PRESS RELEASE

Heidelberg Pharma Presents New Preclinical Data from its Proprietary ATAC Technology Platform at AACR Annual Meeting 2023

Ladenburg, Germany, 4^th April 2023 – Heidelberg Pharma AG (FSE: HPHA) will present data from preclinical studies at this year's American Association for Cancer Research (AACR) annual meeting that provide positive evidence of the efficacy and tolerability of the company's proprietary ATAC technology. Heidelberg Pharma is active in cancer research and works with antibody drug conjugates (ADCs) that use the toxin Amanitin as payload. The meeting will be held in Orlando, Florida, USA, from 14^th to 19^th April 2023.

Details of the poster presentation:

Subcutaneous dosing increases the therapeutic index of Amatoxin-based ADCs

The study investigated how the pharmacokinetics, tolerability and efficacy of different ATACs are affected by the route of administration (subcutaneous versus intravenous). While intravenous dosing is the common administration method for marketed ADCs, subcutaneous dosing in general has pharmacokinetic advantages and is preferable for patients. Subcutaneous (s.c.) dosing of ATACs was shown to result in prolonged half-life and lower maximal serum levels in preclinical models compared with intravenous (i.v.) administration. Both factors resulted in improved tolerability of the ATACs. At the same time, antitumor efficacy in a xenograft model using human cancer cell lines was comparable after s.c. or i.v. administration.

The improved tolerability combined with consistent efficacy resulted in an improved therapeutic index of the candidate HDP-103. The present study demonstrates that s.c. dosing not only refines the pharmacokinetic distribution of ATACs but also can improve the therapeutic index. Thus, s.c. dosing may represent a promising route of administration for ATACs in humans as well.

Details of the poster presentation:

Amanitin-based ADCs targeting Guanylyl cyclase C (GCC) as novel therapeutic modality for treatment of colorectal cancer

The poster presentation will cover preclinical data on ATACs targeting GCC (guanylyl cyclase C). This surface protein is overexpressed in many gastrointestinal tumors, and most notably in colorectal cancer. Due to its specific expression profile, GCC represents an exceptionally tumor-specific target. ATACs directed against GCC possess high antitumor activity and inhibit tumor growth in preclinical models even at low concentrations after single or multiple dose treatment. The favorable safety profile due to the good tolerability of these ATACs confirms that they may represent a promising new therapeutic option against colorectal cancer.

Poster presentations can be found from 18^th April 2023, on the company website in the "Research & Development > Scientific Posters" section.

About Heidelberg Pharma's proprietary ATAC technology
Antibody Drug Conjugates (ADCs) combine the high affinity and specificity of antibodies with the efficacy of small toxic molecules to fight cancer. Heidelberg Pharma works with ADCs based on its proprietary ATAC technology using Amanitin as the active ingredient. Amanitin belongs to the amatoxin molecules, bicyclic peptides that occur naturally in the green deathcap mushroom. Amatoxins act by inhibiting RNA polymerase II, which leads to so-called programmed cell death (apoptosis) in cells. Inhibition of RNA polymerase II is a new mode of action for cancer therapy. In preclinical studies, ATACs have shown very high efficacy, overcoming common resistance mechanisms and also targeting dormant tumor cells.

About Heidelberg Pharma
Heidelberg Pharma is an oncology specialist and the first company to develop the toxin Amanitin into cancer therapies using its proprietary ATAC technology and to advance the biological mode of action of the toxin as a novel therapeutic principle. The proprietary technology platform is being applied to develop the company’s own therapeutic ATACs as well as in third-party collaborations.

The proprietary lead candidate HDP-101 is a BCMA-ATAC in clinical development for multiple myeloma. Further ATAC candidates are being developed against different targets such as CD37, PSMA or GCC each in the indications non-Hodgkin's lymphoma, metastatic castration-resistant prostate cancer or gastrointestinal tumors such as colorectal cancer.

Heidelberg Pharma AG is based in Ladenburg, Germany, and is listed on the Frankfurt Stock Exchange: ISIN DE000A11QVV0 / WKN A11QVV / Symbol HPHA. More information is available at www.heidelberg-pharma.com.

ATAC^® is a registered trademark of Heidelberg Pharma Research GmbH in the EU and the USA.

This communication contains certain forward-looking statements relating to the Company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "will" "should" "future", "potential" or similar expressions or by a general discussion of the Company's strategy, plans or intentions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause our actual results of operations, financial condition, performance, or achievements, or industry results, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Given these uncertainties, prospective investors and partners are cautioned not to place undue reliance on such forward-looking statements. We disclaim any obligation to update any such forward-looking statements to reflect future events or developments.