On November 10, 2022 Biodesix, Inc. (Nasdaq: BDSX), a leading data-driven diagnostic solutions company with a focus in lung disease, reported that Wallace Akerley, MD, medical oncologist at the University of Utah Huntsman Cancer Institute, will present new interim data from the large multi-center prospective observational registry study INSIGHT (Clinical Effectiveness Assessment of VeriStrat Testing and Validation of Immunotherapy Tests in NSCLC Subjects) (NCT03289780) at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting (Press release, Biodesix, NOV 10, 2022, View Source [SID1234623690]). The data highlights the ability of the VeriStrat test, a novel predictive and prognostic blood-based host immune classifier, to stratify immune checkpoint inhibition (ICI) treatment response in patients with advanced non-small cell lung cancer (NSCLC). The poster, titled "Host Immune Profiling in First-line Immunotherapy Treated Advanced Stage Non-Small Cell Lung Cancer: Results from the INSIGHT Registry Study," will be presented on Friday, November 11th, 2022.

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Results from a prior analysis of the VeriStrat test published in the Journal for ImmunoTherapy of Cancer (JITC) in October 2021 demonstrated that approximately 2,000 patients with at least one year of follow up classified by VeriStrat as host immune classifier hot (HIC-Hot) had better outcomes, on average living 2-3 times longer when compared to patients classified by VeriStrat as host immune classifier cold (HIC-C). A classification of HIC-H, also known as VeriStrat Good, implies that the normal tumor directed immunity is active and patients are potentially responsive to therapies that boost immune response. HIC-C classification, also known as VeriStrat Poor, correlates to what experts refer to as an "immune desert," where tumor directed immunity is compromised.

The new data expands the analysis population to a total of 3,040 patients and confirms the ability of the VeriStrat test to predict outcomes in patients treated with immunotherapy regimens. Patients with HIC-C classification had superior median overall survival when receiving ICI plus chemotherapy versus ICI alone (8.2 months versus 5.6 months, respectively). Furthermore, patients with high PD-L1 expression and with HIC-C classification had superior median overall survival when receiving ICI plus chemotherapy versus ICI alone (14.3 months versus 3.3 months, respectively).

"Real World data can answer questions not addressed by registrational studies. HIC (VeriStrat) is a biomarker of immune therapy and these results suggest that HIC-C (VeriStrat Poor) patients should not be treated with single agent ICI therapy regardless of their PD-L1 expression," said Dr. Akerley, principal investigator of the INSIGHT study. "Immunotherapy has transformed treatment options for patients with non-small cell lung cancer, but it is challenging to know which standard of care regimens will be most effective. This new data from the INSIGHT study shows how a biomarker-driven strategy can help determine optimal treatment approaches for these patients."

On November 10, 2022 Ikena Oncology, Inc. (Nasdaq: IKNA, "Ikena"), a targeted oncology company forging new territory in patient-directed cancer treatment, reported initial clinical data from its ongoing IK-175 clinical program in urothelial carcinoma at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting in Boston, MA (Press release, Ikena Oncology, NOV 10, 2022, View Source [SID1234623689]).

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"We are glad to share the initial results from this study showing encouraging antitumor activity of IK-175 in urothelial carcinoma. These patients have exhausted all therapeutic options and progressed within 12 weeks of their last checkpoint treatment. It is an exciting development to observe IK-175 as well tolerated, achieving prolonged objective responses and disease control in this refractory patient population," said Sergio Santillana, MD, Chief Medical Officer of Ikena. "These initial data suggest we are making progress towards demonstrating that IK-175 in combination with nivolumab could overcome resistance to immune checkpoint inhibitors in urothelial carcinoma. Ultimately, we hope these data are a step towards IK-175 expanding the number of cancer patients who could benefit from immunotherapy."

Initial results demonstrate durable antitumor activity in heavily pretreated patients in both monotherapy and combination arms in urothelial carcinoma patients who all progressed on prior checkpoint inhibitors.

Key Data Highlights: IK-175 Dose Escalation, Stage 1 of Dose Expansion Monotherapy in Urothelial Carcinoma, and Stage 1 of Combination with Nivolumab Expansion in Urothelial Carcinoma

Durable antitumor activity across evaluable patients

Initial analysis includes 43 patients treated across all arms

Dose expansion in urothelial carcinoma: 20 response evaluable patients (10 monotherapy, 10 combination)

Expansion cohorts each follow a Simon 2-stage design

Patients included in analysis from stage 1 of each expansion cohort; stage 2 of the cohorts continue to enroll

IK-175 monotherapy

1 confirmed partial response with a duration of response (DoR) of 14.9 months and ongoing; 1 stable disease patient

10% overall response rate (ORR), 20% disease control rate (DCR)

IK-175 combination with nivolumab

2 confirmed partial responses with DoR 4.5-6 months and ongoing; 2 stable disease patients

Overall response rate 20% (ORR), disease control rate 40% (DCR)

Dose escalation in all solid tumors; 20 evaluable patients (15 monotherapy, 5 combination)

All solid tumors enrolled, including non-small-cell lung cancer, ovarian, colon, appendiceal carcinoma, pancreatic carcinoma and others; included patients who received up to 10 lines of prior therapy

In dose escalation 3/15 (monotherapy, 20% DCR) and 2/5 (combination, 40% DCR) patients had prolonged stable disease up to over 19 months

IK-175 was well tolerated, with a predictable and manageable safety profile

Maximum tolerated dose was not reached and no dose limiting toxicities were observed; 1200mg was selected as the expansion dose

Most frequently occurring treatment-related adverse events were low-grade rash and nausea (monotherapy) and low-grade fatigue and dysgeusia (combination); there were only 2 serious adverse events

Immune-related events were reported in both monotherapy and combination arms, supporting the immune-modulatory effect of IK-175

Dr. David Aggen, one of the lead investigators on the trial and author on the poster commented: "This bladder cancer patient population are often out of options, and it is extremely challenging to find therapies that can overcome their previous treatment failures. It is exciting to see this type of antitumor activity with IK-175-nivolumab combination therapy for these patients and I am looking forward to seeing how IK-175 advances the bladder cancer treatment paradigm."

Title: Initial results from a Phase 1a/b study of IK-175, an oral AHR inhibitor, as a single agent and in combination with nivolumab in patients with advanced solid tumors and urothelial carcinoma

Presenter: David Aggen, M.D. Ph.D. (MSKCC)

Available in the poster hall November 10, 2022, through the conference website, and on the company website

About IK-175-001

The study is an ongoing Phase 1b, open-label dose escalation and expansion study of IK-175 in those diagnosed with local or advanced solid tumors or unresectable urothelial carcinoma who have exhausted prior therapies and have seen disease progression on or within 12 weeks of the last dose of checkpoint inhibitor. IK-175 treats cancer through a novel mechanism, inhibiting the cancer-driving transcription factor known as the aryl hydrocarbon receptor (AHR) and modulating the tumor microenvironment. Through a body of translational data, including data generated with Ikena’s internally discovered biomarkers and novel assays, AHR has been demonstrated to be upregulated in urothelial carcinoma and other solid tumors leading to an increase in immunosuppressive effects and resistance to checkpoint inhibitor treatment. Responses are evaluated through RECIST 1.1. The expansion cohorts enrolled only urothelial carcinoma patients and are designed as Simon-2-stage cohorts. Both the monotherapy and combination arms advanced to stage 2 and enrollment is ongoing. Ikena’s IK-175 program is being developed in collaboration with Bristol Myers Squibb. Bristol Myers Squibb has an option to exclusively license the program through early 2024. The therapy is also being studied in a Phase 1, open-label, single-arm dose expansion study in combination with nivolumab in advanced head and neck cancer (IK-175-002).

On November 10, 2022 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of potentially best-in-class IL-2 therapeutics, reported that early data from its Phase 1/2 study of AU-007. AU-007 is a human monoclonal antibody computationally designed by Biolojic Design to harness the power of interleukin-2 (IL-2) and eradicate solid tumors (Press release, Aulos Bioscience, NOV 10, 2022, View Source [SID1234623688]). Data were presented in a poster presentation at the 37th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Boston, Massachusetts.

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Initial pharmacokinetic data from the first three patients administered AU-007 as a monotherapy demonstrate characteristics similar to other IgG1 therapeutic human monoclonal antibodies. Further, the data are consistent with the novel mechanism of action of the antibody. AU-007 binds IL-2 with high specificity and picomolar affinity, and completely inhibits IL-2’s binding to the CD25 subunit contained in trimeric IL-2 receptors expressed on immunosuppressive T regulatory cells (Tregs), vascular and pulmonary endothelium, and eosinophils. It does this without hindering IL-2’s binding to dimeric IL-2 receptors that contain CD122 and CD132 and are expressed on T effector and NK cells. Both T effector and NK cells are cell types that can kill tumor cells.

The early clinical data with AU-007 show trends toward decreasing Tregs with corresponding increases in the CD8/Treg ratio, initial interferon-gamma increases, and decreasing absolute eosinophils. The initial clinical findings are consistent with the preclinical in vivo and in vitro data from mice with syngeneic tumors, human peripheral blood mononuclear cells and cynomolgus monkeys treated with AU-007. In contrast, reported clinical data and preclinical data from other IL-2 therapeutics demonstrate that all other agents assessed substantially increase Tregs due to the negative feedback loop that such other approaches elicit and cannot control, likely contributing to disappointing clinical efficacy findings with second-generation IL-2 agents. Among the three evaluable patients treated with monotherapy AU-007, there has been only one drug-related toxicity, a case of Grade 1 diarrhea in a single patient. Two of the three patients have stable disease and continue on study treatment, with tumor shrinkage seen in one patient with metastatic non-small lung cancer treated with 1.5 mg/kg of monotherapy AU-007 every two weeks.

"With this very early data from our Phase 1/2 study, we are encouraged to see that in the initial three patients, AU-007 appears to be safe and well-tolerated to date," said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. "At this early stage, we are also pleased to see an overall trend of decreasing immunosuppressive Tregs, which is consistent with what we found in our preclinical studies. The promise of AU-007 in eradicating solid tumors lies in this highly differentiated mechanism of action, which breaks the negative feedback loop to Tregs, and is completely unlike that of any other IL-2 therapy in development. We continue to believe that AU-007 has significant potential sources of efficacy and safety competitive advantages in the class due to its unique ability to redirect IL-2 to T effector and NK cells and away from immunosuppressive Tregs, vasculature and pulmonary endothelium. We are grateful to the patients and investigators in Australia who are taking part in our clinical trial, and we are excited to add trial sites in the United States following the clearance of our IND application by the FDA two weeks ago."

The company’s Phase 1/2 clinical trial (NCT05267626) is an open label, first-in-human study evaluating the safety, tolerability, immunogenicity and clinical activity of AU-007 in patients with unresectable locally advanced or metastatic cancer. Phase 1 consists of three dose escalation arms evaluating AU-007 either as a monotherapy, in combination with a single loading dose of recombinant human IL-2 (aldesleukin), or with both AU-007 and aldesleukin administered once every two weeks. The aldesleukin will be administered subcutaneously, at much lower doses and much less frequently than the approved regimen of intravenously administered aldesleukin. The Phase 2 portion of the trial will evaluate a dosing regimen selected from dose escalation for expansion in specified tumor types to further define the safety and initial efficacy of AU-007.

In October, the U.S. Food and Drug Administration (FDA) cleared the company’s Investigational New Drug (IND) application for AU-007, allowing expansion of the Phase 1/2 study in the United States. Dosing of patients in the U.S. is anticipated to begin by year-end. The trial is currently enrolling patients in Australia.

The poster presentation is available on the Aulos Bioscience website in the Abstracts and Publications section.

About AU-007
AU-007 is a computationally designed, human IgG1 monoclonal antibody that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by T effector cells, from binding to trimeric receptors on T regulatory cells while still allowing IL-2 to bind and expand T effector and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to trimeric receptors on vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

On November 10, 2022 Anaveon, a clinical stage, immuno-oncology company, reported updated clinical data from the ongoing Phase I study of ANV419 in patients with solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, being held from November 8–12, 2022, at the Boston Convention and Exhibition Center in Boston, MA (Press release, Anaveon, NOV 10, 2022, View Source [SID1234623687]).

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In the ongoing study, 29 patients in 10 dosing cohorts with different cancers progressing after standard therapy, received ANV419 monotherapy once every 14 days at doses up to 364 µg/kg in two-week cycles as an intravenous infusion over 15 minutes. ANV419 is a powerful and selective IL-2 agonist, which has been specifically designed to enable the delivery of high dose IL-2 to patients, with a favourable safety and tolerability profile.

In the study, ANV419 was generally well tolerated, and all drug related events were manageable, reversible, and responsive to supportive care therapy. The most common drug related AEs were low grade (G1 or G2) fever, chills, vomiting and fatigue. No patients have withdrawn from the study due to AEs and no dose limiting toxicities were observed up to and including 243 µg/kg.

In this heavily pre-treated population, 5 patients continue to receive treatment. At ANV419 doses ≥108 µg/kg, 66% of patients achieved at least disease stabilization (9 SD, 1 PR). One patient who continues ANV419 treatment, has a confirmed Partial Response (as per RECISTv1.1) with 31% tumor shrinkage after 2 weeks of ANV419 and a sustained and deepening response of 56% shrinkage at 6 cycles (12 weeks) of ANV419.

Pharmacodynamic evaluation of ANV419 on day 4 post-dosing (cycle 1 and 2) showed a selective and dose dependent proliferation of CD8+ T and NK cells, with a lower increase of proliferating Tregs. ANV419 half-life increases up to 28 hours with increasing doses and ANV419 concentration is overall stable between cycles.

Anaveon has initiated Ph I/II studies to demonstrate efficacy of ANV419 in metastatic melanoma and multiple myeloma.

Dr. Elena Garralda at the Hospital Universitari Vall d’Hebron in Barcelona, and lead investigator on the study said, "These early clinical data are encouraging and I believe ANV419 has the potential to become an important component of therapy for patients with cancer."

Preclinical data for ANV419 in combination with checkpoint inhibitors that builds on the data presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 in September were also presented at SITC (Free SITC Whitepaper). These continue to demonstrate broad activity of ANV419 on effector cells, supporting the initiation of Phase II studies assessing ANV419 treatment in indications in which CD8 T cells and NK cells are involved in tumor resolution as well as supporting combination studies with checkpoint inhibitors and treatments acting through antibody-dependent cellular cytotoxicity.

"It is very exciting to see the continued safety and tolerability of ANV419 at higher doses, demonstrating the ability of ANV419 to deliver high molar equivalents of IL-2 in a tolerable and convenient way. Importantly, tumor response continues to deepen," added Christoph Bucher, MD, Chief Medical Officer of Anaveon. "We have initiated our first Phase II trial, investigating the efficacy of ANV419 in patients with cutaneous melanoma and we look forward to starting our Phase II study in Multiple Myeloma, whilst also broadening our pipeline with therapies that we expect will be effective as both standalone and combination therapies."

Abstracts are available on the SITC (Free SITC Whitepaper) website and the accompanying posters will be available in the publications section of Anaveon’s website.

Details of the poster presentations are:

Title: Phase I dose escalation study in patients with advanced solid tumors with ANV419, a novel fusion protein selective for IL-2Rβ/γ
Authors: Christoph Bucher, MD; Guzman Alonso, Dr; Juanita Lopez; Emiliano Calvo; Markus Joerger, MD; Vicky Sanchez Perez, MD; Elena Corral, MD; Daniela Di Blasi, PhD; Kirsten Richter, PhD; Christoph Huber, PhD; Julie Mouton; Silvio Costanzo; Sangeeta Jethwa, MD; Elena Garralda, MD; Heinz Läubli, MD PhD
Presenter: Daniela Di Blasi, PhD
Abstract Number: 631
Date & Time: Thursday, November 10, 2022 from 9 a.m. to 9 p.m. EST

Title: ANV419 is a novel CD122-biased IL-2/anti-IL-2 fusion protein showing increased efficacy in combination with checkpoint inhibitors and treatments acting through antibody dependent cellular cytotoxicity
Authors: Christoph Huber, PhD; Kirsten Richter, PhD; Laetitia Petersen; Nicole Egli; Patrizia Murer, PhD
Presenter: Christoph Huber, PhD
Abstract Number: 1099
Date & Time: Thursday, November 10, 2022 from 9 a.m. to 9 p.m. EST

Anaveon is undertaking a Phase I/II study to evaluate the safety, dosing and clinical activity of its lead program, ANV419, a powerful and selective interleukin-2 (IL-2) agonist in patients with solid tumors. The Company is pursuing multiple parallel Phase II programs in order to explore the full therapeutic potential of ANV419. In addition, Anaveon continues its work in developing follow-on compounds to expand on the success of ANV419 by delivering the IL-2 agonist to tumor fighting cells and thus expand the therapeutic potential into less immunogenic tumors. Alongside this, the Company is building on its cytokine engineering expertise with preclinical-stage programs harnessing the power of cytokines for therapeutic purposes.

On November 10, 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 that preclinical data for BT7480, a novel Bicycle tumor-targeted immune cell agonist (Bicycle TICA), and BT7455, an EphA2/CD137 Bicycle TICA, will be presented in five poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting, being held in Boston, M.A. and virtually on November 8-12, 2022 (Press release, Bicycle Therapeutics, NOV 10, 2022, View Source [SID1234623686]).

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