1. Cabotegravir-LAI + Rilpivirine-LAI
HIV Pipeline (viral suppression)
Phase I
Phase II
Phase III
Doravirine
Oral nanoformulations
NNRTI
Merck
PRO-140 (PA14)4
Not for X4-tropic HIV
Entry inhibitor; mAb
(not an ARV)
CytoDyn
ABX464
Rev inhibitor6
Abivax
Albuvirtide1
(FB006M)
Entry inhibitor
Frontier Biotech
Filed with CFDA
Bictegravir
(GS-9883)
INI
Gilead
Filed with USFDA
MK-8591 (EFdA)
Oral & long-acting formulations
NRTTI7
Merck
GSK
Requires a booster
Maturation Inhibitor
GSK
Sifuvirtide5
(FS-0101)
Entry inhibitor
FusoGen
Doravirine
(MK-1439; DOR)
NNRTI
Merck
Ibalizumab2
(TMB-355)
Entry inhibitor; mAb
(not an ARV)
TaiMed Biologics, Theratechnologies
Expanded Access
Elsulfavirine (VM1500)
NNRTI
Roche  Viriom
MK-8507
Unknown MOA
Merck
Fostemsavir
(BMS )
Prodrug of BMS
Attachment inhibitor
BMS  ViiV
MK-2048
As IVR
INI
NIH; Merck
Cenicriviroc3
(TBR-652; CVC)
Not for X4-tropic HIV
Entry inhibitor
Takeda  Tobira
Dapivirine
(TMC120; DPV)
As IVR
NNRTI
Janssen  IPM
Cabotegravir-LAI
(GSK-744; CAB)
INI
PrEP with oral induction
NIH; ViiV
Vicriviroc (MK-4176)
As IVR8
Entry Inhibitor
NIH; Merck
Rilpivirine-LAI
(TMC278; RPV)
NNRTI
PrEP with oral induction
PATH, NIH; Janssen
Cabotegravir-LAI + Rilpivirine-LAI
Maintenance strategy with oral induction
ViiV + Janssen
Sources: ClinicalTrials.gov; WHO ICTRP (international clinical trials registry platform); aidsinfo.nih.gov
Footnotes. If a candidate is in investigator-initiated study, the trial sponsor is specified first, separated by a semicolon from the originator.
Albuvirtide: Q1W (weekly) by IV, large synthetic peptides; Ph3 only being run in China, CFDA filing 7/ Note this is a different molecule from T-20 (enfuvirtide), it is not simply a long-acting version of T-20.
Ibalizumab: 800mg Q2W (biweekly) by IV; unclear if monthly IV 2,000mg applicable. Weekly SC injection wasn’t studied further after a Ph1. Humanized mAb targeting CD4 receptor, effective for both R5- and X4-tropic strains. In Ph3 in combination with OBR for MDR-HIV (multi-class resistance). Expanded Access through Wuxi PharmaTech. Commercialisation collaboration with Theratechnologies in US and Canada
Cenicriviroc: oral dual inhibitor of CCR2 and CCR5, does not work for X4-tropic virus. Development focus appears to have shifted from HIV treatment to non-alcoholic steatohepatitis (NASH). There is a Ph2 investigator-led trial on CVC for neuroAIDS
PRO-140: Q1W SC injection, “self injectable”, humanized mAb against CCR5. In Ph2/3, including as single agent maintenance strategy
Sifuvirtide: another synthetic peptide targeting gp41, daily SC injection in Ph2 in China only; topical microbicides also under development
ABX464: potentially first-in-class, this oral candidate that targets the HIV Rev protein and prevents unspliced HIV RNA from being exported out of the nucleus, thereby blocking HIV replication
NRTTI stands for nucleoside reverse transcriptase translocation inhibitor
Development of vicriviroc for HIV treatment was discontinued in Intravaginal rings containing vicriviroc are now being studied in Phase 1, with or without MK-2048 (combination IVR=MK-2048A)
“Long-acting” defined as once monthly or less frequent. Owen A and Rannard S (2016) Advanced Drug Delivery Reviews 103, p144–156
PC-1005
(MIV-150/zinc acetate) NNRTI
Population Council
Oral
Other parenteral
Topical microbicide
List not exhaustive. Shock-n-kill strategies, gene/cell therapies and non-oral immunotherapies are not included.
Medicines Patent Pool. Last updated on: 6/20/2017
Long-acting injection (LAI)9
Potential first-in-class

2. HCV Direct-Acting Antivirals (DAAs)
Marketed or under active clinical development
Phase I
Phase II
Phase III (Filed)
Marketed
CC-31244
NS5B inhibitor – non-nuc
Cocrystal Pharma
AL-335
NS5B inhibitor – nuc
Alios (now Janssen)
Ravidasvir
(PPI-668; ASC16; RDV)
NS5A inhibitor
Presidio  Pharco; Ascletis
Boceprevir
(SCH )
NS3/4A inhibitor
Merck
Sofosbuvir
(GS-7977/PSI-7977; SOF)
NS5B inhibitor – nuc 2
Gilead
GSK
Oral [& LAP]
NS5B inhibitor – non-nuc
GSK
Uprifosbuvir
(MK-3682; UPR)
NS5B inhibitor – nuc Merck
Daclatasvir
(BMS ; DCV)
NS5A inhibitor
BMS
Pibrentasvir
(ABT-530; PIB)
NS5A inhibitor
AbbVie
Telaprevir
(VX-950)
NS3/4A inhibitor
Vertex  Janssen
MK-10759
Unknown MOA
[NS5B inhibitor – nuc?] Merck
Ruzasvir
(MK-8408; RZR)
NS5A inhibitor
Merck
Ombitasvir
(ABT-267; OBV)
NS5A inhibitor
AbbVie
Glecaprevir
(ABT-493; GLE) 5
NS3/4A inhibitor
Enanta + AbbVie
Simeprevir
(TMC435; SIM; SMV)
NS3/4A inhibitor
Janssen
TD-6450
NS5A inhibitor
Theravance  TREKtx
Elbasvir
(MK-8742; EBR)
NS5A inhibitor
Merck
MB-110
NS5A inhibitor
Microbio Co.
Grazoprevir
(MK-5172; GZR)
NS3/4A inhibitor
Merck
Voxilaprevir
(GS-9857; VOX)
NS3/4A inhibitor
Gilead
Danoprevir/r 6
(ITMN-191, ASC08)
NS3/4A inhibitor
Roche; Ascletis
Velpatasvir
(GS-5816; VEL)
NS5A inhibitor
Gilead
Paritaprevir/r
(ABT-450/r)
NS3/4A inhibitor
Enanta + AbbVie
Furaprevir
(TG-2349)
NS3/4A inhibitor
TaiGen
Ledipasvir
(GS-5885; LDV)
NS5A inhibitor
Gilead
Asunaprevir 3
(BMS )
NS3/4A inhibitor
BMS
Sources: ClinicalTrials.gov; WHO ICTRP (international clinical trials registry platform)
Footnotes:
Based on in vitro anti-HCV activity as published. “Pangenotypic” as in effectiveness demonstrated for genotypes 1 – 6. Certain DAAs are referred to as “pangenotypic” by its originator but in vitro evidence for all six genotypes has not been publicly available. Occasionally multi-genotypic DAA (covering most but not all genotypes) may also be referred to misleadingly as “pangenotypic”, hence being differentiated here according to published in vitro evidence.
“Nuc” is short for NS5B nucleoside/nucleotide inhibitors, which are believed to have higher inherent barrier to resistance than non-nuc NS5B inhibitors
Asunaprevir was approved in Japan but US NDA has been withdrawn
4. MK-7009 was approved in Japan, but not by USFDA
ABT-493: its in vitro activity against GT5 has been “N/A” or not mentioned in publications so far. In ILC 2016, AbbVie preferred to it as pangenotypic DAA just like ABT-530. The combination is being studied across GT1-6
Danoprevir: requires ritonavir boosting. Early in vitro results published by InterMune suggested pangenotypic activity. Phase 2 in China only, by Ascletis, combining danoprevir/r with ravidasvir
Faldalprevir had once reached Phase 3 in combination with PegIFN and RBV by BI for GT1, followed by BI withdrawing NDA. Now TREK Therapeutics has in-licensed worldwide rights and is studying this compound in combination with TD-6450 in Phase 2
GSK : long-acting parenteral (LAP) formulation under development, and will be combined in upcoming (likely Q4-2016) Phase 2 study with miRNA therapy RG-101 from Regulus, which targets miR-122 a host factor for HCV infection. RG-101 is not included in this chart as it is not a DAA
MK-1075: mechanism of action unclear, but speculated to be IDX21459 which was an Idenix nuc (The Changing Landscape Of Hepatitis C - Where Do We Go From Here? Presented by DNDi, July 2015)
Preclinical but may enter Ph1 soon (not yet found on clinical trials registry)
MK-8831: Described to be pangenotypic NS3/4A inhibitor but only published activity on GT1-3. Described as entering Ph1 in publication, but none found in clinical trial registry yet
MIV-802: NS5B nuc that Trek therapeutics acquired from Medivir
Odalasvir
(ACH-3102)
NS5A inhibitor
Achillion  Janssen
Vaniprevir 4
(MK-7009)
NS3/4A inhibitor
Merck
Dasabuvir
(ABT-333)
NS5B inhibitor – non-nuc
AbbVie
Faldaprevir 7
(BI )
NS3/4A inhibitor
BI  TREKtx
NUC
Individual pangenotypic potential per published in vitro data:1
Medicines Patent Pool
List not exhaustive. Host-targeting agents are not included
Last updated on: 4/26/2017
Pangenotypic
Pangenotypic coverage not verifiable
Not pangenotypic

3. HCV DAA Combination Regimens
Marketed
HCV DAA Combination Regimens P
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Velpatasvir
(GS-5816)
NS5A
Gilead
Paediatric approval
FDC
GT1~6
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Ledipasvir
(GS-5885)
NS5A
Gilead
Ombitasvir
(ABT-267)
NS5A
AbbVie
Paritaprevir/r
(ABT-450/r)
NS3/4A
AbbVie
Dasabuvir
(ABT-333)
NS5B – non-nuc
AbbVie P
GT1, 4, 5, 6;
+ RBV for GT3a
GT1
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Daclatasvir
(BMS )
NS5A
BMS
Ombitasvir
(ABT-267)
NS5A
Paritaprevir/r
(ABT-450/r)
NS3/4A
GT1~4b
± RBV for GT4
Elbasvir
(MK-8742)
NS5A
Merck
Grazoprevir
(MK-5172)
NS3/4A
Merck
± RBV GT1, 4;
+ SOF for GT3c
Simeprevir
(TMC435)
NS3/4A
Janssen
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
GT1,
± RBV for GT1, 4d +
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Velpatasvir
(GS-5816)
NS5A
Gilead
Voxilaprevir
(GS-9857)
NS3/4A
Gilead
Pibrentasvir
(ABT-530)
NS5A
AbbVie
Glecaprevir
(ABT-493)
NS3/4A
AbbVie
Filed
GT1~6
Filed
GT1~6
Phase III
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Ravidasvir
(PPI-668; RDV)
NS5A
Presidio  Pharco, Ascletis +
Phase II
Sources: ClinicalTrials.gov; WHO ICTRP (international clinical trials registry platform)
Footnotes:
a. SOF/LDV: EMA approved GT1, 3, 4 (GT3 only for cirrhotics as combination with RBV, 24w. But note 24w of SOF+RBV without LDV is an FDA-approved indication for GT3 already). FDA approved SOF+LDV for GT1, 4-6 and the addition of RBV is required in some cases of cirrhosis or liver transplant; also approved in children aged 12 & above weighing at least 35kg.
b. SOF+DCV: FDA approved GT1, 3. EMA approved DCV for GT1, 2, 3, 4, but recommending DCV+SOF specifically for GT1, 3, 4 (data on DCV+SOF for GT2 are considered limited). EASL had recommend SOF+DCV across GT1-6
c. GZR/EBR: GT1a testing for baseline NS5A RAVs required; GT3 approved in Canada only for EBV+GZR+SOF
d. SIM+SOF: FDA approved SIM+SOF only for GT1 (GT4 was for SIM+PEG+RBV). EMA approved SIM+SOF with or without RBV for GT1, 4.
e. AL-335+ODV (without SIM): during ILC2017, company announced “no plans for further evaluation” of this 2DAA combination for GT1 due to “inadequate efficacy” per Study AL There is a long-term follow-up study of patients who completed the study. e
Uprifosbuvir
(MK-3682; UPR)
NS5B – nuc
Merck
Ruzasvir
(MK-8408)
NS5A
Merck
Grazoprevir
(MK-5172)
NS3/4A
Merck
AL-335
NS5B – nuc
Alios / Janssen
Odalasvir
(ACH-3102; ODV)
NS5A
Achillion  Janssen
Simeprevir
(TMC435)
NS3/4A
Janssen + +
Uprifosbuvir
(MK-3682; UPR)
NS5B – nuc
Merck
Ruzasvir
(MK-8408)
NS5A
Merck +
Medicines Patent Pool
List not exhaustive. Last updated on: 5/30/2017