Our innovative approach focuses on the development of a diverse array of next-generation protein therapeutics including Pronectin™ cancer immunotherapies, Pronectin™ drug conjugates (PDCs), T-cell engaging Pronectin™ and bi-specific Pronectin™, enabled chimeric antigen receptor (Pn-CAR-T™) cell therapies.
Antibody therapeutics have revolutionized the treatment of a number of diseases including cancer and inflammation. There are more than 470 antibody therapeutics in clinical testing which is a testimony to the applications of antibody engineering that have played a major role in expanding this family of large molecule therapeutics over the past two decades. Several antibodies have now reached FDA approval and commercialization including: function blocking antibodies that target cancer cell surface receptors (e.g. anti-HER2, anti-EGFR, anti-CD2 and anti-PDL1 antibodies); Antibody-Drug Conjugates (ADCs) (e.g.: Kadcyla®, Adcetris®) and Bi-specific ADCs; Immune-check point T-cell modulators (anti-PD1 or anti-CTLA4 antibodies); Bi-specific T-cell Engagers (BITE®), Immune mobilizing monoclonal TCRs Against Cancer (ImmTACs) that recruit and activate T-cells; Engineered T-cells with Chimeric Antigen Receptors (CARs) (anti-CD19 CARs). Very recently, Novartis CAR-T cell therapy CTL019 was unanimously recommended for approval by FDA advisory committee to treat pediatric, young adult B-cell leukemia.
Our Pronectin™ technology and drug discovery platform that can be exploited to replace many antibody therapeutic modalities as highlighted below.
Each of these therapeutic modalities have shown incredible potential and the opportunity to bring forth new options for better drugs in multiple ways including more selective targeting and improved manufacturability.
1 & 8. Pronectin™ Bi-specific T-cell Engagers (Pn-BITE™), 2. Fc-Pronectin™, 3. Pronectin™ engineered Chimeric Antigen Receptor T-Cells (Pn-CAR-T™), 4. Function blocking Pronectins™ that target cancer cell surface receptors, 5. Pronectin-Drug Conjugates (PnDC ™), 6. Immune-check point Pronectin™ T-cell modulators, 7. Pronectin Bi-specific Drug Conjugates (PnDC™).
A bispecific antibody is a single therapeutic molecule designed to bind two different targets. Bispecific antibodies have the advantage of combining two therapeutic mechanisms with the goal of increasing therapeutic efficacy, in comparison to monospecific antibodies that bind either of the targets individually. We are utilizing our Pronectin™ platform to generate bispecific Pronectins™ that exhibit the desired functional activity to each target.
Chimeric-antigen receptor (CAR)-T cell immunotherapy is a promising type of cancer therapy which consists of a target binding domain of an antibody that is specific to the target antigen on the cancer cell surface. This domain extends out of the engineered T cell into the extracellular space, where it can recognize target antigens. Traditionally, the target binding domain consists of a single-chain variable fragment, or scFv, of an antibody comprising variable domains of heavy and light chains joined by a short linker.
However, there are a number of disadvantages to scFv-based CARs including the limited availability of scFv, their potential to elicit antibody responses, and their association with tonic signaling due, in part, to inherent instability and flexibility of the structure and the potential for both VH/VL domain swapping and multimer formation through framework region interactions. Thus, replacement with alternative binding technologies may improve CAR-T efficacy in the clinic.
We are utilizing our technology platform to use Pronectins™ as alternative scaffold molecules that bind protein targets with high affinity and specificity, similar to scFv molecules. Unlike scFv, Pronectins™ are smaller, derived from human fibronectin 3 domains and are predicted to have no immunogenicity. As Pronectins™ are 1/3 the size of scFv molecules, they provide flexibility for the creation of multi-specificity CARs. Pronectins™ can be isolated against virtually any antigen through ex vivo panning of an extensive Pronectin™ library, yielding many distinct binders with a range of affinities and target epitopes.
Protelica is applying its extensive protein discovery, development, and pre-clinical experience to develop our pipeline of Pronectin™ therapeutic products, with the initial focus on oncology. Beyond cancer, development of highly differentiated Pronectin™ therapeutics accessing novel biology is made possible by the robust nature of our fibronectin building blocks generated by our Pronectin™ discovery platform coupled with our extensive protein engineering expertise.
The pharmacological properties of our Pronectin™ therapeutics offer opportunities to target a broad range of therapeutic applications including: Inflammation and Neurodegenerative Diseases.