On April 11, 2022 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, reported results from the Phase 3 ALPINE trial showing BTK inhibitor BRUKINSA (zanubrutinib) demonstrated superiority versus ibrutinib in overall response rate (ORR) as assessed by an Independent Review Committee (IRC) in adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (Press release, BeiGene, APR 11, 2022, View Source [SID1234611994]).

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After achieving superiority in the primary endpoint of investigator-assessed overall response rate at the interim analysis, in this final response analysis, BRUKINSA met the primary endpoint of superiority over ibrutinib in ORR as determined by IRC, with a response rate of 80.4% versus 72.9% (2-sided p=0.0264). ORR is defined as the combined rate of complete responses (CR) and partial responses (PR). A total of 652 patients were enrolled in the ALPINE trial across Europe (60%), the United States (17%), China (14%), New Zealand and Australia (9%) and were followed for a median of 24.2 months. The next planned analysis of ALPINE data will be the PFS final analysis.

BRUKINSA was generally well tolerated with safety results consistent with previous studies. A prespecified safety analysis showed the rate of atrial fibrillation or flutter continued to be lower in the BRUKINSA arm. The rate of atrial fibrillation or flutter at 24.2 months of median follow-up was 4.6% (n=15) in the BRUKINSA arm and 12.0% (n=39) in the ibrutinib arm. Among 324 patients in each arm, 13.0% (n=42) of patients who received BRUKINSA discontinued treatment due to adverse events compared to 17.6% (n=57) of patients who received ibrutinib. The most commonly reported grade 3 or higher adverse events for BRUKINSA versus ibrutinib, respectively, were neutropenia (14.2% vs. 13.9%), hypertension (12.7% vs. 10.2%), pneumonia (4% vs. 7.4%), neutrophil count decreased (4.3% vs. 4.0%), COVID-19 pneumonia (4.3% vs. 3.1%).

"We are pleased to announce updated topline data from the Phase 3 ALPINE trial for BRUKINSA, which demonstrated a superior overall response rate versus ibrutinib in CLL patients who have seen their disease return or spread after prior therapy," said Dr. Lai Wang, Global Head of Research & Development at BeiGene. "We understand that for people living with CLL and their families, relapse and treatment resistance are especially devastating. That’s why we are encouraged by this final response analysis, which adds to the growing body of clinical evidence for BRUKINSA as a potential treatment for CLL."

BeiGene has submitted results from the ALPINE trial in support of marketing authorization applications for BRUKINSA in CLL in the U.S., EU and other markets around the world. In February 2022, BeiGene announced that the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have accepted supplemental new drug applications for BRUKINSA in CLL. In the U.S., the Prescription Drug User Fee Act (PDUFA) target action date is October 22, 2022.

Interim results from the ALPINE trial representing a 12-month study follow-up were presented at the 26th European Hematology Association (EHA) (Free EHA Whitepaper) 2021 (EHA2021) Virtual Congress in June 2021 and showed BRUKINSA demonstrated superiority in ORR versus ibrutinib, per investigator assessment.

About Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia is the most common form of leukemia in adults. CLL accounts for about one quarter of new cases of leukemia, and in 2021 there were more than 21,000 new cases diagnosed in the U.S. In 2018, there were an estimated 195,129 people living with chronic lymphocytic leukemia in the United States.i CLL begins in cells that become certain white blood cells (lymphocytes) in the bone marrow but then go into the blood. Proliferation of cancer cells (leukemia) in the marrow result in reduced ability to fight infection and spread into the blood, which affects other parts of the body including the lymph nodes, liver and spleen.ii,iii,iv The BTK pathway is a known route that signals malignant B cells and contributes to the onset of CLL.v Small lymphocytic lymphoma is a non-Hodgkin’s lymphoma affecting the B-lymphocytes of the immune system, which shares many similarities to CLL but with cancer cells found mostly in lymph nodes.vi

About ALPINE

ALPINE is a randomized, global Phase 3 trial (NCT03734016) comparing BRUKINSA against ibrutinib in previously treated patients with relapsed or refractory chronic lymphocytic leukemia CLL or SLL.

In the trial, a total of 652 patients were randomized into two arms, with the first receiving BRUKINSA (160 mg orally twice daily) and the second receiving ibrutinib (420 mg orally once daily) until disease progression or unacceptable toxicity. The primary analysis of ORR, defined by pre-specified non-inferiority of BRUKINSA versus ibrutinib, was assessed by investigator and IRC using the modified 2008 iwCLL guidelines, with modification for treatment-related lymphocytosis for patients with CLL, and per Lugano Classification for non-Hodgkin’s lymphoma for patients with SLL. There was hierarchical testing of non-inferiority followed by superiority in ORR as assessed by investigator and IRC. Key secondary endpoints include PFS and event rate of atrial fibrillation or flutter; other secondary endpoints include duration of response, overall survival, and incidence of adverse events. The study is ongoing with a planned formal analysis of PFS when the target number of events is reached.

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA has previously been approved for three indications in the United States: for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (Nov. 2019)*; for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) (Aug. 2021); and for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (Sept. 2021)*.

BRUKINSA is supported by a broad clinical program which includes more than 3,900 subjects in 35 trials across 28 markets. To date, BRUKINSA has received more than 20 approvals covering more than 40 countries and regions, including the United States, China, the EU and Great Britain, Canada, Australia and additional international markets. Currently, more than 40 additional regulatory submissions are in review around the world.

* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 27% of patients, most commonly pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 8% of patients. Other second primary malignancies included malignant solid tumors (4.0%), melanoma (1.7%) and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter were reported in 3.2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse reactions

The most common adverse reactions, including laboratory abnormalities, in ≥ 30% of patients who received BRUKINSA (N = 847) included decreased neutrophil count (54%), upper respiratory tract infection (47%), decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%) and musculoskeletal pain (30%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information at www.beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at www.beigene.com/PDF/BRUKINSAUSPPI.pdf.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 2,900 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 14,500 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU and U.K., Canada, Australia and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, including a biologics license application (BLA) under FDA review, BeiGene and Novartis announced an option, collaboration and license agreement in December 2021 for BeiGene’s TIGIT inhibitor ociperlimab that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis Oncology products across designated regions of China.

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.

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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.

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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]).

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"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.

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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.