An oral small molecule, adjunct therapy to insulin in patients with type 1 diabetes (T1D).

Phase 3

TTP399
Overview:

vTv’s TTP399 is a novel, oral, small molecule, liver selective glucokinase activator being developed as an adjunct therapy to insulin in patients with T1D to reduce the occurrence of hypoglycemic episodes. TTP399 restores the normal function of the liver in the presence of high glucose by trapping glucose inside liver cells, promotes further glucose uptake for energy and storage, and keeps the liver in a “fed” state to prevent ketone production.   In its phase 2 study with T1D patients, TTP399 showed a 40% reduction in hypoglycemic episodes compared to placebo when used as adjunctive treatment to insulin therapy, as well as meaningful improvement to HbA1C. In April 2021, the FDA granted Breakthrough Therapy designation to TTP399 for the treatment of T1D. This past October, vTv announced results of a mechanistic study of TTP399 in patients with T1D demonstrating no increased risk of ketoacidosis. TTP399 has now been tested in almost 600 subjects and demonstrated a good safety and tolerability profile. TTP399 will be studied in additional clinical trials to be initiated in 2023.

Sources:
https://www.jdrf.org/t1d-resources/about/facts/
https://care.diabetesjournals.org/content/44/11/2449

Type 1 diabetes
Metrics:

Over 1.6 million people in the United States have T1D

Estimated projection of 5 million patients in the U.S. by 2050

Relevant Papers:

View all papers

REASONS
TO BELIEVE

Deudomperidone (CIN-102) is a Dopamine 2/3 antagonist with prokinetic and antiemetic effects.

Phase 2

CIN-102
OVERVIEW:

CinDome’s deudomperidone (CIN-102) is a new chemIcal entity, based upon deuteration and novel formulation of domperidone, a frequently prescribed first line therapy for nausea, vomiting, and gastroparesis outside of the United States. In part due to safety concerns around QT prolongation, domperidone is not approved in the U.S. Deudomperidone has been engineered to alter the PK profile for sustained efficacy while significantly reducing cardiac liability. Currently, 20-50% of patients with gastroparesis use off-label treatments or go untreated, leaving a major unmet medical need and significant therapeutic development opportunity.

 

CinDome has studied deudomperidone in multiple clinical trials to date. Deudomperidone was well tolerated in these studies, and there were no sponsor-assessed drug related adverse events (AEs) or clinically meaningful laboratory abnormalities.  Deudomperidone was deemed to have no meaningful impact on QT at exposures well above a therapeutic dose in a TQT study and demonstrated target engagement with trends of improvement in gastric emptying time in a previous Phase 2 clinical trial.

 

 

CinDome is currently enrolling the envision3D Deuterated Domperidone in Diabetic GP – clinical trial. envision3D  is a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of deudomperidone (CIN-102) in adult subjects with diabetic gastroparesis after 12 weeks of treatment. To learn more about the clinical trial and participation information, please visit www.gastroparesistrial.com or NCT Number NCT05832151.

 

Sources:
1. Rey E, Choung RS, Schleck CD, Zinsmeister AR, Talley NJ, Locke GR 3rd. Prevalence of hidden gastroparesis in the community: the gastroparesis “iceberg”. J Neurogastroenterol Motil. 2012 Jan;18(1):34-42
2. Jung HK, Choung RS, Locke GR 3rd, et al. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology. 2009;136(4):1225-1233

GASTROPARESIS
Metrics:

12-16 million patients in the US have symptoms of gastroparesis

>$4B annual prescription market in the US

Currently no chronic treatments available

REASONS
TO BELIEVE

CIN-103 is a novel formulation of phloroglucinol modified to enhance the pharmacokinetic properties to sustain the therapeutic exposure for patients with diarrhea-predominant irritable bowel syndrome (IBS-D).
Phase 2

CIN-103
OVERVIEW:

CinPhloro’s CIN-103 is a novel formulation of phloroglucinol – a non-opioid based, small molecule approved in select countries for the treatment of GI disorders. Designed for long-term use, CinRx’s non-clinical & early development team deployed immediate-release and delayed-release processes to formulate a proprietary, pulsatile release delivery offering sustained drug exposures with less frequent dosing. CIN-103 is believed to target multiple IBS-D action points, including motility, secretion, pain, spasms and inflammation.

 

CIN-103 has progressed from concept through Phase I Multiple Ascending Dose (MAD) trials. Phase I data demonstrated a superior PK profile compared to phloroglucinol, without the anticholinergic side effects associated with other antispasmodics.

 

 

CinPhloro is currently enrolling the enviva clinical trial. The Phase 2 enviva study is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of multiple dose strengths of CIN-103 in adults with IBS-D over 12 weeks of treatment. The study endpoints include patients’ clinical response relative to placebo on abdominal pain and stool consistency (as a composite responder). The trial aims to enroll 450 participants.  More information can be found at www.envivastudy.com or NCT Number NCT06153420.

IBS-D
Metrics:

Prevalence between 10%-15% in North America

Affects approximately 16.2M in the US

Most common reason for a referral to a gastroenterologist

REASONS
TO BELIEVE

CIN-109, CIN-110, CIN-209 and CIN-210 are series of mono and combination therapies for the treatment of obesity.

CIN-109
Phase 2
CIN-110
Phase 1
CIN-209
Pre-clinical
CIN-210
Pre-clinical

CIN-109, CIN-110, CIN-209, CIN-210
OVERVIEW:

CinFina’s portfolio of obesity therapeutics include mono- and combination- therapies designed to support healthy weight loss. The portfolio was licensed from Janssen Pharmaceuticals and includes:

OBESITY
Metrics:

<10% of adults with obesity are currently using or have ever used anti-obesity therapies
KFF.org Poll 2023

40% Loss in lean body mass observed with GLP-1 therapy
Wilding JP et al, NEJM, 2021

50% of patients discontinue GLP-1 therapies within 1 year. 70% quit within year 2. Tolerability continues to be the major reason.
Weiss Tet al, BMJ Open Diab Res Care 2022

66% Of the weight is regained within a year off GLP-1.
Wilding JP et al, Diab Obesity and Metab, 2022

Sources:
Bryan, Stierman, et al. NHSR 158. National Health and Nutrition Examination Survey 2017–March 2020 Pre-Pandemic Data Files. 14 June 2021, stacks.cdc.gov/view/cdc/106273.

Morgan Stanley

Fujioka, K, et al. “The Relationship between Early Weight Loss and Weight Loss at 1 Year with Naltrexone ER/Bupropion ER Combination Therapy.” International Journal of Obesity, vol. 40, no. 9, 22 June 2016, pp. 1369–1375, 10.1038/ijo.2016.67. Accessed 15 Apr. 2020.

REASONS
TO BELIEVE

GDF-15
PYY
Both programs offer dual agonist (GDF-15 / GLP-1 and PYY / GLP-1) next generation therapies, giving patients and physicians options with different mechanisms of action in a single injection

CIN-108 is a small molecule inhibiting defective in cullin neddylation 1 (DCN1) from binding in the pocket where is it necessary to promote neddylation and interfere with the progression of multiple cancers.

Pre-clinical

CIN-108
OVERVIEW:

CinSano’s CIN-108, a small molecule compound that inhibits a novel, well-studied oncogene target, DCN1, which is amplified in multiple cancer types and correlates with more severe prognosis. Licensed in 2021 by CinRx, the goal for CIN-108 is to disrupt the neddylation pathway by preventing binding of DCN1 to the pocket necessary for it to promote neddylation. The CIN-108 compound series is currently being optimized. 

Sources:

American Cancer Society

Solid Tumor
Metrics:

Represent approximatively 90% of adult human cancers

REASONS
TO BELIEVE

Retromer Therapeutics is developing novel therapeutics to treat neurodegenerative diseases.
Pre-clinical

OVERVIEW:

Retromer Therapeutics is a pre-clinical stage biotech company pioneering a new class of therapeutics to treat neurodegenerative diseases by resorting the function of the endolysosmal trafficking system with preclinical programs in neurodegenerative disorders including Alzheimer’s disease.

Sources:
Medline, National Institute of Environmental Health Science, Alzheimer’s Disease Association, Parkinson’s Foundation

Type 1 diabetes
Metrics:

In the United States, as many as 6.2 M people may have Alzheimer’s disease.

Occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die.

REASONS
TO BELIEVE

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