On March 25, 2024 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage global biopharmaceutical company focused on developing innovative cancer therapies, reported that the first patient has been dosed in a Phase 2 investigator-initiated trial (IIT) with Pembrolizumab, Plinabulin, BeyondSpring’s lead asset, plus Etoposide/Platinum (EP) for first-line (1L) Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) [NCT05745350] (Press release, BeyondSpring Pharmaceuticals, MAR 25, 2024, View Source;utm_medium=rss&utm_campaign=beyondspring-announces-first-patient-dosed-with-pembrolizumab-plinabulin-plus-etoposide-platinum-in-a-phase-2-investigator-initiated-study-of-first-line-extensive-stage-small-cell-lung-cancer [SID1234641486]).

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Current treatment for first-line ES-SCLC includes EP and EP plus PD-L1 antibodies. Although the objective response rate (ORR) is high (around 60-65%), median progression free survival (PFS) remains low (< 6 months), with median overall survival at 10-13 months1,2. Therefore, 1L ES-SCLC remains a serious unmet medical need.

Plinabulin, a potent dendritic cell (DC) maturation agent3, has been studied in a triple combination with various immuno-oncology agents and chemotherapy or radiation, with the potential to enhance the efficacy of PD-1/PD-L1 blockade and restore sensitivity in patients who become resistant [NCT04902040, NCT05599789]. Preliminary re-sensitization data in PD-1/PD-L1 antibody failed patients in 8 cancer types [NCT04902040, IIT at MD Anderson] corresponding response with Plinabulin DC maturation was presented at SITC (Free SITC Whitepaper) conference in Nov 20234.

This Phase 2 trial will evaluate the efficacy and safety of Pembrolizumab, Plinabulin plus EP in 1L ES-SCLC. The study5 is conducted in Wuhan Union Hospital in China, with Dr. Xiaorong Dong, Deputy Director of the Oncology Research Department and Director of the Thoracic Oncology Department, as the principal investigator. Patients enrolled are receiving the following interventional treatments. The primary endpoint is the 12-month PFS rate.

Pembrolizumab 200 mg IV every 3 weeks (Q3W) on Day 1
Etoposide 100 mg/m2 IV Q3W on Days 1, 2, and 3
Carboplatin AUC 5 IV Q3W on Day 1 or Cisplatin 75 mg/m2 IV Q3W on Day 1
Plinabulin 30mg/m2 IV Q3W on Day 1
"Although the current therapies in first-line ES-SCLC, including PD-L1 antibody and EP combination have had a high ORR, the duration of response is still short with median PFS of < 6 months. KEYNOTE-604 study revealed that 12-month PFS rate in patients with pembrolizumab plus EP is 13.6% vs. 3.1% with placebo plus EP. According to Dr. Mellman’s recent review on cancer immunity cycle6, mature DC is critical for the maintenance of cytotoxic T-cell response against the tumor. By adding Plinabulin, a potent DC maturation agent, to pembrolizumab plus EP, could potentially enable a durable response and improve PFS. This combination study represents an important step forward to address this unmet medical need. I am eager to evaluate this treatment in clinical settings, ensuring that cutting-edge, advanced therapies are translated to cancer care worldwide," said Dr. Xiaorong Dong, principal investigator for the study.

"We are pleased to start this second IIT study with Merck. Our first Merck IIT study initiated in March 2023 was in 2L/3L NSCLC cancer patients who had failed prior PD-1/PD-L1 blockade [NCT05599789]. We believe in the collateral sensitivity and efficacy potential of this triple IO combination in both front and later lines of cancer treatment. Plinabulin’s unique DC maturation mechanism may pose to be the ‘bridge’ between tumor neo-antigen generation from chemotherapy, and T cells action enabled by PD-1 antibodies. Potential improvements in both duration-of-response and quality-of-life could translate into overall survival benefit. Every moment of a cancer patient’s life is valuable, and our primary goal is to discover innovative treatment strategies that prolong their lives," added Dr. Lan Huang, Co-Founder, Chairman and CEO at BeyondSpring.

On March 25, 2024 Theriva Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported financial results for the full-year ended December 31, 2023, and provided a corporate update (Press release, Theriva Biologics, MAR 25, 2024, View Source [SID1234641417]).

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"With continued advancement of our clinical programs, we have the opportunity to achieve several important milestones this year," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "VIRAGE, our Phase 2b trial of VCN-01 in newly-diagnosed metastatic PDAC remains on track to complete enrollment in the first half of 2024. We completed the first safety review with the IDMC, and with a positive recommendation, VIRAGE will continue to enroll patients as planned with no modifications to the protocol. Our clinical data has demonstrated that repeated systemic dosing of VCN-01 is feasible from a safety perspective, and will now focus on determining whether the repeated-dose regimen of VCN-01 may lead to improved clinical outcomes for patients with PDAC and other solid cancers. In addition to advancing the VIRAGE PDAC trial, we continue to work closely with key opinion leaders, and regulatory agencies to refine our protocol and clinical strategy for VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma. In parallel, our investigator sponsored Phase 1 trial evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma continues to progress and will further inform our clinical development pathway in this area of high unmet need."

Recent Program Highlights and Anticipated Milestones:

VCN-01:

Pancreatic Ductal Adenocarcinoma (PDAC): Dosing is underway and enrollment continues to progress for VIRAGE, the randomized, controlled, multicenter, open-label Phase 2b trial of VCN-01 in combination with standard-of-care chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy in newly diagnosed bmetastatic PDAC patients. The trial is expected to enroll 92 evaluable patients and remains on track to complete enrollment in H1 2024.
The Independent Data Monitoring Committee (IDMC) recommended the continuation of enrollment as planned into the VIRAGE study. According to the IDMC’s expert assessment of clinical data from patients enrolled at six sites open in the U.S. and nine sites in Spain, the ongoing Phase 2b trial will continue without any changes to the protocol. No safety concerns were raised based on the evaluation of data presented at the IDMC meeting. Intravenous VCN-01 has been well tolerated and demonstrated a safety profile consistent with prior clinical trials. Importantly, no additional toxicities were observed in patients receiving a second dose of VCN-01.
Retinoblastoma: The investigator sponsored Phase 1 trial evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma has completed patient treatment. The trial is designed to evaluate escalating doses of VCN-01 administered by two intravitreal injections separated by 14 days. The investigator sponsored Phase 1 trial, which will complete patient follow-up in H1 2024, will help inform the planned Phase 2 trial design.
This builds on positive preclinical results presented by collaborators at Fundació Sant Joan de Déu demonstrating that administration of VCN-01 in combination with topotecan chemotherapy may improve VCN-01 activity against retinoblastoma.
SYN-004 (ribaxamase):

Dosing is underway for the ongoing Phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD). SYN-004 appeared to be well tolerated in HCT patients treated with IV meropenem and SYN-004 was not detected in blood samples from the majority of the evaluable patients. The trial is on track to complete enrollment into the second cohort in Q2 2024.
Business Updates

On November 2, 2023, Theriva signed an exclusive option to license intellectual property from Sant Joan de Déu-Barcelona Children’s Hospital (SJD) to explore the therapeutic potential of VCN-01 in combination with topoisomerase I inhibitors. This strengthens a long-term research collaboration with SJD and builds on ongoing trial evaluating VCN-01 in pediatric cancers.
Theriva is actively pursuing licensing discussions for our SYN-020 intestinal alkaline phosphatase asset.
Full-Year Ended December 31, 2023 Financial Results

General and administrative expenses decreased to $7.1 million for the year ended December 31, 2023, from $9.9 million for the year ended December 31, 2022. This decrease of 28% is primarily comprised of the decrease in the fair value of the contingent consideration of $2.8 million, along with lower salary, investor relations, legal costs, consulting fees related to the VCN acquisition, and director and officer insurance offset by higher audit fees, and other consulting fees. The charge relating to stock based compensation expense was $0.4 million for the year ended December 31, 2023, compared to $0.4 million for the year ended December 31, 2022.

Research and development expenses increased to $14.3 million for the year ended December 31, 2023, from $11.7 million for the year ended December 31, 2022. This increase of 22% is primarily the result of higher clinical trial expenses related to our VIRAGE Phase 2 clinical trial of VCN-01 in PDAC, offset by lower expenses related to our Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic HCT recipients, the completed Phase 1a clinical trial of SYN-020, decreased manufacturing expenses related to our Phase 1a clinical trial of SYN-020 and lower other indirect costs. We anticipate research and development expense to increase as we continue enrollment in our VIRAGE Phase 2 clinical trial of VCN-01 in PDAC and our ongoing Phase 1 clinical trial in retinoblastoma, expand GMP manufacturing activities for VCN-01, and continue supporting our VCN-11 and other preclinical and discovery initiatives. Research and development expenses also include a charge relating to non-cash stock-based compensation expense of $165,000 for the year ended December 31, 2023, compared to $112,000 for the year ended December 31, 2022. In addition, we expect research and development expenses to increase as we incur higher clinical program costs for our VCN product candidates.

Other income was $1,442,000 for the year ended December 31, 2023, compared to other income of $471,000 for the year ended December 31, 2022. Other income for the year ended December 31, 2023 is primarily comprised of interest income of $1,439,000 and an exchange gain of $3,000. Other income for the year ended December 31, 2022 is primarily comprised of interest income of $512,000 offset by an exchange loss of $41,000.

Cash and cash equivalents totaled $23.2 million as of December 31, 2023, compared to $41.8 million as of December 31, 2022.

The audited financial statements for the year ended December 31, 2023 included in the Company’s Annual Report on Form 10-K contain an unqualified audit opinion from the Company’s independent registered public accounting firm that includes an explanatory paragraph related to the Company’s ability to continue as a going concern.

Conference Call

Theriva Biologics will host a conference call on Monday, March 25, 2024 at 8:30 a.m. ET to discuss its financial results for the full-year ended December 31, 2023 and provide a corporate update. Individuals may participate in the live call via telephone by dialing 1-877-451-6152 (domestic) or 1-201-389-0879 (international) and using the conference ID: 13744453. Participants are asked to dial in 15 minutes before the start of the call to register. Investors and the public can access the live and archived webcast of this call via the "News & Media" section of the company’s website, View Source, under "Events" or by clicking here, up to 90 days after the call.

On March 25, 2024 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. ("Biocytogen", HKEX: 02315), a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies, and ABL Bio Inc. ("ABL", KOSDAQ: 298380), a Korean clinical-stage biotechnology company developing novel therapeutics in oncology and CNS diseases, reported a collaboration to develop new bispecific antibody-drug conjugates (bsADCs) (Press release, Biocytogen, MAR 25, 2024, View Source [SID1234641396]).

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Biocytogen’s RenLite mice platform can produce fully human antibodies with diverse epitopes and high affinity. This platform is notable for its ability to generate antibodies in a common light chain format, offering a distinctive combination of design flexibility, simplified manufacturing processes, and optimal developability for bsADC development. Based on this platform, both companies will be able to discuss expanding their collaboration for various types of ADC development.

Dr. Yuelei Shen, President and CEO of Biocytogen, said, "We are very pleased to collaborate with ABL, a company that possesses advanced platforms for cancer immunotherapy and treatments against CNS diseases. ABL’s consistent success in advancing its pipeline strongly showcases its expertise and capabilities in regulatory, clinical development, and business development activities. BsADC drugs derived from our RenLite mice platform have shown preferable potency in various tumor models, while also exhibiting good safety profiles. We believe our fully human bsADC platform technology, which features increased tumor selectivity, target synergized internalization, and convenient CMC development, will complement ABL’s capabilities effectively. Together, we aim to expedite the development of innovative bsADC therapies."

Sang Hoon Lee, CEO of ABL, said, "We are excited to establish this partnership with Biocytogen for bsADCs. This collaboration is one of the stepping stones for getting down to developing bsADCs. We look forward to a productive collaboration, and firmly believe that this partnership will contribute towards creating a distinctive pipeline, ultimately leading to novel therapies that improve the quality of life for patients."

On March 25, 2024 Oncotelic Therapeutics, Inc (OTCQB:OTLC) reported the peer reviewed publication of Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas: Past, Present, and Future Strategies in the Treatment and Management of Gliomas (Press release, Oncotelic, MAR 25, 2024, View Source [SID1234641418]).

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Dr. Vuong Trieu, CEO and Chairman of Oncotelic, stated, "Our R&D team has discovered crosstalk between the TGF-β and IFN signaling pathways, linking gliomas and Systemic Lupus Erythematosus (SLE). This publication has identified IRF5 as a common target for both diseases, opening up a new avenue for combating cancer,"

Our findings place IRF5 at the intersection of inflammation and cancer. Understanding the role of IRF5 in both SLE and cancer opens an avenue for targeting IRF5 or its downstream pathways. This could offer new strategies for treating SLE and various cancers by modulating the immune response.

The article can be accessed for free online: View Source

On March 25, 2024 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM") reported the publication of new data analysis from a long-term Early Access Program ("EAP") studying the company’s drug Ampligen (rintatolimod) for the treatment of advanced pancreatic ductal adenocarcinoma ("PDAC") (Press release, AIM ImmunoTech, MAR 25, 2024, View Source [SID1234641401]). The manuscript titled "Rintatolimod in Advanced Pancreatic Cancer enhances Anti-Tumor Immunity through Dendritic Cell-Mediated T Cell Responses," appears in the journal Clinical Cancer Research, one of oncology’s most prestigious journals.

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Ampligen is a dsRNA product candidate that acts via the TLR-3 receptor present on several immune cells, epithelial cells and tumors. Researchers at the Erasmus University Medical Center ("Erasmus MC") found that Ampligen treatment in pancreatic cancer patients enhances peripheral immune activity at the transcriptomic and proteomic levels, particularly involving type 1 conventional dendritic cells (cDC1s) and T cells. Post-Ampligen, the increased peripheral abundance of BTLA+XCR1+ cDC1s and CD4+SELL+ T cells correlated with improved clinical outcomes. Patients with stable disease exhibited pronounced overexpression of genes related to DC and T cell activation. Notably, the expression of immune checkpoints PD-L1 and PD-L2 decreased post-Ampligen across all patients.

AIM Chief Executive Officer Thomas K. Equels stated: "We have already seen that Ampligen as a single-agent therapy was associated with improved progression-free survival and overall survival in these Early Access Program pancreatic cancer patients. This new data analysis provides us further insight into exactly why that’s the case, which could give us the ability to identify cancer patients who might benefit more from Ampligen treatment than they would from other known cancer treatments. Additionally, the changes in the tumor microenvironment we see in pancreatic cancer are similar to those we have seen in triple-negative breast cancer, ovarian cancer and colorectal cancer metastatic to the liver. We have hypothesized that Ampligen has the potential to be efficacious in almost every solid tumor type based on its direct effect on malignant tumor cells and its effect on the tumor micro-environment. All these data combined lend further credence to the broad applicability of Ampligen in solid tumors."

Prof. Casper H.J. van Eijck, MD, PhD, Pancreato-biliary Surgeon at Erasmus MC and co-author of the published paper, stated, "Based on these results, we believe Ampligen may break immunological tolerance by enhancing anti-tumor immunity through DC-mediated T-cell responses. The data suggests that Ampligen infusions modulate PD-L1 and PD-L2 expression in the tumor microenvironment, while at the same time they upregulate Ki67+CD4+ and Ki67+CD8+ T-cells. We therefore believe that combining Ampligen with an immune checkpoint inhibitor – such as durvalumab – could synergistically circumvent immune blockade and potentially mitigate the T-cell exhaustion known to occur with immune checkpoint therapies. We look forward to further evaluating Ampligen toward potentially meeting the critical need for more effective therapies to treat pancreatic cancer, including with the ongoing DURIPANC trial, which looks at the combination effect of Ampligen and AstraZeneca’s durvalumab."

AIM is currently evaluating Ampligen as a therapy for metastatic pancreatic ductal adenocarcinoma in the Phase 1b/2 DURIPANC clinical study (NCT05927142) and as a therapy for locally advanced pancreatic adenocarcinoma in the Phase 2 AMP-270 clinical study (NCT05494697).