Clostridium difficile infection

Ad hoc announcement pursuant to Art. 53 LR Allschwil, Switzerland – October 29, 2024 Idorsia Ltd (SIX: IDIA) today announced its financial results for the first nine months of 2024. Highlights Net revenue 9M 2024 at CHF 53 million.US GAAP operating loss 9M 2024 of CHF 154 million and Non-GAAP operating loss of CHF 248 million.Improved Guidance for 2024, driven by diligent cost control.QUVIVIQ™ (daridorexant) total net sales of CHF 39 million in 9M 2024.Commercial partnership for QUVIVIQ with Menarini France.QUVIVIQ approved for the treatment of insomnia in Japan.TRYVIO™ (aprocitentan) commercially available in the US since October 2024.JERAYGO™ (aprocitentan) approved by the European Commission in June 2024 and marketing authorization applications submitted in the UK, Canada, and Switzerland.Collaboration with Neurocrine Biosciences comes to an end. André C. Muller, Chief Executive Officer of Idorsia, commented:“The one thing everyone wants to hear about – both internally and externally – is the status of a deal with aprocitentan. I’m pleased to share that our efforts on this front are advancing well. Our improved financial guidance includes our cost-conscious attitude across the whole organization, without compromising advancements, such as making progress in ramping up sales of QUVIVIQ, making TRYVIO available in the US, and expanding marketing authorization for JERAYGO.” Financial results US GAAP resultsNine MonthsThird Quarterin CHF millions, except EPS (CHF) and number of shares (millions)2024202320242023Net revenues531312680Operating expenses(211)(275)(118)150Operating income (loss)(154)(144)(90)231Net income (loss)(180)(181)(101)224Basic EPS(1.00)(1.02)(0.55)1.26Basic weighted average number of shares180.5178.2182.4178.4Diluted EPS(1.00)(1.02)(0.55)0.96Diluted weighted average number of shares180.5178.2182.4232.5 Net revenue of CHF 53 million in the first nine months of 2024 is the result of QUVIVIQ product sales (CHF 39 million), product sales to partners in the Asia-Pacific-Region (CHF 9 million) and contract revenue recognized in connection with Owkin (CHF 3 million). This compares to CHF 131 million in the first nine months of 2023, which included CHF 34 million sales of PIVLAZ in Japan (assigned in the meantime to Nxera Pharma as part of a transaction, more details can be found in the dedicated press release) and CHF 68 million one-off impact of the Nxera deal as well as CHF 4 million revenue share from Johnson & Johnson related to ponesimod sales (revenue-sharing agreement now eliminated as part of the reacquisition of aprocitentan, more details can be found in the dedicated press release). US GAAP operating expenses in the first nine months of 2024 benefited from extraordinary income of CHF 125 million from the Viatris deal resulting in an expense of CHF 211 million (CHF 275 million in the first nine months of 2023), of which CHF 16 million related to cost of sales (CHF 7 million in the first nine months of 2023), CHF 111 million to R&D expenses (CHF 235 million in the first nine months of 2023), and CHF 209 million to SG&A expenses (CHF 318 million in the first nine months of 2023). US GAAP net loss in the first nine months of 2024 amounted to CHF 180 million (CHF 181 million net loss in the first nine months of 2023). The net loss was favorably impacted by a one-off income related to the Viatris deal of CHF 125 million (CHF 302 million one-off income related to the Nxera deal in the first nine months of 2023) and lower operating expenses throughout all functions. The US GAAP net loss resulted in a basic net loss per share of CHF 1.00 (basic and diluted) in the first nine months of 2024, compared to a net loss per share of CHF 1.02 (basic and diluted) in the first nine months of 2023. Non-GAAP* measuresNine MonthsThird Quarterin CHF millions, except EPS (CHF) and number of shares (millions)2024202320242023Net revenues531312680Operating expenses(305)(517)(106)(124)Operating income (loss)(248)(386)(78)(44)Net income (loss)(258)(420)(75)(51)Basic EPS(1.43)(2.36)(0.41)(0.29)Basic weighted average number of shares180.5178.2182.4178.4Diluted EPS(1.43)(2.36)(0.41)(0.29)Diluted weighted average number of shares180.5178.2182.4178.4 * Idorsia measures, reports, and issues guidance on non-GAAP operating performance. Idorsia believes that these non-GAAP financial measurements more accurately reflect the underlying business performance and therefore provide useful supplementary information to investors. These non-GAAP measures are reported in addition to, not as a substitute for, US GAAP financial performance. Non-GAAP net loss in the first nine months of 2024 amounted to CHF 258 million: the CHF 78 million difference versus US GAAP net loss was mainly due to the one-off effect of the Viatris deal (CHF 125 million income), depreciation and amortization (CHF 14 million), share-based compensation (CHF 17 million) and a consent fee paid in shares to the bondholders resulting from amended terms of the 2024 convertible bonds (CHF 14 million). The non-GAAP net loss resulted in a net loss per share of CHF 1.43 (basic and diluted) in the first nine months of 2024, compared to a net loss per share of CHF 2.36 (basic and diluted) in the first nine months of 2023. Viatris collaborationIn March 2024, Idorsia closed agreements with Viatris Inc. (NASDAQ: VTRS), a global healthcare company, for collaboration on the global development and commercialization of two Phase 3 assets – selatogrel and cenerimod – with Idorsia receiving an upfront payment of USD 350 million, and the right to potential development and regulatory milestone payments of up to USD 300 million, potential sales milestone payments of up to USD 2.1 billion, and potential contingent tiered royalties from mid-single- to low-double-digit percentage on annual net sales. A joint development committee is overseeing the development of the ongoing Phase 3 programs for selatogrel and cenerimod up to regulatory approval. Idorsia will contribute up to USD 200 million in the next 3 years and transferred the dedicated personnel for both programs to Viatris. Viatris has worldwide commercialization rights for both selatogrel and cenerimod (excluding, for cenerimod only, Japan, South Korea, and certain countries in the Asia-Pacific region). Idorsia has also granted Viatris a right of first refusal and first negotiation for certain other pipeline assets. Convertible bonds 2024In July 2018, the Group issued CHF 200 million of senior unsecured convertible bonds (ISIN: CH0426820350), which were due to mature on July 17, 2024. On May 6, 2024, a bondholder meeting was held, where 83.5% of the total outstanding bondholders voted in favor of amendments to the terms of the bonds. The approved bond terms include an amended conversion price of CHF 6.00, extended maturity date of January 17, 2025, and the option to call the bonds at par, in full or in part, at any time upon giving ten trading days' notice. A consent fee of 8,000 shares per Bond was paid to bondholders on September 5, 2024. Financial outlook 2024For 2024 – excluding unforeseen events – the company expects QUVIVIQ net sales of around CHF 55 million; SG&A expenses of around CHF 265 million; R&D expense of around CHF 130 million for Idorsia-led pipeline assets; non-GAAP operating expenses around CHF 400 million. This performance would result in a non-GAAP operating loss of around CHF 350 million (excluding contract revenues and the one-off benefit from the Viatris deal). The company expects US GAAP operating loss for 2024 to reach CHF 260 million which includes a one-off benefit of CHF 125 million from the Viatris deal. Arno Groenewoud, Chief Financial Officer, commented:“While closing a deal for TRYVIO is a key focal point, we have also sharpened our cost-conscious approach, which we will increase going forward. Hence, we have been able to stretch the cash runway out to about year-end 2024, which allows us to appropriately plan and execute the next steps of our financial strategy. Furthermore, as a result of lower than expected spending we can upgrade our US GAAP and non-GAAP operating loss guidance by around 60 million Swiss francs each, taking them to 260 million and 350 million Swiss francs, respectively.” Liquidity and indebtednessAt the end of the first nine months of 2024, Idorsia’s liquidity amounted to CHF 92 million. (in CHF millions)Sep 30, 2024Jun 30, 2024Dec 31, 2023Liquidity Cash and cash equivalents92237145Total liquidity*92237145 Indebtedness Convertible loan335335335Convertible bond797797796Other financial debt162162162Total indebtedness1,2941,2941,293 *rounding differences may occur Commercial operationsIn the first nine months of 2024, QUVIVIQ™ (daridorexant) in the US, Germany, Italy, Switzerland, Spain, UK, Canada, Austria, and France generated total product sales of CHF 39 million. United States ProductMechanism of actionIndicationCommercially available sinceDual orexin receptor antagonistTreatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenanceMay 2022 In the US, net sales of QUVIVIQ® (daridorexant) in the first nine months of 2024 reached CHF 21 million, an increase of +41% versus the first nine months of 2023. As of the end of the third quarter 2024, more than 165,000 patients have been treated with QUVIVIQ since launch in the US, over 500,000 prescriptions have been dispensed, and the product has been prescribed by almost 50,000 healthcare professionals. Tosh Butt, President, and General Manager of Idorsia US, commented:“Due to budget constraints we have recently reduced our field force for QUVIVIQ. Despite the reduction, the sales are holding-up for now. Importantly, the citizen petition requesting a review of the evidence from available data, which will hopefully lead to the descheduling of the DORA class of chronic insomnia medications, continues to make progress.” For more information about QUVIVIQ in the US, see the Full Prescribing Information (PI and Medication Guide). ProductMechanism of actionIndicationCommercially available sinceDual endothelin receptor antagonistTreatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugsOctober 2024 On March 19, 2024, the US Food and Drug Administration (FDA) approved TRYVIO™ (aprocitentan) for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. The recommended dosage of TRYVIO is 12.5 mg orally once daily, with or without food. Tosh Butt concluded:“Idorsia is making robust progress with the preparation of everything required for a full commercial launch of TRYVIO by the end of the first quarter of 2025. Both the REMS program and specialty distribution channel are fully up and running, we have begun engaging with hypertension experts through our presence at major cardiovascular and nephrology congresses. The initial discussions with payors are also encouraging. TRYVIO is now available to prescribe to the millions of patients in the US whose high blood pressure is not adequately controlled by other drugs. We have everything in place except a field-force and funding for promotional activities, which is dependent on a partnership deal.” Further details on the approval, together with commentary from company management can be found in the dedicated press release and investor webcast available from the company corporate website. For more information see the Full Prescribing Information including BOXED Warning (PI and Medication Guide). Europe and Canada ProductMechanism of actionIndicationCommercially availableDual orexin receptor antagonistTreatment of adult patients with insomnia characterised by symptoms present for at least three months and considerable impact on daytime functioningSweden: Sept. 2024France: Mar. 2024Austria: Feb. 2024UK: Oct. 2023Spain: Sept. 2023Switzerland: Jun. 2023Germany: Nov. 2022Italy: Nov. 2022 Management of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenanceCanada: Nov. 2023 QUVIVIQ (daridorexant) net sales in the first nine months of 2024 reached CHF 18 million in the EUCAN region. In the third quarter of 2024, net sales have increased by 46% compared to the second quarter of 2024. In Germany, QUVIVIQ was launched in November 2022. By law, sleep medications were then subject to a 4-week prescribing limitation (Anlage III BtMG). Following a review by the Federal Joint Committee (G-BA) this limitation was lifted for QUVIVIQ in November 2023. This makes it the only sleep medication in Germany that can be prescribed for long-term treatment of chronic insomnia. In December 2023, the price negotiated for QUVIVIQ under the AMNOG process became effective. Following the lifting of the prescribing limitation, the company submitted a second AMNOG dossier for the long-term treatment of chronic insomnia disorder (beyond 4 weeks), reflecting the indication approved by the EMA in 2022. The second AMNOG process is expected to end in March 2025. The progress made in Germany is reflected by the performance of QUVIVIQ on the market, with sales doubling in the first nine months of 2024 compared to the first nine months of 2023. In Italy, QUVIVIQ was launched in November 2022. Currently, QUVIVIQ can only be prescribed by neurologists, psychiatrists, and specialists from sleep centers, and no sleep therapy is reimbursed. The company submitted a reimbursement dossier in June 2023 and requested the expansion of the prescriber base. The submission – detailing the efficacy and safety profile of QUVIVIQ and its estimated budget impact and cost-effectiveness in Italy – is under review, with a hearing expected to take place before the end of the year. In Switzerland, QUVIVIQ was launched to the self-pay market in June 2023. Following the launch of QUVIVIQ, awareness and sales have increased solidly. Reimbursement discussions are ongoing and remain a priority for Switzerland. In Spain, QUVIVIQ was launched to the self-pay market in September 2023. Spain represents the largest insomnia market in Europe, as was apparent in the first months of this product’s availability, despite it only being launched to the self-pay market. The company submitted a reimbursement dossier to the Spanish authorities in July 2024, in order to allow equal access for all patients with chronic insomnia. In the UK, QUVIVIQ is recommended as first-line pharmaceutical treatment for patients with chronic insomnia, after, or as an alternative to, cognitive behavioral therapy for insomnia (CBT-I). QUVIVIQ was launched in October 2023 and the team has achieved full reimbursement throughout the UK. The priority in the UK is to secure regional access, which currently stands at around 80%, as well as raising awareness of QUVIVIQ among general practitioners. In Austria, QUVIVIQ was made available in February 2024. A reimbursement dossier was submitted in October 2024, with a conclusion expected in the second half of 2025. In France, QUVIVIQ was included in both the hospital and the retail formulary list of reimbursed pharmaceutical specialties in January 2024 and launched in March 2024 as the first and only pharmacotherapy recommended for the treatment of chronic insomnia disorder. There was a very strong uptake at launch largely due to the excellent market preparation work with psychiatrists. This can be seen by the fact that the majority of prescriptions are being made by the specialists, despite the French market being composed of 55’000 general practitioners who between them represent 75% of the insomnia prescriptions. As a result, the priority becomes expanding awareness to the primary care market to secure strong long-term growth. To address this, Idorsia is expanding its commercial reach from specialist prescribers to general practitioners (GPs) through a new commercial partnership with Menarini in France. In Sweden, QUVIVIQ was made available in September 2024. A reimbursement dossier was submitted in May 2024. As a result, a decision on reimbursement is expected by the end of 2024. In Canada, after being approved in April 2023, QUVIVIQ was launched in November 2023 to the private market, representing 55% of the Canadian insomnia market. The reimbursement dossier was submitted to private market payers in the third quarter of 2023 and currently stands at 80% coverage. The focus is now on public payers with the submission confirmation in Quebec received in October 2024 and submissions in all other provinces ongoing and to be completed by year end. Benjamin Limal, President of Europe and Canada region, commented:“Securing public access to Europe’s only dual orexin receptor antagonist remains our number one priority throughout the EUCAN region – this is the pathway to unlocking the true value of QUVIVIQ. Until then, the performance is satisfactory with a great adoption from specialists and a strong quarterly growth in demand and sales. As one of the newest launches, I have to mention France – QUVIVIQ is really off to a flying start and we are quickly reinforcing the launch momentum through a commercial partnership with Menarini, experts with established relationships in primary care, to handle the promotion of QUVIVIQ to GPs.” For more information about QUVIVIQ in the EU, see the Summary of Product Characteristics. For more information about QUVIVIQ in Switzerland, see the Patient Information and Information for Healthcare Professionals. For more information on the marketing authorization of QUVIVIQ in Canada, see the Product Monograph. ProductMechanism of actionIndicationCommercially available sinceDual endothelin receptor antagonistTreatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal productsApproved Jun. 2024 On June 27, 2024, the European Commission (EC) approved JERAYGO™ (aprocitentan) for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products. The recommended dose is 12.5 mg orally once daily. The dose can be increased to 25 mg once daily for patients tolerating the 12.5 mg dose and in need of tighter blood pressure (BP) control. Further details on the approval, together with commentary from company management can be found in the dedicated press release available from the company corporate website. For more information about JERAYGO in the EU, see the Summary of Product Characteristics. Research & DevelopmentIdorsia has a diversified and balanced portfolio, comprising assets developed and/or marketed by Idorsia and assets that are partner-led to maximize the value we have created. Our drug discovery engine has produced innovative drugs with the potential to transform the treatment paradigm in multiple therapeutic areas, including CNS, cardiovascular, and immunological disorders, as well as orphan diseases. The company also has a vaccine platform for the discovery and development of glycoconjugate vaccines containing synthetic antigenic glycan molecules, with or without a carrier protein, to prevent infection. Idorsia-led portfolio CompoundMechanism of actionTarget indicationStatusQUVIVIQ™ (daridorexant)Dual orexin receptor antagonistInsomniaCommercially available in the US, Germany, Italy, Switzerland, Spain, the UK, Canada, Austria, France, and Sweden; approved throughout the EUTRYVIO™ (aprocitentan) Dual endothelin receptor antagonistSystemic hypertension in combination with other antihypertensivesCommercially available in the USJERAYGO™ (aprocitentan)Dual endothelin receptor antagonistResistant hypertension in combination with other antihypertensivesApproved in the EU; Marketing authorization applications submitted in the UK, Canada, and SwitzerlandLucerastatGlucosylceramide synthase inhibitorFabry diseasePhase 3 primary endpoint not met; open-label extension study ongoingPhase 3 focused on renal function in preparationDaridorexantDual orexin receptor antagonistPediatric insomniaPhase 2 in pediatric insomnia ongoingACT-1004-1239ACKR3/CXCR7 antagonistDemyelinating diseases including multiple sclerosis Phase 2 in preparationACT-777991CXCR3 antagonistVitiligoPhase 2 in preparationSinbaglustatGBA2/GCS inhibitorRare lysosomal storage disordersPhase 1 completeIDOR-1117-2520UndisclosedImmune-mediated disordersPhase 1 ongoingIDOR-1134-2831Synthetic glycan vaccineClostridium difficile infectionPhase 1 ongoing Further details including the current status of each project in our portfolio can be found in our innovation fact sheet. Idorsia partner-led portfolioFor Idorsia, sophisticated partnerships are a way of gaining strategic access to technologies or products and fully exploiting our discovery engine and clinical pipeline. We seek suitable external project partners to maximize the value of internal innovation. CompoundMechanism of actionTarget indicationPartner/statusQUVIVIQ™ (daridorexant)Dual orexin receptor antagonistInsomniaSimcere: Approved for the treatment of insomnia in Hong-KongQUVIVIQ™ (daridorexant)Dual orexin receptor antagonistInsomniaNxera Pharma: license to develop and commercialize for Asia-Pacific region (excluding China)Approved for the treatment of insomnia in JapanDaridorexantDual orexin receptor antagonistInsomniaSimcere: license to develop and commercialize for Greater China regionNDA submitted in Greater ChinaSelatogrelP2Y12 inhibitorAcute myocardial infarctionViatris: worldwide development and commercialization rightsPhase 3 “SOS-AMI” program ongoingCenerimodS1P1 receptor modulatorSystemic lupus erythematosusViatris: worldwide development and commercialization rights (excluding Japan, South Korea, and certain countries in the Asia-Pacific region)Phase 3 “OPUS” program ongoingDaridorexantDual orexin receptor antagonistPosttraumatic stress disorder (PTSD)US Department of Defense (DOD): Idorsia is supporting a clinical study sponsored by the US DOD to develop new therapies to treat PTSDACT-1002-4391EP2/EP4 receptor antagonistImmuno-oncologyOwkin: global license to develop and commercializePhase 1 in preparation On October 1, 2024, Nxera Pharma announced that it had entered a commercial partnership agreement with Shionogi & Co., Ltd regarding the distribution and sales for QUVIVIQ in Japan. At the same time, the previous commercialization agreement between Nxera and Mochida Pharmaceutical Co., Ltd. was terminated. After negotiation among Nxera, Shionogi and Mochida regarding the optimal sales scheme, Shionogi is solely responsible for distribution and sales activities in Japan. Idorsia and Neurocrine Biosciences had a collaboration for ACT-709478, Idorsia’s novel T-type calcium channel blocker. The compound was investigated as a treatment of pediatric patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSCW), a rare form of pediatric epilepsy. The Phase 2 study did not meet the primary endpoint in June 2022, and further analysis from an open-label extension study resulted in the decision to stop further development. As a result, the development agreement has come to an end. Further details including the current status of each project in our partner-led portfolio can be found in our innovation fact sheet. Results Day CenterInvestor community: To make your job easier, we provide all relevant documentation via the Results Day Center on our corporate website: www.idorsia.com/results-day-center. Upcoming Financial Updates Full Year 2024 Financial Reporting together with the publication of the Annual Report 2024 on February 27, 2025 Notes to the editor About IdorsiaIdorsia Ltd is reaching out for more – We have more ideas, we see more opportunities and we want to help more patients. In order to achieve this, we will develop Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland – a European biotech-hub – Idorsia is specialized in the discovery, development, and commercialization of small molecules to transform the horizon of therapeutic options. Idorsia has a 25-year heritage of drug discovery, a broad portfolio of innovative drugs in the pipeline, an experienced team of professionals covering all disciplines from bench to bedside, and commercial operations in Europe and North America – the ideal constellation for bringing innovative medicines to patients. Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 750 highly qualified specialists dedicated to realizing our ambitious targets. For further information, please contactAndrew C. WeissSenior Vice President, Head of Investor Relations & Corporate CommunicationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.relations@idorsia.com media.relations@idorsia.com www.idorsia.com The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Attachment Press Release PDF

REC-3964 is Recursion’s first new chemical entity developed using the RecursionOS.REC-3964 represents a novel, non-antibiotic approach with a unique mechanism of action that binds and blocks catalytic activity of the toxin's innate glucosyltransferase in order to inhibit the toxin produced by C. diff. in the gastrointestinal tract.There are up to 175,000 cases of recurrent C. diff. each year and more than 29,000 patients die in the U.S. from C. diff. annually. Rates of recurrent C. diff. have increased significantly in recent years, representing a major public health challenge. SALT LAKE CITY, Oct. 22, 2024 (GLOBE NEWSWIRE) -- Recursion (NASDAQ: RXRX), a leading clinical stage TechBio company decoding biology to radically improve lives, today announced that the first patient has been dosed in its Phase 2 clinical trial of REC-3964, a potential first-in-class, oral small molecule and new chemical entity for the treatment of recurrent Clostridioides difficile infection. C. diff is a toxin producing bacteria that causes diarrhea and colitis, and can be life threatening. Up to 730,000 cases are estimated to occur in the U.S. and EU5 annually, and the infection is responsible for an estimated 29,000 deaths in the U.S. each year. Recursion’s study will initially address the recurrent C. diff. (up to 175,000 cases in the United States per year) population, which costs the healthcare system approximately two billion dollars per year. Increasing cases of recurrent C. diff. infections pose significant public health challenges. Antibiotics, the standard treatment for C. diff. infections, disturb the gut microbiome due to their non-selective nature. Despite initial success, antibiotics fail to prevent recurrence in 20-30% of primary cases. Further, the risk of subsequent recurrence rises to 40% after the first and 45-65% after two or more. REC-3964 is the first novel small molecule developed through Recursion’s Operating System, and selectively inhibits the glucosyltransferase activity of toxin B produced by C. diff in the gastrointestinal tract, offering a unique mechanism of action. Unlike antibiotics, which disrupt the gut microbiome, REC-3964 precisely targets the bacterial toxin while sparing healthy tissue, potentially minimizing adverse events. It is being studied as part of a treatment regimen to prevent recurrent C. diff infections, a leading cause of antibiotic-associated diarrhea that can lead to significant morbidity and mortality. Presented at the 6th Edition of World Congress on Infectious Diseases, preclinical studies demonstrated its superiority over bezlotoxumab in a human disease-relevant C. diff. hamster model. Additionally, Phase 1 studies in healthy volunteers showed REC-3964 was well tolerated with no serious adverse events (SAEs), underscoring its potential safety and tolerability. “There’s a significant unmet need for new treatment options for patients with C. diff. infection that are easier to use and more cost effective,” said Chris Gibson, Ph.D., Co-Founder and CEO of Recursion. “We are encouraged by the progress of REC-3964, the first new chemical entity from our platform to advance to Phase 2 clinical trials, and now, to the first patient dosed. We look forward to continuing to advance this trial to help patients in need and drive down billions in costs to the healthcare system for treatment.” Christian John Lillie, Co-Founder and CEO of the Peggy Lillis Foundation, shared: "We are so pleased to learn that our partner Recursion has initiated its ALDER trial. All new therapies that can be added to the known standard of care have the potential to decrease the physical and emotional suffering of recurrent C. diff. on patients and the significant burden to the health care system.” “Patients with C. diff face significant challenges, with 20-30% of initial infections recurring after standard treatment and a 40% chance of further recurrence, often leading to severe complications and a diminished quality of life,” said Najat Khan, Ph.D., Chief Commercial Officer and Chief R&D Officer at Recursion. “For these patients and their families, the need for safe, effective, non-antibiotic treatment options is critical. REC-3964 offers a novel, targeted approach by selectively inhibiting the bacterial toxin while sparing the host. With encouraging preclinical data and strong tolerability demonstrated in Phase 1 studies, it’s particularly rewarding to see the first drug developed using the RecursionOS and advancing to Phase 2 trials.” The Phase 2 ALDER clinical trial is a multi-center randomized study to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of REC-3964 at doses of either 250 mg or 500 mg for the reduction of C. diff. and will include an observation only arm. Approximately 80 individuals will ultimately be enrolled in the study across the U.S. and Europe. About Clostridioides difficile infection Clostridioides difficile (C. diff.) infection is a bacterial disease that impacts more than 730,000 people in the U.S. and EU5 every year. Rates of recurrent C. diff. have increased significantly in recent years, representing a major public health challenge, with people 7 to 10 times more likely to get C. diff. infection while taking an antibiotic and the subsequent month. About 20-30% patients who have C. diff. infection will have it again in the subsequent 2 to 8 weeks. After the first recurrence, there’s a 40% likelihood of a second recurrence, and a 45-65% likelihood of recurrence among patients who have recurred more than twice. In total C. diff. infection is estimated to cause 29,300 deaths in the U.S. each year. More than 80% of C. diff. infection deaths occur in people aged 65 and older. On average, one in 11 patients older than 65 years diagnosed with healthcare-associated C. diff. infection will die within a month. Extended stays in healthcare settings, such as hospitals and nursing homes, also increase risk. About REC-3964REC-3964 is a potential first-in-class, orally bioavailable non-antibiotic small molecule that is being investigated for the potential treatment of recurrent Clostridioides difficile (C. diff.) infection. This selective inhibitor is Recursion’s first new chemical entity to reach the clinic, and binds and blocks catalytic activity of the toxin's innate glucosyltransferase. In preclinical studies, REC-3964 was found to be superior to bezlotoxumab in a human disease relevant C. diff. hamster model, with significant difference in probability of survival versus bezlotoxumab alone at the end of treatment. REC-3964 was also well tolerated in Phase 1 healthy volunteer studies, demonstrating potential safety and tolerability with no serious adverse events (SAEs). About the Trial Our Phase 2 ALDER clinical trial is a multi-center, open-label study to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of REC-3964 (doses of either 250 mg or 500 mg PO every 12 hours) for the reduction of Clostridioides Difficile infection (C. diff.). Approximately 80 individuals will be enrolled in this open-label Phase 2 study, randomized 1:2:1 to receive oral doses of REC-3964, 250 mg, 500 mg or observation. The purpose of this study is to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of REC-3964 for the reduction of recurrent Clostridioides difficile infection (rCDI) after initial cure with vancomycin. Participants will receive treatment with REC-3964 for 28 days. About RecursionRecursion (NASDAQ: RXRX) is a clinical stage TechBio company leading the space by decoding biology to radically improve lives. Enabling its mission is the Recursion OS, a platform built across diverse technologies that continuously generate one of the world’s largest proprietary biological and chemical datasets. Recursion leverages sophisticated machine-learning algorithms to distill from its dataset a collection of trillions of searchable relationships across biology and chemistry unconstrained by human bias. By commanding massive experimental scale — up to millions of wet lab experiments weekly — and massive computational scale — owning and operating one of the most powerful supercomputers in the world, Recursion is uniting technology, biology and chemistry to advance the future of medicine. Recursion is headquartered in Salt Lake City, where it is a founding member of BioHive, the Utah life sciences industry collective. Recursion also has offices in Toronto, Montréal, London, and the San Francisco Bay Area. Learn more at www.Recursion.com, or connect on X (formerly Twitter) and LinkedIn. Media ContactMedia@Recursion.com Investor ContactInvestor@Recursion.com Forward-Looking Statements This document contains information that includes or is based upon “forward-looking statements” within the meaning of the Securities Litigation Reform Act of 1995, including, without limitation, those regarding the potential efficacy of REC-3964; timing of the Phase 2 clinical trial of REC-3964; early and late stage discovery, preclinical, and clinical programs; licenses and collaborations; prospective products and their potential future indications and market opportunities; Recursion OS and other technologies; business and financial plans and performance; and all other statements that are not historical facts. Forward-looking statements may or may not include identifying words such as “plan,” “will,” “expect,” “anticipate,” “intend,” “believe,” “potential,” “continue,” and similar terms. 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The data presented indicate a favorable gut bile acid profile which may contribute to ibezapostat's beneficial anti-recurrence effect in patients with C. difficile Infection (CDI) Ibezapolstat treatment of patients with CDI is associated with the restoration of beneficial bacterial classes in the gut Preparation continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI) Preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union to be followed by the United Kingdom, Japan and Canada Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA STATEN ISLAND, N.Y., Oct. 21, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced the presentation of a scientific poster at the Infectious Diseases Society of America (IDSA) IDWeek™ 2024 Conference held October 16-19, 2024 in Los Angeles, CA. Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of Houston College of Pharmacy, Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program, and Acurx Scientific Advisory Board member, and Taryn A. Eubank, PharmD, BCIDP, Research Assistant Professor, University of Houston College of Pharmacy presented a scientific poster entitled: A phase 2, randomized double-blind study of ibezapolstat compared with vancomycin for the treatment of C. difficile infection: clinical and microbiome evaluation. In the Phase 2b clinical trial, ibezapolstat had comparable clinical cure and sustained clinical cure rates and safety profile to vancomycin. Also, 5 of 5 ibezapolstat patients who were followed for 3 months after end of treatment (EOT) experienced no recurrence. Favorable microbiome results were observed in ibezapolsat-treated patients who had increased proportion of Actinobacteriota and beneficial Bacillota. Furthermore, ibezapolstat-treated patients showed decreased concentrations of fecal primary bile acids, and higher ratios of secondary to primary bile acids than vancomycin-treated patients. According to Dr. Garey: "These exciting results demonstrate two properties of ibezapolstat which may contribute to the anti-recurrence effect. First, the preservation and restoration of beneficial bacterial classes in the gut provide resistance to recolonization by C. difficile. Second, these data, presented for the first time, indicate that these beneficial bacteria known to metabolize primary to secondary bile acids persist in ibezapolstat-treated patients providing another important mechanism to prevent recurrent CDI". Robert J. DeLuccia, Executive Chairman of Acurx, stated: "This new impressive bile acid and microbiome data compliment and extend our knowledge of ibezapolstat's pharmacologic profile. These results, when added to previous work showing anti-virulence properties, preclinically, give us a high level of confidence that our excellent Phase 2 clinical results will be confirmed in our Phase 3 studies". The scientific poster is available on the Acurx Pharmaceuticals website at . Acurx has previously announced that it had a successful FDA End-of-Phase 2 Meeting and Phase 3 Readiness for ibezapolstat for the Treatment of C. difficile Infection. Agreement with FDA was reached on key elements to move forward with its international Phase 3 clinical trial program. Agreement was also reached with FDA on the complete non-clinical and clinical development plan for filing of a New Drug Application (NDA) for marketing approval. Planning continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI). Acurx is also preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, to be followed by requests to be submitted in the United Kingdom, Japan and Canada. Key elements for the two Phase 3, non-inferiority, pivotal trials were confirmed and included agreement on the protocol design, patient population, primary and secondary endpoints, and size of the registration safety database. Based on FDA recommendations, and in anticipation of an EMA Scientific Advice Meeting, the primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population consistent with EMA requirements. This will result in an estimated 450 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin, enrolled into the initial Phase 3 trial. The trial design not only allows determination of ibezapolstat's ability to achieve Clinical Cure of CDI as measured 2 days after 10 days of oral treatment, but also includes assessment of ibezapolstat's potential effect on reduction of CDI recurrence in the target population. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority. About the IDSA and IDWeek The Infectious Diseases Society of America (IDSA) is a community of over 12,000 physicians, scientists and public health experts who specialize in infectious diseases. Our mission is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases. IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP). About the Ibezapolstat Phase 2 Clinical Trial The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (see ). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline. from study centers in the United States. In the Phase 2a trial segment, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment). In the Phase 2b trial segment, which was discontinued due to success, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The Company previously reported that the overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug-related. All three events were gastrointestinal in nature and resolved without treatment. There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October 2022). In the Phase 2 clinical trial (both trial segments), the Company also evaluated pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin. The company also recently reported positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 12 patients who agreed to be followed up to three months following Clinical Cure of their infection, 5 of 5 IBZ patients experienced no recurrence of infection. In the vancomycin control arm of the trial, 7 of 7 patients experienced no recurrence of infection. ECC success is defined as a clinical cure at the TOC visit (i.e., at least 48 hours post EOT) and no recurrence of CDI within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post EOT (ECC84) in patients who consented to extended observation. In the Phase 2b trial, 100% (5 of 5) of ibezapolstat-treated patients who agreed to observation for up to three months following Clinical Cure of CDI experienced no recurrence of infection. About Ibezapolstat Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). Ibezapolstat is a novel, orally administered antibiotic, being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome. In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI. About Clostridioides difficile Infection (CDI) According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%. About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa. Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022). About Acurx Pharmaceuticals, Inc. Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram-positive specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP). To learn more about Acurx Pharmaceuticals and its product pipeline, please visit . Forward-Looking Statements Any statements in this press release about our future expectations, plans and prospects, including statements regarding our strategy, future operations, prospects, plans and objectives, and other statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether ibezapolstat will benefit from the QIDP designation; whether ibezapolstat will advance through the clinical trial process on a timely basis; whether the results of the clinical trials of ibezapolstat will warrant the submission of applications for marketing approval, and if so, whether ibezapolstat will receive approval from the FDA or equivalent foreign regulatory agencies where approval is sought; whether, if ibezapolstat obtains approval, it will be successfully distributed and marketed; and other risks and uncertainties described in the Company's annual report filed with the Securities and Exchange Commission on Form 10-K for the year ended December 31, 2023, and in the Company's subsequent filings with the Securities and Exchange Commission. Such forward- looking statements speak only as of the date of this press release, and Acurx disclaims any intent or obligation to update these forward-looking statements to reflect events or circumstances after the date of such statements, except as may be required by law. Investor Contact: Acurx Pharmaceuticals, Inc. David P. Luci, President & CEO Tel: 917-533-1469 Email: [email protected] SOURCE Acurx Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED