On March 11, 2024 Synnovation Therapeutics, a precision medicine company developing small molecule therapies optimized to achieve best-in-class pharmacology against highly validated disease targets, reported that the first patient has been dosed in a Phase I trial evaluating SNV1521 in patients with solid tumors (Press release, Synnovation Therapeutics, MAR 11, 2024, View Source [SID1234641036]). SNV1521 is a potentially best-in-class, potent, highly selective and CNS penetrant PARP1 inhibitor.

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The Phase I trial, which is being led by Timothy Yap, M.D., Ph.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, is designed to assess proof-of-concept with SNV1521 as an oral monotherapy in a dose escalation and preliminary efficacy expansion study. PARP inhibition is clinically validated for homologous recombination deficiency (HRD, a molecular biomarker) driven cancers; however, the safety profile of first generation PARP1 agents limits the potential of the class, particularly in combination with chemotherapy or other novel agents. In preclinical models, selective PARP1 targeting has been shown to improve both the efficacy and safety of the class.

"We believe that a highly potent and selective PARP1 inhibitor – such as SNV1521 – has the potential for both improved efficacy and enhanced safety due to its excellent physicochemical properties," said Kevin O’Hayer, M.D., Ph.D., Senior Vice President, Head of Clinical Development at Synnovation. "Dosing of the first patient in the SNV1521 Phase I trial is a key milestone as Synnovation transitions from a preclinical to clinical stage biotech company. We are excited to collaborate with Dr. Yap and the rest of our SNV1521 study investigators on this program."

On March 11, 2024 Following a strategic portfolio review, the Board of Directors of OBI Pharma, Inc. (4174) reported that they have decided to terminate the OBI-3424-001 trial, while continuing the collaboration of OBI-3424 with partners, given that the OBI-3424 development is still ongoing (Press release, OBI Pharma, MAR 11, 2024, View Source [SID1234641019]).

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Dr. Heidi Wang, the Chief Executive Officer of OBI Pharma, emphasized that this decision was made to allocate limited resources to other priority projects. Other than OBI-3424-001 Phase II study, there is an ongoing Phase I/II clinical trial sponsored by the Southwest Oncology Group (hereinafter referred to as "SWOG"), recruiting patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL). This clinical trial led by SWOG is currently open for enrollment in several medical institutions in the U.S., and OBI will continue to support the drug supply for this trial. In the meantime, the collaboration with Ascentawits Pharmaceuticals, Ltd. also continues. Ascentawits is conducting clinical trials in patients with hepatocellular carcinoma (HCC) and acute lymphoblastic leukemia (ALL) in China.

Dr. Ming-Tain Lai, the Chief Scientific Officer of OBI Pharma, pointed out that OBI-3424 Phase I clinical trial results demonstrated good tolerability and no major safety concerns. OBI-3424-001 Phase II clinical trial on patients with advanced solid tumors has been opened for enrollment in several medical institutions in the U.S. since 2021. Since then, a total of 29 advanced solid tumor patients have been treated, including patients with colorectal, pancreatic, and other cancer types. However, OBI-3424 has not demonstrated therapeutic potentials in these cancer patients. After careful assessment, the Company decided to terminate OBI-3424-001 trial. An estimated NT$300 million (or US~$10 million) will be shifted to support other priority projects after OBI-3424-001 trial is terminated.

The Phase II clinical trial of OBI-3424-001 was originally intended to enroll 62 patients. The Company will continue to provide medical care to patients still on study in accordance with the clinical study protocol and will manage the unused investigational products in compliance with related regulations and the Good Clinical Practice.

OBI-3424 is a first-in-class novel chemotherapeutic prodrug that is selectively converted by AKR1C3 to a potent DNA-alkylating agent that leads to selective killing of cancer cells. The Company acquired the worldwide right (except for China, Hong Kong, Macao, Taiwan, Japan, South Korea, Singapore, Malaysia, Thailand, Turkey, and India) of OBI-3424 from Threshold Pharmaceuticals, Inc. in 2017. OBI-3424 has been granted Orphan Drug Designation for the treatment of HCC and ALL by the US FDA in 2018.

The Company also continues the collaboration with Ascentawits Pharmaceuticals, Ltd., who owns the OBI-3424 right in China, Hong Kong, Macao, Taiwan, Japan, South Korea, Singapore, Malaysia, Thailand, Turkey, and India, through the sharing of clinical data and information.

On March 11, 2024 Cellworks Group Inc., a leader in Personalized Therapy Decision Support and Precision Drug Development, reported the results from a real-world study of gastroesophageal cancer which found that Therapy Response Index (TRI) scores generated using the Cellworks Biosimulation Platform predicted overall survival (OS) above and beyond standard clinical factors, including patient age, sex, and tumor-node-metastasis (TNM) staging (Press release, Cellworks, MAR 11, 2024, View Source [SID1234641037]). The study also showed a significant association between a patient’s TRI score and disease-free survival (DFS) and tumor regression grade (TRG).

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The peer-reviewed paper, ‘Integration of genomic aberrations to predict clinical outcomes for patients with gastroesophageal adenocarcinoma receiving neoadjuvant chemotherapy,’ is available at ESMO (Free ESMO Whitepaper) Gastrointestinal Oncology.

Despite progress in gastroesophageal cancer therapy, only a small proportion of patients attain long-term survival. Previous precision-based strategies have been constrained by focusing on single biomarker–drug associations. This oversimplified approach to the disease has resulted in a wide spectrum of patient outcomes, with long-term survival rates spanning from 25% to 75% using multi-modality therapy — a combination of chemotherapy, radiation, surgical resection, and adjuvant nivolumab, which has become the standard of care.

"The focus for guiding treatment decisions for gastroesophageal patients has centered on specific biomarkers such as HER2, MSI, PD-L1 and CLD18.2," said Dr. Elizabeth Smyth, Oxford University Hospitals NHS Foundation Trust; and Co-Principal Investigator of the study. "However, further refinement of treatment selection using computational biomarkers might be possible. This study highlights the unique value that Cellworks computational biosimulation can bring to the treatment decision process by utilizing a patient’s comprehensive genomic profile and biosimulating all possible therapy combinations. This approach could offer a promising avenue for recommending a treatment strategy at an individual level, thereby improving patient outcomes."

"The size and complexity of comprehensive genomic panels pose a formidable challenge, making it difficult for oncologists to translate the intricate biology into actionable clinical decisions," said Dr. Rebecca Fitzgerald, MD, Professor of Cancer Prevention at the University of Cambridge; Director of the Early Cancer Institute; and Co-Principal Investigator of the study. "This study demonstrates that utilizing whole genome sequencing of a patient’s gastroesophageal cancer along with Cellworks personalized biosimulation approach has the potential to highlight when alternative treatment strategies such as fluoropyrimidines, taxanes, anthracyclines or platinum compounds may yield superior outcomes for a specific patient."

"The transition from small panel NGS to whole exome and whole genome sequencing brings new insights about each cancer’s complex proteogenomic network," said Dr. Michael Castro M.D., Oncologist at Beverly Hills Cancer Center; and Chief Medical Officer at Cellworks, Group Inc. "These insights reveal the basis for drug sensitivity and resistance that allows oncologists to select the optimal combination therapy for individual patients and creates the possibility of targeting the sources of therapeutic resistance. The view that genomic information is ‘unactionable’ is transformed by artificial intelligence (AI)-level molecular diagnosis provided by Cellworks’ biosimulation. Most genomic information that can be measured is highly relevant to tumor biology and treatment response but is beyond the grasp of busy clinicians. With Cellworks biosimulation, the oncogene-only approach to precision medicine is already obsolete."

Clinical Study

Methods
The performance of Cellworks in silico biosimulation and Therapy Response Index (TRI) scores were studied in patients with gastroesophageal adenocarcinoma (OGA) with operable cancers from the UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) International Cancer Genome Consortium study. A total of 270 patients with OGA were selected who had 50x whole genome sequencing carried out on tissue derived from either biopsy or resection within 12 months of treatment. Patients were treated with chemotherapy drugs or regimes according to UK clinical guidelines.

Biosimulation was carried out utilizing the Cellworks computational biology model (CBM), which uses both mechanistic and statistical approaches to integrate a patient’s genomic aberrations, revealing signaling pathway dysregulation and variable drug response. Using patient-specific predictions derived from the CBM, a TRI score was used to predict therapeutic overall survival (OS), disease-free survival (DFS) and tumor regression grade (TRG).

Results
The results of the study revealed that the association of TRI value with overall survival (OS) for gastroesophageal adenocarcinoma patients was significant (P = 0.0012) above and beyond standard clinical factors including patient age, sex, tumor-node-metastasis (TNM) stage and neoadjuvant therapy. The association between TRI values and disease-free survival (DFS) was also significant (P = 0.0288). In addition, the TRI values optimized for tumor regression grade (TRG) displayed a significant association (P = 0.0011).

Conclusions
This study concluded that TRI scores for gastroesophageal adenocarcinoma patients predict OS and DFS beyond clinical factors. These results highlight the clinical value of employing Cellworks biosimulation for personalized therapy selection and warrant additional clinical evaluation.

Cellworks Platform and Therapy Response Index (TRI)

The Cellworks Platform biosimulates the impact of specific drug compounds on an individual patient or class of patients using their genomic profile. Multi-omic data from an individual patient or cohort is used as input to the in silico Cellworks Computational Biology Model (CBM) to generate a personalized or cohort-specific disease model. The CBM is a highly curated mechanistic network of 6,000+ human genes, 30,000 molecular species and 600,000 molecular interactions. This model along with associated drug models are used to biosimulate the impact of specific compounds or combinations of drugs on the patient or cohort and produce therapy response predictions, which are statistically modeled to produce a qualitative Therapy Response Index (TRI) score, scaled from 0 (unfavorable outcome) to 100 (favorable outcome) for a specific therapy. The Cellworks CBM has been tested and applied against various clinical datasets with results provided in over 125 presentations and publications with global collaborators.

On March 11, 2023 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a clinical-stage biotechnology company focused on the treatment and prevention of cancer, reported that Dr. Amit Kumar, Chairman and CEO of Anixa, will participate in the 24th Annual World Vaccine Congress being held April 1-4, 2024 (Press release, Anixa Biosciences, MAR 11, 2024, View Source [SID1234641001]). Dr. Kumar will speak on Thursday, April 4th, in the Cancer Immunotherapy Track.

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Details are as follows:

Location:

Walter E. Washington Convention Center, Washington, D.C.

Tickets:

Visit the conference website.

Session:

April 4, 2024 | Cancer Immunotherapy

Emerging Targets & Strategies track

11:45 a.m.: "Early-stage clinical results from a novel preventative breast cancer vaccine."

Dr. Kumar will speak about positive interim results from the Phase 1 clinical trial of Anixa’s breast cancer vaccine. In the most recent data, 75% of women showed immune responses, with responses observed at all dose levels. The vaccine is designed to direct the immune system to destroy triple negative breast cancer (TNBC) cancer cells through a mechanism that has never previously been utilized for cancer vaccine development. The trial is being conducted in collaboration with Cleveland Clinic with funding by a grant from the U.S. Department of Defense.

Dr. Kumar will be available during the Congress for one-on-one meetings.

The World Vaccine Congress is an award-winning series of conferences and exhibitions that have grown to become the largest and most established vaccine meetings of their kind across the globe since 2000. The World Vaccine Congress Washington 2024 will host 4,000+ attendees, 450+ speakers, and 350+ exhibitors.

On March 11, 2024 Olema Pharmaceuticals, Inc. ("Olema", "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a corporate update (Press release, Olema Oncology, MAR 11, 2024, View Source [SID1234641020]).

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"In 2023 we demonstrated the unique opportunity ahead for palazestrant to make a meaningful impact on improving treatment options for women with ER+/HER2- breast cancer. We believe palazestrant’s activity on both wild-type and ESR1-mutant breast cancer, and its ability to safely combine with ribociclib, result in a highly differentiated profile amongst this emerging new class of estrogen receptor-targeting therapies," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "We have recently completed enrollment in our 60-patient Phase 2 study of 120 mg palazestrant in combination with 600 mg ribociclib, and we are looking forward to sharing an update on this study at the 2024 ESMO (Free ESMO Whitepaper) Breast Cancer Annual Congress. Beyond palazestrant, we recently declared a development candidate for our KAT6 program, OP-3136, and we are advancing towards an IND filing by the end of this year. Our mission at Olema is to improve the lives of women living with cancer and we are very pleased with the progress we are making."

Recent Corporate Highlights

•
Presented interim clinical results of palazestrant in combination with CDK4/6 inhibitors ribociclib and palbociclib at the 2023 San Antonio Breast Cancer Symposium (SABCS), showing no significant drug-drug interaction, no dose-limiting toxicities and a tolerability profile consistent with the FDA-approved labels of ribociclib or palbociclib plus an endocrine therapy.
•
Presented palazestrant monotherapy Phase 2 clinical results at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain, as an oral presentation demonstrating compelling activity in both wild-type and ESR1-mutant tumor types.

•
Initiated OPERA-01, our pivotal Phase 3 monotherapy clinical trial in the second- and third-line setting of ER+/HER2- advanced or metastatic breast cancer, including dosing first patients and activating multiple trial sites globally.
•
Nominated OP-3136, an orally bioavailable KAT6 inhibitor, as a development candidate. OP-3136 demonstrated potent anti-tumor activity alone and in combination with both palazestrant and CDK4/6 inhibitors in preclinical ER+ breast cancer models.
•
Announced the expansion of Olema’s clinical collaboration with Novartis Institutes for BioMedical Research, Inc. (Novartis), increasing the size of the ongoing Phase 1/2 clinical study testing palazestrant in combination with ribociclib to approximately 60 patients. This study is fully enrolled.
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Completed a combined financing for up to $180 million including an equity private placement of approximately $130 million of common stock as well as a new senior secured credit facility with an aggregate principal amount of up to $50 million with Silicon Valley Bank (SVB), $25 million of which is currently available.

Upcoming Milestones

•
Present interim Phase 2 clinical results of palazestrant in combination with ribociclib at ESMO (Free ESMO Whitepaper) Breast Cancer Annual Congress 2024, May 15-17, 2024, in Berlin, Germany.
•
Initiate Phase 1b/2 clinical study of palazestrant in combination with mTOR inhibitor, everolimus, in Q3 2024.
•
File an Investigational New Drug, or IND, application with the FDA for OP-3136, a KAT6 inhibitor, in late 2024, and advance clinical development.
•
Prepare for pivotal Phase 3 first-line trial in combination with CDK4/6 inhibitor, ribociclib.

Fourth Quarter and Full-Year 2023 Financial Results

Cash, cash equivalents and marketable securities as of December 31, 2023, were $261.8 million.

Net loss was $26.8 million and $96.7 million for the quarter and year ended December 31, 2023, respectively, as compared to $26.2 million and $104.8 million for the quarter and year ended December 31, 2022, respectively. The increase in net loss for the fourth quarter was primarily related to increased spending on clinical operations and development-related activities, including personnel-related expenses, as Olema continues to advance palazestrant into late-stage clinical trials. This increase was offset by decreased spending on general and administrative activities and higher interest income earned from marketable securities. The decrease in net loss for the full year 2023 was primarily due to higher interest income earned from marketable securities.

GAAP research and development (R&D) expenses were $25.9 million and $86.1 million for the quarter and year ended December 31, 2023, respectively, as compared to $21.6 million and $82.3 million for the quarter and year ended December 31, 2022, respectively. The increase in R&D expenses was primarily a result of increased spending on clinical operations and development-related activities including personnel-related costs as Olema continues to advance palazestrant into late-stage clinical development, which were offset by decreased spending on research-related activities.

Non-GAAP R&D expenses were $23.0 million and $74.4 million for the quarter and year ended December 31, 2023, respectively, excluding $2.9 million and $11.8 million non-cash stock-based compensation expense, respectively. Non-GAAP R&D expenses were $18.2 million and $69.8 million for the quarter and year ended December 31, 2022, respectively, excluding $3.4 million and $12.5 million non-cash stock-based compensation expense, respectively. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release.

GAAP G&A expenses were $4.5 million and $18.8 million for the quarter and year ended December 31, 2023, respectively, as compared to $5.6 million and $24.7 million for the quarter and year ended December 31, 2022, respectively. The decrease in G&A expenses was primarily due to decreased spending on corporate- and legal-related costs, and personnel-related expenses.

Non-GAAP G&A expenses were $3.1 million and $13.3 million for the quarter and year ended December 31, 2023, respectively, excluding $1.4 million and $5.5 million non-cash stock-based compensation expense respectively. Non-GAAP G&A expenses were $4.1 million and $18.3 million for the quarter and year ended December 31, 2022, excluding $1.5 million and $6.4 million non-cash stock-based compensation expense, respectively. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release.

About Palazestrant (OP-1250)

Palazestrant (OP-1250) is a novel, orally-available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD). It is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In clinical studies, palazestrant completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer and has demonstrated anti-tumor activity along with attractive pharmacokinetics and exposure, favorable tolerability, CNS penetration, and combinability with CDK4/6 inhibitors. Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. It is currently being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib) and a PI3Ka inhibitor (alpelisib). For more information, please visit www.opera01study.com.