On September 14, 2021 KSQ Therapeutics, a biotechnology company developing drugs to treat cancer and autoimmune diseases using its proprietary, integrated discovery platform to systematically screen the whole genome in cancer and immune cells, reported the initiation of dosing in a Phase 1 clinical study of KSQ-4279, a first-in-class USP1 inhibitor, in patients with advanced solid tumors (Press release, KSQ Therapeutics, SEP 14, 2021, View Source [SID1234587683]).

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!

"This is an important milestone for KSQ as we initiate clinical development of KSQ-4279, a compound that offers great potential for robust and durable anti-tumor activity in a number of cancers," said Qasim Rizvi, Chief Executive Officer of KSQ. "This is also a strong proof point for both our team and our CRISPRomics platform, which quickly enabled us to identify and validate USP1 as a promising target that exploits synthetic lethality in cancers with specific DNA repair defects. This work was part of our broader efforts to run expansive genome-scale screens across both a diverse range of cancer cell lines and multiple immune cell types, including T cells, NK cells, and Tregs. We believe that the insights derived from our platform create tremendous opportunities to develop therapies with curative potential for a wide range of cancers, in particular solid tumors and autoimmune diseases."

"KSQ-4279 showed tumor growth inhibition as a single agent and led to deep and durable tumor regressions when administered in combination with a PARP inhibitor in multiple preclinical tumor models," said Frank Stegmeier, Ph.D., Chief Scientific Officer of KSQ. "Based on these data, we believe that KSQ-4279 has the potential to be an important treatment for many different tumor types. Additional preclinical data indicate combination opportunities beyond PARP inhibitors, which sets KSQ-4279 up as a potential pipeline of treatments within a single molecule."

KSQ-4279 preclinical data highlights:

KSQ-4279 is active as a monotherapy in ovarian PDX models, with tumor regressions observed at doses well below its maximum tolerated dose.
KSQ-4279 activity is seen in cancers that harbor specific defects in homologous recombination (HR), a genetic driver event that is prevalent in several solid tumor types.
The combination of KSQ-4279 with a PARP inhibitor led to more pronounced antitumor activity than either agent alone across multiple ovarian and TNBC PDX models, leading to durable tumor regressions in settings where PARP inhibitors only achieved partial tumor control.
Preclinical safety data indicate that KSQ-4279 is well-tolerated.
KSQ-4279 induces cell cycle arrest and DNA damage leading to apoptosis and cell death in BRCA1 mutant cells.
Functional genomic resistance screens indicate that the major genetic drivers of resistance to USP1 and PARP inhibitors are distinct, indicating that combination treatment may be able to delay or prevent the emergence of resistance.
KSQ utilized its proprietary CRISPRomics platform to identify the deubiquitinating enzyme USP1 as an attractive cancer target with established roles in DNA damage repair processes that are distinct from PARP inhibitors and other approaches currently being tested in the clinic. Potent and highly selective inhibitors of USP1 were developed, and profiling of the clinical development candidate KSQ-4279 across a large collection of tumor models confirmed an enriched response rate in cancers with genetic alterations in BRCA1/2 or other HRD lesions.

This Phase 1 clinical trial is being conducted at five centers in the United States and is expected to enroll approximately 140 patients with advanced solid tumors. It is a dose-escalation and expansion study of KSQ-4279 as a monotherapy and in combinations. The study’s primary endpoint is to assess the safety of KSQ-4279 both alone and in combination, determine the maximum tolerated dose, and establish a recommended Phase 2 dose level. Secondary endpoints include characterizing the pharmacokinetics of KSQ-4279 and evaluating its preliminary antitumor activity both alone and in combination. The trial will also explore potential predictive biomarkers and other genetic factors and their correlation with clinical outcomes.

On September 14, 2021 ROME Therapeutics, a biotechnology company harnessing the power of the repeatome for drug development, reported the completion of a $77 million Series B financing led by new investor Section 32 (Press release, Rome Therapeutics, SEP 14, 2021, View Source [SID1234587682]). In addition, new investors Sanofi Ventures, Casdin Capital, Andreessen Horowitz and Alexandria Venture Investments participated in the round, alongside existing investors ARCH Ventures, GV and Mass General Brigham Ventures (formerly Partners Innovation Fund). Concurrent with the financing, Steven J. Kafka, Ph.D., managing partner at Section 32, and Jim Trenkle, Ph.D., head of investments at Sanofi Ventures, were appointed to ROME’s Board of Directors.

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!

ROME’s mission is to harness the power of the repeatome – the roughly 60% of the human genome consisting of repetitive sequences of nucleic acids, known as repeats – to discover powerful new classes of medicines for cancer and autoimmune diseases. Repeats have long been considered part of the "dark genome," but recent discoveries have demonstrated that the repeatome has pathological consequences in cancer, autoimmune disease and other therapeutic areas. Since launching in April 2020, ROME has identified multiple repeatome-derived targets and created an internal data science platform, called repeatomics, to analyze vast quantities of data available through the repeatome.

"In the short time since our founding, ROME has made significant progress uncovering the role and mechanism of the repeatome in cancer and autoimmune disease, which has led to our foundational repeatomics platform and identification of multiple tractable targets for drug discovery," said Rosana Kapeller, M.D., Ph.D., president, chief executive officer and co-founder of ROME. "With the support of this group of premier investors, we are well-capitalized and resourced to continue advancing our lead programs into the clinic, expanding our pipeline of repeatome-derived programs and enhancing our repeatomics platform, as we seek to revolutionize the way cancer and autoimmune diseases are treated."

"Traditional genomics has transformed how we think about drug development, diagnosis and treatment; however, for too long we have been unable to extend this approach to the ‘dark genome,’" said Dr. Kafka. "Leveraging the deep insights garnered by ROME’s experienced team of drug hunters and data scientists, ROME has developed innovative tools and techniques to generate novel insights from the repeatome in order to bring forward an entirely new and important class of disease-modifying medicines."

About New Directors

Steven J. Kafka, Ph.D., is a managing partner at Section 32, a venture capital fund investing at the frontiers of technology and healthcare. Dr. Kafka serves as chairman of the board of Glympse Bio and a director at ImmuneID, as well as CEO and director of DA 32 Life Science Tech Acquisition Corp. Previously, Dr. Kafka served as both founding CEO and executive chairman of Thrive Earlier Detection, which was acquired by Exact Sciences in January 2021. Dr. Kafka also served as executive chairman of ArcherDX, Inc., which was acquired by Invitae in October 2020. Earlier, Dr. Kafka served as president and chief operating officer of Foundation Medicine, Inc., which was acquired by Roche in 2018, and held executive roles at multiple public and private oncology drug discovery and development companies. Dr. Kafka earned a Ph.D. in political economy and government from Harvard University and a B.A. in economics and political science from Stanford University.

Jim Trenkle, Ph.D., is currently head of investments at Sanofi Ventures and has a background in research and development, commercialization and early-stage biotech investing. Dr. Trenkle currently serves on the board of directors at Therini Bio, Glycomine and Veralox Therapeutics. Prior to joining Sanofi, Dr. Trenkle was part of the early team at Pivotal bioVenture Partners in San Francisco, where he served as Board observer for Entasis (ETTX), Inozyme (INZY), Akouos (AKUS), Fusion Pharmaceuticals (FSUN) and Karuna Therapeutics (KRTX). He began his career with Gilead Sciences where he held positions of increasing responsibility in medicinal chemistry, project and portfolio management and commercial strategy, largely focused on hepatitis C and other liver diseases. Dr. Trenkle holds a B.S. in honors chemistry from the University of Michigan, a Ph.D. in organic chemistry from Massachusetts Institute of Technology and an MBA from the University of California Berkeley, Haas School of Business.

On September 14, 2021 Epizyme, Inc. (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company developing and delivering novel epigenetic therapies, reported that clinical data will be presented at the upcoming 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress, taking place on September 16-21, 2021 (Press release, Epizyme, SEP 14, 2021, View Source [SID1234587681]).

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!

At the conference there will be two posters on two of the trials examining tazemetostat use in solid tumors. One details updated data from the ongoing safety run-in portion of the EZH-1101 prostate cancer study evaluating tazemetostat in combination with either abiraterone/prednisone or enzalutamide. The second poster describes the ongoing study investigating tazemetostat’s use in combination with other agents to treat solid tumors.

"Consistent with the preliminary data we shared during our Next Episode vision call earlier this year, the data presented at ESMO (Free ESMO Whitepaper) from our EZH-1101 study suggest tazemetostat combinations in prostate cancer led to a subset of patients having durable ≥50% decline in prostate-specific antigen levels (PSA50) with one patient having a radiographic tumor response," said Dr. Shefali Agarwal, Executive Vice President and Chief Medical and Development Officer at Epizyme. "We are encouraged to see the progression free survival data with a follow-up of almost two years in the safety run-in, and this data, while still maturing, will be shown in the poster session. Additionally, the adverse events data with the combination treatment were consistent with the known safety profile of the individual agents with no new safety signals. The randomized portion of the EZH-1101 study is ongoing with more than one-third of patients enrolled to date. This study is one part of our overall program exploring tazemetostat as both monotherapy and in combinations across multiple hematologic and solid tumor cancers."

Details of the presentations are listed below:

ESMO Poster Presentations

Title: Safety of Tazemetostat in Combination With Abiraterone/Prednisone or Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer
Presenters: Wassim Abida, MD, PhD; Daniel Saltzstein, MD
Abstract Code: 586P
Title: Trial in Progress: Tazemetostat in Combination With a PARP Inhibitor or Durvalumab in Patients With Solid Tumors
Presenter: Charles M. Rudin, MD, PhD; Robert L. Coleman, MD
Abstract Code: 1870TiP
The ESMO (Free ESMO Whitepaper) abstracts are available at View Source All oral and poster presentations will be available on the ESMO (Free ESMO Whitepaper) website on Thursday, September 16, 2021 8:30 a.m. CEST / 2:30 a.m. ET.

About TAZVERIK (tazemetostat)

TAZVERIK is a methyltransferase inhibitor indicated for the treatment of:

Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.
Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies.
Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.
These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

View the U.S. Full Prescribing Information here: Epizyme.com

On September 14, 2021 Seneca Therapeutics, Inc. ("STI"), a clinical-stage biopharmaceutical company dedicated to the development of targeted oncolytic immunotherapeutics for cancer based on Seneca Valley Virus (SVV-001), reported the successful development of a novel SVV-001 Patient Screening Test (Press release, Seneca Therapeutics, SEP 14, 2021, View Source [SID1234587680]). The test uses a unique set of genes to predict sensitivity to SVV-001 in tumor cells obtained from patient samples. The SVV-001 Patient Screening Test can be used on Formalin-Fixed-Paraffin-Embedded (FFPE) tumor blocks allowing for patient screening using previous biopsies. The SVV-001 Patient Screening Test will identify which cancer patients will benefit from SVV-001 treatment either as monotherapy or in combination with other immune therapies like checkpoint inhibitors. The SVV-001 Patient Screening Test can also be used to identify types of cancer patients that will benefit from SVV-001. The test can be used to screen patients for products in the SVV-001 based Armed Construct Cancer Gene Therapy Portfolio currently in development. The selection of patients using the SVV-001 Patient Screening Test will be applicable whether the patient is treated with either the Intra-tumoral or Intravenous route of administration. The SVV-001 Patient Screening Test will be available through CLIA laboratories.

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!

"Using the SVV-001 Patient Screening Test to select patients, it will be possible to identify and select cancer patients that will benefit from SVV-001 therapy either as monotherapy, combination therapy with check point inhibitors or therapy using SVV-001 Armed Constructs," said Dr. Paul Hallenbeck, CSO, President and Founder of Seneca Therapeutics. "We are excited that this pre-screening test offers the ability to selectively identify which patients will likely benefit from SVV-001."

Seneca Therapeutics is also using the SVV-001 Patient Screening Test to identify relevant cancer patient populations that could benefit from SVV-001 therapy. The company recently screened nearly 300 sarcoma samples and determined that more than 94% were sensitive to SVV-001 therapy. The work to screen other cancers for SVV-001 sensitivity is ongoing.

On September 14, 2021 Novocure (NASDAQ: NVCR) reported it has entered into a clinical trial collaboration agreement with Roche (SIX: RO. ROG; OTCQX: RHHBY), to develop Tumor Treating Fields (TTFields) together with Roche’s anti-PD-L1 therapy, atezolizumab, in metastatic pancreatic ductal adenocarcinoma (mPDAC) (Press release, NovoCure, SEP 14, 2021, View Source [SID1234587679]).

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!

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and accounts for 85%–95% of all solid pancreatic tumors. As a highly lethal malignancy, it is the seventh leading cause of cancer death worldwide and is responsible for more than 300,000 deaths per year. PDAC is highly resistant to current therapies, affording patients a 5-year overall survival rate of only 7.2%.

"We are pleased to collaborate with Roche, a global leader in oncology, to explore the efficacy of TTFields together with atezolizumab immunotherapy in pancreatic cancer," said William Doyle, Novocure’s Executive Chairman. "The immune-shielded environment of the pancreas has proved challenging for immunotherapies alone to provide benefit. Our phase 2 pilot trial with Roche will study the ability of TTFields together with atezolizumab to improve clinical outcomes for patients with this deadly disease."

The phase 2 study was designed to test the safety and efficacy of TTFields together with atezolizumab, gemcitabine and nab-paclitaxel as a first-line treatment for mPDAC. The study is designed to enroll approximately 75 patients in the EU and United States. The primary endpoint of the study is disease control rate by RECIST 1.1. The secondary endpoints include overall survival, progression free survival, one year survival, objective response rate, PFS at six months, duration of response, and toxicity profile. Novocure is the study sponsor and Roche is providing atezolizumab for the trial.

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division.

When cancer develops, rapid and uncontrolled division of unhealthy cells occurs. Electrically charged proteins within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. All cells are surrounded by a bilipid membrane, which separates the interior of the cell, or cytoplasm, from the space around it. This membrane prevents low frequency electric fields from entering the cell. TTFields, however, have a unique frequency range, between 100 to 500 kHz, enabling the electric fields to penetrate the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected.

Whether cells are healthy or cancerous, cell division, or mitosis, is the same. When mitosis starts, charged proteins within the cell, or microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts and the two daughter cells separate. TTFields can interfere with these conditions. When TTFields are present in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electrical forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death.

TTFields are intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a network of preclinical collaborators and a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 20,000 patients have been treated with TTFields.