Product Development and Clinical Trials - The lead product candidate, nebokitug, is in early clinical development for primary sclerosing cholangitis (PSC) and systemic sclerosis (SSc) [40]. - A Phase 1a safety study and a Phase 1b multiple ascending dose study of nebokitug have been completed, along with a Phase 2a safety study in metabolic dysfunction-associated steatohepatitis (MASH) patients [40]. - Nebokitug was generally well-tolerated in clinical studies with about 120 participants, with only minor adverse events reported [57]. - The Phase 3 trial for nebokitug in PSC is designed to enroll approximately 350 patients, focusing on moderate to advanced disease, with a primary endpoint of time-to-first clinical event [193]. - The Phase 2 SPRING trial enrolled 76 patients, demonstrating that nebokitug is well tolerated and effective in improving multiple disease-related secondary endpoints over 15 weeks [226]. - The open-label extension of the Phase 2 SPRING trial confirmed continued improvements in liver biomarkers over 48 weeks, with significant reductions in liver stiffness and total serum bile acids [228]. - The Phase 2a trial in MASH patients showed that nebokitug was well tolerated and demonstrated favorable pharmacokinetics and biomarker activity [222][224]. - The clinical development plan for nebokitug is designed to maximize clinical information and support future advancement to registration trials, thereby reducing overall risk [233]. Financial Position and Funding - The company has no products approved for commercial sale and has not generated any revenue to date [38]. - The company expects substantial efforts and expenditures on nebokitug over the next few years, requiring significant investment and marketing efforts before generating any revenues [41]. - The company will need to raise substantial additional funds through public or private equity or debt transactions to complete the development of nebokitug [42]. - Cash and cash equivalents as of December 31, 2024, are expected to fund operations through the first quarter of 2026 [43]. - As of December 31, 2024, the company had incurred an accumulated deficit of $102.6 million and expects to continue incurring significant operating losses for the foreseeable future [81]. - The company had gross proceeds of approximately $1.2 million from sales of equity and grants from the Israel Innovation Authority as of December 31, 2024 [81]. - The company's cash, cash equivalents, and deposits were approximately $14.3 million as of December 31, 2024, which are expected to fund operations through the end of the first quarter of 2026 [81]. - A private placement in July 2024 raised approximately $10 million, extending Chemomab's financial runway through early 2026 [201][211]. - The company may need to raise additional capital, which could lead to dilution or restrictions on operations if financing is not obtained on acceptable terms [163][164]. Regulatory and Market Challenges - The company faces risks related to the lengthy and complex clinical development process, which may result in delays or additional costs [55]. - The approach to treating fibrotic diseases is novel and unproven, with no assurance of developing marketable products [47]. - The company may experience significant setbacks in advanced clinical studies due to lack of efficacy or safety issues [50]. - Regulatory approval processes for product candidates are lengthy and unpredictable, with no guarantee of success, which could significantly harm the company's business [106]. - The company has not yet obtained regulatory approval for any product candidate, including nebokitug, which may hinder market entry [108]. - The FDA may approve product candidates for more limited indications than requested, affecting commercial prospects [112]. - Compliance with extensive regulatory requirements post-approval is necessary, and failure to do so could lead to loss of marketing approval [117]. - The lengthy and unpredictable nature of regulatory approval processes may result in significant resource expenditure without guaranteed outcomes [111]. - The commercialization of product candidates may be delayed if projected development goals are not achieved [128]. Market Opportunity and Competition - The potential market opportunity for nebokitug may be smaller than anticipated, with estimates based on various sources that could prove incorrect [69]. - The company faces substantial competition from major biopharmaceutical and biotechnology companies, which may hinder its product development efforts [130]. - The market acceptance of approved product candidates is uncertain and depends on various factors, including pricing and reimbursement policies [144]. - The inability to obtain adequate reimbursement rates from payors could adversely affect the company's financial condition and ability to raise capital [146]. Operational and Management Considerations - The company anticipates significant growth in employee numbers and operational scope, particularly in product candidate development, regulatory affairs, and sales and marketing [79]. - The company may face difficulties in managing growth, which could disrupt operations and lead to increased expenses and reduced productivity [79]. - The company relies on third-party suppliers for manufacturing clinical drug supplies and lacks internal manufacturing capabilities [135]. - Establishing sales, marketing, and distribution capabilities is crucial for the successful commercialization of products, but the company currently lacks this infrastructure [139]. - The executive team has extensive experience in inflammation, fibrosis, and biologics drug discovery, with key members having over 25 years of relevant experience [232]. Risks Related to External Factors - The ongoing war has led to a downgrade in Israel's credit rating by agencies such as Moody's, S&P Global, and Fitch, indicating a deterioration in economic conditions [153]. - The company is exposed to financial risks due to longer payment cycles and difficulties in collecting accounts receivable, which may be impacted by local and regional financial crises [152]. - The trading price of the company's American Depositary Shares (ADSs) has been highly volatile, with a closing price of $2.46 on September 3, 2024, and $0.51 on January 22, 2024 [166]. - The company is subject to currency fluctuation risks as some expenses are incurred in currencies other than the U.S. Dollar, which may affect operational results [159]. - The company’s commercial insurance does not cover losses from war and terrorism, which could materially affect its business if damages occur [156]. - The global perception of Israel may lead to increased sanctions and boycotts against Israeli companies, potentially impacting business operations [157]. - The company’s ability to operate may be affected by proposed changes to Israel's judicial system, which could lead to political instability or civil unrest [158]. Intellectual Property and Compliance - The company has received Orphan Drug Designation for nebokitug in connection with three indications, which may provide market exclusivity benefits [74]. - The transition to a "first-to-file" patent system in the U.S. may increase uncertainties and costs related to patent applications and enforcement [99]. - The AIA allows third parties to challenge patent validity, potentially impacting the company's patent rights and competitive position [100]. - Non-compliance with patent maintenance requirements could result in abandonment or loss of patent rights, impacting competitive position [105]. - The company has secured new patents for nebokitug in Europe, Brazil, and Israel, covering its use in treating liver diseases like PSC [207]. Strategic Focus and Future Directions - Chemomab has developed nebokitug, a monoclonal antibody targeting CCL24, with a market opportunity exceeding $1 billion for primary sclerosing cholangitis (PSC) and over $1.5 billion for systemic sclerosis (SSc) in the U.S., EU, and Japan [188][189]. - Chemomab's innovative approach targets the dual mechanisms of fibrosis and inflammation, addressing high unmet needs in rare diseases [188][189]. - The company is exploring nebokitug's potential in other fibrotic-inflammatory diseases, including idiopathic pulmonary fibrosis and MASH, based on promising preclinical results [220][230]. - Chemomab completed its End-of-Phase 2 Meeting with the FDA, aligning on a Phase 3 study design for nebokitug in PSC, which aims for regulatory approval based on a single pivotal trial without liver biopsies [199].

Core Insights - Chemomab Therapeutics Ltd. released results from the Open Label Extension (OLE) of the Phase 2 Spring trial for nebokitug in primary sclerosing cholangitis (PSC) patients, showing high patient retention and positive safety profile [1][2][3] Group 1: Trial Results - Over 90% of eligible Spring trial patients opted to continue into the OLE study [1] - Nebokitug was found to be safe and well-tolerated at doses of 10 mg/kg and 20 mg/kg administered every three weeks for up to 48 weeks [1] - Positive effects included improvements in key liver biomarkers such as the ELF score and the fibrosis biomarker PRO-C3 [2] Group 2: Clinical Outcomes - Liver stiffness scores in nebokitug-treated patients with moderate/advanced disease were significantly lower compared to historical controls [3] - Cholestasis-related markers remained stable over the 48-week treatment period, with total serum bile acids reduced [3] - Clinical events in OLE patients with moderate/advanced disease treated for 48 weeks were significantly lower at 4.8% compared to 25.8% in historical controls [3] Group 3: Placebo Group Results - Results from patients who received a placebo during the double-blind period and then transitioned to 33 weeks of treatment in the OLE were consistent with nebokitug-treated patients, showing stabilization of ELF scores and improvements in liver stiffness [4] Group 4: Market Reaction - Following the announcement, Chemomab stock increased by 2.59%, reaching $1.19 [4]

Core Insights - Nebokitug shows potential to be the first approved drug with disease-modifying activity for primary sclerosing cholangitis (PSC), a severe condition with no effective treatments currently available [1][2] - The Open Label Extension (OLE) of the Phase 2 SPRING trial demonstrated that treatment with nebokitug for 48 weeks led to significant improvements in key biomarkers of liver injury, inflammation, and fibrosis [1][2] - The treatment was well-tolerated, reinforcing positive results from the initial 15-week double-blind Phase 2 trial [1][2] Clinical Trial Results - In the OLE study, over 90% of eligible SPRING trial patients chose to continue treatment, with those previously on placebo receiving nebokitug for an additional 33 weeks, totaling up to 48 weeks of treatment [1][8] - Patients treated with nebokitug showed a significantly lower number of clinical events (4.8%) compared to historical controls (25.8%) [2][8] - Improvements were observed in liver stiffness scores, with nebokitug-treated patients showing substantial reductions compared to historical controls [2][4] Biomarker Improvements - Key liver biomarkers, including ELF score and PRO-C3, showed continued improvement over the treatment period [2][7] - Cholestasis-related markers stabilized, and total serum bile acids were reduced during the 48 weeks of treatment [2][8] - The results were particularly strong in patients with moderate/advanced disease, which is the focus for the upcoming Phase 3 trial [2][7] Future Development - The positive results from the OLE study are expected to derisk the Phase 3 clinical trial design, which will focus on the number of clinical events as the primary endpoint [2][7] - Nebokitug has received FDA and EMA Orphan Drug designations and FDA Fast Track status for PSC treatment, indicating a streamlined pathway for regulatory approval [9][13] - The company is preparing for the potential initiation of a Phase 3 trial based on the promising data from the Phase 2 SPRING trial [12][13]

Core Insights - Chemomab Therapeutics is advancing its clinical-stage monoclonal antibody, nebokitug (CM-101), as a potential treatment for systemic sclerosis (SSc), a severe autoimmune disease lacking approved therapies [1][3][12] - New data supporting nebokitug's efficacy will be presented at the CORA 2025 conference, reinforcing its role in targeting CCL24, a key driver of SSc pathology [1][6][12] Company Overview - Chemomab Therapeutics is focused on developing innovative therapeutics for fibro-inflammatory diseases, with nebokitug being a first-in-class dual activity monoclonal antibody that neutralizes CCL24 [12] - The company has received FDA and EMA Orphan Drug designations for nebokitug in the treatment of primary sclerosing cholangitis (PSC) and systemic sclerosis, along with FDA Fast Track status for PSC [12] Disease Context - Systemic sclerosis (SSc) is characterized by extensive tissue fibrosis and microvascular injury, making it one of the most lethal systemic connective tissue diseases, with no approved disease-modifying therapies available [2][8] - Current estimates suggest approximately 100,000 SSc patients in the U.S., predominantly affecting women aged 30 to 50 [8] Clinical Evidence - Extensive preclinical studies indicate that blocking CCL24 with nebokitug reduces inflammatory and fibrotic injuries associated with SSc, including lung, skin, and vascular damage [2][3] - A recent peer-reviewed study found that higher serum CCL24 levels correlate with severe SSc manifestations and predict pulmonary function deterioration [4] Ongoing Research - The upcoming presentation at CORA 2025 will detail a study assessing nebokitug's effects on immune cells in SSc, further validating the therapeutic rationale for targeting CCL24 [3][6] - Positive results from the Phase 2 SPRING trial in PSC have strengthened the rationale for evaluating nebokitug in SSc, demonstrating its dual anti-inflammatory and anti-fibrotic mechanisms [5][12]

Core Viewpoint - Chemomab Therapeutics is advancing its investigational drug nebokitug (CM-101) as a potential treatment for systemic sclerosis (SSc), supported by new preclinical and clinical data to be presented at CORA 2025 [1][3] Company Overview - Chemomab Therapeutics is a clinical-stage biotechnology company focused on developing innovative therapeutics for fibro-inflammatory diseases with significant unmet medical needs [12] - The company has developed nebokitug, a first-in-class dual activity monoclonal antibody that neutralizes CCL24, a protein implicated in fibrosis and inflammation [12] Drug Mechanism and Evidence - Nebokitug targets CCL24, which is a key driver of fibro-inflammatory conditions, including SSc and primary sclerosing cholangitis (PSC) [2][7] - Preclinical studies indicate that blocking CCL24 can reduce inflammatory and fibrotic injuries in the lungs, skin, and vasculature associated with SSc [2] - An investigator-sponsored study demonstrated that nebokitug led to significant reductions in inflammatory biomarkers in patients with acute lung injury, relevant to SSc [2] Clinical Data and Trials - The upcoming presentation at CORA 2025 will include findings from a study assessing nebokitug's effects on immune cells in SSc patients, reinforcing the therapeutic rationale for targeting CCL24 [3][6] - A 2024 peer-reviewed publication highlighted strong associations between CCL24 levels and severe clinical manifestations of SSc, indicating that higher CCL24 levels correlate with worse outcomes [4] - Positive results from the Phase 2 SPRING trial in PSC further support the potential of nebokitug, showing reductions in key fibro-inflammatory biomarkers [5] Regulatory Status - Nebokitug has received FDA and EMA Orphan Drug designations for both PSC and SSc, as well as FDA Fast Track status for PSC treatment [7][12] - The SSc program has an open U.S. Investigational New Drug (IND) application, indicating ongoing efforts to advance clinical trials [7][12] Disease Context - Systemic sclerosis (SSc) is a rare autoimmune disease characterized by severe fibrosis and inflammation, with no approved disease-modifying therapies currently available [8] - The disease predominantly affects women and has a median survival of only 10 years, highlighting the urgent need for effective treatments [8]

Core Insights - Chemomab Therapeutics has successfully completed an FDA End-of-Phase 2 meeting, establishing a clear pathway for potential regulatory approval of nebokitug for the treatment of primary sclerosing cholangitis (PSC) without the need for liver biopsies or confirmatory studies [1][4][3] - The company is on track to release clinical data from the SPRING trial open label extension in the first quarter of 2025, and discussions with potential strategic partners are ongoing [1][5][3] Clinical Development - The Phase 2 SPRING trial for nebokitug demonstrated a favorable safety profile and met its primary endpoint, with significant improvements in multiple secondary efficacy endpoints for patients with moderate/advanced PSC [3][4][7] - The FDA has aligned with Chemomab on a single pivotal Phase 3 trial design that focuses on clinical event-driven endpoints, which is expected to streamline the regulatory approval process [3][4][5] Financial Performance - For the full year ended December 31, 2024, Chemomab reported a net loss of $13.9 million, a decrease from a net loss of $24.2 million in 2023 [11][18] - Research and development expenses for 2024 were $11.3 million, down from $18.4 million in 2023, reflecting reduced clinical costs as the Phase 2 trial neared completion [8][11] Cash Position - As of December 31, 2024, Chemomab had cash, cash equivalents, and short-term bank deposits totaling $14.3 million, down from $19.9 million at the end of 2023, with a cash runway expected to last through the first quarter of 2026 [6][11] Strategic Outlook - The company is actively assessing various strategic paths forward and has received interest from potential partners following the positive FDA meeting [3][5] - Nebokitug has received FDA and EMA Orphan Drug and FDA Fast Track designations, positioning it as a promising candidate for addressing the unmet needs in PSC treatment [13]

Core Insights - Chemomab Therapeutics has successfully aligned with the FDA on a single Phase 3 registration study for its lead product candidate, nebokitug, aimed at treating primary sclerosing cholangitis (PSC) [2][3] - The Phase 3 trial design provides regulatory clarity and eliminates the need for liver biopsies or additional confirmatory studies, focusing on clinically relevant endpoints associated with PSC disease progression [3][5] - Nebokitug is a first-in-class dual activity monoclonal antibody that neutralizes CCL24, showing promise in treating PSC and other fibro-inflammatory diseases [7][11] Group 1: Trial Design and Objectives - The Phase 3 trial is a randomized placebo-controlled study with a 2:1 active to placebo ratio, enrolling approximately 350 PSC patients [6] - The primary endpoint is the time-to-first clinical event, which includes various adverse events related to PSC progression, such as acute cholangitis and liver transplantation [6][4] - The trial aims to collect sufficient clinical events to demonstrate statistically significant changes between treatment and placebo arms, with an estimated two-year timeline for participants to experience a clinically meaningful event without intervention [6][4] Group 2: Regulatory and Strategic Developments - The FDA's agreement on the trial design marks a significant milestone, providing a streamlined path to potential full regulatory approval based on a single pivotal trial [3][5] - The company is actively engaging with potential strategic partners while preparing for the Phase 3 program, which could launch before the end of the year [3][5] - The trial's design is similar to oncology registration trials, focusing on disease progression-related events, which may allow for broader labeling compared to symptom-related endpoints [5][6] Group 3: Clinical Background and Need - PSC is a rare and debilitating liver disease with no FDA-approved therapies, affecting an estimated 30,000 patients in the U.S. and 80,000 worldwide [8] - The disease is characterized by inflammation and fibrosis of the bile ducts, leading to severe complications such as liver failure and increased cancer risk [8] - There is a high unmet medical need for effective treatments to address PSC symptoms and slow disease progression, highlighting the importance of nebokitug's development [8][11]

Core Insights - Chemomab Therapeutics Ltd. is a clinical stage biotechnology company focused on developing innovative therapeutics for fibro-inflammatory diseases with high unmet need [3] - The company will present at the virtual Oppenheimer 35 Annual Healthcare Life Sciences Conference on February 11, 2025, with a live webcast available for 90 days [1][2] Company Overview - Chemomab is developing CM-101, a first-in-class dual activity monoclonal antibody that neutralizes the soluble protein CCL24, which plays a role in fibrosis and inflammation [3] - CM-101 has shown a favorable safety profile and potential to treat multiple severe fibro-inflammatory diseases, with positive results reported from four clinical trials [3] - The company anticipates achieving a clear FDA registrational pathway for the planned Phase 3 pivotal trial of CM-101 in primary sclerosing cholangitis (PSC) and reporting data from the SPRING trial open label extension in early 2025 [3] - CM-101 has received FDA and EMA Orphan Drug and FDA Fast Track designations for PSC treatment [3] - The program for systemic sclerosis treatment is Phase 2-ready with an open U.S. IND [3]

Core Insights - Chemomab Therapeutics Ltd. announced positive results from its Phase 2 SPRING trial for CM-101 in patients with primary sclerosing cholangitis (PSC), demonstrating anti-fibrotic, anti-inflammatory, and anti-cholestatic activity [1][5][6] Study Details - The Phase 2 SPRING trial involved 76 PSC patients receiving two doses of CM-101 (10 mg/kg and 20 mg/kg) every three weeks for 15 weeks [3] - The trial included a double-blinded, placebo-controlled design, focusing on patients who completed all doses and the week 15 visit [2][3] Efficacy and Safety - CM-101 met its primary endpoint with a favorable safety profile, showing mild to moderate adverse events similar to the placebo group [4] - Significant improvements were observed in liver stiffness, ELF scores, PRO-C3 levels, liver biochemistries, total bilirubin levels, and pruritus scores in CM-101 treated patients compared to placebo [4][5] Future Development - Chemomab plans to advance CM-101 into a registrational trial and expects to meet with the FDA by the end of 2024 to discuss the trial design [6][7] - An open-label extension of the Phase 2 SPRING trial is ongoing, with results anticipated in the first quarter of 2025 [7] Company Background - Chemomab is a clinical-stage biotechnology company focused on developing therapeutics for fibroinflammatory diseases, with CM-101 being a first-in-class monoclonal antibody targeting CCL24 [9] - The company has received FDA and EMA Orphan Drug designations and FDA Fast Track status for CM-101 in PSC [9]

Group 1 - Chemomab Therapeutics reported earnings per share of -26 cents for the second quarter of 2024 [1] - The company did not report any revenue for the quarter [1]