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Serina Therapeutics, Inc. |
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January 14, 2019 Issue |
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CEOCFO MAGAZINE |
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Q&A with Dr Brendan P. Rae, Ph.D., J.D., CBO of Serina Therapeutics, Inc. developing their revolutionary Polymer Drug Delivery System for Small Molecules and Protein Therapeutics that will Make Drugs Safer, More Efficacious, and Increase Patient Compliance |
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Chief Business Officer
Serina Therapeutics, Inc.
Interview conducted by: Lynn Fosse, Senior Editor, CEOCFO Magazine, Published – January 14, 2019
CEOCFO: Dr. Rae, what is the focus at Serina Therapeutics Inc today? Dr. Rae: Serina is a polymer drug delivery company based in Huntsville, Alabama. It is focused on the development and application of POZ, its proprietary drug delivery polymer, to improve the pharmacokinetic, safety, and / or efficacy profile of small molecules and protein therapeutics. Serina was founded by Milton Harris and Mike Bentley, pioneers of the first-generation pegylation drug delivery technology, who sold Shearwater Polymers to Nektar in the early 2000s. Serina’s mission is twofold, through the application of POZ: we first want to make known drugs safer, more efficacious, and increase patient compliance; and second, we want to breathe life into new therapeutic molecules that would otherwise be discarded due to pharmacokinetic, solubility, or bioavailability liabilities. In addition to collaborations with pharma companies, Serina, to date, has developed a CNS-centric pipeline consisting of SER-214 and SER-240, POZ versions of rotigotine and apomorphine, respectively, these are improved therapeutics for the treatment of Parkinson’s disease; SER-227, a POZ-buprenorphine for treatment of post-operative pain; and SER-228, POZ-cannabidiol, a weekly subcutaneous administration of cannabidiol for treatment of a variety of neurological indications and potentially other unrelated conditions. In addition, Serina has been diligently prosecuting a patent estate designed to give maximum exclusivity to the application of POZ technology and POZylated drugs.
CEOCFO: Would you explain how the POZ platform works? Dr. Rae: During the process of polymerization, a predetermined number of oxazoline monomers containing a pendent alkyne group are incorporated into the polymer. These pendent groups are essentially the hooks to which we attach drugs using a toolkit of proprietary linkers. The linkers have an azide group at one end and the azide-containing linker is attached to a hydroxyl on the drug of interest. The alkyl chain length of the linker also controls the speed at which drug is released from the polymer in vivo. The drug is “clicked” to the pendent alkyne using quantitative copper catalyzed click chemistry to which Serina has a worldwide exclusive license from Scripps. POZ conjugates are delivered via subcutaneous administration. Once in the blood, the drugs are cleaved by butyrylcholinesterase in a uniform and consistent manner providing continuous steady state levels of drug release. Importantly, the enzyme, butyrylcholinesterase is the only esterase activity in human plasma that catalyzes the release of these drugs and release only takes place in the vascular compartment. This is especially important for SER-240, Serina’s POZ-apomorphine conjugate. Apomorphine is the most potent dopamine agonist ever characterized. Unfortunately, it has never reached its true potential as a Parkinson’s disease therapeutic due to its poor solubility, low bioavailability and painful skin reactions that occur even after a single administration. SER-240 provides week-long continuous delivery of apomorphine without the debilitating skin reactions. Because the POZ-apomorphine is not cleaved in the subcutaneous compartment, the apomorphine is only released in the vascular compartment and so the skin is shielded from its deleterious effects. Serina believes that SER-240 will allow apomorphine to fulfill its true potential and will be a powerful addition to the neurologists’ armamentarium for treatment of both early and late Parkinson’s disease.
CEOCFO: How is your material different than what else might be available? Why and how does it work? Dr. Rae: In addition to its clinical validation, Serina believes that POZ is unique by virtue of all of the attributes it embodies in a single polymer. For example, not only can POZ and POZ-conjugates be easily and efficiently manufactured, but also POZ is programmable in terms of the amount of drug attached to the polymer, has virtually unlimited capacity for drug load, is amenable to targeting, is non-immunogenic, does not accumulate in the body, and can prolong the half-life of proteins as well as small molecules. We believe that the breadth of the POZ approach to drug delivery distinguishes Serina from the competition in the drug delivery arena. We realize that POZ is probably not the solution to all drug delivery issues. However, because of its multi-faceted profile and versatility, we believe it should be one of the first solutions to be explored.
CEOCFO: What is it about the polymer that you have developed that allows this to happen? Dr. Rae: In its most impure form, POZ is the glue on top of the cereal box. However, in the hands of Serina, POZ is a highly purified polymer that overcomes many of the limitations of other drug delivery polymers while still retaining the requisite features of biocompatibility, stealth behavior and low dispersity. As already mentioned, POZ is inert in that we have not been able to raise antibodies to it and is excreted unchanged by the kidneys; drug load is totally programmable due to the consistent incorporation of the desired number pendent alkyne groups; it provides continuous drug delivery over the dosing period via cleavage by an esterase that only exists in the blood; and it can be easily and efficiently manufactured.
CEOCFO: How have you decided what conditions to work on, what might be appropriate for this? Dr. Rae: The universe of molecules and therefore conditions where POZ will be successfully applied is extremely large and diverse. In this regard, Serina is therapeutic area agnostic. As mentioned, Serina’s founders were pioneers of pegylation and their work in the late 90s and early 2000s is the basis of today’s multi-billion dollar market for pegylated compounds such as PEGASYS, Movantik, and Neulasta. When it comes to POZ, we believe it is PEG on steroids in terms of potential applications. The paradigm we use to decide which conditions and molecules we will work on is fairly straightforward. We first of all identify molecules that are amenable to improvement through the use of POZ. In addition to looking at the liabilities already mentioned, at this stage we examine if the POZ improvements will make a meaningful difference to patients. If the answer is yes, we continue development. As an example, we followed the development of Epidiolex, GW Pharma’s cannabidiol therapy for epilepsy very closely. Epidiolex is administered orally in sesame seed oil twice per day and many of the adverse events are driven by this mode and manner of administration. We knew that we could design a POZ-cannabidiol conjugate that could be delivered once per week by subcutaneous injection. As the Epidiolex data became more compelling we moved the POZ-cannabidiol conjugate into preclinical animal studies and demonstrated in the monkey that SER-228 is a true once weekly therapy that can deliver cannabidiol continuously over the dosing period at therapeutic levels. In discussions with KOLs in the area, we determined that a therapy capable of delivering a once weekly dosing regimen of cannabidiol would be a significant advance for patients and so we decided to further develop this program.
CEOCFO: Is the public comfortable with a one week treatment rather than a daily treatment or are some people asking “How can it really work?” Do they believing that you can do a one week shot that will replace or hopefully be better than a daily pill or two? Dr. Rae: The short answer is yes. POZ therapeutics are delivered subcutaneously. We recognize that not all patients will be comfortable receiving an injection. However, our market research tells us that the significant majority of patients will welcome an injection when they weigh its benefits against the disadvantages of the manner the same therapy is currently delivered. Case in point is our lead program, SER-214, POZ-rotigotine. Rotigotine is currently delivered transdermally in a daily patch. The patch is associated with significant skin-related side effects that actually cause a significant number of patients to discontinue treatment for a reason completely unrelated to efficacy. Serina’s lead program, SER-214, gives patients suffering from Parkinson’s disease the ability to access rotigotine, a potent dopamine agonist, for a longer period of time and thereby potentially improve the overall prognosis when it comes to disease progression.
CEOCFO: What has been the response from the medical community who are aware of what you are doing? Dr. Rae: To date, the response of the medical community to the work we are doing has been overwhelmingly positive. The physicians and patients we have spoken to are all too well aware of the shortcomings of present treatment and they appreciate the benefits that our approach can bring to patient compliance, safety and efficacy.
CEOCFO: Are you seeking funding or investment? Where are you today? Dr. Rae: Serina has raised $30 million from private investors mainly from the Huntsville area over the last 10 or so years. We have used this funding to develop the POZ platform, to build our pipeline of POZ therapeutics, and to clinically validate the POZ approach. At this juncture, we are now embarking on the next phase of the company’s evolution – the clinical development and commercialization of POZ products. This next phase is capital intensive and we are currently seeking additional investment. We believe that the risk associated with the development of our programs is significantly reduced because of the extensive real world experience already in place with the molecules we have chosen. The time to commercialization is also reduced because we will avail ourselves of the 505(b)(2) pathway. Serina’s intellectual property covers all the uses of POZ and we want to be able to take full advantage of the entire platform. If you look at PEG, it has generated over $170 B in product revenue. We will exploit the full commercial potential of POZ through development of our own pipeline and licensing the technology. In regard to funding our own development, we are considering spinning specialized companies out of Serina. Case in point, we have formed Canaria Therapeutics, Inc., a subsidiary of Serina that will specialize in movement disorders with SER-214 and SER-240. We feel that focused companies will maximize investment potential because they will be attractive to investors with a shorter investment horizon than those who will invest in Serina. This dual investor strategy will speed product selection at Serina and product development in the subsidiaries.
CEOCFO: What have you learned that surprised you so far in the testing? Dr. Rae: I haven’t been surprised by anything I have seen so far. Remember, at the time I joined Serina, much of the ground work had already been laid to prove that POZ was indeed a revolutionary technology for drug delivery. Over the course of my tenure, I have been happy to see the hard work, blood, sweat and tears of the team come to fruition as they successfully tackle increasingly more difficult programs.
CEOCFO: What is the timetable for the next year or so? Dr. Rae: In the coming year we are focusing our energy on raising additional investment and developing our pipeline assets. We will focus on institutional investors as well as non-dilutive sources of financing such as grants and licensing. By 2020, we hope to have demonstrated SER-240’s safety and efficacy in clinical trials in addition to advancing SER-214 in Phase 2.
CEOCFO: Why should people pay attention to Serina Therapeutics Inc? Why does company stand apart in a crowded field? Dr. Rae: Serina is the little company that could. It’s a 10-person company that has developed an elegant and versatile polymer that overcomes many of the issues that have bedeviled efficient delivery of therapeutics in all areas of medicine. No other polymer drug delivery technology incorporates all the attributes of POZ. The Serina founders have spent their entire careers in the polymer drug delivery business and successfully developed the pegylation technology that has provided better outcomes to patients and generated over $170 billion in product revenue to date. In Serina, they brought their formidable knowledge and experience to make a polymer drug delivery technology that was better than pegylation. With the data Serina have generated to date, they succeeded. We see no reason why POZ will not become the new gold standard in polymer drug delivery and surpass pegyation, arguably the most successful polymer approach to drug delivery ever developed, both in the number of patients it benefits as well as product revenue.
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“Serina is the little company that could. It’s a 10-person company that has
developed an elegant and versatile polymer that overcomes many of the issues
that have bedeviled efficient delivery of therapeutics in all areas of
medicine. No other polymer drug delivery technology incorporates all the
attributes of POZ… We see no reason why POZ will not become the new gold
standard in polymer drug delivery and surpass pegyation, arguably the most
successful polymer approach to drug delivery ever developed, both in the
number of patients it benefits as well as product revenue.”
Serina Therapeutics, Inc.
Contact: Brendan P. Rae, Ph.D., J.D. 415 702 7454
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Polymer Therapeutics, Serina Therapeutics, Inc., Drug Delivery Companies, Dr. Brendan P. Rae, Ph.D., J.D., Revolutionary Polymer Drug Delivery System for Small Molecules and Protein Therapeutics that will Make Drugs Safer, More Efficacious, and Increase Patient Compliance, CEO Interviews 2019, Healthcare Company, POZ, The Next Generation of Polymer Therapeutics, drug delivery polymer technology, polymer poly(2-oxazoline), polymer therapeutics for cancer, pain, refractory epilepsy, and movement disorders, Parkinson’s disease, restless leg syndrome, water soluble polymer, low viscosity polymer, Parkinson’s disease drugs, new treatment for Parkinson’s disease, increase drug antibody ratio, Serina Therapeutics, Inc. Press Releases, News |
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Dr
Brendan P. Rae, Ph.D., J.D.