On June 24, 2021 Scandion Oncology A/S reported that positive results from the dose-finding part 1 of the CORIST Phase II study (Press release, Scandion Oncology, JUN 24, 2021, View Source,c3373635 [SID1234584302]). A well tolerated dose of SCO-101 in combination with the chemotherapy regimen FOLFIRI has been determined and the SCO-101 treatment in the optimized combination resulted in notable potentiation of the biological activity of FOLFIRI. Furthermore, the CORIST study has identified the oncogene RAS as a predictive biomarker, which will be used to optimize the inclusion of patients in part 2. These positive data, have significantly de-risked the further development of SCO-101 and the company is now ready to advance to the proof-of-concept study (part 2) of CORIST.

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Part 1 of the CORIST study demonstrates the potential of SCO-101

"The interim CORIST data support our development plans for SCO-101 and at the same time pioneer the important perspectives around the platform potential of SCO-101, where we revert cancer drug resistance in various cancer diseases. We are looking forward to utilizing these learnings in our overall aim of building value for the patients, society and shareholders. We will communicate more about our plans and strategy at our Capital Market Day in September," says Bo Rode Hansen, President & CEO at Scandion Oncology.

Scandion Oncology, The Cancer Drug Resistance Company, is pleased to announce that the Company has obtained positive interim results from the CORIST trial, which substantiates the path for the further development of SCO-101. The CORIST Phase II study is aimed at combating cancer drug resistance in patients with metastatic colorectal cancer (mCRC) with acquired resistance to the chemotherapy regimen FOLIFRI. The patients enrolled in the trial have all failed prior standard chemotherapy due to resistance and have entered a terminal stage of their disease. Several positive take-home messages can be extracted from the data:

Well tolerated dose of SCO-101 in combination with FOLFIRI established
SCO-101 potentiates the biological effect of FOLFIRI in patients
Treatment benefit appears higher in patients without mutation in the RAS gene (RAS wild-type)
RAS biomarker enables de-risking of part 2 proof-of-concept study with SCO-101 in combination with FOLFIRI, in RAS wild-type patients with mCRC resistant to FOLFIRI
To exploit the new knowledge of the biomarker, the clinical protocol for part 2 of CORIST will be amended. Part 2 will commence as soon as the amendment is approved by the regulatory authorities. Timelines for read-out of CORIST part 2 may extend into Q3, 2022 due to this optimization.

All together, the results from the part 1 of the CORIST study have added significantly to our understanding of the effects of SCO-101 and consequently, de-risked the CORIST program.

We are ready to advance to the proof-of-concept part of the CORIST study

"We are satisfied finding a safe dose of SCO-101 in combination with FOLFIRI which displays biological activity in the patients and also favorably changes the adverse effects of the chemotherapy. We are further excited to have identified RAS as a predictive biomarker in the study. This enables us to tailor the treatment to patients who tolerate the treatment best and thereby have a higher likelihood to benefit from the treatment. We thank the patients and investigators who are participating in the trial," says Peter Michael Vestlev, CMO at Scandion Oncology.

Important data collected and predictive biomarker identified

The objective of CORIST part 1 was to study safety, tolerability and early effect measures of SCO-101 in combination with FOLFIRI in patients with metastatic colorectal cancer (mCRC) with acquired resistance to the chemotherapy regimen FOLIFRI. Part 1 of the CORIST study included 12 patients in the first cohort and 6 patients in the second cohort. The patients continue on treatment with SCO-101 and FOLFIRI until progression. Patients from both cohorts are still on treatment in the study, and the preliminary assessment of data show that:

Dose determination: Well tolerated dose of SCO-101 in combination with FOLFIRI has been determined (MTD), and the recommended dose for part 2 of the study has been identified. Repeated daily doses of SCO-101 in combination with a reduced FOLFIRI dose was well tolerated at exposure levels expected to be clinically relevant in this very fragile patient population.

Good safety profile: No treatment related grade 3 or 4 events were observed at the MTD dosis which is very encouraging. Only mild gastrointestinal adverse reactions were observed related to treatment, which is otherwise a common dose limiting adverse reaction to FOLFIRI. The most commonly observed grade 3 or 4 adverse reaction in the first cohort was neutropenia (reduced levels of white blood cells).
SCO-101 potentiates the effect of FOLFIRI: The combination with SCO-101 resulted in a notable potentiation of the biological effect of FOLFIRI on cells targeted by the chemotherapy (e.g. white blood cells and hair follicles).
Predictive biomarker identified: The RAS mutation status of the cancer at diagnosis was identified as a biomarker for segmentation of patients for the treatment with SCO-101 and FOLFIRI. Patients without mutation in the RAS gene (RAS wild-type) tolerated higher doses of SCO-101 and FOLFIRI. Patients with RAS wild-type also stayed longer on treatment than RAS mutated patients. The identified RAS biomarker is present in 50% of all mCRC patients and is already available from the initial diagnosis of the patients before inclusion in the CORIST study. The biomarker will be used for patient inclusion in part 2 of the study.
Preliminary effect measure: Eight of the included patients in CORIST part 1, were identified as RAS wild-type. Five of these eight patients have shown stable disease for more than eight weeks. Two of the five patients experienced a reduction in tumor volume (<30%). One patient has been on trial for more than 24 weeks and is still on therapy as part of the study. All patients in the RAS mutated group have experienced progressive disease after the first status scan.
Following conclusion of part 1, the study will advance to part 2 which will continue the focus on safety, tolerability and efficacy parameters, to establish proof-of-concept for SCO-101 in combination with FOLFIRI.

Timelines adjusted due to required amendment and reduction in eligible patient population

The de-risking of part 2 of the study by only including patients positive for the recently identified predictive biomarker, requires approval of an amendment from the regulatory authorities before part 2 can be initiated. The amendment will be submitted in July and approval is expected within 1-2 months following submission.

Due to the required amendment and the reduction in the eligible patient population for part 2 (RAS wild-type patients), timelines for reporting of results from part 2 may extend into Q3, 2022. The previous plan was to present results in Q1-Q2, 2022.

Additional trial sites in Denmark and abroad are currently being opened to increase recruitment rate and minimize the anticipated change in reporting timelines.

Design of CORIST part 2

The design for part 2 of the study is a standard single arm phase II study with the aim of further assessing safety, tolerability and preliminary effect of SCO-101 in combination with FOLFIRI. The primary efficacy objective is assessment of response (tumor reduction) and secondary efficacy objectives include assessment of Clinical benefit (Stable Disease, Progression Free Survival (PFS), Overall Survival (OS)) as well as biomarker assessment and correlation to treatment tolerability and outcome. Part 2 of the CORIST phase II study will include 25 patients.

Audiocast today, June 24 at 10:00 am CEST

Scandion Oncology A/S will be hosting an audiocast on June 24 at 10:00 am CEST to present the results from the read-out of the CORIST part 1 study, followed by a Q&A session. Representing the company will be President & CEO, Bo Rode Hansen and CMO, Peter Michael Vestlev. Please login to the audiocast via View Source

This information is information that Scandion Oncology A/S is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, on June 24, 2021 at 8:00 am CEST.

On June 24, 2021 Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases, cancer, and other indications, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to cinrebafusp alfa (PRS-343), a 4-1BB/HER2 bispecific, for the treatment of HER2-high and HER2-low expressing gastric cancers (Press release, Pieris Pharmaceuticals, JUN 24, 2021, View Source [SID1234584320]).

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"The granting of orphan drug designation to cinrebafusp alfa underscores the high unmet medical need that persists in the treatment of gastric cancer and reinforces our conviction in the importance of developing this program while setting a high bar for success to help patients with limited therapeutic options," said Stephen S. Yoder, President and Chief Executive Officer of Pieris. "We look forward to beginning the phase 2 trial of cinrebafusp alfa later this summer."

FDA grants orphan drug designation to promote the development of a drug that targets a condition affecting 200,000 or fewer U.S. patients annually. Orphan drug designation provides qualifying therapies with development and commercial incentives, including FDA assistance in clinical trial design, tax credits for eligible clinical trials, waiver of application fees, and market exclusivity for seven years following FDA approval, in addition to other available regulatory exclusivities.

About Cinrebafusp Alfa:
Cinrebafusp alfa (PRS-343) is a 4-1BB/HER2 fusion protein comprising a 4-1BB-targeting Anticalin protein and a HER2-targeting antibody. Based on encouraging phase 1 study results, which demonstrated clinical benefit as single agent and biomarker data indicative of a 4-1BB-driven mechanism of action, the Company is actively working towards initiating a phase 2 study of cinrebafusp alfa in combination with ramucirumab and paclitaxel for the treatment of HER2-high expressing gastric cancer and in combination with tucatinib for the treatment of HER2-low expressing gastric cancer.

On June 24, 2021 City of Hope, a world-renowned cancer research and treatment center, reported that it has identified how cancer cells in patients with early-stage breast cancer change and become resistant to hormone or combination therapies, according to a new study published in Nature Cancer (Press release, City of Hope, JUN 24, 2021, View Source [SID1234584336]).

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About 80% of breast cancer cases are hormone receptor positive, meaning that these cancer cells need estrogen or progesterone to grow, according to the American Cancer Society. Doctors currently treat people with estrogen receptor positive (ER+) breast cancer using therapy that inhibits both estrogen levels and cell cycle activity. While these therapies often initially shrink tumors, about 90% of metastatic patients and 50% of Stage 2 and 3 breast cancer patients develop resistance.

A research team led by Andrea Bild, Ph.D., a professor in City of Hope’s Department of Medical Oncology & Therapeutics Research, used single-cell RNA sequencing to identify resistant traits cancer cells acquire; these cancer cells are able to persist despite therapy. The team also identified when these resistant traits are acquired and found them as early as two weeks after the start of a treatment regimen, which is months faster than current methods used to measure treatment response.

"If health care providers are able to identify the development of tumor resistance earlier, then they can quickly switch gears and offer a different treatment regimen that could eventually bring the breast cancer patient into remission rather than continuing on a path that may fail to achieve a positive outcome," Bild said. "With the current available set of precision medicine tools, medical professionals could measure patient response to treatment earlier to offer treatment options that are more likely to work for each individual patient."

Bild and her colleagues studied the evolution of the DNA and RNA in breast tumor cells of postmenopausal women with ER+ breast cancer who were enrolled in the FELINE trial. These patients were treated with endocrine therapy (letrozole) alone and in combination with cyclin-dependent kinase (CDK) inhibitor therapy (ribociclib), a treatment that restrains tumor cells from growing. Patients were treated with targeted therapy in a neoadjuvant setting, meaning prior to surgery to remove the tumor, to assess response. Biopsies from over 40 patients’ tumors were processed and analyzed from cells taken prior to, two weeks after and six months from the start of endocrine and combination treatments.

City of Hope researchers found that resistant cells that persist even after endocrine and cell cycle (CDK4/6) inhibition therapy tend to shift their growth engine from using estrogen signaling to using alternative growth factor receptors and to rewiring cell cycle pathways. For example, resistant cells bypass the blocked pathways by turning on alternative signaling pathways such as growth receptors and MAPK signaling; this rewiring enables cancer cells to continue growing despite the estrogen and cell cycle drug inhibitors. Targeting these acquired resistance pathways with appropriate therapies may help doctors in the future treat patients with resistant ER+ early-stage breast cancer.

"The study is impressive in its scope, presenting comprehensive genomic profiling of the longitudinal samples from multiple patients," said Suwon Kim, Ph.D., who was not involved in the research and is an associate professor at Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and a faculty member of the University of Arizona College of Medicine. "The results are significant, revealing the emergence of the alternate specific pathways in single tumor cells as they become resistant to CDK inhibitors and endocrine therapy. The study findings offer opportunities for evidence-guided therapeutic intervention for therapy-resistant breast cancer."

Understanding how tumor cells quickly change and rewire signaling pathways so that they can persist after combination neoadjuvant cancer treatment will enable scientists to design novel treatment regimens that target tumor resistance. Bild and colleagues are now identifying drugs that block the traits found specifically in resistant cancer cells.

"Early-stage ER+ and PR+ (progesterone receptor positive) breast cancer is often curable, and we need to continue down this line of research to design therapy strategies that provide a positive patient outcome that lasts," Bild said. "I recommend that, when possible, clinicians continue to collect tumor biopsies so we can measure cancer cell responses during treatment to understand how the patient’s tumors are responding. In addition, we need to look at RNA changes and not just DNA modifications, as these changes may more broadly capture resistance mechanisms."

She added, "I am grateful to patients who participate in clinical trials so that scientists can continue to find better ways to treat this disease."

The study was supported by a Cancer Prevention Research Institute of Texas Core Facility Support Award (RP170668) and by the National Cancer Institute of the National Institutes of Health (U54CA209978).

On June 24, 2021 Anaveon, a clinical stage, immuno-oncology company, reported that it has successfully dosed the first patient in a Phase I/II open label study of ANV419, a powerful and selective interleukin-2 (IL-2) agonist as a monotherapy in patients with advanced solid tumors (Press release, Anaveon, JUN 24, 2021, View Source [SID1234584303]). ANV419 has been designed to overcome known challenges with tolerability and selectivity of recombinant human IL-2.

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The study is an open-label, multi-center Phase I/II trial evaluating the safety, tolerability, dose finding and clinical efficacy of ANV419 in patients with advanced solid tumors. Recruitment is ongoing in Spain. Link to the study.

"Dosing our first patient represents an important validation of our approach and is a significant milestone for Anaveon,"said Dr Christoph Bucher, Chief Medical Officer of Anaveon. "We have initiated a multi part, first-in-human dose finding study of ANV419 as a monotherapy in patients with solid tumors. Our compound has excellent tolerability in non-human primates and marked efficacy in a variety of tumor models and elicits strong and selective proliferation of effector cells in multiple settings."

Martin Murphy, Chief Executive of Syncona Investment Management Limited, added:"We are encouraged by Anaveon’s strong progress since our first investment in the company in 2019. The first patient dosing comes off the back of pre-clinical data which has shown that ANV419 has the potential to be a best-in-class asset. Whilst not without risk, the clinical data generated by the company will be a critical driver of value and there is a fast timeline for the company to show differentiation against competing products. We are excited about its potential."

ANV419 is a novel IL-2/anti-IL-2 fusion protein with preferential signaling through the IL-2 beta/gamma receptor. It has antibody-like pharmacology, behavior and stability and selectively stimulates the proliferation of CD8 T cells and NK cells without promoting the expansion of Regulatory T cells (Tregs). In non-human primate studies, ANV419 demonstrated excellent tolerability, a highly favorable safety profile and pharmacokinetics with strong in-vivo expansion of NK and CD8 T cells but not Tregs. No significant changes in body weight or blood pressure were seen at any dose during the entire study period and no signs of capillary leak syndrome were observed. Anaveon expects to report initial clinical safety and pharmacokinetic (PK)/ pharmacodynamic (PD) data by the end of 2021.

Anaveon was founded in December 2017 by Andreas Katopodis, previously Director at the Autoimmunity, Transplantation & Inflammation Group at the Novartis Institutes for BioMedical Research and Onur Boyman, Professor and Chair in the Department of Immunology at the University of Zurich. The Company is developing selective IL-2 Receptor Agonists, which have the potential to therapeutically enhance a patient’s immune system to respond to tumors. In the body, human IL-2 stimulates a type of immune cell, called a T-cell, to multiply and become activated. Activated T-cells are able to attack tumors and, consistent with this approach, human IL-2 is already approved as a therapeutic for the treatment of metastatic melanoma and renal cancer; however, due to lack of specificity, human IL-2 has severe, dose-limiting side effects and a short half-life that requires frequent infusions. The lead compound, ANV419, is designed to preferentially signal through the IL-2 beta/gamma receptor and therefore overcome known challenges of human IL-2. This novel type of therapeutic, if approved, could potentially have a wide utility in oncology, including in combination with cell therapies, vaccines, checkpoint inhibitors and radiotherapy.

On June 24, 2021 Invivoscribe, a global leader in precision diagnostics, reported the launch of an Immune Biomarker Discovery grant program, focused on supporting development, validation and deployment of novel applications for use of their distributed LymphoTrack NGS products and bioinformatics software (Press release, Invivoscribe Technologies, JUN 24, 2021, View Source [SID1234584337]).

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Massively parallel sequencing coupled with reagents targeting the immune receptor loci have accelerated our understanding of the immune response and immunology related disease processes. The availability of distributed RUO LymphoTrack tests and bioinformatics have eliminated a majority of the barriers of a service model approach, and have accelerated the ability to identify, track and monitor biomarkers associated with hematologic malignancies. These products are also being deployed worldwide to track the manufacture and treatment of immunotherapy, such as CAR T-cell therapies, and provide a comprehensive way to track a subject’s immune response to disease processes and to vaccines.

In conversations with customers and partners worldwide, we have also realized that our Research Use Only (RUO) LymphoTrack sequencing kits and services also have utility far beyond clinical oncology, as these assays and software products are currently being used in research in areas as diverse as, studies of celiac disease and other autoimmune diseases, tracking the immune health of astronauts on the ISS, examining the immune response throughout the course of clinical treatments, and identifying changes in the immune repertoire with onset and progression of disease. Intrigued to learn what innovative applications our RUO LymphoTrack kits and services are being used for, we decided to launch this grant program to support these endeavors.

Successful innovative proposals submitted by applicants to our Invivoscribe’s Immune Biomarker Discovery grant program will receive LymphoTrack kits, controls and software to support their R&D project. Grants will be awarded to support cutting-edge research and development in academic, government and early-stage commercial laboratories conducting promising research studies.

"The combined costs of library preparation reagents, NGS sequencing reagents, and development of bioinformatics software represent an obstacle for researchers. The idea of this grant program is to reduce these financial barriers, thus empowering a few progressive laboratories to bring their groundbreaking applications to fruition," says Tony Lialin, Chief Commercial Officer at Invivoscribe. Those selected as winners of the grant will not only receive NGS products, but will be provided additional opportunities to collaborate with Invivoscribe’s global network of ISO15189 accredited LabPMM laboratories. The laboratories selected for the grant program will also be featured in upcoming webinars and will be invited to speak at a number of symposiums around the world.

Details and How to Apply/Submit a Proposal

If your laboratory is interested in applying for Invivoscribe’s Immune Biomarker Discovery grant program to improve the standard of healthcare, we encourage you to submit research proposals that focus on the development of engineered antibodies to target antigens of infectious pathogens, toxins, allergens, and malignant diseases such as cancer and autoimmune disorders. More information about the program and details about how to submit a proposal can be found at www.invivoscribe.com/NGS-Grant. Proposals will be accepted from qualified laboratories across the world through Aug. 31, 2021 and winners will be announced by September 30, 2021. Additional information about the grant program and our oncology products and services can be requested by emailing [email protected].