In which orphan spaces or unmet medical needs do you think we will see the next treatment innovations?

Neil Desai, Ph.D., Chief Executive Officer, Founder, and President, Aadi Bioscience

We see huge potential for growth in precision medicine, particularly precision oncology, in the near future. Viewing future treatment options for patients with genetically defined cancers through the lens of precision oncology is driving innovation in indications that have historically been untreatable. There has been significant success across our industry in the past few years, with new drugs and clinical trials focused on applying next-generation sequencing of tumors to specifically target genetically defined cancers, in improving clinical benefits for cancer patients. At Aadi, we focus on genetically defined cancers with alterations in mTOR pathway genes to unlock clinical benefits for people with mTOR-driven cancers. As shown in recent data at AACR, an aberrant mTOR pathway has been implicated in several different types of cancer. We are currently exploring the implications of alterations to the genes TSC1 and TSC2, which are known to play essential roles in the mTOR pathway, in combination with our precision targeted therapeutic nab-sirolimus. The innovative nab technology has the potential to make mTOR drugs more effective in cancer treatment when compared with mTOR inhibitors alone. Our early clinical data suggests the potential for using this approach to precision therapy in cancers with TSC1/2 alterations. While optimal target engagement is the goal of all precision medicines, the efficacy of a well-designed compound is enhanced by the identification of a specific target — something that we believe will continue to ring true for other indications across the sector.

Andrea C. Porchia, Ph.D., General Manager of AGC Biologics’ Copenhagen Facility, AGC Biologics

We believe that CDMOs can and should be leaders in developing the next treatment innovations in the orphan drug space. With extensive scientific experience in developing and scaling up to trial and commercial stages, contract development and manufacturing organizations are positioned to help create more innovations to treat rare diseases. 

Developers and pharmaceutical companies that want to be successful in the orphan drug space should look for CDMOs like AGC Biologics that have the historical expertise and can offer end-to-end clinical and commercial manufacturing services, as well as the latest materials needed (pDNA, mRNA) to bring innovative orphan drugs to the market. 

CDMOs offering robust analytical method development by way of rapid methods and reliable assays are also vital, as they are positioned to offer their customers a competitive advantage at a commercial scale but, more importantly, will be able to shorten cycle time to enable faster access for patients.

Lastly, contract manufacturing and development organizations can offer vast experience in process characterization and validation; they understand the key elements needed for regulatory filings. This expertise allows the process to be developed with the end product in mind.

Sergey Vlasenko, Ph.D., Associate Vice President, Pharma and Biopharma End Markets, Agilent Technologies, Inc.

The next innovations in rare disease treatments will likely leverage investments into novel biologic drug modalities, such as oligonucleotide therapeutics and gene editing treatments. These novel modalities offer unique therapeutic routes for mitigating orphan diseases by modulating desired protein expression in target patient populations. The R&D pipeline of the top five companies — Novartis, Bristol Myers Squibb, Pfizer, Roche, and Sanofi — continues to maintain strong focus on rare diseases.

Jeff Cleland, Ph.D., Chief Executive Officer, President, and Chairman, Ashvattha Therapeutics

Many orphan disease indications involve neurological disorders that are difficult to treat due to limitations with currently available therapies, such as an inability to cross selective tissue barriers like the blood–brain barrier (BBB), resulting in disease progression, neuroinflammation, and cognitive loss. Future treatment innovations for neurological disorders will be focused on identifying ways to cross tissue barriers and precisely deliver drugs to where they need to be to achieve therapeutic effects. At Ashvattha Therapeutics, we are leveraging our hydroxyl dendrimer (HD) platform to develop a new class of precision medicines that comprise potent small molecule drugs attached to HD molecules that are small enough to cross tissue barriers and selectively treat diseased cells in regions of inflammation. We’ll also see treatment innovations that aim to increase drug uptake while reducing systemic toxicity. One approach showing promising potential is HDs, because they bypass healthy cells and are only taken up by inflammatory cells in diseased tissue.

The powerful selectivity of HD therapeutics limits off-target effects, and previously toxic drugs take on the safety profile of HDs when conjugated together, creating a potentially safer treatment option. This approach allows for molecules considered effective but associated with toxic side effects to be reconsidered — attaching them to an HD and, as a result, broadening the possibilities for therapeutic benefit.

Ian Scanlon, Subject Matter Expert, Astrea Bioseparations Ltd.

Now that LNPs for the delivery of mRNA have been very widely clinically demonstrated after the vaccination drive during COVID-19, I think we will see a further expansion of not only nucleic acid therapies but other forms of delivery vectors. Non-viral gene delivery is attractive for a number of reasons — favorable immunogenicity, control of formulation, and so on –– but there are options with the biological space where the superior tropism of the alternative vectors offers an advantage. This is particularly true of exosomes, which have a similar immunogenic profile and can take much larger payloads, but also engineered variants such as lentivirus (LV) / adeno-associated virus (AAV) and related vectors, such as anellovirus. All offer viable delivery platforms for genetic therapies.

The advances in the field of non-plasmid DNA payloads are also moving at pace, with a number of companies developing linear DNA solutions that allow for more efficient construction of DNA sequences for therapeutic delivery.

Frank Romanski, Ph.D., Director, Global Head of Marketing, BASF Pharma Solutions

Biologics, which include recent innovations like cell and gene therapy, monoclonal antibody treatments, and mRNA-based treatments, have seen enormous growth in the past few years, and most notably in the past years alone. What is further noteworthy is that the COVID-19 pandemic has catapulted these technologies not only into a high growth phase but further into the daily lexicon of everyday citizens. The speed, sophistication, and specificity of such treatments have brought forth a deluge of investment in this space. Furthermore, some regulatory and acceptance barriers have now been overcome by necessity (e.g., COVID-19 vaccines) and consequently (likely) reduced future barriers to entry. While monoclonal antibody treatments have been used for some time, hundreds more are in clinical trials, and we are really only beginning to see the benefits of mRNA technology for both prophylaxis and treatments — with pipelines very heavily populated in early clinical trials. In this space, there will be considerable opportunities for innovation, most notably in the areas of oncology, neurology, and cardiovascular. It is worth noting that a sizable proportion of these new treatments are considered first-in-class, meaning that the next decade of approvals will include many novel and innovative treatments to some of healthcare’s biggest and most specific challenges. While the treatments themselves are the most visible innovations, they require a litany of ingredients during the upstream manufacturing and formulation of the drug products; this is where our focus remains on continuing to bring innovative, functional ingredients capable of ensuring efficacy, stability, and optimization of these innovative treatments.

Jeff Luber, Chief Executive Officer, binx health

Reducing the time between testing, diagnosis, and treatment, for any disease, represents the greatest opportunity to decrease human suffering. Early detection of cancer has long been the key to saving lives. For infectious diseases, rapid detection can also be the difference between containment/cure and further spread. Sexually transmitted infections (STIs) remain at all-time highs in the United States, with 42 million total cases of human papillomavirus (HPV), more than 1.5 million cases of chlamydia and gonorrhea annually, and only a 12% screening rate for STIs. Under the current care paradigm, patients often receive their test results days later. The gap between identifying and treating the disease leads to continued infection spread. Furthermore, 40% of patients who leave the clinic without treatment fail to adhere to recommendations. Untreated disease can lead to cases of infertility, ectopic pregnancies, pelvic inflammatory disease, further spread, and compounding of the problem.

Point-of-care testing allows testing to be rapidly performed onsite and for the results to be delivered during the same healthcare provider visit, so that that a patient can leave with counseling from a clinician and a prescription in hand. For the two most tested-for STIs, chlamydia and gonorrhea, decreasing the time between test and treat can arrest infection spread, reduce the incidence of comorbidities, and change the outcomes for individuals and families globally.

Anna Codina, Ph.D., Director, Pharmaceutical Business Unit, Bruker BioSpin

Oncology stays prevalent as a major focus therapeutic area and remains an unmet medical need. We are seeing a paradigm shift toward biologics and new drug modalities accelerated by COVID-19 and facilitated by collaborations within the industry, mergers, and acquisitions. I would expect the use of ribonucleic acid as an active pharmaceutical ingredient to continue, which will ensure further innovation in drug delivery systems like lipid nanoparticles.

We are starting to see the increased use of techniques such as magnetic resonance for the characterization, analysis, and testing of biologics, biosimilars, and new drug modalities. Recent technological advances in both liquid and solid-state high resolution magnetic resonance allow quality assessment of formulated biotherapeutic peptides, proteins, and antibodies to be performed in physiological conditions, without the need of labelled compounds. On the other hand, benchtop magnetic resonance is emerging as a powerful process analytical technology tool, able to test these complex molecules in their container (vials or syringes).

Fabian Gerlinghaus, Co-Founder and Chief Executive Officer, Cellares

Over the last decade, cell therapies like chimeric antigen receptor (CAR)-T cell therapies have demonstrated their ability to save patient lives. Beginning in 2017, the U.S. FDA approved a number of gene-modified cell therapies to treat hematologic malignancies in patients that had failed multiple treatment regimens.

Given the unprecedented response rates of CAR-T cell therapies, these treatments are now being approved for use in earlier lines of treatment. For example, Kite Gilead’s CAR-T therapy, Yescarta, was approved in April 2022 as a second-line treatment for large B cell lymphoma (LBCL). In the United States alone, more than 18,000 people are diagnosed with LBCL each year, and about 40% fail first-line treatment. Now, a growing number of these patients will be eligible for treatment with CAR-T cells.

However, approved CAR-T cell therapies are currently only offered as autologous treatments to patients with blood-based cancers. The impact of these groundbreaking therapies will truly be felt when they expand into solid tumor indications with even larger patient populations. At Cellares, we’re building automated and high-throughput technologies to resolve the manufacturing bottleneck and enable access to cell therapies for all the patients who need them. Our technology can support both autologous and allogeneic cell therapy approaches, which reflects our expectation that both modalities will play a significant role in the future. Perhaps even more exciting is the prospect of cell therapies being used to treat autoimmune and infectious diseases as well.

David Fischer, Ph.D., Chief Technology Officer (Early Discovery), Charles River Laboratories

There have been many advances (gene therapy, ASO, siRNA) in recent years to develop treatments and expand access to therapies for patients with unmet medical needs, particularly in patients living with rare genetic conditions, and, while the work is far from complete in that field, I predict that the next wave of innovations will focus on treating non-genetic illnesses. After a long drought, prevalent conditions like depression, chronic pain, migraines, and epilepsy could rise to the forefront of innovation and benefit from new treatment approaches. Over a billion people live with these conditions worldwide, and, despite their prevalence, improved treatment options for these diseases remain disproportionate to the number of people living with them.

In the past couple of years, the drug discovery industry has revolutionized itself on several fronts: novel drug targets now come with much stronger human genetic (population) validation and patient stratification; our war chest of types of drugs has expanded significantly, allowing us to drug targets previously characterized as undruggable, and we’re learning to build upon old molecules with proven human efficacy by dialing out unwanted side effects or dialing up beneficial mechanisms of action. For instance, equipped with an improved understanding of the polypharmacology of psychoactive molecules, which act on multiple targets, we can unlock the next generation of treatment for some of these widespread indications. Hopefully, these treatments allow for improved patient compliance and superior efficacy against complex diseases, as well as an improved safety profile compared with standard of care — and, with non-genetic diseases facing widespread unmet need in the treatment landscape, these elements are key to safe and effective drug development.

Jeff Elton, Ph.D., Chief Executive Officer, ConcertAI

There are two categories that I would highlight, an early-stage and a maturing one.

The earlier one is gene therapy, especially a focus on single-gene–associated diseases, such as different classes of neuromuscular disorder. The challenge with these has been several-fold. First, finding rare disease patients is, in itself, difficult. These diseases present with early symptoms that could be the manifestation of a range of diseases. Second, dosing has proven complex, with liver toxicities and other adverse effects leading to death or organ injury. The promise with gene therapy is enormous, advances are being made in delivery, and the tools to monitor are improving, but this is a new area, and we will see new hurdles. 

On the maturing side, CAR-T are highly targeted, engineered immune cells that can target a number of advanced leukemias and lymphomas. There are seven approved CAR-T therapies, with many more available under institutional protocols at leading cancer centers, and approximately 500 in clinical development. While response rates are positive — 40–80% — they are not assured. But we’re now seeing autologous and allogenic CAR-T, allowing this to advance to a range of different treatment and administration approaches. There are still challenges. Identifying patients that meet the criteria for treatment is difficult — most have a history of failing other treatments before being CAR-T eligible. And cytokine release syndrome, which results from rapid immune activation by “armed” CAR-Ts, is the most significant treatment-related toxicity. However, safety has significantly improved with greater experience in administration. This is an area of enormous potential being realized and advancing rapidly.

Tony Ward, Chief Operating Officer and Chief Technology Officer, Curate Biosciences

The cell therapy space is poised to explode, with growing patient and doctor demand for these potentially curative therapies and the industry scrambling to meet it. Recent reports have estimated that about a fifth of eligible patients die waiting up to two months for a dose of these patient-derived CAR-T therapies to be manufactured.

That’s just among patients who qualified because they failed all other treatments. Even among this group in desperate need, many were ineligible if they were too ill to produce enough immune cells. And the makers of these bespoke medicines have begun securing approvals to move earlier in the course of treatment, meaning that the industry is ramping up efforts to produce even better medicines for more patients, faster.

Much of the effort is focused on new technology to automate many of the manual and labor-intensive steps to improve quality, reduce costs, and shorten manufacturing time. It also has the potential to expand access for currently ineligible patients.

For example, automated cell separation can increase the number of cells that can be turned into a therapy. That’s important not just for cancer patients, who often have disease- or medicine-suppressed immune systems, but also to treat patients with autoimmune diseases, with infectious diseases like HIV, or those who’ve had a transplant. The same technologies could also reduce the need for cell expansion, the most time-consuming piece of CAR-T manufacturing, and reduce labor requirements amid the staffing shortage — all helping more patients get more cell therapies, faster.

Emmanuel Ligner, President and Chief Executive Officer, Cytiva

It is a great achievement that humans are living longer. 13% of the global population will be over 65 years old by 2030, and this percentage will continue to grow over the next few decades. At the same time, we need to age while in good health and enjoy good quality of life. The rise in chronic diseases affecting the population, such as heart disease, diabetes, and cancer, will dramatically increase over the next 10–15 years. Barring any future pandemics, the prevalence of chronic disease is set to outpace infectious diseases within the next decade. This is why society needs to solve how we will age in good health.

The development of personalized therapies for tackling chronic and rare diseases using mRNA will become more prevalent. The successful use of mRNA for COVID-19 vaccines proved that this technology is effective and can be scaled up quickly and manufactured on a global scale. For personalized therapies targeting cancer, this speed will be critical. Treatments, using specific molecular features from an individual’s tumor, must be developed within 1–2 months after tissue collection. For the 18 million people a year who are battling cancer, the clinical trial results of personalized therapies are promising.

If we are to successfully treat or cure chronic diseases and improve human health, the collaboration among scientists, the pharmaceutical industry, and governments that we saw during the COVID-19 pandemic must continue.

Temitope Keyes, Executive Director, Business Development, Encapsia

Definitely central nervous system (CNS) disorders, such as strokes, movement disorders, Guillain-Barré syndrome, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), Huntington’s disease, and Alzheimer’s disease. CNS as a therapeutic area had fallen by the wayside relative to rare/orphan indications and oncology. One in three people in the world are affected by these diseases, and the burden of deaths and disability caused by CNS disorders is increasingly being recognized as a global public health challenge, which is set to rise further over the next few decades as a result of the growing aging population.

This space was lagging due to the lack of efficacy in approved treatments driven previously by a poor understanding of biomarkers and genetic factors that impacted neurological systems. Powerful laboratory analyses and imaging modalities have dramatically broadened the depth of knowledge needed to innovate in CNS. Furthermore, the continued fast pace of the medical device area, especially in neuromodulation, implantables, and wearables, provides yet another avenue for treatment of patients suffering from treatment-resistant depression or PTSD. Extensive research and clinical trials have begun to prove neuromodulation’s ability to decrease chronic pain and improve the quality of life for CNS patients. The other crucial piece of the puzzle in CNS is being able to assess efficacy using validated clinical scales and assessments that capture baseline patient status throughout the course of the clinical study and beyond. CNS trials are no different than oncology, in that they generate significant volumes of clinical data from disparate sources. It’s important to evaluate this data using a technology that offers real-time data visualizations and reports to identify relevant insights sooner and mitigate the risks that may affect the quality or safety of a study.

Nancy Lurker, President and CEO, EyePoint Pharmaceuticals

We are fortunate to see innovation advancing in many therapy areas right now, and some of the next exciting and significant advancements are in ophthalmology. As our population continues to age, diseases in the back of the eye, such as wet age-related macular degeneration (wet AMD), diabetic retinopathy, diabetic macular edema, and retinal vein occlusion, represent a growing area of significant unmet need.

Prior innovations in intraocular injections allowing delivery of sight-preserving therapies directly to the tissue in the back of the eye represented a true turning point in the treatment of these diseases, but the next treatment innovations are targeted at increasing the longevity of action and durability of treatment to relieve patients and their caregivers of the burden of visiting their doctor ever month or two in order to maintain their vision. 

We know that, in the real world, a year or two into their disease, patients can lose much of the visual gains, because they can’t keep up with visits or their treatments. These next treatment innovations on the horizon aimed at maintaining visual gains over the longer term are poised to address what is arguably the largest unmet need in the landscape right now in this area. With trials moving forward every day, it is a truly promising time for patients with serious eye disorders.

Kathy Lee-Sepsick, Founder, Chief Executive Officer, and President, Femasys

Solutions for women’s reproductive health remain costly, inconvenient, and, in extreme cases, deadly. This space represents significant unmet medical need, with over 9 million women struggling with infertility and over 13 million women who are candidates for permanent birth control in the United States alone. Technologies on both ends of the reproductive spectrum are antiquated and have significant limitations, providing significant opportunity to be replaced with next treatment innovations.

For instance, intrauterine insemination (IUI) is the oldest technique in artificial insemination. It remains the first-line treatment option despite low success rates. On the opposite end of the spectrum, the first tubal ligation was performed in 1880, and it remains the only form of permanent birth control. As a surgical approach, tubal ligation has possible risks that include bleeding or damage to the bowel, bladder, or major blood vessels. This is why, at Femasys, we are developing first-in-class solutions to meet women’s unmet medical needs. Our in-office procedures for front-end infertility and permanent birth control are designed to be safe, natural, and minimally invasive.

To my disbelief, conversations around Roe v. Wade have resurfaced, but I am hopeful that the attention that women’s healthcare is receiving will finally push the industry toward greater acknowledgment of the need for advancements and innovation. As a community, we’ll need to work together to ensure that women are able to access improved options for their specific needs. Women deserve to make informed choices when it comes to their reproductive health, and I believe that we’ll begin to see changes in the space in the coming months.

Dan Mandell, Ph.D., Chief Executive Officer, GRO Biosciences

Advances in antigen-specific tolerization will enable innovative treatments for underserved patients with autoimmune disease. These approaches aim to reeducate a patient’s immune system to recognize disease-causing autoantigens as self-proteins, thereby halting or even reversing disease progression. Such strategies will find early applications in orphan indications with well-characterized mechanisms of pathogenesis and a clear understanding of causative autoantigens, such as thyroid eye disease, myasthenia gravis, and pemphigus vulgaris. Methods in preclinical and clinical development include administration with tolerizing nanoparticles, co-administration with tolerogenic co-factors, and engineering of autologous and allogeneic immune cells. Recently, companies like GRO Biosciences have developed techniques to induce recognition of autoantigens as self-proteins by the introduction of glycosylated amino acids. Decorating an antigen with known tolerizing glycans results in presentation of the antigen in a tolerogenic context, ultimately providing durable tolerance via establishment of antigen-specific T regulatory cells.

Beyond autoimmune disease, antigen-specific tolerization will also underlie new treatments for patients suffering from orphan diseases with therapies hampered by neutralizing antibodies. Protein-based medicines like enzyme replacement therapies — as well as vectors for the delivery of gene therapies — are frequently impaired by a neutralizing immune response. Many techniques developed for tolerization of endogenous proteins may be applied to such exogenous therapies, allowing for a new generation of treatments with unprecedented safety and efficacy.

Jamila Louahed, Ph.D., Vice President, Head of Vaccines Global Research and Development, Belgium R&D Center, GSK

GSK’s purpose is to unite science, talent, and technology to get ahead of diseases together. We will do this by prioritizing innovation in vaccines and specialty medicines, maximizing opportunities to prevent and treat diseases. Our aim is to positively impact the health of more than 2.5 billion people over the next ten years.

Our current pipeline consists of 43 medicines and 21 vaccines, almost half of which address infectious diseases. 

Our approach to research and development focuses on science related to the immune system, the use of human genetics, and advanced technologies. It will help us to accelerate the pace at which we develop and deliver transformational medicines and to increase our focus on specialty medicines in areas such as oncology.

In addition, in our vaccines business, we focus on accelerating key assets in our pipeline and looking at innovative technologies so that we can unlock potential in emerging fields. As GSK’s eight consecutive years at the top of the Access to Medicine Index show, diseases affecting the developing world continue to be a key focus for our organization. 

Caroline Cooreman, Global Business Development Manager, Biotechnology, IFF

Investments in biotechnology have reached record-breaking levels. This surge is attributed to gene therapies and cell-based immuno-oncology. Oncology remains the primary indication targeted, with strong pipelines in blood-forming malignancies, breast tumors, and melanomas. There is also growing interest within allogeneic cell-based immunotherapies for cancer treatment, which are appealing due to their cost-effectiveness and global accessibility.

In addition, we’re seeing advancements from biotech start-ups and innovators that target rare diseases, such as ALS, hemophilia, and sickle-cell disease. Yet, the clinical pipelines appear equally invested in prevalent diseases, targeting indications such as diabetes, osteoarthritis, Alzheimer’s, and Parkinson’s. 

The global SARS-CoV-2 pandemic has also accelerated the development of nucleic acid therapies with large curative potential. It will be exciting to see how this new field of therapeutics will advance treatment of solid tumors, infectious diseases — including influenza and RSV — and metabolic and cardiovascular diseases.

Joseph Zeleznik, Technical Director, North America, IMCD

New rare diseases are discovered every year. Most are inherited and caused by genetic mutations or other anomalies. Others are attributed to environmental factors. These unmet medical needs call for innovation; however, there is risk in creating therapies for rare diseases due to development costs and return on investment. To help, financial incentives have been implemented to foster orphan drug development. Another issue is that only five percent of rare diseases have an approved treatment, and consequently, there are still many unmet patient needs. According to some forecasts, orphan drug growth could be as much as 11% annually through 2024 and possibly out to 2026. Trends suggest that the greatest opportunities will be in biologics, particularly for rare cancers, and treatments for CNS disorders such as ALS, as well as diseases related to lipid metabolism and lipid build-up in the body, which can include any number of rare diseases, such as Gaucher or Batten diseases. There are other rare metabolic and autoimmune diseases. Beyond these are those treatments targeted at rare pediatrics disorders. In biologics, RNA vaccines are a promising pathway toward personalized medicine development and treatment for rare diseases, and new platform technologies for cell and gene therapies are also very promising. For example, CRISPR-Cas9 or siRNA have shown good results in controlling gene expression. 3D printing could also be a valuable tool for personalized medicine manufacture, owing to its flexibility, control, and scale in treating rare diseases.

Marie Lamont, General Manager and Vice President, Inteliquet, an IQVIA Business

We at Inteliquet (an IQVIA company) don’t see this issue in terms of one orphan space or another. We rather see it in terms of the opportunity to have the infrastructure to serve more orphan spaces and unmet medical needs that have not been successfully solved with manual efforts and legacy systems. Solving for one space or one unmet need has limited value if we as an industry do not apply the learnings to other areas of need.

This means that if we advance how we engage patients on their healthcare journey and support treatment backed by data — beginning at the healthcare organization’s point of care — the most challenging rare and orphan spaces can find treatments that may have otherwise eluded them. This is important, because clinical trials may be able to meet feasibility for these faster than ever. Addressing an unmet medical need for an oncology patient is not just about identifying a potential treatment that may work for them. Reducing the timeline to identify that treatment is not only innovative, but critical.

Now that healthcare organizations are able to more easily manage and normalize patient data for answers to timely questions around personalized medicine and clinical trials as a care option, we can realize the promise of convergence that better serves patients, including those often marginalized because of hard-to-study, hard-to-treat conditions and small patient populations. This means that opportunity lies within rare and orphan disease states with care options where patients may not have equal opportunity to benefit from telehealth.

Overall, cancer is complicated and a leading cause of death. We still have much work to do to improve the patient journey for all oncology patients, including those with rare and orphan cancers. The interest in oncology remains very high where patient matching through the intelligent use of healthcare data and artificial intelligence (AI)-enhanced biomarker matching can answer questions of study feasibility that may provide breakthroughs to save time and lives, now and in the future.

Alex Morgan, M.D., Ph.D., Partner, Khosla Ventures

It's hard to predict innovation, but we are seeing a lot of promising activity in fetal–maternal health, which I am excited about, as this is an area that has often been neglected, and early development lays the foundation for future health. We will also certainly see innovation in how therapies are used, as the rapid point-of-care diagnostics systems fully commoditized because of COVID-19 find other creative uses. For example, it may make many drugs with narrow therapeutic windows much more feasible candidates for development, or support drugs that need to be deployed in response to rapidly changing physiological conditions in non-hospitalized patients. Delivery of genomic medicines is currently a major challenge, but I think there will be near term significant innovation there, and I believe it will be via non-viral approaches.

Ling Wong, Ph.D., Senior Advisor to Lightspeed and General Partner and Founder at Highbury Group, Lightspeed Venture Partners

The next treatment innovation will come in the transplant ecosystem. This unmet need, due to a lack of organs available for transplantation, is a worldwide problem that leaves thousands waiting every year. There are more than 100,000 people on the United States national transplant waiting list, and more patients could benefit from an organ transplant but aren't eligible. In addition, these procedures are extremely costly and invasive. The price tag for a transplant is nearly $800,000, and patients often need days in a hospital to recover. Researchers have been pursuing potential solutions like xenotransplantation for decades, but, even if successful, it relies on one-to-one organ replacements. These current solutions fall short of meeting transplant needs and do not address the financial and patient concerns. Lightspeed Venture Partners’ portfolio company Satellite Bio is developing a new category of regenerative medicine called Tissue Therapeutics, which turns virtually any cell type into bioengineered tissues at scale that can be integrated into the body to restore natural function. The company’s Satellite Adaptive Tissues (SATs) can be placed in remote locations within the body to deliver the comprehensive cellular response needed to repair or even replace critical organ function in patients with diseases caused by the interaction of genetic and environmental factors. These Tissue Therapeutics can be a stopgap treatment for people waiting for a transplant, improving their quality of life. Satellite Bio is first focused on a liver therapeutic due to the need for new, innovative chronic liver disease treatments. 

Kimberly Shepard, Ph.D., Associate Director, Principal Engineer R&D, Small Molecules, Lonza

Dry powder inhalers (DPIs) are the preferred treatment method for patients with lung disease. In recent years, 30–50% of active pharmaceutical ingredients (APIs) for inhalation delivery are biotherapeutics. Biotherapeutics are fairly delicate in comparison with small molecules and require special formulation and manufacturing considerations to enable use as a dry powder inhaler. Lonza’s work in spray drying of monoclonal antibodies and other biotherapeutics for dry powder inhalation can help realize the benefits of DPIs for a different class of actives.

More than 12 monoclonal antibodies are commercially approved as injectables for the treatment of lung diseases, including asthma, lung cancer, and lung infections. As injectables, these treatments are invasive, require cold-chain storage, and must be administered by a trained individual. In addition, treatments are administered systemically, which can lead to adverse effects in healthy tissue. Particularly for lung cancer, local treatment is a promising means to isolate potent compounds at the affected tissues. Local treatment of lung disease with monoclonal antibodies could improve treatment options for patients.

Advantages of monoclonal antibody (or other biotherapeutic) DPI therapies manufactured by spray-drying include reduced dose and systemic side effects, avoidance of cold-chain storage requirements, reduced cost of treatment, and the possibility of simple, at-home administration.

In a recent publication, Lonza’s team demonstrated a respirable, bioactive spray-dried powder containing bevacizumab (a treatment for non-small cell lung cancer) with 12-month stability at 25 ºC. In a follow-up study, the authors combined this formulation into a single dry powder with cancer-relevant small molecules.

Dirk Lange, Head of Life Science Services, MilliporeSigma, the Life Science business of Merck KGaA, Darmstadt, Germany

It’s a really exciting time to be in this industry. We’re at the forefront of reshaping modern medicine, moving from treating a disease or condition to potentially curing and eliminating it. This is particularly true with the help of novel modalities like nucleic acid–based therapies, such as mRNA and cell and gene therapies.

Traditionally, gene therapies have primarily targeted rare diseases with small patient populations. Looking at the clinical pipeline, we see a shift to larger patient populations. To ensure that all patients who could benefit from these potentially curative treatments have access, it’s imperative that we invest now in improving scale-up and manufacturing. As manufacturing practices advance, biosafety testing must also evolve to deliver faster results and to safeguard the continued quality and safety of these therapies.

Emerging biotechs are a big driver of innovation and diversification of drug pipelines to support the growing demand for curative treatments. These small- and medium-sized firms need partners with the capabilities and resources to help scale up their molecules. This has led to an acceleration in outsourcing efforts to help speed up time to market, with biotechs leveraging the scientific, operational, and regulatory expertise of contract development and manufacturing organizations (CDMOs) or contract testing organizations (CTOs.)

While many companies focus solely on development, manufacturing, or testing, we are a true “CTDMO” and seamlessly integrate our CDMO services with biosafety testing. This integration enables us to reduce interfaces and streamline the development and release timelines, ultimately bringing new, curative therapies to patients sooner.

Robert Barrow, Chief Executive Officer and Board Director, MindMed

Many researchers consider the brain the “final frontier” of medical innovation. While this offers exciting new possibilities for future drug development, we cannot forget that we are currently in a mental health epidemic. The need to find faster, more durable, and more effective brain health treatments has never been greater. Added stressors from the COVID-19 pandemic and other global crises have only worsened the situation for those currently suffering from brain health disorders. The one-year prevalence of anxiety disorders in the United States is approximately 21%, over 50 million U.S. adults live with chronic pain, and roughly 250 people die each day as a result of substance abuse disorders. Most drugs in development for brain health are either reformulations of existing drugs or offer only marginal improvements in symptom reduction.

We will see the next treatment innovations in the brain health space derived from psychedelic compounds. We are witnessing a dramatic change in attitudes toward a once stigmatized class of drugs, now greeted with optimism by the medical community, patients, regulators, and investors based on rigorous scientific data demonstrating the potential of these compounds to provide meaningful improvements for patients for whom current treatments have not been successful. At MindMed, we are developing a pipeline of drug candidates to treat brain health disorders, with and without acute perceptual effects, based on LSD, MDMA, and an ibogaine derivative. Our product candidates are based on scientific evidence demonstrating their potential to treat brain health disorders.

Todd Druley, M.D., Ph.D., Chief Medical Officer, Mission Bio

Oncology will see a flood of treatment innovations in the coming years as we pivot from broad, one-size-fits-all therapies to personalized medicine. The future of cancer treatment is one of the increasingly complex therapy combinations and surveillance modalities as new niches are identified and targeted.

To most effectively implement treatment regimens and track disease progression, as well as the emergence of treatment resistance, clinicians and researchers will require a greater understanding of genotypic and phenotypic disease subtypes and their respective response to therapy, as well as patient-specific metadata, comorbidities, and even microbiome genetic variation. Thankfully, sequencing technology is evolving to provide higher, more precise resolution for each patient and each tumor, essentially making all cancers “rare” diseases that require personalized treatment and surveillance.

Single-cell characterization of DNA, protein, gene expression, epigenetic, and functional differences offer novel treatment targets with great promise to improve outcomes. In the meantime, we’re seeing single-cell technologies begin to reshape clinical paradigms: researchers are uncovering mechanisms of resistance to BTK inhibitors in B cell cancers and IDH inhibitors in acute myeloid leukemia and are developing patient surveillance strategies based on the identification of novel risk factors for leukemia in patients with Shwachman-Diamond syndrome, to name just a few. Treatment innovation is about more than just new drugs — it’s also about changing patient experiences by using existing therapies better.

Stefan Weber, Chief Executive Officer and Executive Director, Newron Pharmaceuticals SpA

We are very hopeful that the treatment of schizophrenia, a devastating and intractable disease affecting some 1% of the global population, will begin to see meaningful new developments in the near future. A particular issue with schizophrenia is the high percentage of patients who, over a period of time, develop an inadequate or failed response to the current generation of antipsychotic treatments. For these individuals — by some estimates as high as 60% of all schizophrenia patients — there exists only one approved monotherapy, clozapine, an effective therapy but one with significant potential side effects that tend to limit its broad usage.  But there has been exciting progress in the CNS field over the past year, along with a recognition that treatment resistance — not only for schizophrenia but for a number of other psychiatric disorders — is an area that must be considered for current and future therapeutic directions.   

Russ Trenary, President, Chief Executive Officer, and Board Member, Outlook Therapeutics

Our team at Outlook Therapeutics recognizes a unique unmet medical need in ophthalmology. There are currently a handful of approved anti-VEGF treatment options available for wet age-related macular degeneration (AMD) patients. Meanwhile, 50% of anti-VEGF injections for treatment of wet AMD are off-label bevacizumab, which come from compounding pharmacies and are not designed for ophthalmic use. Bevacizumab is a molecule that has been used to treat retinal disorders for several years but has never received approval from major regulatory agencies to be used as an ophthalmic drug solution.

We believe there is a significant unmet need for an approval by the U.S. FDA for an ophthalmic bevacizumab for treatment of wet AMD. If approved, we hope to see our ophthalmic bevacizumab, ONS-5010, become a valuable on-label therapy offering clinicians and their patients a safe and effective ophthalmic formulation of a treatment whose value has been proven over many years of clinical practice. Recent independent market research conducted by Spherix Global Insights indicates that 80% of retina specialists surveyed hold the view that Outlook Therapeutics’ ONS-5010 would represent an advancement if approved by the FDA.

Craig LaMarca, General Manager, Boston Clinical Trial Services, PCI Pharma Services

The industry continues to shift away from broad, generalized treatment modalities to more individualized treatment approaches. Personalized medicine through development of advanced therapy medicinal products (ATMPs) continues to hold the potential to revolutionize clinical and therapeutic strategies. The industry is shifting from a model of treating symptoms to one that is based on curing diseases. These therapies tend to require an advanced manufacturing process and specialized handling. Because of this, injectable-based products with cold-chain supply requirements will continue to take more market share.

In addition to personalized medicines, biologics, peptide-, and protein-based compounds continue to be a focus area for clinical development organizations, with a large share of these compounds focused on the central nervous system (CNS), oncology, and rare diseases. This will increase the need for highly potent active pharmaceutical ingredients (HPAPIs), as they allow for more targeted therapies to be developed with reduced, generalized adverse effects.

Michelle Mellion, M.D., Senior Vice President and Head of Clinical Development, PepGen

There are three areas in rare disease drug development that in particular need advancements: (1) development of therapies for multifactorial diseases, (2) treatment of very small patient populations that require a bespoke therapeutic approach, and (3) improvements in the delivery of drugs, both nucleic acids and proteins, to tissues currently not accessible or poorly accessible by existing therapies and modalities. The third category is particularly pertinent for the treatment of rare neuromuscular and neurologic diseases. For people with diseases like Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1), treatment is mainly supportive. No curative therapies exist because of limitations in delivering therapies to affected tissues. Therapies for DMD and DM1 must address the root cause of disease to make a meaningful impact on quality of life. Fortunately, broadening research in the space suggests that we are on the cusp of transformative therapies for these disorders.

At PepGen, we are focused on advancing a new generation of therapeutics through our Enhanced Delivery Oligonucleotides (EDOs), which are designed to dramatically increase therapeutic uptake by the tissues most affected in neuromuscular and neurologic disease. Our preclinical data demonstrates that our EDOs have sustained effects in tissues including skeletal muscle, heart, and diaphragm. Our lead program in DMD is now in human trials. We believe that the future of treatments for rare neuromuscular diseases is brightened by the commitment of our team and others working in parallel with patients and their families to develop targeted therapies that can stop or reverse disease progression and have a long-term impact on quality of life.

Roel Gordijn, Chief Commercial Officer, Polyplus-transfection®

The attention being paid to orphan indications has continued to increase over the past decade. According to Research and Markets, growth in the space is expected to increase from $190.8 billion in 2021 to $248.2 billion in 2026. This includes a range of modalities, with the most promising drugs being large molecule or advanced therapy medicinal products (ATMPs).

Steady demand has continued for large molecule drugs, such as monoclonal antibodies. Titers have increased from approximately 0.1 g/L two decades ago to more than 10 g/L today, requiring more integrated and automated platform approaches.

ATMPs are expected to continue growing exponentially as well, but these treatments also present challenges, one of the greatest being that they are dependent on viral vectors for delivery. As such, the viral vector industry is seeing significant increases in upstream and downstream production of viral vectors in the next couple of years.

Both the European Medicines Agency (EMA) and the U.S. FDA expect that there will be 10–20 ATMP approvals each year by 2025. And with more than $30 billion invested in the field and the number of assets moving from drug discovery and preclinical into phase I and phase II, the pace is not slowing down. Still, a slow rate of ATMP regulatory approvals has increased the complexity of these therapies and the need to look closely at the highly novel technologies used in their production.

Mark Gergen, Chief Executive Officer, Poseida Therapeutics

I believe that there are two areas that seem poised for breakthrough innovation. The first is the use of allogeneic cell therapies for the treatment of cancers, including solid tumors. While this has proven a difficult challenge medically and scientifically, we are seeing incremental progress across the industry in terms of new advancements and progress that suggest that breakthrough innovation is coming soon. The second is the treatment of rare monogenetic diseases — especially in infants and juveniles. Most genetic diseases are present from birth, and there is enormous unmet need to treat many of these conditions that are often otherwise fatal for these children at a very early age. Recent advancements in technological innovation in genetic engineering are finally putting effective treatments within reach. At Poseida, we are investing in these innovations and seeing progress that makes us proud to play a role in both areas.

Chris Gibson, Ph.D., Co-Founder and Chief Executive Officer, Recursion

Biology is extraordinarily complex, and so, for far too long, our industry has fallen short in addressing many intractable diseases, especially in areas like neuroscience and fibrosis. Today, the majority of companies researching these diseases are pursuing a limited number of similar target hypotheses based on the relatively narrow understanding of biology we’ve elucidated to date, even in many cases pursuing study after study against the same targets that have failed in clinical trials already. It’s clear to us that, in the face of the enormous complexity of biology, all our biases as humans may be standing in the way of better medicines.

Fortunately, the convergence of new technologies is helping unravel the complexity of biology in a less biased way. Rather than approaching these diseases with a specific set of hypotheses informed by the literature, we can build and navigate maps of biology that may help us identify novel therapeutics and unlock novel biological insights outside of what is known today. That’s our focus at Recursion, where we apply machine learning to our proprietary high-dimensional data sets of genome-scale biology and chemistry to identify relationships between biological contexts and chemical entities. This enables us to expand the scope of potential therapeutic candidates and accelerate the drug discovery process.

I’m particularly excited about our work in neuroscience and fibrosis, where we’re partnering with experienced, top-tier biopharma leaders to explore these areas together. Each of us brings something unique to the partnership, and I believe that together we have the potential to radically improve people’s lives.

Irene Meier, Ph.D., Clinical Trial Lead, Reify Health

Alzheimer’s disease is the most common form of dementia and is expected to affect over 50 million people by 2030. There is no cure despite decades and billions of dollars invested into clinical research. It is one of the biggest threats to our aging population. The disease is disruptive to patients, caregivers, and entire families, and it poses large strains on our healthcare systems.

Despite daunting results of clinical trials in the last two decades, thanks to recent innovations such as digital and blood biomarkers, we are getting better at diagnosing patients earlier in the process. These solutions are available at a large scale and relatively low cost. 

While biological underpinnings are undisputed, the disease phenotypes may hold key indicators that help shed light on pathophysiological processes of the disease. The ability to better differentiate the various clinical disease expressions — typically assessed through neuropsychological tests and, more recently, supported by digital biomarkers — is crucial for the development of new approaches. Through the addition of wearable data that is able to detect subtle changes in everyday behavior, we will be able to gain insight into the patient’s behavior leading up to the disease and into changes over the disease course. Increasing diversity and researching a broader patient variety will further grow our overall knowledge of Alzheimer’s disease and its risk factors. Together, I believe that these components will improve our understanding of the natural history and progression of Alzheimer’s disease and thus lay the foundation for novel treatment approaches of this devastating disease.

Christiane Bardroff, Senior Vice President of Client Program Management and Senior Vice President of Clinical and Commercial Manufacturing, Rentschler Biopharma SE

I strongly believe that personalized medicine and the treatment of rare diseases will continue to gain significance. As a premium service provider, Rentschler Biopharma offers innovative solutions to ensure the best results in collaboration with our clients. This translates to fast and high-quality product development all the way to market production. In the future, small- or medium-sized bioreactors up to 3,000 L will play an increasingly important role. This is also one of the reasons why Rentschler Biopharma is investing in four 2,000 L single-use bioreactors at our site in Milford, MA. In this way, we are contributing, within a strong network and together with our clients, to providing a better life for patients with serious or rare diseases. Furthermore, new modalities will also open up new possibilities. The COVID-19 pandemic has demonstrated how innovative drugs based on mRNA can play a key role. In addition, viral vectors and oncolytic viruses will bring breakthroughs as well. As an innovative company, Rentschler Biopharma has therefore also invested in advanced therapy medicinal products (ATMPs) at our center of excellence, Rentschler ATMP, in Stevenage, U.K. We plan to partner with entrepreneurial players, enabling them to transform their ideas into products with the potential to treat and even cure patients.

Kyung-Ah Kim, Ph.D., Executive Vice President and Leader of the Development Division, Samsung Bioepis

Recently, more therapeutic options have become available for patients with hard-to-cure diseases as more innovative biologics are being developed. It is certainly great news for patients, healthcare providers, and many other stakeholders. However, healthcare costs continue to rise due to the high price tags of these innovative biologics, and “unequal access” to medicines will continue to be an issue; as a result, there will be a growing number of patients with unmet medical needs who cannot afford these innovative biologics.

Biosimilars, on the other hand, can increase patient access to innovative drugs at a significantly reduced price after the loss of exclusivity of the original biologics. In turn, the healthcare savings generated by biosimilars can create “legroom” for healthcare budgets to be invested in next-generation innovations, such as cell and gene therapies, that can tackle diseases with high unmet needs.

And we should not forget that innovation happens not just in orphan or rare disease areas with no viable treatment but also in therapeutic areas with viable treatments, where innovation is driven by competition among biosimilars as well as between biosimilars and reference biologics. Biosimilars are not just biologics that “replicate” reference products; biosimilar companies seek to improve their products by adding value-added features around biosimilar formulation and/or devices.

At Samsung Bioepis, we believe in the value of biosimilars: by being more affordable, they are the pressure valve that allows innovations in next-generation biologics. And by stimulating market competition, biosimilars drive the market to seek higher-quality biologics with value-added features through innovative use of science and technology.

Dirk Gevers, Ph.D., Chief Scientific Officer, Seed Health

Undoubtedly, the microbiome space promises the next generation of novel therapeutic targets and treatment modalities. Microbiome-modulating therapies for C. difficile infections have made the news lately, but targets across psychiatric, cardiovascular, and metabolic health have also seen an uptick in mechanistic insights.

At Seed Health, we’re working to realize the potential of microbes to steward the future of microbial intervention for both consumer probiotics and therapeutics. One area ripe for innovation is irritable bowel syndrome (IBS), a chronic disorder that impacts millions. While some aspects can be treated pharmacologically, treatment for many symptoms are limited to experimental dietary and lifestyle recommendations. Recently, the U.S. FDA authorized an IND to evaluate the impact of DS-01™ — our multi-strain 2-in-1 probiotic and prebiotic — on the gut microbiota of patients with IBS.

Another is vaginal health. While UTIs continue to impact millions of women worldwide, antibiotics are currently the only frontline treatment — despite the alarming rise in antibiotic resistance, infection recurrence, and patient side effects. Emerging from 15 years of research, our partner company, LUCA Biologics, develops living medicines targeting the vaginal microbiome for urogenital and reproductive health.

The final is mental well-being. The gut microbiome has emerged as one of the critical regulators of brain function, but existing treatments in mental health do not yet consider or target the underlying role of the gut microbiome. While research is still underway, the potential to modulate the gut microbiota for neuropsychiatric health could unlock a promising future for the millions who experience and suffer from these conditions.

Carsten Brunn, Ph.D., President and Chief Executive Officer, Selecta

The autoimmune disease space will see significant advancements due to the need for more tolerable and effective treatment options that mitigate unwanted immune responses. Autoimmune diseases afflict ~4.5% of the world population and more than 24 million people in the United States. The current standard of care is broad immunosuppression, which is often associated with side effects and leaves patients vulnerable to serious infection and malignancies. Targeted immune tolerance to autoantigens would provide a transformative solution for patients without the risks associated with immunosuppression. IL-2 therapies have gained traction due to their expansion of regulatory T (Treg) cells. Selecta’s approach co-administers IL-2 with our precision immune tolerance platform ImmTOR® (ImmTOR-ILTM). Not only does this approach expand Treg cells via IL-2, but the addition of ImmTOR® increases the magnitude and durability of antigen-specific Treg cells, providing targeted immune tolerance to autoantigens and avoiding chronic and systemic immune suppression. We are investigating ImmTOR® in primary biliary cholangitis (PBC), a chronic, progressive liver disorder where the immune system mistakenly attacks tissue in the liver, causing inflammation, damage, and scarring of the small bile ducts. Treatments to help slow progression and prevent complications are available. However, they ultimately fail to control PBC, and patients require a liver transplant. Co-administration of ImmTOR® with PDC-E2, the autoantigen implicated in PBC, has the potential to restore antigen-specific immune tolerance in the liver to directly address the precise cause and prevent liver transplant. Through ImmTOR®-driven antigen-specific immune tolerance, we have the potential to provide a true innovative solution for autoimmune disease.

Philip M. Toleikis, Ph.D., President and Chief Executive Officer, Sernova Corp.

The biopharma industry has always been one to push the envelope of better treatment options. Without innovation, modern medicine and patient care would remain stagnant to classic modalities that often leave much room for improvement. A prime example of this is the treatment for type 1 diabetes. Since the discovery of insulin in the early 20th century, little has been done to alter the way we treat diabetes to provide a significant improvement in quality of life and disease outcomes. Patients are reliant on multiple insulin injections daily, followed by repeated blood glucose checks to ensure that their blood sugar is in an acceptable range, and still the long-term prognosis for these people is poor.

At Sernova, we saw this unmet need and sought to develop a “functional cure” for insulin-dependent diabetes. We designed our Cell Pouch SystemTM, a small, implantable medical device with immune-protected therapeutic cells placed deep under the skin to create a vascularized, organ-like environment for new insulin-producing cells to produce insulin naturally as required, without the need for injections. To solve the limitation of donor islets used in our first clinical trials, which have already shown encouraging initial results, we partnered with Evotec to obtain a virtually unlimited supply of insulin-producing, ethically derived induced pluripotent stem cells (iPSCs), allowing us to potentially treat millions of people with insulin-dependent diabetes. As the cell therapeutics field evolves, I believe that we will see these treatment innovations leading to “functional cures” for a multitude of chronic diseases.

Carla Balch, Chief Executive Officer and Founder, Spesana

A rare disease often takes years and a highly innovative clinician to diagnose. Most clinicians are evaluating a symptom or symptom cluster based on their clinical education, patient population, and pharmaceutical education. If these mechanisms for diagnosing a rare disease are all there is, medical progress is stymied. Clinical education does not generally focus on the “rare” diagnosis, but the “most likely.” A clinician’s patient population likely cannot inform a “rare” diagnosis. Pharma education is not sufficient. Less than 10% of known rare disease have an approved treatment.  

With molecular diagnostics, it’s reasonable to expect valuable information from a molecular test result. But molecular testing is still not mainstream, and clinician ordering behavior varies widely. A multi-national study on molecular diagnostic uptake in oncology found, “across countries and cancer types, uptake rates for molecular testing ranged between two percent and 98 percent.”  If molecular testing is not better adopted in oncology, we have very little innovation that can take place for rare diseases.  

We need innovation to remove barriers to clinicians ordering molecular diagnostics from a clinical, operational, and financial perspective, paired with new solutions to support data-based decision making when a molecular diagnostic test result is received. The ability to find the smallest populations with rare disease requires automation, deep data, and simple-to-consume clinical hypothesis generation and, more importantly, corporate collaborations around innovation.

Tim Clackson, Ph.D., President and Chief Executive Officer, Theseus Pharmaceuticals

Addressing cancer treatment resistance is a major hurdle in the development of current therapies. Over the course of a patient’s life, most cancers will develop mutations that are resistant to treatment, rendering current therapies ineffective and leaving patients with little to no options. These mutations can present a “whack-a-mole” problem, as new mutations crop up in response to each line of targeted therapy. I am hopeful that researchers will prioritize the development of effective treatments that tackle treatment resistance by targeting both cancer-causing and resistance mutations that arise.

Gastrointestinal tumors (GIST) represent a perfect example — it is an area of high unmet medical need largely driven by known mutations in a single protein called KIT. Even though we know how this cancer tends to mutate in response to each successive line of targeted therapy, there isn’t yet a drug that effectively addresses GIST in the face of all possible mutations that can emerge. Therefore, patients often progress through successive lines of treatment as their cancer develops resistance to each line until they run out of targeted treatment options. We see this phenomenon in other cancers as well, including in subsets of non-small cell lung cancer (NSCLC).

At Theseus Pharmaceuticals, we aim to outsmart treatment resistance in these cancers by developing small molecule “pan-variant inhibitor” therapies that successfully target cancer cells in the face of any cancer-causing and resistance mutations with a single agent. We believe that effective drugs in this space must be rationally designed to be effective against all known mutations instead of attacking only a few mutations at a time.

James Peterson, Global Vice President of Pharmaceutical Ingredients, Univar Solutions

The orphan space represents significant future growth for the pharma industry. Recent data show that more than 50% of drugs approved by the U.S. FDA in the last two years are used to treat rare diseases.   Univar Solutions supports the rare disease sector no differently than we support organizations focused on treating common illnesses.

Regarding unmet medical needs, it seems that biopharmaceuticals can’t reach the market fast enough, because many ingredients and excipients used in these applications haven’t been qualified yet. Suppliers that produce these ingredients and excipients are working to expand and accelerate the qualification of their biopharmaceutical ingredient and excipients portfolios. We need to give the medical community access to more excipients and ingredients to accelerate biopharmaceutical production and work with governing bodies to support this cause.

As these organizations reach commercialization, we work closely alongside them, sourcing the specialty excipients and ingredients that they require to bring products to market, including offering support with inventory planning and supply chain risk mitigation. As a value-added partner, there are instances where we have invested in our infrastructure to accommodate the unique ingredient handling needs that our customers in the orphan space have in order to do our part to help keep communities healthy.

Weichang Zhou, Ph.D., Chief Technology Officer and Executive Vice President, WuXi Biologics

A new generation of product modalities is being developed for the treatment of cancers, genetic diseases, neural degeneration diseases, and emerging infectious diseases. These modalities include monoclonal antibodies, antibody–drug conjugates, bispecific or multispecific antibodies, CAR-T cell therapies, and gene therapies, including mRNA. While more and more antibody-based molecules have been used for treating blood and solid cancers, new CAR-T cell therapies have recently been approved for rare blood cancer treatment. Gene therapies are being developed for the treatment of orphan diseases due to genetic defects that deliver certain genes into the cells via viral vectors, and vaccines act by delivering mRNA encapsulated by lipid nanoparticles (LNP-mRNA), which produce certain proteins, into the body. With the recent broad successes in using adenovirus vectors and LNP-mRNA encoding a subunit of the SARS-CoV-2 virus for the development of vaccines against COVID-19, now used globally, these innovations are now being adopted to develop both prophylactic and therapeutic treatments for other infectious diseases, rare diseases, and cancers. Manufacturing this new generation of complex product modalities requires innovative bioprocessing technology platforms. The biopharmaceutical industry needs to further rise to meet these new challenges in developing comprehensive manufacturing technologies to produce these therapeutics and vaccines faster and more cost-effectively than thought possible just a couple of years ago.

Paula Ragan, Ph.D., Chief Executive Officer and President, X4 Pharmaceuticals

There is an exciting and growing clinical pipeline of rare disease drugs, with more than 700 candidates in development for a broad range of diseases, including rare cancers and autoimmune, infectious, and neurologic diseases, among many others. Disease selection for rare disease drug development is informed by the unmet need, with priorities in many cases given to diseases with the most severe presentation or highest prevalence. However, the key and most relevant aspect is disease knowledge. As such, the largest treatment innovations will most likely continue to be for those rare diseases where we have gained the most understanding of the underlying cause of disease, which will enable the screening and development of novel drugs that tackle the specific pathways to provide disease-modifying treatments versus tackling symptoms individually. Luckily, advances in genomics and technological tools are speeding up our understanding of the genetic factors of these diseases. At X4, our lead drug candidate, for instance, could potentially be the first disease-modifying treatment for the rare immunodeficiency WHIM syndrome, which typically results from mutations in a gene called CXCR4 that is involved in healthy maturation and trafficking of white blood cells. In parallel to our regulatory pathway, with anticipated phase III data in the fourth quarter of 2022, we continue to prioritize novel research to better elucidate genetic variants associated with the disease to increase our ability to identify undiagnosed patients and explore new rare disease indications that could benefit from mavorixafor’s mechanism of action. In addition to treatment innovation, I anticipate that there will be an increasing effort by biopharmaceutical industries to access the large undiagnosed rare disease population that could benefit from promising treatments.

Diem Nguyen, Ph.D., Chief Executive Officer, Xalud Therapeutics, Inc.

There have been significant advancements in nucleic acid–based therapeutics, including mRNA-based COVID-19 vaccines and AAV-based gene therapies for rare diseases. This has resulted in interest in other nucleic acid delivery modalities, which have advantages over RNA and viral approaches. This era of non-viral DNA-delivered therapeutics has the potential to allow for gene therapies to be developed for diseases that affect larger patient populations.

At Xalud, we’ve developed XT-150, a locally injectable plasmid DNA (pDNA) gene therapy that expresses IL-10v, a proprietary version of the cytokine IL-10. XT-150 enables the body to supplement IL-10 locally at the site of inflammation and break the proinflammatory cycle. In addition, since XT-150 uses pDNA delivery, it doesn’t have the safety issues that the viral approach has presented, such as genomic integration and immune response. Xalud has a robust pipeline across multiple inflammatory and neurological indications, with a lead program in osteoarthritis of the knee in phase IIb. In multiple clinical studies completed to date, XT-150 has demonstrated durable efficacy, no dosing restrictions, and a highly favorable safety profile.

In the years ahead, we believe that through non-viral approaches, gene therapy will continue to expand beyond rare monogenic conditions to highly prevalent diseases that affect tens of millions of patients, with the hope of providing new treatment modalities for them globally.

Nice Insight

Nice Insight, established in 2010, is the research division of That’s Nice, A Science Agency, providing data and analysis from proprietary annual surveys, custom primary qualitative and quantitative research as well as extensive secondary research. Current annual surveys include The Nice Insight Contract Development & Manufacturing (CDMO/CMO), Survey The Nice Insight Contract Research - Preclinical and Clinical (CRO) Survey, The Nice Insight Pharmaceutical Equipment Survey, and The Nice Insight Pharmaceutical Excipients Survey.