Type 1 diabetes cure and prevention competitive landscape – November 17, 2022

Company

Product

Type

Status

Timeline

ViaCyte

PEC-Direct/VC-02

Direct vascularization, requires immunosuppressive therapy

Phase ½

Acquired by Vertex in July 2022 – status of projects unknown; Preliminary data from phase 2 study published December 2021 and shared at ADA Scientific Sessions in June 2021, additional patient data expected in 3Q22; Preliminary phase 1/2 data presented at Cell & Gene Meeting on the Mesa in October 2019, company plans to seek RMAT designation in 2H20; “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

ViaCyte

PEC-Encap/VC-01

Macroencapsulation, no direct vascularization

Phase 1/2

Acquired by Vertex in July 2022 – status of projects unknown; Anticipate launching clinical study under a new protocol for VC-01 in 2022; Data in 2021 provided learnings applied to guide optimization of approach, existing study protocol closed; ViaCyte and Gore enter clinical phase agreement for membrane technology in August 2020, clinical evaluation “resumed”; Data from new Gore device expected in coming months from JPM 2020; Phase 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

First two patients dosed in second cohort of phase 1/2 trial in November 2022: Preliminary data presented at ADA 2022 for first patients dosed in first cohort; Partnership with Evotec announced in May 2022 to combine stem cell-derived beta cells + pouches; Five out of seven patients enrolled in phase 1/2 trial, full enrollment on track for 1Q21 as of November 2020; Sernova pens license agreement with U. of Miami for conformal cell coating technology in August 2020; Sernova acquires conformal coating technology from Converge Biotech in June 2020; Sernova partners with AgeX Therapeutics to develop immune-protected cells in June 2020; Positive preliminary phase 1/2 results released July 2019; Phase 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

Defymed/Semma Therapeutics

MAILPAN

Macroencapsulation, no direct vascularization

Preclinical

“Safety and function of a new pre-vascularized bioartificial pancreas in an allogeneic rat model” published in Journal of Tissue Engineering in May 2020; Semma acquired by Vertex for $950 million in September 2019; Positive preclinical data released in July 2019; $114M Series B financing in December 2017; Received 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

Fall 2020 progress report; Spring 2020 progress report; Collaboration announced

September 2019

Lilly/Sigilon

Undisclosed

Macroencapsulation using FBR-resistant Afibromer encapsulation device

Preclinical

Collaboration announced April 2018

Novo Nordisk/Procyon Technologies

Undisclosed

Oxygen-enabled cell encapsulation device

Preclinical

Partnership announced December 2020

Novo Nordisk/UCSF/Cornell

Undisclosed

Stem cell derived insulin producing cells

Preclinical

Collaboration announced May 2018

Encellin (fka Dr. Tejal Desai lab at UCSF)

nanotemplating

Next-generation encapsulation approach

Preclinical

Research contributed to UCSF spinout Encellin, “hopes to move into the clinic in 2020” as of August 2019; 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

“Standardized GMP-compliant scalable production of human pancreas organoids” published in Stem Cell Research & Therapy in March 2020; 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; Boston Scientific to help develop minimally invasive injection procedure

Preclinical

Participated in TERMIS EU 2019; 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

In the midst of three-year $2.4 million NIH grant and two year $1.1 million CIRM grant as of September 2018. 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

Acquired by Vertex in July 2022 – status of projects unknown; Health Canada approved initiation of a Phase 1 trial of immune-evasive, stem cell-derived therapy for the treatment of T1D in November 2021; “Moving into pre-IND activities” as of May 2020; Preclinical data reported at EASD in 2019 showed gene-edited immune-evasive cells demonstrated in vitro protection against activated T-cells compared to controls; 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

Betalin Therapeutics

Undisclosed

Micro-pancreas

Preclinical

“Currently raising capital to further optimize the therapy and complete submission of the New Drug (IND) application to the FDA” as of December 2020 on company website; Betalin announces plans to advance into UK clinical testing by early 2021 in July 2020

Seraxis Therapeutics

SR-01

Implantable biocompatible device

Preclinical

The Maryland-based company completed $40 million series C in February 2021 that included investment from JDRF T1D fund, SR-01 is comprised of lab-grown pancreatic islets from Seraxis’ proprietary stem cell line SR1423 and its SeraGraft “implantable biocompatible device,” which protects the cells from immune recognition.

Company

Product

Status

Timeline

Vertex (Semma Therapeutics technology)

Stem cell-derived insulin producing cells

Phase 2

FDA hold lifted on clinical trial in July 2022; Data shared at ADA 2022 shows additional metrics for first three patients dosed in the trial; Clinical trial placed on hold by FDA in May 2022 with concerns about dosing; Preliminary data from phase 2 study released in October 2021 shows extremely promising results; Naked cell phase 1/2 launch and FDA Fast Track Designation received in March 2021; Naked cell program IND approved January 2021; Vertex on track to submit IND filing for islet cell transplant program in “late 2020,” phase 2 to commence in 2021 as of 3Q20 update; 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

Partnership with Sernova in May 2022 to partner on stem cell + cell pouch therapy; Evotec regains global rights to beta cell replacement therapy in April 2020, “exploring partnering options to bring this therapy to patients”; Sanofi discontinues R&D in diabetes in December 2019; Management expressed enthusiasm in January 2019 (interview); Partnership announced in August 2015

AZ MedImmune/Evotec

Biologic beta cell regeneration

Preclinical

Status unknown as of 2020; Partnership announced in December 2010

ViaCyte

Stem cell-derived insulin producing cells

Phase 1/2

Acquired by Vertex in July 2022 – status of projects unknown; 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; ViaCyte is currently in phase 1/2 clinical studies with its stem cell-derived insulin producing cells

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

Frequency

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

Preclinical

No longer active in diabetes as of 2020; Received JDRF funding in February 2017 to optimize the PCA platform for type 1 diabetes

eGenesis

Islet cell transplantation

Preclinical

Completed $125 million Series C in March 2021; HuCo islet cells are currently in preclinical development; working on islet cell transplantations

Pancryos

PanINSULA stem cell-derived islet cell replacement

Preclinical

In May 2022, Pancryos announced a global exclusive license agreement with Brigham and Women’s Hospital to combine PanINSULA with the Harvard Stem Cell Institute’s convection-enhanced microencapsulation device

Organization

Product

Type

Status

Timeline

Provention (previously TrialNet)

teplizumab

Anti-CD3

Phase 3

Approved by FDA in November 2022 under brand name Tzield; Teplizumab’s original PDUFA date of August 17. 2022 was extended to November 17, 2022; Provention received a CRL from the FDA in July 2021; In January 2021 ProventionBio filed the BLA with the FDA for type 1 diabetes delay, under the company’s requested Priority Review, MAA filing in Europe slated for 2021, BLA submission completed to FDA with AdComm expected as of 3Q20 update; Follow-up data showing sustained delay of three years presented at ADA 2020; 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 acquisition of candidate from MacroGeneics

Immune Tolerance Network

alefacept

Anti-CD2

Phase 2

No new dedicated trials as of December 2020; Long-term effect study for multiple ITN candidates recruiting as of December 2020, estimated to complete in March 2025; Alefecept removed from market for psoriasis due to “business reasons” in 2015; Two year T1DAL phase 2 trial results presented at ADA 2015

TrialNet

ATG/GCSF

Combination approach

Phase 2

Two year phase 2 results presented at ADA 2020, combination did not reach statistical significance on primary endpoint; Phase 2 results presented at ADA 2018; ClinicalTrials.gov lists full phase 2 completion in October 2018

TrialNet

CTLA4-lg (abatacept)

Immunosuppressant

Phase 2

Primary completion pushed to November 30, 2022 as of November 2022; Phase 2 trial expected to complete in November 2024, pushed back from February 2018; Results released in 2020 showed preservation of C-peptide levels and improvements in insulin sensitivty

Caladrius Biosciences

CLBS03

Treg

Phase 2

Negative topline phase 2a T-Rex (pediatric) results released in February 2019, two-year follow-up data to determine next steps; Phase 1 results presented at ADA 2014; Phase 2 clinical studies launched in March 2016, full completion is expected in March 2020

GeNeuro

GNbAC1

Monoclonal antibody that neutralizes pathogenic protein MSRV-Env

Phase 2a

Positive 12-month results released in May 2019, “GeNeuro believes these data open the door to further development in early-onset T1D pediatric patient population;” Positive six-month phase 2a data released in September 2018; 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

Positive interim phase 1b/2a results in combination with teplizumab released in October 2021.  Positive topline results in phase 1b/2a trial released in June 2021. Advancing through phase 2a with teplizumab as of 4Q20, positive topline phase 1b results released in August 2020; 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

Phase 2 trial (IMPACT study) of IMCY-0098 ongoing and actively recruiting, with expected completion in September 2024; Joined INNODIA in March 2020; 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 completed July 2021, positive results published in September 2021

Novo Nordisk

Undisclosed

DNA immunotherapy

Phase 1

A disease modifying treatment using a tolerogenic DNA plasmid to prevent clinical T1D onset in high-risk people is in phase 1 clinical development as of 3Q22

City of Hope

PIpepTolDC

Combination of patient’s own dendritic cells, vitamin D3, and fragment of pro-insulin

Phase 1

Patient enrollment for phase 1 trial announced in December 2020; Candidate previously delivered positive phase 1 results in the Netherlands in May 2020

Dr. Camillo Ricordi and Dr. Jay Skyler

Undisclosed

Combination of ATG, GCSF, IL-2, etanercept, and exenatide

Phase 1

Phase 1 trial to initiate in December 2021 (pushed from December 2018), with estimated completion of December 2027Highlighted by Dr. Jay Skyler at WCIRDC 2020 and EASD 2018

Pfizer

nanoformulations (tolerance molecule + antigen) 

Immune tolerance therapy

Preclinical

Licensed from AnTolRx in March 2019

Provention Bio

PRV-101 vaccine

Vaccine targeting Coxsackievirus B infection

Phase 1

Still in pipeline as phase 1 as of November 2020. Positive results from first in-human study announced in October 2021. Proof-of-concept data released in May 2020; Announced July 2017; Funding from J&J Innovation and JDRF T1D Fund

Anokion (fka Kanyos Bio)

KAN-201

Immune tolerance therapy

Preclinical

Type 1 diabetes program active on pipeline page as of November 2022 with KAN-201 in IND-enabling phase; Kanyos Bio acquired by Anokion in September 2019; Kanyos Bio created by partnership between Astellas Pharma and Anokion in July 2015

Selecta

SVP-Rapamycin/SVP-insulin

Synthetic Vaccine Particle (SVP) nanotechnology for immunosuppression

Preclinical

Type 1 program not listed on pipeline page as of December 2020; Series E financing in September 2015

Mesoblast

Undisclosed

Mesenchymal precursor cell (MPC) treatment

Preclinical

Type 1 not listed on pipeline page as of December 2020; “Ex vivo fucosylation” technology licensed from HMS in March 2016; As of January 2016, Mesoblast was investigating a type 1 diabetes application for its MPC treatment

REGiMMUNE/JDRF/Pfizer

RGI-3100

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

Preclinical

Diabetes no longer listed on REGiMMUNE pipeline as of December 2020; “A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice” published in Journal of Diabetes Research in October 2019; Collaboration with JDRF and Pfizer announced in April 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

Novo Nordisk

NN9828

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

Discontinued

Discontinued in 3Q20; Positive full phase 2 results presented at ADA 2020; Positive phase 2 topline results shared in 2Q19; Phase 2 trial expected to complete March 2019; FDA orphan drug designation in January 2017

Janssen

golimumab (Simponi)

TNF-alpha

Discontinued

Type 1 program discontinued in November 2020; Positive phase 2 results presented at ADA 2020; Phase 1 study in youth (n=30) with ≥2 antibodies expected to complete July 2021

Organization

Name

Type

Status

Timeline

TrialNet

Oral insulin

Oral insulin

Phase 3

“Slowed Metabolic Decline After 1 Year of Oral Insulin Treatment Among Individuals at High Risk for Type 1 Diabetes in the Diabetes Prevention Trial–Type 1 (DPT-1) and TrialNet Oral Insulin Prevention Trials” published in Diabetes in August 2020; Negative results in relatives of patients with type 1 released in November 2017; Phase 3 trial fully enrolled; Results presented at ADA 2017; Phase 2 dose-ranging trial expected to complete in December 2017

Evolve Systems

EVC001

B. infantis

Not applicable

March 2021 announced that the primary prevention SINT1A trial of 1,444 participants will be treated with the EVC001 candidate as a potential preventive treatment for type 1 diabetes in infants at-risk of developing the condition; Closed $55 million Series D in February 2021

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; Primary completion slated for January 2025 as of December 2020

Kamada

Undisclosed

Alpha-1 Antitrypsin (AAT)

Phase 2

Type 1 program active on company website as of December 2020; Topline phase 2 data released November 2017; Early signs of efficacy in people age 12-18 with new-onset type 1 diabetes

Massachusetts General Hospital (Dr. Denise Faustman)

BCG vaccine

Bacillus Calmette- Guérin (BCG)

Phase 2

Phase 2 trial slated to complete in July 2020; Boundless Investing webinar highlights BCG vaccine in July 2020; Phase 1 results released in July 2018 controversial; Primary completion expected in July 2020 with full completion expected in July 2023

vTv Therapeutics

TTP399

Liver-selective glucokinase activator

Phase 2

Positive results from mechanistic study announced in October 2021; In April 2021 vTv received an FDA Breakthrough Designation following positive results from phase 2 trial

Novo Nordisk

NN-1845

Glucose Sensitive Insulin

Phase 1

Phase 1 trial of glucose sensitive insulin competed 3Q21 –established proof of concept, shown to be well-tolerated

IM Therapeutics

IMT-002

human leukocyte antigen (HLA)

Phase 1

In July 2021, announced positive results from a phase 1b trial assessing the safety, tolerability, pharmacokinetics, and mechanistic action with small drug molecule IMT-002. IMT-002 works by blocking HLA-DQ8, which inhibits the activation of T-cells, effectively “starving the autoimmune process” and ultimately preserving beta-cell function. IM Therapeutics, a Boston area based company, closed a $10 million Series A funding round in 2019 with investment from the JDRF T1D Fund.

Sonoma Biotherapeutics

SBT-11-5301

Teff debulking

Preclinical

Closed $265 million oversubscribed Series B in August 2021 that included funding from JDRF T1D Fund; Technology selectively depletes T effector cells

GentiBio

Undisclosed

Regulatory T cells

Preclinical

GentiBio closes $157 million Series A in August 2021;GentiBio technology converts the more abundant T effector cell from a patient into potent, durable engineered Treg cells that can be injected back into the patient’s body

Calibr

Neratinib

Mammalian sterile 20–like kinase-1 (MST1) inhibitor

Preclinical

“Neratinib protects pancreatic beta cells in diabetes” published in Nature Communications in November 2019; Discussed at 2016 JDRF Mission Summit

Kriya Therapeutics

KT-A112

AAV

Preclinical

Closed $100 million Series B with help from JDRF T1D Fund in July 2021; Adeno-associated viruses (AAVs) are non-pathogenic viruses engineered to deliver DNA to drive the endogenous production of insulin