Innovation Waves in Immuno-oncology Therapy Development

The Impact of the Top 3 Strategic Imperatives on the Immuno-Oncology (I-O) Therapeutics Industry

Competitive Intensity: Accelerated Drug Discovery and Precision Medicine Initiatives

• Why: The complexity and challenges of effective translation of I-O therapies, coupled with the saturation of companies in the immunomodulator space, are prompting partnerships to explore new modalities that can create a niche and help companies remain competitive.
• Frost Perspective: Companies need to explore innovative product development partnerships and diagnostics partnerships to succeed in this space. A lot of innovations are stemming from academia, and the licensing of technologies is on the rise. Several Tier I biopharma companies are expanding their I-O portfolio and diversifying their assets via acquisitions and licensing of platform technologies such as engineered cell lines, mRNA platforms, etc.

Disruptive Technologies: Advanced Gene-modified Cell Therapies

• Why: Immunotherapies have witnessed significant advances since their inception, and the focus is now on improving their safety, persistence, and efficacy. Advances in drug design, delivery, and the design of new platforms will support this. Therapies that can treat both hematological and solid tumors, and ones that are aggressive, are being developed.
• Frost Perspective: Advances in synthetic biology, integration of AI, advanced preclinical models (organs on chips), automation technologies, and gene editing tools are expected to enable I-O innovations to grow at a rapid pace and make them cost-friendly and accessible. The central stage of growth is expected to be driven by gene-modified cell therapies. This will include newer cell types, genetically engineered immune cells to improve persistence and reduce toxicity, and a growing balance between autologous and allogeneic cell therapies.

Industry Convergence: Multi-platform Collaborations

• Why: I-O therapy development is complex and expensive, and hence partnerships and strategic collaborations are inevitable in this space. Several technologies act synergistically to develop a successful product, and companies working on different types of platforms, both complementary and mutually exclusive, would be essential to driving growth.
• Frost Perspective: Collaborations are usually between pharma and biopharma companies with synthetic biology companies, diagnostics developers (companion diagnostics development), and drug discovery platform developers. The use of AI to improve the predictive ability of preclinical models, drug target discovery, and clinical trial design will be key to driving new therapies. Synthetic biology companies, mRNA developers, and traditional pharma could also find areas of convergence to co-develop combination therapies. Multi-platform collaborations are also enabling competitors to co-test and co-develop products at an accelerated pace.

Scope of Analysis

• I-O therapies refer to the treatment of cancers (both hematological and solid tumors) by harnessing the host's adaptive and immune systems that help recognize and destroy tumor cells. It is a targeted approach and one of the most promising therapeutic areas in oncology.
• Currently, immune checkpoint inhibitors (ICIs), which are considered the foundation of I-O, are the most widely developed class of I-O agents and have the maximum number of FDA-approved drugs, with applicability across multiple cancers, both solid and hematological.
• While immunotherapy is considered a pillar of cancer care, many aspects need to be optimized before it can become mainstream. With the growing incidence and prevalence of various types of aggressive and refractory cancers, there has been growth in the next-generation I-O pipeline.
• Chimeric antigen receptor (CAR)-T cell therapy and tumor-targeted antibody therapies, including monoclonals, antibody-drug conjugates (ADCs), bispecific antibodies, and several therapeutic cancer vaccines, are making rapid strides in clinical trials as effective immunotherapy.
• I-O therapy is generally used as a second line of treatment to treat metastatic cancers and refractory tumors. They are being increasingly included as an earlier line of treatment to improve patient outcomes.
• While immunotherapies are expected to overcome most challenges of conventional chemotherapy in terms of efficacy, selectivity, and safety, certain challenges, such as immune evasion, high costs, and the lack of durability of responses, remain. Spatio-temporal control of therapeutic delivery and making them more targeted and programmable is the aim of current I-O therapies in development.
• Improving the manufacturing of cell therapies and cancer vaccines could also pave the way for more accessible therapies. The manufacturing of CAR-T, ADCs, and viral vectors has been excluded from the study.

Growth Drivers

Neoantigen Discovery Advances:

New technology platforms for neoantigen discovery, identification, and screening could be useful for identifying patient-specific signatures to drive personalized therapies. There are promising pipelines for T cell therapy targeting neoantigens and mRNA vaccines targeting both personalized and public neoantigen signatures.

Significant Funding and Collaborations:

The momentum in the I-O space has increased, and this trend is likely to continue with several big biopharma companies collaborating to license assets and platforms from I-O-focused startups. Many VC investors are also backing cell therapy developers, ADC developers, and cancer vaccine companies such as Arsenal Bio, Iovance, Cellarity, Iksuda Therapeutics, and Mersana Therapeutics.

Advances in Delivery Systems:

The development of targeted delivery vehicles for antibodies and cell therapies is improving the performance and safety of I-O therapies and expanding their potential for the treatment of new cancers. Nanoformulations and R&D on delivery carriers such as exosomes, lipid nanoparticles (LNPs), and others aim to address the drawbacks of existing systems, such as poor stability, efficacy, targeting, and durability.

Improved and Decentralized Manufacturing:

Bioprocess improvements, along with the use of digitization and AI in process optimization and developments, are resulting in the efficient and cost-effective manufacturing of cell therapies and vaccines, which had been a challenge for several years. Along with this, decentralized manufacturing near the patient site is improving accessibility and reducing vein-to-vein time.

Growth Restraints

Restraint

High Costs: The high costs of immunotherapy have been a major limiting factor for adoption. While cell therapies are not accessible in most parts of the world, antibody therapies are also prohibitively expensive for many patients. Developing cost-effective technologies for R&D and manufacturing with pricing regulations would be an effective way to tackle the high costs.

Resistance Development: Tumors can evade the immune system in multiple ways to escape immune surveillance, leading to resistant metastatic tumors. The heterogeneity of the tumor microenvironment (TME), immune-suppressed TME, lack of inflammatory markers, and microsatellite instability (MSI) are a few features of resistance development. Many patients with "cold tumors" develop resistance to ICIs or relapse, which has prompted the development of next-gen strategies that can modulate tumors and make them amenable to immunotherapy.

Sluggish Clinical Translation: Hundreds of I-O therapies, especially cell therapies and cancer vaccines, have been under development for several decades. However, there are still very few FDA-approved products on the market. This slow clinical translation has stirred doubts and dampened developments. Effective preclinical models, drug delivery developments, and collaborations for combination approaches could accelerate the translation.

Clinical Study Design: I-O therapies act via multiple mechanisms of action, and developing standardized assays is a challenge. Measuring efficacy and safety with fixed clinical endpoints is also still a challenge. Patient recruitment bottlenecks and a lack of effective biomarkers for prediction are also limiting the effectiveness of clinical trial designs.