Q: What truly novel therapies in the earliest stages of discovery and development do you believe will have a significant impact in the future?

Novel Therapies

Yochi Slonim,
Co-founder and CEO, Anima Biotech

A: Drug discovery has traditionally been focused on small molecule drugs designed to bind directly to target proteins to decrease their activity. However, around 80% of protein targets are still very hard targets or even undruggable through this approach. 

A major and still underexploited area for drug discovery is mRNA. RNAi technologies have been developed to “knock down” mRNAs to prevent protein production. Recently, synthetic mRNA has been suggested as a drug to treat diseases where lack of protein is the problem, but it faces delivery problems and other issues that limit its widespread use. 

Small molecules targeting mRNA biology is one of the most promising areas for the discovery and development of new medicines. 

In this space, Anima’s Translation Control Therapeutics is the first and only platform for the discovery of small molecule drugs that control the translation of mRNA by ribosomes as a novel strategy against a wide range of hard and undruggable targets. Unlike other approaches that target the mRNA itself, we identify small molecules that can bind to the proteins that regulate translation. Through this approach, we can decrease or increase the production of almost any target protein, leading to drugs for the broadest range of diseases. 

Frank Romanski, Ph.D.
Global Technical Marketing Manager, Pharma Solutions, BASF Corporation

A: There are few things as transformative to the pharmaceutical industry as the advent of biologics. Everything from monoclonal antibodies to cell and gene therapy technologies are transforming the way patients are treated and even fully cured. From a pharmaceutical formulator’s perspective, we continue to rely on older technology for administering these types of large molecule formulations — namely, as parenterals.

The manufacturing and dosing of these formulations rely on excipients, surfactants and processing aids that are often out-of-date or not designed for large molecule manufacturing or dosing purposes. The cutting edge is where scientists aim to administer biologics using more patient-friendly means; for example, inside of an oral capsule or through the skin as a micro-needle patch. These are revolutionary ideas for administering large molecules, but they rely heavily on having tools, techniques and excipients to bring these ideas into reality. Often, in pharma, we wonder where the new molecules are. Well, the new molecules are here today, but they are fundamentally different and far more sensitive to external forces than their small molecule predecessors. Therefore, the innovation will come not just from the molecule itself, but also how it is formulated and administered to the patient.

Tiffani A. Manolis,
Senior Director, Pharma Strategic Program, Agilent Technologies Inc.

A: Currently, cell and gene therapies, along with advances in gene editing through CRISPR, offer impacts to patients that in many cases have not been effectively treated in the past, including rare disease patients. The broader impact and potential for these therapies is yet unrealized. Additionally, CAR-T therapies and their potential impact to treat cancer patients, as an example, with personalized therapies, has also not yet been fully realized.  

Daniel A. de Boer,
Chief Executive Officer, ProQR Therapeutics N.V.

A: One truly novel technology that could have significant impact on the lives of patients in the future is the use of RNA editing. Targeted RNA editing has the potential to directly correct the causes of genetic conditions. While therapies are still in the early stages of development, RNA editing potentially combines the benefits of both gene therapy and small molecule therapies. Like gene therapy and gene editing, RNA editing can specifically repair a disease-causing gene mutation but can do so without permanently changing a person's genetic code, reducing the chance of permanent off-target effects. Additionally, like small molecule drugs and unlike gene-editing therapies, small molecule RNA-editing therapies can often be administered in simple fashion and delivered without viral vectors. There are thousands of diseases caused by genetic mutations that can be corrected with RNA editing, and we have only just begun to witness the impact these types of therapies can have on the lives of people suffering from devastating genetic conditions.

David Fischer, Ph.D.,
Executive Director, Charles River Laboratories

A: In the past few years, antisense oligonucleotides (ASO) have become a trendsetting class of marketed drugs. The best known ASO is nusinersen/Spinraza®, developed by Ionis and Biogen for spinal muscular atrophy (SMA). The same oligonucleotide sequence can be used for all patients with SMA. This is a life-changing drug, as infants with the most aggressive form of SMA have a projected life span of less than a year.  Instead of being on a respirator, infants are thriving and meeting developmental milestones. The success of nusinersen has opened up opportunities for other diseases of the central nervous system (CNS), especially life-threatening congenital diseases with rare genetic causes. Charles River is working with a number of early stage companies on both cellular and IND-supporting studies to advance this novel drug class.

The second critical technology that is enabling treatment of genetic diseases is the increasing access to whole genome sequencing (WGS), allowing neonatalogists and genetics professionals to learn the exact mutation driving a patient’s disease. There are a number of synergies here that can reduce the time between diagnosis and drug treatment. The sequencing data allows a precision diagnosis, but also defines the target sequence for oligo drug development for that patient. Studies on the patient’s own cells can be used to screen ASOs in vitro for the best cellular genetic and functional readouts. Additionally, the ASO chemistry (the “backbone”) can be kept similar to nusinersen, which provided good penetration of CNS tissues and duration of activity. These are key accelerations for treating ultrarare diseases, even when only a single patient with a given mutation has been identified. As we learn more about these rare conditions, the data obtained from a single patient might be cross-applied to multiple patients with related but nonidentical mutations. The cost and time involved in WGS has come down to a few thousand dollars, and less than a month’s time — we can only hope that more patients will have access to this key technology soon, so that treatments can start as early as possible and prevent more life-threatening diseases from developing.

Chris Vernall,
Business Development Director, Intertek Pharmaceutical Services

A: Inhaled biologics have been forecast to grow in importance due to the fact that inhalation presents a highly attractive route for the administration of various classes of large molecules, particularly for the treatment of respiratory diseases. The major driver here is the potential for local, targeted delivery to the lung, opening up new treatment pathways for diseases such as cystic fibrosis, asthma and lung cancer. Delivery directly to the lung is likely not only to be more efficacious, but also to require less of the active ingredient compared with other routes of delivery. Systemic delivery of biologics is also possible via the lungs or the nose. Drug delivery via these routes is more convenient and less painful compared with other routes of administration for biologic drugs, which are generally administered intravenously.

Anil Busimi,
Senior Global Product Manager for iQ Platform at SCHOTT

A: Of course, pharmaceutical companies would be able to provide further insights on the topic of novel therapies. However, from our perspective as a primary packaging supplier, we see a rise in highly sensitive and complex biologics in the injectable drug pipeline. These drugs are used for various therapy areas, such as oncology, infectious disease, immunology and cell and gene therapies, to name a few.

Andrew Bulpin,
Head of Process Solutions at MilliporeSigma

A: It seems not that long ago that monoclonal antibodies were considered novel, and using gene therapies to cure rare diseases was just a dream — however, the mAb process is about 30 years old. In that time, the industry has become smarter and more agile and is keener than ever to make the dreams of the 1990s a reality.

This industry paradigm shift, fueled by forward-looking bioprocessing applications, has reinforced the need for better integration, collaboration and education. High-growth regions like China are moving at the speed of light, and the entire APAC region is poised to train its workforce in biologics GMP best practices to meet the demand for skilled labor. Emerging regions like Africa, the Middle East, Eastern Europe and LATAM are all in the race to get affordable medication to local patients.

MilliporeSigma’s deep-rooted industry experience and expertise is relied upon by customers worldwide. Our BioContinuum™ Platform will revolutionize drug manufacturing by setting the standard for improvements in process efficiency, simplified plant operations and consistency in manufacturing. Our Emprove® program helps our customers meet evolving quality and regulatory standards for pharmaceuticals. Our Synthia™ software innovation helps chemists optimize their synthetic pathways for parameters such as yield or raw material cost. These are just a few examples of how MilliporeSigma is defining the future and leading the evolution of drug development and manufacturing of life-enhancing and life-saving drugs, helping to shape the possibilities of tomorrow.

Amit Raj Dua,
Global Marketing Director, Cell & Gene Therapy, GE Healthcare Life Sciences

A: From an autologous therapy perspective, CAR-T therapies have shown promising clinical outcomes for lymphoma and myeloma, while T cell receptor (TCR) and tumor-infiltrating lymphocytes (TIL) therapies are growing in focus for solid tumors.

From an allogeneic therapy perspective, CAR-T, along with natural killer (NK) cell and induced pluripotent stem cell (iPSC) approaches, are being explored to enable off-the-shelf therapy manufacturing.

Lastly, in vivo gene therapies are showing good clinical outcomes for patients with genetic disorders and cardiovascular and ophthalmological diseases. Many of these therapies have curative potential.

Jason Spacek,
Vice President of Commercial Operations, Alcami

A: Cell and gene therapies represent the leading edge of medicine and have the potential to impact many patients’ lives. The advent of CRISPR technology catapulted these emerging therapies into the world, with the first FDA IND approval for clinical trials occurring very recently. This targeted gene-editing technology also enabled the next generation of CAR-T therapy development, which has been shown to drastically improve the quality of life for patients with several different types of lymphoma. By harnessing the potential of genetic engineering, these cutting-edge therapies can be used for tumor-targeting cancer therapies, neurodegenerative disorders, orphan diseases, and so much more.


Read Part 1: Manufacturing Technology

Yochi Slonim

Yochi Slonim is a serial entrepreneur with a successful track record in software and biotech. As Co-founder and CEO of Anima, he is driving the company's vision, strategy, fundraising and partnering efforts. Prior to Anima, Yochi built several companies from startup through product development, marketing and sales, all the way to successful IPOs and large M&A exits.