSK/Vir Biologics |
Phase I/II R |
BC/CPs | IgG1κ M428L, N434S HLE and GAALIE FCIN | IV dosing; FCIN version of VIR-7831, which itself was derived from anti-SARS-CoV-1 mAb S309. | [209] |
| REGN14256 | Regeneron |
Phase I/II (R) |
ND | ND (presumed human IgG) | SC dosing; alternative partner for imdevimab combination | NP |
| BGB-DXP593 (BD-368-2) | BeiGene/Singlomics |
Phase II C |
BC/CPs | Human IgG | IV dosing | [228] |
| BGB-DXP604 (BD-604) | BeiGene/Singlomics |
Phase I C |
BC/CPs | Human IgG | IV dosing; neutralizes Omicron BA.1 | [228] |
|
BGB-DXP604 plus BGB-DXP593 |
BeiGene/Singlomics |
Phase I C |
See above | Cocktail of two Human IgGs | IV dosing; neutralizes Omicron BA.1 | [228] |
| JS026 | Shanghai Junshi Bioscience |
Phase I R |
BC/CPs | Human IgG | IV dosing; alternative partner for JS016 combination | [229] |
| SI-F019 | Sichuan Baili Pharma/SystImmune |
Phase I R |
Recombinant FcFP | ACE2-Fc fusion | IV dosing; recombinant human bivalent ACE2-Fc fusion protein injection | NP |
|
LYCovMab BA4101 (CA521 FALA) |
Boan Biotech/Luye Pharma |
Phase I ANR |
Immunized Tg mice followed by phage library |
Human IgG4κ S228P/F234A/L235A | IV dosing; Reduced Fc effector function for reduced ADE | [230] |
|
ABBV-47D11 (HBM9022) |
Abbvie/Harbour Biomed |
Phase I C |
Immunized Tg mice |
Human IgG1κ | IV dosing; Harbour tg mice | [231, 232] |
| ABBV-2B04 | Wash U/Abbvie |
Phase I C |
Immunized C57BL/6 mice |
IgG1 | IV dosing; either chimeric or humanized | [233, 234] |
|
ABBV-47D11 plus ABBV-2B04 |
Abbvie |
Phase I C |
See above | IgG1 Cocktail | IV dosing; Fixed dose combination | NP |
|
HFB30132A (P4A1-2A) |
HiFiBiO/Shanghai Jiaotong Univ. |
Phase I ANR |
BC/CPs | Human IgG4κ-L234F, L235E, M252Y, S254T, T256E, P331S HLE and FCM | IV dosing; Human IgG Fc modified to reduce effector function | [235] |
| COR-101 (STE90-C11) | Corat Therapeutics |
Phase I R |
PDHAL-CP | Human IgG1κ PVALδGQS FCM | IV dosing; Library constructed from convalescent patients; Human IgG Fc modified to reduce effector function | [236] |
|
JMB2002 (Ab2001.08 N297A) |
Jemincare Group |
Phase I CTR2100042150 |
PDNHAL; yeast display selections | Human IgG1 N297A FCM | Human IgG1 Fc non-glycosylated at residue 297 to reduce effector function | [237] |
| XVR011 (humVHH_S56A/LALA-Fc/Gen2) | ExeVir Bio BV |
Phase I R |
Immunized llamas |
Humanized VHH-IgG1 LALA Fc fusion FCM | IV dosing; Unique Llama-derived VHH72-Fc antibody (XVR011) affinity optimized S56A | [238, 239] |
|
HMBD-115 (AOD01, SC31) |
Hummingbird Biosciences (Singapore) |
Phase I (Singapore) (No NCT) |
BC/CPs | Human IgG1 | IV dosing; Intact Fc function required for maximal activity (not engineered) | [240] |
| CT-P63 | Celltrion |
Phase III NYR |
NA | Human IgG | To be added to CT-P59 (regdanvimab) to make cocktail for a nebulized formulation for inhalation; neutralizes Omicron BA.1 | [241] |
| HLX71 | Hengenix Biotech Inc |
Phase I NYR |
Recombinant FcFP | ACE2-Fc fusion | IV dosing; Recombinant Human Angiotensin-Converting Enzyme 2-Fc fusion Protein | [242] |
| HLX70 (P17) |
Henlius Biotech / Hengenix Biotech |
Phase I NYR |
ST-ST-HuNAL | Human IgG1κ | IV dosing; Research papers suggest combining HLX70 mAb and HLX71 ACE2-Fc fusion protein | [242, 243] |
|
IGM-6268 (COV2-14) |
IGM Biosciences |
Phase I R |
PDNHAL | Human IgM | IN dosing; IgM format; neutralizes Omicron BA.1 | [244–246] |
| IBI314 | Innovent Biologics (Suzhou) |
Phase I/II R |
UNK | Cocktail of 2 human IgG1 antibodies | IBI-314A IgG plus IBI-314B IgG in 1:1 fixed dose ratio; ambulatory patients | NP |
| COVAB 36 | Memo Therapeutics AG |
Preclinical (No NCT yet) |
BC/CPs MD | Human IgG1 | Retains the ability to mediate ADCC, ADCP and CDC; being developed for inhalation delivery | [247, 248] |
| DIOS-202 and DIOS-203 | DiosCURE |
Preclinical (No NCT yet) |
Immunized llama | Humanized VHH-VHH heterodimers | Small (ca. 25 kDa) VHH dimers, possibly VHH-VE and VHH-EV (not confirmed) | [249] |
| TATX-03 | ImmunoPrecise |
Preclinical (No NCT yet) |
PDNHAL | Cocktail of 4 human IgGs | TATX-03 is a “Polytope” cocktail of four proprietary monoclonal antibodies (mAbs) directed against distinct regions of the SARS-CoV-2 spike protein | [250] |
|
AR712 (AR-711 (1212C2) + AR-720) |
Aridis Pharma-ceuticals |
Preclinical (No NCT yet) |
BC/CPs | Cocktail of 2 human IgG1 antibodies with HLE | Formulated for inhaled delivery | [251] |
| PiN-21 (Nb21) | University of Pittsburgh |
Preclinical (No NCT yet) |
Immunized llama | Homo-trimeric VHH | IN delivery; Homo-trimerized VHH; IN delivery at 0.2-0.5 mg/kg protects animals | [252, 253] |
| ZRC-3308 | Zydus Cadila |
Preclinical (No NCT yet) |
BC/CPs | Cocktail of 2 human IgGs with FCM, HLE | Combination of two antibodies binding different epitopes | NP |
| IMM-BCP-01 | Immunome |
Preclinical (IND filed; CRL) (No NCT yet) |
BC/CPs | Cocktail of 3 human IgG antibodies | Antibody cocktail neutralizes VOCs and VOIs, including Delta and Omicron, in preclinical studies | NP |
| RB-100 | RenBio/Columbia University |
Preclinical (No NCT yet) |
UNK; BC/CPs likely | Bispecific, bivalent IgG | DNA delivery; bispecific antibody targets RBD and NTD of the SARS-CoV-2 spike protein | NP |
| Centi-B9 | Centivax, Inc |
Preclinical (No NCT yet) |
PDNHAL most likely |
Likely human IgG | Dosing either SC or IM, not IV | NP |
| STI-9167 and STI-9199 | Sorrento Therapeutics, Inc/Mount Sinai |
Preclinical (No NCT yet) |
Immunized Tg mice |
Human IgG1-LALA (FCM) | STI-9167 (COVI-SHIELD) is likely IV dosed; STI-9199 is IN formulation of STI-9167; both are active against the Omicron variant | [254] |
| IDB003 | IDBiologics/Vanderbilt Univ |
Preclinical (No NCT yet) |
BC/CPs likely | Likely human IgG | Identified in Dr. James Crowe’s lab at the Vanderbilt Vaccine Center; Presumed IgG | NP |
ACE2 angiotensin converting enzyme-2, ADCC antibody-dependent cellular cytotoxicity, ADCP antibody-dependent cellular phagocytosis, ADE antibody-dependent enhancement, ANR active not recruiting (clinical trial), BC/CPs B-cells from convalescent patients, BMS Bristol Myers Squibb, C clinical trial completed, CRL complete response letter, DARPin designed ankyrin repeat protein, EMA European Medicines Agency, EMMPRIN extracellular matrix metalloproteinase inducer, EU European Union, EUA emergency use authorization, Fc fragment crystallizable, FcFP Fc fusion protein, FCIN Fc increased activity with Fc receptors, FCM Fc muting (silencing activity on Fc receptors), FE/YTE/S L234F L235E M252Y S254T T256E P331S mutations of hinge/Fc, GAALIE G236A/A330L/I332E Fc mutations to increase activity with Fc receptors, GMNDAL Sorrento’s G Mab Naive donor antibody library, GSK GlaxoSmithKline, HLE half-life extension, IM intramuscular, IN intranasal, IND investigational new drug (application), IV intravenous (administration), LALA L234A L235A mutations of IgG1 hinge to dampen Fc activity with Fc receptors, LALAPG/LS L234A/L235A/P329G/M428L/N434S hinge/Fc mutations, LS M428L/N434S mutations for increasing half-life, MD mammalian display, MHRA Medicines and Healthcare products Regulatory Agency (UK), NA not available, NCT National Clinical Trial (registry number prefix), ND no data available, NMPA National Medical Products Administration, NP no publication (press release only), NTD N-terminal domain, NYR not yet recruiting (clinical trial), PDHAL-CP phage displayed human antibody library constructed from convalescent patients, PDNHAL phage displayed naive human antibody library, PVALδGQS E233P/L234V/L235A/G236D/D265G/A327Q/A330S mutations to dampen Fc and complement activity, R recruiting (clinical trial), RBD receptor binding domain, SARS-CoV-1 severe acute respiratory syndrome coronavirus-1, SC subcutaneous (dosing), ST-ST-HuNAL name of Henlius phage displayed naïve human antibody library, T clinical trial terminated, Tg transgenic (mice producing human antibodies), UK United Kingdom, UNK unknown to authors, US-FDA United States Food and Drug Administration, VHH single domain antibodies (regardless of origin), VLI VelocImmune mice (producing human antibodies), VOCs variants of concern, W clinical trial withdrawn, YDAF yeast display affinity maturation, YTE M252Y/S254T/T256E mutations for increasing half-life
aNCT registries can be found using reference [7]