On April 11, 2022 OncXerna Therapeutics, Inc. ("OncXerna") is a precision medicine company using an innovative RNA-expression based biomarker platform to predict patient responses to its targeted oncology therapeutic candidates (Press release, OncXerna Therapeutics, APR 11, 2022, View Source [SID1234611969]). Today the company reported biomarker data demonstrating the Xerna TME Panel’s prognostic value across multiple indications in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Data also suggest the potential for Xerna TME Panel to predict patients most likely to benefit from immune- and angiogenic-targeted therapy.

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The Xerna TME Panel analyzes proprietary RNA-based gene expression data, which is inherently continuous, with a machine learning-based algorithm to classify patients into distinct subtypes based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). This enables potential for patients to be matched with targeted therapies that directly address their dominant biology and expand the reach of precision medicine to significantly more patients.

RNA expression signatures to predict therapeutic response have struggled with defining thresholds that clearly distinguish patients more likely to benefit from those that are not. RNA sequencing datasets are complex, and linear statistical tests used to set thresholds have proved difficult to reproduce across multiple studies. "Using artificial intelligence, we have been able to unlock the potential of RNA-based expression gene signatures," said Laura Benjamin, CEO of OncXerna Therapeutics. "We have achieved nearly binary outcomes with the Xerna TME panel that are similar to DNA-sequencing that detects the presence or absence of a specific mutation. This allows us to use our panel as a robust pan-tumor biomarker platform and potential to predict patient response to multiple targeted oncology drugs."

Data featured in the AACR (Free AACR Whitepaper) poster show the Xerna TME Panel is robust, resulting in high confidence scores and a lack of indeterminate or ambiguous calls when classifying subjects into biomarker types. The lack of reliable biomarkers to predict responses to anti-angiogenic treatment is a significant unmet medical need. When the Xerna TME Panel was applied to a cohort of gastric cancer patients treated with an anti-angiogenic agent (ramucirumab), the panel showed potential to predict clinical benefit. In a separate gastric cancer cohort treated with immune checkpoint inhibitor monotherapy, the panel had better positive predictive value (PPV) than PD-L1, and better sensitivity than MSI-H. Both PD-L1 and MSI-H rely on setting thresholds in a continuous variable space. Xerna TME Panel classifications were also shown to be prognostic in second-line gastric cancer patients receiving chemotherapy and/or radiation, and in melanoma and colorectal cancer cohorts.

The Xerna TME Panel has been licensed to Qiagen and Exact Sciences, who will partner with OncXerna to support clinical trials for OncXerna’s two clinical stage compounds, Navicixizumab and Bavituximab. Through their partnerships with OncXerna, Qiagen and Exact Sciences also intend to support the development of compounds from other companies, including novel immune-targeting agents.

An electronic copy of the AACR (Free AACR Whitepaper) poster entitled "Xerna TME Panel: A Pan-Cancer RNA-Based Investigational Assay Designed to Predict Patient Responses to Angiogenic and Immune Targeted Therapies," is available to registered attendees of the AACR (Free AACR Whitepaper) annual meeting on the meeting website, as well as on the OncXerna website here. The in-person presentation will take place during the "Biomarkers Predictive of Therapeutic Benefit 1" poster session on April 11, 2022, from 9:00 AM – 12:30 PM CT.

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 April 11, 2022 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported interim Phase I results from the Phase I/II trial of BT8009, a second-generation BTC targeting Nectin-4 (Press release, Bicycle Therapeutics, APR 11, 2022, View Source [SID1234611967]). The results were presented in an oral presentation on Sunday, April 10 at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, LA.

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"Since our initial BT8009 Phase I/II trial interim results last year, we are encouraged to see BT8009’s promising profile endure over time. Over the last six months, the preliminary anti-tumor findings have been confirmed, the initial responses have deepened and remained durable, and the tolerability profile remains unchanged," said Dominic Smethurst, MRCP, Chief Medical Officer of Bicycle Therapeutics. "We believe BT8009 has the potential to offer clinically meaningful differentiation compared to currently available therapies and we look forward to advancing the program once the escalation phase is complete."

"As previously hypothesized, we believe that the differentiated pharmacokinetic profile of BTCs has the potential to deliver improved outcomes for patients and it is pleasing to see these clinical data mature and with it, the promise for a potentially industry-leading product profile," said Kevin Lee, Ph.D., Chief Executive Officer. "We look forward to providing additional updates on BT8009 as well as updates from our broad Bicycle oncology pipeline this year."

As of March 7, 2022, thirty-seven patients have been dosed in the Phase I/II trial of BT8009. A total of twelve response evaluable urothelial cancer (UC) patients have been dosed in monotherapy cohorts of 2.5mg/m2 and 5.0mg/m2 weekly in the ongoing trial.

Four response evaluable UC patients were dosed at 2.5mg/m2 weekly. Among these four patients, one patient was observed to have tumor reductions constituting a confirmed partial response (PR) and two patients were observed to have stable disease (SD), reflecting a 25% overall response rate (ORR) and 75% disease control rate (DCR) in patients in this cohort.
Eight response evaluable UC patients were dosed at 5.0mg/m2 weekly. Among these eight patients, four patients were observed to have a confirmed complete response (CR) or PR, including one patient with a CR and three patients with a PR, and two patients with SD, reflecting a 50% ORR and a 75% DCR in UC patients for this cohort. Prior to enrollment, all patients in this cohort had previously received at least two prior lines of therapy, with a median of three.
The median duration of response has not yet been reached in either the 2.5 mg/m2 or 5.0mg/m2 cohort. Four of the five responders have ongoing Response Evaluation Criteria in Solid Tumors (RECIST) tumor responses. As of the March 7, 2022 data cutoff date, all four of these patients have a treatment duration of at least 24 weeks and all four remain on therapy.
Tolerability profile remains consistent with earlier results from this trial. No dose limiting toxicities have been observed in the 2.5mg/m2 or the 5.0mg/m2 cohorts, and with longer-term follow-up, incidence of skin and eye toxicity, neuropathy and hyperglycemia remains low.
Phase I dose escalation is ongoing. Exploration of additional doses and frequencies continues, and Bicycle intends to provide further updates this year.
Conference Call Details

Bicycle Therapeutics will host a conference call and webcast today at 8:30 a.m. ET to review the data being presented. To access the call, please dial (800) 377-9118 (domestic) or (409) 937-8920 (international) and provide the Conference ID 2775710. A live webcast of the presentation will be available on the Investors & Media section of the Bicycle website, bicycletherapeutics.com.

On April 11, 2022 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers, reported a summary of clinical and preclinical data reviewed during the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held in New Orleans, Louisiana from April 8-13, 2022 (Press release, Zentalis Pharmaceuticals, APR 11, 2022, View Source [SID1234611965]).

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Dr. Anthony Sun, Chairman and Chief Executive Officer of Zentalis, commented, "The data presented at AACR (Free AACR Whitepaper) demonstrate the encouraging anti-tumor activity and tolerability of our potentially best-in-class candidates across our pipeline. Following the positive initial data of ZN-c3 in combination with chemotherapy in advanced ovarian cancer patients reviewed at AACR (Free AACR Whitepaper), today we presented a mini symposium presentation on our Phase 1 expansion cohort of ZN-c3 in USC patients. ZN-c3 showed robust clinical activity in an advanced, sicker patient population (57% had prior pembrolizumab/lenvatinib use), specifically demonstrating a deepening of tumor response, which included one patient who achieved an unconfirmed complete response. We believe ZN-c3’s anti-tumor activity and tolerability profile observed to date has the potential to address a significant unmet need for improved therapeutic options in advanced USC patients."

Recap of Clinical and Preclinical Updates Presented During AACR (Free AACR Whitepaper)

Advanced ovarian cancer – Initial update from the Phase 1b trial of ZN-c3 in combination with chemotherapy

As of the January 28, 2022, data cutoff (n=43 evaluable), ZN-c3 in combination with chemotherapy demonstrated strong anti-tumor activity in a heavily pretreated population, with an Objective Response Rate (ORR) of 30.2% across all evaluable chemotherapy cohorts – achieving up to 62.5% with one cohort (n=8 evaluable).
ZN-c3 in combination with chemotherapy was well-tolerated and exhibited lower hematologic toxicity and a better gastrointestinal tolerability profile in a cross-trial comparison to the Wee1 inhibitor class.
Uterine serous carcinoma – Interim data from the Phase 1 monotherapy expansion cohort in patients dosed ≥300mg QD was presented at a mini symposium earlier today:

As of the January 21, 2022 data cutoff (n=11 evaluable), ZN-c3 demonstrated an ORR of 27.3%, a Disease Control Rate (DCR) of 90.9% and included one subject who achieved an unconfirmed complete response.
In a cross-trial comparison, the overall safety profile of ZN-c3 suggests that it is better tolerated than a competing Wee1 inhibitor.
Preclinical poster updates

The three posters demonstrated the broad potential of ZN-c3 in multiple settings including AML, PARP-resistant ovarian cancer, and in novel biology when combined with Zentalis’ BCL-2 inhibitor, ZN-d5.
CAMPRO – CAspase Mediated PROteolysis (CAMPRO) describes novel biology elucidated by Zentalis that demonstrates the synergy between BCL-2 and Wee1 inhibition. Zentalis is the only company to have both a Wee1 inhibitor (ZN-c3) and a BCL-2 inhibitor (ZN-d5) in clinical development.
These findings further support ZN-c3 as a potential cornerstone treatment, creating a significant market opportunity across a broad range of solid and liquid tumors.

On April 11, 2022 CureVac N.V. (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid ("mRNA"), and GSK reported that they have entered into a contract with the German federal government to supply mRNA vaccines within a broader tender for pandemic preparedness in Germany (Press release, CureVac, APR 11, 2022, View Source [SID1234611963]). Following a setup period of a maximum of two years, the contract grants the German federal government access to CureVac’s manufacturing capacity until 2029, enabling rapid availability of 80 million mRNA-based vaccine doses during the remainder of the current pandemic or in future infectious disease outbreaks. By reserving this manufacturing capacity, the tender seeks to mitigate risks associated with potential supply bottlenecks in a pandemic situation. Under the contract, the federal government will pay CureVac and GSK an annual standby fee after successful completion of the setup period, which requires the companies to maintain manufacturing capacity at constant readiness. By ensuring the availability of manufacturing capacities in Germany, the arrangement will significantly contribute to strengthening pandemic preparedness.

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"Over the last two years, our social and economic lives as well as global healthcare systems and medical supply infrastructures were severely challenged by the COVID-19 pandemic," said Dr. Franz-Werner Haas, Chief Executive Officer of CureVac. "This underscored the importance of having access to innovative technology platforms, such as mRNA technology, as well as corresponding robust manufacturing capacities to rapidly develop and deliver life-saving vaccines – particularly as a protective measure in case of future infectious disease emergencies. Considering the unpredictable and variant-driven course of the COVID-19 pandemic, we are fully committed to safeguarding public health today and into the future."

"We welcome this announcement of the German federal government, which aims to strengthen the country’s preparedness against future pandemics," said Roger Connor, President of Vaccines and Global Health, GSK. "Our mRNA development program in collaboration with CureVac could play a key role for pandemic preparedness thanks to adaptability of the mRNA technology and its potential for a rapid response, in combination with our significant vaccine manufacturing expertise."

On April 11, 2022 NANOBOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a clinical-stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported new data from an open-label preclinical study evaluating the combination of first-in-class radioenhancer, NBTXR3, with the triple blockade of PD-1, LAG-3, and TIGIT ("Combination therapy") (Press release, Nanobiotix, APR 11, 2022, View Source [SID1234611962]). The data were published via E-Poster presentation at the 2022 Annual Meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper), held April 8-13, 2022, by researchers from The University of Texas MD Anderson Cancer Center (MD Anderson).

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"We believe that the potential immune priming effect of radiotherapy-activated NBTXR3 could prove to be a game-changer for cancer immunotherapy," said Laurent Levy, co-founder and chairman of the executive board at Nanobiotix. "Our view is that while new immunotherapy treatment modalities with the potential to improve outcomes for patients continue to emerge, they remain reliant upon an underlying immune response. This new preclinical gene expression data showing that the addition of NBTXR3 enhanced activity in key immune pathways associated with innate and adaptive immunity, and outperformed all other combinations in efficacy, survival, and induction of long-term anti-cancer memory, adds to a growing body of support for NBTXR3 as a product candidate that could potentially help expand the benefits of immunotherapy to larger share of the patients we serve."

PRECLINICAL DATA ON IMMUNOTHERAPY BLOCKADE PLUS RADIOTHERAPY-ACTIVATED NBTXR3

Previously reported preclinical and clinical data evaluating NBTXR3 in combination with diverse immune checkpoint inhibitors (ICIs) including anti-PD-1, anti-CTLA-4, anti-LAG-3, and anti-TIGIT suggest that, after activation by radiotherapy, the radioenhancer may induce an "immune priming" effect that could help improve and expand the benefits of ICIs to more patients.

This new analysis, presented at AACR (Free AACR Whitepaper), assessed immune gene expression associated with multiple combinations of NBTXR3, anti-PD-1, anti-LAG-3, and anti-TIGIT.

Key Findings Include:

The Combination therapy outperformed all other tested treatment regimens in efficacy, survival, and induction of long-term anti-cancer memory
The Combination therapy significantly promoted the upregulation of mRNA transcripts involved in innate immunity, the humoral response, B cell function, dendritic cell function, and antigen processing within primary, irradiated tumors relative to untreated controls
Within non-irradiated tumors, the Combination therapy produced elevations in multiple immune-related pathways that were significantly higher than those produced by other treatment combinations and these pathways included both adaptive and innate immunity; B, T, natural killer, and dendritic cell function; and antigen processing
The Combination therapy promoted immune activation at the irradiated site, abscopal immune responses are improved with the addition of LAG-3 and TIGIT to PD-1 and radiotherapy-activated NBTXR3, and the data suggest that the Combination therapy may be effective against metastatic cancers
***

About NBTXR3
NBTXR3 is a novel, potentially first-in-class oncology product, composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physics-based mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly, with immune checkpoint inhibitors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy.

Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company sponsored phase I clinical study, evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC and for patients with lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy, either naïve or resistant to prior PD-1 (either primary or secondary as per SITC (Free SITC Whitepaper) criteria).

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in strategic collaborations to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations. In 2021, the Company entered into an additional strategic collaboration agreement with LianBio to support its global phase III study in Asia along with four future registrational studies.