Polyomavirus-associated nephropathy

WUPPERTAL, Germany--( BUSINESS WIRE )-- AiCuris Anti-infective Cures AG , announced today multiple milestone achievements for letermovir (marketed by MSD as PREVYMIS ® ) and across its pipeline of anti-viral therapeutics serving the growing population of people whose immune systems are impacted due to disease or immunosuppressive therapies. These achievements recognize AiCuris’ rapid progress in developing a clinical pipeline of precise therapies to effectively treat infections in a population for whom an otherwise manageable infection, can mean life or death. “Our mission is to make a difference for people with weakened immune systems, by giving them options in preventing or treating infections that are life-threatening for them. The expanded approval of PREVYMIS ® in Japan highlights its unique drug profile in diverse transplant settings where CMV infections pose a significant risk to adult patients on immunosuppressive therapies. Combined with the existing approvals in the U.S. and Europe, it provides further validation for the outstanding drug development capabilities of the AiCuris team and the benefit PREVYMIS ® can provide for immunocompromised patients,” said Larry Edwards, CEO of AiCuris. “It is our goal to achieve the same level of success for patients with our two follow-on pipeline programs pritelivir, which is close to pivotal Phase 3 read-out, and AIC468’s first-in-human study starting in the near-term.” PREVYMIS ® Update In May, PREVYMIS ® (letermovir) achieved approval in Japan for the use in adult patients receiving solid organ transplants (SOT). This significant milestone represents the first pan transplant indication approval for PREVYMIS ® , a first-in-class antiviral agent commercialized by our partner MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA) for the prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant and prophylaxis of CMV in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]). PREVYMIS ® is marketed in over 60 countries. Following this achievement, AiCuris will receive a milestone payment of EUR €7.5 million from MSD. Pipeline Updates AiCuris published pharmacokinetic data for its lead candidate pritelivir (AIC316), an innovative therapeutic candidate targeting HSV replication, in May 2024. Pritelivir is currently being evaluated in a Phase 3 trial for the treatment of acyclovir-resistant HSV infections in immunocompromised patients. The study expects to complete patient enrollment in 1H 2025. The study titled “ Evaluation of the Clinical Drug-Drug Interaction Potential of Pritelivir on Transporters and CYP450 Enzymes Using a Cocktail Approach ” was recently published in the journal Clinical Pharmacology in Drug Development and provides data on the drug-drug interaction profile of pritelivir. The results demonstrated that pritelivir has a low risk of drug-drug interaction, as there was no effect on intestinal uptake and efflux transporters. These findings are crucial for ensuring the safety and efficacy of pritelivir as a treatment option for patients with resistant HSV infections, who are often receiving a range of additional treatments. In addition, AiCuris’ third pipeline candidate AIC468 is rapidly nearing the clinic after the regulatory approval of its clinical trial application by the German national authority. AIC468, an antisense RNA therapeutic candidate, is designed to treat BK virus (BKV) infection, which can lead to BKV-associated nephropathy, increasing the risk of chronic kidney failure or graft loss. AIC468 will be investigated in a first-in-human Phase 1 trial in healthy volunteers starting in Q3 of 2024. Up to 88 healthy individuals are expected to be enrolled in multiple single and multi-ascending dose cohorts with the objective to investigate safety and tolerability of AIC468. AIC468 specifically inhibits BKV replication, addressing the critical need to target the virus directly. By not compromising ongoing immunosuppressive treatments - the current standard of care – it helps to reduce the risk of graft loss. Preclinical studies have shown AIC468's mechanism of action effectively inhibits BKV replication in human kidney cells and achieved efficacious concentrations in kidney tissues in vivo . Additionally, a favorable pharmacokinetic and safety profile as well as a broad therapeutic window could be demonstrated preclinically warranting the start of clinical development. “AiCuris is driving innovation in antiviral therapies with our pipeline candidates pritelivir and AIC468. The recent publication on pritelivir underscores its potential as a breakthrough treatment for acyclovir-resistant HSV infections for immunocompromised patients,” said Larry Edwards . “Additionally, achieving Phase 1 approval for AIC468 marks a significant milestone in our efforts to address BK virus infections, showcasing promising preclinical efficacy data. We look forward to the upcoming data from these programs which will be important steppingstones in developing novel therapies for immunocompromised people.” About Prevymis ® PREVYMIS ® (letermovir), developed by AiCuris and marketed by MSD, is indicated for prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant and prophylaxis of CMV in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]. The drug is marketed in more than 60 countries outside the U.S., including in the E.U., Canada, Japan and China, and has received approval for prevention of CMV infections in adult solid organ transplant (SOT) recipients in Japan in 2024. The recent approval for SOT in Japan is supported by robust clinical trials demonstrating its efficacy and safety in preventing CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative). About Pritelivir Pritelivir, a novel helicase-primase inhibitor developed by AiCuris, targets both HSV-1 and HSV-2. These viruses are responsible for genital, oral or disseminated infections with increasing severity and resistance development in immunocompromised people. Unlike traditional antivirals, pritelivir blocks viral DNA synthesis by inhibiting the helicase-primase complex, a mechanism distinct from nucleoside analogues like acyclovir. Earlier Phase 1 and Phase 2 trials in immune competent and immune compromised individuals showed a favorable safety profile and an improved clinical efficacy compared with standard of care treatments like valaciclovir and Foscarnet (including resistant or intolerant infections). Recognized with Breakthrough Therapy designation by the FDA for immunocompromised patients, pritelivir is currently advancing through a pivotal Phase 3 trial. The results of this trial will serve as a basis for filing for marketing authorization in 2026. About AIC468 AIC468 is a pioneering RNA-based therapy designed to treat BK virus (BKV) reactivation in kidney transplant patients. BKV infections prove to be a significant clinical challenge, particularly for kidney transplant recipients, as they can lead to BKV-associated nephropathy, resulting in chronic kidney failure or graft loss. To date, there are no approved antiviral treatments for BKV; the only option is to reduce immunosuppression therapy, increasing the risk of graft rejection. AIC468 is an antisense oligonucleotide that targets viral replication within infected cells by inhibiting the splicing of mRNA coding for the BKV master regulator large T-antigen. This innovative approach has demonstrated favorable pharmacokinetics and significant inhibition of BKV replication in preclinical studies. AiCuris expects to initiate the first human trial for AIC468 in Q3 of 2024, aiming to provide a much-needed therapeutic option for kidney transplant patients at risk of BKV reactivation. About Herpes Simplex Virus Herpes Simplex Virus (HSV) includes two types, HSV-1 and HSV-2, both of which cause lifelong infections. HSV-1 typically leads to oral herpes, resulting in cold sores around the mouth, while HSV-2 is commonly associated with genital herpes. These viruses can cause recurrent painful blisters and sores, and in severe cases, complications such as encephalitis, disseminated disease and neonatal herpes. HSV infections are widespread globally, with a significant impact on public health, especially immunocompromised patients, due to their high prevalence, more severe and more frequent manifestations and increased potential for drug resistance. About BK Virus BK virus (BKV) is a polyomavirus that commonly infects the urinary tract. While it remains latent in most healthy individuals, it can reactivate in immunocompromised patients, such as those undergoing organ transplantation. Reactivation of BKV can lead to serious complications, including BK virus-associated nephropathy (BKVN), which can cause kidney dysfunction and graft loss in transplant recipients. Managing BKV infections is essential in immunocompromised patients to prevent significant morbidity and improve transplant outcomes. About AiCuris AiCuris is meeting the needs of the growing population of immunocompromised people who require precise therapies to effectively treat infection. Our flagship product, PREVYMIS ® , marketed by our partner MSD, prevents CMV in a defined group of transplant recipients. Our pivotal Phase 3 candidate pritelivir aims to address recurrent and resistant HSV infections in a broad population of patients with weakened immune systems. For immunocompromised people, an otherwise manageable infection can mean life or death. AiCuris, with its expertise and growing pipeline, is committed to providing therapeutic solutions for them now and in the future.

PRESS RELEASE Memo Therapeutics increases Series C financing to CHF 45 million Additional CHF 20 million raised from new investors Ysios Capital and Kurma Partners as well as from existing investors Proceeds will be used to expand Phase II of best-in-class anti-BK Virus antibody to become the largest study ever conducted for BK virus infection in kidney transplantation Schlieren / Zurich, Switzerland, 7 May, 2024 – Memo Therapeutics AG (or “MTx”), a late-stage biotech company developing a best-in-class BKV-neutralizing antibody for BKV infection in kidney transplantation, today announces that it has successfully raised CHF 20 million as part of an extension of its Series C financing, bringing the total amount raised in the funding round to CHF 45 million. The new funding will be used to bolster the clinical advancement of MTx’s lead asset, AntiBKV, expanding the Phase II trial with a dose evaluation extension to be the largest BK viremia therapeutic study ever conducted in kidney transplant recipients. The disease represents a potential market in excess of $1 billion and is caused by the BK virus, which can become reactivated in immunosuppressed kidney transplant patients leading to severe complications. Initial data from the Phase II trial is expected in the first half of 2025. The funding will further support the development of MTx’s pipeline by leveraging its B-cell screening platform to select best-in-class humanized antibodies in other viral infections and oncology. Erik van den Berg, CEO of Memo Therapeutics, commented: “This financing provides further external endorsement of the potential of our highly potent anti-BK virus mAb and our clinical strategy to bring it to patients as quickly as possible. There are more than 100,000 kidney transplants worldwide each year and 20,000 of these are at risk from developing BK virus associated nephropathy. With no disease modifying therapies available, there is an urgent need for a treatment. With FDA fast track status already obtained for the product, we look forward to rapidly progressing the development of AntiBKV.” New investors Ysios Capital and Kurma Partners participated in the extension round, joining existing Series C round investors including Pureos Bioventures, Swisscanto, Vesalius Biocapital, Adjuvant Capital, Verve Ventures, Schroders Capital, GF Group, Fresenius Medical Care Ventures and Red Alpine. Thomas Harth, Principal at Ysios Capital stated: “We believe Memo Therapeutics has developed a very powerful antibody that can address the growing concern of BKV infections in kidney transplant recipients. By being able to preserve the kidney and ensure graft outcome, this antibody could offer a tremendous benefit to patients. Deriving antibodies in screening of the B-cell repertoire offers a route to best-in-class antibody medicines for multiple diseases. We believe MTx has one of the best engines to do so within the industry. We are encouraged to support MTx in its mission to address the unmet medical need of BK viremia and beyond. MTx fits strongly with the investment strategy at Ysios to support breakthrough medicines.” Hadrien Bouchez, Partner at Kurma Partners added: “MTx has an exceptional leadership team with a proven track record of success. We are very excited to support the development of AntiBKV, an agent which has a unique efficacy and safety profile. Our investment underscores our commitment to supporting companies that are poised to make a significant impact on global healthcare.” Thomas Harth, Principal at Ysios Capital and Hadrien Bouchez, Partner at Kurma Partners will join the Memo Therapeutics Board of Directors. Alongside AntiBKV, Memo Therapeutics is developing a panel of pre-clinical assets in cancer and viral infections. These are based on the ability of MTx’s antibody discovery platform DROPZYLLA®, to interrogate the antibodyomes of elite controllers of infection and cancer. -Ends- Contacts Memo Therapeutics AG info@memo-therapeutics.com ICR ConsiliumAmber Fennell, Ashley Tappmemotx@consilium-comms.com+44 (0)20 3709 5700 About Memo Therapeutics AGMemo Therapeutics AG (“MTx”) is a late-stage biotech company developing best-in-class therapeutic antibodies to transform the lives of patients with viral infections and cancer. MTx’s lead program, AntiBKV, is a highly effective and safe neutralizing antibody to treat BK virus infection in kidney transplant recipients. This infection can lead to nephropathy, loss of kidney function, as well as organ failure and rejection. MTx’s pipeline consists of additional candidate therapeutic antibodies focusing on infectious diseases, such as cytomegalovirus (“CMV”), immuno-oncology targets alone and in partnership with Ono Pharmaceutical. MTx is a private company located in Schlieren / Zurich, Switzerland. About BK VirusBKV infection occurs mostly in childhood and remains dormant in healthy individuals. However, BKV infection poses a significant threat following kidney transplantation, with serious adverse effects on graft function, kidney failure and ultimately patient survival. Due to the immunosuppressive drug regimen transplant patients receive, reactivation of BKV is triggered in approx. 40% of kidney transplant recipients, with 20% experiencing systemic virologically exposure. Up to 10% then progress to BKV associated nephropathy, which is the leading cause of graft loss. There is currently no disease modifying therapy available to treat BKV infection; it can only be addressed by lowering immunosuppression. However, this significantly increases the risk of a graft rejection reaction, also leading to impaired functionality and longevity, or graft failure. About Ysios Capital Ysios Capital is a leading Spanish venture capital firm that provides private equity financing to early- and mid-stage, highly innovative life science companies bringing life-changing treatments to patients, with a focus on indications with high unmet need. They have a diverse international team in San Sebastián and Barcelona, driven by science, with the ambition to transform capital into medical breakthroughs. Ysios Capital was founded in 2008 and has over $450 million in assets under management through its three funds. About Kurma Partners Kurma Partners is a key European player in the financing of innovation in Healthcare and Biotechnology, from pre-seed to growth capital, in particular through its funds Kurma Biofund I, II, III, IV, Kurma Growth, Kurma Diagnostics and Kurma Diagnostics 2, as well as the links the company has forged with a network of prestigious research institutes and hospitals. Kurma Partners was founded in July 2009 and is based in Paris and in Munich.

Posoleucel demonstrated clinically meaningful reductions in BK viral load as compared to placebo with the greatest antiviral activity seen among patients with higher viral loads and those who received more frequent posoleucel dosing At Week 24, the percentage of patients with a ≥1-log viral load reduction in the biweekly dosing group was 50% (10/20) vs. 28% (5/18) in the monthly dosing group and 14% (2/14) in the placebo group In the high viral load stratum (≥10,000 copies/mL), 69% (11/16) of patients who received posoleucel overall and 75% (6/8) of patients in the biweekly dosing group, achieved a ≥1-log viral load reduction vs. 25% (1/4) of patients in the placebo group Biomarker data demonstrate that BK viral load reductions coincided with substantial expansion of functional BK-directed T cells specific for both posoleucel-targeted and non-targeted antigens – indicating both direct and bystander T cell benefit not observed in placebo patients Repeat administration of posoleucel was generally well tolerated, with balanced safety across posoleucel dosing groups and placebo WALTHAM, Mass.--(BUSINESS WIRE)-- AlloVir, Inc. (Nasdaq: ALVR), a late-clinical stage allogeneic T cell immunotherapy company, today announced the presentation of final results from a Phase 2 study of posoleucel, an investigational, allogeneic, off-the-shelf, multi-virus-specific T cell (VST) therapy, being studied for the treatment of BK viremia in adult kidney transplant recipients. The findings, presented yesterday at the American Transplant Congress (ATC 2023) in San Diego, CA, during a late-breaking oral abstract session (LB001), support the safety and antiviral activity of posoleucel in adult kidney transplant recipients with BK virus (BKV) infection. Currently, there are no effective treatment options for BKV infection. Top line data were shared earlier this year. "Our virus-specific T cell therapies have the potential to offer new hope to immunocompromised patients by preventing or treating devastating viral infections such as that caused by BKV," said Diana Brainard, M.D., CEO, AlloVir. "The Phase 2 data presented at ATC continue to support the potential benefits of posoleucel use across transplant indications. The patients treated with posoleucel had greater increases in BKV-specific T cells as compared to placebo patients, and these cells persisted through week 24 post-dose, which reinforces posoleucel's mechanism of action. Additionally, in posoleucel-infused patients we see bystander benefit with endogenous BKV-specific T cell activation, increasing the likelihood of durable benefit. As we continue enrollment in three Phase 3 clinical studies exploring the potential of posoleucel to prevent or treat infections in allo-HCT patients, we are also consulting with key opinion leaders and preparing to meet with the FDA to gain alignment on a Phase 3 clinical study design to evaluate posoleucel’s treatment of BKV infection in kidney transplant patients." BKV infection poses a significant threat to kidney graft survival. Over 90,000 kidney transplants are currently performed each year globallyi, and the virus reactivates in up to 20% of these patients.ii In patients who have reactivated BKV, a substantial portion will develop high-level viremia. Approximately half of those will develop BKV-associated nephropathy (BKVAN)iii, which can lead to decreased kidney survival and a return to end-stage renal disease and dialysis. About the Phase 2 Study The Phase 2 study evaluated the safety and efficacy of posoleucel to treat BKV infection in adult kidney transplant recipients with plasma BK viral load between 350-10,000,000 copies/mL (stratified by low (<10,000 copies/mL) or high (≥10,000 copies/mL) viral load at study screening). Consensus groups, including the American Society of Nephrology and the American Society of Transplantation, consider BK viral load of greater than or equal to 10,000 copies/mL to be presumptive BKVAN. The primary endpoint of the study was the safety and tolerability of posoleucel versus placebo, and the secondary endpoint of the study was the change in BK viral load in patients receiving posoleucel versus those receiving placebo. Top line results from this study were shared earlier this year. About BK Viremia in Kidney Transplant Recipients Due to the long-term immunosuppression required to prevent graft rejection, solid organ transplant recipients are at high risk for reactivating common viruses that are typically controlled by the body's natural immune system. Uncontrolled, these viruses can have devastating consequences. There are no approved or effective antiviral treatments for BKV infection. The only approach to managing BKV infection is a reduction in immunosuppression to allow the body's immune system to fight the virus; this is typically triggered by a plasma BK viral load that nears or exceeds 10,000 copies/mL. However, this reduction in immunosuppression can also lead to graft rejection, mediated by alloreactive T cells, and the development of donor-specific antibodies, putting the success of the kidney transplant at risk. BK virus-specific T cells appear to play a key role in protection against disease. Kidney transplant recipients who do not develop BKVAN have been shown to have approximately 10-fold higher BKV-specific T cell responses versus those with BKVAN. Kidney transplant recipients with BK viremia who develop robust BKV-specific T cell responses have also been shown to clear the virus, while those who progressed to BKVAN required interventions such as a reduction in immunosuppression. These data suggest that VST therapy may help manage BKV infection and BKVAN. About Posoleucel AlloVir's lead product, posoleucel, is in late-stage clinical development as an allogeneic, off-the-shelf, multi-virus-specific T cell therapy targeting six viral pathogens in immunocompromised individuals: adenovirus (AdV), BKV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and JC virus (JCV). In a Phase 2 open-label study of posoleucel for the prevention of clinically significant infections due to the six viruses posoleucel targets, 88% of allo-HCT patients who received posoleucel remained free of clinically significant infections through week 14, the primary endpoint. Moreover, the non-relapse mortality rate in patients who received posoleucel was 0% through the 52-week follow-up visit. Additionally, in the positive Phase 2 proof-of-concept CHARMS treatment study which enrolled allo-HCT recipients infected by one or more of the six viruses posoleucel targets, more than 90% of patients who failed conventional treatment and received posoleucel demonstrated a complete or partial clinical response based on predefined criteria. Based on the strength of the posoleucel Phase 2 data for both prevention and treatment, the FDA has granted posoleucel Regenerative Medicine Advanced Therapy (RMAT) designation for each of the three indications being evaluated in Phase 3 clinical trials – for the treatment of hemorrhagic cystitis (HC) caused by BKV, for the treatment of AdV infection in adults and children following allo-HCT, and for the prevention of clinically significant infections and disease caused by posoleucel's six target viruses. The FDA also granted posoleucel Orphan Drug Designation for the treatment of virus-associated HC. The European Medicines Agency (EMA) has granted posoleucel PRIority MEdicines (PRIME) designation for the treatment of serious infections with AdV, BKV, CMV, EBV and HHV-6, and Orphan Medicinal Product designation as a potential treatment of viral diseases and infections in patients undergoing HCT. About AlloVir AlloVir is a leading late-clinical stage, cell therapy company with a focus on restoring natural immunity against life-threatening viral diseases in pediatric and adult patients with weakened immune systems. The company's innovative and proprietary technology platforms leverage off-the-shelf, allogeneic, single- and multi-virus-specific T cells for patients with T cell deficiencies who are at risk from the life-threatening consequences of viral diseases. AlloVir's technology and manufacturing process enable the potential for the treatment and prevention of a spectrum of devastating viruses with each single allogeneic cell therapy. The company is advancing multiple mid- and late-stage clinical trials across its product portfolio. For more information, visit or follow us on Twitter or LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the potential of posoleucel as a treatment of BKV in kidney transplant recipients, the safety and antiviral activity of posoleucel in adult kidney transplant recipients with BK infection, AlloVir's development and regulatory status of our product candidates, the planned conduct of its preclinical studies, and clinical trials and its prospects for success in those studies and trials, and its strategy, business plans and focus. The words "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to the safety and efficacy of posoleucel as a treatment of BKV in kidney transplant patients, AlloVir's financial results, the timing for the initiation and successful completion of AlloVir's clinical trials of its product candidates, whether and when, if at all, AlloVir's product candidates will receive approval from the U.S. Food and Drug Administration (FDA), or other foreign regulatory authorities, competition from other biopharmaceutical companies, supply chain, and business operations and other risks identified in AlloVir's SEC filings. AlloVir cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. AlloVir disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions, or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent AlloVir's views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. i Kidney transplants worldwide by region 2021 | Statista ii Gras J, Le Flécher A, Dupont A, et al. Characteristics, risk factors and outcome of BKV nephropathy in kidney transplant recipients: a case-control study. BMC Infect Dis. 2023;23:74. iii Hirsch HH, Randhawa PS. BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33:e13528.