Investment and partnering opportunity
Simplexia is developing a new modality of genital herpes vaccines. Our ambition is to launch the first vaccine on the market for treatment and prevention of genital herpes, a global unmet medical need.
Simplexia’s scientific strategy
Simplexia’s scientific strategy is to leverage ground-breaking research from the University of Gothenburg in Sweden and experience from earlier clinical trials to develop a first in class vaccine for prevention and treatment of genital herpes based on the safe and well-proven protein subunit vaccine technology.
Trapping the virus
A vaccine for genital herpes using a radically different scientific approach.
Current options are not enough
Current therapies aim to manage genital herpes by prevention of symptoms after virus activation to improve the quality of life of patients with recurrent disease or prevention of transmission to sexual partners. The therapeutic options available, oral antiviral drugs, can suppress symptoms but only when the virus is activated.
There is a need for a long-term solution
The development of one or more herpes simplex virus (HSV) vaccines has therefore been identified by the World Health Organization as an important goal for sexual and reproductive health (SRH) worldwide. Cross-reactive immune responses from a prior HSV-1 infection do not provide protection against subsequent HSV-2 infection. Several human vaccine trials using cross-reactive antigens found on both HSV-1 and -2 virus have failed. Therefore, Simplexia’s vaccine is based on a type-specific protein of HSV-2, gG-2. Simplexia has developed a soluble version of the membrane-bound region of gG2 (mgG2) as an HSV-2 vaccine antigen.
Simplexia’s business strategy
A unique, novel approach
A genital herpes vaccine unaffected by previous oral herpes virus infection.
Wordclass team of experts
The Simplexia management team consist of seasoned biotech entrepreneurs with hands-on experience of developing vaccines from idea to launch.
Solid IP-protection
Simplexia has secured the intellectual properties rights for its proprietary protein subunit technology and has established manufacturing processes that can be scaled to demand.
Clear business model
Simplexia has a clear scientific and financial milestone plan leading to proof of concept in man and beyond.
With a vast, global unmet medical need
Genital herpes has been described as a silent pandemic since so many are unaware that they are infected until they pass the virus on to a partner who develops symptoms.
Epidemiology
Both HSV-1 and HSV-2 are easily transmissible diseases, with high levels throughout the world. The World Health Organization estimates that 3.7 billion individuals under the age of 50 (67%) have HSV-1 infection globally. Approximately 417 million individuals aged 15 to 49 are infected with HSV-2 worldwide. The WHO identifies development of one or more herpes simplex virus (HSV) vaccines as an important objective for sexual and reproductive health worldwide.
Frequent reactivation
It is now well established that HSV-2 reactivation is far more frequent than is apparent from the observation of symptoms. Approximately 80% of genital mucosal HSV reactivations are subclinical and half last less than 12 hours. Only 20% of genital shedding episodes are associated with any symptoms and even fewer with visible genital lesions. Frequent subclinical shedding of virus HSV-2 from latently infected nerve cells is the major route of transmission and not the clinical lesions.
Neonatal severe HSV-2 infection
Neonatal herpes occurs when mothers acquires the virus in the 12 weeks before delivery. The infection may affect the skin, eyes, and mouth herpes (SEM herpes), internal organs (disseminated herpes, DIS herpes), and central nervous system herpes (CNS herpes).Depending on the type, symptoms vary from a fever to small blisters, irritability, low body temperature, lethargy, breathing difficulty, and a large abdomen due to ascites or large liver. Globally, it is estimated to affect one in 10,000 births.
Recurrent meningitis
Herpes meningoencephalitis is an infection of the brain and brain covering (meninges) caused by the herpes simplex virus. Symptoms can include headache, fever, changes in consciousness, confusion, neck stiffness, sensitivity to light, seizures, and changes in mood, personality, or behavior. Among patients with primary genital herpes, 36% of women and 13% of men have been reported to develop meningitis as a complication. HSV-2 meningitis can also occur without any genital herpes symptoms. Once a person develops HSV-2 meningitis, there is a 20-40% chance that meningitis will recur over his or her lifetime.
Scientific rationale for the Simplexia approach for HSV-2
Cross-reactive immune responses from a prior HSV-1 infection do not provide protection against subsequent HSV-2 infection. Several human vaccine trials using cross-reactive antigens found on both HSV-1 and -2 virus have failed. Therefore, Simplexia’s vaccine is based on a type-specific protein of HSV-2, gG-2.
The Simplexia vaccine candidate contains a soluble recombinant variant, of the normally membrane bound region of glycoprotein G-2 (mgG-2).
The rationale for the use of gG2 EXCT4 as a vaccine candidate is as follows:
- Unlike other HSV-2 glycoproteins mgG-2 has low sequence homology with its HSV-1 counterpart and has been shown to only induce an HSV-2 type specific antibody response (1). In fact, the mgG-2 protein has been used for several years as a type-specific antigen for HSV-2 specific diagnosis (2). Since gG2 is unique for HSV-2, vaccination with Simplexia’s vaccine is not affected by previous HSV-1 infection.
- Virus studies using an mgG-2-negative HSV-2 mutant show that mgG-2 is involved in the extracellular release of infectious particles (3). Although glycoprotein gG2 is not essential for replication in cultured cells it is important for the exit of HSV-2 virus from cells and intact mgG-2 in clinical HSV-2 isolates is of importance for human infection, as mgG-2-negative HSV-2 isolates are rarely detected (4).
- Proliferative helper T-cells responses are seen in HSV-2 infected patients after stimulation with gG2 protein, with greater responses seen in asymptomatic than symptomatic individuals (5).
- Full-length mgG-2 protects against HSV-2 infection in a mouse genital herpes challenge model (6).
- A soluble recombinant variant of mgG-2, designated EXCT4, protects against HSV-2 infection in a mouse genital herpes challenge model (7).
- gG2 is proposed to have a similar function to VZV gE the antigen in the “HZ/su” herpes zoster “shingles” vaccine. VZV glycoprotein gE is the predominant viral cell surface molecule of VZV and although it behaves as a receptor for IgG antibodies, a function similar to that of its HSV cousin, its central function may be more closely related to viral egress and cell-to-cell spreading of virus and the formation of “virus highways”. (8 and 9).
[1] Ashley RL, Militoni J, Lee F, Nahmias A, Corey L. Comparison of Western blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex virus types 1 and 2 in human sera. J Clin Microbiol. 1988 Apr;26(4):662-7.
[2] Ashley RL. Genital herpes. Type-specific antibodies for diagnosis and management. Dermatol Clin. 1998 Oct;16(4):789-93, xiii-xiv.
[3] Adamiak B, Ekblad M, Bergström T, Ferro V, Trybala E. Herpes simplex virus type 2 glycoprotein G is targeted by the sulfated oligo- and polysaccharide inhibitors of virus attachment to cells. J Virol. 2007 Dec;81(24):13424-34.
[4] Liljeqvist JA, Svennerholm B, Bergström T. Herpes simplex virus type 2 glycoprotein G-negative clinical isolates are generated by single frameshift mutations. J Virol. 1999 Dec;73(12):9796-802.
[5] Eriksson K, Bellner L, Görander S, Löwhagen GB, Tunbäck P, Rydberg K, Liljeqvist JÅ. CD4(+) T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals. J Gen Virol. 2004 Aug;85(Pt 8):2139-2147.
[6] Görander S, Harandi AM, Lindqvist M, Bergström T, Liljeqvist JÅ. Glycoprotein G of herpes simplex virus 2 as a novel vaccine antigen for immunity to genital and neurological disease. J Virol. 2012 Jul;86(14):7544-53.
[7] Görander S, Honda-Okubo Y, Bäckström M, Baldwin J, Bergström T, Petrovsky N, Liljeqvist JÅ. A truncated glycoprotein G vaccine formulated with Advax-CpG adjuvant provides protection of mice against genital herpes simplex virus 2 infection. Vaccine. 2021 Sep 24;39(40):5866-5875.
[8] Berarducci B, Ikoma M, Stamatis S, Sommer M, Grose C, Arvin AM. Essential functions of the unique N-terminal region of the varicella-zoster virus glycoprotein E ectodomain in viral replication and in the pathogenesis of skin infection. J Virol. 2006 Oct;80(19):9481-96.
[9] Olson JK, Bishop GA, Grose C. Varicella-zoster virus Fc receptor gE glycoprotein: serine/threonine and tyrosine phosphorylation of monomeric and dimeric forms. J Virol. 1997 Jan;71(1):110-9.
Simplexia’s development status
- Vaccination of mice with either mgG2 or Simplexia’s soluble version of mgG2, together with several different adjuvants, has been shown to protect mice against genital HSV-2 infection in a laboratory challenge model
- A manufacturing strategy that allows the production of soluble recombinant antigen mgG2 in a conventional mammalian expression system widely used in commercial manufacturing of biologics has been established. This recombinant protein, designated mgG2 EXCT4 can be expressed in Chinese hamster ovary (CHO) cells and purified by conventional chromatographic methods.
- The pilot scale manufacturing process together with analytical methods for antigen potency is being transferred to a commercial contract manufacturing organization (CMO) for scale-up and manufacturing according to cGMP.
- Regulatory safety studies are planned to start in the Q3, 2024.
- Combined phase I/II clinical trials are planned to start in Q3, 2025.
A few words from our team
“Simplexia has a unique vaccine approach and a solid scientific rationale for further development of our first-in-class vaccine against genital herpes.”
Lena Degling Wikingsson
Chairman Simplexia AB
“More than half a billion people are infected with HSV-2 globally. A vaccine for HSV-2 would not only help them. It would also decrease the spread of HIV, since people infected with HSV-2 are three to four times more likely to transmit HIV to a sexual partner.”
Jan-Åke Liljeqvist
MD, associate professor at Gothenburg University
”Simplexia has built up an ambitious and knowledgeable team with decades of experience of pharmaceutical development.”
Tim Wood
CEO Simplexia AB
Lena Degling Wikingsson
Chairman Simplexia AB
Jan-Åke Liljeqvist
MD, associate professor at Gothenburg University
Tim Wood
CEO Simplexia AB