T790M

• The same forces that turned dinosaurs into birds turn normal cells into cancer: genetic mutations and traits that confer a survival advantage.
• Evolution in animals is largely driven by mutations in the DNA of germ cells – the sperm and egg that fuse to form an embryo.
• We believe that understanding evolution is key to understanding how cancer arises and how to treat it.

Timing is of the essence

• However, if one survives and duplicates itself many times over, it can form a tumor made of multiple mutant cells.
• These tumor cells continue to reproduce and mutate, evolving until the tumor ultimately gains the ability to spread throughout the body.
• Precancerous polyps are easily removed during colonoscopy screenings, preventing them from evolving to invasive colon cancer.

Different cancers require different treatments

• In general, cancers from different organs look distinct from one another and contain different proteins.
• Tumors arising in a given organ also tend to have mutations in the same set of genes, even among different patients.
• For example, thyroid cancers typically have a low number of mutations while colon cancers have many mutations, a number that is increased dramatically in tumors that have lost genes involved in DNA repair.
• However, thyroid cancer and melanoma respond minimally to chemotherapy and require different approaches.

Treatments can drive cancer evolution

• Treatment can also push cancer to evolve further, gaining advantageous mutations that help them survive and resist therapy.
• For example, a subset of lung cancers is driven by mutation in a gene called EGFR.
• Similarly, metastatic prostate cancer is often treated with drugs that block androgen receptors, because it depends on them for growth and survival.

Not an easy fight

• The fight against cancer is a fight against evolution, the fundamental process that has driven life on Earth since time immemorial.
• This is not an easy fight, but medicine has made tremendous progress.
• Much of this is attributable to cancer screening programs and recently developed, more effective drugs.

• THE-630 is a pan-variant inhibitor of the receptor tyrosine kinase KIT, designed for patients with gastrointestinal stromal tumors (GIST) which have developed resistance to earlier lines of therapy.
• Theseus is treating patients in cohort 5 of dose escalation as of the end of 2022.
• Based on clinical data from the ongoing Phase 1/2 study, Theseus plans to pursue parallel registration trials in second- and fifth-line patients with advanced GIST.
• "Today, we are happy to introduce BCR-ABL as the target for our next development program," said Bill Shakespeare, Ph.D., Co-Founder and President of R&D at Theseus.

• The data will be presented at the 2022 Annual Meeting of the American Association for Cancer Research (AACR), April 8-13, 2022 in New Orleans.
• H002 will initially be evaluated for treating C797S mutation-driven resistance to EGFR TKIs in NSCLC.
• H002 is the first drug candidate expected to enter clinical trials from RedCloud Bio's pipeline.
• RedCloud Bio is developing a fourth-generation EGFR inhibitor, H002, with a wide spectrum and high selectivity to address the growing unmet needs in NSCLC patients harbouring C797S mutation.

• "Our preclinical studies have shown that EO1001 is potent against multiple activating mutations in the intracellular domain of EGFR.
• The Phase I/IIa clinical trial will enroll up to 50 patients and is being conducted in Australia under contract service provided by Senz Oncology Pty Ltd.
• The objective of this first-in-human clinical trial is to examine the safety and tolerability of EO1001 in patients with metastatic or advanced stage ErbB-1(EGFR), ErbB-2(HER2) and/or ERbB-4 (HER4) positive cancer.
• On February 9, 2021, Edison Oncology and Apollomics announced an exclusive licensing agreement whereby Apollomics will develop and commercialize EO1001 (APL-122) globally, except in Mainland China, Hong Kong and Taiwan.