EBI3

On September 11, 2024, Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved Tremfya (guselkumab) for the treatment of moderate to severe active ulcerative colitis (UC) in adult patients. The company claims that Tremfya is the first and only dual-acting inhibitor targeting interleukin 23 (IL-23) to be approved for this indication, solidifying Johnson & Johnson’s leadership position in the field of inflammatory bowel diseases. About GuselkumabGuselkumab is the first IL-23 inhibitor globally approved, selectively binding to the p19 subunit of IL-23 and blocking its interaction with the IL-23 receptor. This mechanism of action yields significant therapeutic effects across various autoimmune diseases. Guselkumab not only inhibits IL-23 but also interacts with the CD64 receptor on cells that produce IL-23. Tremfya has garnered approvals for treating plaque psoriasis, active psoriatic arthritis, and UC. Additionally, in June 2024, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the FDA for the treatment of moderate to severe active Crohn's disease (CD) in adults. Study Data Supporting ApprovalThe FDA's approval for UC was primarily based on data from the Phase 2b/3 QUASAR study. This study assessed the efficacy and safety of Tremfya in adult patients with moderate to severe active UC who had an inadequate response or intolerance to conventional therapies, other biologics, and/or JAK inhibitors. The results demonstrated that 50% of patients receiving Tremfya 200 mg subcutaneously (SC) every four weeks (q4w), and 45% of patients receiving Tremfya 100 mg SC every eight weeks (q8w), achieved the primary endpoint of clinical remission at Week 44, compared to 19% of those receiving placebo (p<0.001). Additionally, one year after maintenance therapy, 34% (200 mg) and 35% (100 mg) of patients achieved endoscopic remission, as opposed to 15% in the placebo group (p<0.001). During the induction treatment phase, the most common adverse reactions (>2%) for both Tremfya and placebo groups were respiratory infections. In the maintenance phase, the most frequent adverse reactions (>3%) among patients treated with Tremfya or placebo included injection site reactions, joint pain, and upper respiratory infections. About IL-23 p19 DrugsIL-23 p40 serves as a common subunit for both IL-12 and IL-23, with p40 antibodies providing a classical immunotherapy by blocking both IL-12 and IL-23 pathways. However, recent developments in IL-23 p19 antibodies, exemplified by guselkumab, have shown superior efficacy and safety profiles compared to p40 antibodies. The p19 subunit, besides forming the classical inflammatory cytokine IL-23 with p40, can also combine with EBI3 to form IL-39, which activates pathways involving IL-23R and gp130. Both IL-23 and IL-39 can trigger intracellular JAK-STAT signaling pathways, thereby stimulating the secretion of IL-17A/F. This sophisticated approach to targeting IL-23 not only reaffirms Johnson & Johnson’s innovative footprint in treating inflammatory and autoimmune diseases but also signals a promising horizon for patients battling these chronic conditions. In October 2023, Eli Lilly's Omvoh (mirikizumab) received FDA approval for the treatment of adults with moderately to severely active ulcerative colitis (UC). This marks the first IL-23p19 antagonist approved for this patient group. Additionally, AbbVie's risankizumab was the first IL-23 inhibitor to receive FDA approval for inflammatory bowel disease (IBD). It was approved for Crohn’s disease (CD) in June 2022 and for UC in June 2024. About Inflammatory Bowel Disease (IBD)IBD is a nonspecific, chronic, relapsing inflammatory condition of the intestines, commonly presenting with symptoms such as diarrhea, rectal bleeding, abdominal pain, fatigue, and weight loss. The precise cause and mechanism of IBD are not fully understood. However, the prevailing theory suggests that it involves an autoimmune dysfunction triggering an abnormal immune response, leading the immune system to attack normal cells in the digestive tract. IBD includes two main disorders: ulcerative colitis (UC) and Crohn's disease (CD).  UC causes inflammation and ulcers on the surface lining of the colon and rectum, whereas CD can affect any part of the digestive tract, typically involving deeper layers of the gut lining. In rare cases, it can also affect the colon and upper gastrointestinal tract. In 2019, the global prevalence of IBD was approximately 4.9 million, with China accounting for 910,000 patients. From 1990 to 2019, the incidence of IBD in Chinese men increased from 1.72 cases per 100,000 to 3.35 cases per 100,000, while in women, the numbers rose from 1.20 to 2.45 per 100,000. The current global market for IBD therapies has expanded to $18 billion. Research indicates that the migration of white blood cells into intestinal tissue is key to the onset and persistence of IBD. This process depends on the specific binding between adhesion molecules on endothelial cells (such as VCAM-1, MAdCAM-1) and integrins on white blood cells, composed of α and β subunits. Targeting and inhibiting these specific interactions can effectively treat intestinal inflammation in IBD. Elevated levels of cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-12/23 (IL-12/23), and leukocyte adhesion molecules are commonly seen during active disease phases of IBD. Inhibiting these cytokines can effectively disrupt downstream inflammatory responses and leukocyte chemotaxis, which lead to mucosal damage. Other targets such as the Janus kinase (JAK)/STAT pathway and gut microbiota are increasingly being recognized for their roles in IBD. Since the etiology and pathogenesis of IBD remain unclarified, it cannot be cured. Current drug therapies focus on reducing inflammation, maintaining remission, lowering relapse rates, and reducing the need for surgery. Common treatments include anti-inflammatory drugs, immunosuppressants, antibiotics, small molecule oral drugs, and biologics. Compared to traditional drugs like 5-aminosalicylic acids, steroids, and immunosuppressants, biologics are becoming the mainstream treatment for IBD due to their clearer efficacy and better safety profiles. Johnson & Johnson's Position in IBDIn the IBD sphere, Johnson & Johnson has developed TNF-α inhibitors infliximab and golimumab, each generating over $2 billion in sales in 2023. In addition to guselkumab, the company is developing the first IL-12/23 antibody Stelara (ustekinumab) and the oral IL-23 inhibitor JNJ-2113 for IBD indications. Furthermore, the company is working on a combination therapy for recurrent patients using guselkumab and golimumab (JNJ-8408). According to incomplete statistics, Johnson & Johnson currently has nearly 20 drugs in development for the treatment of inflammatory bowel disease. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!

CAMBRIDGE, Mass., April 09, 2021 (GLOBE NEWSWIRE) -- Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, will present preclinical findings supporting the company’s lead product programs, SRF388 (targeting IL-27) and SRF617 (targeting CD39). These data will be presented as part of the American Association for Cancer Research (AACR) 2021 Annual Meeting, which is being held virtually April 10-15 and May 17-21, 2021. “These findings further support the biological rationale that both of our lead product candidates, SRF388 and SRF617, promote increased proinflammatory activity within the tumor microenvironment in the hopes of ultimately providing novel treatment options to patients with cancer,” said Vito Palombella, chief scientific officer. “We look forward to sharing data from the ongoing Phase 1 clinical trials for both programs this June.” The e-poster website will be launched at 8:30 a.m. ET on Saturday, April 10, and will remain available for viewing through Monday, June 21. The two e-posters will also be viewable on the Surface Oncology website. Presentation Type: e-poster (Abstract: 1802) Title: CD39 inhibition shapes the transcriptional landscape of myeloid cells and induces proinflammatory states in the CT26 syngeneic tumor model Lead Authors: Devapregasan Moodley, Ph.D. and Mayra Carneiro Summary: SRF617 is a potent inhibitor of CD39 enzymatic activity both in vitro and in vivo. Increased activity of CD39 results in significant reductions in extracellular ATP and subsequent accumulation of adenosine, contributing to tumor immune escape, induction of angiogenesis and metastatic progression. Immunological mechanisms associated with CD39 blockade reveal major changes to immunocyte transcriptional landscapes, including upregulation of several proinflammatory genes. CD39 inhibition predominantly shaped the transcriptional landscape of myeloid cells and dendritic cells, and generally induced proinflammatory conditions. These findings indicate that CD39 blockade induces proinflammatory responses, supporting future clinical studies of SRF617 for treating patients with cancer. Presentation Type: e-poster (Abstract: 1607) Title: IL-27 signaling serves as an immunological checkpoint for NK cells to promote hepatocellular carcinoma in multiple murine models Lead Author: Turan Aghayev Summary: IL-27 signaling suppresses natural killer (NK) cells within the tumor microenvironment, promoting hepatocellular carcinoma (HCC) development in vivo. Elevated IL-27RA expression in cancer tissue and elevated EBI3 serum levels are associated with poor prognosis in patients with HCC. Inhibiting IL-27 signaling leads to tumor growth inhibition and suppressed HCC development in a non-alcoholic steatohepatitis (NASH)-driven HCC model with concomitant enhancement of NK cell activity. These findings indicate that IL-27 blockade regulates NK cell-mediated control of HCC and is a promising therapeutic target in liver cancer. About SRF617: SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39, allowing for a dual mechanism of action to promote anti-tumor immunity via reduction of immunosuppressive adenosine in addition to increasing levels of immunostimulatory ATP. A substantial body of research supports a role for CD39 in allowing cancer to evade immune responses. For example, pancreatic cancer stromal cells within the tumor micro-environment express high levels of CD39 which may inhibit anti-cancer immune responses. In preclinical studies, SRF617 has exhibited strong affinity for and inhibition of CD39, the ability to reduce adenosine and increase ATP levels and anti-tumor activity both as a single agent and in combination with multiple therapeutic agents. About SRF388: SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver and kidney cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immuno-suppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of hepatocellular carcinoma from the FDA. About Surface Oncology: Surface Oncology is an immuno-oncology company developing next-generation antibody therapies focused on the tumor microenvironment. Its pipeline includes two wholly-owned clinical-stage programs targeting CD39 (SRF617) and IL-27 (SRF388), as well as a preclinical program focused on depleting regulatory T cells via targeting CCR8 (SRF114). In addition, Surface has two partnerships with major pharmaceutical companies: a collaboration with Novartis targeting CD73 (NZV930; Phase 1) and a collaboration with GlaxoSmithKline targeting PVRIG (SRF813; preclinical). Surface’s novel cancer immunotherapies are designed to achieve a clinically meaningful and sustained anti-tumor response and may be used alone or in combination with other therapies. For more information, please visit . Cautionary Note Regarding Forward-Looking Statements: Certain statements set forth in this press release constitute “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements can be identified by terms such as “believes,” “expects,” “plans,” “potential,” “would” or similar expressions, and the negative of those terms. These forward-looking statements are based on Surface Oncology’s management’s current beliefs and assumptions about future events and on information currently available to management. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Surface Oncology’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks include, but are not limited to, risks and uncertainties related to Surface Oncology’s ability to successfully develop SRF388 and SRF617 and its other product candidates through current and future milestones or regulatory filings on the anticipated timeline, if at all, the therapeutic potential of Surface Oncology’s product candidates, the risk that results from preclinical studies or early clinical trials may not be representative of larger clinical trials, the risk that Surface Oncology’s product candidates, including SRF388 and SRF617, will not be successfully developed or commercialized, the risks related to Surface Oncology’s dependence on third-parties in connection with its manufacturing, clinical trials and preclinical studies, and the potential impact of COVID-19 on our clinical and preclinical development timelines and results of operations. Additional risks and uncertainties that could affect Surface Oncology’s future results are included in the section titled “Risk Factors” in our Annual Report on Form 10-K for the year ending December 31, 2020, which is available on the Security and Exchange Commission’s website at and Surface Oncology’s website at . Additional information on potential risks will be made available in other filings that Surface Oncology makes from time to time with the Securities and Exchange Commission. In addition, any forward-looking statements contained in this press release are based on assumptions that Surface Oncology believes to be reasonable as of this date. Except as required by law, Surface Oncology assumes no obligation to update these forward-looking statements, or to update the reasons if actual results differ materially from those anticipated in the forward-looking statements. Contacts: Investors Matt Lane matt@gilmartinir.com 617-901-7698 Media Chris Railey chris@tenbridgecommunications.com 617-460-3579

March 8, 2016 By Alex Keown , BioSpace.com Breaking News Staff SOUTH SAN FRANCISCO – Privately-held Tizona Therapeutics, Inc. , a new company focusing on developing immuno-oncology treatments and therapies for autoimmune diseases, announced $43 million in Series B financing to help drive its treatments into clinical trials. The new round of financing brings the total funds raised by the company to more than $70 million, Tizona said in a statement. The financing will be used to advance Tizona’s immunotherapy programs, including its lead candidate, an anti-CCR4 monoclonal antibody for the treatment of cancer, the company said in a statement. On Tizona’s website, the company said its anti-CCR4 antibody is “expected to play an instrumental role in potentiating anti-tumor immune responses by selectively depleting Tregs (regulatory T cells) and preventing them from migrating into the tumor microenvironment.” Regulatory T cells regulate the body’s immune system activity. Tizona’s lead therapy is expected to enter the clinic in 2017, the company said. Pablo Cagnoni , president and chief executive officer of Tizona, said in a statement that he expects Tizona’s anti-CCR4 antibody to play an important role in inducing antitumor activity in cancer patients. Tizona’s therapies are designed to “modulate the activity of immunosuppressive cells,” which will ignite the body’s ability to fight cancer or prevent the immune system from attacking healthy tissues in autoimmune diseases, the company said on its website . “We have an opportunity to contribute a potentially valuable new addition to the group of novel immunotherapies that is changing standards of care in cancer treatment. With support from this investor group, along with our renowned scientific founders and accomplished team, Tizona is well-positioned to be a leader in the development of next generation immunotherapies,” Cagnoni said. In addition to Tizona’s anti-CCR4 antibody, the company pipeline also includes the company’s IL-35 programs. IL-35 is a recently discovered immunosuppressive cytokine, predominantly expressed by Tregs, the company said. IL-35 is involved in suppression of anti-tumor immunity through its modulation of effector T cells, as well as myeloid cells. Tzona believes blocking IL-35’s activity may reverse immune suppression in the tumor microenvironment and “lead to a robust and effective anti-tumor immune response.” Given IL-35’s potent suppressive properties, targeting this pathway also holds significant promise as a potential first-in-class treatment for autoimmune diseases, Tizona said. The latest financing round was led by Abingworth and Canaan Partners with investments from Lightstone Ventures . Additionally MPM Capital , Amgen Ventures , Astellas Venture Management and InterWest Partners also played a role in the latest financing round. As part of the financing, Shelley Chu , a partner of Abingworth, Nina Kjellson , a partner of Canaan Partners and Jean George , general partner of Lightstone Ventures, have joined Tizona’s board of directors, the company announced.