-- STX-721 demonstrates potential best-in-class selectivity and strong anti-tumor activity across multiple EGFR and HER exon 20 mutant CDX and PDX models --

-- Investigational new drug (“IND”) application submission expected in 2023 --

Scorpion Therapeutics, Inc. (“Scorpion”), a pioneering oncology company redefining the frontier of precision medicine through its Precision Oncology 2.0 strategy, today announced preclinical proof-of-concept data for STX-721, the Company’s first development candidate from its STX-EGFR-EXON-20 program. STX-721 is a next-generation, orally delivered therapy, designed with potential best-in-class selectivity for exon 20 insertion mutations in epidermal growth factor receptors (“EGFR”), a well-known, clinically validated oncogenic driver in non-small cell lung cancer (“NSCLC”). The data will be presented today in a poster session at the European Organisation for Research and Treatment of Cancer, the National Cancer Institute, and the American Association for Cancer Research (“EORTC-NCI-AACR”) Symposium 2022 in Barcelona, Spain.

“We are excited to share the first preclinical data for STX-721, our next-generation, highly-differentiated EGFR exon 20 inhibitor,” said Axel Hoos, M.D., Ph.D., Chief Executive Officer of Scorpion. “The discovery and progression of this development candidate in less than two years is further validation of our Precision Oncology 2.0 strategy, designed to exceed the speed, efficiency and quality of traditional target and drug discovery approaches. The data presented at EORTC-NCI-AACR support our selection of STX-721 as our second clinical program, demonstrating potentially best-in-class selectivity that we anticipate will result in a wider therapeutic index and greater efficacy compared to currently marketed therapies and other drug candidates in development. We look forward to submitting an IND application for STX-721 next year, as we aim to transform the lives of thousands of people living with exon 20 insertion mutant EGFR-driven NSCLC who are underserved by existing therapeutics.”

NSCLC is the most common form of lung cancer and EGFR mutations are one of the most common mutations in NSCLC. For cancers resulting from an EGFR L858R or exon 19 deletion, osimertinib is a highly selective EGFR mutation-targeting therapy, which achieves a high and durable objective response rate (“ORR”) of approximately 80 percent.¹ Commercially available therapies for NSCLC patients with EGFR exon 20 insertion mutations have more moderate clinical efficacy (28-40% ORR^2,3) and are further limited by significant toxicities associated with the inhibition of wild-type EGFR in healthy tissues such as the skin and GI tract. These toxicities can lead to dose reductions or interruptions which in turn, may reduce the overall efficacy of the treatment.

In the poster presented at EORTC-NCI-AACR, Scorpion scientists will share data from preclinical studies evaluating STX-721 across a broad panel of exon 20 mutant cell lines, with the high selectivity of osimertinib against EGFR T790M mutant cells used as a benchmark for EGFR mutant selectivity. In these studies, STX-721 demonstrated strong EGFR exon 20 mutant potency and selectivity in isogenic Ba/F3 models and human cancer cell lines, as well as signaling and biochemical assays. Importantly, the selectivity of STX-721 for EGFR exon 20 was observed to well exceed that of clinical-stage competitor benchmarks in each of these model systems, while also approaching the selectivity of osimertinib against EGFR L858R and exon 19 deletion mutations.

In addition, STX-721 demonstrated strong in vivo anti-tumor activity across a variety of EGFR and HER2 exon 20 mutant cell line-derived xenograft (“CDX”) and patient-derived xenograft (“PDX”) models. STX-721 also demonstrated a clear exon 20 genotype-selective in vivo efficacy window in isogenic cancer CDX models, which was not observed with clinical-stage competitor benchmarks. All efficacious and in vivo selective doses of STX-721 were well-tolerated throughout these preclinical studies.

“Leveraging our prowess in covalent drug discovery, a foundational pillar of our drug-hunting platform, we developed an entirely new chemical scaffold for our STX-EGFR-Exon-20 program. This allowed us to overcome the lack of intrinsic selectivity for exon 20 insertion mutations that has hindered most approved or investigational EGFR exon 20 inhibitors and to design a molecule with selectivity comparable to osimertinib, the standard-of-care therapy for patients with L858R or exon 19 deletion,” said Darrin Stuart, Ph.D., chief scientific officer of Scorpion Therapeutics. “The data presented at EORTC-NCI-AACR underscore STX-721’s potential to provide a best-in-class option for patients harboring cancers with EGFR exon 20 mutations, and we look forward to advancing our candidate to deliver a transformational therapy to this underserved population.”

Based on the data being shared at EORTC-NCI-AACR, Scorpion named STX-721 as the lead development candidate from its STX-EGFR-EXON-20 program in June 2022. STX-721 is currently advancing through preclinical development, with an investigational new drug application submission expected in 2023. Scorpion anticipates advancing STX-721 as a monotherapy and in relevant combinations with approved standard-of-care agents.

The poster presentation is now available here and under “Media” in the News section of Scorpion’s website: https://www.scorpiontx.com/news.

About Scorpion Therapeutics

Scorpion is a pioneering oncology company redefining the frontier of precision medicine to deliver optimized and transformational therapies for larger populations of patients with cancer, a strategy Scorpion refers to as Precision Oncology 2.0. Scorpion has built a proprietary and fully integrated platform of the most advanced technologies across cancer biology, medicinal chemistry, and data sciences, with the goal of consistently and rapidly creating exquisitely selective small molecule compounds against an unprecedented spectrum of targets. Scorpion aims to leverage its platform to advance a broad pipeline of wholly owned, optimized compounds across three target categories: best-in-class molecules targeting validated oncogene targets; first-in-class molecules for previously undruggable targets; and first-in-class molecules for novel cancer targets. For more information, visit www.scorpiontx.com.

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¹ N Engl J Med 2018; DOI: 10.1056/NEJMoa1713137

² Clin Cancer Res 2020; DOI: 10.1158/1078-0432.CCR-22-2072

³ J Clin Onc 2021; DOI: 10.1200/JCO.21.00662

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