On November 6, 2024 Senhwa Biosciences, Inc. (TPEx: 6492), a new drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, reported that the enrollment of the first patient at Penn State Health Children’s Hospital in its Phase I/II clinical study evaluating the efficacy of Silmitasertib (CX-4945) in combination with chemotherapy for children and young adults with relapsed or refractory solid tumors (Press release, Senhwa Biosciences, NOV 6, 2024, View Source [SID1234647855]). This innovative trial seeks to establish a recommended dose of Silmitasertib in combination with chemotherapy and assess the safety, tolerability and efficacy in patients with cancer, with a focus on neuroblastoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma.

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"This clinical trial is a critical piece in understanding the mechanism of how the medicine works and develop more precise treatments for our patients," said Dr. Chandrika Behura, study chair and principal investigator, Four Diamonds researcher and associate professor of pediatrics at the College of Medicine. "It’s very important to develop the right combination that can be the most toxic to cancer cells, but the least harmful to the normal cells around them."

The study is projected to enroll up to 114 participants nationwide through the Beat Childhood Cancer Research Consortium member hospitals. By evaluating the activity of the study treatments based on individual responses and duration of disease control, the trial aims to develop novel therapeutic approaches.

"We are thrilled to be able to move this important research forward on a larger scale," said Dr. Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium. "The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally."

With the College of Medicine serving as its home, the Beat Childhood Cancer Research Consortium is a worldwide network of more than 50 universities and children’s hospitals focused on saving lives and helping the Children’s Hospital make a lasting difference around the world. Funding for this clinical trial is provided by the Beat Childhood Cancer Foundation and the Little Warrior Foundation. Funding for Behura’s research which led to the clinical trial was provided by Four Diamonds.

"This is the culmination of the work of many people over the years," said Suzanne Graney, executive director of Four Diamonds. "Without the dedication of our physician-scientists and the generosity of our donors and community, this kind of essential work to improve treatments with an ultimate goal of curing cancer would not be possible."

The pediatric cancer care specialists at Beat Childhood Cancer Research Consortium hospitals and researchers at the College of Medicine are dedicated to turning groundbreaking discoveries into lifesaving treatments for childhood cancer.

"By expanding our research and increasing clinical trials, we are exploring immunotherapy, cellular therapy and precision medicine to deliver the most optimized care to each unique patient," said Dr. Dr. Yatin Vyas, pediatrician-in-chief and chair of the Department of Pediatrics at the Children’s Hospital.

"We are greatly honored to collaborate with the Penn State College of Medicine and Beat Childhood Cancer Research Consortium, which have been diligently fighting childhood cancers by infusing invaluable resources from over 50 universities and children’s hospitals across the United States for the clinical study," said Jin-Ding Huang, PhD, CEO of Senhwa Biosciences, Inc. "We appreciate for having the opportunity of providing Silmitasertib as a potential effective treatment and look forward to realizing its therapeutic value in this urgently needed field for childhood cancers though this study".

On November 6, 2024 AstraZeneca reported its ambition to redefine cancer care with new data across its industry-leading and diverse pipeline in haematology at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition 7 to 10 December 2024 (Press release, AstraZeneca, NOV 6, 2024, View Source [SID1234647854]).

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A total of 57 abstracts will feature 13 approved and potential new medicines from across AstraZeneca’s portfolio and pipeline in haematology, including from Alexion, its rare disease group, with data in key settings including chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), paroxysmal nocturnal haemoglobinuria (PNH) and other haematologic diseases.

Anas Younes, Senior Vice President, Haematology R&D, AstraZeneca, said: "Our data at ASH (Free ASH Whitepaper) from the AMPLIFY Phase III trial will demonstrate the efficacy and safety of our leading second-generation BTK inhibitor, Calquence, as a fixed-duration therapy in first-line CLL. In addition, new results for our novel T-cell engager, AZD0486, will reinforce its promising clinical profile in lymphomas, and data for our novel CAR T cell therapy, AZD0120, will highlight the potential of this therapy to transform treatment in multiple myeloma."

Christophe Hotermans, Senior Vice President, Head of Global Medical Affairs, Alexion, said: "Our ASH (Free ASH Whitepaper) presentations will highlight the transformative impact of our medicines, including new analyses from the ALPHA Phase III trial reaffirming the safety and efficacy of our first-in-class Factor D inhibitor Voydeya as add-on to Ultomiris or Soliris for the subset of patients with PNH experiencing clinically significant extravascular haemolysis. Further, new insights from our robust pipeline will enhance the understanding of several rare haematologic and cardiovascular conditions, underscoring our commitment to innovation in rare disease."

Calquence combinations demonstrate significant benefits across CLL and MCL

An oral presentation on interim results from the pivotal AMPLIFY Phase III trial will demonstrate the potential of fixed-duration Calquence in combination with venetoclax, with or without obinutuzumab, in previously untreated adults with CLL compared to standard-of-care chemoimmunotherapy.1 These results will be featured during the ASH (Free ASH Whitepaper) Press Briefing on Sunday 8 December.

An updated analysis from the pivotal ECHO Phase III trial will further highlight the use of Calquence in combination with bendamustine and rituximab as a first-line treatment option by demonstrating high and durable undetectable minimal residual disease (MRD) rates in previously untreated patients with mantle cell lymphoma (MCL) as well as showing the benefit of Calquence across all patients including those with high-risk disease characteristics.2 Results from ECHO were first presented as a late-breaking oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress in June.3

Results will also be shared from the ChangE Phase III trial, evaluating Calquence compared with chlorambucil plus rituximab in first-line CLL in patients in China.4

New data show promise of next generation T-cell engagers and chimeric antigen receptor T-cell (CAR T) therapy

Two oral presentations will share results for the novel CD19xCD3 bispecific T-cell engager AZD0486, reinforcing the potential of this novel medicine as a new treatment option for B-cell malignancies.5,6 Phase I results demonstrate high response rates, with a 96% overall response rate, 85% complete response rate and high rates of undetectable MRD in patients with relapsed/refractory follicular lymphoma (R/R FL) at doses of 2.4 mg and above.5 Additionally, interim Phase I results will show the early potential of AZD0486 in patients with heavily pretreated diffuse large B-cell lymphoma (DLBCL).6 Data will also reinforce the safety profile of AZD0486, with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events effectively mitigated by the double step-up dosing schedule.7

Early data for AZD0120 (GC012F), a novel BCMAxCD19 dual-targeting autologous CAR T developed using the Gracell FasTCAR rapid manufacturing process, will show potential as a first-line therapy for elderly patients with newly diagnosed transplant ineligible MM.8 Preliminary results from the ongoing investigator-initiated trial of AZD0120 suggest deep responses and an acceptable safety profile, with no ICANS and no ≥Grade 2 CRS events observed in this patient population.8

An oral presentation will share preclinical data demonstrating the anti-tumour activity of AZD5492, a next-generation CD8 selective, CD20-targeting T-cell engager, designed using AstraZeneca’s innovative Target Induced T-cell Activating Nanobody (TITAN) platform. AZD5492 is currently being evaluated in Phase I clinical trials in R/R Non-Hodgkin lymphoma (NHL) and CLL.9

Voydeya (danicopan) as add-on to Ultomiris (ravulizumab) or Soliris (eculizumab) demonstrates low rate of mild or moderate BTH events and improves quality of life measures in patients with PNH and clinically significant EVH

Data will be presented detailing events of breakthrough haemolysis (BTH), a key indicator of intravascular haemolysis and PNH disease control, reported in the ALPHA trial evaluating Voydeya as add-on to Ultomiris or Soliris in patients with PNH experiencing clinically significant extravascular haemolysis (EVH) and separately in the PEGASUS Phase III trial evaluating pegcetacoplan in patients with PNH previously treated with Soliris. Data will show that 5/84 patients (6.0%) in the ALPHA trial and 19/80 patients (23.8%) in the PEGASUS trial experienced one or more BTH events. Moreover, most BTH events (6/7 or 85.7%) in the ALPHA trial were either mild or moderate, and all events were resolved without transfusion, dose modification or treatment withdrawal.10

Separately, final long-term patient-reported outcomes from the ALPHA trial will demonstrate Voydeya as add-on to Ultomiris or Soliris resulted in sustained improvements in fatigue, quality of life and physical function for up to 72 weeks in the subset of patients with PNH who experience clinically significant EVH.11

Advancing understanding of life-threatening rare diseases

A US, retrospective chart review will provide real-world evidence showing haematologic and renal improvements in adults with atypical haemolytic uraemic syndrome (aHUS) who switched to Ultomiris after short-term use of Soliris, with early responses and continued improvements through one year of treatment with Ultomiris.12

Additionally, two presentations on amyloid light chain (AL) amyloidosis will highlight unmet medical needs in this progressive, debilitating disease, reinforcing the importance of bringing forward novel therapies to improve cardiovascular outcomes and organ function.13,14

Key presentations during the 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition

Lead Author

Abstract Title

Presentation details (PST)

Calquence (acalabrutinib)

Brown, JR et al.

Fixed-Duration Acalabrutinib plus Venetoclax with or without Obinutuzumab versus Chemoimmunotherapy for First-Line Treatment of Chronic Lymphocytic Leukemia: Interim Analysis of the Multicenter, Open-label, Randomized, Phase 3 AMPLIFY Trial

Abstract #1009

Oral Session 642: Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Frontline Targeted Therapy Combinations

9 December 2024

4:30 PM

Qiu, L et al.

Acalabrutinib Versus Chlorambucil Plus Rituximab in Patients with Previously

Untreated Chronic Lymphocytic Leukemia: A Randomized, Multicenter, Open Label, Phase 3 Study

Abstract #3251

Poster Session 642: Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II

8 December 2024

6:00 – 8:00 PM

Dreyling, M et al.

High-risk Subgroups and MRD: An Updated Analysis of the Phase 3 ECHO Trial of Acalabrutinib with Bendamustine/Rituximab in Previously Untreated Mantle Cell Lymphoma

Abstract #1626

Poster Session 623. Mantle Cell, Follicular, Waldenstrom’s and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I

7 December 2024

5:30 – 7:30 PM

Simon, F et al.

Efficacy and Safety of Acalabrutinib Treatment in Very Old (≥80y) and/or Frail

Patients with Chronic Lymphocytic Leukemia (CLL) – Primary Endpoint Analysis of the Phase II CLL-Frail Trial

Abstract #4618

Poster Session 642: Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III

9 December 2024

6:00 – 8:00 PM

Swaminathan, M et al.

Early Obinutuzumab Significantly Increases Bone Marrow Undetectable MRD (10-4 sensitivity) (uMRD4) Rate when Combined with Acalabrutinib and Venetoclax in a Randomized Phase II Trial for Treatment Naïve CLL

Abstract #1855

Poster Session 642: Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I

7 December 2024

5:30 – 7:30 PM

Jerkeman, M et al.

Acalabrutinib and Rituximab in Elderly Patients with Newly Diagnosed Mantle Cell Lymphoma Including a Matched Population-Based External Comparator- the Nordic Lymphoma Group NLG-MCL8 (ALTAMIRA) Phase II Trial

Abstract #747

Oral Session 623: Mantle Cell, Follicular, Waldenstrom’s and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Updates on Drug Treatments for Mantle Cell Lymphoma, and CAR-T and Transplants for Indolent Lymphomas

9 December 2024

11:00 AM

Christofyllakis, K et al.

Toxicity of R-mini-CHOP with or without Acalabrutinib in Older Adults with Untreated DLBCL – An Interim Analysis of Serious Adverse Events in the ARCHED / GLA 2022-1 Randomized, Open-Label, Phase 3 Trial

Abstract #4498

Poster Session 627: Aggressive Lymphomas: Pharmacologic Therapies: Poster III

9 December 2024

6:00 – 8:00 PM

AZD0486

Gaballa, S et al.

Evaluation of AZD0486, a Novel CD19xCD3 T-Cell Engager, in Relapsed/Refractory Diffuse Large B-cell Lymphoma in an Ongoing First-in-Human Phase 1 Study: High Complete Responses Seen in CAR-T–naive and CAR-T–exposed Patients

Abstract #868

Oral Session 627: Aggressive Lymphomas: Pharmacologic Therapies: Novel Monotherapies or Novel Disease Indications

9 December 2024

3:30 PM

Hou, J et al.

Escalating Doses of AZD0486, a Novel CD19xCD3 T-cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma

Abstract #341

Oral Session 623: Mantle Cell, Follicular, Waldenstrom’s and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Novel Treatment Strategies and New Data on Old Standards for Follicular Lymphoma

7 December 2024

5:00 PM

Zhu, X et al.

Exposure-Response analysis and Quantitative Systems Pharmacology modelling for an optimal dose selection of AZD0486 in follicular lymphoma patients

Abstract #2794

Poster Session 605: Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II

8 December 2024

6:00 – 8:00 PM

AZD0120

Du, J et al.

A phase I study of dual targeting BCMA and CD19 FasTCAR-T cells (GC012F)

as first-line therapy for transplant-ineligible newly diagnosed multiple myeloma

Abstract #2072

Poster Session 704: Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I

7 December 2024

5:30 – 7:30 PM

AZD5492

Lawrence, R et al.

Pre-Clinical Evaluation of AZD5492, a Novel CD8-Guided T Cell Engager, for B-Non-Hodgkin Lymphoma Indications

Abstract #959

Oral Session 605: Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Novel Therapeutic Approaches in Lymphoma

9 December 2024

5:30 PM

Voydeya (danicopan)

Schrezenmeier, H

Breakthrough Hemolysis Events in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from Danicopan and Pegcetacoplan Trials

Abstract #2694

Poster Session 508: Bone Marrow Failure: Acquired: Poster II

8 December 2024

6:00 PM

Piatek, C

Danicopan as Add-On Therapy to Ravulizumab or Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Long-Term Patient-Reported Outcomes from the Phase 3 ALPHA Trial

Abstract #2692

Poster Session 508: Bone Marrow Failure: Acquired: Poster II

8 December 2024

6:00 PM

Ultomiris (ravulizumab) and Soliris (eculizumab)

Griffiths, E

Real-World Drug Adherence, Persistence, and Healthcare Resource Utilization in Patients with Paroxysmal Nocturnal Hemoglobinuria in the USA: The ADVANTAGE Study

Abstract #5074

Poster Session 905: Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies

9 December 2024

6:00 PM

Chaturvedi, S

Real-World Effectiveness of Ravulizumab Among Adults with Atypical Hemolytic Uremic Syndrome (aHUS) who Switched to Ravulizumab Within 3 Months of Eculizumab Treatment: A Physician Panel-Based Chart Review Study (aHUS IMPACT)

Abstract #2613

Poster Session 330: Vascular Biology, Thrombosis, and Thrombotic Microangiopathies: Basic and Translational

8 December 2024

6:00 PM

Iori, AP

REACTION – Real Life Use of Ravulizumab in Italian PatiEnts with PAroxysmal NoCturnal Hemoglobinuria a MulTicenter ObservatIONal Retrospective and Prospective Cohort Study, Final Results

Abstract #2464

Poster Session 101: Red Cells and Erythropoiesis, Excluding Iron

8 December 2024

6:00 PM

PNH

Wagner-Ballon, O

High Proportion of PNH Type II Neutrophils, l.e Relative Percentage 3%, Is Associated with Thrombosis in Patients Displaying a PNH Clone >1%: Evidence from Analysis of the 5-Year French Nation-Wide Multicenter Observational Study

Abstract #4080

Poster Session 508: Bone Marrow Failure: Acquired: Poster III

9 December 2024

6:00 PM

HSCT-TMA

Dandoy, C

Survival Outcomes in Adult and Pediatric Patients Who Experienced Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis

Abstract #7286

Online Publication

Amyloidosis

Laires, P

Comparison Of Alternative Mayo Staging Classification Systems Used in Light-Chain Amyloidosis

Abstract #6887

Online Publication

Thompson, J

Evaluation of Functional Cardiac Measures and Response to Treatment Initiation in Patients with Systemic Light-Chain (AL) Amyloidosis: Results from a Single Site Retrospective Study

Abstract #4677

Poster Session 652: MGUS, Amyloidosis, and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological

9 December 2024

6:00 PM

On November 6, 2024 Oncotelic Therapeutics, Inc (OTCQB:OTLC) reported its presentation at SITC (Free SITC Whitepaper) 2024. Dr. Cynthia Lee, VP of R&D will be presenting Sapu Bio pipeline of TGFB2 therapeutics (Press release, Oncotelic, NOV 6, 2024, View Source [SID1234647853]). For additional information please go to: View Source

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Dr. Lee has been leading our R&D programs for the past several years including the buildout of our GMP facility in San Diego. The presentations are:

Abstract Number 198: TGFB2 mRNA levels prognostically interact with Interferon-alpha receptor activation of IRF9 and IFI27, and makers for tumor-associated macrophages impacting overall survival in PDAC. Authors Sanjive Qazi, Cynthia Lee, Vuong Trieu

Abstract Number 218: Evaluating the prognostic impact of Transforming growth factor beta 2 mRNA levels, in conjunction with Interferon-gamma receptor activation of IRF5 and expression of CD276/B7-H3 in low-grade gliomas. Authors Sanjive Qazi, Anthony Maida, Vuong Trieu

Abstract Number 1444: Meta-analysis comparing the incidence of serious adverse events, overall survival, and progression-free survival in PDAC patients harboring unresectable tumors treated with mFOLFIRINOX or FOLFIRINOX. Authors Vuong Trieu, Sanjive Qazi, Seymour Fein, Anthony Maida, Tenshang Joh

On November 6, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported business updates and announced financial results for the third quarter ended September 30, 2024 (Press release, Verastem, NOV 6, 2024, View Source [SID1234647852]).

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"In the third quarter of 2024, we made advancements in our recurrent low-grade serous ovarian cancer program, including sharing updated Phase 2 RAMP 201 data demonstrating robust and durable response rates, tumor reductions across a majority of patients regardless of their KRAS mutation status, and low discontinuation rates due to adverse events. We also completed our rolling NDA submission for recurrent KRAS mutant low-grade serous ovarian cancer and strengthened our balance sheet," said Dan Paterson, president and chief executive officer of Verastem Oncology. "Looking ahead to the fourth quarter of 2024, we anticipate an FDA decision on the acceptance of our NDA, plan to submit our updated RAMP 201 trial data for publication and expect to prepare a U.S. IND application for VS-7375, an oral KRAS G12D (ON/OFF) inhibitor."

Third Quarter 2024 and Recent Updates

Avutometinib and Defactinib Combination in Low-Grade Serous Ovarian Cancer (LGSOC)

Completed the rolling New Drug Application (NDA) submission for the combination of avutometinib and defactinib for adult patients with recurrent KRAS mutant LGSOC, who received at least one prior systemic therapy, in October 2024. The Company submitted the NDA under the U.S. Food and Drug Administration (FDA) Accelerated Approval pathway and requested Priority Review based on the combination’s potential to address significant unmet medical need among patients with recurrent LGSOC.
RAMP 301, which is currently enrolling patients with recurrent LGSOC regardless of KRAS mutation status across the U.S., UK, EU, Canada, and Australia, will serve as a confirmatory study for the initial indication and has potential to expand the indication regardless of KRAS mutation status. The Company plans to complete enrollment in RAMP 301 by the end of 2025. The Company plans to map out a path forward with the FDA for the KRAS wild-type indication, including the ability to leverage data from the ongoing RAMP 301 Phase 3 trial.
Announced mature data from the RAMP 201 trial that continued to show robust and durable response rates with low discontinuation rates due to adverse events in patients with recurrent KRAS mutant or KRAS wild-type LGSOC who had a minimum follow-up of 12 months, at the International Gynecologic Cancer Society (IGCS) 2024 Annual Meeting on October 17, 2024. The primary analysis of the RAMP 201 trial, with a data cutoff of June 30, 2024, showed a confirmed overall response rate (ORR) by blinded independent central review (BICR) of 31% (34/109; 95% CI: 23-41), 44% (25/57; 95% CI: 31-58) in KRAS mutant LGSOC, and 17% (9/52; 95% CI: 8-30) in KRAS wild-type LGSOC. The majority (82%) of all patients had a reduction in their tumors, regardless of KRAS status. The updated data continue to demonstrate avutometinib in combination with defactinib is generally well-tolerated, with a 10% discontinuation rate due to adverse events (AEs) and no new safety signals.
The Company continued its commercial preparation activities for a potential U.S. launch in mid-2025.
The Japanese Gynecologic Oncology Group (JGOG) dosed the first patient in a Phase 2 Verastem sponsored clinical trial, called RAMP201J, evaluating the safety and efficacy of avutometinib in combination with defactinib for recurrent LGSOC in Japan in October 2024.
Avutometinib in Combination with KRAS G12C Inhibitors in Non-Small Cell Lung Cancer (NSCLC)

Following a thorough evaluation of the Company’s lung cancer clinical development program, Verastem has decided to discontinue the Phase 1/2 RAMP 204 clinical trial evaluating the combination of avutometinib and adagrasib in patients with KRAS G12C-mutant NSCLC. There are no safety concerns with the RAMP 204 trial. The Company is prioritizing the Phase 1/2 RAMP 203 clinical trial, which is evaluating the doublet of avutometinib and sotorasib and the triplet combination of avutometinib and sotorasib plus defactinib in similar patient populations.

Since the last update of RAMP 203 in October of 2023, enrollment to the doublet of avutometinib plus sotorasib for the KRAS G12C inhibitor naïve Stage I Part B cohort has recently completed, and per protocol patients are being followed to determine if the efficacy supports further expanded enrollment into Stage II. The KRAS G12C inhibitor prior-treated Stage I Part B cohort enrollment is nearly complete.
Earlier this year, RAMP 203 was modified to include the triplet combination of avutometinib and sotorasib plus defactinib and the first safety cohort of this triplet has been fully enrolled. Preclinical data provide strong evidence that addition of a FAK inhibitor to the sotorasib and avutometinib doublet has the potential to deepen anti-tumor response and significantly delay tumor progression.
Expect to report updated interim data from the doublet combination of avutometinib plus sotorasib and provide initial safety data and a status of enrollment for the triplet combination of avutometinib, sotorasib and defactinib in the RAMP 203 trial by the end of 2024.
Avutometinib and Defactinib Combination in First-Line Metastatic Pancreatic Cancer

Preclinical data outlining the scientific rationale for the combination of avutometinib plus defactinib with standard of care chemotherapy was published in the October 23, 2024 edition of Science Translational Medicine.
Presented initial interim safety and efficacy results from the ongoing RAMP 205 trial of avutometinib and defactinib in combination with current standard of care gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer on June 1, 2024, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
Expect to report updated data from the ongoing RAMP 205 trial in Q1 2025.
VS-7375/GFH375: Oral KRAS G12D (ON/OFF) Inhibitor

GenFleet began dosing several patients in the Phase 1/2 trial in China evaluating VS-7375/GFH375 in patients with KRAS G12D-mutated advanced solid tumors in July 2024.
After evaluating initial dose escalation data from the Phase 1 study of VS-7375/GFH375 in China, Verastem anticipates filing a U.S. investigational new drug (IND) application by Q1 2025​.
Discovery/lead optimization continues for the second and third programs in the GenFleet collaboration.
Third Quarter 2024 Financial Results

Verastem Oncology ended the third quarter of 2024 with cash, cash equivalents and short-term investments of $113.2 million which provides an expected cash runway through the potential approval of avutometinib and defactinib for recurrent LGSOC in mid-2025.

Total operating expenses for the three months ended September 30, 2024 (the "2024 Quarter") were $37.0 million, compared to $21.3 million for the three months ended September 30, 2023 (the "2023 Quarter").

Research & development expenses for the 2024 Quarter were $24.8 million, compared to $13.9 million for the 2023 Quarter. The increase of $10.9 million, or 78.4%, was primarily related to contract research organization costs, consulting costs, investigator fees associated with ensuring continued rapid start-up of RAMP 301, and a clinical milestone expense that was reached in the GenFleet G12D program.

Selling, general & administrative expenses for the 2024 Quarter were $12.3 million, compared to $7.4 million for the 2023 Quarter. The increase of $4.9 million, or 66.2%, was primarily related to a one-time cost associated with July 2024 financing activities, personnel costs, including non-cash stock compensation and additional costs in anticipation of a potential launch of avutometinib and defactinib in LGSOC.

Net loss for the 2024 Quarter was $24.0 million, or $0.60 per share (basic and diluted), compared to $20.0 million, or $0.75 per share (basic and diluted) for the 2023 Quarter.

For the 2024 Quarter, non-GAAP adjusted net loss was $35.3 million, or $0.88 per share (diluted) compared to non-GAAP adjusted net loss of $19.0 million, or $0.71 per share (diluted) for the 2023 Quarter. Please refer to the GAAP to non-GAAP Reconciliation attached to this press release.

Use of Non-GAAP Financial Measures

To supplement Verastem Oncology’s condensed consolidated financial statements, which are prepared and presented in accordance with generally accepted accounting principles in the United States (GAAP), the Company uses the following non-GAAP financial measures in this press release: non-GAAP adjusted net loss and non-GAAP net loss per share. These non-GAAP financial measures exclude certain amounts or expenses from the corresponding financial measures determined in accordance with GAAP. Management believes this non-GAAP information is useful for investors, taken in conjunction with the Company’s GAAP financial statements, because it provides greater transparency and period-over- period comparability with respect to the Company’s operating performance and can enhance investors’ ability to identify operating trends in the Company’s business. Management uses these measures, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of the Company’s operating results as reported under GAAP, not in isolation or as a substitute for, or superior to, financial information prepared and presented in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. The determination of the amounts that are excluded from non-GAAP financial measures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between these non-GAAP financial measures and the most comparable GAAP financial measures for the three and nine months ended September 30, 2024 and 2023 are included in the tables accompanying this press release after the unaudited condensed consolidated financial statements.

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 RAMP 201 trial.

Verastem has completed its submission of a New Drug Application (NDA) 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 in October 2024, with a potential FDA decision mid-2025. The FDA granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib for the treatment of 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 a clinical collaboration with Amgen to evaluate LUMAKRAS (sotorasib) in combination with avutometinib and defactinib in both treatment naive and in patients who progressed on a G12C inhibitor as part of the RAMP 203 trial (NCT05074810). Verastem has received Fast Track Designation from the FDA for the triplet combination in April 2024. 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.

About VS-7375/GFH375

VS-7375/GFH375 is a potential best-in-class, potent and selective oral KRAS G12D (ON/OFF) inhibitor, identified as the lead discovery program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. GenFleet’s IND for VS-7375/GFH375 was approved in China in June 2024 and the Phase 1/2 trial in KRAS G12D-mutant solid tumors was subsequently initiated and the first patient was dosed in July 2024. The collaboration includes three discovery programs, the first being the KRAS G12D inhibitor, and provides Verastem Oncology with exclusive options to license three compounds selected for collaboration after successful completion of pre-determined milestones in Phase 1 trials. The licenses would give Verastem Oncology development and commercialization rights outside of the GenFleet territories of mainland China, Hong Kong, Macau, and Taiwan.

On November 6, 2024 Allakos Inc. (the "Company") (Nasdaq: ALLK), a biotechnology company developing antibodies for the treatment of allergic, inflammatory and proliferative diseases, reported a business update and announced financial results for the third quarter ended September 30, 2024 (Press release, Allakos, NOV 6, 2024, View Source [SID1234647847]).

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Recent Allakos Events

Reported safety, pharmacokinetics (PK), and pharmacodynamic (PD) results from the Phase 1 trial of subcutaneous (SC) AK006 in healthy volunteers.
Bioavailability of subcutaneous AK006 was approximately 77%.
Subcutaneous administered AK006 showed an estimated half-life of 12-22 days.
Consistent with the IV formulation, skin biopsies taken from subcutaneous AK006 treated healthy volunteers showed high levels of receptor occupancy confirming AK006 reaches skin tissue mast cells.
The 720 mg dose of AK006 showed 98% receptor occupancy at day 113 suggesting the potential for infrequent dosing.
Single and multiple doses of IV AK006 and single dose subcutaneous AK006 up to 720 mg were well tolerated with a favorable safety profile.
Completed enrollment of over 30 patients in the randomized, double-blind, placebo-controlled Phase 1 trial of intravenous (IV) AK006 in patients with chronic spontaneous urticaria. Data from these patients expected in early Q1 of 2025.
Upcoming Allakos Anticipated Milestones

Report randomized double-blind, placebo-controlled data on over 30 patients from the Phase 1 trial of AK006 in patients with CSU in early Q1 of 2025.
Cash Guidance

Allakos ended the third quarter of 2024 with $92.7 million in cash, cash equivalents and investments. Allakos’ financial outlook, restructuring activities and estimated cash runway as reported by the Company in January 2024 remain unchanged. The Company reiterates that it expects the restructuring activities will extend the cash runway into mid-2026 and to end 2024 with total cash, cash equivalents and investments in its previously stated $81 to $86 million guidance range. The Company has substantially completed its exit of the lirentelimab development program.

Third Quarter 2024 Financial Results

Allakos ended the third quarter of 2024 with $92.7 million in cash, cash equivalents and investments resulting in a net decrease in cash, cash equivalents and investments of $30.4 million during the third quarter of 2024. Approximately $18 million of this third quarter decrease was paid in connection with exiting the lirentelimab development program.

Research and development expenses were $10.9 million in the third quarter of 2024 compared to $36.7 million in the third quarter of 2023, a decrease of $25.8 million. This quarter over quarter decrease is attributed to $16.4 million of lower contract research and development costs, primarily due to halting lirentelimab development and includes a $4.6 million decrease relating to a change in estimated manufacturing costs upon resolution of the related work orders with the vendor, $5.7 million of decreased compensation costs and a $3.7 million decrease in other research and development expenses.

General and administrative expenses were $8.9 million for the third quarter of 2024 compared to $11.5 million for the third quarter of 2023, a decrease of $2.6 million. The quarter over quarter change included $2.4 million of decreased compensation costs and $0.2 million of decreased other general and administrative expenses.

Allakos reported a net loss of $18.4 million in the third quarter of 2024 compared to $45.6 million in the third quarter of 2023. Net loss per basic and diluted share was $0.21 for the third quarter of 2024 compared to $0.52 in the third quarter of 2023.