New Data Analyses from Phase 3 Study of Investigational Gene Therapy Nadofaragene Firadenovec Presented at Society of Urologic Oncology Annual Meeting

Adds More Evidence to Data Published in Lancet Oncology

CAMBRIDGE, Mass. December 2, 2020 – FerGene Inc. today announced new data analyses results from the landmark Phase 3 clinical trial evaluating nadofaragene firadenovec (rAd-IFN/Syn3) for the treatment of patients with high-grade, Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC). In the study, published in The Lancet Oncology on November 27, patients received nadofaragene firadenovec, an intravesical therapy given once every three months that is believed to target the patient’s own bladder wall cells to enhance the body’s natural defenses to fight cancer.1 The three new analyses from the pivotal study presented during the Society of Urologic Oncology (SUO) 21st Annual Meeting provide more evidence that nadofaragene firadenovec is a promising option for patients where BCG has failed.

The incidence and time to cystectomy was a key secondary objective of the Phase 3 study. A total of 40 (26.5%) patients underwent cystectomy, including 30 (29.1%) in the CIS +Ta/T1 cohort with median time to cystectomy being 8.87 months, and 10 (20.8%) in the HG Ta/T1 cohort with median time to cystectomy being 8.31 months. Patients who achieved complete response (CR) had significantly longer median time to cystectomy compared to those who did not (p=0.0432; 11.35 vs. 6.36 months, respectively. The estimated cystectomy-free survival among all treated patients was 64.5% at 24 months and was similar between the cohorts.2

The most common adverse events (AEs) observed in the Phase 3 study that occurred in patients in order of decreasing frequency were: instillation site discharge, fatigue, bladder spasm, micturition urgency, and hematuria. The discontinuation rate due to AEs was 1.9%.1

“This data further reinforces the potential of nadofaragene firadenovec to help with the lack of treatment options available to high-grade NMIBC patients after BCG stops working for them,” said Robert Svatek, M.D., M.S.C.I., Professor and Chair, Department of Urology, UT Health, San Antonio, TX and nadofaragene firadenovec study investigator. If approved, nadoferegene firadenovec will be used by urologists in their offices giving us a new tool for the management of our patients.”

Patient Characteristics or Prior Treatment History Do Not Influence Response

The post hoc subgroup analysis of the Phase 3 study in high-grade, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) were based on the efficacy population of 151 patients. There were no significant differences in response rate at 3 and 15 months between males and females, age groups, BCG-refractory vs. BCG-relapsed, <3 or >3 prior course of BCG. There were also not significant differences between the subgroups in duration of response, except in the CIS+Ta/T1 cohort, where patients had received <3 prior courses of BCG had significantly longer duration of response compared to patients who received >3 courses (12.68 vs 4.96 months; p=0.0172).3

Significant Anti-Adenovirus Antibody Response Does Not Appear to Affect Patient Outcomes

Of the 151 patients included in the analysis for this secondary objective,129 had anti-adenoviral antibody titer results and were included in this analysis. Among the 55 patients who achieved CR in the CIS+Ta/T1cohort, significantly more patients had positive post-baseline immunogenic response (43 vs. 8; p=0.0033). Similar results were found in the high-grade Ta/T1 cohort where among the 34 patients who remained free of high-grade recurrence at 3 months, significantly more patients had positive post-baseline immunogenic response (30 vs. 4; p=0.0003). At 15 months, the same trends were noted although the differences were not significant.4

“The research suggests that nadofaragene firadenovec may answer the need for additional targeted treatments that reduce the rate of bladder cancer recurrence and progression in patients where BCG has failed,” said Vikram Narayan, M.D., Assistant Professor of Urology, Emory University School of Medicine and Director of Urologic Oncology, Grady Memorial Hospital, Atlanta, GA and nadofaragene firadenovec study investigator.

In addition to these studies, a poster titled “Bladder Tumor Metabolic Alterations in Response to IFNA Gene Therapy Predict Clinical Disease Response and Identify Clinically Targetable Tumor Escape Pathways,” will be presented on nadofaragene firadenovec.5

About Non-Muscle Invasive Bladder Cancer (NMIBC)

NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.6 It is estimated that there will be approximately 81,000 new cases of bladder cancer in the U.S. in 20207; 75% of these cases present as NMIBC.8 In patients with high-grade NMIBC, intravesical BCG is the recommended treatment; however, up to 50% of high-grade patients will experience disease recurrence within one year.6,9 The outcome for BCG-unresponsive patients is poor, with chemotherapy and radiation or total cystectomy (complete removal of the bladder) often being the recommended next treatment options.10

About the Phase 3 Study

The Phase 3 study of nadofaragene firadenovec in 157 patients from 33 U.S. sites met its primary endpoint with more than half (53.4%) of CIS ± Ta/T1 patients (carcinoma in situ; with or without concomitant high-grade Ta or T1 disease) achieving a complete response (CR), all by three months.
Of the patients who achieved a CR, 45.5% continued to remain free of high-grade recurrence at
12 months. In the study, nadofaragene firadenovec was administered directly into the patient’s bladder once every three months by a healthcare professional. The long-term follow-up phase of the four-year study is ongoing, and patients are continuing to be monitored.1

“This additional evidence supports what we believe to be a positive benefit/risk profile of nadofaragene firadenovec in treating BCG-unresponsive NMIBC,” said Vijay Kasturi, M.D., Vice President of Medical Affairs at FerGene Inc. “In collaboration with the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC) we are pleased to advance the science that shows this novel gene therapy may fulfill a significant unmet medical need and has the potential to change the treatment paradigm for these patients.”

A Biologics License Application (BLA) for nadofaragene firadenovec is currently with the U.S. Food and Drug Administration (FDA).

About Nadofaragene Firadenovec

Nadofaragene firadenovec (rAd-IFN/Syn3) is an investigational gene therapy being developed as a treatment for patients with high-grade, BCG-unresponsive NMIBC. It is a non-replicating adenovirus vector-based gene therapy containing the gene interferon alfa-2b, administered by catheter into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene to do its work. The internal gene/DNA machinery of the cells ‘picks up’ the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient’s own bladder wall cells into interferon microfactories, enhancing the body’s natural defenses against the cancer. Nadofaragene firadenovec has been studied in a clinical trial program that includes 221 patients with high-grade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment.

About the SUO-CTC

Created, owned and operated by its members, the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC) is a clinical research investigator network of over 500 members from more than 200 clinical sites in the U.S. and Canada. This national alliance of leading academic and community based uro-oncologists is committed to furthering urology research. The SUO-CTC is a registered 501c3 not-for-profit corporation and has a cooperative relationship with the Society of Urologic Oncology (SUO).The SUO-CTC pursues clinical trials, in concert with sponsors, to investigate therapeutic interventions which address urological cancers including, but not restricted to: Bladder Cancer, Prostate Cancer and Renal Cancer. Together with industry, the SUO-CTC offers enhanced research options for ultimately delivering better quality of life to our patients.

About FerGene Inc.

FerGene Inc. is a gene therapy company committed to revolutionizing the treatment of bladder cancer through its innovative science and unparalleled commitment to patient care. Founded in 2019, through a collaboration between Blackstone Life Sciences and Ferring Pharmaceuticals, FerGene Inc. is singularly focused on evolving the bladder cancer treatment landscape through its novel approach to gene therapy. A trusted partner to medical and advocacy communities, FerGene Inc. is dedicated to bringing new hope to a patient population which has seen little improvement in their standard of care over the past twenty years. For more information, please visit www.FerGene.com or engage with us on Twitter at @FerGeneBio or on LinkedIn.

Media Contact:

Communications@FerGene.com

© 2020 FerGene Inc. 20/11 US-ADST-2000117

References

  1. Boorjian, S., Alemozaffar, M., Konety, B., Shore, N., Gomella, L., Kamat, A. et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2020;2045(20)30540. doi:101016/ S1470.
  2. Narayan, V. Low Rate of Cystectomy and Delayed Median Time to Cystectomy Among Patients Who Achieved Complete Response with Nadofaragene Firadenovec. Society of Urologic Oncology 21st Annual Meeting. Poster #38.
  3. Narayan, V. Subgroup Analyses of the Phase 3 Study of Intravesical Nadofaragene Firadenovec in Patients with High-Grade, BCG-Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). Society of Urologic Oncology 21st Annual Meeting. Poster #23.
  4. Narayan, V. Significant Anti-Adenovirus Antibody Response Positively Correlates with Efficacy in Patients Treated with Nadofaragene Firadenovec for High-Grade BCG-Unresponsive NMIBC. Society of Urologic Oncology 21st Annual Meeting.
  5. Miest, T. Bladder Tumor Metabolic Alterations in Response to IFNα Gene Therapy Predict Clinical Disease Response and Identify Clinically Targetable Tumor Escape Pathways. Society of Urologic Oncology 21st Annual Meeting. Poster #39.
  6. Sanli, O., Dobruch, J. Knowles, M. et al. Bladder cancer. Nat Rev Dis Primers. 3,17022 (2017) doi:10.1038/nrdp.2017.22.
  7. American Cancer Society. Key Statistics for Bladder Cancer. https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html. Updated 2020. Accessed March 5, 2020.
  8. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur urol. 2013;63(2):234-41. 10.1016./j.eururo.2012.07.033.
  9. Kamat AM, Li R, O’Donnell MA, et al. Predicting response to intravesical Bacillus Calmette-Guérin immunotherapy: Are we there yet? A systemic review. Eur Urol. 2018;73(5):738-748. Doi:10.1016/j.eururo. 2017.10.003.
  10. Marqueen K, et al. Identifying high surgical risk in muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC). JNCI Cancer Spectrum. 2018 Oct; 2(4):pky075.