Sorrento Provides Updates on CD38 Immunotherapies and Implementation of Disruptive GMP Manufacturing for “Off-The-Shelf” Cell Therapy
- “CD38 Therapeutics” Business Unit formed to focus on development of CD38-directed immunotherapies for potential out-licensing, collaboration and/or other strategic considerations
○ Clinical “Proof-of-Concept” CD38 CAR-T Phase 1 trial progressing and to be concluded in 2019
○ Next-Gen “Off-the-Shelf” CD38 Dimeric Antigen Receptor (“DAR”)-T cell therapy with IND submission targeted for second half of 2019
○ CD38 Antibody-Drug Conjugate (“ADC”) IND to be submitted in Q4 2019
○ CD38-directed immunotherapies demonstrate potent cytotoxicity in preclinical models and against Daratumumab-resistant multiple myeloma patients’ tumor cells in vitro
- State-of-the-Art cGMP Facility in
San Diegofully operational with manufacturing capacity for thousands of allogeneic cell therapy doses per year thus, drastically reducing treatment cost
Key progress update areas that will be discussed include:
Clinical Proof-of-concept Study for Anti-CD38 Autologous CAR-T Cell Therapy
The Sorrento suite of anti-CD38 immunotherapies is based on a fully human anti-CD38 antibody mined from the Sorrento G-MAB™ antibody library. This antibody has demonstrated unique functional binding properties, which make it a promising candidate for therapeutic applications.
The current anti-CD38 CAR construct has also enabled successful manufacturing of autologous CAR-T cells using retrovirus-based cGMP manufacturing processes. The CAR-T cells obtained in this traditional approach have been successfully administered to multiple myeloma patients. Patient recruitment is currently ongoing at two clinical sites and additional sites will be opened in the second half of 2019.
“Our CD38 CAR-T program remains an active clinical stage trial with relapsed or refractory multiple myeloma (“RRMM”) patients being dosed and recruitment proceeding as expected. We are particularly proud of our production site at Sorrento in
Next-Generation Anti-CD38 Non-viral KOKI Allogeneic DAR-T Cell Therapy
The key components/steps of current state-of-the-art CAR-T cell therapy programs are: a) CAR architecture; b) viral-based transduction of the CAR construct into the T cells; and c) using the patients as their own source for these autologous T cells. Sorrento has developed disruptive next-gen technology platforms to address each of these components/steps. The research and development team at Sorrento has pioneered an allogeneic (“off-the-shelf”) cell therapy technology (KOKI DAR-T) that utilizes healthy donor T cells and genetically (“non-virally”) modifies them with a novel DAR construct (see the public presentation accompanying this press release).
Our proprietary design of the dimeric antigen receptor (“DAR”) is based on utilizing the complete antigen-binding fragment (Fab) of the parental antibody. It is generally accepted that Fabs more closely mimic the functional and biophysical properties of natural antibodies. Utilizing the same antibody binding domain sequence, we have compared CAR constructs to their corresponding DAR constructs. Our data showed that the DAR-T cells exhibited a higher cytotoxicity against target-expressing tumor cells as compared to CAR-T cells. In preclinical mouse models, the DAR-T cells demonstrated increased anti-tumor potency as well.
Our non-viral KOKI technology may offer several potential benefits over existing virus-based technology, such as transgene-encoding lentiviruses or retrovirus, to introduce antigen receptor constructs into pre-screened healthy donor (allogeneic) T cells. These potential advantages of our non-viral KOKI technology include: a) site-specific integration of transgenes into a pre-selected locus in the T cell genome; b) enhanced clonal expansion of the DAR-T cells; and c) streamlined method for transgene construct production without need for laborious and time-consuming virus production, release and validation processes, resulting in a shorter research and development timelines for IND-enabling activities.
Another major drawback of current CAR-T therapy is the reliance on patients’ own T cells (autologous therapy). This leads to delays in treatment (vein-to-vein time of several weeks) and substantial manufacturing costs due to the individual processing of each patient sample. By utilizing healthy donor T cells as the starting point in our KOKI DAR-T cell technology these concerns can be effectively addressed.
Sorrento has developed a robust manufacturing process in which these donor-derived KOKI DAR-T cells are expanded and purified resulting in the production of hundreds of KOKI allogeneic DAR-T cell doses per manufacturing run from a single healthy donor in about 2 weeks. This has the potential to substantially reduce cost of goods sold (“COGS”) and expand access to cell therapy to patients. This KOKI DAR-T manufacturing process will enable Sorrento with its current manufacturing staff to produce in its existing
“Our first clinical program will be KOKI allogeneic CD38 DAR-T cell therapy. Preclinical data and clinical trial designs will be shared and discussed with the clinical and scientific community as well as investors once the IND has been accepted and the clinical study initiated”, said Dr.
Anti-CD38 Antibody-Drug Conjugate STI-6129
In keeping with off-the-shelf immunotherapy strategy, Sorrento is developing STI-6129 (or LNDS1001 for
“In total, all of our anti-CD38 immunotherapies have been discovered, developed and manufactured in-house by our outstanding R&D and manufacturing team members. This demonstrates the unique and efficient “turn-key” approach as we are able to perform with our immunotherapy R&D teams utilizing internal expertise and capabilities without being dependent on external service providers,” said Dr.
Sorrento is a clinical stage, antibody-centric, biopharmaceutical company developing new therapies to turn malignant cancers into manageable and possibly curable diseases. Sorrento's multimodal multipronged approach to fighting cancer is made possible by its extensive array of immuno-oncology platforms, including key assets such as fully human antibodies (“G-MAB™ library”), clinical-stage immuno-cellular therapies (“CAR-T”), antibody-drug conjugates (“ADC”), and clinical-stage oncolytic virus (“Seprehvir®”).
Sorrento's commitment to life-enhancing therapies for cancer patients is also demonstrated by our effort to advance a first-in-class (TRPV1 agonist) non-opioid pain management small molecule in Resiniferatoxin (“RTX”) and ZTlido®. Resiniferatoxin is completing a Phase 1b trial in terminal cancer patients. ZTlido was approved by US FDA on 02/28/18.
For more information visit www.sorrentotherapeutics.com
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Source: Sorrento Therapeutics, Inc.