Pulrodemstat

Positive early Phase 1 results for BMS-partnered programme ‘4318 (PKC-theta inhibitor) GTAEXS617 (CDK7 inhibitor) initial Phase I data expected in 2H24 LSD1 and MALT1 inhibitor programmes expected to advance into clinic in 2H24 and early 2025, respectively AI-design integration enhanced with full experiment automation driving towards maximum speed, quality and autonomous drug design Leveraging technology advancements and streamlining operations to realise annualised savings of $40 million OXFORD, U.K.--(BUSINESS WIRE)-- Exscientia plc (Nasdaq: EXAI): Recent advancements in the Company’s pipeline, collaborations and operations, as well as financial results for the first quarter 2024, are summarised below. Exscientia will host a conference call Tuesday, May 21 at 1:30 p.m. BST / 8:30 a.m. EDT. “With the ramp up of activities at our automation lab, we are beginning to see the transformative power of fully integrating AI drug design with the sheer capacity of comprehensive robotic automation across the entire experimentation cycle,” said Dr. David Hallett, interim Chief Executive Officer and Chief Scientific Officer of Exscientia. “In addition, this year, we are excited about the potential for both GTAEXS617 (or ‘617) and EXS4318 (or ‘4318) to show superior clinical profiles over complex candidate therapies created through traditional methods. We will continue expanding our oncology-focused internal clinical stage pipeline and anticipate advancing both our LSD1 and MALT1 inhibitor programmes forward. The investments into our platform which we have made over the years are bearing fruit. This, in combination with ever-increasing focus on efficiency, allows us to further streamline our operations while delivering on our mid-term goals.” Key Business Updates Pipeline Patient enrolment for the dose escalation phase of the Company’s adaptive Phase 1/2 ELUCIDATE trial evaluating ‘617, a potential best-in-class CDK7 inhibitor for the treatment of advanced solid tumours, is ongoing. Exscientia anticipates moving into a combination phase of the trial in the second half of 2024 The Company expects to announce topline pharmacokinetics and safety data from the dose escalation phase of the trial in the second half of 2024 EXS74539 (‘539), Exscientia’s highly differentiated LSD1 inhibitor, is advancing through IND/CTA-enabling studies. The Company anticipates submitting an IND or CTA in the third quarter of 2024, with the goal to initiate a Phase 1/2 clinical trial in AML patients by the end of 2024 Based on patient unmet need, supporting preclinical data and the unique precision designed properties of Exscientia’s MALT1 inhibitor, EXS73565 (‘565), the Company is preparing to submit an IND or CTA in the second half of 2024 to study ‘565 in a Phase 1/2 clinical trial in B-cell malignancies, including CLL, which Exscientia expects to launch in early 2025 This clinical development programme aims to support the assessment of ‘565 in combination with current standard of care options Collaborations & Partnerships EXS4318 (‘4318), a potential first-in-class PKC-theta inhibitor designed by Exscientia and in-licensed by Bristol Myers Squibb, has shown positive early results in its Phase 1 study and has the potential to be a first-in-class immunology drug Exscientia designed the first potent and selective PKC-theta inhibitor after over ten biopharma companies halted programmes for drug candidates designed using traditional drug discovery techniques Exscientia retains rights to receive milestone payments and potential royalties for ‘4318 The Sanofi partnership continues to make strong progress across multiple programmes, primarily focused on inflammation & immunology targets Exscientia received a $4.0 million payment in the first quarter of 2024 related to the additional programme that entered the portfolio in December 2023 Exscientia’s collaboration with Merck KGaA, Darmstadt, Germany continues to advance with multiple programmes now in early discovery Advancing autonomous drug design and experimentation The first three drug discovery programmes have been initiated in the Company’s novel, industry leading discovery automation laboratory The facility is expected to be fully operational by year end - additional drug discovery programmes are expected to commence on the platform in the coming months The automation lab tightly integrates artificial intelligence with robotic experimentation creating fully automated, generative design-make-test-learn (DMTL) loops This has the potential to dramatically reduce the time and cost of discovery cycles and lower the need for contract research organisations as well as redefining how AI-based design can be autonomously integrated with laboratory experimentation Benefits from integration of technology and streamlining activities continues to improve operational efficiencies While continuing to focus on its strategic priorities, Exscientia will initiate efficiency measures through the rest of the year designed to streamline the Company’s operations, which it expects to result in annualised savings of $40 million or more beginning in 2025 A number of Exscientia’s multi-year investments, including projects related to its proprietary technology platform, are coming to conclusion and expected to result in efficiency gains The changes also leverage the expected efficiency gains from the Company’s automation laboratory and will not impact the internal pipeline, partnership or drug design activities As part of these cost efficiency measures, a 20-25% headcount reduction is expected to be completed by the end of 2024, targeting some areas of target identification, precision medicine, experimentation, engineering and infrastructure The initiative is expected to result in severance and termination-related costs that will be between approximately $7.4 million and $9.6 million. Exscientia expects to record these charges in the second quarter of 2024 and pay these costs throughout the remainder of the calendar year Excluding any potential cash inflows from new business development or financing, these changes are expected to extend the Company’s cash runway well into 2027 Investor Call and Webcast Information Exscientia will host a conference call on Tuesday, May 21st at 1:30 p.m. BST / 8:30 a.m. EDT. A webcast of the live call can be accessed by visiting the “Investors and Media” section of the Company’s website at investors.exscientia.ai. Alternatively, the live conference call can be accessed by dialling +1 (888) 330 3292 (U.S.), +44 800 358 0970 (U.K.), +1 (646) 960-0857 (International) and entering the conference ID: 8333895. A replay will be available for 90 days under “Events and Presentations” in the “Investors and Media” section of the Exscientia website. First Quarter 2024 Financial Results For the convenience of the reader, the Company has translated pound sterling amounts to U.S. dollars at the rate of £1.000 to $1.2637, which was the noon buying rate of the Federal Reserve Bank of New York on March 29, 2024. Revenue: Revenue for the first quarter of 2024 was $6.7 million, compared to $7.3 million for the three months ended March 31, 2023. Research and development expenses (R&D): R&D expenses for the three months ended March 31, 2024 were $29.8 million, as compared to $42.2 million for the three months ended March 31, 2023. The quarter over quarter decrease in R&D expenses was primarily due to cost reductions relating to pipeline prioritisation activities implemented during the second half of 2023 and cost savings from operational efficiencies, including achieving faster cycle times and lower outsourcing costs. General and administrative expenses (G&A): G&A expenses for the three months ended March 31, 2024 were $4.3 million, or 9.9% of total operating expenses. For the first quarter 2024, G&A expenses decreased by $9.4 million compared to the first quarter 2023, primarily associated with cost savings from operational efficiencies and offsetting credits totalling $7.5 million relating to amounts recognised in February 2024 on the forfeiture of share options held by the Company’s prior CEO upon his exit from the company. Cash inflows: For the three months ended March 31, 2024, Exscientia received $4.5 million in cash inflows from its collaborations as compared to $0.5 million during the first quarter 2023. The quarter over quarter increase in cash inflows from collaborations were primarily associated with the $4.0 million payment received as part of the addition of the new programme within the Sanofi collaboration. Net operating cash flow and cash balance: For the three months ended March 31, 2024, net operating cash outflows were $39.0 million, in comparison to $54.8 million for the three months ended March 31, 2023. Cash, cash equivalents and short-term bank deposits as of March 31, 2024 were $416.9 million, as compared to $458.8 million as of December 31, 2023 using the March 29, 2024 constant currency rate. Based on its current operating plans, including the addition of the Sanofi programme and after accounting for the headcount reduction and other anticipated cost efficiencies, the Company believes that its existing cash, cash equivalents and short-term bank deposits and anticipated milestones will be sufficient to fund its operations and capital expenditure requirements well into 2027. This estimate excludes any potential cash inflows from new business development or financing activities. SELECTED CONSOLIDATED STATEMENT OF OPERATIONS, CONSTANT CURRENCY CONVERSION (unaudited) ($ millions, except per share data, at the rate of £1.000 to $1.2637) Three months ended March 31, 2024 2023 Revenue 6.7 7.3 Cost of sales (9.4) (10.7) Research and development expenses (29.8) (42.2) General and administrative expenses (4.3) (13.8) Operating expenses (43.5) (66.7) Foreign exchange gains/(losses) 1.1 (1.5) Other income 1.6 3.3 Operating loss (34.1) (57.6) Net finance income 4.6 4.2 Share of loss on joint ventures (0.7) (0.6) Loss before taxation (30.2) (54.0) Income tax benefit 3.7 6.5 Loss for the period (26.5) (47.5) Net loss per share (0.21) (0.39) Weighted average shares outstanding (basic and diluted) 125,975,607 123,257,529 SELECTED CONSOLIDATED BALANCE SHEET, CONSTANT CURRENCY CONVERSION (unaudited) ($ millions, except per share data, at the rate of £1.000 to $1.2637) March 31, 2024 December 31, 2023 Cash, cash equivalents and short term deposits 416.9 458.8 Total assets 598.4 645.4 Total equity 417.7 449.5 Total liabilities 180.7 195.9 Total equity and liabilities 598.4 645.4 SELECTED CONSOLIDATED STATEMENT OF CASH FLOWS, CONSTANT CURRENCY CONVERSION (unaudited) ($ millions, except per share data, at the rate of £1.000 to $1.2637) March 31, 2024 March 31, 2023 Net cash outflows from operating activities (39.0) (54.8) Net cash flows used in investing activities (63.0) (206.5) Net cash used in financing activities (1.1) (0.9) Net decrease in cash and cash equivalents (103.1) (262.2) Exchange gain/(loss) on cash and cash equivalents 0.6 (2.1) Net decrease in cash, cash equivalents and short-term bank deposits* (41.9) (73.9) * Includes both increases in short term bank deposits and foreign exchange gains/(losses) on cash and cash equivalents About Exscientia Exscientia is an AI-driven precision medicine company committed to discovering, designing, and developing the best possible drugs in the fastest and most effective manner. Exscientia developed the first-ever functional precision oncology platform to successfully guide treatment selection and improve patient outcomes in a prospective interventional clinical study, as well as to progress AI-designed small molecules into the clinical setting. Our internal pipeline is focused on leveraging our precision medicine platform in oncology, while our partnered pipeline broadens our approach to other therapeutic areas. By pioneering a new approach to medicine creation, we believe the best ideas of science can rapidly become the best medicines for patients. For more information visit us on or follow us on LinkedIn @ex-scientia and X @exscientiaAI. Forward-Looking Statements This press release contains certain forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “expects,” “intends,” and “projects” or similar expressions are intended to identify forward-looking statements. These forward-looking statements, include statements with regard to Exscientia’s expectations regarding: the initiation, timing and progress of, and data collected during and reported from, the Company’s and its partners’ clinical trials, as well as expectations with respect to the outcome or benefit of such trials; the progress of Exscientia’s collaborations and partnered programmes; the commencement of additional discovery programmes using Exscientia’s platform and automation facility; the timing and outcome of and any anticipated savings from Exscientia’s planned headcount reduction and other cost efficiency measures; and the Company’s expectation that its existing cash, cash equivalents and short-term bank deposits will be sufficient to fund its operations well into 2027. Such statements are subject to a number of risks, uncertainties and assumptions, including those related to: the initiation, scope and progress of Exscientia’s and its partners’ planned and ongoing preclinical studies and clinical trials and ramifications for the cost thereof; clinical, scientific, regulatory and technical developments; the development and deployment of new technology and facilities; the timing and effects of the planned headcount reduction and other cost efficiency measures; and the process of discovering, developing and commercialising product candidates that are safe and effective for use as human therapeutics and the endeavour of building a business around such product candidates. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section and other sections of Exscientia’s Annual Report on Form 20-F, filed with the Securities and Exchange Commission (SEC) on March 21, 2024, and other filings that Exscientia makes with the SEC from time to time (which are available at ), the events and circumstances discussed in such forward-looking statements may not occur, and Exscientia’s actual results could differ materially and adversely from those anticipated or implied thereby. Although Exscientia’s forward-looking statements reflect the good faith judgement of its management, these statements are based only on facts and factors currently known by the Company. As a result, investors are cautioned not to rely on these forward-looking statements. Exscientia undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. View source version on businesswire.com: Contacts Investor Relations: Sara Sherman / Chinedu Okeke investors@exscientia.ai Media: Oliver Stohlmann media@exscientia.ai Source: Exscientia plc View this news release online at:

MADRID, Spain and CAMBRIDGE, Mass., April 08, 2024 (GLOBE NEWSWIRE) -- ORYZON Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced today that the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application to initiate a Phase I/II trial with iadademstat plus immune checkpoint inhibitors in first line small cell lung cancer (SCLC) patients with extensive disease. This will be the first clinical trial testing the combination of iadademstat with immune checkpoint inhibitors. The trial (NCT06287775) is entitled “A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer”. This Phase I/II clinical study will be conducted and sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, where Dr. Noura Choudhury from the Memorial Sloan Kettering Cancer Center (MSKCC) will be the main PI for this trial and will be implemented by a number of prestigious cancer centers in the US, including the MSKCC, the JHU Sidney Kimmel Comprehensive Cancer Center and many others. The trial plans to enroll 45-50 patients and will be carried out under a Cooperative Research and Development Agreement (CRADA) that Oryzon has in place with the NCI. Dr. Noura Choudhury stated, “This trial presents a novel opportunity to translate promising results derived from the laboratory indicating a role for LSD1 inhibition in small cell lung cancer.” “We are very pleased that NCI has received the regulatory approval from the FDA to initiate this first-in-human Phase I/II combination trial with iadademstat plus immune check point inhibitors” stated Dr. Carlos Buesa, Chief Executive Officer of Oryzon. “The molecular mechanisms underlying the ability of iadademstat to render small cell lung cancer cells visible to the immune system while simultaneously enhancing immune activity to aggressively target these malignant cells have been clearly elucidated. These unique anti-cancer epigenetic actions of iadademstat should greatly enhance the activity of the current standard of care in this critically underserved patient population.” About Oryzon Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS and iadademstat in oncology, in several Phase II clinical trials. The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit About Iadademstat Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and efficacy data in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is being evaluated in a collaborative Phase II basket study with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and the company is preparing a new trial in combination with immune checkpoint inhibitors (ICI) in SCLC. Oryzon has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI) to collaborate on potential further clinical development of iadademstat in different types of solid and hematological cancers; a first trial in combination with ICI in SCLC has recently received FDA approval. In total iadademstat has been dosed so far to more than 130 cancer patients in four clinical trials. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This press release is not an offer of securities for sale in the United States or any other jurisdiction. Oryzon’s securities may not be offered or sold in the United States absent registration or an exemption from registration. Any public offering of Oryzon’s securities to be made in the United States will be made by means of a prospectus that may be obtained from Oryzon or the selling security holder, as applicable, that will contain detailed information about Oryzon and management, as well as financial statements. IR, US IR & Media, Europe Spain Oryzon Ashley R. Robinson Sandya von der Weid Patricia Cobo/Mario Cordera Emili Torrell LifeSci Advisors, LLC LifeSci Advisors, LLC Atrevia Chief Business Officer +1 617 430 7577 +41 78 680 05 38 +34 91 564 07 25 +34 673 33 97 65 +34 93 515 1313 arr@lifesciadvisors.com svonderweid@lifesciadvisors.com pcobo@atrevia.com mcordera@atrevia.com etorrell@oryzon.com