PIPELINE

Precision Pipeline for CNS Disorders with High Unmet Need

Despite extensive research, many central nervous system (CNS) disorders lack effective treatments. Denovo is addressing this gap with a pipeline of first-in-class therapies guided by our unique biomarker discovery platform, which enables us to identify the patients most likely to respond. This precision approach has been clinically validated by our lead asset, liafensine, which demonstrated success in a global Phase 2b trial for treatment-resistant depression. Liafensine is poised to become the first precision medicine with a companion diagnostic in psychiatry, paving the way for a new era of targeted CNS therapeutics.
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DB104

Psychiatric Drug Liafensine

Liafensine is a first–in–class triple reuptake inhibitor targeting transporters for serotonin, norepinephrine, and dopamine. Using its unique big data based Denovo Genomic Marker (DGM™) biomarker platform, Denovo discovered a novel genetic biomarker, termed DGM4™, which was hypothesized to predict liafensine's efficacy in TRD patients. In a prospective, biomarker-guided global phase 2b study, liafensine demonstrated robust efficacies in all clinical endpoints in treating TRD, one of the toughest indications to treat. This success represents perhaps the first precision medicine used in CNS field, and validated Denovo’s innovative model to revive the abandoned medicines with biomarkers.

DB103

Psychiatric Drug Pomaglumetad Methionil

Currently the drugs used in the clinical treatment of psychosis mainly work on dopamine (DA) D2 receptors in the central nervous system. DB103 selectively acts on the glutamic acid mGlu2/3 receptor and has no cross-reaction with other receptors in the central nervous system, and hence can avoid some usual side effects of psychiatric drugs currently on the market. Eli Lilly completed 37 clinical trials with more than 3,800 subjects. DB103 has shown significant promise when applied to the right sub-population of patients through personalized medicine or targeted therapy. Denovo licensed DB103 development rights from El Lilly. Denovo is currently conducting biomarker discovery for this program.

DB105

Psychiatric Drug ORM-12741

In-licensed from Orion Corporation/J&J, DB105 modulates neurotransmitters in addition to the noradrenergic system and is being developed for Alzheimer’s Disease (AD). Most AD programs target beta amyloid and tau, whereas DB105 offers a distinct mechanism of action. Orion completed two Phase 2 clinical trials in patients with AD with encouraging results that require further validation. DB105 has a reduced side-effect potential compared to non-specific Alpha-2 adrenoceptor antagonism. A total of 540 subjects was exposed to DB105 across 13 studies and a good safety and tolerability profile was observed.

DB109

Idalopirdine

DB109 is an oral antagonist of the serotonin (5-HT6) receptor, which is primarily expressed in the brain and is hypothesized to be involved in Alzheimer’s Disease, schizophrenia, and other indications. DB109 has been extensively evaluated in numerous clinical studies encompassing more than 2,500 subjects. Although Phase 3 trial results were negative, subsets of patients who showed signs of beneficial activity of DB109 were identified.

Expanded Access

Expanded access, also called compassionate use, enables patients with serious or immediately life-threatening diseases who do not meet the enrollment criteria for clinical trials in progress to gain access to investigational treatments. At this time, Denovo does not offer an expanded access program and does not accept expanded access requests. We believe that investigational drugs should be studied in patients as part of clinical trials designed to produce data on safety and efficacy that may be used to support approval of the product, thereby leading to its broader availability for patients in need of treatment. Denovo strongly encourages patients to speak with their treating physicians, and when possible, to participate in clinical trials. Denovo is aware that in rare cases patients with serious life-threatening diseases are unable to participate in clinical trials and may have exhausted all available therapies.

In these rare cases, Denovo may consider providing an investigational product outside of a clinical trial. However, we currently do not have an expanded access program that allows patients to have access to our investigational products prior to FDA approval. As authorized by the 21st Century Cures Act, Denovo may revise this expanded access policy at any time. Additionally, the posting of this policy by Denovo shall not serve as a guarantee of access to any specific investigational drug by any individual patient. In the event Denovo decides toconsider expanded access, we will evaluate and respond to each request that it receives on a case-by-case basis.

Reference information about our investigational drugs and ongoing clinical trials can be found on https://www.denovobiopharma.com and https://clinicaltrials.gov. If you have additional questions, please speak with your physician or contact us at info@denovobiopharma.com.