On May 15, 2024 Nutcracker Therapeutics, Inc., a biotechnology company dedicated to developing transformative RNA therapies through its proprietary technology platform, reported data presented by its partners at the University of California, San Francisco (UCSF) on foundational prostate cancer antigen research utilized to inform the development of its mRNA drug candidate, NTX-470 (Press release, Nutcracker Therapeutics, MAY 15, 2024, View Source [SID1234643371]). The data were presented by lead author Elena Montauti, Ph.D., from UCSF on May 4, during the 2024 Annual Meeting of the American Association of Immunologists (AAI) in Chicago.

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It is well established that prostate cancer is a "cold cancer" with low immunogenicity. Its low mutation burden has resulted in very few druggable neoantigens – leaving shared tumor-associated antigens (TAAs) as the primary targets for immunotherapeutic development. However, the larger landscape of which shared prostate TAAs are immunogenic targets is challenging to assess and has not been systemically studied across patients. Further, it is unknown how antigen immunogenicity evolves as the disease progresses. The research presented at AAI aimed to map antigen reactivity in prostate cancer to inform possible combinations of TAAs that could be used as treatment for the disease.

Using its Nutshell technologies, Nutcracker Therapeutics’ scientists worked with UCSF researchers to create mRNAs encoding eight common and shared prostate TAAs, and employed a novel antigen recall assay to systematically study T cell immune responses in blood samples of patients with localized and metastatic prostate cancer. Cellular immune responses to shared TAAs were tracked across cohorts and correlated with treatment and disease outcomes after immunotherapy. Single-cell genomic analysis was used to characterize TAA-reactive T cell effector phenotypes and to track TCR expansion. Together, this in-depth analysis of TAA-reactive cellular responses in prostate cancer patients provides potentially transformative insights for the development of shared antigen-directed immunotherapeutics.

"We’re proud to have a partnership with the talented individuals at the University of California, San Francisco," said Chief Scientific Officer Samuel Deutsch, Ph.D. "The data presented at AAI reflects our deep commitment to new therapeutic strategies for prostate cancer, including the development of NTX-470. We’re hopeful that with our continued work with our partners at UCSF, we can continue conducting research that sheds a light on the unknowns of different cancers, and informs the development of much-needed novel therapeutics – whether by Nutcracker Therapeutics or others in the field."

"There are many knowledge gaps that currently exist in prostate cancer research," said UCSF Assistant Professor of Medicine David Oh, M.D., Ph.D. "The means by which antigen recognition changes as the cancer progresses is still unknown – making it difficult to design and develop effective drugs for more advanced forms of prostate cancer. By systematically researching antigen reactivity using this programmable platform, and relating this to known clinical outcomes after immunotherapy, we aim to lay the groundwork to address these existing knowledge gaps, with the hopes of inspiring the development of a new generation of mRNA-based immunotherapeutics for prostate cancer."

The research presented at AAI was the result of a longstanding partnership between Nutcracker Therapeutics and UCSF. Currently, Nutcracker Therapeutics has partnerships with Dr. Lawrence Fong and Dr. Oh’s labs in cancer immunotherapy. This data – resulting from a collaboration with Dr. Oh – expands upon a previous demonstration of the data by UCSF at last year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in 2023.

Previously, Nutcracker Therapeutics presented preclinical data at this year’s AACR (Free AACR Whitepaper) Annual Meeting for NTX-470. This multimodal mRNA therapy for prostate cancer encodes both PSMA and STEAP1 antigens, and was shown to effectively engage CD3 T cells with reduced off-tumor binding, which may result in diminished treatment toxicity.

On May 15, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that the latest results from five studies have been selected for Poster Presentations at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress (EHA 2024) (Press release, Ascentage Pharma, MAY 15, 2024, View Source;results-from-five-studies-of-ascentage-pharmas-key-drug-candidates-selected-for-presentations-at-2024-european-hematology-association-hybrid-congress-302147047.html [SID1234643370]). These posters will feature olverembatinib (HQP1351), the first and only China-approved third-generation BCL-ABL1 inhibitor; investigational lisaftoclax (APG-2575), a Bcl-2 selective inhibitor; and investigational APG-5918, an EED selective inhibitor.

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The European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress is the largest gathering of the hematology field in Europe. It showcases the most cutting-edge research and state-of-the-art innovative therapies, attracting over 10,000 clinical experts and researchers from more than 100 countries every year. This year, the EHA (Free EHA Whitepaper) Hybrid Congress will take place on June 13 – 16, 2024, in Madrid, Spain.

"I am delighted to showcase the strength and progress of Ascentage Pharma in hematology at this year’s congress, especially the therapeutic potential and clinical value of its drug candidates in chronic myeloid leukemia (CML), Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), multiple myeloma (MM), immunoglobulin light-chain (AL) amyloidosis, and anemia diseases," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We look forward to sharing the detailed results at the congress. In the future, we will continue to advance those development programs in efforts to bring more treatment options to patients around the world."

The five studies to be presented at EHA (Free EHA Whitepaper) 2024 are as follows:

Olverembatinib
Olverembatinib Overcomes Ponatinib and Asciminib Resistance in Patients (Pts) with Heavily Pretreated Chronic Myeloid Leukemia (CML) and Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph⁺ ALL)

• Abstract#: P722
• Presentation Type: Poster presentation
• Topic: Chronic myeloid leukemia – Clinical
• Date & Time: Friday June 14, 2024, 18:00 – 19:00 CEST
• Presenting Author: Dr. Elias Jabbour, The University of Texas MD Anderson Cancer Center

Combination of Third Generation TKI Olverembatinib and Chemotherapy or Blinatumomab for New Diagnosed Adult Ph+ ALL Patients

• Abstract#: P427
• Presentation Type: Poster presentation
• Topic: Acute lymphoblastic leukemia – Clinical
• Date & Time: Friday June 14, 2024, 18:00 – 19:00 CEST
• Presenting Author: Junjie Chen, Nanfang Hospital, Southern Medical University

Patient Reported Outcomes in Adults with TKI-Resistant Chronic Myeloid Leukemia Receiving Olverembatinib-Therapy

• Abstract#: P1862
• Presentation Type: e-Poster presentation
• Topic: Chronic myeloid leukemia – Clinical
• Date & Time: Friday June 14, 2024, 18:00 – 19:00 CEST
• Presenting Author: Lu Yu, Peking University People’s Hospital

Lisaftoclax
Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (Pts) with Relapsed or Refractory (R/R) Multiple Myeloma (MM) or Immunoglobulin Light-Chain (AL) Amyloidosis

• Abstract#: P917
• Presentation Type: Poster presentation
• Topic: Myeloma and other monoclonal gammopathies – Clinical
• Date & Time: Friday June 14, 2024, 18:00 – 19:00 CEST
• Presenting Author: Dr. Sikander Ailawadhi, Mayo Clinic Florida

APG-5918
Embryonic Ectoderm Development (EED) Inhibitor APG-5918 Improves Chronic Kidney Disease- (CKD)-Induced Hemoglobin (HB) Insufficiency in Preclinical Models of Anemia

• Abstract#: P1550
• Presentation Type: Poster presentation
• Topic: Enzymopathies, membranopathies and other anemias
• Date & Time: Friday June 14, 2024, 18:00 – 19:00 CEST
• Presenting Author: Dr. Eric Liang, Ascentage Pharma Group Inc.

On May 15, 2024 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported financial results for the first quarter, ended March 31, 2024, and provided a corporate update (Press release, Ryvu Therapeutics, MAY 15, 2024, View Source [SID1234643369]).

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Pawel Przewiezlikowski, co-founder, largest shareholder, and Chief Executive Officer of Ryvu Therapeutics, said:
"We are progressing rapidly with our clinical and preclinical pipeline programs and expect several key milestones in 2024. With RVU120 now in Phase II, we have achieved our development goals established last year. By the end of this year, we anticipate RVU120, our first-in-class CDK8/19 inhibitor, enrolling patients across four independent and potentially high-value development paths. We are well-positioned with a cash runway through Q1 2026 and numerous potential non-dilutive capital sources ahead of us."

Q1 2024 SUMMARY AND RECENT CORPORATE EVENTS

RVU120 clinical development plan progress

In early 2024, Ryvu launched two Phase II studies with RVU120: the RIVER-52 study investigating RVU120 as monotherapy in two genetically defined cohorts of patients with r/r AML or HR-MDS, and the RIVER-81 study investigating RVU120 in combination with venetoclax in patients with AML.
POTAMI-61, a Phase II study evaluating the efficacy of RVU120 in patients with myelofibrosis (MF), is expected to initiate in Q3 2024. On March 28, Ryvu signed an agreement with Fortrea for the operational execution of POTAMI-61 clinical study.
REMARK, a Phase II study of RVU120 in patients with low-risk myelodysplastic syndromes (LR-MDS), is expected to initiate in mid-2024. REMARK will be conducted as an investigator-initiated study through the EMSCO network with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator.
The company plans to enroll approximately 100 patients across all RVU120 Phase II studies this year and aims to present initial Phase II data by the end of 2024.
Preclinical updates

At the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (April 5-10, San Diego, California), Ryvu presented preclinical data from its synthetic lethality pipeline and RVU120:
Ryvu’s PRMT5 inhibitors have potentially best-in-class profiles and favorable drug-like, oral administration properties, including a solid antiproliferative effect on MTAP-deleted cell lines and a good safety window for MTAP WT cells. Ryvu anticipates nominating a PRMT5 clinical candidate and initiation of IND-enabling studies in 2024.
Ryvu’s WRN inhibitor program demonstrates target engagement and selective potency with a synthetic lethal effect, providing pharmacological proof-of-concept; in vivo efficacy studies showed pronounced tumor growth inhibition in an MSI-H colorectal cancer xenograft model and supported WRN inhibition as a new, targeted oncological therapy.
RVU120 shows efficacy both as a monotherapy and synergistically in combination with ruxolitinib in preclinical myeloproliferative neoplasms models (MPN), including myelofibrosis (MF) and polycythemia vera.
UPCOMING INDUSTRY AND INVESTOR EVENTS

Myelofibrosis Webinar, Friday, May 17 at 3:00 PM CEST: Ryvu will host a webinar discussing RVU120 and spotlighting MF. Registration is available at: View Source
10th Annual Oncology Innovation Forum, Chicago, May 31: Ryvu will give a corporate presentation and conduct investor/partner meetings.
Pekao I Technology & Consumer Conference, Warsaw, June 3: Ryvu will conduct investor meetings
Erste | CEE Consumer & Technology Conference 2024, Warsaw, June 4: Ryvu will conduct investor meetings
EHA Congress, Madrid, June 13-16: Ryvu will present clinical and preclinical data from RVU120 and host an exhibition booth; three posters will be presented on RVU120:
Updated data from the Phase Ib trial of RVU120 in patients with relapsed/refractory acute myeloid leukemia (r/r AML) or high-risk myelodysplastic syndromes (HR-MDS) demonstrate promising clinical activity.
Preclinical data support the synergistic combination of RVU120 and venetoclax in patients with AML, including RVU120’s potential to overcome resistance to venetoclax treatment.
In vivo data further supported CDK8 inhibition as a potential novel therapeutic strategy in myeloproliferative neoplasms (MPNs), focusing on myelofibrosis (MF).
Q1 2024 FINANCIAL UPDATE

Cash Position – On March 31, 2024, Ryvu Therapeutics held $62.7M in cash, cash equivalents, and bonds, compared to $63.7M on December 31, 2023. On May 9, 2024, Ryvu Therapeutics held $59.0M in cash, cash equivalents, and bonds, including €8M of venture debt from the EIB, received on March 13. 2023.

Operating Revenues— In Q1 2024, Ryvu recognized total operating revenues (including grants) of $6.4M, compared to $4.3M in Q1 2023.

Operating costs, related primarily to research and development expenditures, excluding the valuation of NodThera shares and non-cash cost of valuation of the Incentive Program ($0.3M) in Q1 2024, amounted to $11.7M, compared to $7.5M in Q1 2023.

Net Loss Attributable to Common Shareholders – In Q1 2024, the net loss attributable to common shareholders, excluding the non-cash cost of valuation of the Incentive Program, amounted to $4.6M compared to $3.3M in the same period last year.

On May 15, 2024 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, reported it will host a KOL webinar on Monday, May 20, 2024, at 8:00 AM ET (Press release, Actinium Pharmaceuticals, MAY 15, 2024, https://www.prnewswire.com/news-releases/actinium-to-host-kol-webinar-to-discuss-iomab-act-commercial-car-t-cell-therapy-trial-design-objectives-and-potential-market-opportunity-302145688.html [SID1234643368]). The call will highlight and discuss Actinium’s recently announced Iomab-ACT commercial CAR T-cell trial being conducted at the University of Texas Southwestern (UTSW) including the study design, objectives and potential commercial opportunity for Iomab-ACT. To date, Iomab-ACT has been studied in a clinical trial with an investigational CD19 targeting CAR-T cell therapy developed by Memorial Sloan Kettering Cancer Center (MSKCC) under a National Institutes of Health funded grant. The trial at UTSW will be the first trial to study Iomab-ACT or any targeted radiotherapy conditioning agent with an FDA approved CAR T-cell therapy. Dr. Farrukh Awan, Professor of Medicine, Division of Hematology Oncology at University of Texas Southwestern, specializes in the treatment of patients with leukemia and lymphoma including CAR-T therapy and bone marrow transplantation. Dr. Awan will serve as principal investigator for this study being led by UTSW.

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Webinar Details and Registration:

Date: Monday, May 20th, 2024

Time: 8 AM ET

Register here or on the investor relations page of Actinium’s website here.

Iomab-ACT is an ARC that targets CD45, a marker expressed on blood cancer cells and immune cells that is intended to enable conditioning prior to cell and gene therapies such as CAR T-cell therapy and replace the non-targeted chemotherapy that is currently used for conditioning. There are six CAR-T cell therapies approved to treat patients with leukemias, lymphomas and multiple myeloma that collectively reached sales in 2023 exceeding $3.5 billion.

Iomab-ACT Phase 1 CAR-T Conditioning Results

Actinium presented results from its ongoing phase 1 trial using Iomab-ACT as conditioning prior to CD19 CAR-T therapy for patients with relapsed or refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) or Diffuse Large B-cell Lymphoma (DLBCL) at the Tandem Meetings I Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR the combined annual meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR) in February 2024. Importantly, no patients (0/4) developed immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade, a major safety measure of the study and minimal Cytokine Release Syndrome (CRS). ICANS is observed in 25% or more of pts w/ R/R B-ALL and DLBCL treated with various currently approved CAR T-cell products. Iomab-ACT demonstrated transient depletion of peripheral blood lymphocytes and monocytes. Persistence of CAR T-cells up to 8 weeks and minimal non-hematologic toxicities have been observed to date.

Targeted Radiotherapy Conditioning Opportunity

The opportunity exists for better conditioning in other areas of cellular therapy, such as CAR-T as well as gene therapies. The pipeline of CAR-T and gene therapies has rapidly expanded, with the addressable patient population expected to nearly double and reach approximately 93,000 patients in the U.S. by 2030 based on the current pipeline of cellular therapies. The CAR-T market size in terms of revenue is estimated to grow at a CAGR of approximately 11% over the next 5 plus years. Currently, there are six CAR T-cell therapies approved by the FDA that are used to treat patients with lymphomas, leukemia, and multiple myeloma, which collectively had total sales of over $3.5 billion in 2023. The addressable market for Iomab-ACT is in line with the patient population for cell and gene therapies as all patients must receive some type of conditioning prior to these treatments. We will continue to develop Iomab-ACT, our next-generation conditioning program for rapidly growing cell and gene therapies based on early promising results, ultimately with the value proposition of improving overall access and outcomes for patients who need cellular or gene therapies. A potential blockbuster revenue opportunity exists for Iomab-ACT assuming it can provide one or more clinical benefits related to lower CRS, less ICANS, longer duration of response with selective lymphodepletion or a higher overall success rate of cellular therapy due to benefits of targeted conditioning.

On May 15, 2024 Amplia Therapeutics reported the successful completion of its $4.27 million fully underwritten, non-renounceable entitlement offer which was well supported by existing eligible shareholders and new institutional and sophisticated investors (Entitlement Offer) (Press release, Amplia Therapeutics, MAY 15, 2024, View Source [SID1234643366]).

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Under the Entitlement Offer eligible shareholders were entitled to apply for two (2) fully paid ordinary shares (New Shares) for every five (5) shares held on Friday 19 April 2024 (Record Date) at the offer price of $0.055. The Entitlement Offer will issue 77,602,838 New Shares raising a total of $4.27 million (before costs).

In total, Amplia received valid applications from eligible shareholders for 36,049,966 New Shares ($1.983 million). The resultant shortfall of 41,552,872 New Shares ($2.285 million) (Shortfall) was placed by the Lead Manager and Underwriter, Taylor Collison Limited (Lead Manager), to new and existing institutional and sophisticated investors.

Amplia’s CEO and Managing Director Dr Chris Burns commented "Amplia’s Board and Management are extremely grateful for the ongoing support of our shareholders and advisors and we welcome new shareholders to the Company. Our successful Entitlement Offer permits the Company to continue to actively progress development of our best-in-class FAK inhibitor narmafotinib, with specific focus on delivering critical interim data in our ongoing Phase 2 ACCENT trial in pancreatic cancer."

Director Participation
As previously announced, US based Company Director, Dr Robert Peach, committed to sub-underwrite A$150,000 in the Entitlement Offer and was proportionally allocated A$105,000 in the Shortfall. In addition, Managing Director and CEO, Chris Burns, and Company Director, Jane Bell, cumulatively took up $78,000 of their rights under the Entitlement Offer.

Use of funds
The proceeds from the Entitlement Offer will be used to fund the ongoing Phase 2 ACCENT trial in pancreatic cancer to an Interim Analysis (expected in Q3 2024), as well as undertake production of additional narmafotinib capsules and support a pilot Investigator Initiated trial in ovarian cancer currently in planning.

ACCENT Trial Update
The Company is pleased to announce that the ongoing Phase 2a ACCENT trial in advanced pancreatic cancer patients is progressing to plan. In this stage of the trial, newly diagnosed advanced (metastatic) pancreatic cancer patients receive orally-dosed narmafotinib (at the optimal 400 mg dose identified from the Phase 1b trial) combined with the standard-of-care chemotherapy gemcitabine and Abraxane. At present, nineteen (19) patients of a total of 26 are enrolled in trial sites in Australia and South Korea. An interim analysis will be conducted to determine whether six (6) or more patients on the trial record a partial response, and if so, a further 24 patients will be enrolled, bringing the patient cohort to 50 patients in total. The Company previously disclosed that six (6) patients out of fourteen (14) recorded a partial response in the Phase 1b stage of the trial. Dr Burns commented: "The excellent recruitment progress and support from clinicians seen to date in the ACCENT trial is extremely encouraging and we expect it to allow us to report Interim Data in Q3 this year."

About the ACCENT Trial
The protocol for the ACCENT trial is entitled ‘A Phase 1b/2a, Multicentre, Open Label Study of the Pharmacokinetics, Safety and Efficacy of AMP945 in Combination with Nab-paclitaxel and Gemcitabine in Pancreatic Cancer Patients’.

The trial is a single-arm open label study conducted in two stages. The first stage (Phase 1b) determined an optimal dose of narmafotinib (AMP945) by assessing the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of narmafotinib when dosed in combination with gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer.

This second stage (Phase 2a) of the trial currently underway will assess efficacy of narmafotinib in combination with gemcitabine and Abraxane, along with continued assessment of safety and tolerability. The primary endpoints are Objective Response Rate (ORR) and Duration on Trial (DOT) with secondary endpoints being Progression Free Survival (PFS) and Overall Survival (OS).

More information about the ACCENT trial, including a list of participating sites, can be found via the Amplia Therapeutics website and at ClinicalTrials.gov under the identifier NCT05355298.

The Company will provide further updates on the trial as recruitment proceeds.

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics.