Phio Pharmaceuticals Announces Presentation at the Annual Meeting of the American Society of Clinical Oncology (ASCO)

On May 23, 2024 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a clinical stage biotechnology company whose proprietary INTASYL siRNA gene silencing technology is designed to make immune cells more effective in killing tumor cells, reported it is presenting data about its lead product candidate, PH-762, an INTASYL compound, at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) to be held in Chicago, Illinois (Press release, Phio Pharmaceuticals, MAY 23, 2024, View Source [SID1234643629]).

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Phio is reporting on the completion of the first dose cohort for its on-going open-label Phase 1b clinical study (NCT 06014086) which is designed to evaluate the safety and tolerability of neoadjuvant use of intratumoral PH-762 in cutaneous squamous cell carcinoma (cSCC), melanoma and Merkel cell carcinoma. Stages 1 and 2 cSCC represent 77% of all new cSCC annually. There are no drug products approved for treatment of Stages 1 and 2 cSCC.

"We are pleased to share our progress in this trial with the oncology community," said Mary Spellman MD, Phio’s acting Chief Medical Officer. "We believe that this immuno-oncology therapy may offer patients meaningful clinical benefit, while minimizing surgical interventions."

Presentation Details:

Title: INTASYL PH-762: PD-1 Intratumoral Immunotherapy for Cutaneous Carcinoma

Poster Number: TPS9620
Topic: Melanoma/Skin Cancer
Presenting Author: Mary Spellman, M.D.
Date and Time: June 1, 2024: 1:30-4:30 PM CDT

Blueprint Medicines to Present the First Promising and Most Advanced Clinical Data for a CDK2 Inhibitor in Combination with an Approved CDK4/6 Inhibitor in HR+/HER2- Breast Cancer at the 2024 ASCO Annual Meeting

On May 23, 2024 Blueprint Medicines Corporation (Nasdaq: BPMC) reported updated data from the ongoing Phase 1 dose escalation portion of the VELA clinical trial of BLU-222, an investigational, highly selective and potent CDK2 inhibitor, in combination with ribociclib and fulvestrant in patients with hormone-receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (Press release, Blueprint Medicines, MAY 23, 2024, View Source [SID1234643628]). The data, which mark the first promising clinical results for a CDK2 inhibitor in combination with an approved CDK4/6 inhibitor, will be presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 2, 2024.

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"At ASCO (Free ASCO Whitepaper), we will present highly encouraging clinical data showing that our selective CDK2 inhibitor BLU-222, in combination with ribociclib, a standard of care CDK4/6 inhibitor for HR+ breast cancer, is very well-tolerated and delivers early evidence of clinical activity. This represents a highly significant milestone and holds promise as an important new cornerstone for the treatment of breast cancer, including in the front-line metastatic setting," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "These data validate the potency and selectivity of BLU-222, its potential as a first- and best-in-class CDK2 inhibitor, and its use as the combination partner of choice in breast cancer. With these data in hand, we are advancing ongoing partnering discussions that aim to accelerate development of BLU-222 into registration-directed clinical trials."

Updated Phase 1/2 VELA Trial Results

Based on previously reported positive BLU-222 monotherapy clinical data, a combination dose escalation arm was initiated in the VELA trial to assess the safety and clinical activity of BLU-222 in combination with ribociclib, a CDK4/6 inhibitor approved by the U.S. Food and Drug Administration for advanced or metastatic HR+/HER2- breast cancer, and fulvestrant, a commonly used estrogen receptor antagonist. As of the data cutoff date, 19 patients with HR+/HER2- breast cancer who had progressed on prior CDK4/6 inhibitors were treated with 100 mg to 400 mg twice daily (BID) of BLU-222 plus 400 mg once daily (QD) of ribociclib and combined with fulvestrant.

The combination of BLU-222, ribociclib, and fulvestrant was well-tolerated at all BLU-222 dose levels tested. No dose-limiting toxicities, treatment-related severe adverse events (SAEs), or BLU-222-related treatment discontinuations were reported. Treatment-related hematologic and gastrointestinal AEs were generally mild. The maximum tolerated combination dose has not been identified, and combination dose escalation is ongoing.

Pharmacokinetic data showed dose-proportional exposures of BLU-222, with sustained coverage above the predicted efficacious concentration at the 400 mg BID dose level. In addition, the combination of BLU-222 with ribociclib and fulvestrant had no clinically meaningful impact on individual drug exposures.

Preliminary clinical activity showed compelling reductions in thymidine kinase 1 (TK1) and circulating tumor DNA (ctDNA), biomarkers that have been shown to be predictive of clinical benefit. TK1, a biomarker of tumor proliferation, had the deepest reduction among patients treated with BLU-222 400 mg BID, ribociclib 400 mg QD, and combined with fulvestrant, and was statistically significantly correlated with BLU-222 exposure. All patients with evaluable ctDNA, a biomarker of tumor burden, treated with the BLU-222 400 mg BID combination dose regimen showed ctDNA reductions. Early evidence of clinical benefit includes an unconfirmed partial response in a patient who had previously progressed following six lines of therapy in the metastatic setting, including prior palbociclib and trastuzumab deruxtecan. These data highlight the impact of CDK2 inhibition when BLU-222 is combined with other therapies.

Detailed data will be presented by Dr. Dejan Duric from the Henri and Belinda Termeer Center for Targeted Therapies at Massachusetts General Hospital on June 2, 2024, during the "Breast Cancer – Metastatic" poster session at 9:00 a.m. CT. At the time of presentation, a copy of the poster will be available in the "Science—Publications and Presentations" section of the company’s website at www.BlueprintMedicines.com.

About BLU-222

BLU-222 is a highly selective and potent investigational CDK2 inhibitor with first- and best-in-class potential, designed by scientists at Blueprint Medicines. CDK2 is a cell cycle regulator and an important cancer target, with relevance in HR+/HER2- breast cancer and other malignancies, such as subsets of ovarian and endometrial cancer. Across multiple cancer types, aberrant CCNE1 hyperactivates CDK2, resulting in cell cycle dysregulation and tumor proliferation. Aberrant CCNE1 has been observed as a primary driver of disease, as well as a mechanism of resistance to CDK4/6 inhibitors. In HR+/HER2- breast cancer, the advent of CDK4/6 inhibitors has improved treatment; however, disease progression is nearly universal, and new innovation is needed to improve outcomes and prolong clinical benefit. Historically, CDK2 inhibitor development by others has been challenged due to poor selectivity limiting tolerability and combination potential. Beyond BLU-222, Blueprint Medicines is advancing additional preclinical therapeutic candidates for cell cycle targets including BLU-956, a next-generation CDK2 inhibitor, a CDK2 targeted protein degradation program, and an additional undisclosed research program.

Breakthrough Data on Botensilimab/Balstilimab in MSS CRC Presented at the 2024 ASCO Annual Meeting

On May 23, 2024 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, reported a novel analysis from the Phase 1b trial of botensilimab in combination with balstilimab (BOT/BAL) in relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC) with no active liver metastases (NLM) will be presented at the upcoming 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 1, 2024 (Press release, Agenus, MAY 23, 2024, View Source [SID1234643627]). The analysis shows that BOT/BAL is active in metastatic sites beyond the lungs and lymph nodes, including the peritoneum, soft tissue, and brain, which have historically been unresponsive to treatment.

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"The findings observed in this analysis are notable in that they are seen within challenging and historically unresponsive metastatic sites of disease," said Dr. Steven O’Day, Chief Medical Officer at Agenus. "Seeing broad activity beyond the lungs and lymph nodes is rare for immunotherapy in MSS mCRC, making BOT/BAL stand out from other treatments. We are committed to advancing BOT/BAL for those living with cancer, with the intent to provide durable long-term benefits."

Patient Demographics

A total of 77 patients with NLM MSS mCRC were treated with 1 or 2 mg/kg BOT every 6 weeks plus 3 mg/kg BAL every 2 weeks.
Patients were heavily pre-treated, with a median of four prior lines of therapy, including 21% who received prior PD-(L)1/CTLA-4 therapy.
Location of NLM sites: 62 patients (81%) had lung involvement, 33 patients (43%) had peritoneal involvement, 32 (42%) patients had lymph node involvement, 15 patients (19%) had soft tissue involvement, and 18 patients (23%) had other sites including the bone and brain.
Clinical Findings

Across different NLM sites, overall response rates (ORR) ranged from 18-33% and disease control rates (DCR) ranged from 67-82%. Overall survival (OS) remained consistent and ranged from 20.7 months to not reached (NR).
No new safety signals were observed.
Presentation Details:

Abstract Title: Botensilimab plus balstilimab in microsatellite stable metastatic colorectal cancer: Assessing efficacy in non-liver metastatic sites.

Abstract Number: 3556

Presenting Author: Marwan Fakih, MD, Division Head, GI Medical Oncology, City of Hope Comprehensive Cancer Center

Session: Poster Session – Gastrointestinal Cancer – Colorectal and Anal

Session Date and Time: June 1, 2024, at 1:30 p.m. – 4:30 p.m. CT

About Botensilimab

Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 900 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

Merus Announces Publication of an Abstract on Petosemtamab with Pembrolizumab as 1L treatment of r/m HNSCC at the 2024 ASCO® Annual Meeting

On May 23, 2024 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported the publication of an abstract regarding petosemtamab in combination with pembrolizumab on the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting website (Press release, Merus, MAY 23, 2024, View Source [SID1234643626]). The abstract presents interim clinical data from a cohort of 26 patients enrolled as of the abstract cutoff date, evaluating the combination in first line (1L) recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) for presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, May 31-June 4, 2024.

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The full dataset for these patients will be discussed on a conference call on Tuesday, May 28 at 8:00 a.m. ET.

"We believe petosemtamab continues to demonstrate potential best in class safety and efficacy in head and neck cancer. We are encouraged with the well tolerated safety profile of the combination of petosemtamab and pembrolizumab, particularly with a low rate of Grade 3 or greater adverse events, and a low rate of infusion-related reactions observed," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "These data in the abstract provide encouraging efficacy albeit from an early cutoff date, with less mature data. And we look forward to our conference call, Tuesday May 28, to discuss the more mature clinical update from a later cutoff date where the response rate further improved."

Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics): Solid Tumors

Rapid oral presentation title: Petosemtamab (MCLA-158) with pembrolizumab as first-line (1L) treatment of recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 study.
Observations in the abstract include:

As of a November 6, 2023 data cutoff date, 26 patients (pts) were treated; with 24 continuing therapy
10 pts were evaluable for response (≥2 cycles and ≥1 post-baseline scan, or early progressive disease [PD]) and 6 responses were observed. This included 1 confirmed complete response, 2 confirmed partial responses, and 3 unconfirmed partial responses (2 confirmed as of the abstract submission and the 3rd also subsequently confirmed) by Response Evaluation Criteria in Solid Tumors v1.1
The combination was well tolerated and no significant overlapping toxicities were observed. Treatment-emergent adverse events were reported in all patients, most were Grade 1 or 2 in severity. Infusion related reactions (composite term) were reported in 26.9% (all Grades) of which 3.8% were Grade 3, and all occurred during first infusion and resolved.
Presentation Details:
Abstract #: 6014
Session Title: Head and Neck Cancer
Session Date and Time: June 3, 2024, 8:00-9:30 a.m. CT

As full presentations become available at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, they will contemporaneously be available on the Merus website.

Company Conference Call and Webcast Information
Merus will hold a conference call and webcast for investors on Tuesday, May 28, 2024 at 8:00 a.m. ET. A replay will be available after the completion of the call in the Investors and Media section of our website for a limited time.

Date & Time: May 28, 2024 at 8:00 a.m. ET
Webcast link: Available on our website
Dial-in: Toll Free: 1 (800) 715-9871/ International: 1 (646) 307-1963
Conference ID: 4160163

Theriva™ Biologics Announces Fast Track Designation Granted by the U.S. FDA for VCN-01 for the Treatment of Metastatic Pancreatic Cancer

On May 23, 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 that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to lead clinical candidate VCN-01 in combination with gemcitabine and nab-paclitaxel to improve progression-free survival and overall survival in patients with metastatic pancreatic adenocarcinoma (Press release, Theriva Biologics, MAY 23, 2024, View Source [SID1234643625]). In VIRAGE, the ongoing multinational Phase 2b clinical study, intravenous VCN-01 is being evaluated in combination with standard-of-care (SoC) chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy for patients with pancreatic ductal adenocarcinoma (PDAC). Previously, the FDA granted orphan drug designation to VCN-01 for treatment of PDAC.

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"The FDA’s decision to grant FTD to VCN-01 highlights the urgent need for new treatment options for PDAC, which accounts for the 4th highest cause of cancer-associated deaths in the US and Europe," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "VIRAGE, our Phase 2b trial evaluating VCN-01 in metastatic PDAC continues to progress, with enrollment expected to complete in the third quarter of 2024. FTD is an important step that furthers our ability to expedite the review of, and build upon the compelling clinical data that underscores VCN-01’s multiple modes of action and therapeutic potential in combination with chemotherapy or immunotherapy. We will continue to deliver on our mission to advance new therapeutic options for these patients."

FTD is designed to help treatments reach patients faster by facilitating the development and expediting the review of therapies with potential to treat serious conditions and fill an unmet medical need. Benefits of FTD to programs include early and frequent interactions with the FDA during the clinical development process and, if relevant criteria are met, the FDA may also review portions of a marketing application before the sponsor submits the complete application.

About Pancreatic Ductal Adenocarcinoma

Cancer of the pancreas consists of two main histological types: cancer that arises from the ductal (exocrine) cells of the pancreas or, much less often, cancers may arise from the endocrine compartment of the pancreas. Pancreatic ductal adenocarcinoma ("PDAC") accounts for more than 90% of all pancreatic tumors. It can be located either in the head of the pancreas or in the bodytail. Pancreatic cancer usually metastasizes to the liver and peritoneum. Other less common metastatic sites are the lungs, brain, kidney and bone. In its early stages, pancreatic cancer does not typically result in any characteristic symptoms. In many instances, progressive abdominal pain is the first symptom. Therefore, in most cases, pancreatic cancer is diagnosed in its late stages (locally advanced non-metastatic or metastatic stage of the disease) when surgical resection and possibly curative treatment is not possible. It is generally assumed that only 10% of cases are resectable at presentation, whereas 30-40% of patients are diagnosed at local advanced/unresectable stage and 50-60% present with distant metastases.

About VCN-01

VCN-01 is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode-of-action enables VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient’s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. VCN-01 has been administered to over 80 patients in Phase 1 and investigator-sponsored clinical trials of different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection). More information on these clinical trials is available at Clinicaltrials.gov.