Memorandum

NASH Competitive Landscape – January 29, 2022

The table below includes an overview of the NASH competitive landscape. It includes all companies we are aware of with NASH candidates in phase 2b development and later, though we acknowledge that it may be incomplete.

Approved drugs seeking NASH indication (SGLT2/GLP-2/PPAR)

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

Other candidates

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

Combination studies

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;

Discontinued studies

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

Early phase studies

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.