Memorandum

NASH Competitive Landscape – December 15, 2020

The table below includes an overview of the NASH competitive landscape. It includes all companies we are aware of with NASH candidates in development, though we acknowledge that it may be incomplete. We will continuously update the table as timelines change. Clinical phases abbreviated as “P1-P4.”

Sponsor

Drug Name

Class

Status

Other Remarks

Intercept Pharma

Obeticholic acid

FXR agonist

NDA; P3

FDA issued CRL in June 2020; Company had October 2020 FDA meeting to clarify CRL; expects to refile NDA in 2021. REGNERATE and REVERSE trials in F1-F3 fibrosis/cirrhosis expected to complete Oct 2022 and June 2021, respectively

AbbVie

Cenicriviroc (CVC)

CCR2/CCR5 inhibitor

P3

AURORA trial in F2-F3 fibrosis, completion expected Oct 2021; Allergan acquired Tobira September 2016; AbbVie acquired Allergan May 2020

Madrigal

MGL-3196

THR-β agonist

P3

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

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

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.

Novartis

LJN452 (tropifexor)

FXR agonist

P2/3

Safety study (LDL elevation) begun May 2020 and est end in March 2021; Phase 2 FLIGHT-FXR study was completed April 2020.

Novo Nordisk

Semaglutide

GLP-1 agonist

P2b

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.

Novartis/AbbVie

Tropifexor/

Cenicriviroc

FXR agonist + CCR2/5

P2b

Phase 2b study expected completion September 2020. No results announced.

Inventiva

IVA337

Triple PPAR a/b/g agonist

P2b

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

BMS

BMS-986036

Pegylated FGF21 analog

P2b

Two phase 2 studies in F4 (completion expected Oct 2021) and F3 (completion expected December 2021); Phase 2a data presented at EASL 2017

NGM Biopharma

NGM282

FGF19 agonist

P2b

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 Nov 2021; phase 2 results announced September 2018;

Lilly

Tirzepatide 

(LY3298176)

GIP/GLP-1 agonist

P2b

Study began Nov 2019, results expected June 2022

Enanta Pharma

EDP-305

FXR Agonist

P2b

Phase 2b to complete in December 2022; Positive phase 2a results announced September 2019; Fast Track designation in January 2017

Merck (from NGM Bio)

MK-3655 (formerly NGM313)

KLB-FGFR1c receptor complex agonist

P2b

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

Poxel

PXL770

AMPK activator

P2b

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.

CymaBay Therapeutics 

Seladelpar

PPARδ agonist

P2b

Clinical development for PBC resumed in July 2020; NASH on hold, with potential development in combination with partner.

Akero Therapeutics

efruxifermin (EXR, AKR-001)

FGF21 analog

P2a

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

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

2a

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

HighTide Therapeutics

HTD1801

 

P2a

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

Novo Nordisk/

Gilead

Injectable Semaglutide + cilofexor + firsocostat

GLP-1+ FXR agonist + ACC inhibitor

P2a

Mixed phase 2 results announced in November 2020; Partnership announced in April 2019

AZ

cotadutide (MEDI0382)

GLP-1/glucagon dual agonist

P2a

Safety/PD trial initiated in 3Q19. Expected completion May 2021. 

Axcella 

AXA1125 and AXA1957

Endogenous metabolic modulators

P2a

Positive phase 2a data for AXA1125 presented at The Liver Meeting 2020; Phase 2b trial planned 

Can-Fite

Namodenoson (CF102)

Adenosine A3 receptor  agonist

P2a

Phase 2 trial results expected May 2020

Novartis

LIK066

SGLT-1/SGLT-2 inhibitor

P2a

Completed Nov 2019; awaiting results

Pfizer

PF-06835919

Ketohexokinase (KHK) inhibitor

P2a

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

Hanmi 

HM151211

GLP-1/GIP/glucagon triple agonist 

P1

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

Lipocine

LPCN 1144

Oral prodrug of bioidentical testosterone

P1

Interim phase 2 results announced January 2019

AZ

AZ 2693 (formerly IONIS-AZ6-2.5-LRx)

PNPLA3 inhibitor

P1

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

Allergan

Evogliptin

DPP-4 inhibitor

P1

Acquired from Tobira Therapeutics September 2016; Phase 1 trial investigating evogliptin in combination with CVC initiated September 2016

Allergan

AGN-242266

FXR agonist

P1

Acquired from Akarna Therapeutics September 2016

Shire

SHP626

Apical sodium bile acid cotransporter inhibitor

P1

Phase 1 trial completed July 2015

Pfizer

PF-06865571

DGAT2 inhibitor

P1

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

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

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

Genentech

BFKB8488A

bispecific FGFR1/Klothoβ antibody

P1

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

Arrowhead

ARO-ANG3

Angiopoietin-like protein 3 inhibitor

P1

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

GSK/Arrowhead

ARO-HSD

RNAi

P1

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

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

Discontinued Candidates

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

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-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