Breakthrough Clinical Results
RyboDyn, a biotechnology company developing first-in-class immunotherapies targeting the 'dark proteome' (previously uncharacterized proteins), has been selected to join Lilly Gateway Labs (LGL). This collaboration provides RyboDyn with access to Eli Lilly and Company's resources to advance its lead programs. RyboDyn's platform, RyboCypher™, identifies cancer-specific targets abundantly expressed on the cell surface. The company's work, partly conducted with Moffitt Cancer Center, shows these targets are conserved across patients, making them promising for precision immunotherapies. The LGL residency accelerates RyboDyn's progress toward first-in-human studies and strengthens its pursuit of strategic partnerships.
Key Highlights
- RyboDyn selected to join Lilly Gateway Labs (LGL)
- Access to Eli Lilly's scientific and business network
- Focus on developing first-in-class immunotherapies targeting the 'dark proteome'
- Collaboration with Moffitt Cancer Center demonstrates conserved cancer-specific targets
Incidence and Prevalence
Global Cancer Statistics (2022):
- New Cases: Close to 20 million new cancer cases were estimated in 2022, including non-melanoma skin cancers (NMSCs).
- Deaths: Approximately 9.7 million deaths from cancer occurred in 2022, including NMSCs.
- Lifetime Risk: Roughly one in five men or women develop cancer during their lifetime.
- Mortality Risk: About one in nine men and one in 12 women die from cancer.
Most Frequent Cancers (2022):
-
Lung Cancer: The most frequently diagnosed cancer and leading cause of cancer death globally.
-
New cases: 2.5 million (12.4% of all cancers)
-
Deaths: 1.8 million (18.7% of cancer deaths)
-
Breast Cancer: Most frequent cancer in women (both cases and deaths).
-
New cases: 2.3 million
-
Deaths: 0.67 million
-
Colorectal Cancer:
-
New cases: 1.9 million (9.6% of all cancers)
-
Deaths: 0.93 million (9.3% of cancer deaths)
-
Prostate Cancer: Most commonly diagnosed cancer in men after lung cancer.
-
New cases: 1.47 million (7.3% of all cancers)
-
Stomach Cancer:
-
New cases: 1 million (4.9% of all cancers)
-
Deaths: 0.77 million (6.8% of cancer deaths)
Geographic Variability:
Incidence rates (including NMSC) varied significantly across world regions, with four- to five-fold differences observed. The highest incidence rates were found in Australia/New Zealand, while the lowest were in Western Africa (men) and South-Central Asia (women).
Future Projections:
Demographic projections suggest a substantial increase in the global cancer burden by 2050, with an estimated 35 million new cases and 18.5 million deaths. This increase is expected to disproportionately affect low-HDI countries, where cancer cases and deaths are projected to nearly triple.
Key Observations:
- Lung cancer remains a major global health concern, being both the most common cancer and the leading cause of cancer death.
- Breast cancer is the most frequent cancer in women, highlighting the need for continued focus on prevention, early detection, and treatment.
- Significant disparities in cancer incidence and mortality exist across different regions and socioeconomic groups, emphasizing the importance of equitable access to cancer care.
- The projected increase in the global cancer burden underscores the urgency of investing in prevention and control efforts, including targeting key risk factors such as smoking, obesity, and infections.
Emerging Mechanism of Action
Advances in Cancer Treatment Mechanisms of Action (MoA)
Recent publications in PubMed highlight several key mechanisms of action (MoA) emerging in cancer treatment over the past few years. These MoAs reflect a shift towards more targeted and personalized approaches, aiming to improve efficacy and reduce side effects compared to traditional methods like chemotherapy and radiotherapy.
-
Targeted Therapies: These therapies focus on specific molecular vulnerabilities within cancer cells, maximizing tumor cell death while minimizing harm to healthy cells. Examples include:
-
Kinase inhibitors: These drugs target specific kinases, enzymes involved in cell signaling pathways that regulate cell growth and proliferation. Kinase inhibitors are the dominant product class by the number of approved products and indications.
-
VEGF/VEGFR pathway inhibitors: These agents target vascular endothelial growth factor (VEGF) and its receptors (VEGFR), which play a crucial role in angiogenesis, the formation of new blood vessels that tumors need to grow and spread. Over a dozen drugs targeting this pathway have been approved for approximately 20 solid tumor types, often in combination with other therapies. While initially designed to starve tumors, these agents also normalize tumor vessels, potentially improving treatment outcomes. A key development is the combination of VEGF/VEGFR pathway inhibitors with immune checkpoint blockers, with seven such combinations approved by the FDA in the past 3 years.
-
Hormonal therapies: For hormone-sensitive cancers like breast and prostate cancer, hormonal therapies aim to block the effects of hormones that fuel cancer growth. For ER-positive early breast cancer, endocrine therapy for 5-10 years is essential. In advanced breast cancer, endocrine therapy is combined with targeted agents like CDK4/6 inhibitors and PI3K inhibitors.
-
PARP inhibitors: These drugs target poly(ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair. PARP inhibitors are particularly effective in cancers with defects in other DNA repair pathways, such as those with BRCA1/2 mutations.
-
Immunotherapy: This approach harnesses the power of the patient's own immune system to fight cancer. Key examples include:
-
Immune checkpoint inhibitors: These drugs block immune checkpoints, molecules that normally suppress immune responses. By blocking these checkpoints, immune checkpoint inhibitors can unleash the anti-tumor activity of T cells. These have seen the second most approvals since 2011, and are often combined with other therapies, such as VEGF/VEGFR pathway inhibitors.
-
CAR T-cell therapy: This innovative therapy involves genetically engineering a patient's T cells to express chimeric antigen receptors (CARs) that recognize specific tumor antigens. These modified CAR T cells are then infused back into the patient, where they can target and destroy cancer cells. Advances in CAR T-cell therapy include understanding how various molecular modules of the CAR influence signaling and function, as well as developing strategies to overcome toxicity and resistance.
-
Other Emerging Approaches:
-
Antibody-drug conjugates (ADCs): These combine the targeting ability of antibodies with the cell-killing power of cytotoxic drugs, delivering potent therapies directly to cancer cells.
-
Epigenetic modifiers: These drugs target epigenetic mechanisms, which regulate gene expression without altering the DNA sequence itself. Epigenetic modifiers can be used to reactivate silenced tumor suppressor genes or inhibit oncogenes.
-
Nanoparticles: These tiny particles can be used to deliver drugs, imaging agents, or other therapeutic payloads directly to tumors, improving efficacy and reducing side effects.
-
Stem cell therapy: This approach shows promise in regenerating and repairing diseased or damaged tissues by targeting both primary and metastatic cancer foci.
-
Ablation therapy: This minimally invasive procedure burns or freezes cancers without the need for open surgery.
-
Natural antioxidants: These substances can track down free radicals and neutralize their harmful effects, potentially treating or preventing cancer.
The development of biomarkers is crucial for identifying patients most likely to benefit from these targeted therapies. The lack of biomarkers for effective patient selection remains a challenge, particularly for cancers like small-cell lung cancer (SCLC). Emerging single-cell RNA sequencing data are providing insights into tumor heterogeneity and plasticity, which may help identify new biomarkers and therapeutic targets.
Overall, the cancer treatment landscape is rapidly evolving, with a growing emphasis on personalized medicine. The increasing rate of oncology indication approvals, driven by targeted therapies and new therapeutic approaches, offers hope for improved outcomes for cancer patients.
Company Mechanism of Action
The provided text does not contain information about drugs from RyboDyn, Inc. Therefore, I cannot describe their mechanisms of action.
However, the text does discuss the mechanisms of action of several other types of drugs, including:
- Pirfenidone (PFD): This drug is used to treat idiopathic pulmonary fibrosis. Its primary mechanism of action involves modulating fibrogenic growth factors, leading to a reduction in fibroblast proliferation, myofibroblast differentiation, collagen and fibronectin synthesis, and extracellular matrix deposition. This is achieved by suppressing TGF-β1 and other growth factors. PFD also exhibits anti-inflammatory and antioxidant properties. It downregulates inflammatory pathways, targets inflammasome pathways, inhibits redox reactions, and regulates oxidative stress-related genes and enzymes.
- Nintedanib: Also used for idiopathic pulmonary fibrosis, nintedanib reduces the expression of collagen I and V, fibronectin, and FKBP10, and attenuates the secretion of collagen I and III. Like pirfenidone, it inhibits collagen I fibril formation and alters the appearance of collagen fibril bundles.
- Antiseizure drugs (ASDs): These drugs work through four main mechanisms: (1) modulating voltage-gated sodium, calcium, and potassium channels; (2) enhancing GABA-mediated inhibitory neurotransmission; (3) attenuating glutamate-mediated excitatory neurotransmission; and (4) modulating neurotransmitter release via a presynaptic action.
- Antipyretics (e.g., aspirin): These drugs primarily inhibit the enzyme cyclooxygenase, reducing prostaglandin E(2) levels in the hypothalamus, which in turn lowers body temperature. Other proposed mechanisms include reducing proinflammatory mediators, enhancing anti-inflammatory signals, and boosting antipyretic messages in the brain.
- Glycopeptide antimicrobials (e.g., vancomycin): These drugs inhibit bacterial cell-wall synthesis by binding to the d-alanyl-d-alanine terminus of the lipid II bacterial cell-wall precursor, preventing cross-linking of the peptidoglycan layer. Newer lipoglycopeptide derivatives may have additional mechanisms of action.
- Antidepressants (e.g., SSRIs): These drugs primarily act as neurotransmitter uptake blockers, enzyme inhibitors, and neurotransmitter receptor blockers, with variations in their pharmacokinetics and effects on CYP450 enzymes.
- Immunosuppressants (e.g., cyclosporine, tacrolimus): These drugs target different sites in the T-cell activation cascade. They can be classified as inhibitors of transcription, nucleotide synthesis, growth factor signal transduction, or differentiation. Some may also stimulate the expression of immunosuppressive molecules or cells.
- Designer drugs: These drugs mimic the effects of traditional drugs of abuse, acting on various receptors and neurotransmitter systems, such as monoamine transporters (stimulants), μ-opioid receptors and GABA receptors (sedatives), N-methyl-D-aspartate receptors (dissociatives), cannabinoid type 1 receptors (synthetic cannabinoids), and serotonergic 5-HT2A receptors (psychedelics).
- Antibiotics: These drugs target bacteria through four main mechanisms: inhibiting cell wall synthesis, disrupting protein synthesis, interfering with nucleic acid synthesis, and disrupting metabolic pathways. However, antibiotic resistance is a growing concern.
- Small molecule drugs: These drugs target specific proteins and affect molecular pathways. Their low molecular weight allows them to easily penetrate cells. They can be designed rationally or isolated from natural resources.
If you have questions about the mechanisms of action of specific drugs not made by RyboDyn, Inc., please provide the drug names, and I will do my best to answer based on the information available in the provided text.
Company drugs in pipeline
RyboDyn, Inc. primarily focuses on developing immunotherapies for cancer. Their novel approach targets the "dark proteome", an expansive and largely uncharted realm of cancer-specific proteins. They have identified over 1,000 novel cancer-specific peptides, with multiple confirmed by secondary analyses.
While their main focus is cancer, their technology has the potential to address a wide range of other diseases as well. They aim to build a premier pipeline of first-in-class, next-generation immunotherapies, developed both internally and in partnership with large pharmaceutical companies.