An oral small molecule, adjunct therapy to insulin in patients with type 1 diabetes (T1D).
TTP399
Overview:
Sources:
https://www.jdrf.org/t1d-resources/about/facts/
https://care.diabetesjournals.org/content/44/11/2449
REASONS
TO BELIEVE
- Hypoglycemic events in people with Type 1 diabetes is a major burden for patients and their families
- TP399 received Breakthrough Therapy Designation by the FDA in 2021, signaling the FDA’s recognition TTP399 may make an impact on the clinical paradigm
- TTP399 has been studied in 13 trials (3 Phase 2) with no significant safety issues, particularly no evidence of risk of DKA
- In 2019 the Endocrine Society made reducing hypoglycemia a strategic priority
- An effective oral pill is a significant advancement and advantage over injections
Deudomperidone (CIN-102) is a Dopamine 2/3 antagonist with prokinetic and antiemetic effects.
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.
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-102 does not cross the blood brain barrier,unlike metroclorpramide, which is currently the only FDA-approved drug for gastroparesis and carries a black-box warning for tardive dyskinesia
- 20-50% patients with gastroparesis use off-label treatments or go untreated, leaving a major unmet medical need and significant therapeutic development opportunity
- CIN-102-121 Phase 2 study is signaling strong safety and efficacy
- A potential for GERD indication is being explored, which could extend the application of CIN-102 into an additional population with a large unmet medical need
CIN-103
OVERVIEW:
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
- High unmet medical need as none of the approved therapies offer optimal efficacy and safety
- Currently available treatments for IBS-D rely on individualized therapies using a variety of different medications and dietary modifications
- phloroglucinol is an antipasmodic with none of the anticholinergic side effacts associated with other classes of antispasmodics
- The impoved formulation allows for decreased frequency of dosing
- Regulatory approval is belived to be highly attainable based upon precedent / despite placebo effact in published data
CIN-109, CIN-110, CIN-209 and CIN-210 are series of mono and combination therapies for the treatment of obesity.
CIN-109, CIN-110, CIN-209, CIN-210
OVERVIEW:
- CIN-109, a Phase 1, first-in-class growth differentiation factor 15 (GDF-15) analog. GDF-15 is a stress-induced “gut-brain” cytokine with multiple effects including appetite regulation leading to weight loss. A Phase 1 SAD study has been completed and a MAD study is planned for 2022.
- CIN-110, a potent and highly selective, large molecule gut hormone peptide YY (PYY) analogue which activates the G protein coupled Y2 receptor of the hypothalamus. PYY analogues are thought to result in weight loss due to reduction in food intake. CIN-110 is expected to enter Phase 1 clinical trials in 2023.
- CIN-209 is a dual agonist consisting of a glucagon like peptide-1 (GLP-1) together with a GDF-15 analog. In combination of the appetite suppressant activity of GDF-15 with the metabolic effects of the GLP-1 receptor agonist, it has the potential to induce weight loss above either of the moieties can do alone.
- CIN-210 is a dual-agonist consisting of a GLP-1 together with a PYY. In combination of the appetite suppressant activity of PYY with the metabolic effects of the GLP-1 receptor agonist, it has the potential to induce weight loss above either of the moieties can do alone.
OBESITY
Metrics:
41.9% of the US population is considered obese (30≤ BMI < 40)
For every 5kg/m2 BMI increment above the range of 22.5-25kg/m2, there is a 30% increase in overall mortality
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
- GLP -1 analogs apporoved (semaglutide and liraglutide) for the treatment of obesity have enjoyed significant market success.
- The global obesity market is pojected to be > $50 billoon by the end of the decade according to analysts
- 30-65% of patients who try pharmacologic intervention are non-responders driving the need for new classes off therapeutics to address this growing concern
- By addding novel gut peptides to GLP-1 analog, the CinFina combination compounds have the potential to deliver anoretic and cardioprotective effects and surpass the weight loss seen by approved therapies – providing weight loss in range seen with bariatric surgery
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.
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
- Cancer is the leading cause of death in US, with solid tumors represnting approximately 90% of adult human cancers.
- DCN1 is well-studied oncogene that increases efficiency of neddylation and has multiple function inlcuding:
- Tumor progression
- Chemosensitivity
- Angiogenesis
- Metastasis
- Neddylation promotes degradation of vrious substrates, including tumor suppressors
- Neddylation pathway is over-activated in multiple tumors types(Lung, liver, colon, glioblastoma, esophageal squmous cell)
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
- There is tremendous need for safe & efficacious therapeutics addressing neurodegenerative diseases.
- Althrough certain treatments may help relieve some of the physical or mental symptoms associated with neurodegenrative diseases slowing ther progression is not currently possible and no cures exits.
- The lack of avaliable treatments underscores the importance of accelerating novel approches to a disease modifying therapeutic.
- The likelihood of developing a neurodegenerative disease rises dramatically with age. In the coming decades, more Americans may be affected by neurodegenerative diseases especially as life expectancy increases.
