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Hummingbird Bioscience to Speak at 2021 Virtual Symposium: "VISTA: A New Immune Checkpoint in Cancer, Autoimmunity and Beyond"

On June 14, 2021 Hummingbird Bioscience, an innovative clinical-stage biotech company focused on developing precision therapies against hard-to-drug targets, reported that its Chief Scientific Officer and co-founder, Dr Jerome Boyd-Kirkup, will be speaking at the 2021 virtual symposium "VISTA: A New Immune Checkpoint in Cancer, Autoimmunity and Beyond", taking place on June 18, 2021 (Press release, Hummingbird Bioscience, JUN 14, 2021, View Source [SID1234583978]).

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Hosted by Randolph Noelle, PhD, Professor of Microbiology and Immunology, Department of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth; and Padmanee Sharma, MD, PhD, Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, the event gathers leading immunology experts across industry and academia to discuss the emerging checkpoint molecule, VISTA, including its function, the role it plays in several disease areas and current development programs.

Hummingbird will be speaking in the following sessions:

Session Title: VISTA regulation of the tumor microenvironment in human cancer
Date/Time: June 18, 2021 from 9:50 AM to 10:35 AM ET

Session Title: VISTA advances into clinical development
Date/Time: June 18, 2021 from 12:20 PM to 1:05 PM ET

"The presence of VISTA is increasingly implicated as a resistance mechanism to other immune checkpoint therapies, including anti-PD-1 and anti-CTLA-4 antibodies. This conference is an excellent opportunity to share insights and knowledge, including Hummingbird’s experience with our highly differentiated clinical stage anti-VISTA antibody, HMBD-002," said Dr Boyd-Kirkup.

Hummingbird’s rationally targeted anti-VISTA neutralizing antibody, HMBD-002, is the only IgG4 isotype anti-VISTA neutralizing antibody that is currently in development for the treatment of cancers with VISTA-mediated immune suppression, including triple negative breast cancer and non-small cell lung cancer. Pre-clinical studies have shown that HMBD-002 as a monotherapy inhibits tumor growth and significantly prolongs survival, with no observed toxicity. It has also shown synergy when used in combination with anti-PD-1 therapy. The Phase 1 clinical trial for HMBD-002 is anticipated to commence later this year.

To learn more about the symposium and register to attend, please visit: https://bit.ly/3hBzIUj.

About HMBD-002

HMBD-002 is a unique anti-VISTA neutralizing antibody, and the only IgG4 isotype anti-VISTA antibody currently in development. It was engineered to bind to VISTA at a specific site that is predicted to be essential for ligand-binding and function, thus inhibiting VISTA and neutralizing its immunosuppressive activity without depleting VISTA expressing cells that play many important roles in the immune system.

Pre-clinical studies have shown that HMBD-002 as a monotherapy inhibits tumor growth and significantly prolongs survival, with no observed toxicity. It has also shown synergy when used in combination with anti-PD-1 therapy.

HMBD-002 is being developed for multiple cancers that have strong evidence of VISTA mediated suppression both as a monotherapy and in combination with PD-1 inhibitor.

Hummingbird’s first-in-class anti-VISTA therapeutic antibody is advancing to clinical trials with support from a US$13.1 million product development grant from the Cancer Prevention and Research Institute of Texas (CPRIT).

Fusion Pharmaceuticals Announces Preliminary Safety and Dosimetry Results from its Single-Dose Portion of the Phase 1 Study of FPI-1434

On June 14, 2021 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported the presentation of preliminary Phase 1 data from the single-dose portion of the study at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Virtual Annual Meeting (Press release, Fusion Pharmaceuticals, JUN 14, 2021, View Source [SID1234583977]). The presentations and posters highlight the potential of Fusion’s targeted alpha therapies (TATs) to enable delivery of alpha particle emitting isotopes (225Ac) to targeted tumor cells.

"The data from our ongoing clinical study of FPI-1434 presented at SNMMI demonstrated that treatment with our actinium-based targeted alpha therapy was well tolerated, and imaging shows uptake of the drug across multiple tumor types," said Chief Executive Officer John Valliant, Ph.D. "Importantly, these data supported our ability to initiate the multi-dosing portion of the study, in which we would expect to begin reaching total cumulative levels of radiation necessary to demonstrate anti-tumor activity."

In both the oral session and the poster titled, "Preliminary Dosimetry Results from a First-in-Human Phase 1 Study Evaluating the Efficacy and Safety of [225Ac]-FPI-1434 in Patients with IGF-1R Expressing Solid Tumors," results from the first three patient cohorts (n=12) demonstrated a favorable safety profile for [225Ac]-FPI-1434. No drug-related serious adverse events and/or dose limiting toxicity were reported in administered activity up to 40 kBq/kg body weight and dosimetric results were within normal organ radiation tolerability limits. The single dose escalation portion of the study has concluded, while enrollment into the multi-dosing cohorts are ongoing.

Preclinical Results Combining FPI-1434 with DNA Damage Response Inhibitor (DDRi) and Immune Checkpoint Inhibitors
In separate oral and poster presentations, Fusion presented preclinical data demonstrating synergistic efficacy against olaparib-resistant colorectal and radioresistant lung cancer xenografts when combining FPI-1434 with olaparib.

The combination of the two therapeutics, using doses that were non-effective as single agents, resulted in anti-tumor efficacy against colorectal and non-small cell lung cancer tumor models. The strongest combination effect appeared to occur at the lowest single agent doses, as FPI-1434’s efficacy dominated at higher dose levels.

Fusion also presented preclinical data showing that treatment with FPI-1434 in combination with immune checkpoint inhibitors resulted in complete tumor eradication. Additionally, an increase in antigen-specific CD8 positive T cells and a strong "vaccine" effect were observed with the combination of IGF-1R TAT and immune checkpoint inhibitors, as noted by the prevention of tumor growth in animals that were reinoculated with the same tumor cells.

Dr. Valliant continued, "We are excited by our preclinical data that show the power of combining a potent TAT with the latest generation of cancer therapies, such as checkpoint inhibitors and DDRis. We view these combinations as an opportunity to bring these next-generation radiopharmaceuticals into earlier lines of therapy for patients, and we look forward to initiating combination studies in human once we have achieved the recommended Phase 2 dose for FPI-1434 monotherapy. Our previously announced collaborations with both Merck and AstraZeneca provide us with multiple opportunities to explore these exciting combination therapies."

Following the conclusion of the SNMMI Annual Meeting, copies of the presentations can be found at View Source

About FPI-1434
FPI-1434 is a radioimmunoconjugate designed to target and deliver alpha emitting medical isotopes to cancer cells expressing IGF-1R, a receptor that is overexpressed on many tumor types. FPI-1434 utilizes Fusion’s Fast-Clear linker to connect a human monoclonal antibody that targets IGF-1R with actinium-225, a powerful alpha-emitting isotope with desirable half-life and decay chain properties.

Protagonist Therapeutics Announces Proposed Public Offering of Common Stock

On June 14, 2021 Protagonist Therapeutics, Inc. (Nasdaq:PTGX), a clinical stage biopharmaceutical company, reported that it has commenced an underwritten public offering of $100,000,000 of shares of its common stock (Press release, Protagonist, JUN 14, 2021, View Source [SID1234583976]). All of the shares of common stock are being offered by Protagonist. In connection with this offering, Protagonist expects to grant the underwriters a 30-day option to purchase up to an additional 15% of the number of shares of its common stock offered in the public offering.

J.P. Morgan Securities LLC, Jefferies LLC and Piper Sandler are acting as joint book-running managers for the offering. JMP Securities LLC and H.C. Wainwright & Co., LLC are acting as co-lead managers for the offering. The offering is subject to market conditions and there can be no assurance as to whether or when the offering may be completed or the actual size or terms of the offering.

A shelf registration statement relating to the offered shares of common stock was filed with the Securities and Exchange Commission (SEC) on December 10, 2020. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website, located at www.sec.gov. Prospective investors should read the preliminary prospectus supplement, when available, and the accompanying prospectus and other documents Protagonist has filed with the SEC for more complete information about Protagonist and the offering. Copies of the prospectus supplement and the accompanying prospectus related to the offering may be obtained, when available from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at 866-803-9204, or by email at [email protected]; Jefferies LLC (Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, New York 10022; telephone: 877-821-7388; email: [email protected]); or Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924 or by email at [email protected].

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

Ascentage Pharma Announces IND Clearance by the US FDA for Lisaftoclax (APG-2575) as Single Agent or in Combinations for the Treatment of ER+ Breast Cancer and Other Solid Tumors

On June 14, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the Investigational New Drug (IND) application for the company’s novel Bcl-2 inhibitor, lisaftoclax (APG-2575), has been cleared by the US Food and Drug Administration (FDA) and the company is poised to initiate a clinical study of lisaftoclax as a single agent or in combination with other antitumor therapies for the treatment of patients with advanced estrogen receptor-positive (ER+) breast cancer or other solid tumors (Press release, Ascentage Pharma, JUN 14, 2021, View Source [SID1234583975]).

This global multicenter, open-label Phase Ib/II clinical study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of lisaftoclax as a single agent in patients with advanced solid tumors, or in combination with palbociclib in patients with metastatic ER+ and human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer relapsed or refractory to prior treatment with cyclin–dependent kinase 4/6 (CDK4/6) inhibitors.

Breast cancer is one of the most common malignancies in women. About 75% of all breast cancer cases are hormone receptor positive (HR+)1, mainly estrogen receptor positive (ER+), and the antiapoptotic protein Bcl-2 is overexpressed in around 85% of this subset2. Endocrine therapy is the standard of care treatment for patients with early-stage or metastatic HR+/HER2- breast cancer. In the first-line treatment of metastatic ER+ breast cancer, an CDK4/6 inhibitor (palbociclib, ibociclib, or abemaciclib) in combination with endocrine therapy can offer longer progression-free survival (PFS) and overall survival (OS), as compared to endocrine therapy alone3,4. In the second-line setting, phosphoinositide 3-kinase (PI3K) inhibitor plus fulvestrant, and everolimus plus endocrine therapy can effectively target the PI3K-AKT-mTOR pathway, thus offering additional treatment options for patients who failed first-line treatments3. However, patients treated with endocrine therapies and targeted therapies commonly develop drug resistances, eventually necessitating chemotherapies. Therefore, there is an urgent clinical need for novel targeted therapies that can effectively blockade mutational pathways and delay chemotherapies.

Lisaftoclax is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. Lisaftoclax is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China. Previously, lisaftoclax had received clearances and approvals for multiple Phase Ib/II clinical studies in China, Australia, the US, and Europe, and is currently being developed in a range of hematologic malignancies globally. As a single agent, lisaftoclax has potent antitumor activity in Bcl-2-dependent tumor cell lines, and has shown broad antitumor effects when combined with other antitumor therapies.

Preclinical data of lisaftoclax in combination with palbociclib showed that palbociclib can induce cell cycle arrest and apoptosis, while lisaftoclax can bolster the expression of proapoptotic proteins such as BIM and downregulate ER levels, while lowering the levels of phosphorylated Rb protein, and the cyclin D1 and E. Therefore, Bcl-2 inhibitors combined with CDK4/6 inhibitors can synergistically enhance cell cycle arrest while inducing the cell death of ER+ tumors.

"Lisaftoclax is a core drug candidate in our apoptosis-targeted pipeline. This IND clearance by the US FDA for lisaftoclax in patients with solid tumors marks another major milestone for this drug candidate," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As the first China-developed Bcl-2 inhibitor entering clinical development in China, lisaftoclax has enormous therapeutic potential, both as a single agent and in combinations. Lisaftoclax has shown promising clinical activity and favorable tolerability in hematologic malignancies, and we look forward to expanding and deepening our investigation of lisaftoclax in solid tumors. We are now advancing the clinical development of this drug candidate globally in the hope of soon benefiting patients in China and around the world."

The U.S. FDA Approved IND Application to Investigate Combination of Asieris’ APL-1202 and BeiGene’s Tislelizumab as Neoadjuvant Therapy for MIBC Patients

On June 14, 2021 Asieris Pharmaceuticals (Asieris) reported that the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application of oral APL-1202 in combination with BeiGene’s tislelizumab as neoadjuvant therapy in patients with muscle invasive bladder cancer (MIBC) (Press release, Asieris Pharmaceuticals, JUN 14, 2021, View Source [SID1234583974]). Asieris will accelerate the initiation of the clinical trial enrollment in the U.S. and also file a Clinical Trial Application (CTA) to the National Medical Products Administration (NMPA) of China in the near future.

This is an open-label, multi-center Phase I/II clinical study with the following objectives: to evaluate the safety in MIBC patients; to determine the RP2D (recommended Phase 2 dose), and to assess efficacy as neoadjuvant therapy for MIBC.

APL-1202 is an orally available reversible MetAP2 Inhibitor with anti-angiogenic, anti-tumor activities and can also modulate tumor immune microenvironment. It is currently in Phase III/pivotal clinical trials in China, either as single agent as first-line treatment for patients with intermediate-risk non-muscle invasive bladder cancer (NMIBC), or in combination with a chemotherapy as second-line treatment in patients with intermediate and high-risk chemo-refractory NMIBC. Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. The China National Medical Products Administration (NMPA) has granted tislelizumab approval in three indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy; and conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies and for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

According to the 2020 Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Urothelial Carcinoma, the Level I recommendation for MIBC is that patients who tolerate cisplatin undergo radical cystectomy (RC) after neoadjuvant chemotherapy. The commonly used chemotherapy regimen is gemcitabine plus cisplatin (GC). However, cisplatin can cause serious side effects such as renal dysfunction, peripheral neuropathy, and bone marrow suppression, and some patients are intolerant. Patients with intolerance to cisplatin don’t have any preoperative/neoadjuvant therapy that can bring survival benefits.

"We are very pleased that FDA approved the IND application for oral APL-1202 in combination with tislelizumab as a neoadjuvant therapy in MIBC patients," said Dr. Xue Yong, MD, PhD, Chief Medical Officer at Asieris. "The approval is expected to accelerate the clinical development, and Asieris will conitnue to explore cutting-edge technologies and therapeutics in our focused areas to meet the urgent medical needs and establish an outstanding portfolio that covers diagnosis and treatment to benefit more patients. "