Our Science

We have a robust pipeline to address emerging unmet medical needs and are continually enhancing our portfolio by developing and in-licensing promising product candidates in transplantation, nephrology, immunology, infectious diseases and other underserved conditions.

PROGRAM NAME	INDICATION	PHASE 3
Budesonide delayed release capsules* +	Immunoglobulin A Nephropathy (IgAN)	Approved
Budesonide delayed release capsules* are immunomodulating agents indicated to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. The delayed-released capsule is designed to release coated beads of budesonide in the ileum to modulate mucosal B cells in the Peyer’s patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-IgA1) causing IgAN.
Pritelivir +	Refractory Herpes Simplex Virus (HSV)	Filed
Pritelivir is an oral innovative therapeutic candidate with a novel mechanism of action designed to inhibit the replication of herpes simplex virus (HSV). As a thiazolylamide-based compound, pritelivir is designed to target both HSV-1 and HSV-2 and has been evaluated for activity against treatment-refractory HSV infection in immunocompromised individuals. Standard of care therapy for HSV infections typically involves antiviral agents such as acyclovir or valacyclovir, that inhibit viral DNA replication. However, these treatments require activation by the viral thymidine kinase enzyme, meaning that mutations in this enzyme can lead to drug resistance — an issue that is particularly prevalent in immunocompromised hosts. Pritelivir is being investigated as a potential approach to treating refractory HSV infection by targeting the viral helicase-primase complex, which is essential for HSV DNA synthesis. This unique mechanism may allow pritelivir to remain effective against acyclovir- and foscarnet-resistant HSV strains, providing a potential oral option for difficult to treat cases if approved. An early access program is available for pritelivir. Click the button below to learn more. EARLY ACCESS PROGRAM
AIC468 +	BK polyomavirus (BKPyV)
AIC468 is an antisense oligonucleotide currently being developed for the treatment of BK polyomavirus (BKPyV) reactivation in kidney transplant recipients. AIC468 is designed to selectively target viral RNA and inhibit BKPyV replication within infected cells. Through this targeted mechanism of action, AIC468 has the potential to directly address a significant complication of kidney transplantation while reducing reliance on immunosuppression reduction, the current standard management strategy for BKPyV reactivation, which has been associated with an increased risk of acute rejection and other alloimmune events.
Pegrizeprument +	Kidney TransplantLiver Transplant
Pegrizeprument is a pegylated monoclonal antibody fragment that binds to and blocks CD28-mediated effector-T cell costimulation, without blocking CTLA-4, an important protein found on T cells that naturally helps keep the body’s immune responses in check. Pegrizeprument is, therefore, expected to have a dual mechanism of action where in a direct manner, it blocks CD28-mediated T cell activation, and indirectly, it allows for CTLA-4 mediated immunosuppressive functions. Pegrizeprument is currently being developed for the prevention of acute rejection in solid organ transplant recipients. Pegrizeprument, also known as VEL-101 and FR104, was licensed by Veloxis Pharmaceuticals from OSE Immunotherapeutics in April 2021. As part of the license agreement, Veloxis Pharmaceuticals obtained worldwide rights to develop, manufacture, and commercialize pegrizeprument for all transplant indications. Watch our video to learn more about pegrizeprument’s proposed mechanism of action: Pegrizeprument and Direct CD28 Costimulatory Blockade PEGRIZEPRUMENT, ALSO KNOWN AS VEL-101, IS AN INVESTIGATIONAL AGENT FOR WHICH THERE IS NO MARKETING AUTHORIZATION IN THE UNITED STATES. THE SAFETY AND EFFICACY OF PEGRIZEPRUMENT HAS NOT BEEN ESTABLISHED. PROPOSED MOA DATA ARE BASED ON IN VITRO/IN VIVO DATA. After an organ transplant, the immune system will target the transplanted organ for destruction.¹ This involves antigen presentation, by antigen-presenting cell to the T-cell receptor, known as signal 1, and costimulatory binding between the APC and T cell, known as signal 2.² Activation of intracellular pathways triggers expression of inflammatory cytokines such as IL-2, providing signal 3 and resulting in T-cell activation, and proliferation.² Costimulation, or signal 2, is essential in driving T-cell responses, via a complex network of signals.² Among the best characterized and most important costimulatory interactions is CD80 and CD86 on antigen-presenting cells, with CD28 on T cells.³ CD28-mediated costimulation is integral to the immune response against a transplanted organ.³ Commonly used small molecule immunosuppressive agents act on intracellular targets. While effective, these strategies are associated with cardiometabolic, nephrotoxic, and neurotoxic side effects.^2,4 Another approach to immunosuppression involves CD28 blockade through binding of CD80/86 molecules on APCs.² This approach, however, additionally blocks CTLA-4, resulting in restoration of T-effector cell proliferation and function and may lead to allograft rejection.^5,6 Pegrizeprument, also known as VEL-101, an investigational agent not yet approved for commercial use, is a pegylated monoclonal antibody fragment that specifically binds to CD28 on T cells.⁵ This action blocks the interaction of CD28 with CD80 and CD86, thereby attenuating T-cell activation and proliferation.⁵ By direct binding to CD28, pegrizeprument is designed to inhibit the stimulatory effect of CD28 activation, while preserving the immunoregulatory function of CTLA-4.⁵ Asahi Kasei Therapeutics is developing pegrizeprument as a maintenance immunosuppressant medication in their pursuit of bringing novel therapies to transplant recipients.⁷ Video References 1. Nankivell BJ, Alexander SI. Rejection of the kidney allograft. N Engl J Med. 2010;363(15):1451-1462. doi:10.1056/NEJMra0902927 2. Gupta G, Womer KL. Profile of belatacept and its potential role in prevention of graft rejection following renal transplantation. Drug Des Devel Ther. 2010;4:375-382. Published 2010 Dec 1. doi:10.2147/DDDT.S10432 3. Ville S, Poirier N, Blancho G, Vanhove B. Co-Stimulatory Blockade of the CD28/CD80-86/CTLA-4 Balance in Transplantation: Impact on Memory T Cells? Front Immunol. 2015;6:411. Published 2015 Aug 10. doi:10.3389/fimmu.2015.00411 4. Azzi JR, Sayegh MH, Mallat SG. Calcineurin inhibitors: 40 years later, can’t live without … J Immunol. 2013;191(12):5785-5791. doi:10.4049/jimmunol.1390055 5. Poirier N, Mary C, Dilek N, et al. Preclinical efficacy and immunological safety of FR104, an antagonist anti-CD28 monovalent Fab’ antibody. Am J Transplant. 2012;12(10):2630-2640. doi:10.1111/j.1600-6143.2012.04164.x 6. Kumar V, Shinagare AB, Rennke HG, et al. The Safety and Efficacy of Checkpoint Inhibitors in Transplant Recipients: A Case Series and Systematic Review of Literature. Oncologist. 2020;25(6):505-514. doi:10.1634/theoncologist.2019-0659 7. National Library of Medicine (U.S.). (2022, May- ). A Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VEL-101. Identifier NCT052384935. https://clinicaltrials.gov/ct2/show/NCT05238493

PROGRAM NAME: Budesonide delayed release capsules*

INDICATION: Immunoglobulin A Nephropathy (IgAN)

PHASE: 4

Budesonide delayed release capsules* are immunomodulating agents indicated to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.

The delayed-released capsule is designed to release coated beads of budesonide in the ileum to modulate mucosal B cells in the Peyer’s patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-IgA1) causing IgAN.

PROGRAM NAME: Pritelivir

INDICATION: Refractory Herpes Simplex Virus (HSV)

PHASE: 3

Pritelivir is an oral innovative therapeutic candidate with a novel mechanism of action designed to inhibit the replication of herpes simplex virus (HSV). As a thiazolylamide-based compound, pritelivir is designed to target both HSV-1 and HSV-2 and has been evaluated for activity against treatment-refractory HSV infection in immunocompromised individuals.

Standard of care therapy for HSV infections typically involves antiviral agents such as acyclovir or valacyclovir, that inhibit viral DNA replication. However, these treatments require activation by the viral thymidine kinase enzyme, meaning that mutations in this enzyme can lead to drug resistance — an issue that is particularly prevalent in immunocompromised hosts.

Pritelivir is being investigated as a potential approach to treating refractory HSV infection by targeting the viral helicase-primase complex, which is essential for HSV DNA synthesis. This unique mechanism may allow pritelivir to remain effective against acyclovir- and foscarnet-resistant HSV strains, providing a potential oral option for difficult to treat cases if approved.

An early access program is available for pritelivir. Click the button below to learn more.

EARLY ACCESS PROGRAM

PROGRAM NAME: AIC468

INDICATION: BK polyomavirus (BKPyV)

PHASE: 1

AIC468 is an antisense oligonucleotide currently being developed for the treatment of BK polyomavirus (BKPyV) reactivation in kidney transplant recipients. AIC468 is designed to selectively target viral RNA and inhibit BKPyV replication within infected cells. Through this targeted mechanism of action, AIC468 has the potential to directly address a significant complication of kidney transplantation while reducing reliance on immunosuppression reduction, the current standard management strategy for BKPyV reactivation, which has been associated with an increased risk of acute rejection and other alloimmune events.

PROGRAM NAME: Pegrizeprument

INDICATION: Kidney Transplant

PHASE: 2

INDICATION: Liver Transplant

PHASE: Pre-Clinical

Pegrizeprument is a pegylated monoclonal antibody fragment that binds to and blocks CD28-mediated effector-T cell costimulation, without blocking CTLA-4, an important protein found on T cells that naturally helps keep the body’s immune responses in check. Pegrizeprument is, therefore, expected to have a dual mechanism of action where in a direct manner, it blocks CD28-mediated T cell activation, and indirectly, it allows for CTLA-4 mediated immunosuppressive functions. Pegrizeprument is currently being developed for the prevention of acute rejection in solid organ transplant recipients.

Pegrizeprument, also known as VEL-101 and FR104, was licensed by Veloxis Pharmaceuticals from OSE Immunotherapeutics in April 2021. As part of the license agreement, Veloxis Pharmaceuticals obtained worldwide rights to develop, manufacture, and commercialize pegrizeprument for all transplant indications.

Watch our video to learn more about pegrizeprument’s proposed mechanism of action:

VEL-101 and Direct CD28 Costimulatory Blockade

VEL-101 IS AN INVESTIGATIONAL AGENT FOR WHICH THERE IS NO MARKETING AUTHORIZATION IN THE UNITED STATES. THE SAFETY AND EFFICACY OF VEL-101 HAS NOT BEEN ESTABLISHED. PROPOSED MOA DATA ARE BASED ON IN VITRO/IN VIVO DATA.

After an organ transplant, the immune system will target the transplanted organ for destruction.¹

This involves antigen presentation by antigen-presenting cell to the T-cell receptor, known as signal 1, and costimulatory binding between the APC and T cell, known as signal 2.²

Activation of intracellular pathways triggers expression of inflammatory cytokines such as IL-2, providing signal 3 and resulting in T-cell activation, and proliferation.²

Costimulation, or signal 2, is essential in driving T-cell responses, via a complex network of signals.²

Among the best characterized and most important costimulatory interactions is CD80 and CD86 on antigen-presenting cells, with CD28 on T cells.³

CD28-mediated costimulation is integral to the immune response against a transplanted organ.³

Commonly used small molecule immunosuppressive agents act on intracellular targets. While effective, these strategies are associated with cardiometabolic, nephrotoxic, and neurotoxic side effects.^2,4

Another approach to immunosuppression involves CD28 blockade through binding of CD80/86 molecules on APCs.2 This approach, however, additionally blocks CTLA-4, resulting in restoration of T-effector cell proliferation and function and may lead to allograft rejection.^5,6

VEL-101, an investigational agent not yet approved for commercial use, is a pegylated monoclonal antibody fragment that specifically binds to CD28 on T cells.⁵

This action blocks the interaction of CD28 with CD80 and CD86, thereby attenuating T-cell activation and proliferation.⁵

By direct binding to CD28, VEL-101 is designed to inhibit the stimulatory effect of CD28 activation, while preserving the immunoregulatory function of CTLA-4.5 Veloxis is developing VEL-101 as an immunosuppressant medication in its pursuit of bringing novel therapies to transplant recipients.⁷

Video References

Nankivell BJ, Alexander SI. Rejection of the kidney allograft. N Engl J Med. 2010;363(15):1451-1462. doi:10.1056/NEJMra0902927

Gupta G, Womer KL. Profile of belatacept and its potential role in prevention of graft rejection following renal transplantation. Drug Des Devel Ther. 2010;4:375-382. Published 2010 Dec 1. doi:10.2147/DDDT.S10432

Ville S, Poirier N, Blancho G, Vanhove B. Co-Stimulatory Blockade of the CD28/CD80-86/CTLA-4 Balance in Transplantation: Impact on Memory T Cells? Front Immunol. 2015;6:411. Published 2015 Aug 10. doi:10.3389/fimmu.2015.00411

Azzi JR, Sayegh MH, Mallat SG. Calcineurin inhibitors: 40 years later, can’t live without … J Immunol. 2013;191(12):5785-5791. doi:10.4049/jimmunol.1390055

Poirier N, Mary C, Dilek N, et al. Preclinical efficacy and immunological safety of FR104, an antagonist anti-CD28 monovalent Fab’ antibody. Am J Transplant. 2012;12(10):2630-2640. doi:10.1111/j.1600-6143.2012.04164.x

Kumar V, Shinagare AB, Rennke HG, et al. The Safety and Efficacy of Checkpoint Inhibitors in Transplant Recipients: A Case Series and Systematic Review of Literature. Oncologist. 2020;25(6):505-514. doi:10.1634/theoncologist.2019-0659

National Library of Medicine (U.S.). (2022, May- ). A Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VEL-101. Identifier NCT052384935. https://clinicaltrials.gov/ct2/show/NCT05238493

*Developed under the program name NEFECON.

To learn about the pipeline led by the Japan team, click here.
To learn about the Open Innovation Program, click here.

Our Disease States of Focus

IgA Nephropathy (IgAN)

Primary immunoglobulin A nephropathy (IgA nephropathy or IgAN or Berger’s Disease) is a rare, progressive, chronic immune-mediated disease characterized by the buildup of immunoglobulin A (IgA) immune complexes in the kidneys, leading to inflammation and damage. In people with IgAN, excess galactose-deficient IgA1 that is predominantly produced in the gut mucosa gets into the bloodstream. This pathogenic IgA is recognized by the immune system and antibodies are formed against it resulting in immune complexes that become deposited in the glomerular mesangium of the kidney. This deposition in the kidney can lead to progressive kidney damage and potentially result in end-stage kidney disease. IgAN most often develops between late teens and late 30s.

Transplantation

Solid organ transplantation is a critical and often life-saving intervention for patients with end-stage organ failure, significantly improving survival and quality of life. To prevent the immune system from rejecting the transplanted organ, lifelong immunosuppression is required. While essential, these therapies are associated with adverse effects that can compromise the long-term health of both the organ and the patient. Beyond immunosuppression, transplant recipients face ongoing challenges such as heightened risk of infection, cardiovascular and metabolic complications, and increased incidence of malignancy, along with the need for lifelong monitoring and support. Consequently, there is a substantial need for innovative, safer and more patient-centric approaches to transplantation care.

BK polyomavirus (BKPyV)

BK polyomavirus (BKPyV) is a common human polyomavirus that infects most individuals during childhood, typically without causing symptoms, and subsequently establishes lifelong latency, primarily in the urinary tract and renal tissue. In immunocompromised individuals, particularly kidney transplant recipients, BKPyV can reactivate and replicate. Reactivation may lead to BK viremia and, in some patients, progress to BK virus-associated nephropathy, a serious complication associated with graft dysfunction that may ultimately result in graft loss. Currently, there are no approved therapies specifically indicated for the treatment of BKPyV infection. The cornerstone of management is reduction of immunosuppressive therapy to restore antiviral immune responses; however, this approach has been associated with an increased risk of acute rejection and other alloimmune events.

Herpes Simplex Virus (HSV)

HSV commonly causes recurrent labial and genital herpes infections. While immunocompetent individuals generally manage these infections effectively, immunocompromised patients face more severe complications, including disseminated disease, keratitis, and encephalitis. Given the frequent resistance of HSV to existing drugs, new treatment options are urgently needed.

Expanded Access Policy

At this time, Asahi Kasei Therapeutics investigational therapies can only be accessed through participation in a clinical trial.

If you’re interested in getting involved in a clinical study, please talk to your healthcare provider. They can help advise you on whether you would be eligible to enroll in a study and if participation could be right for you.

Current Trials for Investigational Therapies

We are currently evaluating pegrizeprument for the prevention of acute rejection in recipients of kidney transplants. Visit clinicaltrials.gov for clinical study information.
We are currently evaluating AIC468 for the treatment of BK polyomavirus (BKPyV) infection in recipients of kidney transplants. Visit clinicaltrials.gov for clinical study information.

Under the 21st Century Cures Act, the manufacturer or distributor of one or more investigational therapies for the diagnosis, monitoring, or treatment of one or more serious diseases or conditions shall make available its policy on how it evaluates and responds to requests submitted under section 561(b) of the Federal Food, Drug, and Cosmetic Act for provision of such a drug.

In cases where a clinical trial isn’t an option, and the patient has exhausted all available treatment options, treating physicians may request investigational drug pre-approval from relevant regulators and health authorities. Such individual use of an investigational drug pre-approval is often called “expanded access” or “compassionate use” but may go by other names.

It’s important to remember that investigational drugs have not yet received regulatory approval; therefore, their potential risks and benefits are not yet established. Doctors and patients should consider all possible benefits and risks when seeking expanded access to an investigational drug.

In general, expanded access may be appropriate when the following conditions are met:

The patient has a serious disease or condition, or their life is immediately threatened by their disease or condition.
There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition.
Patient enrollment in a clinical trial is not possible.
Potential patient benefit justifies the potential risks of treatment.
Providing the investigational medical product will not interfere with investigational trials that could support a medical product’s development or marketing approval for the treatment indication.

Currently, participation in one of our clinical trials is the only way to access our investigational therapies.

In the event that we decide to consider expanded access requests for our investigational therapies, we will evaluate and respond to each expanded access request objectively and on a case-by-case basis. This policy will be updated with a hyperlink to the relevant expanded access record(s) on clinicaltrials.gov after such record(s) becomes active.

As authorized by the 21st Century Cures Act, Asahi Kasei Therapeutics may revise this expanded access policy at any time. Additionally, the posting of this policy by Asahi Kasei Therapeutics shall not serve as a guarantee of access to any specific investigational therapy by any individual patient.

Disclaimer

The information on this website and communications by Asahi Kasei Therapeutics about its services, diseases or indications, marketed products, research, or investigational products (collectively, “Information”) are not professional or medical advice. To the maximum extent permitted by law, Asahi Kasei Therapeutics provides the Information as-is and expressly disclaims all warranties, expressed or implied, and assumes no responsibility for use of the Information. Asahi Kasei Therapeutics’ products and services are not available, approved, or valid in all countries. Product status and Prescribing Information may differ between countries. Refer to local rules and product information regarding any products mentioned on this website or communicated by Asahi Kasei Therapeutics.

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