SutroVax’s existing institutional investors, including TPG Growth, Abingworth, Longitude Capital, Frazier Health Care Partners, Pivotal bioVenture Partners, Medixci, CTI Life Sciences, Roche Venture Fund, and Foresite Capital also participated in the financing.
SutroVax’s mission is to deliver best-in-class conjugate vaccines and novel complex antigen-based vaccines to prevent serious infectious diseases. The company is leveraging its exclusive license to Sutro Biopharma’s Xpress CF platform technology to perform cell-free protein synthesis and site-specific conjugation for the field of vaccines.
“Our primary mission is to deliver the best and most broadly protective vaccines to prevent pneumonia in adults and children. We are delighted to welcome respected life-science investors RA Capital Management and Janus Henderson Investors to join with our syndicate of private equity and venture capital backers, as we work to advance the most broad-spectrum pneumococcal vaccine candidates to the clinic,” said Grant Pickering, Chief Executive Officer and Founder of SutroVax.
Pneumococcal disease is an infection caused by Streptococcus pneumoniae, which can lead to a wide range of serious primary infections including pneumonia, meningitis and bloodstream infections, as well as ear and sinus infections, and can also cause secondary infections due to other respiratory pathogens.
According to the Centers for Disease Control and Prevention (CDC), an estimated 900,000 people suffer from pneumococcal pneumonia in the United States each year, including as many as 400,000 requiring hospitalizations and approximately 28,000 deaths. The market-leading vaccine is a 13-valent PCV or Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein; Prevnar 13®; Pfizer/Wyeth), that has worldwide annual sales of approximately U.S. $ 6 billion, yet does not protect against a significant number of circulating strains of pneumococcus causing invasive disease in adults and children.
Conjugate vaccines consist of antigens (polysaccharides or oligosaccharides) that are chemically coupled to a protein carrier (PC). The conjugation of polysaccharides to proteins converts polysaccharides to T-dependent antigens and provides T-cell epitopes that are necessary for the germinal centers for the affinity maturation of polysaccharide-specific B cells, which elicits robust immune responses in infants and adults.
These so-called glycoconjugate vaccines elicit T-cell help for B-cells that produce IgG antibodies to the conjugated polysaccharide. 
Glycoconjugates induce PS-specific IgM-to-IgG switching, memory B-cell development, affinity maturation, and long-lived T-cell memory.
With the introduction of the first glycoconjugate vaccine for use in humans, a Haemophilus influenzae type b (Hib) conjugate, which was approved by the U.S. Food and Drug Administration (FDA) in 1987, glycoconjugate vaccines have played an enormous role in preventing infectious diseases caused by virulent pathogens such as H. influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. 
However, despite the success of these glycoconjugate vaccines, there are a significant number of other bacterial strains and many other infectious diseases that still have to be addressed using this technology.
The XpressCF™ platform technology, exclusively licensed from Sutro Biopharma, allows for efficient conjugation of antigens to precise positions on carrier proteins via the incorporation of multiple non-natural amino acid (nnAA) substitutions to permit click chemistry attachment.
One of the unique benefits of Sutro’s Xpress CF platform technology, also being used in the development of Sutro’s clinical ADC products, STRO-001 and STRO-002, in which a cytotoxin is conjugated to antibody-containing non-natural amino acids, is that it eliminates the need to maintain cell viability allowing for the optimization of protein synthetic capacity using the cell-free extract to produce discrete proteins in proper conformation.
In addition, the lack of a cellular membrane allows for the direct addition of non-natural factors which can be used to manipulate transcription, translation, and folding, and provide precise modulation of the protein expression process.
Using the Xpress CF platform technology, researchers at SutroVax have been able to rapidly produced a number of difficult to manufacture vaccine antigens in their proper conformation, advancing them into preclinical disease models where they have demonstrated protective efficacy.
SutroVax’s lead vaccine candidate, SVX-24, is a preclinical, 24-valent pneumococcal conjugate vaccine (PCV) that includes 11 incremental strains over and above the 13 in today’s standard of care, Prevnar 13®.
Preclinical proof of concept studies for SVX-24 evaluating the surrogate immune endpoints used for adults and children demonstrated comparable responses to the 13 common strains in Prevnar 13 and superior responses to the 23 common strains in Pneumococcal Vaccine Polyvalent (Pneumovax®23; Merck & Co), the non-conjugate polysaccharide-only vaccine.
The pneumococcal vaccine class is the industry’s largest, accounting for over U.S. $ 7 billion in annual sales. These SVX-24 preclinical data have been accepted for presentation at the 12th International Symposium on Pneumococci and Pneumococcal Disease (ISPPD-12) anticipated to take place in Toronto, Canada, June 21-25, 2020.
The SutroVax PCV pipeline also includes SVX-XP, a PCV with an expanded breadth of coverage of at least 30 strains, including newly emerging strains responsible for invasive pneumococcal disease and antibiotic resistance. SutroVax has generated preclinical proof of concept versus the standard of care vaccines and intends to advance SVX-XP into the clinic as a future successor to SVX-24.
SVX-24 is designed to improve upon the 13-valent PCV standard of care by covering the additional eleven strains that are responsible for the majority of the residual pneumococcal disease currently in circulation in both the United States and European Union and associated with high case-fatality rates, antibiotic resistance and/or meningitis.
Researchers at SutroVax achieve this by employing a cell-free protein synthesis platform, which includes the XpressCF™ platform technology, coupled with its proprietary know-how that offers several advantages over conventional cell-based protein expression methods, which the company believes enables it to generate a more broad-spectrum PCV.
Based on ongoing research, researchers at SutroVax believe they will be able to add more antigenic strains without compromising the overall immune response. This includes, in particular, the ability to specify the attachment point of antigens, including polysaccharides, on protein carriers represents a significant improvement over the random conjugation that occurs with conventional PCVs.
This site-specific conjugation is designed to ensure that T-cell epitopes on the protein carrier are optimally exposed, improving and maximizing the host immune response, whereas random conjugation can block these critical immunogenic epitopes, dampening the immune response and causing a phenomenon known as carrier suppression.
The precise and robust optimization technique to position the antigen on the carrier protein, and control of conjugation chemistry, enables the design and manufacturing of broader-spectrum conjugate vaccine candidates using carrier-sparing conjugates – allowing attachment of multiple antigenic constructs to a single protein carrier – that use less protein carrier without sacrificing immunogenicity.
This, in turn, results in homogeneous and consistent vaccines that promise to confer important immunological and clinical benefits relative to current conjugate vaccines.
These improvements have the potential to design and manufacture best-in-class conjugate vaccines with the potential to deliver heightened immunity and broader protection. These novel conjugate vaccines and can also be easily characterized and consistently produced as a result of our high-yield, streamlined production process.
To date, SutroVax achieved preclinical proof of concept of SVX-24 by demonstrating that this investigational vaccine has the potential to protect against the pneumococcal strains collectively covered by Prevnar 13 and Pneumovax 23 and showing the boostable immune responses that are the hallmark of a conjugate vaccine.
The investigational vaccine includes 24 purified capsular polysaccharides of Streptococcus pneumoniae (1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F), each of which is conjugated to eCRM, the company’s proprietary protein carrier, to produce 24 monovalent conjugates. These conjugates are mixed into a final vaccine formulation and then adsorbed to alum.
There are critical differences between SVX-24 and other currently available PCVs relating to SutroVax’s protein carrier, eCRM, particularly the ability to perform site-specific conjugation and use milder reaction conditions for conjugation.
Researchers at SutroVax achieve site-specific conjugation through the insertion of multiple non-native amino acids (nnAAs) into the protein carrier, which is not possible with the conventional chemistry used for making other PCVs.
Using click chemistry for site-specific conjugation of the polysaccharides to the nnAAs on the protein carrier may also minimize damage to the critical immunogenic epitopes on both the protein carrier and the polysaccharides through milder and shorter reactions, while other PCVs use conventional chemistries that involve harsher and longer reaction conditions.
SVX-24, as tested in preclinical studies, showed nearly double the serotype spectrum of coverage of Prevnar 13, yet contains a similar amount of protein carrier. The company believes the resulting decreased carrier burden per conjugate of SVX-24 is critical for avoiding carrier suppression and producing broader-spectrum PCVs without sacrificing immunogenicity.
Series D financing
In connection with the Series D financing, Derek DiRocco, Ph.D., from RA Capital Management, and Agustin Mohedas, Ph.D., from Janus Henderson Investors, joined the SutroVax Board of Directors as board observers.
“SutroVax is tackling a significant, growing issue given the threat of pneumococcal disease and other infectious diseases, where new strains are hampering effective preventative measures,” DiRocco and Mohedas said in a joint statement.
“SutroVax has made significant strides to date, and we look forward to the advancement of its lead candidate into clinical development as well as the expansion of its innovative platform,” they added.
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