PKCβ

40-site U.S. trial enrolling more than 300 patients could significantly change the way DCIS is treated and reduce possibly unnecessary surgery SAN FRANCISCO, Oct. 30, 2023 /PRNewswire/ -- Quantum Leap Healthcare Collaborative (QLHC) announces the enrollment launch for the Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: Ductal Carcinoma In Situ (RECAST DCIS), a Phase 2 platform study aimed at preventing the progression of DCIS to breast cancer. The study is evaluating three investigational endocrine therapy arms: (Z)-endoxifen, a selective estrogen receptor modulator (SERM) in development by Atossa Therapeutics (Nasdaq: ATOS); HAVAH T+Ai™, a proprietary combination of testosterone (T) and anastrozole (Ai) that targets the androgen and estrogen receptor pathways in development by Havah Therapeutics; and ORSERDU® (elacestrant), the only FDA approved oral selective estrogen receptor degrader (oSERD) in development by Stemline Therapeutics Inc. (Stemline), a wholly-owned subsidiary of the Menarini Group. "DCIS indicates the very earliest, noninvasive stage of the disease, that's why it is important for us to seek out alternative therapies for DCIS patients and find ways to reduce toxicity and unnecessary surgeries. We are excited to partner with three innovative companies to explore new treatments for this large and often over-treated patient population," said Laura Esserman, MD, a lead investigator for the study and founder of QLHC. Surgery is the current standard treatment for DCIS even though many patients never progress to breast cancer, which means that patients are often over-treated with invasive procedures. This new trial, sponsored and operated by QLHC, offers DCIS patients up to six months of endocrine therapy with the intent to forego surgery and instead be monitored via long-term active surveillance, if appropriate. A key element in reducing overtreatment of DCIS is identifying biomarkers that reflect the risk of progression so that those with low-risk lesions are spared surgery. RECAST DCIS features the assessment of imaging and molecular-based biomarkers in addition to evaluating new investigational agents in this setting. The study is open to enrollment with each investigational agent arm expected to enroll up to 110 patients. The three collaborators for this trial, Atossa Therapeutics, Havah Therapeutics, and Stemline, all aim to find alternative solutions for DCIS patients and are providing different agents for assessment. Atossa's (Z)-endoxifen has the potential to mitigate breast cancer risk (by reducing the density of breast tissue); to reduce cancer cell activity before surgery; and to reduce the risk of recurrent or new breast cancer after the initial treatment. According to published studies, (Z)-endoxifen is a competitive inhibitor of ERα and represses ERα transcriptional activity (Z)-endoxifen is 100-fold more potent in anti-estrogen activity compared to other SERMs. (Z)-endoxifen also binds to and disrupts protein kinase C beta one function (PKCb1, a known oncogenic protein). The National Cancer Institute (NCI) and others have studied (Z)-endoxifen and have demonstrated promising results in the treatment of breast cancer as well as for the treatment of other solid tumors. Treatment with (Z)-endoxifen may avoid off target effects of tamoxifen and remaining metabolites potentially increasing adherence by improving the safety profile. Havah Therapeutics' HAVAH T+Ai™ combines T, the natural ligand for the androgen receptior and Ai, an inhibitor of T conversion to estradiol, to modulate the growth of abnormal breast tissues. HAVAH T+Ai™ is a proprietary combination subcutaneously delivered system to overcome hormonal symptoms by balancing hormonal irregularities in the breast, developed from more than 10 years of clinical research into hormonal regulation in women. Havah has extensive clinical experience using HAVAH T+Ai™ to address pre- and postmenopausal prevention of breast disease, and the company generated data from more than 1,000 Australian women with breast disease through an ongoing open label cohort study (more than 6,200 implants), with critical safety pharmacokinetic and early efficacy data already demonstrated. Stemline's Elacestrant (ORSERDU), was approved by the U.S. Food & Drug Administration in January 2023 for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, HER2-negative, ESR-1 mutated advanced or metastatic breast cancer, following at least one line of endocrine therapy. For more information including full prescribing information and important safety information, please visit . About Quantum Leap Healthcare Collaborative Quantum Leap Healthcare Collaborative is a 501c(3) charitable organization established in 2005 as a collaboration between medical researchers at University of California, San Francisco and Silicon Valley entrepreneurs. Our mission is to integrate high-impact research with clinical processes and systems technology, resulting in improved data management and information systems, greater access to clinical trial matching and sponsorship, and greater benefit to providers, patients and researchers. Our goal is to improve and save lives. For more information, visit . About Atossa Atossa Therapeutics is a clinical stage biopharmaceutical company developing innovative medicines in areas of significant unmet medical need in oncology. Atossa's current focus is on breast cancer. More information is available at atossatherapeutics.com. About Havah Therapeutics Havah Therapeutics is a biopharmaceutical company developing innovative, proprietary hormonal therapies that aim to improve quality of life for women. Havah brings together a world-class team passionate about helping women live lives free from the suffering caused by breast pain, debilitating menopausal symptoms and breast cancer. More information is available at . About The Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4.4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit . About Stemline Therapeutics Inc. Stemline Therapeutics, Inc. ("Stemline") a wholly-owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes ORSERDU® (elacestrant) in the United States, an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs), a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States and Europe, which is the only approved treatment for BPDCN in the US and EU to date. Stemline also commercializes NEXPOVIO® in Europe, an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers. SOURCE Quantum Leap Healthcare Collaborative

- Series B led by Double Point Ventures with major support from Viking Global Investors as well as other new and existing investors - - A combined $27.1 million Series B first close and $8.1 million in converting outstanding notes funds the company’s two assets in development, SM-020 for the treatment of seborrheic keratoses and SM-030 for the treatment of melasma, through end of Phase 2 meetings with FDA and commencement of Phase 3 trials - BOSTON--(BUSINESS WIRE)-- DermBiont, Inc., a clinical-stage biotechnology company that is advancing targeted topical therapeutics for the treatment of dermatological indications, today announced a $35.2 million Series B financing, including a $27.1 million Series B first close and $8.1 million in converting outstanding notes. Proceeds will be used to advance two drugs in development, SM-020, a topical novel AKT kinase inhibitor for the treatment of seborrheic keratoses (SKs), and SM-030, a topical novel PKC-beta inhibitor for the treatment of melasma and other hyperpigmentation disorders of the skin. The Series B was led by new institutional investor, Double Point Ventures, and includes continued support from Viking Global Investors, Civilization Ventures, Olive Tree Capital, and others. Concurrent with the financing, Daniel Yadegar, M.D., Managing Partner at Double Point Ventures, joined DermBiont’s board of directors, adding, “I am excited to be working closely with DermBiont’s team to advance two products, one for the treatment of seborrheic keratoses and the other for the treatment of melasma, two of the most frequently diagnosed skin diseases by dermatologists. These products prioritize the patient experience by addressing the root cause of both diseases with excellent efficacy, safety, and tolerability. Physicians understand that patients with SKs and hyperpigmentation disorders of the skin are seeking effective, safe, and well-tolerated topical treatment options compared with existing ablative surgical procedures for treating SKs or ineffective lasers with frequent recurrence or unsafe toxic chemicals with very low efficacy like hydroquinone for treating melasma.” The proceeds from the Series B financing will be used to advance the clinical development of SM-020 and SM-030. They are expected to fund the company through end of its Phase 2 meetings with the U.S. Food and Drug Administration (FDA), which are expected in the second half of 2024 for both programs. In the next twelve months, DermBiont will commence enrollment for three planned seborrheic keratoses clinical trials and one melasma trial as follows: Phase 2b randomized, double-blind, vehicle-controlled clinical trial in 60 subjects with seborrheic keratoses treated with SM-020 gel 1% or vehicle twice daily for 28 days. Phase 2b open label clinical trial in 10 subjects with DPN (Dermatosis Papulosa Nigra) treated with SM-020 gel 1% twice daily for 28 days. Phase 2 open label clinical trial extension in 25 additional subjects with seborrheic keratoses treated with SM-020 gel 0.1% or SM-020 gel 1% daily or twice daily for 28 to 56 days. Phase 2b randomized, observer-blinded, placebo-controlled clinical trial in 138 subjects with melasma treated with SM-030 gel 0.64%, SM-030 gel 0.08%, or placebo gel twice daily for 12 weeks “The addition of Double Point Ventures as a major backer alongside continued financial and strategic support from Viking Global Investors and other investors allows us to accelerate the development of our pipeline of novel topical therapeutics for the treatment of the number one and number three most frequently diagnosed disorders of the skin by dermatologists in the US, seborrheic keratoses and hyperpigmentation, respectively,” stated Karl Beutner, M.D., Ph.D., Chief Executive Officer and Co-Founder of DermBiont. “This funding comes on the heels of our successful Phase 2 proof of concept trials, where SM-030 gel 0.64% achieved greater efficacy than 4% hydroquinone, and where over 80% of SKs responded to treatment with SM-020 gel 1.0% twice daily for 14 to 28 days and over 50% of SK lesions completely cleared in the most effective dosing regimen.” About DermBiont DermBiont’s mission is to become the world’s leading precision dermatology company developing and commercializing targeted topical therapeutics that treat, cure, and prevent skin diseases. The company aims to impact the root causes of skin diseases through the development of first-in-class targeted therapeutics with well-defined mechanisms of action. The company’s targeted topical therapeutics pipeline includes two lead assets: SM-020 for the treatment of seborrheic keratoses and SM-030 for the treatment of melasma and other hyperpigmentation disorders of the skin. For more information, please visit . About Double Point Ventures At Double Point Ventures, we see beyond today's treatments to envision tomorrow's cures. Our fund invests in revolutionary companies developing cutting-edge therapeutics, from gene therapies to precision medicines. While novel drugs are our focus, we also target innovative early revenue-stage diagnostic companies, medical device startups, digital health startups, and healthcare services providers catalyzing the future of healthcare. Backed by visionary investors, our mission is clear - fund the science superstars solving the medical mysteries of our time. By powering pioneering companies, we strive to bring groundbreaking treatments from bench to bedside. Double Point Ventures is led by Managing Partner, Daniel Yadegar, M.D. For more information, please visit .

0.8% SM-030 topical gel achieved safety and efficacy endpoints in a Phase 2 trial for solar lentigos and photoinduced pigmentation. The study enrolled two groups of subjects: 1) a group of subjects with solar lentigos treated with open label 0.8% SM-030 gel and 2) a randomized group of healthy subjects that received either 0.8% SM-030 gel, 4% hydroquinone cream, or vehicle gel applied to an area of sun exposed skin (dorsum of the hand) and a sun protected area (upper inner arm) Solar lentigos results: 100% of subjects treated with SM-030 applied to the entire dorsal hand twice-daily (BID) for 12 weeks achieved at least an IDGA of -1 and 27% achieved an IDGA of -2. Additionally, SM-030 demonstrated a statistically significant (p<0.0001) decrease in pigmentation on the treatment side compared to the contralateral untreated side as measured by colorimetry. Healthy volunteers: SM-030 applied to the entire dorsal hand (sun exposed) twice-daily (BID) for 12 weeks achieved greater efficacy than 4% hydroquinone in the proportion of subjects that obtained an Investigator Dynamic Global Assessment (IDGA) score of -1 (85% vs 75%) and -2 (30% vs 20%). There was no change in the pigmentation of the treated sun protected upper inner arm. BOSTON--(BUSINESS WIRE)-- DermBiont, Inc., a clinical-stage biotechnology company that is advancing targeted topical therapeutics for the treatment of dermatological indications, today announced positive data from its Phase 2 trial with 0.8% SM-030 gel, a product under development capable of regulating pigmentation by controlling the formation of new melanin. Disorders of hyperpigmentation, such as melasma, photoinduced hyperpigmentation, and solar lentigos (lentigines), are common skin conditions affecting between 5% and 30% of the general population and are caused by an over production or irregular dispersion of epidermal melanin. There is no existing product that effectively and safely specifically inhibits the production of excess epidermal melanin. Tyrosinase, the key enzyme in the melanin synthetic pathway, requires phosphorylation by PKCβ for activity. SM-030 is a first-in-class selective and potent topical PKCβ inhibitor designed to inhibit PKCβ to reduce the production of excess epidermal melanin. DermBiont’s Phase 2 trial with SM-030 was conducted with two different groups of subjects. The first treatment group was an open-label within-subject bilateral-comparison group in 15 subjects with at least four solar lentigos on each dorsal hand treated twice-daily (BID) on one dorsal hand for 12 weeks with 0.8% SM-030 gel. The contralateral hand was untreated. The second group treated consisted of a group of 60 healthy volunteer subjects with Fitzpatrick Skin Type IV or V who were randomized 1:1:1 to receive either 0.8% SM-030 gel, vehicle gel, or 4% hydroquinone cream (an active comparator) applied to the dorsum of the hand (sun exposed skin) and upper inner arm (sun protected skin) with the contralateral hand and arm serving as untreated controls. Evaluations were observer blinded. Efficacy Analysis: Subjects in both groups (solar lentigos subjects and normal healthy volunteers) were assessed by way of the Investigator Dynamic Global Assessment (IDGA) Score at week 12. The IDGA score is a numerical score based on physician scoring of the pigmentation in the area of test article application relative to the untreated control site. The IDGA score ranges from -3 to +3 defined as markedly less pigmentation than the untreated control site (IDGA = -3); moderately less pigmentation than the untreated control site (IDGA = -2); slightly less pigmentation than the untreated control site (IDGA = -1); similar pigmentation to the untreated control site (IDGA=0); slightly more pigmentation than the untreated control site (IDGA = 1); moderately more pigmentation than the untreated control site (IDGA = 2); or markedly more pigmentation than the untreated control site (IDGA = 3). The Melanin index measured by colorimeter, defined by L* and ITA (degrees) calculations was also evaluated at each visit using a non-invasive biophysical measurement with a colorimeter (Chromometer CM-700: Konica-Minolta, Osaka, Japan). Results: Solar Lentigos Open Label Subjects: on the dorsal hand with the treated lentigos, 100% of subjects (n=15) achieved either an IDGA of –2 (moderately less pigment) or –1 (slightly less pigment) with 27% (n=4) achieving an IDGA of –2. There was also a statistically significant difference between the change in colorimetry from screening readings (p<0.0001) between treated and untreated lentigos at Week 12. Healthy Volunteer Randomized Subjects: on the sun exposed dorsal hand, 85% of subjects treated with 0.8% SM-030 gel, 75% with 4% hydroquinone, and 35% with vehicle gel achieved an IDGA score of –1 or less (p<0.01 comparing 0.8% SM-030 vs. vehicle). 30% of subjects treated with 0.8% SM-030 gel, 20% with 4% hydroquinone, and 0% with vehicle gel achieved an IDGA score of –2 or less (p<0.05 comparing 0.8% SM-030 vs. vehicle). There were no observed changes in the sun protected upper inner arm. All Subjects: The treatment was well tolerated, with 99% of safety observations having no local tolerability reactions. Any local tolerability reactions that occurred were all mild in nature, transient, and resolved without sequelae. There were no serious adverse events. “The data seen in this Phase 2 trial of SM-030 is highly encouraging as we have demonstrated IDGA improvement as well as a clear separation from placebo from baseline to the end of treatment,” stated Karl Beutner, M.D., Ph.D., CEO, and Co-Founder of DermBiont. “The existing options for treating hyperpigmentation lack sufficient efficacy, safety, and tolerability, and we believe that the successful development of SM-030 could bridge this gap and provide patients with an alternative treatment option that is safe for long-term use and very well tolerated amongst patients.” Based on positive results from this initial Phase 2 trial with 0.8% SM-030 gel, DermBiont plans to commence a 140 subject double-blind placebo-controlled trial treating melasma with 0.8% SM-030 topical gel in the second half of 2023. Nichola Eliovits, Co-Founder and Chief Business Officer at DermBiont, added, “The results of this initial trial are particularly exciting for melasma patients who currently treat dermal melanin with lasers but do not have any option to inhibit excess production of epidermal melanin, the root cause of patients’ melasma. SM-030 will efficaciously and safely inhibit excess production of epidermal melanin that leads to hyperpigmentation, resulting in monochromatic skin while providing desirable results to patients without the hypopigmentation side effects or the array of safety concerns associated with current treatments, including hydroquinone which is toxic to melanocytes and has been banned as a monotherapy at both 2% (OTC) and 4% (Rx) concentrations by the FDA.” About SM-030 PKCβ has the ability to increase melanin production by phosphorylating and increasing the activity of tyrosinase, which is the key and final enzyme in the melanin synthetic pathway. SM-030 is a first-in-class selective and potent topical PKCβ inhibitor intended to reduce the production of epidermal melanin. About DermBiont DermBiont’s mission is to become the world’s leading precision dermatology company developing and commercializing targeted topical therapeutics that treat, cure, and prevent diseases. The company aims to impact the root causes of skin diseases through the development of targeted small molecule therapeutics with well-defined mechanisms of action and biotherapeutics that repair an imbalance of the microbiome. The company’s targeted topical therapeutics pipeline includes two lead assets: SM-020 for the treatment of seborrheic keratosis and SM-030 for the treatment of hyperpigmentation disorders of the skin. For more information, please visit .