NASH Competitive Landscape – September 18, 2023

Sponsor

Drug Name

Class

Status

Other Remarks

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

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.

Hanmi 

HM151211

GLP-1/GIP/glucagon triple agonist 

P2

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

Inventiva

IVA337

Triple PPAR a/b/g agonist

P2b

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

Inventiva

Lanifibranor

PPAR agonist

P3

Phase 2 investigator-led trial announces positive results in June 2023; 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

SURPASS 3 substudy shows significant improvements in liver fat in April 2022; Study began Nov 2019, results expected 2H2023

Novo Nordisk

Semaglutide

GLP-1 agonist

P2

Novo Nordisk grants $9.57 million to support phase 2 semaglutide trial; expected to complete in June 2025

Novo Nordisk

Semaglutide

GLP-1 agonist

P3

Phase 2 semaglutide trial in cirrhotic NASH fails to meet primary endpoint in June 2022; Phase 3 trial initiated in March 2021 and expected to complete in 2029; 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.

Zydus

Saroglitazar 4 mg

TZD

P4

EVIDENCES-XI trial, investigating saroglitazar in people with NAFLD, was announced in June 2023; trial expects to enroll 1500 participants, establishing one of the largest prospective registry of patients with NASH in the world

Sponsor

Drug Name

Class

Status

Other Remarks

89Bio

BIO89-100

Long-acting glycopegylated FGF21 analog

P2b

Full results in September 2023 show that treatment with pegozafermin at doses of 30 mg once weekly and 44 mg every 2 weeks for 24 weeks led to significant improvements, as compared with placebo, in fibrosis without worsening of NASH, published in NEJM; topline results in March 2023 find that 44 mg every-two-weeks dosing conferred placebo-adjusted effect size of 20%, with full results published in NEJM in June 2023; phase 3 development expected to begin “pretty rapidly”; Enrollment for phase 2b ENLIVEN trial complete in August 2022; Positive topline phase 1b/2a results shared in September 2020. Positive preclinical data presented April 2019.

Akero Therapeutics

efruxifermin (EXR, AKR-001)

FGF21 analog

P2b

Results from the phase 2b expansion cohort released in June 2023; Topline results from phase 2b study announced in September 2022; 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

Axcella 

AXA1125 and AXA1957

Endogenous metabolic modulators

P2b

Expected trial completion in fall 2023; Phase 2b trial with AZA1125 initiated in May 2021; Positive phase 2a data for AXA1125 presented at The Liver Meeting 2020;

Can-Fite

Namodenoson (CF102)

Adenosine A3 receptor agonist

P2b

Results for trial expected in April 2023; Phase 2b trial initiated in December 2021; Phase 2a trial results shared October 2021; Phase 2a trial results published in 2020

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

Belapectin (polysaccharide polymer that targets extracellular galectins)

P2b/3

Enrollment for trial completed January 2023; 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.

Galmed Pharma

Aramchol

Oral SCD1 modulator

P3/4

Trial recruitment suspended “due to Aramchol Meglumine being formulated” in August 2022; 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.

Genentech

BFKB8488A

bispecific FGFR1/Klothoβ antibody

P2

Trial completed March 2023 – no results posted; As of 1Q23, completion delayed until February 2023; 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

Intercept Pharma

Obeticholic acid

FXR agonist

NDA; P3

FDA granted CRL to Intercept for OCA for NASH in June 2023, indicating the NDA cannot be approved in its current state; in response, Intercept has decided to discontinue all investments related to NASH and focus on rare and serious liver diseases; FDA Advisory Committee meeting votes against Intercept’s approval in May 2023; FDA accepts the NDA resubmission for the NDA in January 2023; Intercept resubmits NDA to FDA for OCA in NASH in December 2022; OCA fails to meet primary endpoint in phase 3 REVERSE trial for compensated cirrhosis in September 2022; Intercept announces positive topline results of OCA in F2/F3 fibrosis in July 2022; 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

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

Madrigal

MGL-3196

THR-β agonist

P3

NDA completed July 2023; Madrigal announces positive results from phase 3 MAESTRO-NASH trial in December 2022; 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.

NGM Biopharma

NGM282

FGF19 agonist

P2b

NGMBio announces topline results from phase 2b ALPINE 4 trial announced in May 2023; 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.

Poxel

PXL770

AMPK activator

P2b

Trial completed in March 2023; Positive topline results for phase 2b study reported in August 2022; 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.

Viking Therapeutics

VK2809

Liver-selective thyroid beta receptor agonist

P2b

Positive phase 2b results announced in May 2023; Enrollment completed in January 2023; VOYAGE trial announced Dec 2019; expected completion December 2022; phase 2 results announced September 2018

Sponsor

Drug Name

Class

Status

Other Remarks

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.

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

Pfizer

 ervogastat + clesacostat

DGAT2i+ACC inhibitor

P2b

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

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

Albireo

Elobixitat 

Oral ileal bile acid transporter inhibitor

P2a

Discontinued August 2020

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

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

AstraZeneca

cotadutide (MEDI0382)

GLP-1/glucagon dual agonist

P2b/3

Discontinued in 1Q23; Phase 2b/3 PROXYMO-ADV study initiated in July 2022; Phase 2 trial completed in 2Q21; Safety/PD trial initiated in 3Q19.

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

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

Gilead

Simtuzumab

LOXL2 monoclonal antibody

P2

Discontinued 3Q16

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

GSK

GSK3008356

DGAT-1 inhibitor

P1

No longer appears in GSK pipeline as of 1Q23; Added to GSK’s pipeline in 1Q16

J&J

JNJ-0795

undisclosed

P1

Discontinued in 1Q23; Announced in 2Q22

Merck (from NGM Bio)

MK-3655 (formerly NGM313)

KLB-FGFR1c receptor complex agonist

P2b

Trial terminated in late 2022; Phase 2b study began November 2020, est completion September 2023 ; Merck optioned from NGM Bio in January 2019.

Novartis

LJN452 (tropifexor)

FXR agonist

P2/3

Phase 2 FLIGHT-FXR study was completed April 2020.

Novartis

LIK066

SGLT-1/SGLT-2 inhibitor

P2a

Presumed discontinued 3Q21; Completed Nov 2019;

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

Pfizer

PF-06667272 

Myeloperoxidase Inhibitor

P1

Discontinued 4Q17

Pfizer

PF-06835919

Ketohexokinase (KHK) inhibitor

P2a

Discontinued in 3Q21; Phase 2 study with metformin in NASH/diabetes patients;

Pfizer

PF-05221304

ACC inhibitor

P2a

Discontinued in October 2020; possible future combination product

Shire

SHP626

Apical sodium bile acid cotransporter inhibitor

P2

Phase 1 trial completed July 2015

Sponsor

Drug Name

Class

Status

Other Remarks

Boston Pharmaceuticals

BOS-580

FGF21

P2a

Positive phase 2a results announced in June 2023

THR-beta agonist

P2a

Positive phase 2a results announced in August 2023

Terns

TERN-101

FXR agonist

P2a

Recruitment complete in April 2023; Phase 2a combination study with THR-beta agonist TRN-501 initiated in July 2022; 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

Oramed

ORMD-0801

Oral insulin

P2a

Phase 2a topline results announced in November 2022; no information shared on future development

HighTide Therapeutics

HTD1801

Anti-inflammatories

P2a

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

Hepagene

HPG1860

FXR agonist

P2a

Positive results from phase 2a RISE trial announced in January 2023

Hepion

rencofilstat

cyclophilin inhibitor

P2a

Phase 2a results from the ALTITUDE-NASH trial (n=70) announced in May 2023

Chemomab

CM-101

CCL24-neutralizing monoclonal antibody (MAb)

P2a

Phase 2a topline results announced January 2023 – no information on future trials shared to date

Merck/Hanmi

Efinopegdutide

(formerly JNJ-5111/ HM12525A )

GLP-1/glucagon dual agonist

P2a

Results expected at EASL 2023; see outline of trial design here; 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)

NeuroBo Pharmaceuticals

DA-1241

GPCR 119 agonist

P2a

Finished dosing of the first patient in September 2023; interim analysis expected in 1H2024, and full data expected in 2H2024. Received first site IRB Approval for phase 2a trial in August 2023; in May 2023, NeuroBo announced that the FDA has cleared the IND submission, with a phase 2 trial expected to begin in 3Q23; Announced FDA IND submission for phase 2 development in April 2023

Pfizer

PF-06865571

DGAT2 inhibitor

P2

As of 1Q23, completion delayed to early 2024; 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

Arrowhead

ARO-ANG3

Angiopoietin-like protein 3 inhibitor

P2

Phase 2 study estimated completion in December 2024; Phase 1 study completed December 2019; potential treatment for dyslipidemia and other metabolic diseases, including NASH

Altimmune

Pemvidutide

GLP-1/glucagon dual agonist

P1b

Phase 2b IMPACT trial initiated in August 2023; Phase 1b topline results announced in December 2022

Eccogene

ECC4703

THR-beta agnoist

P1

Phase 1 trial investigating ECC4703 in healthy volunteers; expected completion is July 2023; announced a $25 million Series B raise in June 2023

Novartis

IFM-2427

NLRP3 inhibitor

P1

Acquired from IFM Tre in April 2019

Arrowhead

ARO-PNPLA3

PNPLA3 inhibitor

P1

Acquired by J&J in 2018; full rights returned to Arrowhead in February 2023

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

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

AstraZeneca

AZ 2693 (formerly IONIS-AZ6-2.5-LRx)

PNPLA3 inhibitor

P1

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

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

Better Therapeutics

BT-001

Prescription cognitive behavioral therapy

n/a

Topline results announced December 2022

Novartis

RLX030

Relaxin receptor

Undisclosed

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

Lynkogen/Alteogen

Undisclosed

Long-acting "GLP-1 fusion" combination therapies

Undisclosed

Partnership announced July 2018

Biostax Corp

JKB-122 

long-acting TLR4 antagonist

N/A

FDA acceptance of IND in NASH and NAFLD announced in August 2023