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

HDP-101, a Bcma-Targeting Antibody-Drug Conjugate with a Novel Amanitin Payload, Establishes the Recommended Phase 2 Dose (RP2D) in a Clinical Phase 1 Trial on Relapsed/Refractory Multiple Myeloma (IMS 2026) - "HDP-101 demonstrates clinical activity with a favorable safety profile in heavily pretreated RRMM patients, supporting the potential of HDP-101 as a novel payload BCMAtargeted ADC therapy. Definition of the RP2D at 175 μg/kg establishes an effective and tolerable dose and enables immediate transition into clinical Phase 2a expansion study, which is started."

ADC • Clinical • First-in-human • IO biomarker • P1 data • P2 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Thrombocytopenia

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

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...announced that the China National Medical Products Administration (NMPA) has granted Clinical Trial Approval for a Phase Ib/II clinical trial evaluating pamlectabart tismanitin (HDP-101), the Company’s novel BCMA-targeting ADC, in combination therapy for the treatment of patients with relapsed/refractory multiple myeloma. (DGAP-EQS Group) - "The trial will evaluate the safety, tolerability, and preliminary efficacy of pamlectabart tismanitin in combination either with pomalidomide and dexamethasone, or with daratumumab and dexamethasone, in adult patients with relapsed/refractory multiple myeloma who have received at least one prior line of therapy. The trial will be conducted by Heidelberg Pharma’s partner Huadong Medicine Co., Ltd. in China who will bear the development cost."

New P1/2 trial • 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 2026 ➔ Sep 2028 | Trial primary completion date: Aug 2025 ➔ Mar 2028

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Study to Assess Safety and Efficacy of HDP-101 in Chinese Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

Heidelberg Pharma AG: Heidelberg Pharma Determines Recommended Dose for Phase II Trial with ADC Candidate HDP-101 (DGAP-EQS Group) - "Further details will be published at a future scientific conference...Heidelberg Pharma’s Benefit and Risk Assessment team agreed with the recommendation by the study’s Safety Review Committee (SRC), which had conducted a comprehensive review of safety, tolerability and pharmacokinetic (PK) data from the Company’s ongoing Phase I/IIa trial...The candidate showed promising efficacy results in the last dose cohorts; therefore, the SRC recommended stopping further dose escalation and accrual into the Phase I study part and proceeding to the study for the Phase IIa dose expansion part...The Phase IIa part of the study will include up to 30 patients on the selected dose; patient enrollment is planned to start in existing study centers in the next few weeks."

DSMB • Trial status • Multiple Myeloma

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."

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

Heidelberg Pharma AG…announced that its partner Huadong Medicine Co., Ltd., Hangzhou, China...has reached a development milestone under the terms of the license agreement from February 2022. (Heidelberg Pharma Press Release) - "With the dosing of the first patient in a clinical study with HDP-101 (INN: pamlectabart tismanitin) in China, a planned milestone payment to Heidelberg Pharma became due and is being processed. Financial details were not disclosed."

Financing • Multiple Myeloma

The Efficacy and Safety of B-Cell Maturation Antigen (BCMA) Antibody-Drug Conjugates (ADC) in Development against Cancer: A Systematic Review. (PubMed, Oncol Res) - "Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates (32%-85%) and a broad range of progression-free survival (PFS) (2.8-36.6 months), albeit with ocular toxicities in 51%-96%. Among newer candidates, MEDI2228 showed median PFS 5.1-6.6 months with 14% discontinuation for ocular symptoms, while AMG 224 had an overall response rate (ORR) of 23% (9/40) with anemia 21%, thrombocytopenia 24%, and ocular adverse events (AEs) 21%. Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates, although safety signals such as hepatic and renal toxicity were noted with HDP-101...However, frequent AEs, especially ocular and hematologic toxicities, underscore the need for optimization in ADC design. Further research should prioritize enhancing safety while maintaining clinical benefit."

Journal • Review • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Thrombocytopenia

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

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

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