On June 4, 2021 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, reported that presentation of initial data from NEON-1, the company’s Phase 1 clinical trial of ALPN-202, a conditional CD28 costimulator and dual checkpoint inhibitor, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting (Press release, Alpine Immune Sciences, JUN 4, 2021, View Source [SID1234583552]). NEON-1 is a first-in-human, dose escalation and expansion study of ALPN-202 monotherapy in advanced malignancies.

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Presentation highlights include:

ALPN-202 has been generally well-tolerated as of the data cutoff date. The most common treatment-related adverse events have included immune-related toxicities, particularly cutaneous reactions.
Although most enrolled participants have had tumors considered classically non-responsive to immunotherapies, 61% (14 of 23 evaluable) appeared to derive clinical benefit as defined as a best outcome of stable disease or better, as of the data cutoff date. One of these participants, with metastatic colorectal cancer, achieved an unconfirmed partial response.
Dose-dependent pharmacokinetics and pharmacodynamics have been observed, accompanied by expansion of circulating CD4+ T cells with upregulation of the ICOS activation and Ki-67 proliferation markers. An expansion of central memory T cells, and a downregulation of regulatory T cells, were also observed.
"These data represent, to our knowledge, the first demonstration of safe, controlled CD28 agonism in humans, with measurable physiological consequences," commented Dr. Stanford Peng, Alpine’s President and Head of Research and Development. "The circulating T cell changes are particularly exciting and consistent with the expected biology of CD28. Together with the early suggestion of clinical benefit for some cancers not traditionally considered immune-responsive, these findings strongly encourage us to further develop ALPN-202."

The poster is now live on the ASCO (Free ASCO Whitepaper) meeting website. A copy of the presented data is available on the Scientific Publications page of Alpine’s website.

Additionally, Alpine will hold an investor event on Friday, June 4th, 2021 at 7:00pm EDT. During the investor event, Alpine will review these data. Following the presentation, Alpine will hold a question-and-answer discussion.

Investor Event – Conference Call and Webcast Details

Alpine will hold an investor event on Friday, June 4th, 2021 at 7:00pm ET, to coincide with the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting. To access the investor event by phone, dial (800) 816-3005 (domestic) or (857) 770-0069 (international) and reference conference ID: 3439769.

A live webcast of the investor event will be available online in the investor relations section of the company’s website at View Source A replay will be available on the company website for 90 days following the webcast.

About ALPN-202

ALPN-202 is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor with the potential to improve upon the efficacy of combined checkpoint inhibition while limiting significant toxicities. Preclinical studies of ALPN-202 have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. NEON-1 (NCT04186637), a Phase 1 study of ALPN-202 in patients with advanced malignancies, is currently enrolling. Alpine also plans the initiation of NEON-2, a combination study of ALPN-202 and a PD-1 inhibitor, later this year.

On June 4, 2021 iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of highly differentiated immuno-oncology therapeutics for patients, reported new clinical data from its ongoing Phase 1/2a clinical trial of inupadenant (EOS-850), a next-generation adenosine receptor (A2AR) antagonist, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2021 (Press release, iTeos Therapeutics, JUN 4, 2021, View Source [SID1234583569]). Updated results from the single-agent dose-escalation and expansion portions of the trial provided evidence of durable antitumor activity in patients with advanced solid tumors and indicated safety consistent with previously reported results. Three serious adverse events considered possibly related to treatment with inupadenant had plausible alternate causes and do not represent a new safety concern for the program. Additionally, preliminary analyses of pre-treatment tumor biopsies indicated that the expression of A2AR is associated with clinical outcomes in patients with solid tumors treated with single agent inupadenant.

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"We are pleased with the durability of the anti-tumor responses we have observed to date with our highly selective A2AR antagonist, inupadenant, in patients with advanced cancers. These early-stage results support the development for the treatment of cancer of inupadenant, a selective inhibitor of A2AR, which is known to play a crucial role in immunosuppression in the tumor microenvironment." said Joanne Jenkins Lager, M.D., chief medical officer of iTeos Therapeutics. "We have used a proprietary assay to identify A2AR expression as a biomarker that may be predictive of clinical benefit. These new biomarker findings provide insight into the mechanism of action of inupadenant, informing our selection of potential indications, and may allow us to identify patients more likely to benefit from inupadenant. We are continuing to evaluate combinations with pembrolizumab and chemotherapy in our ongoing Phase 1b/2a trial with the goal of improving outcomes for patients."

Phase 1/2a monotherapy Study Design and Results
The ongoing Phase 1/2a trial is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of inupadenant monotherapy to define the maximum tolerated dose (MTD) and recommended Phase 2 dose of inupadenant as a single agent and in combination with pembrolizumab and/or chemotherapy in patients with advanced solid tumors. As of the data cut-off (February 26, 2021), 43 patients had enrolled in the single-agent dose-escalation and expansion parts of the study.

Results presented at ASCO (Free ASCO Whitepaper) 2021 provided an update on 21 patients enrolled in the single-agent dose-escalation and new data on 22 patients enrolled in the dose expansion.

Durable responses and stable disease greater than six months were observed in five patients with advanced solid tumors, including:

previously reported partial responses: ongoing for more than 12 months in one patient with castrate-resistant prostate cancer, and lasting for more than 8 months in one patient with melanoma resistant to both pembrolizumab and ipilimumab; and
stable disease in a patient with non-small cell lung cancer enrolled in the expansion, with ongoing treatment for more than 10 months.
The safety of inupadenant monotherapy was consistent with previously presented data. The most frequent adverse events were fatigue, anemia, decreased appetite and constipation. Drug-related serious adverse events (acute myocardial infarction, atrial fibrillation, and pericardial effusion) were reported in three of the 43 enrolled patients.

Evaluation of pre-treatment biopsies indicated that higher expression of A2AR was associated with longer survival and either tumor regression or stable tumor size in patients with solid tumors treated with single agent inupadenant.

The e-poster and abstract can be accessed on the ASCO (Free ASCO Whitepaper) conference website. The abstract and presentation details are as follows:

Title: Phase 1 trial of the adenosine A2A receptor antagonist inupadenant (EOS-850): Update on tolerability, and antitumor activity potentially associated with the expression of the A2A receptor within the tumor.
Session Title: Developmental Therapeutics—Immunotherapy
Abstract #: 2562
Authors: Laurence Buisseret, et al.

Further Clinical Development of Inupadenant
Based on the promising Phase 1/2a data to date, iTeos plans to further evaluate inupadenant in combination with pembrolizumab and in combination with chemotherapy in Phase 1b/2 studies, with an initial focus on patients with castrate-resistant prostate cancer, anti-PD-1-resistant melanoma and triple negative breast cancer. iTeos will continue to evaluate A2AR and other potential predictive biomarkers in the inupadenant clinical development program to ensure optimal therapeutic combinations and identify patients most likely to benefit from treatment.

About Inupadenant
Elevated levels of adenosine found in the tumor microenvironment are known to be immunosuppressive, by inhibiting A2AR, the only high-affinity adenosine receptor expressed on different immune cells found in the tumor micro-environment. Inupadenant (EOS-850) is the first insurmountable A2AR antagonist tailored for application in immuno-oncology, currently in clinical development. Inupadenant was designed by iTeos’ scientists to remain potent at the high adenosine concentrations found in the tumor micro-environment and maintain continuous target coverage in multiple tumor types. Inupadenant has a very high selectivity for A2AR compared to the other adenosine receptors and is non brain penetrant, two characteristics that should improve its safety. With this profile, we believe that inupadenant has the potential for enhanced antitumor activity as compared to other A2AR antagonists currently in clinical development.

On June 4, 2021 Agendia, Inc., a world leader in precision oncology for breast cancer, reported that an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting revealed new data from the national FLEX registry that identify differences in tumor biology between ethnic groups that can lead to meaningful treatment decisions, reinforcing the need for appropriate representation of diverse patient populations in breast cancer studies (Press release, Agendia, JUN 4, 2021, View Source [SID1234583583]).

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A major theme of this year’s ASCO (Free ASCO Whitepaper) meeting centers around disparities in care and outcomes, which Agendia’s FLEX study aims to combat by prospectively enrolling 30,000 patients from various ethnicities, ages and demographic groups representative of the total breast cancer population. The data presentation from this study, "Disparities within Luminal breast cancer: clinical and molecular features of African American and non-Hispanic White patients," delivered by first author of the study Kent Hoskins, MD, Co-Leader of the Breast Cancer Research Group and Director of Cancer Genetics at the University of Illinois Cancer Center, details significant biological differences in luminal breast tumors from African American and non-Hispanic White women, suggesting that shared adverse socioeconomic exposures and/or genetic ancestry may be driving disproportionately aggressive tumor biology in African American women. This finding further underscores the need for inclusion of diverse patient groups in clinical trials to ensure equity in drug development.

"The data presented at ASCO (Free ASCO Whitepaper) 2021 show significant transcriptomic differences between Luminal tumors from African American and non-Hispanic White patients, seen even more starkly as our study controlled for age, obesity, and genomic classification," said Dr. Hoskins. "The data show ER+ breast cancers in African American women more often had upregulation of the mTOR pathway and cell cycle genes, which require different treatment approaches than other ER+ breast cancers. These data tell us that we desperately need proper representation of diverse populations in clinical trials, and future studies focused on the efficacy of these agents specifically in African American women with breast cancer, so that all patients can benefit from precision medicine, tailored to them, and accounting for their ancestry and genomic profiles."

Additional data from Agendia regarding breast cancer in African American women was shared in an abstract titled "Genomic risk classification by the 70-gene signature and 21-gene assay in African American, early-stage breast cancer patients." This study was triggered by recent research showing less accurate prognostic performance of OncotypeDX in African American women with early stage breast cancer. The abstract compared MammaPrint and OncotypeDX results in a cohort of African American women with ER+ breast cancer, and observed an overall discordance of 51% between the two tests in African American patients; notably, of tumors with a TAILORx intermediate risk score (11-25), 61% were classified as MammaPrint High Risk. Combined with previously published data in African American patients, 57% of OncotypeDX low risk score tumors are re-classified as MammaPrint High Risk, suggesting that OncotypeDX results could be less accurate in African American patients.

In addition, recent data indicate that African American patients who receive a low or intermediate OncotypeDX risk score have higher recurrence rates and lower survival than Caucasian patients with early stage breast cancer with the same risk score, a difference that can have meaningful clinical implications and requires further investigation.1

"It is essential that genomic tests either work consistently across diverse groups of patients, or have the ability to be calibrated to do so," said Patricia Robinson, MD, Associate Professor of Hematology and Oncology at Loyola University Medical Center, and Assistant Dean of Diversity, Equity and Inclusion at the Strich School of Medicine, "We cannot be using genomic tests that work for some people and not others, or accepting that the tests, which offer such crucial information, work better for some than for others. While the clinical evaluation of the discrepancy between OncotypeDX and MammaPrint may be ongoing, this data still captures the diversity of pathways driving tumor metastasis, and reinforces the importance of proper representation in trials and in test development and optimization."

Agendia’s large-scale, prospective FLEX registry continues to highlight data from real-world practices in one of the most flexible and inclusive studies in breast cancer research to date, playing an important part in the company’s mission to help guide the diagnosis and personalized treatment of breast cancer for all patients throughout their treatment journey.

On June 4, 2021 Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, reported data from their collaboration with the University of Cologne (Köln, Germany) demonstrating that decreased microbiome diversity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is associated with poor clinical outcomes including mortality and increased incidence of intestinal graft-versus-host disease (GvHD) (Press release, Seres Therapeutics, JUN 4, 2021, View Source [SID1234583601]). The data are being presented in an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place virtually. A separate poster presentation, including data from a collaboration with Memorial Sloan Kettering Cancer Center (New York, NY), established a significant association between microbiome composition and response to immune checkpoint inhibitor (ICI) treatment in patients who have metastatic melanoma, metastatic lung (NSCLC), urothelial, or renal cancer.

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Seres is advancing development programs in oncology to evaluate the potential of microbiome therapeutics to modulate host immunity or inflammation to improve response and tolerability of cancer treatments. This includes SER-155, an investigational, oral, rationally-designed, cultivated microbiome therapeutic, which is advancing into a Phase 1b clinical trial to reduce the incidence of antibiotic-resistant bacterial infections and GvHD in patients following transplant procedures.

"Disruption of microbiome-modulated functions can impact clinical outcomes for patients being treated for cancer, including those who are undergoing allogeneic hematopoietic stem cell transplantation and those treated with cancer immunotherapy," said Lisa von Moltke, M.D., Chief Medical Officer at Seres. "The findings we are presenting at ASCO (Free ASCO Whitepaper) provide further evidence that our SER-155 program, as well as our earlier stage oncology programs, will help to advance our understanding of the potential of microbiome therapeutics to work with the body’s immune system to improve cancer treatment outcomes."

Clinical Evidence of Impact of Microbial Diversity on Mortality and GvHD in HSCT Patients

In collaboration with the University of Cologne, a prospective observational study was conducted to evaluate changes in microbial diversity over time in acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients undergoing allogeneic HSCT and the impact on clinical outcomes. Patients were administered antibiotics as empiric treatment for febrile neutropenia or as targeted treatment and were monitored for incidence of GvHD. Stool was collected on a weekly basis prior to an HSCT procedure and up to 28 days post HSCT, with additional samples collected at days 56, 90, and 365, as well as upon diagnosis of intestinal GvHD. Gut microbiome profiles were generated from 381 stool samples (representing 65 subjects) to evaluate the relationship between gastrointestinal microbial diversity over time and clinical outcome.

"Frequent complications associated with stem cell transplantation include antibiotic-resistant infection and GvHD. Current treatments for the prevention of GvHD rely on increased immunosuppression, leaving the patient susceptible to a host of bacterial infections – and offer limited efficacy. The findings from this prospective study demonstrate a need for continued investigation into the use of microbiome therapeutics to reduce morbidity and mortality among transplant recipients," said Christopher Ford, Ph.D., Senior Director, Computational Microbiome Sciences at Seres Therapeutics and co-author of the presentation.

Twenty-eight patients (42%) developed intestinal GvHD and 16 (25%) died prior to study completion. Across all subjects, a decline in microbiome diversity was observed immediately following HSCT. Decreased diversity and intestinal domination by two bacterial groups – Enterococcus and Enterobacteriaceae – was significantly associated with mortality across the study time course (p<0.001). Further, patients who ultimately developed intestinal GvHD had a significantly lower diversity at the time of stem cell engraftment (p<0.05) and that lower diversity was maintained throughout the study period.

Evaluation of Microbiome Composition in Correlation to Cancer-Specific Immune Checkpoint Inhibitor (ICI) Response

A study conducted with Memorial Sloan Kettering explored the relationship between microbiome composition and ICI response in patients with metastatic melanoma, metastatic lung (NSCLC), urothelial, or renal cancer. Fecal microbiome samples were collected from 94 patients (metastatic melanoma, n=17, NSCLC, n=44, urothelial, n=23, renal cancer, n=10) immediately before ICI therapy. Bacterial genomic DNA was isolated and profiled by whole metagenomic sequencing to evaluate bacterial signatures associated with response (R) and nonresponse (NR).

Treatment included anti-PD(L)1 monotherapy (n=51), anti-PD1 + anti-CTLA4 combination therapy (n=17), or a combination of anti-PD1 and chemotherapy (n=26). Clinical response was observed in 58% of patients, including partial or complete response (45%) and on treatment for more than 6 months (55%, with 31% on treatment for more than 1 year). Ordination of microbiome data from all four cancers reveals a small cluster of patients that were NR regardless of cancer type. Although the variance in the composition of pretreatment microbiome samples did not explain response alone (R vs. NR, PERMANOVA, p=0.273), a significant portion of the variance in microbiome composition was explained by the interaction of cancer type and outcome (PERMANOVA, p=0.014), suggesting a cancer-specific microbiome relationship. Notably, there was some similarity in the signature of NR across three of the four cancer types. The relationship observed in this study was also identified and corroborated in pre-clinical models of ICI response. In these models, NR was characterized by active tumor growth in mice and a lack of induction of cytotoxic CD8+ T cells after ICI treatment.

About SER-155

SER-155, an investigational oral consortium of cultivated bacteria, is a microbiome therapeutic candidate intended to advance into clinical development. SER-155 is designed using microbiome biomarker data from human clinical data, human cell-based assays, and in vivo disease models, with the aim to decrease infection and translocation of antibiotic-resistant bacteria in the gastrointestinal tract and modulate host immune responses to decrease GvHD. The rationale for this program is based in part on published clinical evidence from Seres’ collaborators at Memorial Sloan Kettering Cancer Center showing that allogeneic HSCT patients with decreased diversity of commensal microbes are significantly more likely to die due to infection and/or lethal GvHD. SER-155 was developed using Seres’ reverse translational discovery platform to reduce morbidity and mortality due to gastrointestinal infections, bacteremia and GvHD in immunocompromised patients, including in patients receiving allogeneic HSCT or solid organ transplants.

On June 3, 2021 Eli Lilly and Company (NYSE: LLY) reported that it will participate in the Goldman Sachs Healthcare Conference on June 9 and 10, 2021 (Press release, Eli Lilly, JUN 3, 2021, View Source [SID1234583435]). Anne White, senior vice president and president, Lilly Oncology and Jake Van Naarden, CEO, Loxo Oncology at Lilly, will participate in a virtual fireside chat on Wednesday, June 9 at 8:50 a.m., Eastern Time .

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A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s Investor website at View Source A replay of the presentation will be available on this same website for approximately 90 days.