On April 11, 2022 SQZ Biotechnologies (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported that enhanced antigen presenting cell (eAPC) preclinical data demonstrating that delivery of multiple mRNAs encoding for disease-specific antigens together with immune stimulators (CD86 costimulatory factor and membrane bound IL-2 and IL-12 cytokines) had a synergistic effect that substantially increased killer T cells in humanized mouse models (Press release, SQZ Biotech, APR 11, 2022, View Source [SID1234611992]). The preclinical data, presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, showed this in vivo enhancement can be seen with a variety of disease antigen mRNAs across a range of HLA types. The findings indicate the potential of the company’s eAPC platform to induce a robust killer T cell response against specific diseases, and the opportunity to increase the number of patients who could potentially benefit from eAPC therapeutic candidates.

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 company’s first eAPC therapeutic candidate, SQZ-eAPC-HPV, is in a Phase 1/2 clinical trial (COMMANDER-001) in patients who have human papillomavirus positive (HPV16+) solid tumors. SQZ-eAPC-HPV delivers mRNA for HPV-specific E6 and E7 antigens, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines. This new platform represents sophisticated engineering that we believe to be an advancement over the company’s APC platform candidate, which has demonstrated promising preliminary monotherapy clinical activity in a patient with HPV16+ solid tumors.

"Our eAPC preclinical data, both in vitro and in vivo, demonstrate the synergistic potential of our multiple mRNA delivery approach on activating CD8+T cells," said Howard Bernstein, M.D., Ph.D., Chief Scientific Officer at SQZ Biotechnologies. "The inclusion of disease-specific antigens, costimulatory factor, and cytokines into a single cell therapy offers tremendous opportunity for patient impact. With the capability to engineer all three T cell activating signals simultaneously, we can pursue additional preclinical activities that could extend our eAPC platform to additional indications."

In addition to the eAPC preclinical data, a Trial in Progress poster presentation of the ENVOY-001 Phase 1/2 clinical trial will be delivered by Victoria Villaflor, M.D., City of Hope Medical Center. The presentation will summarize the ENVOY-001 study design of SQZ-AAC-HPV, the company’s first engineered red blood cell clinical candidate being investigated in patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors.

AACR EAPC MRNA HIGHLIGHTS IN HUMANIZED MOUSE MODEL

Synergistic Impact of Multiple mRNA T cell Stimulators

Mice treated with human eAPCs including mRNA for CMV antigen, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines were shown to have a dramatic increase in killer T cells compared to APCs with mRNA for antigen alone
Mice treated with human eAPCs including mRNA for influenza (Flu) antigen, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines were shown to have a three-fold increase in killer T cell compared to APCs with mRNA for antigen alone
Strong T Cell Responses Across Multiple HLA Types

Mice treated with human eAPCs including mRNA for CMV antigen, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines were shown to have higher killer T cells responses across a range of HLA types (A*01, A*02, A*11, A*24, B*07, B*35) compared to those squeezed with CMV peptide alone
AACR mRNA HIGHLIGHTS IN HUMAN PBMCs (B cell, T cell, NK cell, Monocytes)

Expansion of CD8 T Cells & Cytokine Signaling

Human PBMCs with antigen-encoding mRNA for CMV, Flu, HPV16 E6, HPV16 E7 and KRAS G12V substantially increased activation of antigen-specific T cells in vitro compared to untreated PBMCs
Membrane-bound IL-2 and IL-12 mRNA delivery in PBMC subsets led to surface expression of the cytokines and functional signaling
AACR eAPC Poster Presentation

Title: Co-delivery of antigen-encoding mRNA and signal 2/3 mRNAs to PBMCs by CellSqueeze technology generates SQZ eAPCs that prime CD8 T cells in humanized mouse model
Presenter: Scott Loughhead, PhD, SQZ Biotechnologies
Session Date and Time: Tuesday, Apr 12, 2022 9:00 AM – 12:30 PM ET
Poster Board Number: 19
Abstract Number: 2853

AACR Trial in Progress Presentation

Title: ENVOY-001: A phase 1, multicenter, open-label study of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors
Presenter: Victoria M. Villaflor, MD, City of Hope Medical Center
Session Date and Time: Wednesday, April 13, 2022 9:00 AM – 12:30 PM ET
Poster Section: 35
Abstract Number: 7645

About SQZ-AAC-HPV

SQZ Activating Antigen Carriers (AACs), derived from engineered red blood cells (RBCs), are designed to transport tumor-specific antigens and adjuvant to a patient’s own professional antigen presenting cells (APCs). The APCs would then activate CD8 killer T cells that travel to tumor sites and attack specific diseased cells. SQZ-AAC-HPV is the company’s first AAC clinical candidate, and it is being evaluated in a Phase 1/2 clinical trial (ENVOY-001 or SQZ-AAC-HPV-101) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate is being studied as a monotherapy and in combination with immune checkpoint inhibitors.

ENVOY-001 Trial Design

SQZ-AAC-HPV is being evaluated in a Phase 1/2 clinical trial (ENVOY-001) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immune checkpoint inhibitors. The study consists of two parts. The first part is designed to assess the safety and tolerability of multiple doses of SQZ-AAC-HPV monotherapy in treatment-experienced patients. The second part of the study will assess safety and tolerability of SQZ-AAC-HPV in combination with nivolumab and/or ipilimumab.

About SQZ-eAPC-HPV

SQZ Enhanced Antigen Presenting Cells (eAPC) are derived from peripheral blood mononuclear cells (PBMCs), which are primarily composed of monocytes, T cells, B cells, and NK cells, and engineered with various mRNA encoding for multiple target antigens and immuno-stimulatory signals, including CD86 and membrane-bound IL-2 and IL-12. The company has presented preclinical findings showing that SQZ eAPCs have generated robust T cell responses in human in vitro and in vivo models. Additionally, it was demonstrated that HPV16-encoding mRNA delivery to PBMCs stimulated CD8+ T cells across a range of HLA haplotypes, supporting eAPC clinical development in broader HPV16+ patient populations.

COMMANDER-001 Trial Design

SQZ-eAPC-HPV is being evaluated in a Phase 1/2 clinical trial (COMMANDER-001) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with pembrolizumab, an immune checkpoint inhibitor. The study consists of two parts. The first part is designed to assess safety and tolerability of multiple doses of SQZ-eAPC-HPV in treatment-experienced patients, following a dose-escalation scheme for monotherapy, and a dose de-escalation for the combination with pembrolizumab. The second part of the study will assess clinical response of SQZ-eAPC-HPV monotherapy in combination with pembrolizumab in immune checkpoint inhibitor treatment-naïve patient populations.

About Human Papillomavirus Positive Cancers

Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years, often leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer, HPV+ tumors account for 4.5% of all cancers worldwide resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.

On April 11, 2022 Bristol Myers Squibb Foundation (BMSF), together with its partners, National Medical Fellowships (NMF) and the American Association for Cancer Research (AACR) (Free AACR Whitepaper), reported a new name for the $100 million, five-year initiative launched in 2020 to increase diversity in clinical trials: The Robert A. Winn Diversity in Clinical Trials Award Program (Press release, Bristol-Myers Squibb, APR 11, 2022, View Source [SID1234611991]). Also, the program welcomed a donation of $14 million over the next four years from new program supporter, Gilead Sciences, Inc.

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 program, created as one of a number of commitments to health equity and diversity and inclusion made in 2020 by the BMSF and its donor Bristol Myers Squibb, has been named in honor of Robert A. Winn, M.D., Director, Massey Cancer Center, Virginia Commonwealth University. Winn is the first African-American director of a National Cancer Institute (NCI)-designated cancer center, and the recipient of numerous honors and awards, such as the NCI Center to Reduce Cancer Health Disparities Continuing Umbrella of Research Experiences Program Lifetime Achievement Award. Serving as Chair of the National Advisory Committee of the BMSF Diversity in Clinical Trials Career Development Program from its inception, Winn’s guidance was instrumental in shaping the program.

"We are proud and overjoyed that Dr. Winn has agreed to put his name on this program," said John Damonti, president, Bristol Myers Squibb Foundation. "He has been a tireless advocate for the goal of this program — enabling people of color and underserved populations to benefit more from clinical research. Throughout his distinguished career, he has demonstrated extraordinary commitment to community-engaged research focused on eliminating health inequities. It is largely due to his leadership, expertise, and passion that the program became a reality."

"I am honored to be such a small part of a big program that will have tremendous impact for years to come," said Winn.

"We congratulate Dr. Winn on this richly deserved honor," said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR (Free AACR Whitepaper). "The AACR (Free AACR Whitepaper) and the cancer research community as a whole have benefited greatly from his leadership on issues of diversity, equity, and community engagement. His innovative efforts are helping to transform cancer research into a more inclusive field of investigation that supports minority scientists and physicians and understands the urgency of addressing the disparities that have impacted underserved communities for far too long. It is fitting to name this exciting, impactful program after him, and we were pleased to celebrate him and our partnership with BMSF and NMF yesterday at the AACR (Free AACR Whitepaper) Annual Meeting Opening Ceremony in New Orleans."

Developing world-class community-oriented clinical researchers

The Robert A. Winn Diversity in Clinical Trials Award Program includes two awards: the Robert A. Winn Career Development Award for early-stage investigator physicians who are from diverse backgrounds and/or committed to increasing diversity in clinical trials, and the Robert A. Winn Clinical Investigator Pipeline Program Award for medical students who are underrepresented in medicine (URM). The BMSF has committed to support 250 Winn Career Development Awards and 250 Winn Pipeline Awards. In addition, Gilead Sciences has committed to support 10 of each award per year for the next four years.

"This program is already developing the capabilities of a diverse group of clinical researchers who are committed to engaging their communities and ensuring that all impacted people are represented in clinical trials, which is essential for a full understanding of how medicines work," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "Gilead is proud to support this work that builds on our existing efforts to ensure that greater inclusion and diversity are embedded into the design of clinical trials and to put the needs of patients first."

The first cohort of Winn Career Development Award Scholars entered the program in November 2021. These physicians are from 22 states across the U.S. and include 34 women and 18 men who represent a diverse cross section of races and ethnicities, as well as a range of experiences in the therapeutic focus areas of cancer (hematologic and solid tumors), immunologic disorders and cardiovascular diseases. Their two-year participation in the program began with an intensive AACR (Free AACR Whitepaper) educational workshop on "best-in-class" clinical trial design, followed by training in the skills and competencies needed to effectively engage with communities to foster trusted relationships aimed at recruiting diverse clinical trial participants. The Winn Career Development Award Scholars are paired in mentoring relationships with established clinical investigators, and also serve as mentors to URM medical students in the Winn Pipeline Award program.

"This program is a game-changer in the fight to advance health equity and to make both the field and practice of clinical research more inclusive. It provides a critical on-ramp for physicians and students underrepresented in medicine to become clinical investigators and lead community-oriented research that benefits all populations," said Michellene Davis, Esq, President & CEO of National Medical Fellowships. "Community-oriented research, led by diverse clinical trialists, is essential to help dismantle systemic and structural racism and to overcome the well-earned historical and present-day mistrust that communities of color have of medical research. The mentorship woven into the program is essential to career advancement and professional resiliency, which are especially important for those underrepresented in medicine."

For more information about The Robert A. Winn Diversity in Clinical Trials Award Program established by the Bristol Myers Squibb Foundation, visit diversityinclinicaltrials.org.

On April 11, 2022 Pillar Biosciences, an innovative, next-generation sequencing (NGS) solutions, in-vitro diagnostics (IVD) company, reported the presentation of clinical validation data for the FDA-PMA1 approved oncoReveal Dx Lung & Colon Cancer Assay, along with three additional posters at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Pillar Biosciences, APR 11, 2022, View Source [SID1234611990]).

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!

"Results of the validation study of Pillar’s oncoReveal Dx Lung & Colon Cancer Assay established that this FDA-approved IVD assay can accurately identify key companion diagnostic targets," said Helen Fernandes, Ph.D., Professor of Pathology at Columbia University Medical Center. "These findings are important, as they enable clinicians to confidently use results from the oncoReveal Dx test to inform therapeutic decisions, helping patients begin their treatment journey with confidence that their physician has selected the appropriate treatment for the specific cancer."

The validation study was conducted using various DNA input amounts between 5-160ng, from Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissues. Results demonstrate that oncoReveal Dx detects clinically significant variants (KRAS G12/G13, EGFR L858 and exon 19 deletion, and BRAF V600E) from as low as 10ng of DNA input with LoD between 1.5% and 2.6% (VAF, Variant Allele Frequency). In addition, across 263 clinical samples, positive percent agreement (PPA) and negative percent agreement (NPA) between oncoReveal Dx and an externally validated comparator were >99% each. For reproducibility, the average percent positive agreement (APA) and average percent negative agreement (ANA) were each >95%. These results show that oncoReveal Dx is highly accurate for the detection of clinically relevant variants and specification of associated approved therapy, and can accurately identify key companion diagnostic targets within KRAS and EGFR genes, as well as additional variants outside the companion diagnostic targeted list.

"The collective data presented at AACR (Free AACR Whitepaper) adds to the robust body of evidence supporting the accuracy and efficiency of Pillar’s suite of diagnostic testing solutions," said Randy Pritchard, CEO of Pillar Biosciences. "We believe that by decentralizing NGS testing and providing physicians with actionable, highly accurate genetic data in as little as 48 hours, we can significantly optimize selection of precision therapies to treat various cancers. We are pleased to share these data with the industry and to continue developing our NGS test portfolio in order to help make the selection of an appropriate therapy a more efficient process for the oncology community."

Three additional posters were presented at AACR (Free AACR Whitepaper). These studies were designed to support the technology of Pillar’s NGS testing platform. In a poster entitled "Single tube PCR-based NGS assay for detection of multiple gene fusions from cell free total nucleic acid", results demonstrated that Pillar’s single tube assay successfully detected fusion from cfRNA down to 0.5% VAF, and had over 99% sensitivity and specificity down to 4% VAF with as low as 10ng of DNA input. In the poster entitled, "Accurate detection of microsatellite instability (MSI) in matched and unmatched clinical tumor samples using the Pillar oncoReveal MSI panel", investigators evaluated the oncoReveal MSI Panel’s accuracy in the detection of tumor microsatellite instability (MSI) status without a matched normal tissue comparator, and found that results were comparable to the normal matched tissue context. The company also presented data on the accurate detection of tumor sequence of low tumor content samples in MRD monitoring, in a study entitled, "Accurate detection of tumor sequence at low tumor content for MRD".

The four posters are available in the "Posters" section of the company’s website at www.pillar-biosciences.com/our-presence/.

Poster Presentation Details

Abstract 5795: Validation of FDA approved oncoReveal Dx lung and colon cancer assay (oRDx-LCCA)
Date/Time: Friday, April 8, 2022, 12:00 PM – 1:00 PM ET
Session: Genomics
Session Type: E-Poster Session
Presenter: Gloria Chan Johnson

Abstract 5996: Single tube PCR-based NGS assay for detection of multiple gene fusions from cell free total nucleic acid
Date/Time: Friday, April 8, 2022, 12:00 PM – 1:00 PM ET
Session: Metastasis
Session Type: E-Poster Session
Presenter: Tejashree Modak

Abstract 5694: Accurate detection of microsatellite instability (MSI) in matched and unmatched clinical tumor samples using the Pillar oncoReveal MSI panel
Date/Time: Friday, April 8, 2022, 12:00 PM – 1:00 PM ET
Session: DNA Damage and Repair
Session Type: E-Poster Session
Presenter: Jordan Aldersley

Abstract 5066: Accurate detection of tumor sequence at low tumor content for MRD
Date/Time: Friday, April 8, 2022, 12:00 PM – 1:00 PM ET
Session: Convergence Science and Systems Biology
Session Type: E-Poster Session
Presenter: Andrew Conley

On April 11, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported the randomization of the 300th patient and thus the successful completion of patient recruitment in its phase III clinical trial COMPETE, evaluating the efficacy and safety of its lead Targeted Radionuclide Therapy candidate, ITM-11 (n.c.a. 177Lu-edotreotide), in grade 1 and 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (Press release, ITM Isotopen Technologien Munchen, APR 11, 2022, View Source [SID1234611989]). Completing patient recruitment is an important milestone demonstrating the progress of the COMPETE study, with which ITM aims to prove the potential of its therapeutic approach to provide added value to patients with GEP-NETs by improving both, treatment outcomes and the patient’s quality of life.

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!

GEP-NETs are rare types of tumors originating in the pancreas or other parts of the gastrointestinal tract. Due to their heterogeneity and unique characteristics, diagnosing GEP-NETs early is difficult, increasing the likelihood of metastatic disease and severely limiting treatment options. With ITM-11, the company is striving to address the existing unmet need, providing patients options with an effective approach to treating these life-threatening tumors. This goal is supported by results from previous studies and compassionate use, which suggest a high potential for this therapeutic approach. To further broaden its reach, ITM-11 is also being evaluated in a second phase III trial, COMPOSE, for patients with high grade 2 and grade 3 GEP-NETs.

"Targeted Radionuclide Therapy with ITM-11, may provide an effective and well tolerated treatment option for patients with GEP-NETs, who have a high unmet medical need. This highly targeted, precise approach minimizes radiation exposure of surrounding healthy tissue and helps to maintain quality of life during treatment," commented Prof. Jaume Capdevila, Principal Investigator of COMPETE at the University Hospital Vall d’Hebron in Barcelona, Spain. "We look forward to collecting further data from the study and evaluating ITM-11 in this large patient population."

"This is a very important step forward for ITM as our lead candidate continues through the final stages of the clinical trial," added Steffen Schuster, CEO of ITM. "Completing patient recruitment for COMPETE underscores the progress of our broad proprietary pipeline of radiopharmaceuticals which we hope will improve the lives of patients living with solid tumors and severely limited treatment options such as GEP-NETs. With our research and clinical studies, we strive to meet the needs of a patient population that could benefit from precision oncology treatments."

COMPETE (NCT03049189) is an international, prospective, randomized, controlled, open-label, multi-center phase III study to evaluate the efficacy and safety, of Targeted Radionuclide Therapy with ITM-11 (n.c.a. 177Lu-edotreotide) compared to targeted molecular therapy with everolimus in patients with inoperable, progressive, grade 1 and 2, somatostatin receptor-positive (SSTR+) neuroendocrine tumors of gastroenteric or pancreatic origin. The study has randomized 300 patients across multiple participating study sites worldwide. The primary endpoint of the study is progression-free survival (PFS), and secondary outcome measures include overall survival (OS).

The COMPETE study design was presented at the AACR (Free AACR Whitepaper) annual meeting 2021. ITM’s second phase III trial with ITM-11 for grade 2 and 3 GEP-NETs, COMPOSE (NCT04919226), is ongoing and was introduced at the 2021 North American Neuroendocrine Society (NANETS) symposium as well as at the 2022 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI). Sponsor of both studies is ITM’s subsidiary ITM Solucin GmbH.

About Targeted Radionuclide Therapy

Targeted Radionuclide Therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule (e.g., peptide, antibody, small molecule) that can precisely recognize tumor cells and bind to tumor-specific characteristics, such as receptors on the tumor cell surface. As a result, the radioisotope accumulates at the tumor site and decays, releasing a small amount of ionizing radiation, thereby destroying tumor tissue. The highly precise localization enables targeted treatment with minimal impact to healthy surrounding tissue.

About ITM-11 (n.c.a. 177Lu-edotreotide)

ITM-11, ITM’s therapeutic radiopharmaceutical candidate being investigated in the phase III clinical studies COMPETE and COMPOSE, consists of two components: the medical radioisotope no-carrier-added lutetium-177 (n.c.a. 177Lu) and the targeting molecule edotreotide, a synthetic form of the peptide hormone somatostatin that targets neuroendocrine tumor-specific receptors. Edotreotide binds to these receptors and places the medical radioisotope n.c.a. lutetium-177 directly onto the diseased neuroendocrine cells so that it accumulates at the tumor site. N.c.a. lutetium-177 is internalized into the tumor cells and decays, releasing medical radiation (ionizing β-radiation) with a maximum radius of 1.7 mm and destroying tumor tissue. The highly precise localization can result in the healthy tissue surrounding the targeted tumor being minimally affected.

On April 11, 2022 Circle Pharma, a pre-clinical stage company focused on developing macrocycle therapeutics against targets previously considered to be undruggable, reported that it will present a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 8-13, in New Orleans, Louisiana (Press release, Circle Pharma, APR 11, 2022, View Source [SID1234611987]).

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 Company’s presentation will provide details of its progress towards structure-guided macrocycles that inhibit the protein-protein interaction between the cyclin A:CDK2 complex and key substrates that are phosphorylated by this complex. Inhibition of Cyclin A substrate binding has been postulated to be synthetic lethal in Rb mutated cancers. The data presented include evidence that macrocycle inhibitors of cyclin A induce G2/M arrest and apoptosis in small cell lung cancer (SCLC) cell lines and have anti-tumor efficacy in SCLC xenograft animal models. Circle plans to advance its cyclin A inhibitor program to the clinic for testing in a range of cancer types, including SCLC where Rb mutations are highly prevalent.

The presentation will be made as part of the Mechanisms of Drug Action / Experimental and Molecular Therapeutics session at the AACR (Free AACR Whitepaper) meeting, Abstract No. 5379.