CodaLytic is a novel Oncolytic virus that Codagenix, Inc is developing in the context of breast cancer. Oncolytic viruses in general are a relatively novel modality. These are live viruses (or live vaccines) engineered in a way that they can specifically infect and replicate, and cancer cells destroy some of these cancer cells and then trigger an anti-tumor immune response that ultimately alert the immune system to the cancer, fights it, and induces responses that can hopefully lead to durable responses in patients and transform their lives. There is one FDA approved Oncolytic virus (development) in the US the agent is called T-VEC.
It is marketed by Amgen under the brand name Imlygic (T-VEC) and it is approved for specific subsets of stage 3 and stage 4 metastatic melanoma patients. However, in breast cancer which is the focus for Codagenix, Inc is agent Oncolytic there is no such agent that is currently approved. The unique aspect about Oncolytic viruses is that they actually activate the cancer unity cycle in a variety of different ways and can recruit immune cells to tumors.
Importantly CodaLytic is a unique Oncolytic Virus engineered using cryogenics and a synthetic attenuation viral engineering platform. It is an engineered influenza virus based on an H1N1 influenza strain that's circulated in California in 2009. And our engineering platform harnesses the redundancy in the genetic code to generate viruses (genetic material) that are very finely tuned with respect to the safety profile, which is obviously very important for administering live viruses (or live vaccines) into potentially immunosuppressed cancer patients, while maintaining their potent immune stimulatory capacity that we are leveraging with respect to the mechanism of action.
The intended clinical trial that we are planning to start in early 2023, pending FDA feedback, will assess code Oncolytic as a monotherapy in breast cancer, specifically in metastatic, inoperable breast cancer. And this is the first time that this agent is being used in cancer patients. I will note however, that we as Codagenix, Inc have used the same synthetically engineered virus in the context of infectious disease prophylaxis as a live attenuate (vaccine) vial (primary) vaccine (or live vaccines) where we have administered this virus in a phase 1 trial into healthy individuals without any signs of safety or tolerability issues. But with respect to cancer therapy, this is a completely novel agent that we're using in a first in human clinical trial.
In this context, I will review the standard of care therapies for metastatic breast cancer patients. Again, in contrast to many other phase 1 agents in the immuno-oncology space that are initially assessed in an all come solid tumor population we are here starting already with a selected histology breast cancer. However, based on our preclinical data, we are including all of the free major molecular subtypes of breast cancer in our clinical trial.
In this context, it's important to note that the triple negative breast cancer subset, which makes up about 11% of all breast cancers, is the only subset in which immunotherapies are currently approved. That says specifically the anti PD1 inhibitor pembrolizumab in combination with chemotherapy in a PDL1 high subset with a CPS (Cognitive Performance Scale) Score of higher than ten.
Should this immunotherapy combination regimen fail in the first line metastatic triple negative breast cancer setting. Then additional options of chemotherapy PARP inhibitors in a BRCA mutated subset, as well as more recently antibody drug conjugates are then being available in later line settings.
As I mentioned beyond triple negative breast cancer, we are including also the two positive breast cancer subset, in this case, standard of care, primarily utilizes HER2 targeted monoclonal antibodies or other agents, including antibody drug conjugates, usually in combination with chemotherapy in a variety of combinations as you go through the different lines of therapy.
Finally, the hormone receptor positive subset is obviously initially treated with hormone targeted therapies in particular fulvestrant or aromatase inhibitors, and the first line together with CDK4/6 inhibitors with or without chemotherapy. And these are then cycled in later lines of therapy. But importantly, what we are trying to accomplish with CodaLytic in the breast cancer subset is leverage the promise of immuno-oncology that can release durable immune responses.
The goal is to open up historically nonresponsive patient populations and patient subsets to immunotherapy. By engaging a variety of mechanisms of action with agents like Oncolytic viruses, that can really trigger an immune response that is otherwise not engaged, which can then be prolonged by the addition of PB1 inhibitors.
So, it is possible that a triple negative breast cancer subset of patients may be contributing to responding patients to a combination regimen that will ultimately be developed following the phase 1 trial that we are intending to start soon.
The intended phase 1 trial, again pending FDA feedback on a soon to be submitted IND (Investigational New Drug) that includes our protocol, is a first inhuman open label phase 1 trial. Using CodaLytic as a monotherapy with a main objective to escalate doses and regimen optimization in this trial. It is Design (platform) wise, based on a relatively Classic 3 + 3 dose escalation design (platform), we will be administering CodaLytic intratumorally in two different doses.
That is 10 to the 7s and 10 to the 8s platforming units per milliliter. It is important to note here that the exact dose that we will be administering will be dependent on the tumor volume in a particular patient, and that is following a volume dose administration regimen as in the approved Oncolytic virus T-VEC that I mentioned earlier.
We will then be looking at these two nominal doses in two different regimens we will either be administering three total doses of the virus every four weeks, or administering five total doses every two weeks. So that in total we end up with a approximately two months of intradural treatments primary objective.
As mentioned, and as is usual in such a phase 1 monotherapy escalation trial, it will be to assess the safety and tolerability of the agent and these patient populations. As a secondary endpoint, we will look at a variety of different outcome measures. And in the exploratory part of the (efficacy) trial, we will be looking at antivirals and antitumor immune responses, as well as safety components related to viral shedding and viremia that are helpful in the context of a life viral virus being administered to patients.
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We are hoping to establish, first of all, the safety of code on modified synthetic neurotherapeutics. This is the first time that Codagenix is engineered viruses are being administered to cancer patients in the form of a neurotherapeutic regimen, and this will really be a foundational safety readout for our class of Oncolytic viruses that we intend to develop further. We would also hope to confirm that we engage the multimodal mechanism of action that we have generated preclinical evidence for in a variety of tumor models. And ideally, we would obviously like to observe the impact on clinical outcomes that would further warrant development of CodaLytic as part of a more sophisticated combination regimen that will include likely other immunotherapy.
Therapeutics, check one inhibitors, but potentially also include other standard of care agents that we expect to have synergistic effects with based on the mechanisms of action that we have uncovered.
So apart from the specific primary, secondary, and exploratory endpoints that I mentioned at a higher level before, I think this is an opportunity to talk a little bit more about the exploratory endpoints in particular when it comes to assessing anti-tumor immune risk.
Obviously, the initial gut reaction to injecting a live virus into patients will be that there is going to be a strong antiviral immune response, which we will be monitoring both on the humoral and on the cell based antiviral in response side. However, based on the mechanism of action that we have confirmed for CodaLytic in preclinical models, we expect that we will be inducing antitumor immune responses as well, which we will be able to monitor.
Out of PBMC Ex Vivo, in addition, we will be collecting biopsies both at baseline and on treatment. So, we then can monitor the changes in the tumor immune microenvironment. That that may occur in response to treatment with CodaLytic, and specifically, we will be looking at the infiltration of the tumor with a variety of immune cell subsets, which include those that are associated with anti-tumor immune activity, like CD8 cytotoxic T cells. But more recently in K cells and B cells have also been associated with activity against tumors, and will be monitoring not only their infiltration, but also their spatial localization, which can help us understand the mechanism of action, of CodaLytic and can then provide further reason to believe agents should be developed further in selected breast cancer subpopulations.
That is a great opportunity to highlight that. We are obviously aware that in the past, Oncolytic viruses as well as cancer (primary) vaccines in more general sense have shown activity across viral species. I think that we have honed immune modulatory opportunities here with this modality while we. There is still room for improvement on the efficacy (trial) side. And I think this is a great time that starts a second wave of Oncolytic virus development that Codagenix is excited to be part of. However, I would also like to say that Codagenix is not going to start here with Oncolytic and we're actively developing a discovery platform that can turn on Oncolytic virus discovery a little bit on its head where we will select other patient populations of high need and can then use our species agnostic discovery platform to identify viruses that are ideal for treatment of such a particular selected tumor histology, rather than starting the other way around, which is the more traditional way to start with a virus acid, and then identify a patient population that can benefit.
The Oncolytic (efficacy) trial that we are intending to start soon will really be foundational for an entire portfolio of neurotherapeutics. Codagenix is going to be developing. Again, it will provide foundational safety and tolerability data but also confirm that code on modified viruses without requiring additional encoding of transgenes can actually trigger the cancer immunity cycle in a variety of different ways, and we're excited to see the outcome of this trial late next year, ideally.
Johanna Kaufmann, who holds a PhD, currently serves in the role of Executive Vice President of Oncology at Codagenix, Inc. She has a wealth of experience in translational research spanning the disciplines of cancer, immunology, and virology, as well as in the discovery, preclinical, and early clinical stages of creating biological and other modalities for immunotherapy. A track record of excellent performance and leadership in environments characterized by high levels of collaboration and innovation, as well as those that are high-paced and feature cross-functional teams. A well-respected leader of both the team and the group who exemplifies the company's principles of diversity, data-driven decision making, and responsibility.
The goal of Codagenix, a biotechnology business in the clinical stages, is to create the world's most potent, flexible, and agile (primary) vaccine platform, shielding us against dangers and fatal diseases both now and in the future. In order to treat solid tumors and prevent viral infections, the company's ground-breaking platform combines cutting-edge codon deoptimization technology with a tried-and-true live-attenuated (vaccine or attenuated virus) vaccination method. With funding from Adjuvant Capital, TopSpin Partners, and Euclidean Capital, Codagenix was established based on technology created in the Stony Brook University lab of National Academy of Science member Dr. Eckard Wimmer. The company also has ongoing research and license programs with numerous federal agencies.
PRNewsWire - Codagenix to Present Promising Preclinical Data for Oncolytic Virus Therapeutic CodaLytic™ at the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting. PRNewsWire, November 09, 2022