On January 18, 2024 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs reported the publication of clinical data from studies of CPP-1X (also known as α-Difluoromethylornithine (DFMO) or Eflornithine) in neuroblastoma (Press release, Panbela Therapeutics, JAN 18, 2024, View Source [SID1234639332]). According to Hogarty et al, children with relapsed refractory neuroblastoma have dismal outcomes and new therapeutic options are needed. Data published in the British Journal of Cancer investigated the tolerability and activity of depleting polyamines by high dose CPP-1X and celecoxib in combination with standard of care chemotherapy in heavily pretreated neuroblastoma patients. Results showed that DFMO treatment was well tolerated, and the median time-to-progression was 19.8 months. The work reflects the Company’s previous collaboration with New Advances in Neuroblastoma Therapy Consortium (NANT) (View Source). A link to the publication can be found here: View Source

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From the Phase 1 dose range finding study of CPP-1X in heavily pretreated neuroblastoma patients, CPP-1X was well tolerated. The best overall response included 2 partial responses (PR), 4 minor responses (MR), 10 Stable disease (SD), 7 progressive disease (PD) and 1 unevaluable. All patients with an overall response of PR or MR sustained this response until stopping or completing protocol therapy. The overall objective response rate (CR+PR) was 9% and rate of any response (CR+PR+MR) was 26%. At 2 years, PFS (progression free survival) for the entire cohort was 29.5%. Notably, three patients completed protocol therapy and remain without disease progression or event at >4 years from treatment end in the absence of additional therapy.

These results build upon the recent FDA approval of CPP-1X or DFMO to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB) who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. Results from these studies suggest that CPP-1X is a safe, oral treatment option that may improve response rates in heavily pretreated relapsed refractory neuroblastoma patients and are the basis for the ongoing ANBL-1821 Phase 2 trial.

"We are excited about the publication of these Phase 1 trial results in light of the recent DFMO FDA approval for patients in maintenance therapy. From this dose escalation study, our collaborators were able to demonstrate high dose DFMO is well tolerated and demonstrated activity in patients with heavily pretreated neuroblastoma," said Elizabeth Bruckheimer, PhD, Vice President & Chief Scientific Officer of Panbela. "Moreover, three patients remain alive over four years from treatment end without any additional therapy which suggests that high dose DFMO treatment in combination with chemotherapy may be a potential treatment option for this high unmet need population."

"Overall, these results in addition to the recent approval of DFMO as a maintenance therapy, suggests a role for polyamine inhibition therapy for neuroblastoma that may impact other cancer types such as prostate cancer. We are excited by these results and the potential role for CPP-1X in the clinical management of neuroblastoma and cancer as a whole." said Dr. Bruckheimer. "These studies were the basis for the ongoing Children’s Oncology Group Phase II trial in relapsed refractory neuroblastoma to support the goal of developing effective novel therapies for patients with unmet medical needs."

First author Michael Hogarty, MD, Professor of Pediatrics at the University of Pennsylvania, and Children’s Hospital of Philadelphia said, "The results from the Phase 1 study have built upon the preclinical work performed in my laboratory demonstrating a role of deep polyamine depletion as a potential therapeutic target for relapsed or refractory neuroblastoma. By understanding the underlying biology and role of MYC signaling and the polyamine pathway in neuroblastoma, we are able to show the potential impact of high-dose DFMO in neuroblastoma."

On January 18, 2024 Ikena Oncology, Inc. (Nasdaq: IKNA, "Ikena," "Company"), a targeted oncology company forging new territory in patient-directed cancer treatment, reported an organizational update outlining key objectives toward advancing the development of its lead targeted oncology assets, IK-930 and IK-595 (Press release, Ikena Oncology, JAN 18, 2024, View Source [SID1234639330]). The Company also announced an organizational streamlining that allows for the reallocation of resources from exploratory research and discovery towards the ongoing targeted oncology clinical programs. These efforts reinforce the Company’s dedication to maximize impact and drive advancements in patient-directed treatments for cancer.

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"We are laser focused on driving IK-930 and IK-595 forward in the next year to interpretable and clear data reads as we continue to build value for investors," commented Mark Manfredi, Ph.D., Chief Executive Officer of Ikena. "Our extended team has achieved many significant milestones together, and IK-930 and IK-595’s clinical progress is evidence of these collective efforts. Ikena will be forever grateful for the impact that each of the members of our discovery and research team has had. The renewed focus on our lead assets, IK-930 and IK-595, underscores our dedication to delivering the full therapeutic potential of our clinical candidates that we believe could transform the lives of cancer patients."

IK-930: TEAD1-Selective Hippo Pathway Inhibitor

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An optimized formulation is now being dosed in the clinic concurrently with the original formulation

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The Company has expanded and accelerated targeted recruitment of mesothelioma patients and additional epithelioid hemangioendothelioma (EHE) patients

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A clinical data update is planned for the second half of 2024

IK-595: MEK-RAF Molecular Glue

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The initial cohort was dosed with IK-595 in December 2023 and has subsequently cleared the safety evaluation window

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Enrollment of targeted RAS and RAF mutant cancer patients in dose escalation continues, where multiple dosing schedules are being explored

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Backfill and expansion cohorts are planned in multiple indications where IK-595 may have differentiated advantages

Strategic and Corporate Updates

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With the advancement of IK-930 and IK-595, the Company has made the strategic decision to reallocate resources from the discovery organization to the clinical programs

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This includes a workforce reduction of approximately 35%, to be implemented over the course of the first quarter of 2024

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With approximately $175 million in cash, cash equivalents and marketable securities as of December 31, 2023 (unaudited), and as a result of the organization changes, the Company’s runway is extended into the second half of 2026

On January 18, 2024 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported that it has granted non-statutory stock options to purchase an aggregate of 895,930 shares of Geron common stock as inducements to newly hired employees in connection with commencement of employment with the Company (Press release, Geron, JAN 18, 2024, View Source [SID1234639329]).

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The stock options were granted on January 17, 2024, at an exercise price of $1.92 per share, which is equal to the closing price of Geron common stock on the date of grant. Stock options representing an aggregate of 873,000 shares have a 10-year term and vest over four years, with 12.5% of the shares underlying the options vesting on the six-month anniversary of commencement of employment for the respective employees and the remaining shares vesting over the following 42 months in equal installments of whole shares, subject to continued employment with Geron through the applicable vesting dates. Stock options representing an aggregate of 22,930 shares have a 10-year term and vest in full upon achievement of a certain regulatory milestone, subject to continued employment with Geron through the applicable vesting date. All of the stock options were granted as material inducement to employment in accordance with Nasdaq Listing Rule 5635(c)(4) and are subject to the terms and conditions of the stock option agreements covering the grants and Geron’s 2018 Inducement Award Plan, which was adopted December 14, 2018, and provides for the granting of stock options to new employees.

On January 18, 2024 Exelixis, Inc. (Nasdaq: EXEL) reported that it has successfully defended European Patent number EP2593090 (c-MET Modulator Pharmaceutical Compositions) against three opponents, STADA Arzneimittel AG, Teva Pharmaceutical Industries Ltd., and Generics (U.K.) Ltd. in a hearing before the Opposition Division of the European Patent Office (EPO) (Press release, Exelixis, JAN 18, 2024, View Source [SID1234639328]). The three-member panel of the Opposition Division rejected all grounds of opposition, thus upholding the patent as granted. The patent at issue, which expires on July 18, 2031, covers tablet formulations of cabozantinib, including the tablet formulation approved as CABOMETYX (cabozantinib) tablets by the European Medicines Agency. The decision is specific to the European patent at issue and is subject to appeal to the EPO Technical Boards of Appeal.

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On January 18, 2024 Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd. and a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, reported that it will present two posters and give an Industry Expert Theater presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) (Press release, Elevar Therapeutics, JAN 18, 2024, View Source [SID1234639327]).

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The posters examine post hoc analyses of clinical data and patient-reported outcomes tied to Elevar’s CARES-310 study (NCT03764293), which assessed the combination of the company’s drug candidates camrelizumab, a PD-1 inhibitor, in combination with rivoceranib, an oral TKI, as a first-line therapy for unresectable hepatocellular carcinoma (uHCC).

ASCO GI will be held Jan. 18-20, 2024, at the Moscone Convention Center (West) in San Francisco, and online. Elevar’s poster presentations are:

Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Date and Time: Jan. 19, 2024, at 12:30 p.m. – 2 p.m. PT Abstract Number: 509 Abstract Title: Impact of baseline liver function on survival outcomes in patients with unresectable hepatocellular carcinoma (uHCC) treated with camrelizumab + rivoceranib vs sorafenib: A post hoc analysis of study CARES-310.

Date and Time: Jan. 19, 2024, at 12:30 p.m. – 2 p.m. PT Abstract Number: 456 Abstract Title: Patient-reported outcomes (PROs) <65 or ≥ 65 years old (yo) from CARES-310 camrelizumab + rivoceranib vs sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).

Industry Expert Theater presentation details:

Date and Time: Jan. 19, 2024; 5:15 p.m. – 6 p.m. PT Presentation Title: Impact of liver function on survival outcomes during treatment with camrelizumab + rivoceranib (cam+rivo) vs sorafenib in uHCC patients: therapeutic implications Speaker: Natalia Raphael, Ph.D., Elevar executive director of medical affairs

Session Description: Impact of baseline liver reserve and drug induced hepatotoxicity (DIH) on survival outcomes assessed; time to resolution/discontinuation, impact on QoL of DIH determined. The results of this post-hoc analysis may have implications for selection of initial and subsequent therapies for uHCC patients.

"Elevar is pleased that CARES-310 continues to yield results that support the combination of camrelizumab plus rivoceranib as a potentially important therapy for those confronted with hepatocellular carcinoma," said Saeho Chong, Elevar chief executive officer. "We look forward to detailing these findings while meeting with our peers at ASCO (Free ASCO Whitepaper) GI."

One ASCO (Free ASCO Whitepaper) GI poster is a post hoc analysis of the impact of baseline liver function on survival outcomes in patients with uHCC treated with camrelizumab and rivoceranib in CARES-310. The analysis found the efficacy of camrelizumab plus rivoceranib was superior to sorafenib regardless of baseline liver function as measured by both albumin-bilirubin (ALBI) grade and Child-Pugh (CP) class. Despite a higher rate of grade 3/4 adverse effects, there was no detrimental effect of camrelizumab plus rivoceranib on liver function and overall survival in patients with both mildly and moderately preserved liver function compared to sorafenib.

The other poster assessed patient-reported outcomes during CARES-310. Camrelizumab plus rivoceranib demonstrated clinically meaningful benefits in key aspects of the patient experience. Although patients treated with camrelizumab and rivoceranib exhibited higher rate of treatment-related adverse events, the combination did not adversely impact quality of life when compared to sorafenib.

Supported by the CARES-310 results, Elevar and Jiangsu Hengrui Pharmaceuticals Co., Ltd. in May 2023 submitted a new drug application (rivoceranib) and biologics license application (camrelizumab) to the U.S. Food and Drug Administration (FDA) for the combination as a first-line treatment option for uHCC. The FDA assigned Prescription Drug User Fee Act (PDUFA) target action dates in May 2024.

About Hepatocellular Carcinoma (HCC) HCC is the most common type of primary liver cancer. It most frequently occurs in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. HCC typically has a poor prognosis and a lack of treatment options and is therefore a condition with an urgent medical need.

About Rivoceranib Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China in combination with camrelizumab as a first-line treatment for uHCC (February 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S.). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan.

About Camrelizumab Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 6,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer) and treatment settings. Camrelizumab, under the brand name AiRuiKa, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021. Elevar has rights to commercialize and develop Hengrui Pharma’s camrelizumab in combination with rivoceranib for unresectable hepatocellular carcinoma (uHCC) worldwide, excluding Greater China Region and Korea (Oct. 2023).