Oncology Drug Discovery: Key Preclinical Small Molecule Candidates from Leading Biotech Companies

Introduction

Oncology drug discovery is transforming profoundly, with innovative technologies and strategies reshaping how cancer therapies are developed. The field is driven by small—to medium-sized biotech companies that are pushing the boundaries of science to address one of the most complex diseases known to humanity. From AI-assisted drug discovery to advancements in immunotherapy, a multitude of new approaches are emerging, creating a more dynamic and multidimensional approach to cancer treatment.

One of the critical drivers behind this transformation is the integration of cutting-edge artificial intelligence (AI). Traditionally, oncology drug discovery was a time-intensive and laborious process, often spanning over a decade from discovery to commercialization. However, AI is revolutionizing this by enabling rapid analysis of vast biological datasets, predicting drug interactions with cancer cells, and designing novel molecules that traditional methods may have missed. AI’s predictive power is now accelerating preclinical development and improving the precision of cancer treatments.

At the same time, precision oncology redefines the therapeutic landscape by tailoring cancer treatments to an individual’s genetic profile. With the help of genomic sequencing, researchers can identify specific mutations driving cancer growth, allowing the development of targeted therapies that directly attack these mutations. This precision offers more effective treatments while reducing side effects, marking a shift towards a more personalized and patient-centered approach.

Another essential element driving oncology drug discovery is the focus on the tumor microenvironment. Researchers have realized that treating the tumor alone is not enough, as the surrounding cells, immune components, and blood vessels play a critical role in cancer’s progression and resistance to therapy. By modulating the tumor microenvironment, scientists can make tumors more susceptible to therapies, particularly immunotherapies, which are gaining ground as powerful weapons against cancer.

Moreover, the development of targeted protein degradation presents an exciting avenue in oncology. Unlike traditional small molecule inhibitors, which block protein function, targeted protein degraders such as PROTACs work by removing disease-causing proteins entirely from cancer cells. This novel approach unlocks previously undruggable targets, offering new hope for cancers driven by proteins that have long been difficult to inhibit.

Another pivotal development has been the rise of immuno-oncology and therapies such as CAR-T cell therapy. By harnessing the body’s immune system to recognize and destroy cancer cells, these therapies are not only extending lives but also offering the possibility of long-term remission. CAR-T therapy, in particular, has shown remarkable success in treating blood cancers like leukemia and lymphoma and is now being adapted for solid tumors, which have proven more challenging. immuno-oncology and therapies such as CAR-T cell therapy has been another pivotal development. By harnessing the body’s immune system to recognize and destroy cancer cells, these therapies are not only extending lives but offering the possibility of long-term remission. CAR-T therapy, in particular, has shown remarkable success in treating blood cancers like leukemia and lymphoma and is now being adapted for solid tumors, which have proven more challenging.

From a financial standpoint, oncology remains one of the most attractive areas for investment in the pharmaceutical and biotech industries. Billions of dollars are being funneled into these emerging technologies. Venture capital firms and pharmaceutical giants recognize the transformative potential of AI, immunotherapy, and targeted treatments, pouring resources into early-stage biotech companies with promising pipelines. For example, Relay Therapeutics has raised over $ 900 million to fund its pioneering work on small molecule cancer therapies, while Kymera Therapeutics raised $225 million in a public offering to support its innovative protein degradation technologies.

Overall, the rapid pace of technological advancement and substantial financial backing create an unprecedented environment of innovation in oncology drug discovery. Biotech companies are not only advancing promising new therapies but are also reshaping the very foundation of how cancer is understood and treated. This multi-angled approach—leveraging AI, precision medicine, the tumor microenvironment, protein degradation, and immuno-oncology—is giving rise to the next generation of cancer therapies with the potential to offer more personalized, effective, and less toxic treatments for patients worldwide.

Leading Biotech Innovators: Preclinical Pipelines and Financial Backing

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1. Odyssey Therapeutics

• Candidate  Overview: Odyssey Therapeutics is focused on developing small-molecule therapies that target previously undruggable pathways in solid tumors. Their pipeline emphasizes modulating immune pathways and signaling in the tumor microenvironment.
• Current Progress: Odyssey’s oncology programs are still in preclinical stages but are centered on modulating novel biological pathways that have been difficult to target with traditional therapies. Their focus includes immune checkpoint modulation and tumor microenvironment targeting, which could offer a new approach to treating solid tumors like melanoma, lung cancer, and colorectal cancer.
• Funding: Odyssey Therapeutics raised $168 million in an oversubscribed Series B round in 2022, bringing their total raised to over $386 million across financing rounds. This funding will accelerate the advancement of Odyssey's oncology and immunology pipelines, bringing their innovative small molecules closer to clinical trials.
• Learn more: Odyssey Therapeutics Pipeline

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2. Relay Therapeutics

• Candidate: RLY-4008 (lirafugratinib)
   
  • Overview: RLY-4008 is one of Relay Therapeutics' most promising candidates. It is a selective FGFR2 (fibroblast growth factor receptor 2) inhibitor designed to target tumors driven by FGFR2 alterations, including cholangiocarcinoma, breast cancer, and gastric cancer. Unlike pan-FGFR inhibitors, RLY-4008 demonstrates high selectivity, reducing the risk of side effects caused by off-target inhibition of FGFR1, FGFR3, and FGFR4.
   
  • Current Progress: RLY-4008 has shown remarkable results in preclinical studies, with selective inhibition of FGFR2-driven tumors and minimal impact on other FGFR family members. This makes RLY-4008 particularly valuable for treating FGFR2-altered cancers with limited treatment options. The candidate has also demonstrated strong activity against FGFR2 mutations, amplifications, and fusions.
   
  • Funding: Relay Therapeutics has raised over $900 million, with significant investments coming from a $400 million IPO in 2020. These funds have allowed Relay to advance multiple small molecule programs, including RLY-4008, through preclinical and early clinical trials. Relay aims to transform oncology drug discovery with the support of this financial backing.
 
• Learn more: Relay Therapeutics Pipeline

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3. Accent Therapeutics

• Candidate: RNA-Modifying Protein (RMP) Inhibitors some text
   
  • Overview: Accent Therapeutics is advancing small molecules that inhibit RNA-modifying proteins (RMPs), which play a critical role in cancer progression. By targeting these proteins, Accent aims to develop therapies for aggressive cancers such as leukemia and solid tumors.
   
  • Funding: Accent secured $63 million in Series B funding, which will help drive its preclinical RMP inhibitor programs forward.
 
• Learn more: Accent Therapeutics Pipeline

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4. Bicycle Therapeutics

• Candidate: Bicycles® (Bicycle-PROTAC Conjugates)
   
  • Overview: Bicycle Therapeutics is developing a class of small molecules known as Bicycles, which are highly specific for cancer-related targets. These molecules offer a novel approach by selectively binding to proteins involved in cancer progression and degradation. Bicycles are being explored as treatments for various cancers, including melanoma, prostate cancer, and other solid tumors. Their small size allows them to penetrate tumors more effectively than larger molecules.
   
  • Current Progress: Bicycle Therapeutics has developed preclinical candidates that have demonstrated the ability to target and degrade proteins involved in tumor growth. These Bicycles hold the potential for better tumor selectivity and fewer side effects compared to traditional therapies. Bicycle’s programs are in pre-clinical stages, but the data collected thus far show strong potential for clinical translation.
   
  • Funding: Bicycle Therapeutics raised $60 million in a 2020 follow-on offering after their $60.5 million IPO in 2019. These funds have enabled the company to expand its oncology pipeline and push preclinical candidates toward clinical development.
 
• Learn more: Bicycle Therapeutics Pipeline

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5. Kymera Therapeutics

• Candidate: KT-333 (STAT3 Degrader)
   
  • Overview: Kymera’s KT-333 is a small molecule designed to degrade STAT3, a protein implicated in the survival and growth of many cancers, including lymphomas and certain solid tumors. The company’s approach uses targeted protein degradation to inhibit cancer growth.
   
  • Funding: Kymera Therapeutics has significantly bolstered its financial foundation through a series of successful public offerings and funding rounds. As of January 2023, the company closed an upsized public offering of $225 million, adding to its financial resources to advance its drug discovery and development efforts. This follows the company's previous $174 million IPO in 2020 and a $102 million Series C prior to going public.
• Learn more: Kymera Therapeutics Pipeline

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How ARSI Canada Can Support Biotech in Oncology

At ARSI Canada, we offer a comprehensive range of services tailored to biotech companies involved in oncology drug discovery. Our expertise in custom synthesis, analytical development, and bioanalytical method development & validation helps streamline the development of preclinical candidates, from early discovery to clinical readiness.

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Conclusion

The biotech companies highlighted in this blog—Odyssey Therapeutics, Relay Therapeutics, Accent Therapeutics, Bicycle Therapeutics, and Kymera Therapeutics—are at the forefront of oncology drug discovery, developing innovative small molecule therapies with substantial financial backing. These developments promise to reshape cancer treatment by offering more targeted and effective therapies.