On March 14, 2023 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," reported it will present two poster presentations on the company’s CBL-B program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, FL (Press release, Ascentage Pharma, MAR 14, 2023, View Source [SID1234628707]). One poster will describe preclinical data for the CBL-B program, and one Clinical Trials in Progress poster will describe the first-in-human Phase 1/2 clinical trial of HST-1011.

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Presentation details are as follows:

Title: Inhibition of the E3 ligase CBL-B enhances the effector function and proliferation of natural killer cells
Session Title: Late-Breaking Research: Immunology 3
Session Date and Time: Wed., Apr. 19, 9:00 AM-12:30 PM ET
Location: Poster Section 36
Poster Board Number: 5
Abstract Number: LB337

Title: Phase 1/2 study of HST-1011, an oral CBL-B inhibitor, alone and in combination with anti-PD1 in patients with advanced solid tumors
Session Title: Phase I and First-in-Human Clinical Trials in Progress
Session Date and Time: Tue., Apr. 18, 1:30-5:00 PM ET
Location: Poster Section 46
Poster Board Number: 14
Abstract Number: CT251

About HST-1011
HST-1011 is an investigational orally bioavailable, selective, small molecule allosteric inhibitor of CBL-B, an E3 ubiquitin protein ligase critically involved in immune cell response. Because CBL-B functions as a master regulator of effector cell (T cell and natural killer cell) immunity, its inactivation removes its endogenous negative regulatory functions to substantially enhance anti-tumor immunity. Preclinical data has demonstrated HST-1011’s ability to bind to and inhibit a natural hotspot on CBL-B, yielding the activation and propagation of a targeted anti-tumor immune response. Enabled by HotSpot’s proprietary Smart AllosteryTM platform, HST-1011 is designed with tight binding, low nanomolar potency, a slow dissociation rate from the target to enable sustained pharmacology, and greater selectivity for CBL-B relative to C-CBL.

In March 14, 2023 Jacobio Pharma (1167.HK) reported that the company will present the results of three preclinical studies of KRASmulti inhibitor JAB-23425, CD73-STING iADC JAB-X1800, and Aurora kinase A inhibitor JAB-2485 in form of the abstract during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (the "AACR 2023") from April 14 to 19, 2023 (Press release, Jacobio Pharmaceuticals, MAR 14, 2023, View Source [SID1234628706]).

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Details for the 2023 AACR (Free AACR Whitepaper) abstracts are as follows:

Abstract Number:1660
Abstract Title: Preclinical investigation of orally bioavailable, potent KRASMulti inhibitor JAB-23425
Session: Novel Antitumor Agents 4
Time: April 17, 2023, 9:00 AM – 12:30 PM (ET)

KRASmulti inhibitor JAB-23425 targets multiple KRAS mutants in both RAS(ON) and RAS (OFF), with good selectivity over HRAS and NRAS. JAB-23425 has significant antitumor effect on cancer models with multiple KRAS mutations (such as G12D, G12V, and G13D) and amplification of wild type KRAS, and has no inhibitory effect on KRAS-independent cells. The KRASmulti inhibitor JAB-23425 is expected to solve the unmet clinical needs of patients with KRAS-mutated tumors. JAB-23425 is a leading compound of Jacobio’s KRASmulti inhibitor.
View Source!/10828/presentation/6635

Abstract Number: 2923
Abstract Title: JAB-X1800: a potent immunostimulatory antibody-drug conjugate (iADC) targeting CD73
Session: Therapeutic Antibodies 2
Time: April 17, 2023, 1:30 PM – 5:00 PM (ET)

JAB-X1800 is the world’s first iADC by conjugating Jacobio’s STING agonist to CD73 antibody, which is expected to turn the tumor from "cold" to "hot," and combine synergize with anti-PD-1 mAb.
View Source!/10828/presentation/3620

Abstract Number: 1645
Abstract Title: JAB-2485: a potent, highly selective small-molecule Aurora kinase A inhibitor that targets cell division
Session : Novel Antitumor Agents 4
Time: April 17, 2023, 9:00 AM – 12:30 PM (ET)

JAB-2485 is one of the top two highly selective Aurora A inhibitors with 1500-fold selectivity over Aurora kinase B and Aurora kinase C, with high activity and low bone marrow toxicity as well as favorable PK properties.
View Source!/10828/presentation/6620

"Jacobio leverages our IADDP (Induced Allosteric Drug Discovery Platform) to develop drugs aiming specific undruggable targets," said Dr. WANG Yinxiang, chairman and CEO of Jacobio, "These preclinical data are part of the research and development achievements of Jacobio since its establishment 8 years ago, and we will continue to transform the fundamental research in academia into clinical achievements through independent R&D in the future."

The 2023 AACR (Free AACR Whitepaper) Annual Meeting will be held in Orlando, Florida, USA from April 14th to April 19th. For more information, please visit the official website of the AACR (Free AACR Whitepaper): View Source

On March 14, 2023 Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, reported the enrollment of the first patient in its Phase Ib trial of iadademstat in combination with gilteritinib in patients with relapsed/refractory acute myeloid leukemia (AML) harboring a FMS-like tyrosine kinase mutation (FLT3mut+), at the Massachusetts General Hospital in Boston, US (Press release, Oryzon, MAR 14, 2023, View Source;utm_medium=email&utm_campaign=NdP.07+15-03-2023+FPI+FRIDA+ENG562 [SID1234628705]).

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FRIDA (NCT05546580) is an open-label, multicenter study of iadademstat plus gilteritinib for the treatment of patients with relapsed or refractory AML (R/R AML) with FLT3·mutations. The trial’s primary objectives are to evaluate the safety and tolerability of iadademstat in combination with gilteritinib in patients with FLT3mut+ R/R AML and to establish the Recommended Phase 2 Dose (RP2D) for this combination. Secondary objectives include evaluation of the treatment efficacy, measured as the rate of complete remission and complete remission with partial hematological recovery (CR/CRh), the duration of responses (DoR) and the assessment of measurable residual disease (MRD). The trial’s principal investigator is Amir Fathi, M.D., Associate Professor at Harvard Medical School and Director of the Leukemia Program at Massachusetts General Hospital. FRIDA will be conducted in 10-15 sites in the US. The study will enroll up to approximately 45 patients and if successful, the Company and FDA have agreed to hold a meeting to discuss the best plan to further develop this combination in this much in need AML population.

Dr. Carlos Buesa, President and CEO of Oryzon, said: "FRIDA’s initiation is a significant corporate milestone for Oryzon, marking a further expansion of our clinical pipeline as we seek to improve the treatment options for patients. Iadademstat has already shown strong efficacy data in AML. We hope this combination will open up new ways to treat these patients and make an important difference to their outlooks."

Oryzon’s Global Chief Medical Officer, Dr. Douglas Faller, said: "We are pleased to announce the first patient entering into the FRIDA trial. It is our hope that the combination of iadademstat and gilteritinib will safely provide deep and durable responses for patients whose leukemias are driven by FLT3 mutations."

FRIDA’s scientific rationale is based on iadademstat’s ability to inhibit the lysine specific demethylase 1 (LSD1), thereby triggering a powerful differentiating effect in hematologic cancers, as well as producing an anti-leukemic effect by targeting leukemic stem cells. Furthermore, the combination of iadademstat with

gilteritinib demonstrated a very strong synergy in FLT3·mut+ AML preclinical models. This together with the fact that iadademstat has been administered to more than 100 cancer patients (including AML patients) demonstrating a good safety profile, activity and excellent pharmacologic properties supports exploring its combination with FLT3 inhibitors in FLT3·mut+ AML, targeting between 30-40% of AML patients. In a recently finalized, Phase IIa study (ALICE trial) in elder/unfit AML patients, iadademstat demonstrated robust efficacy in combination with azacitidine, with 81% ORR in the evaluable patients, of which 64% were CR/CRi. Final data from the ALICE trial were presented as an oral communication at the recent 64th ASH (Free ASH Whitepaper) annual conference (see here for more details).

On March 14, 2023 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, reported that it will present data from five preclinical investigations in poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held in Orlando, Fla., April 14-19, 2023 (Press release, Harpoon Therapeutics, MAR 14, 2023, View Source [SID1234628703]).

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"The breadth of data from Harpoon’s five poster presentations at AACR (Free AACR Whitepaper) supports further investigation of additional tumor targets, combination approaches with TriTACs, as well as our next-generation technology platform with conditionally active T cell engager prodrugs, or ProTriTACs," said Julie Eastland, President and Chief Executive Officer of Harpoon Therapeutics. "Additionally, the preclinical data investigating the activity of TriTAC in an immunocompetent mouse model provide further validation of our ongoing and planned clinical efforts with HPN328 and HPN217, leveraging our proprietary TriTAC T cell engager platform. We look forward to further validation in the clinic as our research efforts continue."

Details of the AACR (Free AACR Whitepaper) poster presentations are as follows:

Title: Long-term anti-tumor immunity induced by HPN328, a DLL3-targeting tri-specific, half-life extended T cell engager, in a preclinical immunocompetent mouse model
Abstract Number: 4131
Session: Immunology/Determinants of Immunotherapeutic Effectiveness
Session Date, Time: Tuesday, April 18, 9 a.m. – 12:30 p.m. ET
Location: Poster Section 24

Title: Anti-tumor activity of HPN328, a DLL3-targeting tri-specific, half-life extended T cell engager, is enhanced by combining with an anti-PD-L1 antibody in an immunocompetent mouse model
Abstract Number: 5070
Session: Immunology/Combination Immunotherapies 1
Session Date, Time: Tuesday April 18, 1:30 – 5 p.m. ET
Location: Poster Section 21

Title: Anti-tumor activity of HPN217, a BCMA-targeting tri-specific T cell engager, is enhanced by γ-secretase inhibitors in preclinical models
Abstract Number: 5081
Session: Immunology/Combination Immunotherapies 1
Session Date, Time: Tuesday April 18, 1:30 – 5 p.m. ET
Location: Poster Section 21

Title: TROP2 ProTriTAC, a protease-activated T cell engager prodrug targeting TROP2 for the treatment of solid tumors
Abstract Number: 2928
Session: Immunology/Therapeutic Antibodies 2
Session Date, Time: Monday April 17, 1:30 – 5 p.m. ET
Location: Poster Section 23

Title: ITGB6 ProTriTAC, a protease-activated T cell engager prodrug targeting Integrin-β6 for the treatment of solid tumors
Abstract Number: 2927
Session: Immunology/Therapeutic Antibodies 2
Session Date, Time: Monday April 17, 1:30 – 5 p.m. ET
Location: Poster Section 23

The posters will also be available on Harpoon’s website following the presentations.

For more details about the AACR (Free AACR Whitepaper) Annual Meeting, please visit:
View Source

On March 14, 2023 Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, reported that two abstracts on mRNA-4157/V940 an investigational mRNA personalized cancer vaccine, have been accepted for presentation at the 2023 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 14-19 in Orlando, FL (Press release, Moderna Therapeutics, MAR 14, 2023, View Source [SID1234628702]). mRNA-4157/V940 is being jointly developed by Moderna and Merck, known as MSD outside of the United States and Canada.

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The two abstract titles are:

Presentation #CT001: A personalized cancer vaccine, mRNA-4157, combined with pembrolizumab versus pembrolizumab in patients with resected high-risk melanoma: Efficacy and safety results from the randomized, open- label Phase 2 mRNA-4157-P201/Keynote-942 trial. Harnessing the Immune System in the Clinic.
Session: Clinical Trials Plenary; Sunday, April 16 at 1:00-3:00 PM ET.
Presenter: Dr. Jeffrey S. Weber
Poster Session #CT224: Evaluation of minimal residual disease as a predictive biomarker of recurrence free survival in high-risk melanoma patients treated with a combination of mRNA-4157, a personalized cancer vaccine, and pembrolizumab.
Session: Phase II Clinical Trials 2; Tuesday, April 18 at 9:00 AM – 12:30 PM ET.
Author: Dr. Ryan J. Sullivan
AACR will post the text of late-breaking and clinical trials abstracts in the AACR (Free AACR Whitepaper) Annual Meeting online itinerary planner and Annual Meeting app on April 14, 2023 at 12:00 PM ET.

Moderna’s exhibit booth at the AACR (Free AACR Whitepaper) Annual Meeting is booth #2664.

About mRNA-4157/V940

Personalized cancer vaccines are designed to prime the immune system so that a patient can generate a tailored antitumor response specific to their tumor mutation signature. mRNA-4157/V940 is a novel investigational messenger ribonucleic acid (mRNA)-based personalized cancer vaccine consisting of a single synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the patient’s tumor. Upon administration into the body, the algorithmically derived and mRNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.

mRNA-4157/V940 is being developed in combination with KEYTRUDA. mRNA-4157/V940 is designed to stimulate an immune response by generating specific T cell responses based on the unique mutational signature of a patient’s tumor. KEYTRUDA is an immunotherapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.

Moderna and Merck plan to initiate a Phase 3 study in adjuvant melanoma in 2023 and expect to rapidly expand to additional tumor types, including non-small cell lung cancer.