On May 17, 2023 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a Cayman Islands incorporated biopharmaceutical company focused on developing and commercializing innovative therapeutics and pharmaceutical products, reported its financial results for the three months ended March 31, 2023 (Press release, CASI Pharmaceuticals, MAY 17, 2023, View Source [SID1234631826]).

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Wei-Wu He, Ph.D., CASI’s Chairman and Chief Executive Officer, commented, "Revenue for EVOMELA was $8.3 million in the first quarter of 2023, down 8% from the same period in 2022. This decline is primarily due to the enhanced impact of the COVID-19 restrictions in major cities in China since fourth quarter 2022. We are also facing competition from a generic melphalan for injection product with lower cost and undifferentiated formulation in China market. CASI’s commercial and medical marketing team has implemented a strategy to defend our market leadership position. CASI has a strong foundation for our commercial franchise in the oncology malignant hematology therapeutic area. We will continue to grow our commercial franchise throughout 2023 and beyond."

Dr. He continued, "Advancement, development, and commercialization of the portfolio remains our strategic focus. We have achieved a major milestone with our partner Juventas Biotechnology (Tianjin) ("Juventas") on the CNCT-19 CART cell therapy. CNCT-19’s New Drug Application (NDA) was accepted by National Medical Products Administration (NMPA) in December 2022. We are now diligently preparing for the anticipated CNCT-19 launch in China. We are advancing the clinical development of BI-1206 in combination with rituximab and presently undertaking the enrollment of patients for the second cohort of the phase I trial in China. CB-5339 also received Clinical Trial Application approval from the NMPA in January 2023. We are transitioning the development of CID-103 into China for the malignant hematology indications and have submitted the multiple myeloma IND to the Chinese Health Authority. We plan to build on the momentum to drive our portfolio forward by executing on several milestones as well as bringing in new potential opportunities for synergy in the quarters ahead."

First Quarter 2023 Financial Highlights

Revenues consist primarily of product sales of EVOMELA. Revenue was $8.3 million for the three months ended March 31, 2023, compared to $9.0 million for the three months ended March 31, 2022.

Costs of revenues were $3.4 million for the three months ended March 31, 2023, compared to $3.8 million for the three months ended March 31, 2022.

Research and development expenses for the three months ended March 31, 2023 were $2.5 million, compared with $4.0 million for the three months ended March 31, 2022. The decrease was mainly due to reduced R&D expenses on CID-103.

General and administrative expenses for the three months ended March 31, 2023 were $5.7 million, compared with $5.3 million for the three months ended March 31, 2022.

Selling and marketing expenses for the three months ended March 31, 2023 were $4.0 million, compared with $3.3 million for the three months ended March 31, 2022. The increase was mainly due to increased marketing activities.

Other income for the three months ended March 31, 2023 was $1.3 million, compared with $0.04 million for the three months ended March 31, 2022. The increase was mainly attributed to the $1.3 million refund from Pharmathen Global BV with respect to the termination of the exclusive distribution license agreement of product Octreotide LAI.

Net loss for the three months ended March 31, 2023 was $5.8 million, compared with $8.4 million for the three months ended March 31, 2022.

As of March 31, 2023, CASI had cash, cash equivalents, short term investments and long-term deposit of $44.8 million compared to $51.6 million as of December 31, 2022. Cash and cash equivalents are expected to fund current operations beyond the first quarter of 2024.

Further information regarding the Company, including its Quarterly Report for the quarter ended March 31, 2023, can be found at www.casipharmaceuticals.com.

On May 17, 2023 Kyverna Therapeutics ("Kyverna"), a cell therapy company with the mission of engineering a new class of therapies for serious autoimmune diseases, reported that it will present for the first time preclinical findings on the development of KYV-101, a novel CD19 CAR T-cell therapy, at the 26th Annual meeting of the American Society for Gene and Cell Therapy (Press release, Kyverna Therapeutics, MAY 17, 2023, View Source;cell-therapy-26th-annual-meeting-301826412.html [SID1234631825]).

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The study demonstrates the successful manufacture and functional activity of KYV-101 from the blood of patients with systemic lupus erythematosus (SLE). KYV-101 is a novel therapy for lupus nephritis (LN), a serious complication of SLE, more commonly known as lupus.

"These results are encouraging and demonstrate the promise of KYV-101 as a transformative therapy for patients with LN and other B cell-driven autoimmune diseases," said James Chung, M.D., Ph.D., chief medical officer of Kyverna.

Poster details:

Development of KYV-101, a Novel CD19 CAR-T Cell Therapy for the Treatment of B Cell-Driven Autoimmune Diseases
Abstract Number: 636
Session: Wednesday Poster Session
Presenter: Charles Kaplan, Ph.D., Kyverna Therapeutics
Date/Time: Wednesday, May 17, 2023; 12:00 p.m. – 2:00 p.m. PT

About Lupus Nephritis (LN)
Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), more commonly known as lupus. Approximately 40 percent of adults diagnosed with lupus eventually develop LN and 60 percent of LN patients will fail standard of care and approved treatments1. Aside from modest efficacy, current treatments expose these young adults to the well-demonstrated detrimental consequences of chronic treatment with corticosteroids and other powerful immunosuppressants. Up to 10 percent of patients with LN and 40 percent with diffuse LN (class IV) will ultimately develop kidney failure, requiring dialysis or a kidney transplant to stay alive2.

About KYV-101
KYV-101 is an autologous version of a novel, fully human clinical-stage anti-CD19 chimeric antigen receptor T-cell (CAR T) construct with properties well suited for use in B cell-driven autoimmune diseases such as lupus nephritis and other B-cell driven autoimmune diseases. In a 20-patient Phase 1/2 study in oncology, expected anti-lymphoma activity was associated with a significant reduction of cytokines released that translated into a strong reduction of cytokine-driven side effects such as the rate of immune effector cells-associated neurotoxicity syndrome (ICANS)3. The fully human anti-CD19 CAR also translated into reduced immunogenicity that favorably impacted cell persistence at one month. Kyverna recognized that these properties singled out KYV-101 as a product ideally poised for use in autoimmune disease patients, and the company obtained exclusive, worldwide licenses from the National Institutes of Health (NIH) to use this CD19 construct in both autologous and allogeneic CAR T-cell therapies.

On May 17, 2023 Avenge Bio, Inc. ("Avenge"), a clinical stage, oncology-focused biotechnology company developing the LOCOcyte Immunotherapy platform for the precision administration of potent immune effector molecules to treat solid tumors, reported participation in the upcoming scientific and investor conferences (Press release, Avenge Bio, MAY 17, 2023, View Source;investor-conferences-301826580.html [SID1234631824]):

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5th Annual Allogenic Cell Therapies Summit – May 22-25, 2023
Location: The Westin Boston Seaport District | Boston, MA
Date & Time: Thursday, May 25, 2023 – Advancing Durability & Persistence Focus Day – 12:30 PM ET
Presenter: Omid Veiseh, PhD (Rice University & Co-Founder, Avenge Bio)
Seminar: Cell Generated Immunotherapies Eradicating Solid Tumors

American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting – June 2-6, 2023
Location: McCormick Place | Chicago, IL
Session Type/Title: Poster Session – Gynecologic Cancer
Date & Time: Monday, June 5, 2023 – 1:15-4:15 PM CT
Abstract #: TPS5616
Poster Board #: 309a
Poster Title: A Phase 1/2 Open-Label, Multicenter, Dose Escalation, and Expansion Study of AVB-001, an Intraperitoneally Administered, Cell-Generated, Human IL-2 Immunotherapy in Patients with Platinum-Resistant, High-Grade, Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube
Clinical Trial #: NCT05538624
Presenter: Shannon N. Westin, MD, MPH (MD Anderson Cancer Center)

BIO International Convention – June 5-8, 2023
Location: Boston Convention & Exhibition Center (BCEC) | Boston, MA
Members of the executive team will be participating in one-on-one partnering meetings. To schedule a meeting, please submit a request via the partnering platform.

Jefferies Healthcare Conference – June 7-9, 2023
Location: Marriott Marquis | New York, NY | Track 3
Date & Time: Wednesday, June 7, 2023 – 11:00-11:25 AM ET
Avenge will have an in-person presentation by Michael Heffernan, Chief Executive Officer. Members of the executive team will be available to participate in one-on-one investor meetings.

About LOCOcyte Platform

Our LOCOcyte allogeneic cell-based immunotherapy platform enables potent localized modulation of the immune system which also precipitates a systemic immune response, allowing us to treat previously intractable cancers. The technology leverages three unique advantages:

Potent immune effector molecules are generated by synthetically engineering allogeneic cells creating a ready-to-use therapy,

Therapy is localized in proximity to the primary tumor site and generates innate and adaptive immune response, and

The immunomodulator trains the patient’s immune system generating a robust immune response that seeks and eradicates distal metastasis without systemic toxicity.

On May 17, 2023 Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standards of care to cure cancer and infectious diseases, reported the start of its open-label Phase 1/2 study evaluating Debio 0123, a brain-penetrant and highly selective WEE1 inhibitor, in combination with temozolomide (TMZ) in patients with recurrent or progressive glioblastoma and in combination with TMZ/RT (SOC) in newly diagnosed patients (Press release, Debiopharm, MAY 17, 2023, View Source [SID1234631823]). The initial phase of this study aims to define the recommended phase 2 doses of Debio 0123.

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GBM is among the most aggressive and common lethal tumors of the central nervous system. This disease represents a major cause of morbidity and mortality affecting more than 13,000 Americans and causing the death of about 10,000 patients in 2022 1. If left untreated, in some cases GBM can lead to the patient’s death in approximately 3 months. This type of cancer tends to occur more often in adults between 65-75 years of age. Throughout the continuum of this devastating disease, patients face serious quality of life issues including motor deficits, personality changes, cognitive deficits, language disorders (aphasia) or visual field defects. The disease’s poor prognosis constitutes a serious public health concern.

With its Debio 0123 WEE1 inhibitor, Debiopharm is seeking to meet the urgent need for novel treatment interventions to improve clinical outcomes and quality of life for patients suffering from newly diagnosed or recurrent GBM. In cancer cells, DDR pathways are often upregulated due to genomic instability, elevating the chances of resistance to DNA-damaging therapies. Therefore, blocking DNA repair pathways through inhibition of essential kinases such as WEE1 might contribute to increase the cancer’s vulnerability to standard of care therapies. Moreover, preclinical results presented at AACR (Free AACR Whitepaper) 2023 have shown that Debio 0123 successfully crosses the blood brain barrier and inhibits tumor growth. Furthermore, the in vivo combination of Debio 0123 with TMZ demonstrated significantly increased antitumor activity.

"I am very excited to witness the development of a new generation of brain penetrant drugs. Having drugs like this allows us to explore novel treatments for brain tumors, which remains an ongoing challenge." Dr. Jordi Rodon Ahnert, MD, PhD, MD Anderson Cancer Center, Houston, Texas.

"The combination of Debio 0123 with temozolomide is promising. Treatment with Debio 0123 to inhibit WEE1 has the advantage of selectively impacting tumor cells, which, due to the increasing replication stress during the S-phase, become more reliant on the proper functioning of the G2-M checkpoint. Debio 0123 acting at both S-phase and G2-M checkpoint can thus make GBM cells more vulnerable to DNA-damaging agents like temozolomide" expressed Dr. Victor Rodriguez-Freixinos, Associate Medical Direction in Oncology at Debiopharm.

"Due to its physiological and structural properties, the blood brain barrier represents a unique challenge for drug delivery and a massive obstacle to patient’s care. Thus, Debio 0123 brain permeability represents an important source of hope to patients suffering from brain cancers" stated Dr. Patrick Roth, University Hospital Zürich.

About Glioblastoma

Glioblastomas are fast-growing and aggressive brain tumors that can arise de novo or evolve from lower grade gliomas. GBM may be asymptomatic until it reaches a significant size. Aside from diagnostic challenges, nearly all GBM recur, and effective treatment options are limited. The widely accepted SOC for patients with newly diagnosed GBMs consists of surgical resection, followed by radiation therapy with concurrent TMZ. Despite treatment, nearly all GBM recur, the 5-year survival rate is still only 6.8% 1 and treatment options are very limited.

About Debio 0123

Debio 0123 is a brain-penetrant, highly selective WEE1 kinase inhibitor. WEE1 is a key regulator of the G2/M and S phase checkpoints, activated in response to DNA damage, allowing cells to repair their DNA before resuming their cell cycle. WEE1 inhibition, particularly in combination with DNA damaging agents, induces an overload of DNA breaks. In conjunction with abrogation of other checkpoints such as G1, the compound pushes the cells through cycle without DNA repair, promoting mitotic catastrophe and inducing apoptosis of cancer cells. Currently in research for solid tumors in monotherapy and combination, Debio 0123 is being developed to respond to high unmet needs of patients living with the burden of difficult-to-treat cancers.

About DNA-Damage Repair (DDR)

When cells have damaged DNA, they need to undergo a repair process called DDR to be able to survive. Cancer cells use their hyperactive DDR response to divide and grow uncontrollably, which promotes cancer expansion. Inhibition of DDR, particularly in combination with other anticancer agents, induces an overall arrest in the uncontrollable cancer cell cycle. This ultimately activates a self-destruction program in cancer cells. DDR inhibitors such as Debiopharm’s WEE1 and USP1 inhibitors, are being tested in clinical and preclinical studies.

On May 17, 2023 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that the Investigational New Drug (IND) for a Phase I study of the first-in-class anti-CD24 monoclonal antibody ATG-031 has received clearance from the U.S. Food and Drug Administration (FDA) (Press release, Antengene, MAY 17, 2023, View Source [SID1234631822]).

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The PERFORM trial is a first-in-human, multi-center, open-label, Phase I dose-finding study of ATG-031 in patients with advanced solid tumors or B-NHL. The primary objective of the study is to evaluate the safety and tolerability of ATG-031 as a monotherapy, and to determine the appropriate dose for Phase II studies. The secondary objective is to characterize the pharmacology, evaluate the immunogenicity, and assess the preliminary efficacy of ATG-031.

ATG-031 is a first-in-class humanized anti-CD24 monoclonal antibody which inhibits the "don’t eat me" signal in the tumor microenvironment (TME). ATG-031 was designed to specifically bind with the CD24 expressed on cancer cells with high affinity and block the interaction between CD24 and the Siglec-10 receptor expressed on the surface of tumor associated macrophages (TAMs), to enhance the macrophage-mediated phagocytosis of cancer cells and promote cytotoxic T-cell function in the tumor microenvironment.

"Targeting the so-called ‘don’t eat me’ signal is a promising therapeutic strategy for cancer treatment. In comparison to existing ‘don’t eat me’ blockers such as anti-CD47 monoclonal antibodies, ATG-031 demonstrated a wider therapeutic window and the ability to overcome the on-target-off-tumor toxicities observed with CD47 inhibitors," said Dr. Bing Hou, Antengene’s Executive Director of Drug Discovery and a co-inventor of ATG-031. "CD24 is a small and highly glycosylated protein that makes the development of antibodies particularly challenging. Through our persistent experimental efforts and by adopting unique discovery and screening strategies as well as leveraging our deep expertise on the target’s biology, Antengene’s discovery scientists successfully advanced ATG-031, an antibody with optimal characteristics, into clinical development in just three years. We are thrilled to see our in-house developed first-in-class drug entering the clinic and taking a major step towards benefiting patients."

"We believe that therapies that can effectively mobilize the macrophage activity in the tumor microenvironment will be a very important element of cancer care," said Dr. Bo Shan, Antengene’s Chief Scientific Officer. "The potential role of ATG-031 is supported by robust preclinical data that showed potent single agent in vivo efficacy and synergistic effects with chemotherapy or checkpoint inhibitors (CPIs). Therefore, we are very optimistic about the clinical development of ATG-031 and look forward to initiating the patient enrolment as early as possible."

"In this clinical program for ATG-031, we will deploy an in-house developed companion diagnostic (CDx) antibody, thus adding a precision-medicine element to the program," said Dr. Amily Zhang, Antengene’s Chief Medical Officer. "In addition to serving as a patient selection tool, the CDx antibody will help us to better understand the CD24 expression in normal and cancerous tissue. We are excited to learn more about the safety, tolerability and efficacy of ATG-031 through the clinical program and look forward to sharing the first data from this study in 2024."

"ATG-031 is the world’s first anti-CD24 antibody to be advanced to the clinic in oncology and Antengene’s third drug candidate cleared to enter clinical studies in the U.S.," said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO. "I am very proud of the entire R&D organization, for innovating and advancing this proprietary asset, from bench to patient, in such a robust and efficient manner. We believe that targeting CD24 could represent a major oncological advancement and anticipate more exciting progress with this clinical program."

About ATG-031

ATG-031 is a first-in-class humanized CD24 monoclonal antibody which inhibits the "don’t eat me" signal and enhances macrophage-mediated phagocytosis of cancer cells. Tumor cells evade the surveillance of the human immune system by over-expressing "don’t eat me" surface proteins that signal macrophages to prevent the detection and phagocytosis of cancer cells. CD24 (cluster of differentiation 24) is a prominent "don’t eat me" signal that plays a significant role in tumor immune evasion by suppressing macrophage-mediated phagocytosis. Compared to CD47, another well-known "don’t eat me" target, CD24 has more restricted distribution in normal tissue and higher expression in cancerous tissue. In addition，unlike CD47，CD24 is not expressed on human red blood cells，allowing for a wider therapeutic window and minimal on-target-off-tumor toxicity as a CD24-targeted therapy.

As a novel innate immune checkpoint, CD24 orchestrates immune evasion through its interaction with the inhibitory receptor called Siglec-10 (sialic-acid-binding Ig-like lectin 10) expressed on tumor-associated macrophages (TAMs). Preclinical data presented in 2023 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR 2023) demonstrated that ATG-031 can specifically bind to CD24 with nM affinity and block the interaction of CD24 and Siglec-10. Furthermore, ATG-31 induces efficient phagocytosis with a picomolar EC50 and stimulate the pro-inflammatory cytokines production by macrophages.