On September 12, 2022 OncXerna Therapeutics, Inc. ("OncXerna"), a precision medicine company using an innovative RNA-expression based biomarker platform to predict patient responses to its targeted oncology therapeutic candidates, reported new biomarker data suggesting the Xerna TME Panel has predictive and prognostic potential in esophagogastric adenocarcinoma (Press release, OncXerna Therapeutics, SEP 12, 2022, View Source [SID1234619399]). The data are featured in a poster being presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022.

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The data featured in the ESMO (Free ESMO Whitepaper) poster are from retrospective analyses of results from PLATFORM, a randomized Phase 2 trial that evaluated maintenance therapies such as the anti-PD-1 antibody durvalumab in esophagogastric adenocarcinoma patients treated with first-line chemotherapy. Analyses were performed using the Xerna TME Panel, a novel RNA gene expression-based diagnostic panel that uses a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME).

Using the Xerna TME Panel, researchers analyzed pre-treatment tumor biopsies to classify patients who went on to receive durvalumab maintenance therapy or active surveillance only as immune score "high" or immune score "low." These classifications were compared against clinical outcomes recorded in the trial. Results showed that immune score high patients had a poorer prognosis with active surveillance compared to immune score low patients. However, despite this poorer prognosis, immune score high patients had improved 6- and 12-month progression free survival and 24-month overall survival with durvalumab maintenance therapy compared to the immune score high patients that received active surveillance. Analyses in the poster also compared the predictive potential of Xerna TME Panel classifications in esophagogastric adenocarcinoma to that of classifications based on PD-L1 combined positive score (CPS) status.

"Though specifically tailoring therapeutic regimens for individual patients can be an effective technique in the treatment of GI cancers, its application is limited by a lack of predictive biomarkers," said Professor Ian Chau, M.D., FRCP, co-author on the poster and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Professor at the Institute of Cancer Research, London & Surrey. "Data being presented at ESMO (Free ESMO Whitepaper) suggest the Xerna TME Panel can expand the applicability of personalized medicine in esophagogastric adenocarcinoma by predicting the patients who may benefit from anti-PD-1 maintenance therapy more accurately than PD-L1 CPS status. Moreover, classifications incorporating both PD-L1 CPS status and the Xerna TME Panel appear to further distinguish the subset of patients that will derive the most durable clinical benefit from checkpoint inhibitors. Taken together, these encouraging findings support the Xerna TME Panel’s potential as a diagnostic that can help us understand which patients are more likely to benefit from treatment and those that will not. This will hopefully lead to better treatment decisions and improved clinical outcomes for patients."

Key data featured in the ESMO (Free ESMO Whitepaper) poster are summarized in Tables 1A (patients randomized to active surveillance) and 1B (patients randomized to durvalumab maintenance therapy) below.

Table 1A: Survival function estimates for patients enrolled in the active surveillance arm according to Xerna TME Panel and PD-L1 CPS status. Data presented as: rate (97.5% confidence interval)

PFS: Progression-free survival; OS: Overall survival

Additionally, in PD-L1 CPS ≥5 patients who received durvalumab, 24-month OS rates were 38% and 0% in Xerna TME Panel immune score high (n=17) and low (n=9) subgroups, respectively. Twelve-month OS rates in the same subgroups were 44% and 33%, respectively.

Laura Benjamin, Ph.D., Chief Executive Officer of OncXerna Therapeutics and co-author on the ESMO (Free ESMO Whitepaper) poster, commented, "These results add to an emerging dataset suggesting the Xerna TME Panel can improve the probability of success in clinical trials of not only our internally developed product candidates, navicixizumab and bavituximab, but in trials of a wide range of precision therapies. We are fortunate to be collaborating with leading experts from industry and academia on these efforts, including my co-authors from QIAGEN GmbH, Genialis, and The Royal Marsden. I look forward to continuing our work together as we strive to leverage the XERNA TME Panel to increase the number of cancer patients that can benefit from a precision medicine approach."

A copy of the ESMO (Free ESMO Whitepaper) poster, entitled: "Predicting benefit from maintenance durvalumab after first-line chemotherapy (1L CTx) in oesophagogastric adenocarcinoma (OGA) using a novel tumour microenvironment (TME) RNA assay," will be available on the OncXerna website following the conclusion of the ESMO (Free ESMO Whitepaper) Congress.

About PLATFORM
PLATFORM was a Phase 2, randomized, multicenter, adaptive study sponsored by The Royal Marsden NHS Foundation Trust that assessed various maintenance therapies in locally advanced or metastatic esophagogastric adenocarcinoma patients. Patients initially received standard chemotherapy according to local practice based upon their HER2 status. HER2-negative patients who completed at least six cycles of standard chemotherapy, achieved stable disease or better on the end-of-treatment CT scan, and met additional eligibility criteria were then randomized to receive active surveillance only or a selected maintenance therapy, one of which was durvalumab. Results showed durvalumab maintenance therapy did not prolong PFS or OS compared to active surveillance in HER2-negative patients unselected for PD-L1 status. For more information on the trial, see Clinicaltrials.gov Identifier: NCT02678182.

About the Xerna TME Panel
The Xerna TME Panel uses proprietary RNA-based gene expression data and a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). The Xerna TME Panel is an investigational assay that has not been approved and has not been demonstrated to be safe or effective for any use.

On September 12, 2022 NuCana plc (NASDAQ: NCNA) reported that data from the ongoing NuTide:302 study of NUC-3373 in combination with other agents at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting being held from September 9 to 13, 2022 (Press release, Nucana BioPharmaceuticals, SEP 12, 2022, View Source [SID1234619398]).

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Poster 345P: NUC-3373, a ProTide transformation of 5-FU, in combination with oxaliplatin (NUFOX) or irinotecan (NUFIRI) in patients with advanced colorectal cancer (NuTide:302)

NUC-3373, a phosphoramidate transformation of 5-FU, that was designed to overcome the key limitations and challenges associated with 5-FU has previously demonstrated promising anti-tumor activity and a favorable safety and pharmacokinetic profile as a single agent and in combination with leucovorin in heavily pre-treated patients with advanced colorectal cancer (CRC). Data presented at ESMO (Free ESMO Whitepaper) describe NUC-3373 plus leucovorin in combination with either oxaliplatin (NUFOX) or irinotecan (NUFIRI) in the dose-finding part of the study.

Both NUFOX and NUFIRI demonstrated encouraging anti-tumor activity in heavily pre-treated CRC patients with progressive disease who had all previously received regimens containing 5-FU, oxaliplatin and irinotecan. Of the 46 patients who received either NUFOX or NUFIRI, twelve (six from each cohort) achieved progression-free survival (PFS) of greater than three months, including three patients who achieved PFS of six months or longer. The disease control rates for the NUFOX and NUFIRI regimens were 80% and 55%, respectively. Data presented also indicate that NUFOX and NUFIRI have favorable safety profiles when compared to historical data for the 5-FU-containing regimens FOLFOX and FOLFIRI, with lower rates of toxicities such as neutropenia and gastrointestinal disturbances that limit their clinical utility. With these data, NuCana has established the recommended Phase 2 dose for NUC-3373 as part of NUFOX and NUFIRI regimens.

Andrew Coveler, Associate Professor, Medical Oncology at the University of Washington School of Medicine, Associate Professor, Clinical Research Division at the Fred Hutchinson Cancer Center, and lead author of the ESMO (Free ESMO Whitepaper) presentation said: "I am excited by the results of the NuTide:302 study in light of the heavily pre-treated nature of these patients. It is noteworthy to observe a high disease control rate and extended periods of progression-free survival in patients who had previously been treated with multiple lines of therapy that included oxaliplatin and irinotecan with 5-FU. There is a significant unmet need for new medicines to treat patients with colorectal cancer and I look forward to continuing the investigation of NUFIRI and NUFOX in combination with bevacizumab in earlier-line CRC patients."

"These data are highly supportive of our strategy to develop NUC-3373 as a replacement for 5-FU, one of the most widely used medicines for the treatment of patients with cancer," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "Based on the data from NuTide:302, we have initiated a randomized study in second-line CRC patients called NuTide:323 comparing NUFIRI plus bevacizumab to FOLFIRI plus bevacizumab, the global standard of care. Due to NUC-3373’s compelling biological rationale and strong clinical potential, we have also initiated the NuTide:303 study, investigating NUC-3373 in combination with either pembrolizumab in patients with various solid tumors or in combination with docetaxel in patients with non-small cell lung cancer."

About NUC-3373
NUC-3373 is a phosphoramidate transformation of 5-fluorouracil, or 5-FU, which is designed to overcome the key limitations and pharmacologic challenges that hinder the clinical utility of 5-FU, with the aim of improving 5-FU’s efficacy, safety and administration challenges.

5-FU (and its other forms including capecitabine) is an inactive prodrug and its anti-cancer activity is dependent on its conversion to the active anti-cancer metabolite (FUDR-MP), which binds to and inhibits thymidylate synthase (TS), a critical enzyme in de novo nucleotide synthesis and cell survival. TS is required to convert uridine (specifically dUMP) to thymidine (specifically dTMP), one of the four nucleotides that comprise DNA. The inhibition of TS results in an imbalance in the ratio of dUMP and dTMP, thereby disrupting DNA synthesis and repair, ultimately leading to cancer cell death. However, due to multiple limitations, 5-FU is not efficiently converted to FUDR-MP.

NUC-3373 generates much higher concentrations of FUDR-MP in patients’ cells. It also has a more convenient administration schedule and does not produce toxic levels of metabolites such as FBAL or FUTP (which are associated with hand-foot syndrome, neutropenia, mucositis and diarrhea) resulting in an improved safety profile.

In addition to preventing the synthesis of thymidine via TS inhibition, NUC-3373 treatment also results in the release of Damage Associate Molecular Patterns (DAMPs) and pro-inflammatory cytokines by cancer cells. These act as molecular signals to the immune system, encouraging them to kill cancer cells. Furthermore, NUC-3373 has been shown to induce the expression of PD-L1 on treated cells. In vitro experiments using NUC-3373 treated CRC cells co-cultured with immune cells have shown that NUC-3373 is able to potentiate the effects of PD-1 inhibitors, thus providing a strong scientific rationale for combining NUC-3373 and PD-1/PD-L1 inhibitors in patients.

On September 12, 2022 Nimbus Therapeutics, a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, reported the closing of a $125 million private financing (Press release, Nimbus Therapeutics, SEP 12, 2022, View Source [SID1234619397]). The round involves participation from new investors Bain Capital Life Sciences and SV Health Investors, along with existing investors including Access Biotechnology, Atlas Venture, BVF Partners L.P., Bill Gates, Lightstone Ventures, Pfizer Ventures, RA Capital Management and SR One.

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"The strong support from investors in this financing validates the promise and differentiation of Nimbus’ current portfolio of clinical and preclinical programs, and the success of our productive drug discovery engine," said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. "I’m pleased to welcome SV Health Investors and Bain Capital Life Sciences to Nimbus’ investor syndicate at this very exciting time in our history, and look forward to generating and sharing critical data for our medicines in development in the near term."

The financing will support the completion of the ongoing Phase 2b clinical trials of NDI-034858, Nimbus’ oral allosteric tyrosine kinase 2 (TYK2) inhibitor, in moderate-to-severe plaque psoriasis and active psoriatic arthritis, the initiation of psoriasis Phase 3 trials, as well as the initiation of additional Phase 2b clinical trials of NDI-034858 in other autoimmune indications, including inflammatory bowel disease (IBD) and lupus.

The financing also will support the ongoing Phase 1/2 clinical trials of NDI-101150, Nimbus’ hematopoietic progenitor kinase 1 (HPK1) inhibitor, in patients with solid tumors, as well as preclinical development of programs targeting Casitas B-lineage lymphoma b (Cbl-b) and Werner syndrome helicase (WRN), along with ongoing discovery efforts across a range of targets.

"We’re proud to lead this financing round to advance Nimbus’ exciting pipeline of clinical and preclinical candidates," said Nikola Trbovic, Ph.D., Partner at SV Health Investors. "Nimbus has a remarkable track record of success in discovering and developing differentiated small molecule therapies to address substantial unmet medical needs, and we’re excited to support their current portfolio of programs."

In addition to this financing, Nimbus has recently appointed Gorjan Hrustanovic, Ph.D., Managing Director of BVF Partners, L.P., to its Board of Directors. Dr. Hrustanovic serves on a number of other public and private biotech boards, and trained in cancer biology and translational medicine at the University of California, San Francisco.

On September 12, 2022 Enterome, a clinical stage biopharmaceutical company developing first-in-class immunomodulatory drugs based on its bacterial Mimicry drug discovery platform, reported new data from its two Phase 1/2 clinical trials of EO2401 in combination with nivolumab (Opdivo) +/- bevacizumab (Avastin), in patients with first progression/recurrence of glioblastoma (ROSALIE trial), and in combination with nivolumab in patients with non-resectable adrenocortical carcinomas (ACC) and metastatic pheochromocytoma/paraganglioma (MPP) (SPENCER trial) (Press release, Enterome, SEP 12, 2022, View Source [SID1234619396]). The data were presented in a poster (ROSALIE) and an oral presentation (SPENCER) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, on September 10 and 12, respectively, in Paris (France). The poster and presentation can be found here.

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EO2401 is Enterome’s first-in-class off-the-shelf OncoMimics cancer immunotherapy. It combines three OncoMimics peptides that closely mimic IL13Ra2, BIRC5 and FOXM1, all of which are known driver antigens present on aggressive solid tumors. In addition, EO2401 contains a CD4 helper peptide UCP2. Enterome selected these OncoMimics peptides using its Mimicry platform, which applies best-in-class biocomputational tools and bioassays to identify novel therapeutics from its proprietary database of 20+ million bioactive gut microbiome peptides and proteins.

Dr. Jan Fagerberg, Chief Medical Officer of Enterome said, "We are excited that EO2401 therapy continues to show promising and sustained efficacy with a good safety profile. These data from the ROSALIE and SPENCER trials are providing important insights that will enable us to select appropriate treatment regimens and patient populations for the next clinical studies with EO2401 in solid tumor indications."

Pierre Belichard, CEO of Enterome added, "The data presented at ESMO (Free ESMO Whitepaper) reinforces the positive findings that we communicated at ASCO (Free ASCO Whitepaper) in June and confirm the power of Enterome’s Mimicry platform to generate novel and highly promising cancer vaccine candidates. These promising data provide a compelling proof-of-concept for our unique Mimicry approach and give us confidence in our ability to generate an extensive pipeline of OncoMimics-based immunotherapies targeting unmet needs across a wide range of solid and hematologic cancers. Alongside EO2401, we are pursuing recruitment for EO2463 in B cell malignancies and plan to promptly start treating the first patient with ctDNA-defined, minimal residual disease in colorectal cancer with EO2040. We are also actively preparing the next OncoMimics candidate EO4010, developed for the treatment of colorectal cancer, to enter the clinic."

Highlights from the EO2401/ ROSALIE poster presentation at ESMO (Free ESMO Whitepaper) 2022:

Follow-up data confirm that EO2401 in combination with nivolumab +/- bevacizumab is well tolerated with a safety profile consistent with the safety profiles of nivolumab and bevacizumab.
EO2401 in combination with nivolumab generated strong systemic immune responses through activation of specific effector memory CD8+ T cells, correlating with efficacy.
Addition of bevacizumab to EO2401 and nivolumab supported longer treatment durations, and an increase of objective response rate (ORR – 54.5% vs. 10.3%), disease control rate (DCR – 81.8% vs. 34.5%), and progression-free survival (PFS – 5.5 months vs 1.8 months), with 3 out of the first 11 patients showing complete remission.
Additional patients are to be treated with EO2401/nivolumab/ bevacizumab combination to support final regimen selection for further studies.

Highlights from the EO2401/ SPENCER oral presentation at ESMO (Free ESMO Whitepaper) 2022:

EO2401 in combination with nivolumab is well tolerated in patients with ACC and MPP with a safety profile consistent with the safety profiles of nivolumab monotherapy.
Clinical efficacy was observed that correlates with the strength of generated immune responses.
Best efficacy observed in a post-hoc defined subgroup of patients with ACC, including
Prolonged duration partial responses (ORR 29%)
12-month survival rate of 78.6%, highest achieved in any relevant study in this indication
A randomized study to evaluate EO2401 in combination with nivolumab versus EO2401 monotherapy versus nivolumab monotherapy in this defined ACC population is ongoing.

On September 12, 2022 Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS), reported that senior management will participate at the H.C. Wainwright 24th Annual Global Investment Conference on Wednesday, September 14 at 10:00 am ET (Press release, Coherus Biosciences, SEP 12, 2022, View Source [SID1234619395]).

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An audio webcast of the fireside chat will be available on the investor’s page of the Coherus website at View Source Please access the website prior to the start of the presentation to ensure a timely connection to the webcast. The webcast will be archived on the Coherus website for 30 days.