pamlectabart tismanitin (HDP-101) / Heidelberg Pharma, Huadong Medicine - LARVOL DELTA

HDP-101: "Multiple efficacy endpoints show dose-dependent and promising anti-cancer activity (Cohort 5-8)"; Multiple myeloma (Heidelberg Pharma) - Equity Forum 2025: "38% ORR in Cohort 5 to 8 with 11 responders out of 29 patients (7 PR, 1 VGPR and 3 sCR"

P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Hdp-101, an Anti-BCMA Antibody-Drug Conjugate with a Novel Payload Amanitin in Patients with Relapsed Multiple Myeloma, Initial Findings of the First in Human Study (ASH 2023) - "Currently the study is enrolling patients in Cohort #4 at the dose of 80μg/Kg. Additional updates will be provided at the 2023 ASH Annual Meeting."

Clinical • First-in-human • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • Ophthalmology • SDC1

The Anti-BCMA Antibody-Drug Conjugate Hdp-101 with a Novel Amanitin Payload Shows Promising Initial First in Human Results in Relapsed Multiple Myeloma (ASH 2024) - "These promising findings support the continuation and further optimization of dosing strategies. Updated data and further analysis will be presented at the ASH 2024 meeting."

First-in-human • P1 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Ophthalmology • Thrombocytopenia • SDC1

Heidelberg Pharma to Present New Clinical Data of Lead ADC Candidate HDP-101 at the World ADC Congress 2025 and to Host Webinar (Yahoo Finance) - "Professor Andreas Pahl...will present an update from patient cohort 8 including efficacy data of the open-label, multicenter Phase I/IIa study evaluating HDP-101 in patients with relapsed or refractory multiple myeloma."

P1/2 data • Multiple Myeloma

PR: Heidelberg Pharma’s Lead ADC Candidate HDP-101 Granted Fast Track Designation by US FDA for the Treatment of Multiple Myeloma (Heidelberg Pharma Press Release) - "This designation was supported by nonclinical data as well as clinical data from the ongoing Phase I/IIa study with HDP-101 (INN: pamlectabart tismanitin), evaluating the safety and antitumor activity of the candidate in patients with relapsed or refractory multiple myeloma."

Fast track • Multiple Myeloma

HDP-101: "Multiple responses were seen (from 90 µg/kg) across different dosing arms, confirming that changes in the dose distribution maintained the anti-tumor effect while improving drug tolerability"; Multiple myeloma (Heidelberg Pharma) - IMS 2025

P1/2 data • Multiple Myeloma • Oncology

The Anti-BCMA Antibody-Drug Conjugate HDP-101 with a Novel Amanitin Payload Shows Promising Data in Relapsed/Refractory Multiple Myeloma in a Phase 1/2a Clinical Trial as it Advances into Cohort 7 (IMS 2025) - "HDP-101 showed a favorable safety profile up to 112.5 µg/ kg/cycle, with MTD not reached. Dose escalation continues at 140 µg/kg. Responses observed from 90 µg/kg suggest that optimized dosing maintains antitumor efficacy while enhancing tolerability."

Clinical • P1/2 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Thrombocytopenia

PR: Heidelberg Pharma Reports on First Half-Year 2025 and the Positive Course of Business (Heidelberg Pharma Press Release) - "Progress in the HDP-101 (BCMA-ATAC) program: The ATAC candidate HDP-101 is currently in a Phase I/IIa clinical trial for the treatment of relapsed or refractory multiple myeloma. The first seven patient cohorts and dose levels have been completed. After completion of the seventh cohort, the Safety Review Committee (SRC) confirmed that the dose of 112.5 µg/kg used is safe and well tolerated and that the study can be continued with the eighth cohort and a dose of 140 µg/kg. Similar to the dosing regimen for the seventh cohort, patients in the eighth cohort will also be dosed in two different arms. As long as patients in the seventh cohort do not progress, they will continue to be treated at the current dose level....Currently, five patients are still being treated. Patient recruitment for the eighth cohort is proceeding as planned."

Trial status • Multiple Myeloma

THE ANTI-BCMA ANTIBODY-DRUG CONJUGATE HDP-101 WITH A NOVEL AMANITIN PAYLOAD SHOWS PROMISING DATA IN RELAPSED/ REFRACTORY MULTIPLE MYELOMA IN A PHASE 1/2A CLINICAL TRIAL AS IT ADVANCES INTO COHORT 7. (EHA 2025) - "The novel BCMA targeting ADC HDP-101 shows promising results in heavily pre-treated RRMM patients. These results support the continuation and further optimization of dosing strategies during the Phase 1/2a clinical trial. Updated efficacy and safety data, as well as additional PKPD simulations, which evaluated the dose-exposure response effect on thrombocytes, will be presented at the EHA 2025 meeting."

Clinical • P1/2 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Thrombocytopenia

PR: Heidelberg Pharma to Present Promising New Clinical Data on its Lead ATAC Candidate HDP-101 at EHA 2025 (Heidelberg Pharma Press Release) - P1/2 | N=78 | NCT04879043 | Sponsor: Heidelberg Pharma AG | "Heidelberg Pharma AG...today announced that it will be presenting new clinical data on its lead Amanitin-based ADC candidate, HDP-101 at the 30th European Hematology Association (EHA) Congress, taking place in Milan, Italy, from 12 – 15 June 2025....HDP-101 is showing encouraging results, including an ongoing complete response in a female patient from cohort 5 who had been heavily pretreated and who has been treated continuously with HDP-101 alone for more than 19 months....In addition, promising biological activity and objective improvements were observed in several patients, underscoring the potential of HDP-101 as a treatment option for Multiple Myeloma. The study is advancing in cohort 8 at a dose of 140 µg/kg."

P1/2 data • Multiple Myeloma

From Bench to Bedside: Translating Safe Toxicity Profiles of Amanitin-Based ADCs to Clinical Applications (ADC London 2025) - "• Addressing how the preclinical toxicity profile of HDP-101 can predict clinical safety outcomes • Comparing the toxicity profile of amanitin-based ADCs across preclinical models and patients • Exploring strategies to refine the pharmacokinetics and treatment regimens of amanitin-based ADCs"

Clinical

Targeted Cancer Therapy for Patients With 17p Deletion (ADC London 2025) - "Synopsis • Breaking down clinical profile and new phase I escalation data of HDP-101 targeting BCMA in myeloma patients • Laying out retrospective analysis and investigation in deletion models of 17p deletion as a biomarker and patient selection tool for amanitin payload ADCs • Discussing future directions for clinical development and potential for patient selection investigation for precision medicine ADC development"

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

PR: Heidelberg Pharma Progresses into Cohort 7 in a Phase I/IIa Study with BCMA ATAC Candidate HDP-101 Targeting Multiple Myeloma (Heidelberg Pharma Press Release) - P1/2a | N=78 | NCT04879043 | Sponsor: Heidelberg Pharma AG | "Previously, in Cohort 6, dose optimization regimens were introduced with three different settings. These included premedication or different dose distribution to ameliorate the short-term reduction in platelet count that was observed with the prior dosing regimen. HDP-101 was well tolerated across all 10 patients in Cohort 6 dosed with 90 µg/kg, with no dose-limiting toxicities (DLTs) detected in any of the three parallel treatment arms. The Safety Review Committee (SRC) recommended to progress into Cohort 7 with an escalated dose above 100 µg/kg, in two parallel treatment arms with different split dosing....First patients of Cohort 7 have already been dosed....Clinical data from Cohort 5 demonstrated complete remission in one patient who had been heavily pre-treated across nine prior lines of therapy, including another BCMA-targeting agent."

P1/2 data • Trial status • Multiple Myeloma

HDP-101 Shows Early Efficacy and Manageable Safety Profile in Relapsed/Refractory Multiple Myeloma (OncLive) - P1/2 | N=78 | NCT04879043 | Sponsor: Heidelberg Pharma AG | "Treatment with the BCMA-directed antibody-drug conjugate (ADC) HDP-101 demonstrated early efficacy and a tolerable safety profile in patients with relapsed/refractory multiple myeloma, based on results from the phase 1 HDP-101-01 trial...that were presented at the 21st Annual International Myeloma Society Meeting and Exposition....At [100 μg/kg] every 3 weeks, [HDP-101] demonstrated in penta-refractory multiple myeloma an overall response rate of technically 50%, with 3 responding patients of 6 in this dose cohort....The phase 1 trial will proceed with additional schedule-modified dose-escalation cohorts, Raab said, adding that a dose-expansion portion is anticipated to launch in 2025."

P1 data • Trial status • Multiple Myeloma • Oncology

The Anti-BCMA Antibody-Drug Conjugate HDP-101 with a Novel Amanitin Payload Shows Promising Initial First in Human Results in Relapsed Multiple Myeloma (IMW 2024) - "Efficacy: In cohort 3 (60µg/kg), one patient had 17 cycles with stable disease (SD). In Cohort 5 (100µg/kg), 3 patients achieved partial response (PR), 2 patients showed progressive disease, one with dose reduced after C1, one patient had stable disease as best response. One patient is ongoing in partial remission after 9 cycles with a decreasing trend in M-protein levels."

P1 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Ophthalmology • Thrombocytopenia • SDC1

PR: Heidelberg Pharma Announces New Clinical Data on Lead ATAC Candidate HDP-101 to be Presented at International Myeloma Society Annual Meeting 2024 (Heidelberg Pharma Press Release) - "Heidelberg Pharma AG...announces 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....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....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."

P1/2 data • Trial status • Multiple Myeloma

HDP-101-01: Study to Assess Safety of HDP-101 in Patients With Relapsed Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=78 | Recruiting | Sponsor: Heidelberg Pharma AG | Trial completion date: May 2025 ➔ May 2026 | Trial primary completion date: Aug 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

The anti-BCMA antibody-drug conjugate HDP-101 with a novel amanitin payload shows promising initial first in human results in relapsed multiple myeloma (AACR 2024) - "Preliminary data shows that pharmacokinetics of HDP-101 aligns with expectations, and exposure to HDP-101 is dose proportional. Free payload was not detected in serum at a limit of detection of 30 ng/mL, and no anti-drug antibodiesor immunogenic reactions were noted. 17 of 18 patients were evaluable for dose limiting toxicities (DLT) in the 5 treatment cohorts."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1

PR: Heidelberg Pharma to host R&D Webinar following novel data presented at AACR (Heidelberg Pharma Press Release) - "Heidelberg Pharma AG...is pleased to announce that it will be hosting an R&D Webinar on 23 April 2024....The event will provide information on Heidelberg Pharma’s lead clinical ATAC product candidate HDP-101 targeting relapsed and refractory multiple myeloma as well as its proprietary ADC toolbox and therapeutic product pipeline. A clinical presentation of first efficacy data from the Phase I/IIa clinical trial with HDP-101 will take place at the upcoming American Association for Cancer Research (AACR) Annual Meeting..."

P1/2 data • Multiple Myeloma

PR: Heidelberg Pharma granted orphan drug designation by FDA for its proprietary ATAC candidate HDP-101 (Heidelberg Pharma Press Release) - "Heidelberg Pharma AG...is pleased to announce that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for the treatment of multiple myeloma to its lead candidate HDP-101. Heidelberg Pharma is investigating the candidate in a clinical Phase I/IIa study for the treatment of relapsed/refractory multiple myeloma (RRMM)....The team at Heidelberg Pharma will be presenting early safety and preliminary efficacy data at the upcoming American Association for Cancer Research (AACR) Annual Meeting, being held in San Diego, California on the 5 - 10 April 2024."

Orphan drug • P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Heidelberg Pharma announces progress into Cohort 6 with its proprietary ATAC candidate HDP-101 in Phase I/IIa multiple myeloma study (Heidelberg Pharma Press Release) - "Heidelberg Pharma AG...announces that it will be advancing into an expanded Cohort 6 dose escalation following submission of a protocol amendment to the US Food and Drug Administration (FDA) for its Phase I/IIa study with lead ATAC candidate HDP-101 for the treatment of multiple myeloma....Heidelberg Pharma’s Phase I/IIa clinical study is an ongoing, non-randomised, open label study which is actively enrolling patients with relapsed or refractory multiple myeloma or other plasma cell disorders expressing BCMA....The Company submitted a protocol amendment to the FDA in February 2024 allowing planned modification and optimization of the medication regimen to lessen the initial transient and reversible reduction of thrombocyte count. Upon ethics committee approval patients will be enrolled in Cohort 6....Further data readouts will be reported at upcoming scientific conferences in 2024."

Clinical protocol • P1/2 data • Trial status • Multiple Myeloma

Heidelberg Pharma Presents New Clinical Data from its Lead Candidate HDP-101 at the ASH Annual Meeting 2023 (PharmiWeb) - "Heidelberg Pharma AG...will present new findings of its clinical Phase I/IIa study with the proprietary ADC candidate HDP-101 at the 65th Annual Meeting of the American Society of Hematology (ASH)....Dr. Strassz will present the poster showing safety data and preliminary findings from four patient cohorts of the ongoing open-label, multicenter Phase I/IIa trial evaluating HDP-101 in multiple myeloma....The first four patient cohorts and dose levels of the clinical study have been completed and proved to be safe and well tolerated. Currently, the trial is enrolling patients in the fifth cohort."

P1/2 data • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Heidelberg Pharma Provides Update on Phase I/IIa Clinical Trial with Lead Candidate HDP-101 (Heidelberg Pharma Press Release) - P1/2 | N=78 | NCT04879043 | Sponsor: Heidelberg Pharma AG | "Heidelberg Pharma AG...announced today that the clinical Phase I/IIa study with the lead development candidate HDP-101 has already started to recruit patients for the fifth patient cohort with a dosing of 100 µg/kg. The Safety Review Committee's (SRC) evaluation of patient data concluded that no dose-limiting toxicities have occurred to date. The first four dose levels have shown to be safe and well tolerated. So far 12 patients have been treated in the trial. With the expansion of study sites this summer, patient enrollment has significantly accelerated. One patient from the third cohort has now been on HDP-101 monotherapy for over nine months and has been treated with eleven doses....The BCMA antibody Amanitin conjugate HDP-101 is being tested in an open-label, multicenter study for the treatment of relapsed or refractory multiple myeloma..."

P1/2 data • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Antibody Targeted Amanitin Conjugates: A New Payload Provides New Options for Cancer Therapy (PEGS 2023) - "ATACs comprise a new class of antibody-drug conjugates (ADCs) using amanitin as toxic payload. HDP-101 is directed against BCMA for the treatment of relapsed and refractory Multiple Myeloma patients. ATAC introduces a new payload with a new mode of action into oncology therapyPhase I study using ATAC is ongoingHDP’s lead program HDP-101 is targeting BCMA for r/r Multiple Myeloma"

Hematological Malignancies • Multiple Myeloma • Oncology

Subcutaneous dosing of amatoxin-based ADCs increases the therapeutic index (AACR 2023) - "HDP-101 is the first ATAC in the clinic, currently being tested in a phase I/II clinical trial in multiple myeloma patients... The present study demonstrates that s.c. dosing is a promising route of administration for ATACs as it not only refines the pharmacokinetic distribution of ATACs but may improve the TI in patients. By reducing Cmax, s.c. dosing improves the tolerability of ATACs in mice and cynomolgus monkeys. At the same time the anti-tumor efficacy of ATACs is maintained as the AUC is not negatively impacted."

Hematological Malignancies • Multiple Myeloma • Oncology