On April 10, 2021 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 initial efficacy and safety data from the Phase 1 dose-escalation portion of its ongoing Phase 1/2 clinical trial of ZN-c3 in patients with advanced solid tumors who are refractory to or ineligible for standard therapy or for whom no standard therapy is available (Press release, Zentalis Pharmaceuticals, APR 10, 2021, View Source [SID1234577815]). Initial results showed that monotherapy ZN-c3 use resulted in Exceptional Responses in heavily pre-treated patients in a range of solid tumors, including Partial Responses (PRs) in ovarian cancer, colorectal cancer, non-small cell lung carcinoma and uterine serous carcinoma. Data were reviewed as a late-breaking abstract during the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held virtually April 10-15, 2021 and May 17-21, 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The initial clinical data on our WEE1 inhibitor are extremely promising and showcase ZN-c3’s strong potential to improve outcomes in patients with advanced solid tumors who have exhausted available treatment options," commented Dr. Anthony Sun, Chairman and Chief Executive Officer of Zentalis. "Our WEE1 candidate, which we believe is potentially a best-in-class small molecule, demonstrated favorable safety results with a wide therapeutic window, and resulted in Partial Responses in five patients with a range of cancers. Having identified a recommended dose for future studies, we look forward to advancing clinical trials in a larger number of patients, as well as novel biomarkers that may help select patients who are likely to respond to treatment with ZN-c3. We are looking to make Exceptional Responses commonplace."

Initial Efficacy and Safety Data

In the Phase 1 dose-escalation trial, ZN-c3 was dosed starting at 25 mg and going as high as 450 mg QD in patients with advanced or metastatic solid tumors. At the time of the data cutoff on February 12, 2021, 55 patients were evaluated for safety, the primary endpoint. The study remains ongoing and based on the data presented at AACR (Free AACR Whitepaper), ZN-c3 generated 5 Partial Responses.

Best Overall Responses:

Two confirmed PRs in ovarian cancer and colorectal cancer (CRC) patients

After receiving 18 prior lines of therapy, 11 prior lines in the advanced metastatic setting, a patient with Stage IV ovarian cancer had a RECIST-confirmed PR with a 56% reduction in overall target lesions. The patient also experienced a large rapid drop in CA-125 from 610 kU/L at baseline to 125 kU/L within 4 weeks on treatment, with her CA-125 level normalizing 3 weeks later. The patient was on study for 186 days and remains on study drug.

After receiving 5 prior lines of therapy in the advanced metastatic setting, a patient with Stage IV CRC had a RECIST-confirmed PR with a 42% reduction in overall target lesions, as well as a rapid decrease in CEA tumor marker from 327 ng/mL at baseline to <50 ng/mL after 3 weeks on treatment. The patient remained on study for 169 days until clinical disease progression.

In addition, three unconfirmed PRs—one in non-small cell lung carcinoma (NSCLC) and two in uterine serous carcinoma (USC) patients

After receiving 3 prior lines of therapy in the advanced metastatic setting, a patient with Stage IV NSCLC had an unconfirmed (per RECIST) PR with a 50% reduction in overall target lesions. The patient was on study for 145 days and remains on study drug.

ZN-c3 was generally well-tolerated as a single agent. As of the cutoff date, the most common treatment-related adverse events were mainly Grade 1/2, including nausea (49.0% of patients), diarrhea (32.7% of patients), fatigue (29.0% of patients) and vomiting (29.0% of patients) across all doses. Significant hematological adverse events were limited; treatment-related white blood cell count decrease / neutropenia (7.2% all Grades, 3.6% Grade ≥3), anemia (7.2% all Grades, 5.4% Grade ≥3) and thrombocytopenia (7.2% all Grades, 3.6% Grade ≥3).

Results from this study indicate that an oral dose of 300 mg QD with continuous dosing is the recommended Phase 2 dose of ZN-c3 when used as a monotherapy. The 300 mg QD dose demonstrated high plasma exposure levels, while minimizing adverse events. In addition, the pharmacodynamic marker of pCDK1 levels in skin punch biopsies showed active target engagement at relevant pharmacological doses. The Company initiated the Phase 1 expansion portion of the trial with the 300 mg QD dose earlier in 2021 and is exploring this candidate’s potential in combination trials including in ovarian cancer and osteosarcoma. Using this recommended dose, Zentalis will also coordinate with Zentera Therapeutics, Zentalis’ majority-owned joint venture, to initiate a Phase 1b trial investigating ZN-c3 as a single agent in China.

"WEE1 is a promising target for cancer therapy, and this dataset provides further validation on the importance of candidates like ZN-c3 that are designed to inhibit the DNA damage checkpoint, resulting in tumor cell death," said Dr. Anthony Tolcher, CEO, Founder and Director of Clinical Research at NEXT Oncology. "ZN-c3 was shown to be tolerable in this heavily pretreated patient population. Furthermore, this candidate’s early signals of anti-tumor activity are very exciting, and I am even more optimistic that WEE1 inhibition may become an important treatment approach for a wide range of cancers."

KOL Webcast Event:

Zentalis will host a webcast event with key opinion leaders Monday, April 12, 2021 at 4:00 p.m. EDT. To register and access the event, the webcast link is available on the Investors & Media section of the Zentalis website at www.zentalis.com.

About ZN-c3

ZN-c3 is an oral inhibitor of WEE1 in development for the treatment of advanced solid tumors. The inhibition of WEE1, a DNA damage response protein, aims to generate sufficient DNA damage in cancer cells, causing cell death, thereby preventing tumor growth and potentially causing tumor regression. Zentalis is currently conducting a Phase 1/2 clinical trial in patients with advanced solid tumors and reported initial data from the Phase 1 portion at the AACR (Free AACR Whitepaper) Annual Meeting 2021. In addition, the Company is also conducting a Phase 1b trial evaluating ZN-c3 in combination with chemotherapy in patients with advanced ovarian cancer, with plans to initiate a Phase 1/2 in combination with chemotherapy in osteosarcoma and a Phase 2 trial investigating ZN-c3 as a monotherapy in patients with uterine serous carcinoma in 2021.

On April 10, 2021 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 for the first time, preclinical work describing the discovery of BT7480, a novel Nectin-4/CD137 tumor-targeted immune cell agonist (TICATM), will be presented virtually in a "New Drugs on the Horizon" session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 10-15, 2021 (Press release, Bicycle Therapeutics, APR 10, 2021, View Source [SID1234577833]). Additional work covering TICAs and Bicycle Toxin Conjugates (BTCs), will also be covered in a late-breaking mini-symposium, as well as in five e-posters.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our TICA platform has made significant progress, and we are thrilled to present information about the discovery of BT7480, as well as preclinical data across multiple programs in our immuno-oncology pipeline," said Nicholas Keen, Ph.D., Chief Scientific Officer of Bicycle Therapeutics. "These presentations highlight the potential utility of Bicycle-based therapeutic candidates for treating multiple tumor types via diverse mechanisms as we pursue our goal of improving the treatment paradigm for patients with cancer."

Bicycle TICAs are potent, fully synthetic compounds that represent an immuno-oncology approach engineered to overcome the limitations of other immunomodulatory mechanisms. Bicycles are small, structurally constrained peptides discovered via phage display and optimized using structure-driven design and medicinal chemistry approaches. Bicycle has applied this disruptive technology by identifying CD137 Bicycles and chemically linking these to tumor antigen binding Bicycles to generate multifunctional molecules that induce tumor antigen-dependent, tumor-localized agonism of CD137. Bicycle expects BT7480 to enter the clinic in the second half of 2021.

Details on Bicycle’s presentations and posters at AACR (Free AACR Whitepaper) are as follows:

Poster Title: Molecular-based enrichment strategy for Nectin-4 targeted Bicycle toxin conjugate BT8009
Abstract #: 391
Session, Date and Time: Biomarkers Predictive of Therapeutic Benefit, April 10, 8:30 AM

Poster Title: Nectin-4-dependent immune cell stimulation and anti-tumor efficacy by BT7480, a Nectin-4/CD137 Bicycle tumor-targeted immune cell agonist (TICA)
Poster #: 1728
Session, Date and Time: Immunomodulatory Agents and Interventions, April 10, 8:30 AM

Poster Title: Microinjection of Nectin-4/CD137 tumor-targeted immune cell agonist (TICA) activates the local tumor microenvironment
Poster #: 1724
Session, Date and Time: Immunomodulatory Agents and Interventions, April 10, 8:30 AM

Poster Title: A multi tumor survey of Nectin-4 expression to guide BT8009 indication selection
Poster #: 1197
Session, Date and Time: Molecular Classification of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes, April 10, 8:30 AM

Poster Title: Rapid Accumulation of Cytotoxic Payload in Tumor Tissue Drives BT5528 Activity in Tumor Models
Poster #: 1319
Session, Date and Time: Novel Drug Delivery Systems, April 10, 8:30 AM

Presentation Title: BT7480, a novel Nectin-4 dependent agonist of the immune cell costimulatory receptor CD137
Session, Date and Time: New Drugs on the Horizon: Part 1, April 10, 1:30 – 3:15 OM, Channel 1

Presentation Title: Integrative surfaceome profiling identifies immunotherapeutic targets in osteosarcoma and preclinical testing of BT1769, an MT1-MMP-targeted Bicycle toxin conjugate, in osteosarcoma by the Pediatric Preclinical Testing Consortium (PPTC)
Session, Date and Time: Late-Breaking Mini-symposium 2, April 12, 1:35 – 1:45 OM, Channel 7

The posters will be available on the Publications section of bicycletherapeutics.com following each session.

On April 10, 2021 Agenus (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, cell therapies, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported new clinical data on AGEN1181, its next-generation anti-CTLA-4 antibody, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 10 – 15, 2021 (Press release, Agenus, APR 10, 2021, View Source [SID1234577849]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The preclinical and translational data in conjunction with our updated clinical data with AGEN1181 alone or in combination with our PD-1, balstilimab, continue to strongly support and differentiate our next-generation CTLA-4 antibody," said Steven O’Day, MD, Chief Medical Officer of Agenus. "AGEN1181 is showing activity in patients with tumors which typically do not respond to first-generation CTLA-4 and PD-1 antibodies. Equally important, the safety data continues to show no immune mediated hypophysitis, pneumonitis, or hepatitis to date. Given the efficacy and favorable safety profile, we have expanded AGEN1181 into Phase 2 in colorectal cancer patients as a first step in our efforts to expand to additional important cancer indications."

In two separate presentations at AACR (Free AACR Whitepaper), Agenus showcased the optimal performance of AGEN1181 in relevant models. In addition, as the clinical data matures, additional responses as well as a conversion from a partial response to a complete response, have been observed. The new data announced today include the following clinical responses:

New partial response in the first melanoma patient treated (monotherapy)

New conversion to complete response in ovarian cancer patient (AGEN1181 plus balstilimab)

Partial response in microsatellite stable (MSS) colorectal cancer patient (AGEN1181 plus balstilimab)

Partial response in PD-L1(-) ovarian cancer patient (AGEN1181 plus balstilimab)

Partial response in MSS colorectal cancer patient (AGEN1181 plus balstilimab)

Complete response in PD-L1(-) MSS endometrial cancer patient (monotherapy)

Complete response by PET in PD-L1(-) MSS endometrial cancer patient (AGEN1181 plus balstilimab)
Presentation Details:
E-poster presentations were made available on the conference platform on April 10 at 8:30am ET. Posters with accompanying audio will be available for viewing to meeting registrants until June 21.

Session: PO.IM02.10 – Therapeutic Antibodies, Including Engineered Antibodies
Poster title: Fc-enhanced anti-CTLA-4 antibody, AGEN1181: New mechanistic insights for potent antitumor immunity and combination potential in treatment-resistant solid tumors
Abstract number: 1878
Presenting author: Antoine Tanne, PhD

Session: PO.IM02.05 – Immune Monitoring / Clinical Correlates
Poster title: Characterization of the pharmacodynamic activity of AGEN1181, an Fc-enhanced CTLA-4 antibody, alone and in combination with the PD-1 antibody balstilimab
Abstract number: 1677
Presenting author: Irina Shapiro, PhD

In addition, Dr. Steven O’Day, Chief Medical Officer, Dr. Dhan Chand, Scientific Director, Head of Drug Discovery, and Dr. Jennifer Buell, President and COO, at Agenus, will participate in a webcast hosted by Dr. Matt Phipps of William Blair on Saturday, April 10, 2021 at 10:30 a.m. ET.

Registration for the webinar can be done in advance at View Source

A replay will be available after the call on the Events & Presentations page of the Agenus website at View Source

On April 10, 2021 Biodesix, Inc. (Nasdaq: BDSX), a leading data-driven diagnostic solutions company with a focus in lung disease, reported that three abstracts from multiple clinical studies will be showcased at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held virtually April 10-15, 2021 and May 17-21, 2021 (Press release, Biodesix, APR 10, 2021, View Source [SID1234577865]). Findings from these studies address the utility of physicians using blood-based proteomic testing as an approach to interpret each patient’s immune response to cancer, which can help guide treatment decisions.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Abstract #520: Potential role of serum proteome in predicting immune-related adverse events from immunotherapy in non-small cell lung cancer

An abstract authored by Young Kwang Chae, MD, MPH, MBA of Northwestern University Feinberg School of Medicine, with lead author Dr. Myungwood Nam, reports data from a study on the Primary Immune Response (PIR) test. PIR is a serum-based proteomic classifier that, in this case, was used to study the correlation between immunotherapy and the development of immune-related adverse events (irAEs) in patients with non-small cell lung cancer (NSCLC). Following a baseline PIR test, patients were categorized as sensitive or not sensitive to immunotherapy treatment, then monitored for irAEs after the start of immunotherapy. The study found that patients who had been categorized as sensitive were more likely to tolerate immunotherapy without developing irAEs. The abstract concludes that the PIR test may be able to predict the development of irAEs, and identify patients who should be monitored more closely during treatment with immunotherapy. The data will be available for viewing at 4:30 p.m. ET on April 10 and poster sessions will be available at 8:30 a.m. ET on April 10.

Abstract #673: The role of mass spectrometry-based serum proteomics signatures in predicting clinical outcomes in cancer patients treated with immune check point inhibitors (ICI)

A second abstract, also authored by Dr. Chae, presents an analysis of a recent study using PIR to predict patient responses to ICI therapy. The study found the PIR test was able to reliably stratify patients into groups based on their expected prognosis. This information can be used by physicians to help guide their frontline ICI treatment decisions for patients with NSCLC who are identified as not sensitive to immunotherapy treatment and may benefit from more aggressive treatment. This data will become available at 4:30 p.m. ET on April 10 and poster sessions will be available at 8:30 a.m. ET on April 10.

Abstract #662: Longitudinal blood-based proteomic testing in advanced non-small cell lung cancer

An abstract authored by Eric Schaefer, MD, of Highlands Oncology Group, demonstrates that the VeriStrat blood-based immune profiling test is capable of monitoring changes in disease state and patient immune response for patients with advanced NSCLC. The INSIGHT observational study (NCT03289780) found that the VeriStrat test was able to group patients according to their disease state and then monitor changes in disease state in response to treatment at 6- and 12-month follow-ups. This result suggests that longitudinal immune profile testing may be a viable option in monitoring such changes, and that the resulting data can be used to help guide treatment strategy. The data will become available for viewing at 4:30 p.m. ET on April 10.

"Our aim is to help patients access the most targeted treatment possible by providing physicians with timely, actionable data, that will assist their treatment decisions," said Scott Hutton, CEO of Biodesix. "By continuing to invest in and increase our understanding of patient immune response, we can equip physicians with critical information to help them determine the best treatment strategy for patients with NSCLC."

On April 10, 2021 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that an abstract presenting the results of a recent preclinical study on the therapeutic effects of GMI-1757, a new glycomimetic with dual antagonism to E-selectin and galectin-3, has been accepted for a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting, to be held virtually on April 10-15 and May 17-21 (Press release, GlycoMimetics, APR 10, 2021, View Source [SID1234577817]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study demonstrates that GMI-1757 significantly improved anti-PD-L1 therapeutic activity in a pancreatic adenocarcinoma model. Results showed 50% partial regressions and an approximate 99% reduction of median tumor volume. Microscopic evaluations also showed that in groups treated with GMI-1757 both the incidence and area of intratumoral fibrosis were markedly reduced. Additionally, GMI-1757 strongly increased the incidence of mononuclear cell tumor infiltration. These results suggest that the decreased intratumoral fibrotic development and increased mononuclear cell infiltration obtained with GMI-1757 created a favorable immune environment so that when combined with anti-PD-L1 it produced a more robust anti-tumor effect compared to anti-PD-L1 treatment alone. Investigations will continue on GMI-1757’s impact when combined with immune modulators where fibrosis and restricted host cell infiltration negatively impact tumor response.

GlycoMimetics Senior Vice President, Research and Chief Scientific Officer John Magnani commented, "We look forward to presenting the latest research on our novel glycomimetic compound at AACR (Free AACR Whitepaper)’s annual meeting. Our hope is that as this research progresses, we will move ever closer to achieving promising therapies for individuals living with forms of cancer where medical needs remain unmet."

Details on GlycoMimetics e-presentation at the AACR (Free AACR Whitepaper) Meeting are as follows:

Title: A novel glycomimetic compound (GMI-1757) with dual functional antagonism to E-selectin and galectin-3 attenuates fibrosis, facilitates mononuclear cell infiltration and optimizes anti-PD-L1 therapeutic activity in a pancreatic adenocarcinoma model
Presenter: William E. Fogler, Ph.D., GlycoMimetics
Session: e-Presentation
Date and Time: Saturday, April 10, 2021 (available online through Monday, June 21)

About GMI-1757

An innovative dual antagonist of E-selectin and galectin-3, GMI-1757 has shown anti-thrombotic and anti-fibrotic activity in preclinical models presented at major scientific meetings. Data suggest the compound may be able to play a role in the treatment of a variety of cancers and fibrotic conditions.