On September 23, 2024 Heidelberg Pharma AG (FSE: HPHA), a clinical stage company developing innovative Antibody Drug Conjugates (ADCs), reported that new data from its Phase I/IIa clinical study with lead Amanitin-based ADC candidate, HDP-101, will be presented at the 21st International Myeloma Society (IMS) Annual Meeting, being held in Rio De Janeiro, Brazil on 25 to 28 September 2024 (Press release, Heidelberg Pharma, SEP 23, 2024, View Source [SID1234646818]).

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HDP-101 is an Anti-BCMA antibody-Amanitin drug conjugate for the treatment of relapsed or refractory multiple myeloma, a bone marrow cancer with a high unmet medical need. Phase I of the trial is a dose escalation study to determine an optimal and safe dose level of HDP-101 in patients in preparation for Phase II clinical studies.

Professor Marc-Steffen Raab, Head of the Myeloma Center at the University Hospital Heidelberg and clinical investigator of the study will present new clinical findings from five patient cohorts of the ongoing open-label, multicenter Phase I/IIa trial evaluating HDP-101 in multiple myeloma.

Details of the presentation are as follow:

Presentation title: The Anti-BCMA Antibody-Drug Conjugate HDP-101 with a Novel Amanitin Payload Shows Promising Initial First in Human Results in Relapsed Multiple Myeloma (OA – 60)

Session:

Abstract Session 5

Speaker:

Professor Marc-Steffen Raab

Date and time:

Friday, 27 September 2024, 9:48 am – 10:00 am (BRT)

Location:

Plenary Hall, Pavilion 3; Room name: 101 A1-A2

Previous data from cohort five have demonstrated biological activity in three out of five patients, and an objective improvement in disease was detected ("partial remission"). The trial is currently treating patients in its sixth cohort with further data to be presented at upcoming scientific conferences.

Following the presentation at IMS, Heidelberg Pharma will host a R&D Webinar on 15 October 2024 at 17:00 pm CEST/ 11:00 am ET, for investors, analysts and media. Further registration information will be announced in due course.

On September 23, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation (FTD) to EO-3021, a differentiated antibody drug conjugate (ADC), for the treatment of patients with advanced or metastatic gastric and gastroesophageal junction (GC/GEJ) cancer expressing Claudin 18.2 that has progressed on or after prior therapy (Press release, Elevation Oncology, SEP 23, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-receives-fast-track-designation-from-the-fda-for-eo-3021-for-the-treatment-of-adult-patients-with-advanced-or-metastatic-gastric-or-gastroesophageal-junction-cancer-expressing-claud [SID1234646817]).

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"We are delighted to receive Fast Track designation for EO-3021, which marks an encouraging recognition of the unmet medical need in patients with Claudin 18.2-expressing tumors, as well as the potential for EO-3021 to deliver improved therapeutic outcomes," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "This designation is based on nonclinical and initial clinical data from our ongoing Phase 1 clinical trial. As we announced in August, early results showed a confirmed overall response rate of 42.8% in a Claudin 18.2-enriched subset of gastric and GEJ cancer. In addition, we observed differentiated tolerability, with minimal MMAE-associated toxicities, including no neutropenia or peripheral neuropathy/hypoesthesia. We are grateful for the opportunity to potentially expedite the delivery of EO-3021 and look forward to advancing through monotherapy dose expansion and reporting additional data from our ongoing trial in the first half of 2025, and to initiating the combination portion of our study later this year."

Fast Track is a process designed by the FDA to facilitate the development and expedite the review of therapeutic candidates intended to treat serious or life-threatening conditions, for which nonclinical or clinical data demonstrate the potential to address unmet medical needs. Therapeutic candidates that receive FTD may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan. Therapeutic candidates with Fast Track designation may also be eligible for priority review and accelerated approval if supported by clinical data.

About EO-3021

EO-3021 is a differentiated, clinical-stage antibody drug conjugate (ADC) with best-in-class potential comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2 and a monomethyl auristatin E (MMAE) payload with a cleavable linker that is site-specifically conjugated to Glutamine 295 providing a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 trial (NCT05980416) in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

Elevation Oncology has the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China.

On September 23, 2024 Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd., reported the resubmission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for its investigational drug rivoceranib, an oral VEGF-TKI, in combination with camrelizumab, a PD-1 inhibitor, as a first-line systemic treatment option for unresectable hepatocellular carcinoma (uHCC) (Press release, Elevar Therapeutics, SEP 23, 2024, View Source [SID1234646816]).

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In May, the FDA issued a Complete Response Letter (CRL) for the original NDA submitted in May 2023. The CRL cited GMP deficiencies at the Hengrui Pharma facility where camrelizumab is manufactured and incomplete Bioresearch Monitoring (BIMO) clinical inspections due to FDA travel restrictions. The FDA did not indicate any issues related to clinical data or with the manufacturing site for rivoceranib. During a Type A meeting with the FDA in July, the FDA confirmed the responses to observations at the Hengrui manufacturing site were sufficient, resubmission could occur without further delay and BIMO inspections may occur after resubmission.

"Elevar’s timely resubmission of the NDA for the combination of camrelizumab and rivoceranib marks a critical milestone in our mission to bring a novel combination therapy for uHCC to patients and healthcare providers. HCC remains an area of significant unmet medical need," said Dr. Saeho Chong, chief executive officer of Elevar Therapeutics. "This achievement would not have been realized without the extraordinary dedication of Elevar’s teams. We are eager to work with the FDA in the coming months as we focus on the commercialization of our combination therapy." The resubmission is supported by the Phase 3 CARES-310 study landmark analysis presented during the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 1, which reported median overall survival (mOS) of 23.8 months, the longest mOS for any treatment in a global Phase 3 trial for patients with uHCC, confirming the combination of camrelizumab and rivoceranib continued to show sustained long-term survival as a first-line treatment for uHCC.

"The combination of camrelizumab and rivoceranib shows distinct promise as a potential therapy for patients suffering from advanced hepatocellular carcinoma with efficacy results generally consistent across all subgroups," commented Ahmed Omar Kaseb, M.D., professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston. "The resubmission is strengthened by the recent CARES-310 landmark analysis, which reported the longest median overall survival for any treatment in a global Phase 3 trial in the uHCC setting."

About Hepatocellular Carcinoma

Worldwide each year more than 800,000 people are diagnosed with liver canceri and the disease is the cause of more than 830,000 deaths.ii Hepatocellular Carcinoma (HCC) is the most common type of liver cancer and most frequently develops in people with chronic underlying liver inflammation which may be from viral and non-viral causes. HCC typically has a poor prognosis with limited treatment options and continues to be a diagnosis with an ongoing urgent medical need.

About Rivoceranib

Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor (VEGFR), a primary pathway for tumor angiogenesis. VEGFR inhibition is a clinically validated target to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China in combination with camrelizumab as a first-line treatment for uHCC (January 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S. and EU). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese -territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan.

About Camrelizumab

Camrelizumab (SHR-1210) is a humanized monoclonal antibody that binds to the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 5,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer, etc.) and treatment settings. Camrelizumab, under the brand name AiRuiKa, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021 and by the EMA in August 2024.

In October 2023, Elevar licensed camrelizumab, an anti-PD-1 antibody, for commercialization from Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma) worldwide excluding Greater China and Korea.

On September 23, 2024 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib (CA-4948), an orally available, small molecule IRAK4 inhibitor, reported the 3rd Annual Symposium on IRAK4 in Cancer taking place virtually on September 26, 9:00 AM-1:00 PM E.T (Press release, Curis, SEP 23, 2024, View Source [SID1234646815]).

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Hosted by Dr. Eric S. Winer (Dana-Farber Cancer Institute) and Dr. Grzegorz S. Nowakowski (Mayo Clinic Comprehensive Cancer Center), this symposium will focus on IRAK4, an emerging target in the treatment of hematologic malignancies and solid tumors. Experts will discuss the promise of IRAK4 inhibition in cancer, including current clinical studies of emavusertib and opportunities for future development.

Symposium presentations will include updated data for 10 evaluable R/R PCNSL patients as of the July 10, 2024 cutoff date. The Company continues to enroll patients in the PCNSL study and is on track to enroll 15-20 patients by year-end.

"As the leader in IRAK4 inhibition in oncology with emavusertib, we are honored to provide a forum for discussing the biology of the IRAK4 pathway and IRAK4 inhibition in the research and development of therapies to benefit patients living with cancer," said James Dentzer, President, and Chief Executive Officer of Curis.

Symposium co-chairs:

Eric Winer, MD, Clinical Director and Adult Leukemia Institute Physician, Dana-Farber Cancer Institute; Assistant Professor of Medicine, Harvard Medical School
Grzegorz Nowakowski, MD, Professor of Oncology and Medicine, Division of Hematology, Deputy Director of Mayo Clinic Comprehensive Cancer Center for Clinical Research and Vice-Chair of Division of Hematology
Joining our hosts will be the following speakers and participants:

Bently Doonan, MD, Assistant Professor, Division of Hematology and Oncology, University of Florida College of Medicine
Andrés Ferreri, MD, Contract Professor of Oncology, University Vita-Salute San Raffaele; Head of the Lymphoma Unit, I.R.C.C.S. Ospedale San Raffaele
Klaus Metzeler, MD, Professional of Translational Hematology, University of Leipzig
Guillermo Garcia-Manero, MD, Professor, Chief of Section of Myelodysplastic Syndromes, Deputy Chair of Translational Research and Fellowship Program Director Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Marina Konopleva, MD, PhD, Professor of the Department of Oncology, Professor of the Department of Molecular Pharmacology, and Miriam Mandel Faculty Scholar in Cancer Research, Albert Einstein College of Medicine
Kian Lim, MD, PhD, Associate Professor, Department of Medicine, Division of Oncology, Washington University School of Medicine in St. Louis
Lakshmi Nayak, MD, Director of the Center for CNS Lymphoma Dana‑Farber Cancer Institute; Associate Professor of Neurology, Harvard Medical School
Han Tun, MD, Hematologist, Internist, Oncologist, Departments of Hematology and Mayo Clinic Comprehensive Cancer Center
To learn more about this free-to-attend symposium and register, please visit View Source

On September 23, 2024 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported initial Phase 2 data demonstrating encouraging clinical responses and durability of BDTX-1535 in patients with relapsed/refractory epidermal growth factor receptor (EGFR)-mutant (EGFRm) non-small cell lung cancer (NSCLC) (Press release, Black Diamond Therapeutics, SEP 23, 2024, View Source [SID1234646811]).

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"Patients often become resistant to osimertinib with the emergence of on-target resistance EGFR mutations," said Sergey Yurasov, M.D., Chief Medical Officer of Black Diamond Therapeutics. "Our preliminary Phase 2 data demonstrate the potential of BDTX-1535 to deliver durable responses for these patients."

"Patients with recurrent EGFRm NSCLC have few treatment options, with chemotherapy delivering limited benefit and significant toxicity, and initial Phase 2 data with BDTX-1535 look quite promising," said Danny Nguyen, M.D., Assistant Clinical Professor, Department of Medical Oncology and Therapeutics Research at City of Hope. "There is a significant unmet medical need for an effective and well-tolerated oral therapy for patients who progress on osimertinib, as well as newly diagnosed patients with non-classical mutations."

Phase 2 preliminary data overview:

The phase 2 trial began in August of 2023, and enrolled relapsed/refractory patients with non-classical EGFR mutations (NCMs) (Cohort 1) and those with C797S resistance mutations (Cohort 2). Safety assessment and dose selection were based upon the first 40 patients randomized to receive BDTX-1535 once daily at either 100 mg or 200 mg across both Cohorts. Preliminary response rate and durability were assessed in 27 patients at 200 mg with an August 17, 2024, data cutoff, including 22 response-evaluable patients who met protocol eligibility criteria.

Key takeaways:

200 mg daily selected for pivotal clinical development. Dose selection was based primarily on pharmacokinetics, safety and tolerability data from 20 patients at 100 mg, and 20 patients at 200 mg.
Favorable tolerability profile at 200 mg, consistent with prior BDTX-1535 clinical data. The majority of adverse events were mild or moderate, and no new safety signals were observed. The most common on-target treatment-related adverse events were rash (70%) and diarrhea (35%). There were 2 cases of grade 3 rash, and no reported cases of grade 4 rash or grade 3/4 diarrhea.
Preliminary objective response rate (ORR) of 42% achieved in 19 patients. For the 22 response-evaluable patients, the preliminary ORR was 36%. Nineteen of these 22 patients expressed known osimertinib resistance mutations: either C797S or P-loop alpha-C helix compressing (PACC, a major subset of NCMs). Of these 19 patients, 8 achieved a response (42%): 5 with a confirmed partial response (PR), including 1 patient who converted from a PR to an unconfirmed complete response (CR) at 8 months (and awaits confirmatory scan); and 3 with an unconfirmed PR at first scan and awaiting a confirmatory scan. An additional 9 patients experienced stable disease.
Encouraging durability observed, with duration of response (DOR) of approximately 8 months or more for first 3 patients with PR; 14 of 19 patients remain on therapy. Mean follow-up time is 4.7 months.
"We are pleased to see significant Phase 2 clinical activity and tolerability that are consistent with our Phase 1 results," said Mark Velleca, M.D., Ph.D., Chief Executive Officer of Black Diamond Therapeutics. "We believe that the activity observed in the recurrent setting can translate to robust clinical benefit in the first-line setting, and we look forward to sharing data from our trial in newly diagnosed patients in Q1 2025."

Black Diamond continues to enroll patients in the second- and third-line cohorts, as well as in the first-line setting for patients with non-classical EGFR mutations. In Q1 2025, the Company expects to disclose initial results from the first-line cohort and to outline potential registrational paths in the recurrent setting based on FDA feedback.

About BDTX-1535

BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic EGFR mutations in NSCLC, including classical driver mutations, non-classical driver mutations, and the acquired resistance C797S mutation. BDTX-1535 is a fourth-generation tyrosine kinase inhibitor (TKI) that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. A "window of opportunity" trial of BDTX-1535 in patients with GBM is ongoing (NCT06072586) and a Phase 2 trial is ongoing in patients with NSCLC (NCT05256290).