Memorandum

Insulin Competitive Landscape – December 10, 2018

The table below includes an overview of the basal insulin and rapid-acting insulin competitive landscapes. It includes all companies we are aware of with basal insulin or rapid-acting insulin candidates in development, though we acknowledge that it may be incomplete. We will continuously update the table as timelines change.

Basal Insulin

Sponsor

Drug Name

Type

Status

Timeline

Lilly/BI

Basaglar/Abasaglar

Biosimilar insulin glargine

Approved

Launched in US on December 15, 2016 under terms of patent lawsuit settlement agreement with Sanofi

Biocon/Mylan

Semglee

Biosimilar insulin glargine

IND received CRL from FDA; Approved by EMA; first European launch in UK

CRL received from FDA June 2018 following September 2017 submission; Sanofi filed a patent infringement lawsuit against Mylan in October 2017; Approved by EMA in March 2018; Launched in Japan (where it’s not partnered with Mylan)

Oramed

ORMD-0801

Oral insulin

Phase 2

Phase 2b results reported July 2016; further phase 2 trials expected

Lilly Basal Insulin-Fc Once-weekly basal insulin Phase 2 Movement into phase 2 announced during 2018 Investor Day; Phase 1 data yet to be released

Novo Nordisk

LAI287 (NN1436)

Once-weekly injectable basal insulin

Phase 2

Phase 2 trial slated to start by end of 2018, following positive phase 1 results; Phase 1 trial completed 3Q15

Sanofi

LAPSInsulin-115

Undisclosed

Phase 1

Acquired from Hanmi in November 2015; Hanmi is leading early development efforts and Sanofi will revisit this candidate in ~2019 or later; Expected to support once-weekly dosing

AntriaBio

AB101

PEGylated insulin

Phase 1

Phase 1 trial initiated July 2017; Preclinical data for presented at ADA 2015; IND submitted to FDA June 2017

Lilly Undisclosed Next-gen acylated basal insulin Phase 1 Phase 1 initiated 4Q18; Announced in May 2016 R&D update; Potential for combination with Trulicity
Lannett Undisclosed Biosimilar insulin glargine Phase 1 First clinical trial announced June 2019

Lilly

Next-generation basal insulin

Undisclosed

Preclinical

Announced in May 2016 R&D update; potential for a combination with Trulicity

Novartis Undisclosed Biosimilar insulin glargine Undisclosed Gan & Lee will develop and manufacture

Merck

Lusduna Nexvue

Biosimilar insulin glargine

Discontinued

Discontinued for commercial reasons in October 2018 following tentative FDA approval granted July 2017; Full approval contingent on resolution of Sanofi’s patent infringement lawsuit, filed September 2016; Phase 3 data reported at ADA 2016

Lilly

Once-weekly insulin

Discontinued

Discontinued

Discontinued 3Q17; Advanced into phase 1 in 1Q17

Arecor

Insulin glargine with improved thermostability

Biosimilar insulin glargine

Discontinued

Preclinical program removed from company website

Arecor

Ultra-long-acting insulin glargine

Biosimilar insulin glargine

Discontinued

Preclinical program removed from company website

Rapid-Acting Insulin

Sponsor

Drug Name

Type

Status

Timeline

Novo Nordisk

Fiasp

 

Faster-acting insulin aspart (Novo Nordisk’s NovoLog)

Approved

FDA-approved September 2017 after initial CRL in October 2016; EMA-approved January 2017

Sanofi

Admelog (SAR342434)

 

Biosimilar insulin lispro (Lilly’s Humalog)

Approved

FDA-approved December 2017, US launch April 2018EMA-approved July 2017; SORELLA 1 trial presented at ADA 2016SORELLA 2 trial presented at ADA 2017, along with one-year SORELLA 1 data

Lilly LY900014 Ultra-rapid-acting insulin Phase 3 Topline results for PRONTO-T1D and PRONTO-T2D announced October 2018; Phase 3 trials began 3Q17; Phase 2 data presented at ADA 2017

Sanofi

SAR341402

Ultra-rapid-acting insulin

Phase 3

GEMELLI 1 (open-label vs. Novo Nordisk’s NovoLog) expected to complete January 2019; FDA submission slated for 2019; Added to pipeline in 4Q16

Adocia

BioChaperone Lispro

Ultra-rapid-acting insulin lispro (Lilly’s Humalog)

Phase 3

Phase 3 trials to begin in 2019; Data presented at ADA 2017; Lilly terminated partnership January 2017; Phase 1b pump study completed November 2016

Diasome

HDV Insulin Lispro

Liver-targeted insulin lispro (Lilly’s Humalog)

Phase 2

Phase 2 ISLE-1 trial completed June 2018; Phase 2 OPTI-1 study underway; Two other phase 2 studies ongoing

Biocon/Mylan

Insulin Tregopil

Oral insulin

Phase 2/3

Phase 2 of phase 2/3 trial ongoing in India; Positive phase 1 results in January 2016; JDRF to support phase 2 dose optimization trial vs. insulin aspart in Europe

Biocon/Mylan

Undisclosed

Biosimilar insulin lispro (Lilly’s Humalog)

Preclinical

Preclinical program listed on company website

Biocon/Mylan

Undisclosed

Biosimilar insulin aspart (Novo Nordisk’s NovoLog)

Preclinical

Phase 1 study being planned

Thermalin

Fluorolog

Rapid-acting, ultra-concentrated (U500) analog

Preclinical

Preclinical data shows superiority to Humulin U500; Phase 1a study has been planned

Thermalin

Undisclosed

U1000 monomeric insulin analog

Preclinical

Discussed at 2016 NIH AP Workshop; Potential for use in miniaturized artificial pancreas

Arecor

Ultra-concentrated insulin

U1000 stable, rapid-acting insulin formulation

Preclinical

Preclinical program complete, to enter in-human trials in 2018; Funded by JDRF in July 2016; Potential use in miniaturized artificial pancreas

Arecor

Ultra-rapid-acting prandial insulin

Undisclosed

Preclinical

First patient dosed in EU PK/PD phase 1 in May 2019

Novartis Undisclosed Biosimilar insulin lispro Undisclosed Gan & Lee will develop and manufacture
Novartis Undisclosed Biosimilar insulin aspart Undisclosed Gan & Lee will develop and manufacture

Novo Nordisk

PI406 (NN1406)

Liver-preferential prandial insulin analog

Discontinued

Program terminated in 1Q18 after phase 1 trial results

Glucose-Responsive Insulins

Sponsor

Drug Name

Type

Status

Timeline

Merck

Undisclosed

Undisclosed; Likely this candidate

Phase 1

Announced to be clinical at IDF (December 2017); Data expected 2018

Novo Nordisk

Undisclosed

Synthetic glucose-binding protein (lectin-based) attached to NN insulin

 

Preclinical

Announced in August 2018; Glucose-binding proteins acquired from Ziylo

Gubra

Undisclosed

Circulating locked insulin depot w/ basal and prandial properties

 

Preclinical

Announced with JDRF funding in June 2018

Lilly/Glycostasis

Undisclosed

Bi-directional antibody-based insulin

Preclinical

Glycostasis technology acquired by Lilly in February 2016

UNC/NC State

Smart insulin patch

Undisclosed

Preclinical

Positive preclinical data presented at ADA 2016; Funded by ADA Pathway and JDRF/Sanofi grants

MIT/University of Utah

Undisclosed

Synthetic glucose-responsive insulin

Preclinical

Positive preclinical results published February 2015; Funded by JDRF/Sanofi grant

Protomer

Undisclosed

Modified circulating insulin formulation (“case four”)

Preclinical

Funded by JDRF GRI Grand Challenge Prize and JDRF/Sanofi grant

Monash University

Undisclosed

Glucose-sensing nanoparticles

Preclinical

Funded by JDRF/Sanofi grant

Calibr

Undisclosed

Antibody-based, reversible intramolecular switch (“case four”)

Preclinical

Showcased at JDRF Mission Summit in 2016

Sensulin

Undisclosed

Biodegradable hydrogel using native insulin (“case one”)

Preclinical

Featured at Lyfebulb Social Club in June 2015

Thermalin

Undisclosed

Insulin modified with tailored carbohydrates targeting lectins

 

Preclinical

Preclinical program listed on company website

Biodel

Undisclosed

Glucose-coupled, pH-controlled dissolution of insulin

Discontinued

Biodel no longer a company

Merck

MK-2640

Glucose-responsive insulin

Discontinued

Discontinued following phase 1 study, completed August 2016 (following several delays)

Other Insulins (Pre-mixed, Human)

Sponsor

Drug Name

Type

Status

Timeline

Adocia

BioChaperone Combo

Insulin glargine (Sanofi’s Lantus) & insulin lispro (Lilly’s Humalog)

Phase 1/2

Phase 1 data presented at ADA 2016; Phase 1/2 complete; licensed to Tonghua Dongbao in China + other countries

Adocia

HinsBet U100

BioChaperone human insulin

Phase 1/2

Phase 1/2 study completed August 2016; Company intends to license phase 3-ready candidate to regional player in emerging markets

Adocia

HinsBet U500

BioChaperone human insulin

Preclinical

Preclinical program listed on company website

Biocon/PiSA

Rh-insulin

Recombinant human insulin

Phase 2

Partnership formed in March 2016; Phase 3 study planned; Biocon already markets the product in >60 countries including India and emerging markets

TD Solutions Levellor HypoSpray Insulin Human insulin U100 and U200, applied to skin Preclinical Annuonced May 2018; phase 0 trial complete