On April 7, 2024 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported real-world evidence of the evolving epidermal growth factor receptor (EGFR) mutation landscape in non-small cell lung cancer (NSCLC), and the potential of BDTX-1535 to address a broader range of mutations compared to existing therapies (Press release, Black Diamond Therapeutics, APR 7, 2024, View Source [SID1234641842]). The results were disclosed in an oral presentation on April 7, 2024, at the 2024 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held in San Diego, California.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The oral presentation, titled "BDTX-1535 – A MasterKey EGFR Inhibitor Targeting Classical, Non-Classical and the C797S Resistance Mutation to Address the Evolved Landscape of EGFR Mutant NSCLC," evaluated more than 235,000 sequenced cases of NSCLC sourced from Guardant Health (GuardantINFORM) and Foundation Medicine (FoundationInsights). The analyses reveal a broad spectrum of non-classical mutations, as well as an increased prevalence of the acquired resistance mutation, C797S. Over 100 unique non-classical EGFR oncogenic driver mutations were identified in newly diagnosed patients with NSCLC, and these non-classical EGFR mutations were present in 20-30% of patients across all lines of treatment.

"The landscape of EGFR mutations in NSCLC continues to evolve, revealing classical and non-classical driver mutations," said John Heymach, M.D., Ph.D., Chair of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center. "Non-classical mutations fall into categories including kinase domain PACC mutations and ectodomain mutations; therefore, next generation EGFR targeted therapies must effectively cover multiple subgroups of mutations."

"Novel targeted therapies are still needed to continue to improve clinical outcomes for patients with EGFR-mutant lung cancers," added Xiuning Le, M.D., Ph.D., Associate Professor, Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center. "To extend survival for our patients, newer drugs need to have good mutational coverage, good tolerability, and good brain penetrance."

Preclinical data demonstrated that BDTX-1535 potently inhibits more than 50 clinically relevant, non-classical EGFR mutations (as well as the classical L858R and exon19-del mutations) while sparing wild-type EGFR. The compound also potently inhibits the drug resistance C797S mutation, which emerges following treatment with third-generation EGFR inhibitors, including osimertinib. Real-world data indicate non-classical EGFR mutations can be co-expressed with classical mutation L858R, a setting that has been characterized by shorter duration of response to osimertinib first-line therapy. Preclinical data show that BDTX-1535 potently inhibits these co-expressed non-classical mutations.

"BDTX-1535 was designed to address a broad spectrum of more than 50 non-classical oncogenic EGFR mutations, as well as the C797S resistance mutation," said Elizabeth Buck, Ph.D., Chief Scientific Officer and co-founder of Black Diamond Therapeutics. "We believe that the potency of BDTX-1535 against the full spectrum of classical, non-classical, and C797S mutations positions the compound as the first and best-in-class fourth-generation EGFR inhibitor potentially offering NSCLC patients a well-tolerated, brain-penetrant, oral therapy across various lines of treatment."

Phase 1 proof-of-concept data demonstrating durable responses in recurrent NSCLC patients with both non-classical and acquired resistance C797S mutations were presented in October 2023. Black Diamond is currently advancing BDTX-1535 in a Phase 2 trial for patients with EGFRm NSCLC across multiple lines of therapy. Patients are being enrolled both in a first-line (1L) setting (for those expressing EGFR non-classical mutations) and in second- and third-line (2L/3L) settings following prior treatment with an EGFR inhibitor. Initial results from 2L/3L patients are anticipated in the third quarter of 2024.

About BDTX-1535
BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), including classical driver mutations, non-classical driver mutations, and the acquired resistance C797S mutation. BDTX-1535 is a fourth-generation tyrosine kinase inhibitor (TKI) that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. A "window of opportunity" trial of BDTX-1535 in patients with GBM is ongoing (NCT06072586) and a Phase 2 trial is ongoing in patients with NSCLC (NCT05256290).

On April 7, 2024 Ribometrix, a biotechnology company developing small molecule therapeutics that modulate RNA biology, reported the full data from two posters highlighting advancements across two distinct modalities presented at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held April 5-10 in San Diego, CA (Press release, Ribometrix, APR 7, 2024, View Source [SID1234641840]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The posters include the company’s first public disclosure of data validating its RNA-targeting platform for designing small molecules to bind directly to RNA; the ability of these small molecules to selectively bind mRNA encoding the important cancer driver c-MYC and reduce c-MYC protein expression; and data supporting the multi-tumor therapeutic potential of the company’s program targeting the RNA-binding protein eukaryotic translation initiation factor 4E (eIF4E).

Ribometrix’s RNA-targeting platform identifies small molecules that bind oncogene mRNA; proof-of-concept delivered via c-MYC program

These data support Ribometrix’s world-leading expertise in RNA structural analysis which informs its identification of novel small molecule binders of RNA intended to disrupt downstream protein translation.

The data in the first poster demonstrate how Ribometrix:

Identified druggable RNA structure motifs and used them to screen for RNA binders with properties comparable to approved protein-targeting drugs, suggesting the ability to leverage established small molecule development processes in future development.
Generated RNA-targeting compounds that directly engage c-MYC mRNA.
Selectively reduced c-MYC protein and downstream effectors in a c-MYC expressing cell line.
"For the first time, we are sharing data demonstrating our ability to directly target RNA with a small molecule and deliver a concomitant reduction in associated protein and downstream targets, the longtime scientific goal of our field," said Michael Solomon, Ph.D., Chief Executive Officer of Ribometrix. "Our ability to bind c-MYC mRNA and show functional consequence validates our platform and demonstrates the potential to use this approach to address other high-value targets that are currently intractable to traditional small molecule approaches."

Novel eIF4E inhibitors potently and selectively suppress tumor growth

These preclinical data are the most advanced-to-date demonstration that inhibiting RNA-binding protein (RBP) eIF4E can serve as a potential anti-cancer therapy. These data build on presentations at last year’s Society for Melanoma Research and San Antonio Breast Cancer Symposium. eIF4E is a main regulator and rate limiting factor for protein synthesis and is elevated in many kinds of tumors. These attributes make it a promising target for multiple hard-to-treat cancers as both an effector of several targeted therapy pathways and a key part of many resistance mechanisms. These roles create opportunities for combining eIF4E inhibition with standard-of-care (SOC) to improve efficacy and duration of response in treatment naive patients as well as restoring sensitivity to patients with resistance.

The data in the second poster demonstrate how Ribometrix:

Synergistically enhanced in vivo anti-tumor efficacy of SOC though combination with its eIF4E inhibitor across many tumor types including non-small cell lung cancer, breast cancer, and melanoma.
Caused tumor regression in mouse models of aggressive melanoma, ER+ breast cancer and non-small cell lung cancers through combination treatment with SOC.
Restored sensitivity to SOC in multiple resistant cell lines in vitro through combination with its eIF4E inhibitor, providing a potential mechanism for re-sensitizing resistant patient populations to initial lines of treatment.
"The ability to target RNA-binding proteins that regulate oncogenes is a powerful modality with the potential to address cancer indications with high unmet need. Our eIF4E inhibitor has demonstrated broad applicability to amplify the benefit of current therapies through enhancing the anti-tumor effects or reversing resistance," said Jessica Sorrentino, Ph.D., SVP of Translational Medicine. "We are making excellent progress towards our goal of filing an IND in the first half of 2025. Together with our c-MYC data, we are demonstrating multiple unique and innovative strategies that leverage our deep RNA expertise to tackle currently intractable targets with new RNA-directed modalities."

The posters are available to view on the "Publications" page of Ribometrix’s website.

About eIF4E

Eukaryotic translation initiation factor 4E (eIF4E) is a crucial regulatory component of mRNA translation and well-documented driver of oncogenesis. Clinically, eIF4E activity is elevated in many tumor indications and it is typically associated with poor prognosis. Targeting eIF4E has the potential to enhance anti-cancer activity when given in combination with standard-of-care. Additionally, eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Based on substantial external and in-house data, Ribometrix is developing eIF4E inhibitors as a promising combination therapy approach and treatment for treatment-resistant tumors.

About c-MYC

c-MYC is a well-validated oncogene with broad anti-cancer potential, as c-MYC expression is dysregulated in more than 70% of cancers and a key regulator in nearly every aspect of the oncogenic process. c-MYC has remained intractable to traditional small molecule drug discovery, primarily due to its lack of a defined small molecule binding pocket. By targeting the c-MYC mRNA with small molecules, Ribometrix is bypassing the "undruggable" challenges to successfully reduce c-MYC protein levels and develop a novel anti-cancer therapeutic for c-MYC-driven cancers.

On April 7, 2024 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel portfolio of oncolytic immunotherapies, reported the presentation of interim results from ARTACUS, a Phase 1/2 clinical trial evaluating RP1 monotherapy for the treatment of skin cancers in patients who have had solid organ or hematopoietic cell transplants, by Michael R. Midgen, M.D., of the University of Texas MD Anderson Cancer Center during an oral session at the AACR (Free AACR Whitepaper) 2024 Annual Meeting in San Diego (Press release, Replimune, APR 7, 2024, View Source [SID1234641839]). The results were initially presented late last year at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the study, treatment with RP1 as monotherapy, for up to 25 doses, resulted in an overall response rate (ORR) of 34.8 percent (8 of 23 evaluable patients, including 5 complete responses and 3 partial responses) with most responses ongoing as of the data cutoff date of September 18, 2023. In the evaluable patient population (n=23), 20 had cutaneous squamous cell carcinoma (CSCC) and three had merkel cell carcinoma. Of note, a patient treated with RP1 for CSCC also had a complete response of a new primary basal cell carcinoma which appeared post baseline. There was no evidence of allograft rejection including of hepatic and lung allografts. RP1 monotherapy was well tolerated, and the safety profile was similar to the profile in non-immunocompromised patients with advanced skin cancers. Additional biomarker data collected showed an increase in CD+8 T, a type of immune cell, and an increase in the expression of PD-L1, after treatment suggesting immune activation. The slides are available on the Replimune website under presentations.

"Organ transplant recipients are at a higher risk for skin cancer when compared to the broader population and have access to a limited number of treatment options given that systemic immunotherapy is typically contra-indicated," said Sushil Patel, Ph.D., CEO of Replimune. "These data show RP1 as monotherapy has clear anti-tumor activity and may be a safe and effective treatment option for these patients with an overall response rate of nearly 35 percent with good durability of benefit to date."

About ARTACUS
ARTACUS is a multicenter, open-label, two-part Phase 1b/2 study evaluating RP1 as monotherapy for the treatment of locally advanced or metastatic cutaneous malignancies in patients who underwent a kidney, liver, heart, lung, or other solid organ transplant, or hematopoietic cell transplantation, who are on chronic immunosuppressive treatment, in whom systemic immunotherapy is typically contra-indicated. Researchers will assess the safety of RP1 and also evaluate its ability to shrink tumors. ARTACUS is currently recruiting patients. To learn more, contact [email protected] or +1-781-222-9570.

About RP1
RP1 is Replimune’s lead product candidate and is based on a proprietary new strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response.

On April 7, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported the oral plenary session presentation of positive pivotal data from the Phase 1/2 LINKER-MM1 trial of linvoseltamab in patients with relapsed/refractory (R/R) multiple myeloma (MM) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 in San Diego (Press release, Regeneron, APR 7, 2024, View Source [SID1234641838]). Linvoseltamab is an investigational bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on multiple myeloma cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The presentation of these pivotal results in an oral plenary session at AACR (Free AACR Whitepaper) recognizes the exciting potential of linvoseltamab to advance the treatment of multiple myeloma," said Sundar Jagannath, M.D., Director of the Multiple Myeloma Center of Excellence at Tisch Cancer Center at Mount Sinai in New York City and a trial investigator. "In clinical trials, linvoseltamab treatment led to responses that occurred early, were durable and deepened over time – all critical efficacy measures for this heavily pre-treated patient population. Further, among patients who had at least 24 weeks of treatment, the majority achieved a very good partial response, enabling them to transition from every two-week to every four-week dosing. This is an important accomplishment that I’ve seen firsthand in my trial patients, and I eagerly anticipate the FDA decision expected this August."

With an 11-month median duration of follow up, the linvoseltamab data among 117 patients presented at AACR (Free AACR Whitepaper) reinforce the strength of previously shared findings and included a:

71% objective response rate (ORR), with 46% of patients achieving a complete response (CR) or better and 62% achieving a very good partial response (VGPR) or better, as determined by an independent review committee.
1-month median time to response (range: <1-6 months). In responders, the median time to a VGPR or better was 3 months (range: <1-13 months) and to a CR or better was 8 months (range: 2-14 months).
Median duration of response (DoR), median progression-free survival (PFS) and median overall survival (OS) were not reached. At 12 months, the estimated probability of maintaining a response was 78%, being progression free was 69% and survival was 75%.
Among patients who had a CR or better and were minimum residual disease (MRD) evaluable, 93% (25 of 27 patients) were MRD negative at 10-5.
The trial included a response-adapted regimen that enabled linvoseltamab patients to shift to every four-week dosing if they achieved a VGPR or better and completed at least 24 weeks of therapy. In the dose expansion portion of the trial (n=105), of the patients who had at least 24 weeks of therapy at data cutoff, 90% (56 of 62) achieved a VGPR or better and were able to transition to every four-week dosing. Of the 29 patients who transitioned to the extended dosing regimen prior to achieving a CR, 48% (14 of 29) subsequently experienced a deepening of response to CR or better.

In addition, high ORRs were observed across prespecified subgroups – including high-risk and high-disease burden populations – as follows:

85% among Black or African American patients (17 of 20 patients)
71% among those aged 75 years or older (22 of 31 patients)
67% among those with high cytogenetic risk (31 of 46 patients)
62% among those with International Staging System stage III disease (13 of 21 patients)
53% among those with extramedullary plasmacytomas (10 of 19 patients)
Cytokine release syndrome (CRS) was the most commonly occurring treatment-emergent adverse event (TEAE) and was observed in 46% of patients; 35% were Grade 1, 10% were Grade 2 and one case (1%) was Grade 3. Adjudicated immune effector cell-associated neurotoxicity syndrome (ICANS) events of any grade occurred in 8% of patients, including three cases that were Grade 3 and no cases that were ≥Grade 4. Infections occurred in 73% of patients, with their frequency and severity decreasing after 6 months; 34% were Grade 3 or 4. The most common Grade 3 or 4 TEAEs (≥20%) were neutropenia (40%) and anemia (31%). Six deaths occurred on treatment or within 30 days of the last treatment dose due to TEAEs; five were due to infection, and one was due to renal failure.

Linvoseltamab has been granted Fast Track Designation and was accepted for Priority Review for the treatment of R/R MM by the FDA, with a target action date of August 22, 2024. In addition, linvoseltamab is being reviewed by the EMA. Linvoseltamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.

The Phase 3 confirmatory trial for linvoseltamab in patients with R/R MM (LINKER-MM3) is underway.

About Multiple Myeloma
As the second most common blood cancer, there are over 176,000 new cases of MM diagnosed globally, and 35,000 cases are diagnosed in the U.S. every year. In the U.S., there are approximately 8,000 people who have MM that has progressed after three lines of therapy, and 4,000 whose disease has progressed after four or more therapies. The disease is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable and while current treatments are able to slow progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.

About the Linvoseltamab Phase 1/2 Trial and Clinical Development Program
The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in 282 enrolled patients with relapsed/refractory MM. The Phase 1 dose-escalation portion of the trial – which is now complete – primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab and explored different administration regimens. The ongoing Phase 2 dose expansion portion is assessing the safety and anti-tumor activity of linvoseltamab, with the primary endpoint of ORR. Key secondary endpoints include DoR, PFS, rate of MRD negative status and OS.

Eligibility in the Phase 2 portion requires patients to have received at least three prior lines of therapy or have triple-class refractory MM. Linvoseltamab is administered with an initial step-up dosing regimen followed by the full 200 mg dose administered weekly. At week 16, all patients transition to every two-week dosing. A response-adapted regimen further enables patients to shift to every four-week dosing if they achieve a VGPR or better and have completed at least 24 weeks of therapy. The regimen requires a total of two 24-hour hospitalizations for safety monitoring.

The broader linvoseltamab clinical development program includes additional trials in earlier lines of therapy and stages of disease that are planned or underway. They include a Phase 1/2 trial in first-line MM, a Phase 2 trial in high-risk smoldering MM, and a Phase 2 trial in monoclonal gammopathy of undetermined significance. A Phase 1 trial of linvoseltamab in combination with a Regeneron CD38xCD28 costimulatory bispecific in MM is also planned. For more information, visit the Regeneron clinical trials website, or contact via [email protected] or 844-734-6643.

On April 7, 2024 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported three-year follow-up data from a Phase 1 trial with the mRNA-based individualized neoantigen-specific immunotherapy ("iNeST") candidate autogene cevumeran (also known as BNT122, RO7198457) in patients with resected pancreatic ductal adenocarcinoma ("PDAC") (Press release, BioNTech, APR 7, 2024, View Source [SID1234641837]). The data show that in 8 out of 16 patients autogene cevumeran elicited an immune response up to three years post administration measured by activated T cells. The persistence of T cels was associated with a longer median recurrence-free survival in cancer vaccine responders.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These new data are an early signal for the potential of our individualized mRNA cancer vaccine approach in this indication with an unmet medical need. The results indicate that our uridine mRNA-LPX technology can promote activation of cytotoxic T cells that may help to eliminate residual tumor foci at early stages of the disease to delay or prevent recurrence," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "Our ongoing Phase 2 trial with Genentech aims to confirm these findings on benefit for patients with PDAC compared with the current standard of care treatment in the post-surgical, adjuvant setting in a larger patient population. We remain committed to our vision of personalized cancer medicine and aim to help advance the standard of care for many patients."

The results featured in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting 2024 show the following:

In 8 of 16 patients, autogene cevumeran elicited high-magnitude T cells specific to the encoded neoantigens.
98% of the T cells targeting individual neoantigens on the tumor and induced by autogene cevumeran were de novo in that they were not detected in blood, tumors, and adjacent tissues prior to administration of the investigational treatment.
Over 80% of the vaccine-induced neoantigen-specific T cells could still be detected up to three years post administration in patients with an immune response. These patients showed a prolonged median recurrence-free survival compared to non-responders.
6 of 8 patients with an immune response to autogene cevumeran remained disease free during the three-year follow-up period, while 7 of the 8 patients without an immune response to the treatment during the trial showed tumor recurrence.
The investigator-initiated, single center Phase 1 trial (NCT04161755) evaluated the safety of autogene cevumeran in sequential combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and standard-of-care chemotherapy in 16 patients with resected PDAC. Data from the 1.5-year median follow-up were published in Nature in May 2023. The current data update includes a three-year median follow-up and was presented in a late-breaking oral presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2024 in San Diego, California, by principal investigator Vinod Balachandran, M.D., surgeon-scientist at Memorial Sloan Kettering Cancer Center and principal investigator of the study.

An ongoing open-label, multicenter, randomized Phase 2 trial (NCT05968326), sponsored by Genentech in collaboration with BioNTech, was started in October 2023. The trial will investigate the efficacy and safety of adjuvant autogene cevumeran in combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and chemotherapy compared with the current standard of care chemotherapy (mFOLFIRINOX) in patients with PDAC. The Phase 2 trial is currently enrolling patients at clinical trial sites in the United States, with additional sites planned to open globally. Autogene cevumeran is being jointly developed by BioNTech and Genentech and is currently being evaluated in three ongoing randomized Phase 2 clinical trials in adjuvant PDAC (as mentioned above), first-line melanoma, and adjuvant colorectal cancer.

About resected pancreatic ductal adenocarcinoma (PDAC)
PDAC is amongst the leading causes of cancer-related deaths in the United States4 with approximately 90% of patients dying within two years of their diagnosis5. A combination of surgical removal and systemic cytotoxic chemotherapy has shown to improve clinical outcomes; however, even with surgical resection, the relapse rate remains high, and the 5-year overall survival is only approximately 20%6 in patients who undergo surgery followed by adjuvant chemotherapy ("ACT") and only 8-10%i,ii in those who do not receive ACT. Thus, there is an unmet medical need for novel therapies for patients with resected PDAC.

About iNeST (individualized Neoantigen Specificimmuno Therapy)
iNeST immunotherapies are investigational individualized cancer therapies tailored to a specific patient’s tumor. They contain unmodified, pharmacologically optimized mRNA encoding up to 20 patient-specific neoantigens, identified using real-time next-generation sequencing and bioinformatic neoantigen discovery. Neoantigens are proteins that are produced by cancer cells that differ from the proteins produced by healthy cells and are recognized by immune cells. The mRNA is encapsulated in BioNTech’s proprietary intravenous RNA-lipoplex delivery formulation which is designed to enhance stability as well as enable targeted delivery to dendritic cells. By analyzing each patient’s tumor, BioNTech is able to identify the cancer mutations that may act as neoantigens. Each individual cancer vaccine encodes for neoantigen candidates with the highest likelihood of helping the immune system recognize the cancer. For this purpose, BioNTech has developed an on-demand manufacturing process, following Good Manufacturing Practice (GMP) conditions. Autogene cevumeran is currently being evaluated in various solid tumor indications, including three Phase 2 clinical trials in first-line melanoma, adjuvant colorectal cancer, and adjuvant pancreatic ductal adenocarcinoma.

An iNeST Fact Sheet and images from the iNeST manufacturing process are available in the newsroom section on BioNTech’s website at this link.