Memorandum

Type 1 Diabetes Cure and Prevention Competitive Landscape – May 21, 2019

  • The table below includes an overview of the competitive landscape for type 1 diabetes cure or prevention therapies.  It includes all the companies we are aware of with projects in development for beta cell replacement, immune therapy, or other approaches with the aim of preventing, delaying, slowing, or curing type 1 diabetes. We will continuously update the table as timelines change. Our glucose-responsive insulin and automated insulin delivery competitive landscapes are hosted on separate pages.

Beta Cell Encapsulation

Company

Product

Type

Status

Timeline

ViaCyte

PEC-Encap/VC-01

Macroencapsulation, no direct vascularization

 

Phase 1/2

Data from new Gore device expected in coming months from JPM 2020Phase 1/2 trial initiated in 2014; Clinical development halted due to issues with FBR, but expected to resume in 1H19

Sernova

Cell Pouch System (CPS)

Microencapsulation within vascularized tissue matrix

Phase 1/2

Positive preliminary phase 1/2 results released July 2019Phase 1/2 trial recruiting with expected primary completion July 2019; IND application cleared by FDA in December 2017; Positive interim phase 1/2 results reported at JPM 2016 from a Canadian trial, but the trial has since been terminated; Announced collaboration with CTI Clinical Trial and Consulting Services in November 2016

ViaCyte

PEC-Direct/VC-02

Direct vascularization, requires immunosuppressive therapy

Phase 1/2

 “On track” to have a Regenerative Medicine Advanced Therapy (RMAT) designation from FDA as of JPM 2020; European clinical program initiated January 2019; Phase 1/2 trial initiated August 2017, expected to complete December 2020; Phase 3 was expected to initiate mid-2018 with approval projected for 2020 or beyond; Proof-of-efficacy now expected mid-2019

Defymed/Semma Therapeutics

MAILPAN

Macroencapsulation, no direct vascularization

Preclinical

Semma acquired by Vertex for $950 million in September 2019; Positive preclinical data released in July 2019; $114M Series B financing in December 2017Received funding for preclinical trials from JDRF in July 2016; Partnered with Semma Therapeutics for an unlimited stem cell-derived beta cell source in December 2016

JDRF/UCSF/Stanford

Undisclosed

Cell Replacement Cures Without Immunosuppresion

Preclinical

Collaboration announced

September 2019

Lilly/Sigilon

Undisclosed

Macroencapsulation using FBR-resistant Afibromer encapsulation device

Preclinical

Collaboration announced April 2018

Novo Nordisk/UCSF/Cornell

Undisclosed

Undisclosed

Preclinical

Collaboration announced May 2018

Dr. Tejal Desai lab at UCSF

nanotemplating

Next-generation encapsulation approach

Preclinical

Presented at the 2016 JDRF Bay Area Annual Meeting and Research Update

Goethe University/DRIVE Consortium

LSFM4Life

“Organoid” (insulin-producing cells derived from adult stem cells and embedded in a three-dimensional matrix)

 

Preclinical

Project launched in April 2016 with goal of entering clinical trials by end of 2019

DRIVE Consortium/Boston Scientific

Undisclosed

Encapsulation device containing gel-embedded clusters of islet cells; capsule releases immunosuppressant

Preclinical

Announced in June 2015

Dr. Shuvo Roy lab at UCSF

Bioartificial pancreas

Islets contained in semi-permeable silicon ultrafiltration capsule with active blood flow; Graft rather than subcutaneous implant

Preclinical

Presented at the 2016 JDRF Bay Area Annual Meeting and Research Update

ViaCyte/CRISPR Therapeutics

PEC-QT

Islets are derived from genetically engineered stem cells that are immune-evasive

Preclinical

Announced at JPM 2018; Received $1.4 million from CIRM for development of immune-evasive stem cells in December 2017; Subsequently partnered with CRISPR Therapeutics

Beta Cell Replacement Sources

Company

Product

Status

Timeline

Semma Therapeutics

Stem cell-derived insulin producing cells

Preclinical

Cell therapy to move into clinic by late 2020/early 2021, as of JPM 2020; Acquired by Vertex Pharmaceuticals for $950 million in September 2019; Partnership with AZ, Novartis, and Defymed; Published in Nature in 2019 detailing improved beta cell generation/purification process; Semma Therapeutics founded in April 2015 to translate Dr. Doug Melton’s beta cell generation procedure into therapy

Sanofi/Evotec

Functional stem cell-derived human beta cells for replacement therapies and for identification of active therapeutic targets

Preclinical

Possibly discontinued following Sanofi's decision to discontinue R&D in diabetes; Management expressed enthusiasm in January 2019 (interview); Partnership announced in August 2015

AZ MedImmune/Evotec

Biologic beta cell regeneration

Preclinical

Partnership announced in December 2010

ViaCyte

Stem cell-derived insulin producing cells

Preclinical

In 2006, ViaCyte published the first study demonstrating successful in vitro differentiation of human embroyonic stem cells into pancreatic tissue; In 2014 BetaLogics (now part of ViaCyte) published the first paper on using in vitro stem-cell derived beta cells to reverse diabetes in mice

Frequency

Progenitor Cell Activation (PCA) platform, which induces stem cell-like properties in somatic cells

Preclinical

Received JDRF funding in February 2017 to optimize the PCA platform for type 1 diabetes

UCSF Hebrock Lab Stem cell-derived enriched beta clusters (more advanced insulin-producing cells) Preclinical Published methodology for growing enriched beta clusters (eBCs – more mature, insulin-producing cells) from stem cells

Immune Therapies

Organization

Product

Type

Status

Timeline

Provention teplizumab Anti-CD3 Phase 3 FDA Breakthrough Therapy Designation in August 2019; First therapy shown to delay type 1 diagnosis (ADA 2019); Phase 3 PROTECT study underway as of April 2019, following aquisition of candidate from MacroGeneics

Novo Nordisk

NN9828

Anti-IL21/GLP-1 agonist (liraglutide) combination

Phase 2

Positive phase 2 topline results shared in 2Q19; Phase 2 trial expected to complete March 2019; FDA orphan drug designation in January 2017

Immune Tolerance Network

alefacept

Anti-CD2

Phase 2

Two year T1DAL phase 2 trial results presented at ADA 2015

TrialNet

ATG/GCSF

Combination approach

Phase 2

Phase 2 results presented at ADA 2018ClinicalTrials.gov lists full phase 2 completion in October 2018

TrialNet

CTLA4-lg (abatacept)

Immunosuppressant

Phase 2

Phase 2 trial expected to complete in November 2020, pushed back from February 2018; Results expected in 2020

Caladrius Biosciences

CLBS03

Treg

Phase 2

Topline phase 2a T-Rex (pediatric) results released; Phase 1 results presented at ADA 2014; Phase 2 clinical studies launched in March 2016, full completion is expected in March 2020

TrialNet

teplizumab

Anti-CD3

Phase 2

Positive phase 2 results presented at ADA 2019Phase 2 trial expected to complete in January 2019, moved up from January 2022

GeNeuro

GNbAC1

Monoclonal antibody that neutralizes pathogenic protein MSRV-Env

Phase 2a

Phase 2a trial initiated April 2017 and expected to complete March 2019

ActoBio

AG019

Engineered Lactococcus Lactis bacteria that releases proinsulin + IL-10 into gut

Phase 1b/2a

Phase 1b/2a in combination with teplizumab expected to complete in June 2020

Imcyse

Imotopes

Auto-antigen derived epitopes + thioreductase motif to reprogram autoimmune T-cells

Phase 1b

Positive poster presented at EASD 2019; Results expected 3Q19; Moving into phase 2 on back of Series B financing

UCSF (Dr. Jeffrey Bluestone)

Tregs + IL2

Combination of CD4, CD127, and CD25 Tregs with IL2

Phase 1

Phase 1 TILT study expected to complete July 2021

Janssen golimumab (Simponi) TNF-alpha Phase 1 Phase 1 study in youth (n=30) with ≥2 antibodies expected to complete July 2021
Pfizer nanoformulations (tolerance molecule + antigen)  Immune tolerance therapy Preclinical Licensed from AnTolRx in March 2019

Provention Bio

Enteroviral vaccine

Vaccine targeting Coxsackievirus B infection

Preclinical

Announced July 2017; Funding from J&J Innovation and JDRF T1D Fund

REGiMMUNE/JDRF/Pfizer

RGI-3100

Type 1 diabetes-specific antigen, to be used with reVax immunomodulatory platform to promote Tregs

Preclinical

Collaboration with JDRF and Pfizer announced in May 2015

Mesoblast

Undisclosed

Mesenchymal precursor cell (MPC) treatment

Preclinical

As of January 2016, Mesoblast was investigating a type 1 diabetes application for its MPC treatment

Calibr

Undisclosed

Voltage-gated potassium channel (Kv1.3) inhibitor

Preclinical

Discussed at 2016 JDRF Mission Summit

Selecta

SVP-Rapamycin

Synthetic Vaccine Particle (SVP) nanotechnology for immunosuppression

Preclinical

Series E financing in September 2015

Selecta

SVP-insulin

Synthetic Vaccine Particle (SVP) nanotechnology for immunosuppression

Preclinical

Series E financing in September 2015

Kanyos Bio

Undisclosed

Immune tolerance therapy

Preclinical

Kanyos Bio created by partnership between Astellas Pharma and Anokion in July 2015

GSK

otelixizumab

Anti-CD3

Discontinued

No longer listed in GSK pipeline; Negative phase 3 results in 2011; Revived phase 2 program completed September 2018 ahead of schedule

Other

Organization

Name

Type

Status

Timeline

TrialNet

Oral insulin

Oral insulin

Phase 3

Phase 3 trial fully enrolled; Results presented at ADA 2017; Phase 2 dose-ranging trial expected to complete in December 2017

Global Platform for the Prevention of Autoimmune Diabetes

Oral insulin

Oral insulin (high-dose in infants)

Phase 2b

Primary Oral Insulin Trial (POInT) currently screening in Europe

Kamada

Alpha-1 Antitrypsin (AAT)

 

AAT protein

Phase 2

Topline phase 2 data released November 2017; Early signs of efficacy in people age 12-18 with new-onset type 1 diabetes

Calibr

MST1

Beta cell proliferator

Preclinical

 

Discussed at 2016 JDRF Mission Summit

Massachusetts General Hospital (Dr. Denise Faustman)

Bacillus Calmette- Guérin (BCG)

 

Repeat Vaccination

Phase 2

Phase 1 results released in July 2018 controversial;   primary completion expected in July 2020 with full completion expected in July 2023

-- by Abigail Dove, Helen Gao, Zhazira Irgebay, Sahaj Shah, Rhea Teng, and Kelly Close