Lucicebtide

- ST101 poster to highlight novel macrophage-driven mechanism of action - - ST316 poster to highlight its potential to address Wnt-driven cancers with poor clinical responses to immunotherapeutic agents - HARRISON, N.Y., April 14, 2023 /PRNewswire/ -- Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, announced today the presentation of two late-breaking research posters during the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, Florida. "We are thrilled to showcase late-breaking results at this year's AACR meeting with data from our ST101 and ST316 programs that address difficult-to-drug cancer targets, C/EBPβ and β-catenin," said Dr. Barry Kappel, founder, CEO and President of Sapience. "These datasets demonstrate the roles of ST101 and ST316 in shifting an immune-suppressive tumor microenvironment to an immune-active state, and support evaluating both agents in coordination with immune-oncology (I/O) therapeutic strategies. In particular, with ST316 set to begin patient dosing in a Phase 1-2 clinical study in mid-2023, we are excited that these datasets further elucidate its unique mechanism of action." ST101 Abstract Highlights: ST101 is a first-in-class antagonist of C/EBPβ that has demonstrated clinical proof-of-concept in advanced solid tumors. ST101 is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). As a critical regulator of the immunosuppressive tumor microenvironment, activation of C/EBPβ triggers macrophage polarization toward immunosuppressive M2-type myeloid-derived suppressor cells (MDSCs) and correlates with poor prognosis in several types of human cancer. ST101 reprograms tumor-associated macrophages (TAMs) from the M2 phenotype toward the immune-promoting M1 phenotype, representing an attractive strategy to enhance antitumor immunity. In preclinical models, ST101-mediated macrophage polarization to the M1 phenotype enhances the in vivo anti-tumor activity of anti-PD1 checkpoint inhibition. In patient biopsies, ST101 modulates the tumor immune microenvironment by suppressing genes required for M2 macrophage polarization, culminating in an enhanced CD8 T-cell/Treg ratio. The data support a novel, macrophage-driven mechanism of action for ST101 and suggest the exploration of ST101 in I/O therapeutic strategies. Title: "ST101, a peptide antagonist of novel I/O target C/EBPβ, reprograms MDSCs and promotes an immunoactive tumor microenvironment" Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 2 Session Date and Time: Tuesday April 18, 2023, 1:30 PM - 5:00 PM Location: Poster Section 34 Abstract Presentation Number: LB236 ST316 Abstract Highlights: ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator BCL9, a complex that drives oncogenesis in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. In March of this year, Sapience announced that it received clearance from the U.S. Food and Drug Administration (FDA) to proceed with a Phase 1-2 clinical trial of ST316 for the treatment of solid tumors. In addition to its direct oncogenic role, dysregulated Wnt/b-catenin signaling also promotes tumorigenesis by suppressing the tumor immune microenvironment (TIME). Nonclinical data indicate that ST316 exposure to human peripheral blood mononuclear cells shifts M2 macrophages to the M1 phenotype and increases CD8 T-cell activation in macrophage/T-cell mixed cultures. ST316 enhances the anti-tumor activity of anti-PD-1 checkpoint inhibition in a preclinical triple-negative breast cancer model. These results support the immuno-therapeutic potential of ST316 to enhance current I/O therapeutic approaches. Title: "Immunotherapeutic potential of ST316, a peptide antagonist of β-catenin" Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 1 Session Date and Time: Sunday April 16, 2023, 1:30 PM - 5:00 PM Location: Poster Section 35 Abstract Presentation Number: LB016 Abstracts and full session details are available through the AACR Annual Meeting planner: AACR Annual Meeting 2023 | Meetings | AACR About ST101 ST101, a first-in-class antagonist of C/EBPβ, is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). ST101-101 is an open-label, Phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 in patients with advanced solid tumors. The study consists of two phases: Phase 1 dose escalation/regimen exploration and Phase 2 dose expansion. In the ongoing Phase 2 dose expansion, Sapience is evaluating patients with GBM, metastatic cutaneous melanoma, castration-resistant prostate cancer and locally advanced or metastatic hormone-receptor positive breast cancer. In the ongoing dose escalation part of the study, ST101 has demonstrated clinical proof-of-concept with a durable RECIST 1.1-confirmed partial response (PR) in a patient with cutaneous melanoma and evidence of long-lasting stable disease in several additional patients. In the ongoing Phase 2 dose expansion part of the study, ST101 has demonstrated clinical proof-of-concept with a mRANO-confirmed partial response in a patient with recurrent GBM and evidence of long-lasting stable disease in several additional patients. ST101 has been granted Fast Track designation for recurrent GBM and advanced cutaneous melanoma in patients who have disease progression on or after anti-PD-1/anti-PD-L1 therapy, as well as orphan designations from the FDA for Stage IIb-IV melanoma, glioma and AML, and from the European Commission for the treatment of glioma. About ST316 ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator BCL9, a complex that drives oncogene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. The interaction between β-catenin and BCL9 has previously been considered an 'undruggable' target due to the inability of small molecules to inhibit complex formation and antibodies to gain access to the cytoplasm or nucleus to disrupt the interaction. ST316 contains a cell penetration moiety to allow intracellular access and a domain designed to bind the first armadillo repeat domain of β-catenin, a site utilized by BCL9 but no other β-catenin binding partners. ST316 suppresses transcription of oncogenic Wnt target genes regulating proliferation, migration, invasion and the metastatic potential of tumor cells, as well as genes regulating the immunosuppression of the tumor microenvironment. Sapience has received IND clearance to proceed with a Phase 1-2 clinical study of ST316. The Phase 1 dose-escalation portion of the study is designed as a basket study to enroll patients with tumors likely to harbor abnormalities of the Wnt/β-catenin signaling pathway. Sapience expects to begin dosing patients in the Phase 1 portion in mid-2023 to evaluate the safety, clinical activity, pharmacokinetics and pharmacodynamics of ST316. The Phase 2 dose-expansion portion of the study will enroll patients in four specific tumor types known to harbor abnormalities of the Wnt/β-catenin signaling pathway, including cholangiocarcinoma, colorectal, triple negative breast and ovarian cancers. About Sapience Therapeutics Sapience Therapeutics, Inc. is a privately held, clinical-stage biotechnology company focused on discovering and developing peptide therapeutics to address oncogenic and immune dysregulation that drive cancer. Its pipeline of SPEARs™ (Stabilized Peptides Engineered Against Regulation) disrupt intracellular protein-protein interactions, enabling targeting of transcription factors which have traditionally been considered undruggable. Sapience's lead program, ST101, is a first-in-class antagonist of C/EBPβ that has demonstrated clinical proof-of-concept in advanced solid tumors. Sapience has received IND clearance to proceed with its second program, ST316, a first-in-class antagonist of β-catenin, and expects to begin dosing patients in mid-2023. For more information on Sapience Therapeutics, please visit and engage with us on LinkedIn. Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements. Any statements herein other than statements of historical fact could be deemed to be forward-looking statements. These forward-looking statements may include, among other things, statements regarding future events that involve significant risks and uncertainties (including with respect to Sapience's preclinical and clinical development programs). These forward-looking statements are based on management's current expectations, and actual results and future events may differ materially as a result of certain factors, including, without limitation, our ability to obtain additional funds, and meet applicable regulatory standards and receive required regulatory approvals. Forward-looking statements speak only as of the date of this press release. Sapience does not undertake any obligation to update any forward-looking statements as a result of new information, future events, changed assumptions or otherwise, except as required by law. Contacts Sapience Therapeutics, Inc.: Barry Kappel, Ph.D., M.B.A. President and Chief Executive Officer [email protected] Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Sapience Therapeutics, Inc.

- Announced topline results from STS101 SUMMIT Phase 3 efficacy trial that the company believes demonstrate STS101 provides differentiated, robust and sustained anti-migraine effects - - Submitted STS101 New Drug Application (NDA) to U.S. Food and Drug Administration (FDA) in March 2023 - - Company seeking to maximize value for stockholders via strategic transaction - - ~36% workforce reduction to be implemented effective March 31, 2023 - - $52.5 million in cash, cash equivalents and marketable securities as of December 31, 2022 - SOUTH SAN FRANCISCO, Calif., March 28, 2023 (GLOBE NEWSWIRE) -- Satsuma Pharmaceuticals, Inc. (Nasdaq: STSA), a development-stage biopharmaceutical company developing STS101 (dihydroergotamine (DHE) nasal powder), a novel investigational therapeutic product candidate for the acute treatment of migraine, today reported financial results for the fourth quarter and full-year 2022 and summarized recent business highlights. “After having had the opportunity to review complete results from the SUMMIT trial, discuss them with headache specialists, and undertake further qualitative and quantitative primary market research that takes into account the results of the SUMMIT trial, we continue to believe that STS101, if approved, could be a differentiated and important treatment option for many people with migraine,” stated John Kollins, President and Chief Executive Officer. “Although we have decided not to build commercial infrastructure and independently commercialize STS101, we believe STS101 could ultimately be an attractive addition to the portfolio of an established pharmaceutical company.” “In parallel with our efforts to conclude a strategic transaction, we have implemented necessary cost-saving initiatives, including the workforce reduction announced today. While it’s difficult to part company with committed employees who have made significant contributions to Satsuma and its STS101 development efforts, given the challenging environment we face, it’s imperative that we optimally position Satsuma and STS101 to maximize potential value for our stockholders. I thank and recognize all of our employees for their commitment and hard work over the past six-plus years in taking STS101 from an abstract concept to an NDA-stage product candidate that has the potential to address the unmet needs of many people with migraine.” Recent Business Highlights STS101 New Drug Application (NDA) Submitted to FDA Earlier this month, Satsuma submitted an NDA to the FDA seeking approval of STS101 for the acute treatment of migraine with or without aura in adults. As has been its longstanding plan, the company is seeking FDA approval under the 505(b)(2) regulatory pathway that allows for referencing of some of the information required for STS101 approval from studies not conducted by Satsuma. The FDA has 60 days to conduct a preliminary review of the NDA to determine and notify the company as to whether the NDA is sufficiently complete for it to perform a complete review. STS101 SUMMIT Phase 3 Efficacy Trial Results In November 2022, Satsuma announced topline data from its 1,591-subject, double-blind, placebo controlled STS101 SUMMIT Phase 3 efficacy trial. Although single-dose treatment of subjects’ migraine attacks with STS101 demonstrated numerical superiority versus placebo on the SUMMIT trial co-primary outcome measures, freedom from pain and freedom from most-bothersome-symptom (from among photophobia, phonophobia and nausea) assessed at the two-hour post-administration regulatory timepoint, the difference did not reach statistical significance (p<0.05). STS101 was, however, statistically superior (p<0.001) to placebo on the freedom from pain and most-bothersome-symptom endpoints by three hours post-administration and at all subsequent timepoints (4, 6, 12, 24 and 48 hours). Additionally, STS101 was statistically superior to placebo on multiple key secondary endpoints, including pain relief at 2 hours post-administration and all timepoints thereafter and total migraine freedom at 3 hours post-administration and all timepoints thereafter. The company believes the results of the SUMMIT trial convincingly demonstrate that a single dose of STS101 provides differentiated, robust and sustained anti-migraine effects. STS101 was safe and well-tolerated, consistent with clinical trial experience to date. Based on previous interactions with the FDA, Satsuma believes that the efficacy results of the SUMMIT trial, which were not required by the FDA to support the STS101 NDA filing and its potential approval, provide a totality of evidence supporting the efficacy of STS101 for the acute treatment of migraine. The company further believes that ST101, if approved, can address the unmet needs of many people with migraine, and that the efficacy results from the SUMMIT trial, if included in the STS101 labeling approved by the FDA, would provide important treatment information to physicians and patients. STS101 ASCEND Phase 3 Long-term, Open-label Safety Trial In January 2023, the Company completed the STS101 ASCEND Phase 3 long-term safety trial, the primary goal of which was to establish the local nasal safety pro STS101 following repeated administration over time. STS101 was safe and well-tolerated, consistent with clinical experience to date, and final results from the trial were similar to previously-reported interim results, with no new safety signals identified. Final results include data from more than 150 subjects who treated their migraines with STS101* for more than six month and 50 subjects who treated their migraines with STS101* for more than 12 months, satisfying the long-term safety exposure requirements previously communicated to Satsuma by the FDA. Based on its communications with the FDA, the Company believes the results from the 12-month cohort are not required to support the NDA filing and approval, but as previously agreed with the FDA, the company plans to submit these results to the STS101 NDA at the 120-Day Safety Update. ___________________________ * STS101 incorporating the improved, second-generation nasal delivery device. Business update As previously announced, Satsuma does not intend to independently commercialize STS101 and is seeking to maximize value for stockholders via a strategic transaction. Upcoming Events and Milestones Three poster presentations featuring interim analyses from the STS101 ASCEND Phase 3 open-label, long-term safety study at the American Academy of Neurology (AAN) Annual Meeting, which is being held April 22-27 in Boston, MA and virtually Potential acceptance of the STS101 NDA in May 2023 Multiple abstracts submitted for presentation at the American Headache Society (AHS) 65th Annual Scientific Meeting, which is being held June 15-18 in Austin, TX Potential marketing approval of STS101 by January 2024 Financial results for the fourth quarter and full-year of 2022 Net losses for the fourth quarter and full year 2022 were $23.1 million and $70.1 million, respectively, or $0.70 and $2.19 per common share, respectively. This compared to a net loss of $15.6 million and $51.2 million, respectively, or $0.49 and $1.75 per common share, respectively, for the same periods in 2021. Research and development expenses were $8.7 million and $44.1 million for the fourth quarter and full year 2022, respectively, compared to $11.9 million and $37.6 million for the same periods of 2021, respectively. Fourth quarter expenses decreased by $3.2 million due to decreases in clinical expenses for SUMMIT and ASCEND and lower payroll and personnel expenses due to decreases in annual bonuses, partially offset by an increase in NDA preparation work and other clinical analysis. Impairment loss was $11.7 million for the fourth quarter and full year 2022 to write down the property and equipment to its fair market value, to write off prepaid expenses and other current assets related to purchase of property and equipment and accrue non-cancelable future payments related to purchase of the property and equipment. The impairment loss was a result of our reported topline results from the STS101 SUMMIT Phase 3 efficacy trial and our plan not to invest in commercialization of STS101. No impairment of long-lived asset has been recorded in prior years. General and administrative expenses were $3.2 million and $15.1 million for the fourth quarter and full year 2022, respectively, compared to $3.7 million and $13.5 million for the same periods of 2021, respectively. Fourth quarter expenses decreased due to decreased pre-commercialization expenses and lower payroll and personnel expenses due to decreases in annual bonuses. Satsuma has implemented cost reduction initiatives, including a reduction in force, effective March 31, 2023, of approximately 36%. About Satsuma Pharmaceuticals and STS101 Satsuma Pharmaceuticals is a development-stage biopharmaceutical company developing a novel therapeutic product, STS101, for the acute treatment of migraine. STS101 is a unique and proprietary nasal powder formulation of the well-established anti-migraine drug, dihydroergotamine mesylate (DHE), administered via Satsuma’s proprietary nasal delivery device. STS101 is designed to provide significant benefits versus existing acute treatments for migraine, including the combination of quick and convenient self-administration and other clinical advantages, that current DHE liquid nasal spray products and injectable dosage forms lack. Satsuma’s dry powder DHE formulation has demonstrated fast absorption, rapid achievement of high DHE plasma concentrations which Satsuma believes is necessary for robust efficacy, and sustained DHE plasma levels over time with low dose-to-dose variability. DHE has long been recommended in published migraine treatment guidelines as a first-line acute treatment option for migraine and has significant advantages versus other anti-migraine treatments for many patients. However, disadvantages of current DHE liquid nasal spray and injectable products, including invasive and burdensome administration and/or sub-optimal clinical performance, have limited the widespread use of DHE. Featuring an easy-to-carry and easy-to-use dosage form, STS101 is designed to overcome these shortcomings and provide patients an improved therapeutic solution for acutely treating migraines that consistently delivers robust clinical performance. Satsuma is headquartered in South San Francisco, California with operations in both California and Research Triangle Park, North Carolina. For further information, please visit . Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements concerning the business, operations and financial performance and condition of Satsuma Pharmaceuticals, Inc. (the “Company”), as well as the Company’s plans, objectives and expectations for its business operations and financial performance and condition. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “predict,” “potential,” “positioned,” “seek,” “should,” “target,” “will,” “would,” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements include, but are not limited to, statements about the potential timing and FDA approval of the Company's STS101 NDA submission, the potential for STS101 to be an important and differentiated acute treatment option, the ability of the Company to continue as a going concern, the potential and anticipated success of a strategic transaction, timing and scope of the reduction in force and the risk that the Company may not achieve the intended outcomes of its March 31, 2023 reduction in force. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, filed with the Securities and Exchange Commission, as well as other documents that may be filed by the Company from time to time. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of STS101; the results of preclinical and clinical studies may not be predictive of future results; and the risk that the COVID-19 worldwide pandemic may negatively impact the Company’s business, operations, clinical trials or ability to raise capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. INVESTOR AND CORPORATE CONTACTS: Corey Davis, PhD LifeSci Advisors, LLC 212-915-2577 cdavis@lifesciadvisors.com Tom O’Neil, Chief Financial Officer Satsuma Pharmaceuticals, Inc. tom@satsumarx.com SATSUMA PHARMACEUTICALS, INC. CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (in thousands, except share and per share data) (unaudited) Three Months Ended December 31, Year Ended December 31, 2022 2021 2022 2021 Operating expenses Research and development $ 8,698 $ 11,866 $ 44,092 $ 37,635 General and administrative 3,165 3,694 15,126 13,531 Impairment loss 11,729 — 11,729 — Total operating expenses $ 23,592 $ 15,560 $ 70,947 $ 51,166 Loss from operations (23,592 ) (15,560 ) (70,947 ) (51,166 ) Interest income 462 33 905 157 Interest expense — (24 ) (13 ) (163 ) Net loss $ (23,130 ) $ (15,551 ) $ (70,055 ) $ (51,172 ) Unrealized (loss) gain on marketable securities 33 (30 ) 12 (71 ) Comprehensive loss $ (23,097 ) $ (15,581 ) $ (70,043 ) $ (51,243 ) Net loss per share attributable to common stockholders, basic and diluted $ (0.70 ) $ (0.49 ) $ (2.19 ) $ (1.75 ) Weighted-average shares used in computing net loss per share attributable to common stockholders, basic and diluted 33,130,859 31,532,401 32,024,991 29,174,386 SATSUMA PHARMACEUTICALS, INC. BALANCE SHEET DATA (in thousands) (unaudited) December 31, 2022 December 31, 2021 Balance Sheet Data: Cash, cash equivalents and marketable securities $ 52,481 $ 95,770 Working capital 46,694 91,356 Total assets 54,939 109,832 Debt — 1,080 Accumulated deficit (211,791 ) (141,736 ) Total stockholders’ equity 46,824 101,340