NAMPT

Ladenburg, Germany, 26 March 2025 – Heidelberg Pharma AG (FSE: HPHA), a clinical-stage biotech company developing innovative Antibody Drug Conjugates (ADCs), today announced that it will be presenting its latest ADC research results and advancement for its Exatecan-based ADC technology platform at the American Association of Cancer Research (AACR) Annual Meeting 2025 in Chicago, Illinois, USA, from 25 to 30 April. In addition to its proprietary Amanitin-based ADC technology, Heidelberg Pharma has developed a diverse ADC toolbox designed to overcome tumor resistance through multiple mechanisms, enabling targeted treatment across various cancer types. Dr. Sarah-Jane Neuberth will present preclinical findings on HDP-201, Heidelberg Pharma´s novel Exatecan-based, multimeric linker ADC, called ETAC technology, which is being developed for the treatment of colorectal cancer. The findings indicate target-specific potency, strong anti-tumor efficacy, and high tolerability. Dr. Pablo Ruedas Batuecas will demonstrate the potential of computational modeling for optimizing NAMPT inhibitors (NAMPTi) designed in silico as payloads and as a mode of action (MOA) in ADC technology. This novel technology approach has the potential to overcome the current limitations of cancer therapies by targeting both dividing and non-dividing cancer cells. AACR Annual Meeting 2025 Details of the conference and presentations are as follow: Poster: HDP-201 – a novel multimeric linker exatecan-based ADC targeting Guanylyl cyclase C (GCC) for treatment of gastrointestinal malignancies Abstract number: 1558 Session: Antibody-Based Cancer Therapeutics 1 Presentation time: 28 April, 9:00 am – 12:00 pm CST Speaker: Dr. Sarah-Jane Neuberth, Associate Director In Vivo Biology Link to abstract: https://www.abstractsonline.com/pp8/#!/20273/presentation/2830 The ETAC HDP-201 is directed against the surface protein GCC (guanylyl cyclase C), which is highly overexpressed in gastrointestinal malignancies, including gastric and colorectal cancers. HDP-201 showed potent anti-tumor efficacy in preclinical models, including complete tumor remission of GCC-expressing CDX models and significant inhibition of tumor growth in gastrointestinal PDX models. A single intravenous dose of 60 mg/kg of HDP-201 was well tolerated in cynomolgus monkeys, with no severe toxicity. These findings underscore the potential of HDP-201 as a promising new therapeutic option for GCC-positive gastrointestinal malignancies. Talk (Minisymposium): In silico optimized NAMPT inhibitor for targeted delivery by ADC as novel therapeutic modality for treatment of liquid and solid malignancies Abstract number: 1162 Stream: Antibody-Based Cancer Therapeutic Agents Presentation time: 27 April, 3:00 – 5:00 pm CST Speaker: Dr. Pablo Ruedas Batuecas, Scientist Chemistry Link to abstract: https://www.abstractsonline.com/pp8/#!/20273/presentation/2815 Nearly half of the US Food and Drug Administration (FDA) approved ADCs are based on microtubule inhibitors, that selectively target dividing cancer cells but fail to eradicate non-dividing tumor stem cells, potentially leading to resistance and tumor relapse. Inhibition of NAMPT, the rate-limiting enzyme in the salvage biosynthetic pathway of NAD+ starting from nicotinamide, induces cell death due to energy shortage in both dividing and non-dividing cell populations. This is a promising approach to overcome current therapy limitations by utilizing novel payloads. ADCs based on in silico designed NAMPTi as payloads show promising in vitro and in vivo results, highlighting the potential of NAMPT inhibition as an emerging MOA in ADC technology that enhances the targeted drug delivery to different cell lines.

Trial will evaluate the safety, pharmacokinetics and pharmacodynamics of RPT1G in adult healthy volunteers in anticipation of their upcoming oncology trial to treat patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS)GAITHERSBURG, Md., Dec. 18, 2024 (GLOBE NEWSWIRE) -- Remedy Plan Therapeutics, a privately-held clinical-stage pharmaceutical company transforming the field of NAMPT inhibition, announced today the initiation of an adult healthy volunteer Phase 1 clinical trial of its first-in-class, hyperbolic NAMPT inhibitor, RPT1G. As a hyperbolic NAMPT inhibitor, RPT1G is designed to target cells with high levels of NAMPT that occur in certain cancers, autoimmune and metabolic diseases, while avoiding on-target toxicity and thus preserving biological function in healthy cells. The Phase 1 randomized, double-blind, placebo-controlled clinical trial of RPT1G is being conducted in adult healthy volunteers in Australia (NCT06667765). The trial will evaluate RPT1G’s safety and pharmacokinetic properties while also exploring pharmacodynamic markers. Results from the Phase 1 clinical trial are expected in the first half of 2025 and will accelerate the company’s development of its oncology program in AML and high-risk MDS, currently planned to initiate in the second half of 2025. “We are thrilled to initiate our Phase 1 trial of RPT1G in healthy subjects. RPT1G is not only the first hyperbolic NAMPT inhibitor, but also the first NAMPT inhibitor to be tested in a healthy volunteer study, showcasing the importance of our preclinical work that clearly highlights the favorable safety profile of our hyperbolic NAMPT inhibitors,” stated Greg Crimmins, Ph.D., founder and CEO of Remedy Plan Therapeutics. “The results of this trial will enable us to initiate our subsequent trial in cancer patients at a starting dose that could provide meaningful therapeutic benefit.” About RPT1GRPT1G is a novel, small molecule NAMPT inhibitor that is designed to preserve biological function in healthy cells. The favorable efficacy and tolerability profile of RPT1G in preclinical models, compared to previously developed complete NAMPT inhibitors, provides robust support for its utility in treating hematological malignancies and solid tumors. In addition to single agent activity, preclinical studies have demonstrated that RPT1G strongly synergizes with current standard of care drugs and overcomes cancer cell resistance to venetoclax, and may offer improved treatment benefit for leukemia patients. Given the broad scientific validation of NAMPT upregulation in autoimmune and metabolic diseases, RPT1G analogues are also being evaluated as potential therapies for those diseases. About Remedy Plan TherapeuticsRemedy Plan Therapeutics is a privately-held, clinical-stage pharmaceutical company transforming the field of NAMPT inhibition. Remedy Plan’s lead asset, RPT1G, is the first hyperbolic NAMPT inhibitor to be tested in humans and has potential for broad therapeutic applications in cancer, autoimmune and metabolic diseases. Remedy Plan initiated a Phase 1 clinical trial of RPT1G in adult healthy subjects in November 2024. To learn more about Remedy Plan, please visit https://remedyplan.com/. Investor Relations and Media Contact:Parisa Moghaddam-Taaheripress@remedyplan.com

– RPT1G synergizes with venetoclax to yield an eightfold reduction in AML leukemia burden – RPT1G increases the efficacy of venetoclax in venetoclax-resistant AML cells by fourfold versus venetoclax alone GAITHERSBURG, Md., Dec. 10, 2024 (GLOBE NEWSWIRE) -- Remedy Plan Therapeutics (“Remedy Plan”), a clinical stage pharmaceutical company unlocking the therapeutic potential of NAMPT inhibition, presented new data at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, California demonstrating that RPT1G, a first-in-class hyperbolic NAMPT inhibitor, provides an eightfold reduction in acute myeloid leukemia (AML) burden when combined with B-cell lymphoma 2 protein (BCL-2) family inhibitors, including venetoclax, in preclinical models of AML. Remedy Plan's data also showed that treatment with RPT1G alone, RPT1G in combination with venetoclax, and RPT1G in a triple combination with venetoclax and the Poly (ADP-ribose) polymerase (PARP) inhibitor olaparib resulted in a fourfold increase in efficacy in venetoclax-resistant AML cells. “Remedy Plan's preclinical data demonstrating synergy between RPT1G and venetoclax and other BCL-2 family inhibitors, are incredibly exciting,” said Saul Rosenberg, Ph.D., Scientific Advisor to Remedy Plan and former executive director of Oncology Drug Discovery at AbbVie Inc., where he oversaw the preclinical discovery and advancement of the BCL-2 family inhibitors venetoclax and navitoclax to the status of clinical candidate. “This synergy not only underscores the potential of Remedy Plan’s approach to enhance treatment efficacy, but also opens the door to developing novel combination regimens that could improve outcomes for patients facing challenging hematological malignancies." Greg Crimmins, Ph.D., founder and chief executive officer of Remedy Plan, added, “These are important combination data for our lead asset, RPT1G, which complement the single agent preclinical data we’ve generated showing potent anti-tumor activity and further underscores the highly differentiated safety profile of our novel NAMPT inhibitor that allows well-tolerated combination therapy. With Remedy Plan’s first-in-human Phase 1 clinical trial of RPT1G commencing in Australia, we look forward to generating early first-in-human clinical data in the coming weeks.” About AML AML is the most common type of adult acute leukemia that progresses rapidly without treatment. Despite the emergence of new therapy options, most AML patients still face dire prognosis, with a 5-year survival rate of 37.5%. Venetoclax, a current standard of care in AML, has transformed treatment by targeting BCL-2, but its long-term efficacy is limited as many tumors develop resistance, driven in part by NAMPT overexpression. Thus, there is still a large unmet need for therapeutic options that can address resistance mechanisms and improve outcomes for AML patients. About Remedy Plan Therapeutics: Remedy Plan is a clinical stage pharmaceutical company unlocking the therapeutic potential of NAMPT inhibition with a pioneering approach that allows for hyperbolic inhibition of NAMPT. This groundbreaking mechanism of action turns down NAMPT activity, but never fully turns it off. By allowing for NAMPT activity in healthy cells, hyperbolic NAMPT inhibition avoids the on-target toxicities observed by other investigational NAMPT inhibitor therapies. Remedy Plan’s lead drug candidate, RPT1G, is a first-in-class, hyperbolic NAMPT inhibitor that has been granted Human Research Ethics Committee (HREC) approval and has Clinical Trial Notification (CTN) clearance by the Australian Therapeutic Goods Administration (TGA) to commence a first-in-human Phase 1 clinical trial of RPT1G in November 2024. The company has commenced the Phase 1 trial in healthy subjects and expects first-in-human clinical data from the trial in early 2025. NAMPT inhibition is widely recognized as a high-value target for the treatment of cancer, autoimmune and metabolic disease. Remedy Plan’s RPT1G drug candidate and its analogues are being investigated for the potential treatment of hematological malignancies, solid tumors, obesity, and autoimmune disorders. Remedy Plan is dedicated to addressing unmet needs in patients with cancer, autoimmune and metabolic diseases through innovative science. For more information, visit remedyplan.com. Investor and Media Contact:Parisa Moghaddam-Taaheripress@remedyplan.com