IMMIXBIO N-GENIUS CELL THERAPY PLATFORM
Our N-GENIUS platform, with EXPAND technology, has produced our pioneering lead candidate, CAR-T NXC-201, which has demonstrated an enhanced tolerability profile with the potential to reduce hospitalizations.
Our N-GENIUS platform enables our CAR-Ts to have distinct advantages including: preliminary clinical data — high overall response rate and durable responses; differentiated tolerability profile, resulting in a potential market first “Outpatient CAR-T” in NXC-201; and opportunity to treat a broader group of cancer patients.
Our N-GENIUS cell therapy platform, which has produced NXC-201, consists of three key elements: (1) purpose-built cell therapy evidence capture engine + relational database, which relates ImmixBio internal data to external to accelerate therapy design, manufacture, and preclinical; (2) proprietary EXPAND technology, which is applied to multiple cell therapy indications, already utilized to create NXC-201, to potentially increase efficacy and tolerability; and (3) atomized, novel binding scaffold generation engine, which allows us to make the correct binding for every molecule. We believe key characteristics of NXC-201 may apply to other products candidates produced by the N-GENIUS Platform. Those 3 key characteristics are: (a) high transduction efficiency (lower dose may lead to lower toxicity), (b) low tonic signaling (lower off-target toxicity may lead to lower toxicity), and (c) anti-exhaustion capability (increased persistence may lead to efficacy over an extended period of time).
N-GENIUS PLATFORM
3 KEY ELEMENTS
Purpose-Built Cell Therapy Evidence Capture Engine + Relational Database
Relating Nexcella internal data to external to accelerate therapy design, manufacture, and preclinical
Proprietary EXPAND technology
Applied to multiple cell therapy indications, already utilized to create NXC-201, to potentially increase efficacy and tolerability
Atomized, Novel Binding Scaffold
Generation Engine
Allows us to make the correct binding for every molecule
PRODUCED NXC-201
KEY CHARACTERISTICS
High Transduction Efficiency
(Lower dose may lead to lower toxicity)
*Carvykti data presented at ASH 2019; Abecma data presented at ASH 2017. CART-ddBCMA source Arcellrx
Low Tonic Signaling
(Lower off-target toxicity may lead to lower toxicity)
NXC-201 was co-cultured with the indicated target T cells and TNFα (B) and IL-2 (C) concentrations secreted in the culture supernatant were determined by ELISA.
Anti-Exhaustion Capability
(Increased Persistence may lead to efficacy over an extended period of time)
NXC-201 was co-cultured overnight then analyzed by flow cytometry for the expression of 4-1BB
Tissue Specific Therapeutics (TSTx) – IMX-110
SMARxT Tissue-Specific™ Platform
Tissue-Specific Therapeutics (TSTx)™
TME Normalization™ Technology
Immune Normalization™ Technology
SMARxT Tissue-SpecificTM Platform
The application of the SMARxT Tissue-Specific Platform in oncology is TME Normalization Technology, and in immuno-dysregulated diseases is Immune Normalization Technology.
The 3 pillars of the SMARxT platform are:
System-Tissue Biology Model Development
Interplay of cellular elements define and drive disease states. Based on transcriptional and epigenetic factors operating in key cell types, we have built a proprietary model of network motifs driving human pathologies such as cancer and immuno-dysregulated/inflammatory diseases. We believe this model represents the most complete view of biologic interrelationships on an organismal and tissue level. We apply this model in the early stages of our drug development to overcome systemic factors that have prevented traditional “targeted” therapies’ effectiveness in complex pathologies such as cancer and inflammatory bowel disease.
Purpose-Built Physical Biochemistry Engine
Traditional drug development focuses on “one drug, one target” approach. In contrast, our proprietary physical biochemistry engine is designed to incorporate wide-ranging elements into our drug design, encompassing a diverse target profile, allowing our drugs to operate simultaneously in time and space to jointly combat disease at the tissue and organismal level
Predictive Validation Network
Using our unique relationships and our internal expertise, we have developed a proprietary framework of high-efficiency, rapid development in vitro and in vivo animal models that have high relatability to human disease, minimizing the traditional poor predictive value of animal models
SMARxT Tissue-Specific™ Platform
Tissue-Specific Therapeutics (TSTx)™
TME Normalization™ Technology
Immune Normalization™ Technology
Tissue-Specific Therapeutics (TSTx)™
Tissue-Specific Therapeutics (TSTx) are a novel class of drugs that treat entire diseased tissues, as exemplified by the tumor micro-environment (TME). TSTx are uniquely capable of addressing complex pathologies such as cancer and immuno-dysregulated diseases that are not amenable to traditional single receptor or single mutation pharmaceutical development approaches.
Take a deeper dive into TSTx:
Target all 3 Components of the Gut-Microbiome-Immune Axis Simultaneously
In contrast to traditional approaches of targeting individual cytokine receptors, Immune Normalization Technology simultaneously inhibits inflammatory signal processing across the entire axis, potentially addressing the needs of the vast majority of patients not currently helped by available treatments
Suppress Pathologic Inflammation Irrespective of the Causative Event or Genetic Predisposition
Pathologic inflammatory response that is maintained and propagated throughout tissues often takes place long after the original inciting event. Immune Normalization Technology interrupts this vicious self-sustaining cycle, offering a treatment option along the entire disease continuum to a wide category of patients, by rebalancing gut-microbiome-immune system interactions, stopping the autoimmune destruction of gastrointestinal tissues
Broad-acting Mechanism of Action has Shown Promise in Precedent Studies
In two precedent clinical studies in ulcerative colitis and Crohn’s disease, the treatment arm increased responses/remissions at week 4 many times that of the control arms
SMARxT Tissue-Specific™ Platform
Tissue-Specific Therapeutics (TSTx)™
TME Normalization™ Technology
Immune Normalization™ Technology
TME Normalization™ Technology
TME Normalization Technology for oncology. The TME is made up of a tightly packed mass of: 1) cancer associated fibroblasts (“CAFs”), 2) tumor-associated macrophages/immune cells (“TAMs”), and 3) cancer itself. The TME’s biophysical properties include regions of varying degrees of hypoxia, acidosis and an immunosuppressive milieu. As cancer cells outgrow their blood supply, the resulting hypoxia and acidosis shift their metabolism towards glycolysis, lactate and lipids. This, in turn, shapes the responses of proximal fibroblasts and resident immune cells. Fibroblasts begin to secrete lactate that is taken up by nearby cancer cells and consumed as fuel. Lactate in the TME reprograms the macrophages toward the M2 “tolerant” pro-inflammatory phenotype that drives immunosuppression. At the same time, the TME hypoxia produces increased levels of reactive oxygen species that enhance tumorigenicity (tendency to form tumors) and immunosuppressive functions of Treg T-cells, as well as resistance to immune drugs such as PD-1/PD-L1 inhibitors.
Take a deeper dive into TME Normalization Technology:
Causing Apoptosis, a Non-inflammatory Tumor-cell Death, not Necroptosis
Our TME Normalization Technology causes tumor apoptosis, a non-inflammatory tumor-cell death (instead of necroptosis, which results in repeat reignition of the inflammatory cascade leading to tumor progression). Thus, when the inflammatory cascade is inhibited, tumor resistance can be suppressed, enabling tumor cell apoptosis by TME Normalization Technology
Interrupting Recurring Waves of Inflammation Sustaining Tumor Growth
Waves of inflammation spread through tissues via diffusion of inflammatory cytokines activating inflammation in successive layers of cells. TME Normalization Technology interrupts signal transduction pathways activated by these cytokines extinguishing these inflammatory waves
Target all 3 Components of the TME Simultaneously
In contrast to the traditional modality targeting single receptor or single mutation on one cell type, TME Normalization Technology simultaneously addresses the totality of not just the tumor itself, but also its metabolic and structural support
SMARxT Tissue-Specific™ Platform
Tissue-Specific Therapeutics (TSTx)™
TME Normalization™ Technology
Immune Normalization™ Technology
Immune Normalization™ Technology
Immune Normalization Technology for immuno-dysregulated diseases. Driving inflammatory bowel pathologies are the interactions between 3 components of the immune synapse: 1) gut-lining enterocytes, 2) gut microbes, and 3) immune cells. Cellular contacts and signaling molecules exchanged between these components activate abnormal inflammatory responses in immune cells driving a self-sustaining feed-forward loop of pathological inflammation in gastrointestinal tissues.
Take a deeper dive into Immune Normalization Technology:
Target all 3 components of the gut-microbiome-immune axis simultaneously
In contrast to traditional approaches of targeting individual cytokine receptors, Immune Normalization Technology simultaneously inhibits inflammatory signal processing across the entire axis, potentially addressing the needs of the vast majority of patients not currently helped by available treatments
Suppress pathologic inflammation irrespective of the causative event or genetic predisposition
Pathologic inflammatory response that is maintained and propagated throughout tissues often takes place long after the original inciting event. Immune Normalization Technology interrupts this vicious self-sustaining cycle, offering a treatment option along the entire disease continuum to a wide category of patients, by rebalancing gut-microbiome-immune system interactions, stopping the autoimmune destruction of gastrointestinal tissues