Pamlectabart tismanitin (development code: HDP-101) is a BCMA-ATAC that is being tested in multiple myeloma. BCMA (B-cell maturation antigen) is a surface protein that is highly expressed in multiple myeloma cells. BCMA antibodies specifically bind to this protein, thereby delivering the toxin Amanitin to the cancer cell. Multiple myeloma is a cancer affecting bone marrow and the second most common hematologic cancer; it represents a major unmet medical need where new, more effective therapies are urgently required. The candidate also has potential in further hematologic indications.

Heidelberg Pharma’s Phase I/IIa clinical study is a non-randomized, open-label, dose escalation trial enrolling patients with relapsed or refractory multiple myeloma. The study is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of pamlectabart tismanitin in this patient population.

In the Phase I part of the trial, 53 patients were treated in 10 cohorts during the dose escalation phase. The dose levels ranged from 20 µg/kg in the first cohort to 218 µg/kg in the 10th cohort. In all ten cohorts, Heidelberg Pharma observed no signs of ocular toxicity, no infusion reactions, no marked myelosuppression, and no lung or liver damage related to the treatment. Preliminary safety signals were observed, but these effects were considered manageable and could be mitigated through adjusted dosing and pre- or post-medicine treatment strategies.

In the eighth cohort, at a dose of 140 µg/kg, encouraging signs of clinical efficacy were observed, including one partial remission, one very good partial remission, and two stringent complete remissions in which no tumor cells were detect able in the patients’ blood or bone marrow. These results complement earlier positive observations and support the potential of pamlectabart tismanitin as a possible treatment option for patients with relapsed or refractory multiple myeloma.

In early April 2026, the Phase I part of the study was completed and the recommended dose for the Phase IIa part of the study (Recommended Phase 2 Dose; RP2D) was determined. In the Phase IIa dose expansion phase, at least 30 patients are to be treated with the recommended dose of pamlectabart tismanitin. The primary objective of the Phase IIa part of the trial is to assess the preliminary anti-tumor activity of pamlectabart tismanitin along with further evaluation of the safety of the drug.

The Phase IIa part of the study has already started and is progressing as planned. 

Regulatory status:
In October 2025, the US Food and Drug Administration (FDA) granted fast track designation to pamlectabart tismanitin. This status was supported by both non-clinical data and clinical data from the ongoing Phase I/IIa trial.

Fast track designation is intended to accelerate the development and review of therapies that address serious or life-threatening conditions with unmet medical needs. It enables more frequent engagement with the FDA, allows rolling review of the Biologics License Application (BLA), and may provide eligibility for priority review or accelerated approval.

Together with the orphan drug designation (ODD) granted in March 2024, the fast track designation underlines the significance of pamlectabart tismanitin in potentially treating patients with multiple myeloma.

HDP-102 is an ATAC targeting CD37 that is overexpressed on B-cell lymphoma cells. HDP-102 will be developed for specific indications of non-Hodgkin lymphoma (NHL). In preclinical trials, this development candidate has shown to have a comparatively broad therapeutic window. This means that the difference between its therapeutic dose and a dose that causes unacceptable toxicity is as great as possible.

Heidelberg Pharma announced the dosing of the first patient with HDP-102 at the end of May 2025. The first cohort consisted of three patients treated at a dose of 40 μg/kg. Initial data showed promising results. The treatment was well tolerated, and initial signs of biological activity were observed even at this extremely low dose. Two patients showed stabilization of the disease with regression and reduction of the size of lymph nodes. The safety committee recommended increasing the dose of HDP-102 to 65 μg/kg in Cohort 2.

Recruitment was paused for the trial after the first cohort in line with the Company's strategic review from September 2025 and did not recruit a second cohort. In the meantime all trial centers are closed and no patients are receiving treatment anymore.

Heidelberg Pharma is exploring partnership opportunities to support the continued development of the program.

HDP-103 will be developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The antibody used binds to PSMA, a surface antigen that is overexpressed on prostate cancer cells. This is a promising target for ATAC technology because PSMA shows only very limited expression in normal tissue.

Preclinical studies on in vitro and in vivo efficacy, tolerability and pharmacokinetics have shown that HDP-103 has a promising therapeutic window. This is confirmed by the fact that at 60% there is a very high prevalence of a 17p deletion in mCRPC. The increased Amanitin sensitivity of prostate cancer cells with a 17p deletion has already been preclinically validated. Since tumor cells with a 17p deletion are particularly sensitive to Amanitin, PSMA-ATACs might be particularly suitable for treating mCRPC.

The production of HDP-103 under GMP conditions as well as necessary preclinical and toxicological studies with HDP-103 have been completed. As part of the Company’s current strategic review, we will not continue to develop this program ourselves and we are currently working with our strategic partner Huadong to get additional preclinical data to support them with a possible clinical Phase I study in China. Additionally, we are looking for partners outside of China for the clinical development of HDP-103.

Heidelberg Pharma has been developing further ADC projects with other payloads since fall 2023. The first candidate is HDP-201, an exatecan-based ADC. Exatecan is a topoisomerase I inhibitor that has proven itself in cancer therapy and is used in two already approved ADCs. Its mode of action differs from that of Amanitin, and thus expands the company’s range of active ingredients.

HDP-201 targets guanylyl cyclase-C (GCC), a receptor that is expressed on the surface of intestinal cells and cancer cells in various gastrointestinal tumors. The target protein to which the antibody used binds is overexpressed in over 95% of colorectal cancers and around 65% of esophageal and gastric tumors as well as pancreatic tumors.

 Heidelberg Pharma is currently not pursuing further development of this project, either, and is seeking a partnership.