Researchers at the University of Pittsburgh (Pitt) now pursue three COVID-19 vaccines, including 1) the PittCoVac announced by TrialSite News on April 3; 2) the investigational vaccine out of Pitt’s Center for Vaccine Research in collaboration with Austrian biotech Themis (just acquired by Merck); and 3) an effort at Pitt by Dr. William Klimstra in partnership with Tiba Biotech LLC (Tiba), a brand new Cambridge, MA-based venture. TrialSite News offers a brief breakdown of the three COVID-19 vaccines emanating out of Pitt, including a deeper dive into the recently announced RNA-based investigational vaccine candidate in collaboration with Tiba. Thanks to a solid early-stage research collaboration and savvy administrative maneuvering, a $1 million NIH grant can now be utilized to pursue the promising candidate. Tiba goes under the TrialSite News category of “Investor Watch.”
First is the indigenous effort emanating known as PittCoVac, out of the state-related research institution initially founded what was America’s Western Frontier in 1787. When tested in mice, PittCoVac produces antibodies specific to SARS-CoV-2 at quantities thought to be sufficient to neutralize the virus. Delivered via a finger-sized patch, the Pitt research team published a paper on the experimental product in the April 2, 2020 edition of EBioMedicine.
The scientists at Pitt have devised a new approach to deliver the drug using a microneedle array used to increase potency. Based on a finger-sized patch of 400 tiny needles, the spike protein would be delivered in the skin where the immune reaction is strongest. The preclinical stage research is led by Dr. Andrea Gambotto and Dr. Louis Falo. This vaccine is not anticipated to be among the first group of competitive vaccines, reports Sean D. Hamill with the Pittsburgh Post-Gazette.
Pitt & Themis Collaboration
An international coalition led by Institut Pasteur in Paris, including Austrian-based Themis and University of Pittsburgh’s Center for Vaccine Research (CVR) led by Dr. Paul Duprex, successfully secured $5 million from the intergovernmental and international organization known as Coalition for Epidemic Preparedness Innovations (CEPI). Merck, seeking to move into COVID-19 vaccine development, acquired Themis in what was part of a flurry of deals by the multinational pharmaceutical company involving COVID-19. This vaccine is based on a measles vector technology.
The measles vaccine has proven safe and effective for billions of children worldwide for forty decades, reported PittWire Health back in March 2020. The CEO of Themis declared the development of new measles vector vaccines is a known process. For example, Chikungunya, dengue, Ebola, HIV-1, Lassa, MERS, RSV, SARS, West Nile and Zika have investigational measles-based vector vaccines and several have advanced to clinical trials declared PittWire.
Pitt & Tiba Biotech: RNA-based COVID-19 Vaccine Candidate
Tiba Biotech LLC (Tiba) and Pitt are working on an RNA-based vaccine which has become well known thanks to one of the leading COVID-19 vaccine candidates—Moderna. That company’s mRNA-1273 is the furthest ahead of American-developed vaccines now in Phase II clinical trials. The two organizations came together via a friendship between Tiba’s acting chief science officer Dr. Christian Mandl and both Dr. Duprex and Dr. Klimstra at Pitt.
Led by Dr. William Klimstra, Pitt collaborates with Tiba using a novel approach based on the creation of a synthetic RNA within the investigational product that at least in theory, could trick an individual’s body to identifying this synthetic agent as an actual attacking coronavirus. Hence there would be no need to expose an individual to a live virus as many vaccines in fact require. This experimental vaccine could be safer and more effective than other RNA-based vaccines in development, reports Mr. Hamill with the Pittsburgh Post-Gazette.
Tiba Biotech positions its technology platform as a differentiator in the market. The Boston area venture has developed a proprietary molecular system designed for improved nucleic acid delivery, ensuring greater payload capacity and improved flexibility for support of a wide variety of nucleic acid types. The company positions that its technology platform supports 1) simplification, 2) increased scalability of production, and 3) elimination of deleterious material-induced effects hence giving their vaccine development an advantage in the R&D marketplace.
By utilizing their proprietary molecular platform, the company has already developed a full synthetic RNA platform for what the company claims on their website are cost effective, rapid and adjuvant-free vaccine production advantages. Composed of two parts, Tiba vaccines include 1) self-replicating RNA instruction set programmed to train the immune system to target specific pathogens, and 2) a delivery molecule that safely and efficiently transports the instruction set into the cell, reports the company.
A Longer View
Dr. Klimstra and Tiba are taking a longer view, reports the Post-Gazette. And given what it takes to develop safe and efficacious vaccines, this isn’t a bad approach. After all, now over 100 vaccine projects race for success; however; there will undoubtedly be safety and other issues along the way that must be understood and resolved. Dr. Klimstra summed up the TrialSite News view, articulating for the Post-Gazette that “What’s needed here is a very large multi-pronged approach to vaccine development.” He continued, “Because right now we just don’t know what’s going to be effective. Safety is really key here.” And Dr. Jasdave Chahal, Tiba’s co-founder concurs and concedes that they are not in this effort to be the first across the finish line.
Ultimately, there are many scenarios where a robust, effective vaccine can complement any number of vaccines that are ultimately approved for COVID-19. For example, the Moderna vaccine mRNA-1273 could ultimately be approved but perhaps a certain percentage of the population faces considerable side effects. A novel approved vaccine with less side effects would have a marketplace. So, much is unknown at this point, hence the development effort attracts attention, talent, and resources.
RNA-based Vaccine Benefits
RNA-based vaccines are based on natural systems in the body. As RNA or ribonucleic acid carries instructions from DNA (deoxyribonucleic acid) in order to make proteins that actually direct the cells. In the case of vaccines, the premise is that the RNA instructs the DNA to produce the proteins that instruct the individual’s cells to commence an immune response strong enough to overcome SARS-CoV-2. RNA-based vaccine development has advantages, reports the Post-Gazette, such as 1) ease of producing synthetic RNA in the laboratory, and 2) that unlike the use of attenuated or weakened vaccines (majority), the RNA approach never requires access to the virus itself.
RNA Vaccine Challenges
Tiba is working to overcome two challenges with RNA vaccine in development, including 1) the way most RNA-based vaccines are constructed limit or constrain the amounts of RNA researchers would like, and 2) as lipid nanoparticles are used to enable cell penetration they are also known to actually irritate host cells. This latter scenario can actually shut down the RNA translation, leading to big problems confronting the RNA delivery field, reports Chahal.
Hence, the mission of this early stage company to overcome these delivery challenges. Their solution is premised on the use of dendrimers, repetitively branched “hydrophobic” molecules; they don’t mix easy with water, enabling more stickiness to the RNA.
The collaboration with Pitt has significantly contributed to progress as Pitt’s Dr. Klimstra has focused on RNA vaccine development on a number of mosquito-borne viruses from Yellow Fever to Chikungunya, reports Hamill of the Post-Gazette. Apparently, Klimstra has been working on solving RNA challenges actually based on a method used by Moderna and others with a goal of producing a vaccine that is “more immunogenic than the Moderna-type approach.” How will they do this? Well, Dr. Klimstra offers more in the timely Post-Gazette article authored by Mr. Hamill.
Generally, all of the vaccine developers face a challenge, one that Pitt’s Dr. Klimstra thinks much about lately: what are the issues with the underlying premise of the COVID-19 vaccine model at present: that is, the vaccine actually triggers the SARS-CoV-2 spike protein to trigger an immune system response. This, of course, is not proven yet and there are some skeptics that suspect this process could lead not to cure but rather disease enhancement. Safety is of paramount concern and TrialSite News couldn’t agree more.
The Power of Early Stage Research Collaboration
The Pitt partnership showcases the power of early-stage scientific research collaboration based on mutual interests and agendas. While Tiba continues to develop and refine its technology platform, Pitt’s Dr. Klimstra was able to capitalize on a liberalized National Institutes of Health (NIH) position of greater flexibility, due to the COVID-19 pandemic, and thus switch an existing Pitt NIH grant for development on an Eastern Equine Encephalitis toward a focus on the vaccine for SARS-CoV-2. Thanks to this frankly brilliant maneuvering, the team has $1 million to utilize for this early stage development, a critical infusion of seed capital to support Tiba’s effort.
Tiba Biotech LLC Background
Founded in 2016, this pre-clinical stage biotechnology company seeks to revolutionize the design and delivery of a safer, more effective and affordable generation of nucleic acid products for human and animal health. The company positions that its RNA vaccine platform disrupts existing design, delivery and bio-manufacturing processes while enabling the rapid development of highly effective vaccines against multiple diseases. The intellectual property (IP) actually emerged from a five-year multi-lab collaboration involving MIT’s Koch Institute, the Whitehead Institute, and Boston Children’s Hospital.
Privately held, the company’s technology emanated from the Massachusetts Institute of Technology’s Koch Institute; the leadership has formed strategic partnerships with the U.S. Army Medical Research Institute of Infectious Diseases and a growing list of research centers, such as its strategic alliance with Pitt.
Backed by angel investors, the company still remains at the “seed” level of financing and the recent $1 million NIH grant effort with Pitt adds to a significant opportunity for venture capital groups. Undoubtedly, as Paul McCartney and Wings once crooned, “Someone’s knockin’ at the door” for Tiba. The leadership team should have some options in assessing who to let in.
William B. Klimstra, PhD, Department of Immunology, University of Pittsburgh
Call to Action: TrialSite News believes the Pitt and Tiba Biotech team could be onto a novel approach worth exploring for investors. Hence, this article is included in Investor Watch. Based on our internal metrics we estimate that the TrialSite Network includes several thousand investment professionals operating in venture capital, private equity and investment banking—the distribution of this group is 60% North America, 20% Europe and 15% Asia and about 5% Middle East and Africa.