Murepavadin

Ad hoc announcement pursuant to Art. 53 LR Balixafortide, a potent CXCR4 inhibitor, to be evaluated for the treatment of pancreatic ductal adenocarcinoma (PDAC)Spexis closed capital commitments totaling USD $7.5 million supporting Phase 3 ColiFin® program in cystic fibrosis (CF) infectionsCOPILOT study expected to initiate in fourth quarter 2023Appointed Gonçalo Bernardes, PhD, as acting Head of Chemical BiologyAnnounced strong safety and pharmacokinetics results from first-in-human study with inhaled murepavadin, a novel macrocycle compoundEngaged Maxim Group LLC as M&A advisor to evaluate strategic transactions of which Spexis would be the surviving companyBusiness update conference call to be held in October ALLSCHWIL, Switzerland, Sept. 28, 2023 (GLOBE NEWSWIRE) -- Spexis AG (SIX: SPEX), a clinical-stage biopharmaceutical company focused on macrocycle therapeutics for rare diseases and oncology, today announced its financial results for the first half of 2023 and provided a strategic business update. “Spexis remains on track to deliver on the potential of our robust pipeline with multiple clinical development milestones on the horizon,” said Jeff Wager, M.D., Chairman & CEO of Spexis. “We anticipate initiating our Phase 3 ColiFin® program beginning with the COPILOT study in the fourth quarter supported by our financial partner on this program, SPRIM Global Investments. In addition, we have completed our initial analysis of further indication development potential for balixafortide. Based on our analysis, we are excited to announce balixafortide’s new focus on the treatment of PDAC where patients have long faced bleak and limited treatment options. Balixafortide’s well-documented and encouraging selective antagonism of the CXCR4 chemokine receptor and the new preclinical research illustrating its potential in PDAC have encouraged the company to focus our resources on the clinical development of balixafortide in this indication. We look forward to providing additional updates as our novel macrocycle derived pipeline continues to advance.” Pipeline status and plans The plans outlined below regarding the further development of various programs are subject to Spexis raising additional funds and/or entering into partnering agreements. Lead Program, ColiFin®: Spexis is committed to progressing its lead program ColiFin®, which is currently being developed to treat chronic lung infections in cystic fibrosis patients, but which also has strong therapeutic potential in non-CF bronchiectasis (nCFBE) and chronic obstructive pulmonary disease (COPD), as these patients also suffer from chronic Pseudomonas aeruginosa (PA) lung infections. ColiFin® has been approved in the EU as an inhaled therapeutic and holds Orphan Drug and QIDP designations in the U.S. The company has worldwide rights to ColiFin® ex-Europe and is preparing a Phase 3 program in CF patients which includes the COPILOT safety and tolerability trial, and the COPA efficacy trial. COPILOT is expected to initiate prior to the end of 2023. Capital commitments from SPRIM Global Investments (SGI) and additional institutional investors totaling USD $7.5 million to-date will enable the near-term initiation of COPILOT. The company’s clinical trial partnership with SGI, which includes debt facilities, is expected to provide Spexis with up to half of the Phase 3 clinical development costs of ColiFin®. Future milestones are contingent on securing additional capital and/or partnering agreements. Balixafortide: Today Spexis announced plans to pursue the clinical development of balixafortide, the Company’s potent and selective macrocyclic CXCR4 inhibitor, in PDAC, an aggressive form of pancreatic cancer with a poor survival rate. Balixafortide has been well-studied in clinical trials and has demonstrated a promising safety profile both as a monotherapy as well as in combination with other therapies. PDAC has been traditionally resistant to immunotherapy due to a combination of tumor microenvironment features unique to PDAC, but recent preclinical studies have shown the successful modulation of these factors using anti-CXCR4 antibodies, anti-programmed cell death protein 1 antibodies (anti-PD-1) and focal adhesion kinase inhibitors (FAKi). The combination of anti-CXCR4 antibodies, anti-PD-1 antibodies and FAKi led to a significantly decreased metastatic rates in a well-validated PDAC murine liver metastasis model. These results were subsequently validated substituting anti-CXCR4 antibodies for balixafortide. The synergistic effects of targeting PDAC with this regimen represents a unique opportunity for balixafortide to address the significant unmet need that has persisted in the fight against pancreatic cancer. PDAC accounts for more than 90% of pancreatic cancer diagnoses, and its poor survival rate is due to limited treatment options and the absence of an early diagnosis in many patients. The average 5-year survival rate is less than 10%, and pancreatic cancer represents an increasing and worrying proportion of cancer deaths. In 2023, the American Cancer Society projects over 50,000 patients will die of pancreatic cancer in the United States, the third-leading cause of cancer deaths. Despite a growing patient population, treatment options have remained limited, increasing the demand for novel therapeutics and approaches. Inhaled murepavadin (iMPV): Earlier in 2023, Spexis announced safety and pharmacokinetics results from the company’s first-in-human study with inhaled murepavadin, its novel macrocycle compound. Results indicated that iMPV was well tolerated at all dose levels and no serious adverse events were reported in the Phase 1 double-blind, randomized, placebo-controlled trial. iMPV was derived from Spexis’ macrocycle platform, validating its potential to generate clinically relevant therapeutics capable of drugging specific targets across a variety of rare diseases. The study was supported by the European Innovative Medicines Initiative (IMI), with iMPV successfully targeting the outer membrane of Pseudomonas aeruginosa, showing activity against highly resistant strains of bacteria. Spexis remains committed to addressing antibiotic resistance and progressing iMPV through the clinic. Macrocycle platform: Macrocycles remain a key differentiator at Spexis as this burgeoning area of drug discovery yields additional promise. The company’s leadership in the space represents an opportunity to yield novel therapeutics and the potential to combine macrocycles with a wide variety of complementary technologies, including, but not limited to, molecular glues and degraders. Spexis possesses two distinct, highly diverse and very well characterized macrocycle libraries, together with deep data on each: PEMfinder®, which is comprised of peptidomimetic macrocycles, and MACROfinder®, which are small molecule macrocycles. Each library has distinct applications depending on the targets involved, with several pre-clinical characterized leads for various indications having already been identified and characterized. As one example of the power of Spexis’ macrocycle platform, in June of this year, Spexis announced the publication of promising results for a novel class of macrocyclic, peptidomimetic antibiotics in Science Advances demonstrating potent in vitro and in vivo antimicrobial activity against MDR and XDR Enterobacteriaceae, including carbapenem-resistant and colistin-resistant strains. The novel antibiotics were developed by Spexis in close collaboration with Professor Oliver Zerbe’s group at the University of Zurich with substantial funding by Innosuisse and CARB-X. Corporate updates Spexis announced the appointment of Gonçalo Bernardes, Ph.D., as acting Head of Chemical Biology. Dr. Bernardes is a Full Professor of Chemical Biology and a Fellow of Trinity Hall College, Cambridge. He has co-founded companies using technologies developed in his lab and has been awarded three European Research Council grants, as well as awards from the Royal Society of Chemistry, International Chemical Biology Society, European Federation of Medicinal Chemistry and The Blavatnik Family Foundation. Dr. Bernardes also serves as a Senior Fellow at Flagship Pioneering, the largest global venture incubator. He completed his Ph.D. at the University of Oxford, U.K., and his postdoctoral work at the Swiss Federal Institute of Technology (ETH) in Zürich. Multiple discoveries made in his lab have been translated into leading biopharmaceutical companies. At Spexis Dr. Bernardes will focus his efforts on the company’s leading and proprietary macrocycle platform to produce novel therapeutics for the treatment of cancer and rare diseases. The Company expects to announce specific programs already in development in collaboration with Prof. Bernardes in the coming weeks and months. Financial results In the first half of 2023, Spexis’ total loss was CHF 3.9 million, primarily driven by research and development (R&D) expenditures of CHF 2.7 million. The total cash position was CHF 0.9 million (cash and cash equivalents) as of June 30, 2023. In August, Spexis closed additional capital commitments from SPRIM Global Investments and institutional investors totaling USD $2.5 million supporting the Phase 3 ColiFin® program in cystic fibrosis (CF) infections. Key figures1 CHF million Income Statement 30.06.2023 30.06.2022Total revenue0.00.0Research and development expenses-2.7-6.8Other operating expenses2-1.6-2.8Net loss for the period-3.9-10.0 Balance Sheet30.06.202330.06.2022Cash and cash equivalents0.91.8Total assets29.730.0Total equity17.319.4Average net cash burn30.51.0Number of FTEs2028Equity ratio in %5865 1based on consolidated IFRS financial statements 2net of other income 3represents the average monthly cash used in operating and investing activities The half year report 2023 is available for download on our website: Reporting* – Spexis (spexisbio.com) Spexis business update call to take place in October Management will provide a business and financial update, followed by a Q&A session. The specific date and time of said update shall be announced shortly. About Spexis Spexis (SIX: SPEX) is a clinical-stage biopharmaceutical company based in Allschwil, Switzerland, focused on macrocycle therapeutics for rare diseases and oncology. For further information please visit: www.spexisbio.com. For further information please contact: For Investors: Hernan LevettChief Financial OfficerSpexis AG.+41 61 567 16 00IR@spexisbio.com Or Stephen Jasper Managing DirectorGilmartin Groupstephen@gilmartinir.com For Media: Dr. Stephan FeldhausFeldhaus & Partner+41 79 865 92 56feldhaus@feldhaus-partner.ch Disclaimer This press release contains forward-looking statements which are based on current assumptions and forecasts of Spexis management. Known and unknown risks, uncertainties, and other factors could lead to material differences between the forward-looking statements made here and the actual development, in particular Spexis’ results, financial situation, and performance. Readers are cautioned not to put undue reliance on forward-looking statements, which speak only of the date of this communication. Spexis disclaims any intention or obligation to update and revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Ad hoc announcement pursuant to Art. 53 LR USD 4.5 million capital commitment from SPRIM Global Investments to enable initiation of ColiFin® COPILOT study; first patient dosing expected in mid-2023Reported solid safety and pharmacokinetics results from first-in-human study of inhaled murepavadinAnnounced positive renal impairment clinical trial results with balixafortide ALLSCHWIL, Switzerland, May 29, 2023 (GLOBE NEWSWIRE) -- Spexis AG (SIX: SPEX), a clinical-stage biopharmaceutical company focused on rare diseases and oncology, today announced its financial results for the full year of 2022 and provided a strategic business update. “With the recent closing of the capital commitment from SPRIM Global Investments, Spexis is well-positioned to execute on the clinical development of our Phase 3 ColiFin® program, beginning with the initiation of our COPILOT study expected in the middle of the year,” said Jeff Wager, M.D., Chairman & CEO of Spexis. “In addition to the progress made with our lead asset ColiFin®, we are highly encouraged by the accomplishments across our entire pipeline, including promising clinical results from both our balixafortide and inhaled murepavadin programs. Looking ahead to the rest of the year, we remain laser focused on driving each of these programs forward and will continue to diligently evaluate sources of capital to allow for the advancement of our pipeline through value creating milestones.” Pipeline Status and Plans The subsequent plans regarding further development of various programs in the Spexis’ pipeline are subject to the company raising additional funds and/or entering into partnering agreements. Lead Program: ColiFin® ColiFin® is being developed for the treatment of chronic lung infections in cystic fibrosis (CF) patients. Spexis has worldwide rights to ColiFin® ex-Europe and is focused on developing the product first for the U.S. market. With a “Study may Proceed” letter from the United States Food & Drug Administration (FDA), Spexis is advancing ColiFin® into a Phase 3 clinical program in adult and adolescent CF patients with moderate to severe lung function impairment and chronic Pseudomonas aeruginosa (PA) lung infection. PA infection accounts for two-thirds of CF chronic lung infections and is the leading cause of lung function decline and mortality in CF patients. The Phase 3 program includes the COPILOT safety and tolerability pilot clinical trial which will enroll 38 patients and evaluate and confirm the use of once or twice daily dosing for COPA, the planned single pivotal efficacy and safety Phase 3 trial. In April 2023, Spexis reported the closing of a capital commitment of USD 4.5 million from SPRIM Global Investments (SGI) to enable the initiation of the ColiFin® Phase 3 COPILOT study. COPILOT has study start-up activities ongoing and is expected to enroll its first patient in Q3 2023 with data expected in the first quarter of 2024. Additional financing will be required to continue the clinical development of ColiFin® into the COPA pivotal study. The clinical development of ColiFin® is supported by an FDA Orphan Drug Designation for treatment of respiratory infection in patients with cystic fibrosis, Qualified Infectious Disease Product (QIDP) Designation for ColiFin® for the treatment of PA lung infections in CF patients, and Fast Track Designation. Balixafortide Spexis announced positive results from the Phase 1 clinical trial of balixafortide (BLX) in patients with renal impairment in September 2022. The Phase 1 trial was designed to investigate the pharmacokinetics, safety and tolerability of BLX in subjects with mild (n=8), moderate (n=8), or severe (n=7) renal impairment compared to a control group (n=8) with normal renal function. Each person received a single 2-hour intravenous infusion at the previously studied clinical dose of 5.5 mg/kg of BLX. The data from this trial indicate that BLX doses substantially higher than 5.5 mg/kg, the highest dose previously tested, and can potentially be safely administered while stimulating higher levels of stem cell mobilization for longer durations well beyond 24 hours. Increase of functional stem cells, also called mobilization, is an important prerequisite to the collection and transplantation of bone marrow cells in patients with hematologic malignancies. Inhaled murepavadin In January 2023, Spexis reported promising safety and pharmacokinetics results from a first-in-human study with inhaled murepavadin (iMPV), a novel macrocycle compound. The proprietary compound was derived from the company’s macrocycle platform and targets the outer membrane of Pseudomonas aeruginosa (PA) including resistant strains present in cystic fibrosis infections. The Phase 1 trial was a single center, double blind, randomized placebo-controlled trial to investigate the safety, tolerability, and pharmacokinetics of single ascending doses of iMPV in healthy volunteers. At the highest single dose tested, systemic bioavailability of MPV was lower than 5%, and peak plasma concentrations were observed 1-2 hours post start of inhalation. Pharmakokinetic results showed the concentration of iMPV at the 24-hour timepoint was still above the concentration that would inhibit the growth of 90% of PA isolates (MIC90) obtained from people with CF. The data suggested that iMPV leads to concentrations in the airways of the lung sufficient to target PA, while remaining lower than intravenous administration. This favorable tolerability, safety, and concentration profile provides support for future clinical trials of iMPV in people with CF or non-CF bronchiectasis. Spexis intends to advance iMPV into Phase 1b/2 studies in CF patients in 2023, with the potential to expand development efforts into moderate to severe non-CF bronchiectasis (“nCFBE”), a significant additional market opportunity. Financial Results In the full year of 2022, Spexis’ total loss was CHF 18.6 million, primarily driven by research and development (R&D) expenditures of CHF 12.7 million. R&D expenditures are expected to increase in 2023 as the company launches the Phase 3 trial for ColiFin®, beginning with the COPILOT study in mid-2023. Spexis’ cash position as of December 31, 2022 was CHF 1.8 million (cash and cash equivalents). In April, Spexis received a capital commitment of USD 4.5 million from SPRIM Global Investments, as part of a clinical trial partnership expected to provide up to half of the projected ColiFin® Phase 3 development costs, including those involving both COPILOT and COPA. Key figures1 CHF million Income Statement20222021Total revenue0.00.0Research and development expenses-12.7-0.9Other operating expenses-6.0-3.4Net loss for the period-18.6-11.9Balance Sheet20222021Cash on hand1.814.4Total assets30.050.0Total equity19.430.2Average net cash burn2-1.00.2Number of FTE2828Equity ratio in %6561 1) based on the consolidated IFRS financial statements 2) represents the average monthly cash used in operating and investing activities The annual report 2022 is available for download on our website: https://www.spexisbio.com/investor-relations/reporting/ For further information please contact: For Investors: Hernan LevettChief Financial OfficerSpexis AG.+41 61 567 16 00IR@spexisbio.comFor Media:Dr. Stephan FeldhausFeldhaus & Partner+41 79 865 92 56feldhaus@feldhaus-partner.ch About SpexisSpexis (SIX: SPEX) is a clinical-stage biopharmaceutical company based in Allschwil, Switzerland, focused on rare diseases and oncology. For further information please visit: www.spexisbio.com. Disclaimer This press release contains forward-looking statements which are based on current assumptions and forecasts of Spexis management. Known and unknown risks, uncertainties, and other factors could lead to material differences between the forward-looking statements made here and the actual development, in particular Spexis’ results, financial situation, and performance. Readers are cautioned not to put undue reliance on forward-looking statements, which speak only of the date of this communication. Spexis disclaims any intention or obligation to update and revise any forward-looking statements, whether as a result of new information, future events or otherwise.