Notch-1

SAN DIEGO--(BUSINESS WIRE)-- DermTech International (NASDAQ: DMTK) (DermTech or the Company), a leader in precision dermatology enabled by a non-invasive skin genomics technology, today announced the presentation of two research abstracts at the 2024 American Academy of Dermatology (AAD) Annual Meeting, taking place March 8th-12th in San Diego, California. The first research abstract, “Non-invasive gene expression analyses to rule out melanoma in patients with Fitzpatrick skin types IV-VI” will be presented March 9th at 8:45am PT by Maral K. Skelsey, MD, lead author and Clinical Professor of Dermatology at Georgetown University’s Medical School. In this research, the negative predictive value (NPV) for both Fitzpatrick skin type group I-III and Fitzpatrick skin type group IV-VI was greater than 99%, and the 95% confidence interval indicated that there was no significant difference between the skin phototype groups. “This real-world clinical study demonstrates that the DMT can help clinicians improve outcomes for cutaneous melanomas in patients of all skin types,” commented Dr. Skelsey. “This is especially important because ruling out melanoma in individuals with Fitzpatrick IV-VI skin types can be particularly challenging.” The second research abstract titled, “Skin cancer risk is increased by somatic mutations detected noninvasively in healthy-appearing sun-exposed skin” will be presented March 9th at 10:05am PT by lead author John Whitaker, Ph.D., Senior Director of Bioinformatics at DermTech. The research found that somatic mutations in healthy-appearing sun-exposed skin indicate an increased risk for skin cancer. Furthermore, these mutations capture skin cancer risk information that is not accounted for by other risk factors. A complete description of this research has been accepted for publication in the Journal of Investigative Dermatology and will be published on March 19th: ( (24)00176-3/fulltext) This research study used non-invasively sampled DNA from healthy-appearing skin, in a reference cohort of 1,038 individuals, to measure the occurrence of somatic mutations at skin cancer-associated hotspots located within TP53 and NOTCH1. The number of detected mutations was combined with clinical variables known to be associated with skin cancer risk to create a skin cancer risk model (DNA-Skin Cancer Assessment of Risk, DNA-SCAR). DNA-SCAR’s risk calculation was validated by comparison to the U.S. population and was trained to predict personal history of skin cancer from age, family history, skin tone and mutation count. About DermTech DermTech is a leading genomics company in dermatology and is creating a new category of medicine, precision dermatology, enabled by its non-invasive skin genomics technology. DermTech’s mission is to improve the lives of millions by providing non-invasive precision dermatology solutions that enable individualized care. DermTech provides genomic analysis of skin samples collected using its Smart StickersTM. DermTech develops and markets products that facilitate the assessment of melanoma. For additional information, please visit DermTech. Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. The expectations, estimates, and projections of DermTech may differ from its actual results and consequently, you should not rely on these forward-looking statements as predictions of future events. Words such as “expect,” “estimate,” “project,” “budget,” “forecast,” ”aim,” “runway,” "outlook," “anticipate,” “intend,” “plan,” “strive," “may,” “will,” “sustain,” “could,” “should,” “believe,” “predict,” “potential,” “continue,” and similar expressions are intended to identify such forward-looking statements. These forward-looking statements include, without limitation, expectations and evaluations with respect to: the performance, patient benefits, cost- effectiveness, commercialization and adoption of DermTech’s products and the market opportunity for these products; expectations regarding DermTech’s potential growth, scale, patient reach, financial outlook, including its cash runway and future financial performance DermTech’s ability to increase its test volume, revenue and the proportion of reimbursed billable tests and control or reduce cost, expenses and cash burn, including as a result of DermTech’s recent restructuring actions; and expectations regarding agreements with or reimbursement or cash collection patterns from government payers (including Medicare) or commercial payers and related billing practices or number of covered lives. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from the expected results. Most of these factors are outside of the control of DermTech and are difficult to predict. Factors that may cause such differences include, but are not limited to: (1) the outcome of any legal proceedings that may be instituted against DermTech; (2) DermTech’s ability to obtain additional capital when and as needed or on acceptable terms; (3) the existence of favorable or unfavorable clinical guidelines for DermTech’s tests; (4) the reimbursement of DermTech’s tests by government payers (including Medicare) and commercial payers; (5) the ability of patients or healthcare providers to obtain coverage of or sufficient reimbursement for DermTech’s products; (6) DermTech’s ability to grow, manage growth and retain its key employees and maintain or improve its operating efficiency and reduce operating expenses; (7) changes in applicable laws or regulations; (8) the market adoption and demand for DermTech’s products and services together with the possibility that DermTech may be adversely affected by other economic, business, and/or competitive factors; (9) DermTech’s ability to continue as a going concern and (10) other risks and uncertainties included in the “Risk Factors” section of the most recent Annual Report on Form 10-K filed by DermTech with the Securities and Exchange Commission (the “SEC”), and other documents filed or to be filed by DermTech with the SEC, including subsequently filed reports. DermTech cautions that the foregoing list of factors is not exclusive. You should not place undue reliance upon any forward- looking statements, which speak only as of the date made. DermTech does not undertake or accept any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based.

Researchers used various sequencing technologies to explore the molecular characteristics of myeloid/natural killer cell precursor acute leukemia (MNKPL). They observed activation of the NOTCH1 and RUNX3 genes, with lower expression of the BCL11B gene. MNKPL cells were also highly sensitive to a drug called L-asparaginase. Collectively, these qualities make MNKPL distinct from other leukemia types. These insights will assist with more accurate clinical diagnoses and therapeutic development for MNKPL. Leukemia is a common term used to refer to a form of blood cancer. However, there are different types of leukemia depending on the cell type involved. One unique form is myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL). Because of its rarity, there is no consensus on the specific characteristics needed to clinically identify this disease. In a recent article published in Science Advances, a team led by researchers at Tokyo Medical and Dental University (TMDU) used various approaches to better assess the molecular pro drug sensitivity characteristics of MNKPL. MNKPL was only first proposed as a leukemia subtype in 1997. Extramedullary involvement is one of the hallmarks of MNKPL. It is prevalent in East Asian countries. Although the immunological phenotype of MNKPL was explored previously, a full genetic characterization of this cancer type had not been performed. These details would help support more accurate diagnoses for patients, which would lead to more appropriate therapeutic decisions. Therefore, the TMDU group aimed to investigate MNKPL on a single-cell level. "A single-cell exploration of MNKPL would not only help us better understand its clinical and genomic features, but also clarify the specific cellular origin of this disease," says Dr. Akira Nishimura, lead author of the study. The team first used what is known as a multiomics approach to investigate MNKPL patient samples. They used various sequencing technologies to determine if there were any relevant mutations in specific genes, look for expression differences in certain signaling pathways at the RNA level, and examine any unique DNA methylation patterns. "Our results demonstrate that MNKPL has molecular qualities that are distinct from other similar cancers, such as acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia," explains Dr. Masatoshi Takagi, senior author. "Specific hallmarks of MNKPL include activation of the NOTCH1 and RUNX3, as well as lower expression of the BCL11B." Further work at the single-cell level in MNKPL cells showed that NK cells and myeloid cells come from a common progenitor cell type. The researchers also conducted in vitro drug sensitivity assays where they measured MNKPL cell responses to 79 individual anti-cancer drugs. "We observed that MNKPL cells were highly sensitive to a drug called L-asparaginase, which has already shown clinical effectiveness for this disease," says Dr. Nishimura. "Mechanistically, we found that this was from low expression of asparagine synthetase, a quality that was distinct from other similar types of leukemia." Overall, the robust and comprehensive analysis performed in this study provides crucial molecular details for characterizing MNKPL. This work will undoubtedly help clinicians more effectively diagnose MNKPL and choice of therapeutic option. Additionally, this work provides data that will assist with novel therapeutic target identification and drug development in this leukemia.

Preclinical data highlight potential target engagement biomarkers to support clinical evaluation of CBL-B inhibitors BOSTON, Nov. 3, 2023 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," today announced the presentation of additional preclinical data from the Company's Casitas B-lineage lymphoma proto-oncogene (CBL-B) program in a poster presentation at the 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting. "Our enthusiasm for the therapeutic potential of HST-1011, a potential best-in-class CBL-B inhibitor, is partly driven by our belief that it can drive single-agent biological activity," said Timothy Reilly, Ph.D., Chief Development Officer of HotSpot. "Understanding which peripheral biomarkers are associated with this biology and the reliability of their measurement is critical to our characterization of of HST-1011's activity in patients as we advance our ongoing Phase 1/2 study." The presentation describes preclinical data in which HotSpot CBL-B inhibitors were evaluated in both in vitro and in vivo settings to identify and then characterize a repertoire of potential proximal biomarkers of CBL-B inhibitory activity. Several proteins, including phosphorylated ZAP70, Notch1 and IGF1R, showed robust dose-dependent effects and were further assessed for their reliability and potential feasibility for use in a clinical setting. The results provide support for their potential use in evaluating HST-1011 in our ongoing Phase 1/2, open-label, clinical study designed to evaluate HST-1011 alone and subsequently in combination with Regeneron's anti-PD-1 therapy, Libtayo® (cemiplimab), in patients with advanced solid tumors that are relapsed on or are refractory to anti-PD(L)-1 or standard of care therapies. Information on this clinical trial can be found on (NCT05662397). About HST-1011 HST-1011 is an investigational orally bioavailable, selective, small molecule allosteric inhibitor of CBL-B, an E3 ubiquitin protein ligase critically involved in immune cell response. Because CBL-B functions as a master regulator of effector cell (T cell and natural killer cell) immunity, its inactivation removes its endogenous negative regulatory functions to substantially enhance anti-tumor immunity. Preclinical data has demonstrated HST-1011's ability to bind to and inhibit a natural hotspot on CBL-B, yielding the activation and propagation of a targeted anti-tumor immune response. Enabled by HotSpot's proprietary Smart Allostery™ platform, HST-1011 is designed with tight binding, low nanomolar potency, a slow dissociation rate from the target to enable sustained pharmacology, and greater selectivity for CBL-B relative to C-CBL. About HotSpot Therapeutics, Inc. HotSpot Therapeutics, Inc. is pioneering a new class of allosteric drugs that target certain naturally occurring pockets on proteins called "natural hotspots." These pockets are decisive in controlling a protein's cellular function and have significant potential for new drug discovery by enabling the systematic design of potent and selective small molecules with novel pharmacology. The Company's proprietary Smart Allostery™ platform combines computational approaches and AI-driven data mining of large and diverse data sets to uncover hotspots with tailored pharmacology toolkits and bespoke chemistry to drive the rapid discovery of novel hotspot-targeted small molecules. Leveraging this approach, HotSpot is building a broad pipeline of novel allosteric therapies for the treatment of cancer and autoimmune diseases. To learn more, visit . Investor & Media Contact: Natalie Wildenradt [email protected] SOURCE HotSpot Therapeutics