NASH Competitive Landscape – January 29, 2022

Sponsor

Drug Name

Class

Status

Other Remarks

Novo Nordisk

Semaglutide

GLP-1 agonist

P3

Phase 3 trial initiated in March 2021 and expected to complete in 2028; Fast Track designation granted by FDA in 3Q20; Phase 3 in NASH expected to begin in 2021; Positive phase 2b multiple dose trial completed in 1Q20.

Inventiva

Lanifibranor

PPAR agonist

P3

Phase 3 NATiV3 trial is currently underway and expected to complete in 2028; Breakthrough designation from FDA in October 2020; Positive phase 2 NATIVE trial results announced in June 2020

Lilly

Tirzepatide 

(LY3298176)

GIP/GLP-1 agonist

P3

Study began Nov 2019, results expected 2H2023

CymaBay Therapeutics 

Seladelpar

PPARδ agonist

P3

Primary completion date November 2022; Clinical development for PBC resumed in July 2020; NASH on hold, with potential development in combination with partner.

Inventiva

IVA337

Triple PPAR a/b/g agonist

P2b

Phase 2b safety and efficacy study completed March 2020; positive results announced June 2020.

Hanmi 

HM151211

GLP-1/GIP/glucagon triple agonist 

P2

FDA Fast Track Designation granted in July 2020; Positive phase 1 data in February 2020 

BI/Zealand

BI456906

GLP-1/glucagon dual agonist

P2

Fast track designation received from the FDA in June 2021; Phase 2 study launched in April 2021; expected completion in January 2023

Sponsor

Drug Name

Class

Status

Other Remarks

Intercept Pharma

Obeticholic acid

FXR agonist

NDA; P3

December 2021 update suggests that topline data could be presented in 1Q22 with potentiall FDA resubmission in 1H22; Intercept continues to work on response to CRL, including a new adjudication process of all liver biopsies by a panel of three independent pathologists; FDA issued CRL in June 2020; Company had October 2020 FDA meeting to clarify CRL; expects to refile NDA in 2022. REGNERATE and REVERSE trials in F1-F3 fibrosis/cirrhosis expected to complete September 2025 and August 2021, respectively

Madrigal

MGL-3196

THR-β agonist

P3

Phase 3 MAESTRO-NAFLD data shows “significant and clinically relevant reductions in liver fat; interim data from phase 3 MAESTRO-NASH trial expected 3Q22 and ”; Data from phase 3 trial expected January 2022; 52-week Phase 3 trial announced March 2019 with scheduled completion end 2021.  Phase 2 results announced May 2018.

Galmed Pharma

Aramchol

Oral SCD1 modulator

P3/4

Primary completion date delayed to December 2024; Phase 3/4 study with primary completion date estimated June 2022. Announced ARMOR trial Sep 2019 Phase 2b results announced June 2018.

Cirius

MSDC-0602K

Mitochondrial pyruvate carrier modulator/

insulin sensitizer

P3

Phase 3 trial announced May 2019, expected completion September 2024; Positive phase 2b EMMINENCE trial announced Nov 2019; Significant improvements in metabolic endpoints; Non-significant improvement in liver histopathology. P3 not yet begun.

Galectin Therapeutics

GR-MD-02

Polysaccharide polymer that targets extracellular galectins

P2b/3

P2b/3 trial began June 2020 with December 2023 completion date. Phase 2 trials in NASH cirrhosis and advanced fibrosis completed October 2017 and September 2016.

NGM Biopharma

NGM282

FGF19 agonist

P2b

Phase 2 ALPINE 4 in patients with cirrhosis is continuing and expected to complete in August 2022;  Phase 2 ALPINE2/3 study did not meet primary endpoint and has been discontinued in NASH patients; Fibrosis effectiveness confirmed in Feb 2020 and Nov 2019.  Multiple dose 2b ALPINE results expected 1H2021. Cirrhosis study commencing 2H20.

Viking Therapeutics

VK2809

Liver-selective thyroid beta receptor agonist

P2b

VOYAGE trial announced Dec 2019; expected completion December 2022; phase 2 results announced September 2018;

Merck (from NGM Bio)

MK-3655 (formerly NGM313)

KLB-FGFR1c receptor complex agonist

P2b

Phase 2b study began November 2020, est completion September 2023 ; Merck optioned from NGM Bio in January 2019.

Genentech

BFKB8488A

bispecific FGFR1/Klothoβ antibody

P2

Phase 2 study expected to complete 1H22; Completed recruiting for phase 1b (n = 136) trial Phase 1 study in NASH and type 2 diabetes recruiting, expected to complete June 2019

Lipocine

LPCN 1144

Oral prodrug of bioidentical testosterone

P2

Fast track designation granted in November 2021; Positive results announced following phase 2 trial; Interim phase 2 results announced January 2019

Sponsor

Drug Name

Class

Status

Other Remarks

Novo Nordisk/Gilead

Injectable Semaglutide + cilofexor + firsocostat

GLP-1+ FXR agonist + ACC inhibitor

P2b

Initiation of phase 2b trial in March 2021 with estimated completion date March 2024; Mixed phase 2 results announced in November 2020; Partnership announced in April 2019

Novartis Pharmaceuticals

Tropifexor + Licogliflozin

FXR agonist + SGLT1/2 inhibitor

P2b

Phase 2 ELIVATE study expected to complete in 2023; Safety study (LDL elevation) begun May 2020 and est end in March 2021.

Pfizer

 ervogastat + clesacostat

DGAT2i+ACC inhibitor

P2

Received fast track designation from the FDA in May 2022; Phase 2b trial expected to complete in 2024: Phase 2a trial completed in 2020;

Sponsor

Drug Name

Class

Status

Other Remarks

Gilead

Selonsertib (GS-4997)

ASK-1 inhibitor

P3

Removed from NASH pipeline in 2Q20; Missed primary endpoint in STELLAR 4 announced 1Q19; STELLAR 3 trial in F3 fibrosis missed endpoint June 2019

AbbVie

Cenicriviroc (CVC)

CCR2/CCR5 inhibitor

P3

Phase 3 trial terminated due to lack of efficacy in February 2021; AURORA trial in F2-F3 fibrosis, completion expected Oct 2021; Allergan acquired Tobira September 2016; AbbVie acquired Allergan May 2020

Novartis/AbbVie

Tropifexor +

Cenicriviroc

FXR agonist + CCR2/5

P2b

Removed from pipeline and presumably discontinued; Study completed 1Q21, results posted on clinicaltrials.gov but not yet published; Phase 2b study expected completion September 2020

BMS

BMS-986036

Pegylated FGF21 analog

P2b

Discontinued in November 2021 following disappointing results in phase 2b FALCON study; Two phase 2 studies in F4 (completion expected Oct 2021) and F3 (completion expected December 2021); Phase 2a data presented at EASL 2017

Enanta Pharma

EDP-305

FXR Agonist

P2b

Discontinued internal development of  NASH candidates in October 2021 after interim analysis of phase 2b ARGON-2; Phase 2b to complete in December 2022; Positive phase 2a results announced September 2019; Fast Track designation in January 2017

Gilead

Simtuzumab

LOXL2 monoclonal antibody

P2

Discontinued 3Q16

AstraZeneca/Regulus Therapeutics

AZD4076/RG-125

Anti-microRNA (anti-miR103/107 oligonucleotide)

P2

AZ pulled out of partnership 2Q17; Phase 2 trial initiated 3Q16; Phase 1 trial completed December 2016

Pfizer

PF-06835919

Ketohexokinase (KHK) inhibitor

P2a

Discontinued in 3Q21; Phase 2 study with metformin in NASH/diabetes patients; expected completion April 2021.

Novartis

LIK066

SGLT-1/SGLT-2 inhibitor

P2a

Presumed discontinued 3Q21; Completed Nov 2019; awaiting results

Pfizer

PF-06667272 

Myeloperoxidase Inhibitor

P1

Discontinued 4Q17

Genfit

Elafibranor (GFT505)

Dual PPAR alpha/delta agonist

P3

Program terminated in 2Q20; will continue in PBC; RESOLVE-IT in F1-F3 fibrosis failed phase 3 interim analysis in May 2020

Albireo

Elobixitat 

Oral ileal bile acid transporter inhibitor

P2a

Discontinued August 2020

Pfizer

PF-05221304

ACC inhibitor

P2a

Discontinued in October 2020; possible future combination product

Novartis

LJN452 (tropifexor)

FXR agonist

P2/3

Phase 2 FLIGHT-FXR study was completed April 2020.

Shire

SHP626

Apical sodium bile acid cotransporter inhibitor

P2

Phase 1 trial completed July 2015

Allergan

AGN-242266

FXR agonist

P2

Presumed discontinued as of February 2020; Acquired from Akarna Therapeutics September 2016

Allergan

Evogliptin

DPP-4 inhibitor

P2

Presumbably discontinued following Abbvie’s acquisition of Allergan in 2020; evogliptin no longer in pipeline; Acquired from Tobira Therapeutics September 2016; Phase 1 trial investigating evogliptin in combination with CVC initiated September 2016

Sponsor

Drug Name

Class

Status

Other Remarks

Lilly

Undisclosed

GLP-1/glucagon dual agonist (oxyntomodulin analog)

P1

Announced development for NASH in R&D update in May 2016; Advanced to phase 1 in 4Q16

Merck/Hanmi

Efinopegdutide

(formerly JNJ-5111/ HM12525A )

GLP-1/glucagon dual agonist

Undisclosed

License agreement with Merck in August 2020 to commercialize in US and outside of Korea; Originally licensed to Janssen in November 2015, but returned development rights in July 2019 following subpar phase 2 results in obesity (with and without diabetes)

Lynkogen/Alteogen

Undisclosed

Long-acting "GLP-1 fusion" combination therapies

Undisclosed

Partnership announced July 2018

Poxel

PXL770

AMPK activator

P2a

Phase 2 trial completed October 2021; Phase 2a STAMP-NAFLD reported December 2020 with 2b in 2021 planned; raise of €17.7 million to advance of PXL 770 (and 065) in NASH announced in May 2020.

Akero Therapeutics

efruxifermin (EXR, AKR-001)

FGF21 analog

P2a

Phase 2b study launched in February 2o21 with expected completion in 2027; Phase 2b/3 planned for 1H 2021. Additional positive phase 2a data presented at The Liver Meeting 2020; Positive phase 2a histological results from BALANCED in July 2020; 

Terns

TERN-101

FXR agonist

P2a

Topline results from phase 2a trial announced in June 2021 showing improvement in liver biomarkers; Closed an $87 million Series C in January 2021; First patient dosed in phase 2a LIFT trial in July 2020; Phase 1 results that confirm safety and efficacy announced February 2020; Fast Track designation  in October 2019; Acquired from Lilly in April 2018

89Bio

BIO89-100

Long-acting glycopegylated FGF21 analog

P2a

Positive topline phase 1b/2a results shared in September 2020. Positive preclinical data presented April 2019.

Axcella 

AXA1125 and AXA1957

Endogenous metabolic modulators

P2a

Interim analysis of phase 2b trial announced in September 2022; Positive phase 2a data for AXA1125 presented at The Liver Meeting 2020; Phase 2b trial planned to complete in 2024

Can-Fite

Namodenoson (CF102)

Adenosine A3 receptor agonist

P2a

Phase 2a trial results shared October 2021; Phase 2 trial results expected May 2020

HighTide Therapeutics

HTD1801

Anti-inflammatories

P2a

Positive topline results from phase 2a study announced in May 2020

AstraZeneca

AZ 2693 (formerly IONIS-AZ6-2.5-LRx)

PNPLA3 inhibitor

P1

Added to AZ pipeline in 2Q19; Acquired from Ionis in April 2018

Pfizer

PF-06865571

DGAT2 inhibitor

P2

Phase 2 trial expected to complete November 2023;New phase 1 trial launched May 2018, expected to complete February 2019; Prior phase 1 trial completed July 2017; Other phase 1 studies completed and ongoing in subjects with and without NASH

GSK

GSK3008356

DGAT-1 inhibitor

P1

Added to GSK’s pipeline in 1Q16

J&J

JNJ-2463

CB1 inverse agonist

P1

Phase 1 study underway according to J&J’s 2017 Pharmaceutical Business Review; Collaboration with BirdRock Bio

Arrowhead

ARO-ANG3

Angiopoietin-like protein 3 inhibitor

P2

Phase 1 study expected to complete December 2019; potential treatment for dyslipidemia and other metabolic diseases, including NASH

Arrowhead

ARO-HSD

RNAi

P1

Preliminary phase 1 results suggest ARO-HSD was well tolerated and led to improvements in NASH biomarkers. GSK partnered with Arrowhead in $1 billion exclusive licensing agreement for ARO-HSD; Phase 1 study expected to complete in February 2022, topline results presented at The Liver Meeting establish proof-of-concept

Novartis

IFM-2427

NLRP3 inhibitor

P1

Acquired from IFM Tre in April 2019

Novartis

RLX030

Relaxin receptor

Undisclosed

Data expected to read out in 2019; Also in phase 3 for acute heart failure

AstraZeneca

cotadutide (MEDI0382)

GLP-1/glucagon dual agonist

P2a

Phase 2 trial completed in 2Q21; Safety/PD trial initiated in 3Q19. Expected completion May 2021.