Anti-tumor Drug Enzastaurin
Eli Lilly (Lilly) studied enzastaurin in a variety of tumor indications, including Phase 3 clinical trials in diffuse large B-cell lymphoma (DLBCL) and glioblastoma (GBM), and received orphan drug designations from FDA and EMA. Denovo acquired from Lilly the global rights for enzastaurin, including development, production, and commercialization. Denovo has identified a biomarker (DGM1™) for that will allow a specific subset of patients to receive targeted therapy potentially resulting in better outcomes. Denovo initiated a biomarker-guided global pivotal Phase 3 GBM clinical trial in 2020. In 2018, Denovo in-licensed the rights to use enzastaurin for treatment of pulmonary arterial hypertension (PAH) from Stanford University. In 2021, Denovo out-licensed the use of enzastaurin for treatment of rare genetic pediatric onset or congenital disorders outside of oncology, including vascular Ehlers-Danlos Syndrome (vEDS) to Aytu BioPharma.
Psychiatric Drug Liafensine
DB104 (liafensine) is a potential first-in-class drug targeting treatment-resistant depression (TRD). AMRI was the original innovator of liafensine and licensed the drug to Bristol-Myers Squibb (BMS). A number of Phase 2 TRD trials were conducted by BMS. Denovo acquired the global rights to liafensine, including R&D, production, and marketing. A novel genetic biomarker (DGM4™) was discovered in 2020, a breakthrough in neuropsychiatric diseases, and a biomarker-guided global Phase 2b trial was initiated in 2022.
Anti-tumor Gene Therapy Based Drug Toca 511
DB107, acquired from Tocagen, is a two-part cancer-selective immunotherapy comprising an investigational gene therapy treatment and an investigational small molecule. The gene therapy treatment is a retroviral replicating vector that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, only infected cancer cells carry the CD gene and produce CD. The small molecule is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells resulting in anti-cancer immune activation and subsequent tumor killing. A novel genetic biomarker (DGM7™) was discovered in 2021, enabling further biomarker-guided clinical development.
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.
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.
Anti-tumor Drug Vosaroxin
Vosaroxin is a potent, first-in-class quinolone derivative, nonanthracycline topoisomerase II inhibitor that may be useful for oncology indications such as acute myeloid leukemia (AML) and solid tumors. More than 1,200 patients across 16 clinical studies have been dosed with vosaroxin, which has shown an encouraging safety profile. In the 711-patient Phase 3 VALOR clinical study there were significant improvements in OS and CR rates in certain sub-populations, specifically in patients with the poorest prognosis, such as patients over the age of 60 with relapsed and refractory AML.
Anti-tumor Drug Recombinant Endostatin
DB108 is a recombinant protein drug that inhibits tumor growth and metastasis by inhibiting angiogenesis. DB108 is obtained by expression in E. coli and has the same amino acid sequence as naturally-occurring human endostatin. Wuzhong Pharmaceutical studied DB108 as a first-line treatment for non-small cell lung cancer (NSCLC) in a Phase 3 clinical trial. This trial demonstrated DB108 had a good safety and tolerability profile, and showed significant efficacy benefit in median progression-free survival.
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, 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 email@example.com.