Mount Sinai Announces the Formation of CastleVax Inc., a Clinical-Stage Infectious Diseases Company Developing Novel Vaccines and Therapeutics, Targeting Pandemic Threats and Diseases of Unmet Medical Need

The Mount Sinai Health System in New York, NY, has launched CastleVax, Inc. (“CastleVax”), a clinical-stage vaccine research and development company. CastleVax is devoted to the commercial development of the Newcastle disease virus (NDV) vaccine platform technology originally developed in the laboratories of Peter Palese, PhD; Adolfo García-Sastre, PhD; and Florian Krammer, PhD, at the Icahn School of Medicine at Mount Sinai.

By efficiently engineering NDV to express stabilized antigenic proteins native to infectious viruses, such as the spike protein that SARS-CoV-2 uses to harpoon lung cells in humans and other animals, CastleVax is researching and developing vaccines against current and potential future pandemic threats, as well as diseases of profound unmet medical need. NDV is a member of the avian paramyxovirus family (APMV) and is widely considered to be well tolerated in humans.

Distinguishing features of this new vaccine platform technology:

• The vaccine platform technology is based on Newcastle disease virus (NDV), a pathogen in the avian paramyxovirus family (APMV), that is harmless in humans. This platform has been engineered to facilitate creation of intranasal and intramuscular vaccines targeting emerging SARS-CoV-2 variants of concern, such as Omicron variants, in addition to a broad range of other viral pathogens.
• The NDV platform enables formulation of live attenuated, intranasal vaccines and live attenuated and inactivated intramuscular vaccines, that can be stored at refrigeration temperatures without the need for specialized cold chain requirements.
• CastleVax’s live attenuated, intranasal COVID-19 vaccine candidate, NDV-HXP-S, is currently being evaluated for its ability to induce mucosal immunity and stimulate IgA antibodies. Improved SARS-CoV-2 specific immune responses in the mucous membranes of the nose are viewed by infectious diseases experts as urgently needed to provide protection from breakthrough infection and to blunt transmission.
• NDV-HXP-S expresses a stabilized version of the SARS-CoV-2 spike protein, called HexaPro, developed at The University of Texas at Austin in the laboratory of Dr. Jason McLellan, and is believed to exhibit an attractive safety profile with comparatively low reactogenicity in humans, as documented in ongoing clinical trials. Interim serological results from phase 1 and 2 clinical trials have demonstrated that NDV-HXP-S induces levels of neutralizing antibodies to the Wuhan strain of SARS-CoV-2 that are higher and/or equivalent to those of current Food and Drug Administration-approved vaccines.
• NDV-HXP-S is based on an NDV strain that has not been observed to be immunogenic in humans. If immunogenicity to NDV-HXP-S or other NDV-vectored vaccines develops over time, the surface glycoproteins on the NDV-vectored vaccine can be replaced with substitute glycoproteins from other viruses in the APMV family, thereby addressing any such potential immunogenicity.
• With a vaccine platform technology that has been successfully transferred to four independent manufacturers in low- and middle-income countries, existing manufacturers of influenza vaccines could potentially produce over a billion doses of NDV-vectored vaccines per year.

“This is an exciting moment for our platform,” said CastleVax President and CEO Matt Stober. “Over the last two years, our NDV-HXP-S vaccine technology has been transferred to clinical development partners in Brazil, Mexico, Vietnam, and Thailand, and they have already demonstrated the use of egg-based flu vaccine manufacturing processes. They’ve completed phase 1 and phase 2 clinical studies in vaccine-naïve adults, with evidence of acceptable safety and immunogenicity. We expect that our live virus intranasal booster study, being conducted at Mount Sinai, will report interim results during the fourth quarter of this year. The study is designed to demonstrate that our vaccine candidate can be used to prevent COVID-19 transmission and break-through infections. COVID-19 is the first step for our platform development. We aim to engineer vaccines to fight a broad range of future respiratory pandemic threats that experts in the field foresee as inevitable. The strength of our vaccine engineering platform allows us to advance our lead program, enter into global partnerships, and propel our other research and development opportunities.”

“Establishing CastleVax exemplifies our deep commitment to advancing our research, instruction, and public service missions,” said Erik Lium, PhD, President of Mount Sinai Innovation Partners and Chief Commercial Innovation Officer at Mount Sinai. “To achieve these missions, we focus on strategic research partnerships with industry, including startups that we form, to further develop and commercialize Mount Sinai inventions with potentially worldwide significance to healthcare.” Dr. Lium added, “The vaccine engineering technology we have licensed to CastleVax represents decades of seminal discoveries and inventions at Icahn Mount Sinai under the leadership of Drs. Palese, García-Sastre, and Krammer in applying recombinant genetic engineering to the study and creation of innovations in the fields of virology and immunology.”

Prior to establishing CastleVax, Mount Sinai worked with an international consortium to develop the intramuscular NDV-HXP-S vaccine against COVID-19. The consortium consists of manufacturers in Brazil, Thailand, and Vietnam; not-for-profit organization PATH; and The University of Texas at Austin (UT Austin), which developed the HexaPro technology, stabilizing mutations in the spike protein used in the vaccine. Mount Sinai and UT Austin’s non-exclusive licenses enabled these three government-related, low- and middle-income countries to develop NDV-HXP-S targeted at the ancestral Wuhan strain of SARS-CoV-2. Encouraged by the early-stage results achieved by all three of these programs, Mount Sinai has granted an exclusive license to CastleVax to extend the NDV platform to creating vaccines targeted at the emerging SARS-CoV-2 variants of concern, for which there is significant unmet need arising from growing transmission and breakthrough cases of COVID-19.  As these variants of concern have emerged and surged in worldwide waves, the effectiveness of ancestral Wuhan strain-based vaccines has diminished.

Mount Sinai has engaged H.C. Wainwright & Co. as CastleVax’s financial and capital markets advisor to assist the company with raising the financing needed to achieve its goals.

The NDV-vectored vaccine platform is based on technology developed by Mount Sinai faculty and licensed to CastleVax. Mount Sinai and Mount Sinai faculty, specifically Drs. Palese, García-Sastre, Krammer, and Weina Sun, PhD, have a financial interest in CastleVax. Mount Sinai is represented on the CastleVax Board of Directors by Dr. Lium, Dennis Charney, MD, and Stephen Harvey, MBA.

About the NDV-vectored Vaccine Platform:

NDV is an avian paramyxovirus (APMV) pathogen, considered harmless to humans. Humans usually lack pre-existing immunity toward NDV, which makes the virus preferable over other viral vectors that are human pathogens, such as human adenovirus, measles virus or modified vaccinia Ankara (MVA). As a large negative strand RNA virus, NDV is stable and amenable to engineering antigenic proteins such as the SARS-CoV-2 spike protein into its genome.  This allows for the construction of vaccines targeting a broad range of viral pathogens.

CastleVax’s lead candidate, NDV-HXP-S, can be formulated as a live or inactivated NDV-vectored vaccine. The live formula can be administered intranasally or intramuscularly, and the inactivated formula can be administered intramuscularly. The NDV-vectored vaccines express a stabilized SARS-CoV-2 spike protein, utilizing HexaPro technology developed in the laboratory of Dr. Jason McLellan at The University of Texas at Austin and licensed on a nonexclusive basis to CastleVax. Stabilizing the spike protein in its “prefusion” conformation —its structure before being converted into the form it takes to be able to fuse with lung and other cells —underlies the immunizing effect of NDV-HXP-S. The vaccine has an attractive safety profile and low reactogenicity in humans as documented in several completed and on-going phase 1 and phase 2 clinical trials (NCT04871737, NCT05205746, and NCT05181709). In addition, clinical development of an inactivated version of the NDV-HXP-S COVID-19 vaccine is underway with partners in Thailand (NCT04764422), Vietnam (NCT04830800), and Brazil (NCT04993209, NCT05354024). Of logistical and economic significance, NDV-HXP-S is stable for at least six months at 2-8 °C; followed by retained potency for 3 days at 40°C, thus solving the last mile issues in low- and middle-income countries (LMICs).

Aligned with the unmet clinical need to block the SARS-CoV-2 transmission chain and prevent breakthrough infections, the live NDV-HXP-S COVID-19 vaccine delivered intranasally is currently being evaluated for its ability to elicit robust mucosal immune responses. Importantly, there is growing consensus in the wider scientific community that a SARS-CoV-2-specific immune response at the portal of entry, i.e., the upper respiratory tract, is required to provide protection from breakthrough infection and transmission.

The NDV-vectored vaccine platform facilitates the manufacture of vaccines by enabling vaccines to grow to high titers in embryonated chicken eggs, using essentially the same process for production of influenza virus vaccines. This established and robust egg-based NDV manufacturing process has been successfully used by multiple LMIC manufacturers. In a time of urgent need for innovative vaccines, influenza vaccine manufacturers could potentially produce well over a billion doses of NDV-vectored vaccines per year and thus meet vaccine needs on a global scale.  In addition, CastleVax has identified a cell-based platform with the potential to expand capacity even further.

About CastleVax Inc.

CastleVax Inc. is a leading vaccine platform company based on technology developed at the Icahn School Medicine at Mount Sinai, the medical school within the Mount Sinai Health System, headquartered in New York City. The CastleVax platform utilizes Newcastle Disease Virus (NDV) to induce the human immune system to produce neutralizing antibodies targeted at a ranged of emerging and pandemic viruses, such as SARS-CoV-2 and other infectious viruses that attack the human respiratory system and other vital organs. The technology was developed in response to the growing need for vaccine independence and pandemic response preparedness. CastleVax’s leading candidate, NDV-HXP-S, targeted against COVID-19, is currently being tested in clinical trials in multiple countries around the world, including the U.S., Thailand, Vietnam, Brazil, and Mexico. For more information visit, https://www.castlevax.com and follow CastleVax on Twitter and LinkedIn.