PRAMOMOLECULAR GmbH: Shaping the Healthcare of Tomorrow with New Drugs Against ‘Undruggable Diseases’ 

PRAMOMOLECULAR GmbH Merle Fuchs The Lifesciences Magazine

Addressing diseases rooted in overactive or mutated proteins has become a pressing need. These aberrant proteins play a pivotal role in various serious conditions, posing challenges to effective treatment. Recognizing this, developing targeted and efficient therapeutic interventions has become more crucial than ever. In scenarios as such, a focused approach towards silencing or regulating these problematic proteins can offer a promising avenue for tackling diseases at their core, ushering in a new era of precision medicine and improved patient outcomes.

With that being said, PRAMOMOLECULAR GmbH is focused on developing innovative drug candidates to address serious diseases. Co-founded by Merle Fuchs and her partners, the company’s primary approach involves silencing disease-causing proteins in critical organs like the lungs, heart, and pancreas. Advanced technology, particularly “self-delivering siRNAs,” aims to create potent solutions for aggressive diseases, with a specific emphasis on lung and pancreatic cancer. 

Effective delivery is currently constrained to the liver, creating a significant medical demand for transfecting cells in other organs. Recognizing this challenge, Merle and her cofounders Ida Shaef and Thomas Hiller seized the opportunity to repurpose a technology initially designed for transfecting cells with mononucleotides. 

Leveraging this innovative approach, they successfully adapted the technology for the transfection of small oligonucleotides, addressing a critical need in the medical field of small therapeutic oligonucleotides

This strategic move positioned the company at the forefront of advancing therapeutic solutions, bridging the gap in effective delivery methods for medical treatments. As the Chief Executive Officer, Merle is focused on propelling the company to greater heights and fulfilling its mission while catering to several leadership roles and responsibilities. 

Remarkable Entrepreneurial Leadership Background

With a distinguished career path marked by academic achievements and entrepreneurial leadership, Merle’s professional journey began with a focus on biology, pursuing studies in  Germany, the Netherlands, and the USA. 

During her interdisciplinary doctorate in the laboratory of Nobel Prize winner Manfred Eigen at the Max Planck Institute for Multidisciplinary Sciences in Göttingen (Germany), she also expanded her skills in the laboratory of Richard Lerner at the Scripps Research Institute in La Jolla (CA). Since 2000, she has served as an independent management consultant with her company TechnologieContor. Her impactful focus on business development and financing has been particularly instrumental for technology leaders.

Her influence extended further as a consultant for high-tech startups and growing companies, impacting over  500 innovative companies. She co-founded eight high-tech startups, highlighting her commitment to fostering innovation and technological advancement. As a co-founder, Merle was involved in a venture dedicated to producing therapeutic oligonucleotides. Acknowledging the challenges of delivering these molecules, she particularly emphasizes the difficulty of introducing therapeutic oligonucleotides into their target cells, a prevalent hurdle in medical practices. 

Boasting nearly 25 years dedicated to technology transfer, Merle’s expertise has fostered innovation. Essentially, Merle’s entrepreneurial journey unfolded with a focus on the evolutionary design of new proteins, which led her to establish her own company in 2021. Beyond her roles in these startups, she extends her influence to governance, serving on supervisory boards, advisory boards, and advisory committees of federal and state ministries, networks, scientific institutions, and companies. Merle’s multifaceted career reflects her commitment to driving science, technology, and business advancements. With PRAMOMOLECULAR, Merle and the team seek to solve the problem of diseases caused by overactive or mutated proteins by developing targeted and effective therapeutic interventions.

Cutting-Edge Platform Technology 

PRAMOMOLECULAR is helping shape the future of healthcare by developing new drugs against “undruggable diseases”. The company is at the forefront of developing a cutting-edge platform technology designed to effectively transfect lung, heart, pancreas, and colon cells in vivo with small therapeutic oligonucleotides like ASOs, siRNAs, or miRNAs. The company is actively developing self-delivering therapeutic oligonucleotides to address organs besides the liver. 

PRAMOMOLECULAR has a platform technology protected by international patent applications. The innovative start-up uses it to develop its own active ingredients . In addition it  offers innovative delivery molecules to other developers of therapeutic oligonucleotides  for the codevelopment of promising drug candidates.

Specializing in innovative gene silencing therapies, PRAMOMOLECULAR focuses on addressing diseases currently deemed “incurable.” Leveraging covalently linked, lipid-based delivery molecules, the company facilitates the transportation of nucleic acid-based drugs into lung, heart, and pancreatic cells in vivo. The groundbreaking “self-delivering siRNAs” represent a highly innovative class of drugs, allowing efficient down-regulation of disease-causing proteins, including mutated or overexpressed proteins.

PRAMOMOLECULAR aims to deliver well-tolerated and effective therapeutics for patients facing serious diseases. Their initial drug candidates target conditions such as non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC),  gastric cancer (GC)  and heart failure.

In addition to advancing its proprietary drug candidates, PRAMOMOLECULAR actively seeks collaborations, expressing interest in co-developing and licensing its delivery technology to other developers of nucleic acid-based drugs for specific applications. This strategic approach underscores the company’s commitment to driving innovation and making impactful contributions to gene silencing therapies.

Wide Array of Responsibilities 

Merle entered the industry with a mission –  to tackle challenges that remained unresolved by others. Her commitment to finding innovative solutions led her to PRAMOMOLECULAR, where she faced the formidable task of securing funding in a challenging financial landscape. The impact of the COVID-19 pandemic exacerbated the difficulties, as the promised funding for PRAMOMOLECULAR was diverted to Covid research. At the same time, there has been a global slump in biotechnology financing since 2021, the year PRAMOMOLECULAR was founded.

However, the company secured funding from business angels and subsidies, is located in the BioCampus Berlin-Buch in a cost-effective location with an outstanding technological environment in the field of siRNA development, is organized in a highly virtual manner, which allows for low fixed costs and a high degree of flexibility and professionalism, and uses the combination of artificial intelligence and rational design of RNA drugs, which enables particularly rapid and cost-effective development of drug candidates up to clinical phase II.

Currently, Merle leads the team of PRAMOMOLECULAR efficiently and strategically. Her robust background in molecular biology, coupled with a keen entrepreneurial spirit, has significantly contributed to the continuous success of the startup. Being at the helm, she takes charge of comprehensive responsibilities spanning information gathering, strategic and financial planning, business development, and communication.

Merle excels in acquiring strategic cooperation partners, a skill crucial for the growth and success of the company. Additionally, she is pivotal in securing financing for the company’s ventures. With a multifaceted approach to leadership, Merle Fuchs combines her scientific expertise with entrepreneurial acumen, driving the company towards innovative and successful endeavors. As a dynamic leader, Merle’s leadership is characterized by her efficient leadership style marked by quick decision-making, consistent actions, a strong sense of responsibility, and a keen willingness to take on challenges. Her collaborative spirit is evident in her strong willingness to cooperate with others.

Merle holds a doctorate in evolutionary biotechnology, where she recognizes the paramount importance of diversity, selection pressure, information transfer, and self-organization in evolution. Despite being a compact team of six, PRAMOMOLECULAR boasts diverse backgrounds, training, interests, and experiences, fostering collaboration with exceptional network partners. Acknowledging the significant selection pressure in developing effective and safe medicines amidst financial constraints, the team gathers thorough information from diverse sources, encompassing literature, professional exchange, and intensive reflection. This information is openly shared both internally and externally. The success of their endeavors hinges on the self-organization and high motivation of every team member, creating a dynamic and collaborative work environment at the young biopharma company.

Unique Approach to Leveraging Technology 

PRAMOMOLECULAR utilizes the potential of the outstanding technology of RNA interference (RNAi). The Nobel Prize for Medicine and Physiology was awarded in 2006 for the discovery of this gene silencing by siRNAs. When these siRNAs enter a cell, they can specifically down-regulate disease-causing  proteins: No disease-causing protein – no disease! Collaborating with other companies and research groups, the company designs siRNAs covalently linked to lipid-based delivery molecules. Once these engineered siRNAs bind to mRNA in the cell, the cell perceives a viral attack and cleaves the mRNA, disrupting the blueprint of the disease-causing protein. This disruption results in the elimination of the disease-causing protein, addressing the root of the problem.

However, siRNAs and other therapeutic oligonucleotides, such as miRNAs, shRNAs or antisense oligonucleotides, face challenges due to their larger size than conventional drug molecules. Being approximately 70 times larger than aspirin, these molecules are highly loaded and prone to instability. They undergo degradation by the liver, excretion by the kidneys, enzymatic destruction in the blood, and encounter difficulties in crossing cellular membranes. To facilitate the cellular entry of these molecules, delivery technologies are essential.

Currently, existing delivery technologies primarily function effectively in the liver. This limitation is evident in the fact that the five approved siRNA drugs exclusively target disease-causing proteins in the liver. Recognizing the medical need, PRAMOMOLECULAR aims to extend the application of this technology to downregulate disease-causing proteins in other organs, presenting an exciting prospect for future developments.

At PRAMOMOLECULAR, the company possesses a proprietary platform technology featuring two different covalent lipid-based delivery molecules. These lipids are directly coupled through a defined chemical linker to therapeutic oligonucleotides such as siRNAs or antisense DNAs. Notably, this delivery approach doesn’t require nanoparticulate formulations, relying solely on these lipid-based delivery molecules. 

A Broad Spectrum of Possibilities

PRAMOMOLECULAR can theoretically downregulate every disease-causing protein in its target organs. While the company acknowledges the broad spectrum of possibilities, it strategically addresses oncogenic proteins associated with lung, pancreatic, and gastric cancer. In particular, the company directs attention to undruggable KRAS mutations. KRAS, a pivotal protein in cell metabolism, undergoes alterations in certain mutations, rendering it resistant to downregulation. This persistent activity in cellular metabolism increases the risk of cancer development.

By downregulating specific oncogenic proteins, the company aims to halt tumor growth, a concept validated by experiments on animals. Despite the promising potential, the difficulty in effectively delivering siRNA drugs to cells, such as those in the colon, pancreas, or the lungs, has hindered progress in treating specific cancers, like gastric cancer, lung cancer or pancreatic cancer with these mutations. Primarily, PRAMOMOLECULAR also focuses on proteins that play a role in heart disease. It has thus extended its efforts to a broader spectrum of medical challenges, particularly in the field of metabolic diseases.

Acknowledging and Transcending Beyond Uncertainties

Merle emphasizes that institutions and individuals should invest a lot of energy, talent and money in biotechnology – not only to be prepared for the next health crisis, but also to solve production, food, raw material and energy problems in an environmentally friendly and efficient way – in order to create new technological foundations and application-oriented technologies. Hence, in biopharma entrepreneurship, she dedicates her energy to building and advancing PRAMOMOLECULAR, maintaining a focused perspective amid the dynamic landscape of oncology.

As a biopharma entrepreneur, she dedicates her energy to building and developing the startup while maintaining a focussed perspective in the dynamic landscape of drug development. Despite the remarkable advances in cancer treatment – from vaccines and antibody therapies to CAR-T cell therapy – Merle insists that the diverse arsenal to combat highly aggressive cancer cells is still needed to keep pace with the broad spectrum of different cancers and especially with the high mutation rate of cancer cells.

In view of the increasing developments in the field of gene silencing technologies, Merle sees both increased competition and greater opportunities to improve drug candidates. And in view of the major advances in biotechnology – also in other areas such as nutrition, industrial processes or renewable raw materials – she emphasises the assessment that we are living in the century of biotechnology.

Within the growing gene silencing industry, Alnylam has so far been THE outstanding symbol of the technology’s potential. All five active ingredients that are currently on the market were developed by Alnylam and all address serious diseases with a high medical need. But there are even more inspiring success stories: DTx Pharma, a Californian biotech startup, was acquired by Novartis last summer for the impressive sum of $1 billion while still in the preclinical phase. Similar to PRAMOMOLECULAR, DTx Pharma had a proprietary platform technology that utilized covalent, lipid-based delivery molecules for siRNAs, albeit with different tissue preferences.

A Vivid Analysis of the Latest Transformative Impacts

With continued technological advances and innovations in healthcare, Merle sees a transformative impact of gene silencing in cancer treatment. She believes this approach holds promise for precisely treating different cancer mutations. The specificity of gene silencing allows for the targeted treatment of different mutations in the company’s intended organs. Merle emphasizes that siRNAs are particularly safe and well tolerated, unlike traditional chemotherapeutics.

The company can efficiently create a drug pipeline tailored to combat different mutations by using the appropriate siRNA for each mutation and the optimal carrier molecule for each organ. While Merle recognises that no therapeutic approach, including gene silencing, can be a panacea for all cancers, she expects significant progress, especially in combination with other innovative treatment methods. 

While the healthcare industry is undergoing a promising transformation with remarkable advances in diagnostics and therapy, Merle recognises the challenges posed by increasing cost pressures on healthcare systems. Recognising the inevitable costs, Merle and PRAMOMOLECULAR are working hard to provide efficient and well-tolerated solutions to patients struggling with currently untreatable serious diseases.

In navigating the complexities of the biopharmaceutical landscape, Merle remains determined and draws inspiration from industry leaders and innovative start-ups. Under her leadership, PRAMOMOLECULAR strives to contribute to the century of biotechnology with a vision based on delivering impactful solutions to patients facing major health challenges.  To tomorrow’s leaders seeking a job in the healthcare industry, Merle advises: “Be well prepared and work hard!”

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