TPTE

Primary endpoint met in a Phase 2 trial evaluating the investigational mRNA immunotherapy BNT111 in combination with the PD-1 checkpoint inhibitor cemiplimab Data demonstrated a statistically significant improvement of overall response rate (“ORR”) compared to historical control in patients with anti-PD-(L)1 relapsed/refractory advanced melanoma BioNTech and Regeneron plan to present data from this trial at a forthcoming medical conference; the BNT111 program received a Fast Track designation and an Orphan Drug designation from the U.S. Food and Drug Administration (“FDA”) in 2021 BNT111 is based on BioNTech’s fully owned FixVac platform and proprietary uridine mRNA-LPX technology July 30, 2024 -- BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) today announced positive topline data from the ongoing Phase 2 clinical trial (EudraCT No.: 2020-002195-12; NCT04526899) in patients with unresectable stage III or IV melanoma whose disease had progressed following anti-PD-(L)1-containing treatment. The randomized trial evaluates the clinical activity and safety of the investigational mRNA cancer immunotherapy BNT111 in combination with Libtayo® (cemiplimab), an anti-PD-1 monoclonal antibody being developed by Regeneron, and assesses the two single agents alone. The trial met its primary efficacy outcome measure, demonstrating a statistically significant improvement in ORR in patients treated with BNT111 in combination with cemiplimab as compared to historical control in this indication and treatment setting. Both randomized monotherapy arms showed clinical activity. The ORR in the cemiplimab monotherapy arm was in line with the historical control of anti-PD-(L)1 or anti-CTLA-4 treatments in this patient group. The treatment was well tolerated and the safety profile of BNT111 in combination with cemiplimab in this trial was consistent with previous clinical trials assessing BNT111 in combination with anti-PD-(L)1-containing treatments. The Phase 2 trial will continue as planned to further assess the secondary endpoints, which were not mature at the time of the primary analysis. “These Phase 2 results mark a significant step towards our vision of personalized cancer medicine. We envision mRNA as a centerpiece in future treatment paradigms for cancer, helping to address unmet medical needs, such as for patients with anti-PD-(L)1 refractory or resistant melanoma,” said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. “These data are a proof of concept for us in three dimensions: First, for our decade-long improved mRNA cancer vaccine technology that uses uridine mRNA chemistry, a non-coding backbone that is engineered for optimal translational performance and our proprietary lipoplex formulation for delivery. Second, for our computational approaches for selecting suitable tumor antigens for our cancer indication-specific FixVac platform candidates. Third, for our strategy to combine synergistic modalities, in this case BNT111 with an established immune checkpoint treatment.” BioNTech and Regeneron plan to present data from this trial at a forthcoming medical conference. Further, the companies also intend to submit these data for publication in a peer reviewed scientific journal. BNT111 is based on BioNTech’s fully owned FixVac platform that utilizes a fixed combination of four mRNA-encoded, tumor-associated antigens designed to trigger an innate and tumor-antigen-specific immune response against cancer cells expressing one or more of the respective tumor antigens. In 2021, BNT111 in combination with cemiplimab received Fast Track designation by the FDA for the treatment of anti-PD-1-refractory/relapsed, unresectable Stage III or IV melanoma. In the same year, the FDA granted Orphan Drug designation for BNT111 the treatment of stage IIB through IV melanoma. BioNTech has developed a range of mRNA platforms to establish a novel class of therapeutics and vaccines aimed at improving the health of people worldwide. In oncology, BioNTech utilizes five mRNA platforms. Each platform is designed with the aim to address unique challenges in oncology. BioNTech’s fully owned FixVac (Fix Combination Vaccine) platform candidates target specific cancer indications focusing on tumor-associated antigens which are shared by many cancer patients, while iNeST (Individualized Neoantigen Specific Immunotherapy) platform candidates are personalized immunotherapies tailored to the patient’s individual tumor profile. Both platforms utilize BioNTech’s proprietary optimized uridine mRNA (“uRNA”) technology and the lipoplex (“LPX”) delivery technology that the scientific founders and the researchers at BioNTech have pioneered over decades of scientific discoveries and technological advancements. These technologies are optimized for immunotherapy applications aiming to boost the immunostimulatory effect of the investigational immunotherapies and to trigger targeted immune responses against cancer cells expressing one or more of the respective encoded tumor antigens. Currently, six programs based on the Company’s FixVac and iNeST platforms are being evaluated in randomized Phase 2 trials in various solid tumor indications. In addition to the FixVac and iNeST platforms, BioNTech is leveraging mRNA to deliver the building plan for targeted antibody, cytokine or immunomodulating protein approaches directly to the patient based on the Company’s RiboMab, RiboCytokine and Intratumoral Immunotherapy platforms aiming to help the body to produce its own therapeutic. Melanoma is amongst the leading causes of cancer-related deaths globally, responsible for roughly 58,000 deaths yearly. 1 Anti-PD-1 refractory/relapsed unresectable Stage III or IV melanoma is an aggressive form of melanoma, which remains particularly lethal. Current standard of care includes checkpoint inhibitor therapies that substantially improve the life expectancy of patients with melanoma.2,3 Despite advances in treatment, a high proportion of patients exhibit resistance to approved therapies, leading to limited options for those who progress on targeted or immunotherapy.4 The 5-year survival rate for patients with distant metastatic melanoma is approximately 35%.5 This underscores the significant unmet medical need. BNT111 is an mRNA-based off-the-shelf cancer immunotherapy candidate for intravenous administration encoding a fixed set of four non-mutated melanoma-associated antigens (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE) delivered as uridine mRNA-lipoplex formulation. Over 90% of patients with cutaneous melanomas express at least one of these antigens.6 Data of the Lipo-MERIT Phase 1 clinical trial have shown that BNT111 alone or in combination with blockade of the checkpoint inhibitor PD-1 induces novel antigen-specific anti-tumor immune responses and enhances pre-existing immune responses against the encoded melanoma-associated antigens in checkpoint inhibitor-experienced patients with unresectable melanoma.7 Further, these data have shown that the candidate can prime and activate T cells against the vaccine antigens that persisted for more than one year under continuous monthly vaccination.7 BNT111 is one of three clinical-stage FixVac product candidates within BioNTech’s development pipeline. The candidate is currently being evaluated in a Phase 2 clinical trial in combination with cemiplimab, in patients with anti-PD-1 refractory/relapsed unresectable Stage III or IV melanoma. The BNT111-01 trial (EudraCT No.: 2020-002195-12; NCT04526899) is an open-label, randomized Phase 2 trial evaluating the efficacy of BNT111 and cemiplimab and the contribution of the single components in patients with anti-PD-1/PD-L1-refractory or relapsed, unresectable Stage III or IV cutaneous melanoma. Conducted across approximately 60 sites in 7 countries, this multi-site trial aims to demonstrate anti-tumor activity and ORR of the combination therapy as well as each agent alone. Additional endpoints include duration of response (DOR), disease control rate (DCR), overall survival (OS), safety, and tolerability. Patients were randomized in a 2:1:1 ratio to Arm 1 (BNT111 + cemiplimab), Arm 2 (BNT111 monotherapy), and Arm 3 (cemiplimab monotherapy), with up to 24 months of active treatment. More information on this trial can be found at clinicaltrials.gov or www.clinicaltrialsregister.eu. Biopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (CAR) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (ADC) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Biotheus, DualityBio, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron. 1 Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. CA Cancer J Clin.2021 Feb 4. Epub ahead of print. 2 Nogrady B. Nature 580, S14-S16 (2020). Available at https://www.nature.com/articles/d41586-020-01038-9 3 Huang AC, Zappasodi R. Nat Immunol 23, 660–670 (2022). 4 Hassel JC, et al. Cancers (Basel). 2023 Jul; 15(13): 3448. 5 National Cancer Institute. Cancer Stat Facts: Melanoma of the Skin. Available from: https://seer.cancer.gov/statfacts/html/melan.html. Last accessed 15.07.2024 6 Data on file. 7 Sahin, U., Oehm, P., Derhovanessian, E. et al. Nature 585, 107–112 (2020). Available from: https://www.nature.com/articles/s41586-020-2537-9 The content above comes from the network. if any infringement, please contact us to modify.

Early signs of efficacy are positive for BioNTech’s attempts to develop a cancer vaccine. BioNTech has posted an early win for BNT111, linking a combination of the cancer immunotherapy candidate and Regeneron’s checkpoint inhibitor Libtayo to a better response rate than a historical control in melanoma patients.Investigators randomized 184 patients with anti-PD-(L)1 refractory or relapsed, unresectable advanced melanoma to one of three cohorts. Half of the subjects in the open-label phase 2 trial received BNT111 and Libtayo, Regeneron’s anti-PD-1 drug, in combination. The remaining participants were split evenly into two cohorts that each received one of the molecules as a single agent.BioNTech saw a statistically significant improvement in the overall response rate of the combination arm compared to historical control data, causing the study to hit its primary endpoint. Both monotherapy arms showed clinical activity, BioNTech said, with Libtayo performing in line with the historical control.The partners plan to discuss the data, which were free from safety shocks, with regulators as they think through their plans for further development. The combination of BNT111 and Libtayo has FDA fast-track status in the melanoma population enrolled in the study. It is unclear based on the little publicly available evidence whether the combination is a significant step forward. BioNTech and Regeneron are yet to share the response results, choosing to keep them back for an upcoming medical conference, and data on progression-free and overall survival were immature at the time of the analysis.Even so, the early signs of efficacy are positive for BioNTech’s attempts to develop a cancer vaccine. BNT111 uses a different mRNA format than BioNTech’s COVID-19 vaccine, with the biotech using uridine mRNA chemistry rather than nucleoside-modified mRNA for the cancer candidate. BioNTech designed the non-coding backbone for oncology applications.With BNT111, the biotech is using the technology to trigger T-cell responses against NY-ESO-1, MAGE-A3, tyrosinase and TPTE. More than 90% of patients with cutaneous melanomas express at least one of the antigens. By triggering responses against the antigens, BNT111 could reenergize anti-cancer attacks in patients failed by single-agent checkpoint inhibitors.That promise led BioNTech and Regeneron to team up in 2020. The partners agreed to jointly fund a phase 2 trial of BNT111 and Libtayo. Each company retained full commercial rights to its molecule. The companies expanded the relationship to cover another asset, BNT116, in 2022.