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13:36 EDT SpringWorks Therapeutics announces data from Phase 3 DeFi trial - SpringWorks Therapeutics announced that data from the Phase 3 DeFi trial of nirogacestat, an investigational oral gamma secretase inhibitor, in adult patients with progressing desmoid tumors, was presented as a late-breaking oral presentation during a Presidential Symposium at the European Society for Medical Oncology Congress 2022. The DeFi trial met its primary endpoint of improving progression-free survival, as assessed by blinded independent central review, demonstrating a statistically significant improvement for nirogacestat over placebo, with a 71% reduction in the risk of disease progression. The median Kaplan-Meier estimate of PFS was not reached in the nirogacestat arm and was 15.1 months in the placebo arm. A PFS benefit was observed across all prespecified subgroups, including gender, tumor location, prior treatment or surgery, and mutational status. Confirmed objective response rate based on RECIST v1.1 was 41% with nirogacestat versus 8% with placebo. The complete response rate was 7% in the nirogacestat arm and 0% in the placebo arm. Nirogacestat demonstrated statistically significant and clinically meaningful improvements in patient-reported outcomes, which were key secondary endpoints of the study. Specifically, nirogacestat significantly reduced pain and other DT-specific symptoms and also significantly improved physical/role functioning and overall health-related quality of life. Most PRO benefits were observed as early as Cycle 2, which was the first timepoint for post-treatment evaluation, and were sustained over the duration of the study. At the time of primary analysis, the median duration of treatment was 20.6 months for participants on nirogacestat and 11.4 months for those on placebo, with the majority of nirogacestat patients continuing on treatment. Nirogacestat exhibited a manageable safety profile in the DeFi trial, with 95% of all treatment-emergent adverse events reported as Grade 1 or 2. Forty-two percent of patients in the nirogacestat arm versus 0% in the placebo arm required dose reductions due to TEAEs and 20% of patients in the nirogacestat arm versus 1% in the placebo arm discontinued treatment due to TEAEs. Ovarian dysfunction, which was defined by investigator-reported events of amenorrhea, premature menopause, menopause, and ovarian failure, was observed in 75% of women of childbearing potential receiving nirogacestat. These events resolved in 74% of the affected participants, including 64% of such participants who remained on nirogacestat treatment and 100% of those participants who discontinued treatment for any reason.

13:30 EDT Deciphera presnts initial Phase 1 single agent dose escalation data for DCC-3116 - Deciphera Pharmaceuticals announced initial data from the single agent dose escalation portion of the Phase 1 study of DCC-3116, the company's first-in-class, potent, and selective small molecule switch-control kinase inhibitor of ULK1/2, in patients with advanced or metastatic tumors with a mutant RAS or RAF gene. As of June 9, 2022, 18 patients with locally advanced or metastatic cancer with a RAF or RAS mutation were enrolled across four cohorts dosed with DCC-3116 twice daily: 50 mg BID; 100 mg BID; 200 mg BID; and 300 mg BID. The median number of prior anti-cancer regimens was three. The most common cancer types were colorectal and pancreatic and patients had KRAS and BRAF mutations. Treatment with DCC-3116 was well tolerated and most treatment-emergent adverse events were Grade 1/2. No dose-limiting toxicities or treatment-related serious adverse events were observed with DCC-3116; two asymptomatic, reversible Grade 3 alanine transaminase increases that led to dose interruption and reduction were reported as treatment-related. DCC-3116 exposure appeared to increase dose-proportionally across the four dose levels tested from 50 mg BID to 300 mg BID; at all doses levels, the area under the curve of DCC-3116 was at or above the AUC of the lowest tested dose that was effective in preclinical studies. DCC-3116 demonstrated target inhibition with significant decreases in phosphorylation of ATG14, a direct ULK1/2 substrate, in peripheral blood mononuclear cells; at all dose levels, reductions in phosphorylated ATG14 were observed that were associated with anti-tumor activity in preclinical studies combining DCC-3116 and a MEK inhibitor as measured by reductions in phosphorylated ATG13 in tumors. Fourteen patients were evaluable for response per Response Evaluation Criteria in Solid Tumors version 1.1 as of the cutoff date; best overall response was stable disease and the disease control rate at week 16 was 29%. Dose cohorts 100 to 300 mg BID are being expanded to further characterize the safety, pharmacokinetics, and pharmacodynamics of DCC-3116. In the fourth quarter of 2022, we expect to select the starting dose of DCC-3116 for, and initiate, dose escalation cohorts in combination with MEK and KRASG12C inhibitors.

13:25 EDT Apexigen presents new data from a Phase 2 trial evaluating Sotigalimab - Apexigen announced the presentation of new data from a Phase 2 multicenter clinical trial evaluating sotigalimab, Apexigen's agonist antibody targeting CD40, in combination with neoadjuvant chemoradiation for patients with resectable esophageal and gastroesophageal junction cancers. Encouraging pathologic complete response rates were observed in patients with both adenocarcinoma and squamous cell carcinoma. The primary objective of this study was to assess the efficacy of this novel combination, as measured by the pCR rate, and to further characterize the safety and feasibility of the combination of sotiga with standard of care chemoradiation in the neoadjuvant setting for patients with resectable esophageal and GEJ cancers. Sotiga combined with neoadjuvant chemoradiation for esophageal/GEJ cancers was generally safe and well tolerated. The majority of patients had Grade 1-2 adverse events. Six serious adverse events considered at least possibly related to sotiga included cytokine release syndrome observed in three patients, nausea and vomiting in one patient, dysphagia in one patient and Guillain-Barre Syndrome in one patient. There were no patient withdrawals due to sotiga and no sotiga/neoadjuvant chemoradiation-related deaths. Sotiga combined with neoadjuvant chemoradiation led to "encouraging" rates of pCR in the overall patient population and in the histologic subgroups of AC and SCC, the company said. Of the 29 evaluable patients, 11 patients had a pCR and 19 patients had a mPR with less than 10% of the residual tumor remaining after treatment. By histology, the pCR rate was 33% in patients with AC and 60% in patients with SCC. The pCR rate was 41.2% for patients receiving four doses of sotiga versus 33.3% for patients receiving three doses. R0 resection was achieved in 86% patients and progressive disease was only 7%. Paired biomarker analysis collected before and one to two weeks following a single run-in dose of sotiga alone demonstrated significantly increased tumor infiltration of activated dendritic cells, monocytes and both CD8 and CD4 T cells compared to baseline. The observed immune/inflammatory response in the tumor, changing the immune microenvironment from "cold" to "hot," further validates sotiga's mechanism of action.

13:14 EDT Cabaletta Bio presents new interim data from DesCAARTes Phase 1 trial - Cabaletta Bio presented updated clinical and translational data through 6 months of follow-up in cohorts A1 through A4 as well as 28-day safety data and DSG3-CAART persistence data through day 29 for cohorts A1 through A5 from the DesCAARTes trial at the 31st European Academy of Dermatology and Venereology Congress. The updated interim data included 16 treated subjects, four cohorts with three patients per cohort and one cohort with four patients, with twelve having completed six months of follow-up after DSG3-CAART infusion, and four having completed 28-day follow-up after DSG3-CAART infusion. The data demonstrate: Doses up to 7.5 billion DSG3-CAART cells were generally well tolerated, with no DLTs, and one grade 1 CRS. There was a dose-dependent increase in DSG3-CAART persistence through day 29 in cohorts A1 to A4. DSG3-CAART persistence through day 29 in cohort A5 was similar to that observed in cohort A4. In cohorts A1 to A4: Through six months post DSG3-CAART infusion, no clear pattern was observed in changes in anti-DSG3 Ab levels or disease activity through cohort A4. One subject in cohort A4 demonstrated a transient improvement in several assessments of efficacy, including DSG3-CAART persistence at 3 months, decrease of anti-DSG3 Ab levels greater than20% at 2- and 3-months post-infusion, improvement in PDAI score and decreased steroid usage.

13:09 EDT Concert announces presentation of CTP-543 THRIVE-AA1 Phase 3 data - Concert Pharmaceuticals announced the presentation of data from its Phase 3 clinical trial, THRIVE-AA1. The presentation highlights THRIVE-AA1 study results evaluating Concert's oral investigational medicine CTP-543 in adult patients with moderate to severe alopecia areata, an autoimmune disorder that results in patchy or complete scalp hair loss. In the THRIVE-AA1 study, significant improvements in scalp hair regrowth compared to placebo were achieved at 24 weeks for patients taking 8 mg twice-daily and 12 mg twice-daily doses of CTP-543, as previously disclosed in the positive topline results reported by Concert earlier this year. Treatment with CTP-543 was generally well tolerated. The EADV presentation includes new data from the THRIVE-AA1 study showing the ability of CTP-543 to achieve more stringent criteria for hair regrowth than the study's primary endpoint of absolute Severity of Alopecia Tool score of 20 or less at Week 24. Specifically, 21 percent and 35 percent of the patients in the CTP-543 8 mg twice-daily and 12 mg twice-daily dose groups, respectively, achieved a SALT score of 10 or less at Week 24, compared to 0 percent of patients in the placebo group. Also, the relative change in SALT score from baseline was significantly different for the 12 mg twice-daily dose group compared to placebo as early as Week 4. In addition, new data are presented showing that patients in the THRIVE-AA1 study with loss of eyebrow or eyelash hair at baseline treated with CTP-543 had significant improvement compared to placebo over the 24-week treatment period. The primary efficacy endpoint for THRIVE-AA1 was the percentage of patients achieving an absolute SALT score of 20 or less at Week 24 of treatment, which was met with statistical significance in both the 8 mg twice-daily and 12 mg twice-daily dose groups relative to placebo. A statistically significant proportion of patients treated with either 8 mg twice-daily or 12 mg twice-daily of CTP-543 experienced greater scalp regrowth compared to placebo. The proportion of patients achieving a SALT score of 20 or less at Week 24 was 41.5 percent in the 12 mg twice-daily dose group and 29.6 percent in the 8 mg twice-daily dose group, compared to 0.8 percent of patients in the placebo group. The treatment difference for both dose groups of CTP-543 relative to placebo was statistically significant. In addition, 21 percent and 35 percent of the patients in the CTP-543 8 mg twice-daily and 12 mg twice-daily dose groups, respectively, achieved a SALT score of 10 or less at Week 24 compared to 0 percent of patients in the placebo group. THRIVE-AA1 also met all the key secondary endpoints at both doses of CTP-543. The key secondary endpoints were the percentage of responders on a Satisfaction of Hair Patient Reported Outcome scale at Week 24 and the percentage of patients achieving absolute SALT scores of 20 or less at each of Weeks 20, 16, 12 and 8. All key secondary endpoints were met with statistical significance in both dose groups. The safety profile seen with CTP-543 in THRIVE-AA1 was consistent with previous studies. Serious adverse events were reported in nine patients, with only one patient having events that were assessed as possibly related to treatment. Four patients who reported serious adverse events were in the placebo group.

13:02 EDT Adagene announces publication of data showing best-in-class potential of ADG126 - Adagene announced the publication of data showing the best-in-class potential of ADG126, a masked, anti-CTLA-4 SAFEbody. Interim results from the Phase 1 portion of an ongoing Phase 1b/2 trial of ADG126 are being presented at the European Society for Medical Oncology Congress 2022. The poster, titled "Phase 1 Results Demonstrate Highly Differentiated Safety and PK Profile of ADG126, a Masked anti-CTLA-4 SAFEbody in Patients with Advanced Solid Tumors," reviewed data from the first-in-human, open label, phase 1 dose-escalation and dose expansion. The poster reports data on 26 patients with advanced metastatic solid tumors, the majority of whom received three or more lines of prior therapies and nearly half of whom progressed from prior immuno-oncology therapy. ADG126 monotherapy showed an unprecedented clinical safety profile at dosing levels up to 20 mg/kg when administered to this heavily pretreated patient population once every three weeks. ADG126 was well tolerated, with no dose-limiting toxicities or treatment-related Grade 3 or higher adverse events observed. Dose escalation is completed at 20 mg/kg and dose expansion is ongoing at 10 mg/kg. With 18 cycles of treatment at 1 mg/kg, an ovarian cancer patient experienced significant, continued reduction of an established ovarian cancer biomarker, CA125, dropping 90% to within the normal range for full clinical benefit. As of cycle 16, the patient experienced a 22% decrease in target lesions. Previously, this patient had surgery and five prior lines of systemic therapies. At the data cut-off of August 17, 2022, the disease control rate was 39%. ADG126 plasma pharmacokinetics were approximately linear and activated ADG126 accumulated steadily during repeat dosing across different dose levels. This suggests prolonged exposures of activated ADG126 in the tumor microenvironment, with cleaved ADG126 on average accumulating greater than or equal to3-fold during repeat dosing, resulting from an approximately 1.5-fold longer half-life of total ADG126 compared with its parental antibody. Trials evaluating the combination of ADG126 and anti-PD-1 therapies are ongoing in patients with advanced, metastatic tumors in the US, China and Asia Pacific, evaluating optimized doses of ADG126 in targeted tumors. ADG126 SAFEbody applies precision-masking technology to the parental anti-CTLA-4 antibody, ADG116, for conditional activation in the TME to expand the therapeutic index and further address safety concerns with existing CTLA-4 therapies. Binding to the same unique epitope as ADG116, the masked ADG126 is designed to provide enhanced safety and efficacy profiles due to the combination of the potent Treg depletion in the TME and partial ligand blocking by the activated ADG126, which is accumulated steadily for the prolonged tumor killing effect in TME.

11:03 EDT Immatics presents comprehensive preclinical data set for IMA402 targeting PRAME - Immatics announced a comprehensive preclinical data set for its T cell engaging receptor product candidate IMA402 at the European Society for Medical Oncology Congress 2022 held in Paris, France, from September 9 to 13, 2022. IMA402 is the company's second program in its TCR Bispecifics pipeline and is directed against an HLA-A*02:01-presented peptide derived from PRAME, a cancer target broadly expressed in many solid tumors. The IMA402 TCER utilizes a high-affinity TCR designed to specifically bind to an HLA-A*02:01-presented peptide derived from PRAME on tumor cells. The T cell recruiter domain is a proprietary low-affinity T cell recruiter against the TCR/CD3 complex that demonstrates superior in vivo tumor control compared to analogous TCER molecules designed with higher-affinity variants of a widely used antibody recruiter. The IMA402 TCER is optimized to reduce T cell engager-associated toxicities in patients, which is demonstrated by reduced recruiter-mediated cytokine release in vitro. IMA402 showed potent and selective activity against PRAME-positive tumor cell lines in vitro. In vivo studies in mice demonstrated dose-dependent anti-tumor activity of IMA402. Sufficiently high drug doses were key to achieving the desired anti-tumor effects over a prolonged period. In vitro safety assessment including toxicity screening against 20 normal tissue types, whole blood cytokine release assessment and alloreactivity evaluation confirmed favorable safety profile for IMA402. The half-life extended format of IMA402 confers a serum half-life of greater than1 week in mice suggesting a favorable dosing regimen and prolonged drug exposure at therapeutic levels when compared to TCR Bispecifics lacking half-life extension strategies. To enable the start of the Phase 1/2 trial in 2023, Immatics has completed the manufacturing process development for IMA402 and manufacturing of the clinical batch is on track for the second half of 2022. The Phase 1 part of the trial will start with a minimal anticipated biological effect level dose of IMA402 and will have an adaptive design aimed at accelerating dose escalation to determine the recommended Phase 2 dose. HLA-A*02:01-positive patients with different solid tumors expressing PRAME will initially receive weekly infusions of IMA402. Pharmacokinetics data will be assessed throughout the trial and might provide an opportunity to adapt the treatment interval. The Phase 2a dose expansion part of the trial will be designed to comprise several cohorts to further evaluate IMA402 in specific indications and combination therapies. Submission of the IND1 application is planned for Q2 2023.

10:54 EDT Exelixis announces dose-escalation results from Phase 1 STELLAR-001 trial - Exelixis announced results from the dose-escalation stage of STELLAR-001, an ongoing phase 1b trial evaluating XL092 as a single-agent and in combination with atezolizumab in patients with locally advanced or metastatic solid. STELLAR-001 enrolled patients with advanced solid tumors for which standard of care did not exist or was not effective. For this analysis, patients received XL092 either as a single-agent or in combination with atezolizumab. The most common types of cancer for patients enrolled in the single-agent XL092 cohort were clear cell renal cell carcinoma, metastatic castration-resistant prostate cancer and breast cancer. The most common types of cancer for patients enrolled in the XL092 in combination with atezolizumab cohort were colorectal cancer, metastatic CRPC and sarcoma. The median duration of follow-up was 17.9 months and 6.0 months for those receiving single-agent XL092 and XL092 in combination with atezolizumab, respectively. Median age was 61 years for those receiving single-agent XL092 and 59 years for those receiving XL092 in combination with atezolizumab; 62% and 55% of patients, respectively, had an Eastern Cooperative Oncology Group score of 1. In each arm, 68% of patients had at least three prior lines of therapy. The maximum tolerated dose was determined to be 120 mg, and the recommended dose for the expansion phase is 100 mg for both single-agent XL092 and XL092 in combination with atezolizumab. Tumor reduction was seen in 71% of patients receiving single-agent XL092 and in 56% of patients receiving XL092 in combination with atezolizumab. The objective response rate was 10% for single-agent XL092 and 4% for XL092 in combination with atezolizumab; disease control rate was 90% and 74%, respectively. Confirmed partial responses were observed in four patients treated with single-agent XL092 and one patient treated with XL092 in combination with atezolizumab. In the 19 patients with clear cell RCC who were heavily pretreated with immunotherapy and/or VEGF-targeting tyrosine kinase inhibitors, including 68% who received prior cabozantinib, ORR was 11%, and DCR was 95% with single-agent XL092. The activity of single-agent XL092, as measured by the percent of patients with reduction in tumor size, was similar to that observed with cabozantinib in phase 1: XL092 demonstrated a 71% RTS versus a 74% RTS with cabozantinib; a greater than 30% RTS was seen in 15% of patients treated with XL092 versus 18% of those treated with cabozantinib. Grade 3/4 treatment-emergent adverse events occurred in 60% of those receiving single-agent XL092 and 38% of those receiving XL092 in combination with atezolizumab. There were no grade 5 treatment-related AEs.

10:46 EDT Bristol-Myers announces new two-year results from POETYK PSO LTE trial - Bristol Myers Squibb announced new two-year results from the POETYK PSO long-term extension trial demonstrating clinical efficacy was maintained with continuous Sotyktu treatment in adult patients with moderate-to-severe plaque psoriasis. This analysis assessed patients from the pivotal POETYK PSO-1 trial who transitioned into the LTE trial. At 112 weeks of Sotyktu treatment, modified non-responder imputation response rates were 82.4% for Psoriasis Area and Severity Index 75, 55.2% for PASI 90 and 66.5% for static Physician's Global Assessment 0/1. These data and 25 additional abstracts demonstrating Bristol Myers Squibb's robust body of research in dermatology were presented at the European Academy of Dermatology and Venereology Congress. Of the 262 Sotyktu patients in the analysis, 171 had achieved PASI 75 at Week 16 of the POETYK PSO-1 trial, and among these patients, efficacy was maintained for up to 112 weeks, including response rates for PASI 75, PASI 90 and sPGA 0/1.

10:04 EDT MarketWise major shareholder Frank Stansberry buys $832K in common stock - In a regulatory filing last night, MarketWise disclosed that major shareholder Frank Stansberry bought 331K shares of common stock on September 7th in a total transaction size of $832.2K. Shares of MarketWise were up 9.9% afterhours on Friday.

09:56 EDT FDA approves Bristol-Myers' Sotyktu for moderate-to-severe plaque psoriasis - Bristol Myers Squibb announced that the U.S. Food and Drug Administration approved Sotyktu, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor, for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Sotyktu is not recommended for use in combination with other potent immunosuppressants. The approval is based on results from the pivotal Phase 3 POETYK PSO-1 and POETYK PSO-2 clinical trials, which demonstrated superior efficacy of once-daily Sotyktu compared to placebo and twice-daily Otezla in 1,684 patients aged 18 years and older with moderate-to-severe plaque psoriasis.1 The superior efficacy of Sotyktu compared to placebo and Otezla was demonstrated at both 16 and 24 weeks, and responses with Sotyktu persisted through 52 weeks. In the POETYK PSO trials, at Week 16, the most common adverse reactions in patients on Sotyktu were upper respiratory infections, blood creatine phosphokinase increase, herpes simplex, mouth ulcers, folliculitis and acne. In addition, 2.4 percent of patients on Sotyktu, 3.8 percent of patients on placebo, and 5.2 percent of patients on Otezla experienced adverse reactions leading to discontinuation.