On June 27, 2024 Bicara Therapeutics, a clinical-stage biotechnology company developing transformative bifunctional therapies for patients with solid tumors, reported the presentation of updated interim data from its ongoing, open-label Phase 1/1b dose expansion study of ficerafusp alfa (BCA101) at the 3rd Hawaii Global Summit on Thoracic Malignancies, taking place from June 25-29, 2024 (Press release, Bicara Therapeutics, JUN 27, 2024, View Source [SID1234644561]). Ficerafusp alfa is a bifunctional antibody that combines two clinically validated targets: an epidermal growth factor receptor (EGFR) directed monoclonal antibody with a domain that binds to human transforming growth factor beta (TGF-β).

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In the Phase 1/1b clinical trial, ficerafusp alfa in combination with pembrolizumab has demonstrated clinically meaningful anti-tumor activity, with a 64% overall response rate (ORR), 18% complete response (CR) rate and median progression free survival (mPFS) of 9.8 months in frontline human papillomavirus (HPV)-negative, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), along with a favorable tolerability profile.

"Data from our ongoing Phase 1/1b clinical trial reflected a substantial increase over the historical 19% ORR observed in a Phase 3 trial with pembrolizumab monotherapy, the current standard of care in R/M HNSCC," said David Raben, M.D., chief medical officer of Bicara Therapeutics. "Now with at least a year of follow-up on this cohort, it is encouraging to see a number of patients experience durable responses with the CR and mPFS data that have emerged. We believe these data indicate that ficerafusp alfa in combination with pembrolizumab may become a new chemotherapy-free standard of care treatment for HPV-negative first-line R/M HNSCC."

"Ficerafusp alfa has the potential to exert potent anti-tumor activity by simultaneously blocking both cancer cell intrinsic EGFR survival and proliferation, as well as immunosuppressive TGF-β signaling within the tumor microenvironment to lead to durable responses and improved survival," said Claire Mazumdar, Ph.D., MBA, chief executive officer of Bicara Therapeutics. "Given these data, we intend to initiate a pivotal Phase 2/3 trial of ficerafusp alfa in combination with pembrolizumab in frontline R/M HNSCC excluding HPV-positive patients. We also remain excited about the potential of ficerafusp alfa to expand into other populations of HNSCC patients and across other squamous cell tumor types where there is a strong biologic rationale for the dual inhibition of both EGFR and TGF-β."

Presentation Highlights:

Updated interim data (April 2024 cut-off date) from the Phase 1/1b dose expansion cohort of BCA101 in combination with pembrolizumab include 39 evaluable frontline R/M HNSCC patients with a PD-L1 combined positive score (CPS) of ≥1. 28 patients were HPV-negative and 11 patients were HPV-positive, as determined by p16 testing.
o 54% ORR in total evaluable study population (21/39 patients), including 3 unconfirmed responses1.
o 15% complete response (CR) rate (6/39 patients). 26% (10/39) of patients with 100% reductions in target lesions.
o Favorable tolerability profile with the most common treatment-related adverse events (TRAEs) including acneiform rash (76%, with majority being Grade 1/2 in severity), fatigue (43%), and hypophosphatemia (38%).
In HPV-negative population (n=28):
o 64% ORR (18/28 patients) with responses observed across different levels of PD-L1 expression, including 3 unconfirmed responses1.
o 18% complete response (CR) rate (5/28 patients). 29% (8/28) of patients with 100% reductions in target lesions.
o Median progression free survival (mPFS) of 9.8 months.
o With at least 12 months of follow-up, median duration of response (DOR) and median overall survival (OS) have not yet been reached.
Presentation Details:
Title: Altering the HNSCC landscape: Breaking through the Tumor Defense with EGFR-TGF-β blockade
Presentation Date and Time: Thursday, June 27, 2:50 p.m. HST
Presenter: Dr. David Raben

About Head and Neck Squamous Cell Carcinoma
Head and neck squamous cell carcinomas (HNSCCs) develop from the mucosal epithelium in the oral cavity, pharynx and larynx and are the most common malignancies that arise in the head and neck. HNSCC is one of the most common cancers in the United States and globally with a rising incidence anticipated to reach one million new global cases annually by 20302. Ten percent of HNSCC patients are diagnosed with metastatic disease and up to 30% develop a recurrence or metastases over time after initial treatment for advanced HNSCC.

Most cases of HNSCC are believed to arise from mutations that accumulate due to carcinogenic exposure, such as tobacco smoke, or by HPV. Approximately 80% of patients with R/M HNSCC are HPV-negative. HPV-negative HNSCC tumors typically recur locally and are associated with an increased risk of fatal tumor bleeding, excruciating pain and difficulty swallowing. Thus, there remains a significant unmet need for therapies with a durable anti-tumor response in this population.

About Ficerafusp Alfa (BCA101)
Ficerafusp alfa is a bifunctional antibody designed to inhibit the epidermal growth factor receptor (EGFR) and disable transforming growth factor beta (TGF-β) directly at the tumor site. This approach is designed with the intent to allow ficerafusp alfa to inhibit tumor proliferation, while restoring the cytolytic activity of the local immune cells.

Ficerafusp alfa is currently being evaluated in a dose expansion phase of an open-label Phase 1/1b study in combination with pembrolizumab in HPV-negative patients with R/M HNSCC, advanced squamous non-small cell lung cancer (SqNSCLC), or squamous cancer of the anal canal (SCAC) and as a monotherapy for cutaneous squamous cell carcinoma (cSCC).

On June 27, 2024 Abbisko Therapeutics Co., Ltd. (Abbisko Therapeutics) reported that it has presented new phase II clinical data of its highly selective FGFR4 inhibitor irpagratinib (ABSK011) in combination with atezolizumab for the treatment of advanced hepatocellular carcinoma（HCC）at the 2024 ESMO (Free ESMO Whitepaper)-GI Congress (Press release, Abbisko Therapeutics, JUN 27, 2024, View Source [SID1234644586]). The presentation highlights that 220mg BID of irpagratinib in combination with atezolizumab demonstrated promising antitumor activity with an objective response rate (ORR) of 50% in FGF19+ HCC patients.

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ESMO-GI, a world-renowned gastrointestinal oncology conference, is being held in Munich, Germany, from June 26 to 29, 2024.

Abbisko presentations at ESMO (Free ESMO Whitepaper)-GI 2024:

Title: A Phase 2 Study of Irpagratinib (ABSK-011) plus Atezolizumab in Patients with Advanced Hepatocellular Carcinoma (HCC)
Poster display number：171P
Poster display session: Hepatocellular and non-biliary liver cancer
Poster display date and time: 27 June 2024, 15:35-16:30 PM (UTC+1)

Summary:

At the 2024 ESMO (Free ESMO Whitepaper)-GI conference, Abbisko Therapeutics debuted new clinical trial results with the combination of irpagratinib and atezolizumab. In HCC patients with FGF19 overexpression, the objective response rate (ORR) was 50% (5/10)in the 220 mg BID cohort, demonstrating this novel combination therapy has notable benefits in enhancing the ORR. Notably, strong efficacy and good safety were also observed in patients who had previously received immune checkpoint inhibitor (ICI) therapy, providing further evidence that targeting FGF19-FGFR4 may provide a much-needed differentiated treatment option for HCC.

Given the encouraging preliminary results from this study, Abbisko plans to explore dual/triple combinations with irpagratinib in earlier lines of therapy for HCC. Abbisko continues to look forward to combination approaches with irpagratinib to better address HCC and bring hope to patients, with aims to conduct further research and innovation in this area.

Background:

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and ranks as the sixth most prevalent cancer and third leading cause of death worldwide. Dysregulation of FGF19-FGFR4 signaling accounts for approximately 30% of HCC and plays a pivotal role in driving HCC tumorigenesis. Irpagratinib is a highly potent and selective FGFR4 inhibitor, with potential to become a first-in-class or best-in-class FGFR4 inhibitor. Abbisko Therapeutics previously presented clinical data from its first-in-human study of irpagratinib at the 2023 ESMO (Free ESMO Whitepaper) Annual Meeting, demonstrating promising anti-tumor activity as a single agent with an ORR of 40.7% in FGF19 overexpressed late-line HCC patients.

To further explore the therapeutic potential of irpagratinib, Abbisko is conducting a phase 2 clinical trial of irpagratinib in combination with atezolizumab. This trial is investigating irpagratinib in combination with atezolizumab, a PD-L1 antibody, in FGF19+ advanced HCC patients, to understand safety and efficacy.

On June 27, 2024 Abdera Therapeutics Inc., a biopharmaceutical company leveraging its advanced antibody engineering ROVEr platform to design and develop tunable, precision radiopharmaceuticals for cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ABD-147 for the treatment of patients with extensive stage small cell lung cancer (ES-SCLC) who have progressed on or after platinum-based chemotherapy (Press release, Abdera Therapeutics, JUN 27, 2024, View Source [SID1234644587]). ABD-147 is a next-generation precision radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac) to solid tumors expressing DLL3, a protein found on the surface of neuroendocrine tumors, but rarely expressed on the surface of normal cells or tissues.

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The FDA’s Fast Track program is designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Clinical programs with Fast Track designation may benefit from early and frequent communication with the FDA throughout the regulatory review process and may also be eligible for Accelerated Approval and Priority Review if relevant criteria are met.

"Aggressive neuroendocrine cancers such as SCLC carry a poor prognosis and new treatment options are urgently needed," said Lori Lyons-Williams, president and chief executive officer. "These cancers have the most aggressive clinical course of any type of pulmonary tumor and often rapidly metastasize to other parts of the body. We are thrilled the FDA has recognized the potential of ABD-147 to become a transformative treatment option for SCLC and we are excited to begin clinical development and provide ABD-147 to patients in need."

In the second half of 2024, Abdera plans to initiate a first-in-human Phase 1 clinical trial with ABD-147 in patients with SCLC or large cell neuroendocrine carcinoma (LCNEC) who previously received platinum-based therapy.

About Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma

The global incidence for SCLC and LCNEC has been reported to represent approximately 325,000 patients and is expected to increase 4% annually through 2029. In the U.S., the incidence has been reported to be approximately 35,000 new cases annually. Fifteen percent of all lung cancer cases are high-grade neuroendocrine cancers. These cancers have the most aggressive clinical course of any type of pulmonary tumor and often metastasize to other parts of the body, including the brain, liver and bone. Without treatment, the median survival from diagnosis has been reported to be only two to four months. With treatment, the overall survival at five years is 5% to 10% for SCLC, and 15% to 25% for LCNEC. SCLC and LCNEC generally carry a poor prognosis and new treatment options are urgently needed.

About ABD-147

ABD-147 is a targeted radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope, to solid tumors expressing delta-like ligand 3 (DLL3) with high affinity. DLL3 is a protein in the Notch pathway that is critical for the development and regulation of neuroendocrine versus epithelial cell differentiation in the lungs. In certain high grade neuroendocrine carcinomas including small cell lung cancer (SCLC), DLL3 is upregulated and specifically expressed on the cell surface in more than 80% of cases. In contrast, DLL3 is absent or very rarely expressed on the surface of nonmalignant cells. Given the high specificity of DLL3 expression on cancer cells and the distinct mechanism of action, DLL3 represents a compelling target for treating SCLC and other DLL3+ solid tumors with targeted radiotherapy.

About the ROVEr Platform

Abdera’s Radio Optimized Vector Engineering (ROVEr) platform enables the company to custom-engineer targeted radiopharmaceuticals with tunable pharmacokinetic (PK) properties to achieve high tumor uptake while minimizing renal exposure and mitigating other systemic radiotoxicities such as myelosuppression. Abdera can optimize the delivery and therapeutic index of potent radioisotopes capable of emitting powerful alpha or beta particles to selectively destroy tumor cells while sparing healthy cells, providing patients with potentially transformative new cancer treatments.

Abdera’s approach offers the ability to design radiotherapeutics against virtually any cancer target expressed on the cell surface. Coupled with a highly potent mechanism of cell killing, the ROVEr platform is uniquely poised to exploit both high- and low-expressing targets to selectively deliver therapeutic levels of radioisotope to cancer cells.

On June 26, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported positive 18-month follow-up data from the OPTIMIZE-1 Phase 2 study of the company’s lead asset mitazalimab in 1st line metastatic pancreatic cancer (Press release, Alligator Bioscience, JUN 26, 2024, View Source [SID1234644545]). The open-label, multi-center study assessed the safety and efficacy of mitazalimab (CD40 mAb agonist) in combination with standard of care chemotherapy mFOLFIRINOX, in previously untreated, chemotherapy naïve pancreatic cancer patients.
The data demonstrated a near doubling of the 18-month survival rate to 36.2% in patients treated with mitazalimab in combination with mFOLFIRINOX, compared to 18.6% reported with FOLFIRINOX[1] alone.

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The updated Median Overall Survival (mOS) was 14.9 months, up from 14.3 months at the time of first analysis, comparing favorably to the 11.1 months demonstrated by FOLFIRINOX[1] and more recently by NALIRIFOX[2].

Median follow-up duration for the updated analysis was 18.2 months, indicating the maturity of these outcomes. At the time of the analysis, a total of 17 (30%) patients were still alive, and of these 9 (16% overall) were still on treatment. The longest ongoing treatment duration was 24 months.

The follow-up data further demonstrate:

An additional late responding patient increased the confirmed Objective Response Rate (ORR; as per the Response Evaluation Criteria in Solid Tumors RECIST 1.1) to 42.1% from the 40.4% reported in the top-line readout, comparing favorably to the ORR of 31.6% reported in a similar patient population treated with FOLFIRINOX alone[1] and an ORR of 42% reported by NALIRIFOX[2]
An increase in the unconfirmed ORR to 54.4% was reported in 57 evaluable patients
The median Duration of Response (DoR) was 12.6 months, an unprecedented outcome in this aggressive disease and much longer compared to 5.9 months with FOLFIRINOX[1] and 7.3 months with NALIRIFOX[2]
Median Progression Free Survival (PFS) was 7.7 months, and a nearly 3-fold increase in the 12-month PFS rate was reported; 35.1% in OPTIMIZE-1 against 12.1% previously reported for FOLFIRINOX[1].
"These latest results from the OPTIMIZE-1 study of our lead asset provide a strong validation of the clear and sustained clinical benefit produced by mitazalimab when combined with mFOLFIRINOX in the treatment of first-line pancreatic cancer. In fact, mitazalimab increases your chance of being alive at the 18-month mark by 95 percent, compared to published FOLFIRINOX data," said Søren Bregenholt, CEO of Alligator Bioscience. "These highly promising outcomes warrant continued clinical development of mitazalimab in a confirmatory setting and we are committed to bringing mitazalimab to pancreatic cancer patients as fast as possible."
"These results clearly represent a remarkable outcome in pancreatic cancer, with the robust Duration of Response indicating highly consistent clinical benefit resulting in prolonged Overall Survival," said Prof. Jean-Luc van Laethem, Head of the Digestive Oncology Clinic in the Gastroenterology Department of Erasmus Hospital (ULB) Brussels and Principal Investigator of the OPTIMIZE-1 trial. "Particularly noteworthy is the high proportion of patients surviving at the 18-month landmark, which most patients in this disease unfortunately do not see. With such a strong immunotherapeutic contribution, mitazalimab combined with mFOLFIRINOX has the potential to become the new treatment standard in pancreatic cancer, and we are eagerly awaiting the initiation of a randomized confirmatory study."
Top-line results from the OPTIMIZE-1 study were published in the world-leading oncology journal The Lancet Oncology and will also be presented at the upcoming ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2024 being held in Munich, Germany from June 26-29.

Phase 3 on track to start in first half of 2025
Alligator is continuing its preparations for the global Phase 3 registration study to evaluate mitazalimab in pancreatic cancer and the company remains on track to initiate the study in 2025. This follows Alligator’s discussions with the US Food and Drug Administration (FDA) which established a clear development and approval pathway for mitazalimab in pancreatic cancer.

In 2023, mitazalimab was granted orphan drug designation in pancreatic cancer by both the FDA and the European Medicines Agency (EMA).

On June 26, 2024 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported it has entered into securities purchase agreements with health-care focused institutional investors for the purchase and sale of 568,000 shares of common stock in a registered direct offering and warrants to purchase up to 568,000 shares of common stock in a concurrent private placement (together with the registered direct offering, the "Offering") at a combined purchase price of $2.45 per share (Press release, CNS Pharmaceuticals, JUN 26, 2024, View Source [SID1234644546]). The warrants issued pursuant to the concurrent private placement will have an exercise price of $2.32 per share, will be exercisable immediately following the date of issuance and will expire 5 years from the initial exercise date.

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The closing of the Offering is expected to occur on or about June 27, 2024, subject to the satisfaction of customary closing conditions. The gross proceeds from the Offering are expected to be approximately $1.39 million before deducting financial advisory fees and other offering expenses payable by the Company. The Company intends to use the net proceeds from the Offering for working capital and general corporate purposes.

The common stock will be issued in a registered direct offering pursuant to an effective shelf registration statement on Form S-3 (File No. 333-279285) previously filed with the U.S. Securities and Exchange Commission (the "SEC"), under the Securities Act of 1933, as amended (the "Securities Act"), and declared effective by the SEC on May 17, 2024. The warrants will be issued in a concurrent private placement. A prospectus supplement describing the terms of the proposed registered direct offering will be filed with the SEC and once filed, will be available on the SEC’s website located at View Source

The private placement of the ordinary warrants and the underlying shares will be made in reliance on an exemption from registration under Section 4(a)(2) of the Securities Act and/or Regulation D thereunder. Accordingly, the securities issued in the concurrent private placement may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.