On October 9, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported further details for its late-breaking presentation of mature data from the ongoing Phase 2 RAMP 201 (ENGOT-ov60/GOG-3052) clinical trial to be presented as an oral presentation at a plenary session at the International Gynecologic Cancer Society (IGCS) Annual Global Meeting taking place October 16-18, 2024 in Dublin, Ireland (Press release, Verastem, OCT 9, 2024, View Source [SID1234647125]).

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The late-breaking abstract is embargoed until the morning of the presentation at IGCS. The oral presentation will include updated safety and efficacy data from the RAMP 201 trial evaluating the combination of avutometinib, an oral RAF/MEK clamp, and defactinib, an oral, selective FAK inhibitor, in patients with recurrent low-grade serous ovarian cancer (LGSOC), including overall response rate, progression free survival, and duration of response.

IGCS Oral Presentation Details

Title: Efficacy and Safety of Avutometinib + Defactinib in Recurrent Low Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-ov60/GOG-3052/RAMP 201
Session: Plenary 03: Oral Abstract Presentations
Date/Time: October 17, 2024, at 11:42 AM ET/4:42 PM Irish time [GMT +1].
Presenter: Professor Susana N. Banerjee, MBBS, MA PhD, FRCP, global lead investigator of the study, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research, London
Conference Call and Webcast Information

Verastem will hold an investor conference call and webcast on October 17, 2024 at 4:30 p.m. EDT, to review the mature data from the RAMP 201 trial. To access the conference call, please dial (844) 763-8274 (local) or (412) 717-9224 (international) at least 10 minutes prior to the start time and ask to be joined into the Verastem Oncology conference call. A live audio webcast of the call, along with accompanying slides, will be accessible under "Events & Presentations" in the Investors & Media section of the company’s website at www.verastem.com.

About the Avutometinib and Defactinib Combination

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other MEK-only inhibitors.

Verastem Oncology is currently conducting clinical trials with avutometinib in RAS/MAPK driven tumors as part of its Raf And Mek Program or RAMP. Verastem is currently enrolling patients and activating sites for RAMP 301 (NCT06072781), an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib, a selective FAK inhibitor, versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC). RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and enrollment has been completed for the entire RAMP 201 trial, including regimen selection and expansion of the go forward regimen.

Verastem initiated a rolling New Drug Application (NDA) submission in May 2024 to the U.S. Food and Drug Administration (FDA) for the investigational combination of avutometinib and defactinib in adults with recurrent KRAS mutant LGSOC who received at least one prior systemic therapy and expects to complete its NDA submission in the second half of 2024 with a potential FDA decision in the first half of 2025. The FDA granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib for the treatment of all patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) in combination with avutometinib and defactinib and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials, respectively. The RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award. FDA granted Orphan Drug Designation to avutometinib and defactinib combination for the treatment of pancreatic cancer.

On October 9, 2024 Schrödinger (Nasdaq: SDGR) reported that new preclinical data on SGR-3515, its investigational Wee1/Myt1 inhibitor, and the company’s PRMT5-MTA inhibitor program, will be presented during poster sessions at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium (ENA 2024) taking place October 23-25, 2024 in Barcelona, Spain (Press release, Schrodinger, OCT 9, 2024, View Source [SID1234647124]).

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The SGR-3515 presentation will include data further characterizing SGR-3515 in preclinical oncology models. Wee1 and Myt1 kinases regulate the cell cycle and DNA damage response, allowing time for DNA repair before cell division takes place. Concurrent loss of function or inhibition of Wee1 and Myt1 confers selective vulnerability in cancer cells, a mechanism referred to as synthetic lethality. The preclinical data indicate that SGR-3515 has a differentiated profile and support its continued development as a potential therapy for patients with advanced solid tumors. A Phase 1 clinical trial in this patient population is ongoing.

Additionally, preclinical data will be presented on the discovery of highly selective PRMT5-MTA inhibitors. Schrödinger has identified a novel series of selective, potent PRMT5-MTA inhibitors and is optimizing lead compounds for use in peripheral and brain tumors.

Details of the data presentations are as follows:

Title: Discovery of SGR-3515, a first-in-class Wee1/Myt1 inhibitor with differentiated pharmacological properties in xenograft tumor models
Abstract Number: 147
Presentation Date and Time: Wednesday, October 23, 2024, 12PM-2PM CEST (6AM-8AM EDT)
Location: Exhibit Hall, Barcelona International Convention Centre

Title: Discovery of a highly MTA-synergistic series of PRMT5 inhibitors for the treatment of MTAP-deficient tumors by virtual screening technology
Abstract Number: 372
Presentation Date and Time: Friday, October 25, 2024, 9AM-3PM CEST (3AM-9AM EDT)
Location: Exhibit Hall, Barcelona International Convention Centre

On October 9, 2024 Exscientia plc (Nasdaq: EXAI) reported three abstracts to be presented at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium 2024 from October 23-25, in Barcelona, Spain (Press release, Exscientia, OCT 9, 2024, View Source [SID1234647123]).

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"As our precision-designed LSD1 and MALT1 inhibitors continue to progress towards the clinic, we are excited to share new preclinical data from both programmes," said David Hallett, Ph.D., interim Chief Executive Officer and Chief Scientific Officer of Exscientia. "These posters, as well as an additional focus on our assay development, highlight the potential of our platform to design best-in-class molecules with improved properties. As our state-of-the-art automation facility continues to ramp up in scale, we look forward to further accelerating the design and development of future molecules."

The ENA posters will be available on the Exscientia website from their time of presentation.

Poster Presentations
Title: Combining next-generation BTK and MALT1 inhibitors to enhance efficacy and therapeutic utility in B-cell malignancies
Session Title: Combination therapies
Catalog Number: 218
Poster Board Number: PB206
Date/Time: Thursday, October 24 / 9:00 a.m. – 5:30 p.m. CEST

EXS73565 (‘565) is a potent, selective allosteric MALT1 inhibitor designed to have an improved safety profile, with clinical studies expected to start in early 2025
Combining MALT1 inhibitors, such as ‘565, with BTK inhibitors has the potential to provide enhanced efficacy in B-cell malignancies, by greater inhibition of pathogenic nuclear factor-kappa B (NF-kB) signalling and addressing BTK-resistance mechanisms
Exscientia researchers combined ‘565 with the BTK inhibitor zanubrutinib and observed deeper, more durable efficacy responses in xenograft models of B-cell malignancies, with long-lasting tumour eradication seen for activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL)
Studies also confirmed target pathway biology engagement, with ‘565 alone and in combination with zanubrutinib inhibiting NF-kB target gene expression in in vivo models
Overall, the selective profiles of ‘565 and zanubrutinib may maximise the therapeutic index of MALT1 and BTK inhibition in combination, providing scope for enhanced efficacy for patients with B-cell malignancies
Title: In vivo pharmacokinetics, pharmacodynamics and anti-tumour efficacy of EXS74539: A novel, reversible LSD1 inhibitor for acute myeloid leukaemia
Session Title: Epigenetic modulators (HDAC bromodomain modulators, EZH2)
Catalog Number: 250
Poster Board Number: PB238
Date/Time: Thursday, October 24 / 9:00 a.m. – 5:30 p.m. CEST

‘539 is a novel, potent, selective and reversible LSD1 inhibitor, with a highly differentiated profile and designed to be brain penetrant, expected to enter the clinic in early 2025
The poster highlights that by combining ex vivo perturbation of primary human acute myeloid lymphoma (AML) samples with ‘539 and omics profiling, 12 potential pharmacodynamic (PD) biomarker gene candidates were identified that correlate with LSD1 inhibitor activity
Upregulation of the identified biomarker gene candidates was confirmed in an in vivo AML xenograft model post ‘539 treatment
Treatment of the in vivo model with the reversible inhibitor ‘539 resulted in limited platelet level effects, highlighting how ‘539 was designed to maximise target engagement while limiting thrombocytopenia
Title: Xcellomics: Powering rapid translation of HTS outputs to AI-driven drug discovery programmes
Session Title: Functional genomics
Catalog Number: 414
Poster Board Number: PB402
Date/Time: Friday, October 25 / 9:00 a.m. – 3:00 p.m. CEST

Xcellomics is a collaboration between Exscientia and The Centre for Medicines Discovery at the University of Oxford, used to rapidly translate the results of cell-based, high-throughput screens into transformative oncology therapies
The collaboration has successfully identified and validated novel essential regulators of a key oncogenic pathway
Automated assay development and chemical hit ID performed by Exscientia rapidly pushed these novel therapeutic targets into drug discovery programmes

On October 9, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688; "Zai Lab") reported that data from a Phase 1 study of ZL-1310, the Company’s investigational antibody-drug conjugate (ADC), will be presented during a plenary session at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium (ENA) 2024 taking place October 23-25, in Barcelona, Spain (Press release, Zai Laboratory, OCT 9, 2024, View Source [SID1234647122]). The preliminary results from the ongoing, open-label, multicenter clinical trial (NCT06179069) will address the potential of ZL-1310 as a novel treatment for small cell lung cancer (SCLC).

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DLL3 is overexpressed in many neuroendocrine tumors, including SCLC, and is typically associated with poor clinical outcomes. ZL-1310 comprises a humanized anti-DLL3 antibody and a novel camptothecin derivative as its payload. The compound was designed with a novel linker-payload platform called TMALIN, which leverages the tumor microenvironment to overcome challenges associated with first-generation ADC therapies.

"New therapies that reduce off-target toxicity and increase anti-tumor effectiveness are critically needed to improve treatment options for many cancer patients, including SCLC and other tumors of neuroendocrine origin," said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. "ZL-1310 is an example of our company’s commitment to progressing a differentiated global oncology pipeline that will help fill these types of treatment gaps and provide meaningful benefit to patients. We look forward to sharing preliminary results from the Phase 1 study of this exciting next-generation ADC at ENA 2024."

Details regarding the ZL-1310 oral presentation at ENA 2024 are as follows:

Title: Preliminary Results from a Phase 1a/1b, Open-Label, Multicenter Study of ZL-1310, a DLL3-targeted ADC, to Evaluate the Safety, Tolerability, and Pharmacokinetics in Subjects with Small Cell Lung Cancer
Abstract Number: ENA24-0345
Presenter: Alex Spira, MD, PhD, FACP, FASCO, Virginia Cancer Specialists, Fairfax, VA
Presentation Date and Time: Thursday, October 24, 2024, 11:12 a.m. – 11:24 a.m. CET (presentation), 11:24 a.m. – 11:30 a.m. CET (Q&A)
Location: Centre de Convencions Internacional de Barcelona (CCIB), Room 111 and 112

On October 9, 2024 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported four accepted abstracts at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics being held October 23-25, 2024, in Barcelona, Spain (Press release, Arcus Biosciences, OCT 9, 2024, View Source [SID1234647121]). The data being presented include a growing body of evidence supporting the potential of casdatifan as a best-in-class HIF-2a inhibitor for the treatment of ccRCC.

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The oral presentation will highlight data from the approximately 30 patients in the 100mg daily monotherapy expansion cohort of ARC-20, a Phase 1/1b study evaluating casdatifan in late-line ccRCC. It will include data on safety and efficacy, including objective response rate and rate of primary progression, as well as other data to assess the depth and duration of responses. The presentation will also highlight data from the 50mg monotherapy expansion cohort of approximately 30 patients in the same setting.

"We are thrilled to be presenting the first clinical efficacy data from the ARC-20 study for our HIF-2a inhibitor, casdatifan, in an oral plenary session, as well as two additional posters that further highlight the differentiation of casdatifan in ccRCC and the therapeutic opportunities in other tumor types," said Terry Rosen, Ph.D., chief executive officer of Arcus. "These data support a potential best-in-class profile, and we are rapidly advancing a differentiated development program for casdatifan, including the planned initiation of our first Phase 3 study in the first half of 2025."

Arcus is pursuing a broad development program in both the first-line and post-anti-PD-1 settings with differentiated combinations to maximize the opportunity for casdatifan in ccRCC. In addition to the monotherapy cohorts of ARC-20, the study is also enrolling a cohort to evaluate casdatifan in combination with cabozantinib, a VEGFR tyrosine kinase inhibitor, which is intended to support the initiation of Arcus’s first Phase 3 study, PEAK-1, evaluating casdatifan in combination with cabozantinib versus cabozantinib monotherapy in patients with metastatic ccRCC who have previously received anti-PD-1 therapy. The primary endpoint will be progression-free survival with a key secondary endpoint of overall survival. Arcus also recently announced a clinical collaboration as part of its first-line strategy in advanced first-line ccRCC to evaluate casdatifan in combination with volrustomig, an investigational PD-1/CTLA-4 bispecific antibody.

Investors may dial in to the conference call at +1 (404) 975-4839 (local) or +1 (833) 470-1428 (toll-free), using Conference ID: 595409 on Thursday, October 24, 2024, at 5:00 AM PT / 8:00 AM ET. To access the live webcast and accompanying slide presentation, please visit the "Investors & Media" section of the Arcus Biosciences website at www.arcusbio.com. A replay will be available following the live event.

Four Accepted Abstracts Will Be Presented

Study

Title

Abstract Number

Session Type & Title

Session Date & Time

Casdatifan (HIF-2a Inhibitor)

ARC-20

Casdatifan in Patients (pts) with Previously Treated Clear Cell Renal Cell Cancer (ccRCC) and Other Solid Tumors; Preliminary Results From ARC-20: A Phase 1, Open-Label Dose Escalation and Expansion Study

4

Proffered Papers: Advancing patient care through novel clinical trials – Oral Plenary Session 3

10/24/2024, 10:54 AM – 11:06 AM CEST

AB521 (Casdatifan) Potently and Selectively Inhibits Hypoxia-Inducible Factor 2 Alpha (HIF-2α) Dependent Pro-Tumorigenic Activity

91

Molecular Targeted Agents

10/23/2024, 12:00 PM – 7:00 PM CEST

ARC-20

Clinical Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship for Casdatifan (AB521), a Small Molecule Inhibitor of HIF-2α, Confirms Best-in-class Potential in Treatment of Renal Cell Carcinoma

51

Molecular Targeted Agents

10/23/2024, 12:00 PM – 7:00 PM CEST

AB801 (AXL Inhibitor)

ARC-26

AB801, a Potent and Highly Selective Clinical Stage AXL Inhibitor, Sensitizes Tumors to Standard of Care Therapies

119

New Drugs

10/23/2024, 12:00 PM – 7:00 PM CEST