IFNAR

Responding to some of the challenges of its peers, Synthekine built a molecule called an IL-2 alpha/beta, dubbed STK-012. IL-2 medicines have shown the ability to kill tumors. Unfortunately, they aren’t very specific and have come to be associated with toxicities. Synthekine is hoping to avoid activating lymphocytes such as natural killer cells that can cause these issues, creating a safer and more tolerable medicine. That’s what early data from a phase 1a/1b trial of STK-012 seem to show, CEO Debanjan Ray told Fierce Biotech on the sidelines of the American Association for Cancer Research annual meeting Monday. The results are very early, with just a handful of partial responses. And Ray is well aware of the struggles of other IL-2s in the clinic—see Sanofi’s many challenges with the target. Responding to some of the hurdles faced by his peers, Ray said that with STK-012, Synthekine has built a molecule called an IL-2 alpha/beta that is meant to stimulate CD25+ antigen-activated T cells but avoid the same reaction with the NK cells that can drive toxicity in IL-2 meds. The early-stage trial tested the med in 47 patients with advanced solid tumors including non-small cell lung cancer, renal cell carcinoma and ovarian cancer. Most of the patients had three or more lines of therapy prior to entering the trial, which tested seven dose levels on two dosing schedules. Of the 40 evaluable patients, three had a partial response as of data cutoff and 12 had stable disease. In a group of 15 patients who had not previously responded to immune checkpoint inhibitors and were minimally pretreated, three had a best overall response of partial response and six had stable disease. “The promise of IL-2 in the treatment of solid tumors has yet to be realized as IL-2 analogues developed to date have had limited efficacy and an unacceptable toxicity profile,” said Naiyer Rizvi, M.D., Synthekine’s chief medical officer, in a Tuesday statement. The therapy was associated with favorable safety, pharmacokinetics and pharmacodynamics, with a profile that was different from aldesleukin and non-alpha IL-2 analogues. The early data suggest that STK-012 is selective for T cells that express CD25. Ray also noted that the response was durable in multiple subjects, with some continuing to benefit for as much as a year after the data cutoff. Synthekine’s presentation included one patient case study of a 72-year-old female who had stage 4 clear cell renal cell carcinoma and had previously had two prior lines of therapy. The patient had “innumerable lung metastases and a large primary renal mass.” At Week 12, the photos show a reduction in tumors. “You don't need to be a radiologist to really see this difference,” Ray said. Synthekine has selected the every-three-weeks schedule to go forward. Ray said next steps include focusing on the ongoing dose expansion, monotherapy arm including one cohort focusing on renal cancer. While early, Synthekine’s work has attracted some Big Pharma partners, including Sanofi. The French pharma signed a $40 million deal with Synthekine in January to work on IL-10 receptor agonists designed to treat inflammatory diseases. Merck & Co. has also linked up with the biotech but for autoimmune diseases, signing a deal that could be worth up to $525 million in biobucks in November 2021. Editor's note: This story was updated at 5 p.m. ET to clarify details about the dose expansion and Synthekine's partnership with Sanofi.

--Poster highlights potential of oral small molecule IFNAR agonist program to engage the IFNα pathway through a liver-focused approach to improve tolerability-- SOUTH SAN FRANCISCO, Calif., Nov. 10, 2023 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB), a biotechnology company developing innovative antiviral therapeutics targeting serious viral diseases, today announced new data from its virology portfolio featured in two presentations at the American Association for the Study of Liver Diseases (AASLD), The Liver Meeting®, taking place November 10-14, 2023, in Boston. “These data underscore our continued commitment to advancing innovative programs with the potential to change the treatment paradigm for patients impacted by serious viral diseases and highlight the promise of our preclinical IFNAR agonist program, which is in lead optimization,” said William Delaney, PhD, chief scientific officer of Assembly Bio. “Additionally, the Phase 2 data reported for vebicorvir in combination with Nrtl and Arbutus Biopharma’s AB-729 provide further insights that may inform future studies for the HBV and liver disease scientific community." A poster presentation entitled “In Vitro and in Vivo Profiling of Orally Bioavailable Small Molecules Inhibiting Hepatitis B Virus by Mimicking Interferon Alpha” highlights preclinical data describing the inhibition of hepatitis B virus (HBV) and hepatitis C virus (HCV) in vitro through the activation of interferon (IFN) signaling by novel small molecule interferon-α (IFNα) receptor (IFNAR) agonists. The IFNAR agonists described in this poster closely mimic the biological activity of IFNα in vitro by stimulating cytokine secretion and inducing IFN-stimulated genes (ISG) following treatment of human cells. In addition, oral administration to preclinical species resulted in ISG induction in the liver and peripheral blood mononuclear cells (PBMCs). Additionally, an oral presentation is scheduled entitled “Preliminary Off-Treatment Responses Following 48 Weeks of Vebicorvir, Nucleos(t)ide Reverse Transcriptase Inhibitor, and AB-729 Combination in Virologically Suppressed Patients With Hepatitis B e Antigen Negative Chronic Hepatitis B: Analysis From an Open-Label Phase 2 Study.” Results described in this presentation indicate that first-generation core inhibitor vebicorvir (VBR) in combination with nucleos(t)ide reverse transcriptase inhibitor (Nrtl) and Arbutus Biopharma’s AB-729 in virologically suppressed patients with hepatitis B e antigen negative chronic HBV did not result in significantly greater on- or post-treatment improvements in markers of active HBV infection versus the dual combination without VBR. Assembly Bio discontinued development of VBR in 2022. Assembly Bio intends to make the presentations available on the “Events & Presentations” page in the “Investors” section of its website at www.assemblybio.com. About Assembly BiosciencesAssembly Biosciences is a biotechnology company dedicated to the development of innovative small-molecule antiviral therapeutics designed to change the path of serious viral diseases and improve the lives of patients worldwide. Led by an accomplished team of leaders in virologic drug development, Assembly Bio is committed to improving outcomes for patients struggling with the serious, chronic impacts of herpesvirus, hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections. For more information, visit assemblybio.com. Forward-Looking StatementsThe information in this press release contains forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to materially differ. These risks and uncertainties include: Assembly Bio’s ability to realize the potential benefits of its collaboration with Gilead, including all financial aspects of the collaboration and equity investments; Assembly Bio’s ability to initiate and complete clinical studies involving its therapeutic product candidates, including studies contemplated by Assembly Bio’s collaboration with Gilead, in the currently anticipated timeframes or at all; the occurrence of any event, change or other circumstance that could give rise to the termination of Assembly Bio’s collaboration with Gilead; safety and efficacy data from clinical or nonclinical studies may not warrant further development of Assembly Bio’s product candidates; clinical and nonclinical data presented at conferences may not differentiate Assembly Bio’s product candidates from other companies’ candidates; results of nonclinical studies may not be representative of disease behavior in a clinical setting and may not be predictive of the outcomes of clinical studies; and other risks identified from time to time in Assembly Bio’s reports filed with the U.S. Securities and Exchange Commission (the SEC). You are urged to consider statements that include the words may, will, would, could, should, might, believes, hopes, estimates, projects, potential, expects, plans, anticipates, intends, continues, forecast, designed, goal or the negative of those words or other comparable words to be uncertain and forward-looking. Assembly Bio intends such forward-looking statements to be covered by the safe harbor provisions contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. More information about Assembly Bio’s risks and uncertainties are more fully detailed under the heading “Risk Factors” in Assembly Bio’s filings with the SEC, including its most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Except as required by law, Assembly Bio assumes no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. ContactsInvestor and Corporate: Shannon Ryan SVP, Investor Relations, Corporate Affairs and Alliance Management (415) 738-2992 sryan@assemblybio.com Media: Sam Brown Inc.Hannah Hurdle(805) 338-4752ASMBMedia@sambrown.com

-- One poster and one oral presentation selected, with the poster highlighting new preclinical data from the Company’s interferon-α receptor agonist program -- SOUTH SAN FRANCISCO, Oct. 11, 2023 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB), a biotechnology company developing innovative antiviral therapeutics targeting serious viral diseases, today announced that preclinical and clinical data from its virology portfolio will be featured in two presentations at the upcoming American Association for the Study of Liver Diseases (AASLD), The Liver Meeting®, taking place November 10-14, 2023, in Boston. At the meeting, one poster presentation will share new preclinical data from the Company’s interferon-α receptor (IFNAR) agonist program in chronic hepatitis B virus (HBV), currently in lead optimization. Additionally, an oral presentation will highlight data from the Phase 2 study of first-generation core inhibitor vebicorvir (VBR) in combination with nucleos(t)ide reverse transcriptase inhibitor (Nrtl) and Arbutus Biopharma’s AB-729 in virologically suppressed patients with hepatitis B e antigen negative chronic HBV. “We look forward to presenting data at this year’s AASLD, The Liver Meeting®, featuring the exciting progress of our preclinical IFNAR agonist program and its potential to engage the interferon-α pathway with improved tolerability through an oral, liver-focused approach,” said William Delaney, PhD, chief scientific officer of Assembly Bio. “Additionally, we’re pleased to share further insights from the Phase 2 data reported for vebicorvir in combination with Nrtl and Arbutus Biopharma’s AB-729 with the HBV and liver disease scientific community." Details of the poster and oral presentations are as follows: Interferon-α Receptor Agonist: Poster Presentation: In vitro and in vivo profiling of orally bioavailable small molecules inhibiting hepatitis B virus by mimicking interferon alphaPresenter: Marc P. Windisch, PhD, Assembly BioPoster Number: 1474-CDate and Time: November 10, 12:00 PM–1:00 PM ET Vebicorvir, Nrtl and AB-729: Oral Presentation: Preliminary Off-Treatment Responses Following 48 Weeks of Vebicorvir, Nucleos(t)ide Reverse Transcriptase Inhibitor, and AB-729 Combination in Virologically Suppressed Patients with Hepatitis B e Antigen Negative Chronic Hepatitis B: Analysis From an Open-Label Phase 2 StudyPresenter: Scott Fung, MD, FRCPC, Toronto General HospitalSession: Hepatitis B: New Therapies for HBV and HDVDate and Time: November 12, 8:30 AM ET Assembly Bio intends to make the presentations available on the “Events & Presentations” page in the “Investors” section of its website at www.assemblybio.com. About Assembly BiosciencesAssembly Biosciences is a biotechnology company dedicated to the development of innovative small molecule antiviral therapeutics designed to change the path of serious viral diseases and improve the lives of patients worldwide. Led by an accomplished team of leaders in virologic drug development, Assembly Bio is committed to improving outcomes for patients struggling with the serious, chronic impacts of herpesvirus, hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections. For more information, visit assemblybio.com. Forward-Looking StatementsThe information in this press release contains forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to materially differ. These risks and uncertainties include: Assembly Bio’s ability to maintain financial resources necessary to continue its clinical studies and fund business operations; Assembly Bio’s ability to initiate and complete clinical studies involving its therapeutic product candidates, including studies contemplated by Assembly Bio’s collaboration agreements, in the currently anticipated timeframes; safety and efficacy data from clinical or nonclinical studies may not warrant further development of Assembly Bio’s product candidates; clinical and nonclinical data presented at conferences may not differentiate Assembly Bio’s product candidates from other companies’ candidates; results of nonclinical studies may not be representative of disease behavior in a clinical setting and may not be predictive of the outcomes of clinical studies; and other risks identified from time to time in Assembly Bio’s reports filed with the U.S. Securities and Exchange Commission (the SEC). You are urged to consider statements that include the words may, will, would, could, should, might, believes, hopes, estimates, projects, potential, expects, plans, anticipates, intends, continues, forecast, designed, goal or the negative of those words or other comparable words to be uncertain and forward-looking. Assembly Bio intends such forward-looking statements to be covered by the safe harbor provisions contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. More information about Assembly Bio’s risks and uncertainties are more fully detailed under the heading “Risk Factors” in Assembly Bio’s filings with the SEC, including its most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Except as required by law, Assembly Bio assumes no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts Investor and Corporate:Shannon RyanSVP, Investor Relations, Corporate Affairs and Alliance Management(415) 738-2992sryan@assemblybio.com Media:Sam Brown Inc. Hannah Hurdle (805) 338-4752 ASMBMedia@sambrown.com