Memorandum

Obesity Competitive Landscape – January 18, 2022

We are thrilled to see growing availability and investment in anti-obesity medications. 2021 was headlined by the FDA approval of Novo Nordisk’s Wegovy (semaglutide 2.4 mg) as well as exciting results from the SURPASS program, with both agents delivering 15%+ weight loss. Sustained double-digit weight loss has the potential to close the treatment gap in obesity (i.e. provide weight loss approaching that of bariatric surgery). With widespread use of these agents, we’d imagine that prevention of cardiometabolic disease may soon be possible, which would lead to significant improvements in health outcomes, quality of life, healthcare spending, and productivity. Elsewhere in the obesity landscape, Novo Nordisk’s cagrilintide appears to have strong potential, both as monotherapy and in combination with semaglutide. Conversely, a number of companies have presumably discontinued their anti-obesity candidates, including several of Novo Nordisk’s phase 1 drugs, Amgen’s preclinical GDF15 analog, and J&J’s JNJ-9321 (PYY agonist).

Currently Available and Pipeline Obesity Candidates

The table below includes an overview of the obesity competitive landscape. It includes companies we are aware of with obesity candidates in development, though we acknowledge that it may be incomplete. We will continue to update the table as timelines change.

Company

Product

Status

Timeline

Novo Nordisk

Wegovy (semaglutide  2.4 mg injection; GLP-1 agonist)

FDA approved

US supply shortages announced in December 2021; Approved by Health Canada in November 2021; Positive CHMP opinion in November 2021 with European launch planned for 2H22; submitted to Japanese regulatory authorities in 3Q21; FDA approval in June 2021

 

STEP 5 and STEP 8 presented at ObesityWeek® 2021; post-hoc analyses of STEP 1 and STEP 2 presented at EASD 2021; STEP 4 presented at ENDO 2021 and published in JAMA; STEP 3 presented at ObesityWeek® 2020 and published in JAMA; STEP 2 published in The Lancet in March 2021; STEP 1 published in NEJM in February 2021 following positive topline results in June 2020; Positive phase 2 data presented at ENDO 2018

First-ever obesity CVOT (SELECT) fully enrolled with expected completion in September 2023; phase 3 OASIS 1 trial assessing oral semaglutide initiated 3Q21

Phase 3 trial of semaglutide 2.4 mg in adolescents initiated September 2019, expected completion March 2022

Novo Nordisk

Saxenda (liraglutide 3.0 mg)

FDA and EMA approved

CHMP recommendation for treatment of obesity in youth ages 12-17 in March 2021;

FDA approval for chronic weight management in youth in December 2020; phase 3 study in adolescent obesity published in NEJM in April 2020

EMA approval for adults with obesity in 2015; FDA approval for chronic weight management in adults in 2014

Rhythm

Setmelanotide (MC4R agonist)

FDA and EMA approved for obesity caused by rare genetic variants

EU authorization for treatment of obesity caused by rare genetic variants in July 2021; FDA approval in November 2020

Positive results presented at ObesityWeek® 2020.

Positive phase 3 topline results announced in August 2019Phase 3 trial in POMC deficiency obesity initiated May 2017; Phase 2 data published in NEJM in July 2016; Received Breakthrough Therapy and Orphan Drug Designations in January 2016

Lilly

Tirzepatide (GLP-1/GIP dual agonist)

Phase 3

Submitted to the FDA with Priority Review for type 2 diabetes in 3Q21

SURPASS-4 results published in The Lancet in October 2021; SURPASS-3 CGM and SURPASS-5 patient-reported outcomes analysis presented at EASD 2021; SURPASS-1, SURPASS-2, SURPASS-3, and SURPASS-5 presented at ADA 2021; SURPASS-2 topline results announced in March 2021; SURPASS-3 and SURPASS-5 topline results announced in February 2021; SURPASS-1 topline results shared in December 2020; Positive phase 2 results presented at EASD 2020

First patient dosed in SURPASS-CVOT in June 2020; Phase 3 SURPASS CVOT will test superiority vs. Trulicity with estimated completion in 2024; Phase 3 obesity program started in 2019

SURMOUNT-1 to read out in April 2022; SURMOUNT-2, -3, and -4 expected to complete in 2023; SURMOUNT-MMO and SURMOUNT-OSA announced December 2021

Saniona

Tesofensine (triple monoamine reuptake inhibitor)

Phase 3

Update shared in June 2021 notes that Mexico’s regulatory agency requested additional information, anticipated final approval may be delayed into 2022; Submitted to Mexico’s regulatory agency in December 2019; Positive phase 3 results announced January 2019Phase 3 trial initiated in Mexico in collaboration with Medix in May 2017; Saniona obtained US patent in February 2016; Phase 2 results published in 2009

Pfizer

Danuglipron

Phase 2

Phase 2 trial in obesity has completed enrollment as of 3Q21 with primary completion expected March 2022; phase 2 trial in type 2 diabetes and obesity completed November 2021; phase 2 trial in type 2 diabetes completed July 2021;

phase 1 trial in type 2 diabetes completed July 2021 with positive topline results announced at 2020 Investor Day; highly positive phase 1 results presented at ADA 2020

Innovent Biologics

IBI362 (dual GLP-1/glucagon receptor agonist)

Phase 2

Positive phase 1 results in type 2 diabetes announced December 2021; Phase 2 trial initiated in China in June 2021, expected completion September 2022; IBI362 is the result of a 2019 licensing agreement between Lilly and Innovent

Novartis

Bimagrumab (activin receptor agonist)

Phase 2

Discussed as potential treatment for sarcopenia at Targeting Metabesity 2020; Positive phase 2 data presented at Obesity Week 2019

Saniona

Tesomet (tesofensine plus metoprolol)

Phase 2

Phase 2b trial in hypothalamic obesity initiated November 2021; FDA requested additional information regarding manufacturing in April 2021; Partner Medix intends to investigate for obesity in phase 2/3

Zafgen

ZGN1061 (MetAP2 inhibitor)

Phase 2

No update on ZGN1061 as of 3Q19 financial results, Phase 2 results presented at ADA 2019, FDA hold announced in November 2019; Interim phase 2 data presented at ADA 2018; Expanded phase 2 study ongoing; Phase 1b data reported May 2017

NuSirt Biopharma

NS-0200 (Leucine/PDE5 inhibitor/metformin)

Phase 2

Weight-reducing effect discussed at ADA 2019; Phase 2 trial completed August 2018; Also being evaluated for NASH

OPKO Health/Transition Therapeutics

 

OPK88003 (formerly TT401) (GLP-1/glucagon dual agonist)

 

Phase 2

 

Partnership to develop and commercialize OPK88003 in Asia announced in 3Q21

Topline phase 2b dose-escalation results announced in 2Q19; Topline phase 2 results reported February 2016; Acquired by OPKO Health after Lilly terminated partnership agreement

J&J/Hanmi

Efinopegdutide [formerly known as JNJ-5111/ HM12525A (GLP-1/glucagon dual agonist)]

Phase 2

Set for regulatory filing by 2023 in high-risk obesity; License agreement with Merck in August 2020 to commercialize in US and outside of Korea in NASH; J&J returns development rights to Hanmi in July 2019; Phase 2 trial in obesity launched April 2018, expected to complete March 2019Phase 2 type 2 + obesity trial initiated July 2018; Phase 1b study in type 2 diabetes completed February 2018; Phase 1 results presented at ADA 2015; Preclinical data presented on ADA 2016 poster; Licensed from Hanmi in November 2015

Novo Nordisk

PYY 1875

Phase 2

Phase 2 study of PYY 1875 with semaglutide initiated July 2021 with estimated primary completion May 2022; Phase 1 study completed August 2019

Novo Nordisk

Cagrilintide [formerly known as AM833, NN9838 (long-acting amylin analog)]

Phase 2

Phase 3 trial in combination with semaglutide 2.4 mg to initiate in 1H22; Phase 2 trial of cagri-sema initiated August 2021; Positive topline results from phase 2 monotherapy and phase 1 combo therapy trials released in June 2020; Phase 1 trial completed March 2016

Zealand/BI

BI 456906 (GLP-1/glucagon dual agonist)

Phase 2

Phase 2 trial in obesity initiated in April 2021 with expected completion in August 2022; Phase 2 trial in type 2 diabetes completed in November 2021 following first patient dosed in June 2020; Phase 1 results presented at ObesityWeek® 2021; Positive phase 1 results reported in 3Q19; Phase 1 study initiated 3Q17, Candidate selected 3Q15

Roche/Genentech

RG7992/BFKB8488A (bispecific FGFR1/Klothoβ antibody)

Phase 2

Roche appears to be targeting a potential launch in "2024 and beyond”; First patient enrolled in phase 2 trial in October 2020; phase 1b trial in people with T2D and/or NAFLD completed December 2019; First in-human study completed in May 2017; In development for obesity and type 2 diabetes

Novo Nordisk

NN9747 (formulation of PYY)

Phase 1

Phase 1 trial completed August 2019, results expected 4Q19; Phase 1 trial completed February 2017; Advanced to phase 1 in 3Q15

Novo Nordisk

NN9775 (formulation of PYY)

Phase 1

Phase 1 trial initiated October 2018, completed in August 2019

Novo Nordisk

LA-GDF15 receptor agonist

Phase 1

Phase 1 results expected in 2021; Added to Novo Nordisk pipeline in 2Q19

Zealand/BI

Second-generation long-acting amylin analog (ZP8396)

Phase 1

Phase 1 trial initiated in 3Q21 based on positive preclinical studies; BI to fund all R&D/commercialization activities

Amgen

AMG 133, AMG 171

Phase 1

Phase 1 trial initiated August 2020 with estimated completion May 2022

Amgen

AMG 171

Phase 1

Phase 1 trial initiated December 2019 with estimated completion April 2022

Zealand

GIP agonist (ZP6590)

Preclinical

Significant weight reductions alone and in combination with GLP-1 liraglutide noted at WCIRDC 2021

Kintai Therapeutics

Undisclosed gut microbiome candidate (KTX-0200) 

Preclinical

Kintai advances KTX-0200 to IND-enabling studies in January 2020

Dr. Aaron Cypess’s NIDDK Research Group

Mirabegron (Beta-3 Adrenergic Receptor Agonist)

Preclinical

Research findings reported at ADA 2020; Continued phase 2 investigation of mirabegron activity on brown fat after proof-of-concept study (expected completion February 2023)

Gelesis

PLENITY/Gelesis100 (expandable hydrogel capsule)

FDA approved

FDA approval in April 2019; Positive topline GLOW trial results in November 2017

Epitomee Medical

Epitomee Capsule

Phase 2

Unspecified trial initiated January 2020, currently recruiting

Discontinued Candidates

Company

Product

Status

Timeline

Amgen

GDF15 analog

Preclinical

Presumed discontinued January 2022; Preclinical research in rodent and primate models published October 2017

J&J

JNJ-9321 (PYY agonist)

Undisclosed

Presumed discontinued January 2022; we are not sure if it is being studied since we cannot find any active or planned trials; 2019 study in Cell Metabolism from J&J researchers with long-acting PYY analog; Added to company’s pipeline for type 2 diabetes and obesity according to 2017 Pharmaceutical Business Review

Novo Nordisk

NN9277 (GLP-1/glucagon dual agonist)

Phase 1

Discontinued in 2Q20; Phase 1 study expected to complete May 2019 (pushed back from December ’18); Previous phase 1 trial completed September 2017

Novo Nordisk

NN9423 (GLP-1/GIP/glucagon tri-agonist)

Phase 1

Discontinued in 2Q20; Second phase 1 expected to complete September 2019, results expected 4Q19; Previous phase 1 trial completed August 2017

NGM Biopharmaceuticals

GDF15 receptor agonist (NGM 395)

Preclinical

Merck terminated license in May 2019

Orexigen

Empatic (bupropion/zonisamide fixed-dose combination)

Phase 2

Empatic no longer in Currax products; Nalpropion bought by Currax in November 2019; Filed for bankruptcy and sold to Nalpropion in April 2018; Predicted to reach market by 2019 at AHA 2016; Phase 2 trial completed July 2009; No updates on Orexigen’s pipeline

RTI International

Rimonabant (cannabinoid receptor antagonist)

Preclinical

Discontinued due to psychiatric events; Preclinical research in rodent models published April 2016

Zafgen

Beloranib

Discontinued

Terminated July 2016 following two thrombosis-related deaths in phase 3 clinical trial

Novartis

LIK066 (SGLT-1/2  dual inhibitor)

Discontinued

Discontinued 2Q18

Novo Nordisk

NN9030 (glucagon analogue)

Discontinued

Discontinued 2Q18 

Novo Nordisk

NN9499 (FGF21 analog)

Discontinued

Discontinued 2Q18

Zealand/BI

BI 473494 (long-acting amylin analog)

Discontinued

Discontinued 3Q18 in favor of stronger candidate; Phase 1 safety and tolerability study initiated 3Q17; Preclinical data reported at Keystone Symposia in May 2017

Sanofi

SAR425899 (GLP-1/glucagon dual agonist)

Phase 3

Discontinued in 4Q18; Phase 3 trials in obesity originally slated to start in 2018; Positive commentary from Sanofi management at JPM

 

- April Hopcroft, Hanna Gutow, and Kelly Close