P4, N=25, Not yet recruiting, Ferring Pharmaceuticals

uMRD enables quantitative assessment of molecular response to drug treatment. uMRD-determined pre-treatment disease burden assessment can support stratification of control and intervention arms in future treatment trials.

P1, N=77, Terminated, Sanofi | Completed --> Terminated; Sponsor terminated the study for non-safety reasons

P3, N=475, Completed, Xiamen Amoytop Biotech Co., Ltd. | Active, not recruiting --> Completed

P1, N=77, Completed, Sanofi | Active, not recruiting --> Completed

P1/2, N=17, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed | N=34 --> 17

P=N/A, N=800, Recruiting, Ferring Pharmaceuticals | Trial completion date: Dec 2026 --> Dec 2025 | Trial primary completion date: Dec 2026 --> Dec 2025

P1/2, N=336, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting

P1/2, N=58, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting

P1, N=120, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting

P1/2, N=45, Completed, Takeda | Recruiting --> Completed | Phase classification: P1b/2 --> P1/2 | N=114 --> 45

The estimated follow-up period is 24 months, until study discontinuation, or withdrawal. Final results from this large, prospective, multi-institutional, real-world registry providing early use and outcomes of nadofaragene firadenovec are expected December 2026.

uMRD enables quantitative assessment of molecular response to drug treatment. uMRD-determined pre-treatment disease burden assessment can support stratification of control and intervention arms in future treatment trials.

Prior to ropeginterferon-alfa, the participants were managed with therapeutic phlebotomies, or cytoreduced with either hydroxyurea, pegylated interferon-alpha 2a ( Pegasys), JAK2 inhibitors, or were newly diagnosed and previously untreated. Ropeginterferon-alfa is effective in PV and ET, however, the dose that achieves CHR is highly individualized, necessitating an incremental titration approach. The patients already in CHR from prior therapy needed relatively lower doses of ropeginterferon-alfa to maintain CHR. Clinical trials are ongoing with an alternate accelerated dosing scheme and results are awaited.

Three drugs-pembrolizumab, valrubicin, and most recently, nadofaragene firadenovec-vncg-have been FDA approved for the treatment of BCG-unresponsive NMIBC in patients who are ineligible for or decline RC. Despite the challenges faced in finding effective therapies, many potential treatments are currently under investigation. Addressing the landscape of biomarkers, mechanisms of progression, BCG resistance, and trial design challenges in HR-NMIBC is essential for the discovery of new targets and the development of effective treatments.

P1, N=2, Terminated, University of Nebraska | N=30 --> 2

P1, N=132, Not yet recruiting, Bristol-Myers Squibb

P1, N=177, Recruiting, Jazz Pharmaceuticals | Not yet recruiting --> Recruiting

Here, we report the primary endpoint results of xalnesiran, a small interfering ribonucleic acid (siRNA) targeting the HBsAg coding region of the HBV genome (RO7445482, RG6346) in combination with nucleos(t)ide analogues (NUC), with or without an immunomodulator: pegylated interferon alfa-2a (Peg-IFN-α, Pegasys®), or ruzotolimod (toll-like receptor 7 agonist, RO7020531, RG7854). Xalnesiran combination therapies of 48 wks treatment duration were generally safe and well tolerated. Higher HBsAg loss rates were observed when xalnesiran was combined with an immunomodulator (PegIFN-α or ruzotolimod).

The other four patients with 2 year follow-up were treated with Gamma-Knife followed by bevacizumab (n = 1), regorafenib followed by bevacizumab (n = 1) and bevacizumab only (n = 2). These data corroborate the initial evidence on safety and tolerability of Temferon. They also suggest that Temferon has potential to counteract disease progression in patients affected by uMGMT GBM.

Intravesical nadofaragene firadenovec, administered once every three months, demonstrated a sustained durability of response in patients with BCG-unresponsive CIS±Ta/T1 papillary disease. Nadofaragene firadenovec represents a novel treatment option for BCG-unresponsive NMIBC with a favorable benefit-to-risk ratio. *All patients had passed 36 months at data cutoff on 09 September 2021.

The comparison of the overall ISGs expression at first surgery and second surgery highlighted the activation of IFN-responsive genes at second surgery suggesting the occurrence of the local delivery within the TME of biologically active IFN-a. CONCLUSION The results provide initial evidence of Temferon’s potential to modulate the TME of GBM patients.

Autologous CD34+ HSPC are mobilized with lenograstim and plerixafor, collected by apheresis, purified and ex vivo modified with a lentiviral vector. So far, up to 3 million Temferon cells/kg have been co-administered with a fixed dose of non-manipulated CD34+ supporter cells following a sub-myeloablative conditioning regimen (Thiotepa + BCNU or Busulfan or Busulfan alone)... These data show that Temferon is safe and biologically active at the tumor site and favors anti-tumor immunity. The results provide initial evidence of Temferon's potential to modulate the TME of GBM patients and to counteract disease progression and improve the survival of uMGMT GBM patients.

Follow-up analyses of the correlation of biomarkers with clinical response are in progress and will be presented. Further clinical trials are underway (iinnovate-2, NCT05556616; iinnovate-3, NCT05590377) to evaluate moda's novel immune activating mechanism in combination with standard of care anti-myeloma therapies.

P1, N=177, Not yet recruiting, Jazz Pharmaceuticals

P=N/A; Not yet recruiting --> Recruiting

Ongoing research focuses on improving patient selection, identifying biomarkers for response prediction, exploring alternative vectors for enhanced transfection efficiency, and developing combination strategies targeting resistance mechanisms. The approval of nadofaragene firadenovec marks a significant milestone in the field of gene therapy for bladder cancer, and future developments hold promise for further enhancing its efficacy and impact.

P=N/A; N=800; Not yet recruiting; Sponsor:Ferring Pharmaceuticals

P2, N=60, Completed, Australasian Leukaemia and Lymphoma Group | Recruiting --> Completed

The biological activity of the P. pastoris-produced IFNα2a was confirmed in A549 and HT29 cells by monitoring transcriptional up-regulation of a panel of known interferon-stimulated genes (ISGs). Our results document that the P. pastoris expression system is a suitable system for producing biologically functional IFNα2a in a secreted form.

P2, N=68, Recruiting, Zealand University Hospital | Not yet recruiting --> Recruiting | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Oct 2023 --> Aug 2025

P2, N=29, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: May 2023 --> May 2026

P1, N=36, Recruiting, Akamis Bio | Trial completion date: Dec 2023 --> Oct 2024 | Trial primary completion date: Aug 2023 --> Sep 2024

P1a/1b, N=30, Recruiting, Akamis Bio | Trial completion date: Dec 2022 --> Jul 2024 | Trial primary completion date: Oct 2022 --> May 2024

P3, N=1334, Completed, Children's Oncology Group | Unknown status --> Completed

P2, N=84, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> May 2023 | Trial primary completion date: Jun 2024 --> May 2023

In December 2022, nadofaragene firadenovec received its first global approval in the USA for the treatment of high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumours in adults. This article summarizes the milestones in the development of nadofaragene firadenovec leading to this first approval for this indication.

Finally, the combination of mWTX-613 treatment with various checkpoint inhibitor molecules resulted in improved anti-tumor efficacy in syngeneic models. Together, these data support the advancement of this innovative IFNα therapy into clinical testing.

Our study provides novel insights into the mechanism behind the interferon-mediated upregulation of TRAIL and its protein accumulation in cancer cells. Further investigation is required to understand the role of intracellular TRAIL or depict the mechanisms mediating its apoptosis impairment in cancer cells.

Ruxolitinib was discontinued and the patient received two cycles of RR-EPOCH, four cycles of R-COMP and lenalidomide. While this treatment resulted in complete metabolic response, the patient was deemed eligible for CAR-T cell treatment by the lymphoma-board, because of the high-risk features of this lymphoma (immunosuppression associated, high IPI score and double expressor score of 2).After bridging with polatuzumab-vedotin-bendamustin, the patient received axicabtagene ciloleucel on 22.11.2021... Therapy of JAK1/2 inhibitor associated aggressive B-Cell lymphoma is feasible and results in durable remissions with acceptable toxicity.Figure 1DateJAK2 V617F Allelic burden(Sample site: peripheral blood)17.07.20192,108%27.08.20192,038%29.10.20191,37816.10.20200,889%04.03.20210,814%23.08.20210,275%15.09.20210,528%12.01.20221,101%23.02.20220,645%Table 1

P1/2, N=27, Recruiting, Genenta Science | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2023