A Two-Part Study of REC-994 in the Treatment of Adults With Symptomatic Cerebral Cavernous Malformation (CCM); Part 1: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Two Doses of REC-994; Part 2: A Long-Term Blinded Extension Clinical Trial to Evaluate Long-Term Safety Tolerability and Efficacy of REC-994

This is a two-part, multi-center, randomized, double-blind, placebo-controlled study to investigate the safety, efficacy and pharmacokinetics of REC-994 (200 mg and 400 mg) compared to placebo in subjects with symptomatic cerebral cavernous malformation (CCM).

Start Date17 Mar 2022

Sponsor / Collaborator

Recursion Pharmaceuticals, Inc.

NCT04729595 / TerminatedPhase 2/3

A Phase 2/3, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study to Examine the Effects of Tempol (MBM-02) in Subjects With COVID-19 Infection

An Adaptive, Randomized, Double-blind, Placebo-controlled study to examine the Effects of Tempol in subjects with COVID-19 infection.

Start Date01 Sep 2021

Sponsor / Collaborator

DMK Pharmaceuticals Corp.

NCT04887311 / Unknown statusPhase 2

An Open Label Study to Assess the Safety and Efficacy of MBM-01 for the Treatment of Ataxia Telangiectasia

Ataxia Telangiectasia (A-T) is an autosomal recessively inherited neurodegenerative disorder that also has dramatic effects on the immune and endocrine systems. The disorder results from mutations in the A-T mutated gene (ATM) leading to a loss in the production of the ATM protein.
The active compound in MBM-01 (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) may substitute for the loss of ATM by protecting cells from DNA damage, preventing and reducing oxidative damage, triggering an increase in cellular survival proteins, and preserving the brain and peripheral immune system.

Start Date01 Jul 2021

Sponsor / Collaborator

Matrix Biomed, Inc.

[+1]

100 Clinical Results associated with Tempol

100 Translational Medicine associated with Tempol

100 Patents (Medical) associated with Tempol

1,885

Literatures (Medical) associated with Tempol

31 Dec 2024·CLINICAL AND EXPERIMENTAL HYPERTENSION

Uric acid mediates kidney tubular inflammation through the LDHA/ROS/NLRP3 pathway

Article

Author: Gan, Yumei ; Ouyang, Jun ; Wang, Hui ; Huang, Jiangnan

PURPOSE:

Hyperuricemia (HUA) is an important factor leading to chronic kidney disease (CKD). The kidney tubular inflammatory response is activated in HUA. This study aimed to investigate whether lactate dehydrogenase A (LDHA) is involved in mediating uric acid-induced kidney tubular inflammatory response.

METHODS:

In vivo, an HUA mouse model was established by continuous intraperitoneal injection of potassium oxonate (PO) for one week. A total of 18 C57BL/6J male adult mice were divided into three groups: control group, HUA group, and HUA+oxamate group, with six mice in each group. Oxamate was intraperitoneally injected into the mice one hour after PO injection. In vitro, an HUA model was simulated by stimulating HK-2 cells with uric acid. Oxamate and tempol inhibited LDHA and reactive oxygen species (ROS) in HK-2 cells.

RESULTS:

In HUA mice, blood uric acid levels were significantly elevated. LDHA in kidney tubular cells was significantly increased in both in vivo and in vitro HUA models, accompanied by an increase in kidney tubular inflammation and ROS. Mechanistically, LDHA mediates uric acid-induced inflammation to kidney tubular cells through the ROS/NLRP3 pathway. Pharmacologic inhibition of LDHA or ROS in kidney tubular cells can significantly ameliorate inflammation response caused by uric acid.

CONCLUSIONS:

LDHA in kidney tubular cells significantly was increased in HUA models. LDHA mediates kidney inflammation response induced by uric acid through the ROS/NLRP3 pathway. This study may provide a new intervention target for preventing kidney tubular inflammation caused by uric acid.

31 Dec 2024·CLINICAL AND EXPERIMENTAL HYPERTENSION

Gestational diabetes causes hyperactivity of the sympathetic nervous system and hypertension in adult mice offspring.

Article

Author: Wang, Chunxiang ; Luo, Hao ; Zhu, Jun ; Yang, Li ; Zhu, Xingyu ; Hu, Zegang ; Bai, Xue

BACKGROUND:

Gestational diabetes can lead to increased blood pressure in offspring, accompanied by impaired renal sodium excretion function and vasoconstriction and diastole dysfunction. However, there are few studies on whether it is accompanied by increased sympathetic nerve activity.

METHODS:

Pregnant C57BL/6 mice were intraperitoneally injected with streptozotocin (35 mg/kg) or citrate buffer at day 0 of gestation. The mice of control mother offspring (CMO) and diabetic mother offspring (DMO) at 16 weeks of age were infused with vehicle (artificial cerebrospinal fluid, aCSF, 0.4 μL/h) or tempol (1 mmol/L, 0.4 μL/h) into the bilateral paraventricular nucleus (PVN) of mice for 4 weeks, respectively.

RESULTS:

Compared with CMO group, SBP and peripheral sympathetic nerve activity (increased heart rate, LF/HF and plasma norepinephrine and decreased SDNN and RMSSD) were increased in DMO group, which was accompanied by increased angiotensin II type-1 receptor (AT₁R) expression and function in PVN. The increase in AT₁R expression levels was attributed to a decrease in the methylation level of the AT₁R promoter region, resulting in an increase in AT₁R mRNA levels in PVN of DMO. Moreover, compared with CMO group, the levels of oxidative stress were increased and DNMT1 expression was decreased in PVN of DMO. Bilateral PVN infusion of tempol attenuated oxidative stress increased the level of DNMT1 expression and the binding of DNMT1 to the AT₁R promoter region, which reduced mRNA and protein expression level of AT₁R, heart rate and SBP in DMO, but not in CMO.

CONCLUSIONS:

The present study provides evidence for overactive sympathetic nervous systems in the pathogenesis of gestational diabetes-induced hypertension in offspring. Central antioxidant intervention in the PVN may be an important treatment strategy for fetal-programmed hypertension.

01 Dec 2024·Molecular biology reports

4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) alleviates lung injury by inhibiting SIRT6-HIF-1α signaling pathway activation through the upregulation of miR-212-5p expression

Article

Author: Niu, Xiaoqun ; Li, Ran ; Cao, Yu ; Ai, Li ; Li, Yongxia ; Liu, Zhijuan

OBJECTIVE:

Obstructive sleep apnea is closely related to oxidative stress. 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) can scavenge reactive oxygen species (ROS) and ameliorate oxidative damage in the body. The mechanism by which Tempol alleviates chronic intermittent hypoxia-induced lung injury has rarely been reported. This study aimed to confirm the molecular mechanism by which Tempol alleviates lung injury.

METHODS:

The levels of miR-212-5p and Sirtuin 6 (SIRT6) in injured lungs were analyzed using bioinformatics. In vitro, intermittent hypoxia (IH) treatment induced hypoxia in BEAS-2B cells and we established a model of chronic intermittent hypoxia (CIH) in mouse using a programmed hypoxia chamber. We used HE staining to observe the morphology of lung tissue, and the changes in lung fibers were observed by Masson staining. The levels of inflammatory factors in mouse serum were detected by ELISA, and the levels of the oxidative stress indicators GSH, MDA, SOD and ROS were detected using commercially available kits. Moreover, a real-time qPCR assay was used to detect miR-212-5p expression, and Western blotting was used to detect the levels of SIRT6, HIF-1α and apoptosis-related proteins. CCK-8 was used to detect cell proliferation. Subsequently, we used flow cytometry to detect cell apoptosis. Dual-luciferase gene reporters determine the on-target binding relationship of miR-212-5p and SIRT6.

RESULTS:

SIRT6 was highly expressed in CIH-induced lung injury, as shown by bioinformatics analysis; however, miR-212-5p expression was decreased. Tempol promoted miR-212-5p expression, and the levels of SIRT6 and HIF-1α were inhibited. In BEAS-2B cells, Tempol also increased proliferation, inhibited apoptosis and inhibited oxidative stress in BEAS-2B cells under IH conditions. In BEAS-2B cells, these effects of Tempol were reversed after transfection with an miR-212-5p inhibitor. miR-212-5p targeted and negatively regulated the level of SIRT6 and overexpression of SIRT6 effectively reversed the enhanced influence of the miR-212-5p mimic on Tempol's antioxidant activity. Tempol effectively ameliorated lung injury in CIH mice and inhibited collagen deposition and inflammatory cell infiltration. Likewise, the therapeutic effect of Tempol could be effectively reversed by interference with the miR-212-5p inhibitor.

CONCLUSION:

Inhibition of the SIRT6-HIF-1α signaling pathway could promote the effect of Tempol by upregulating the level of miR-212-5p, thereby alleviating the occurrence of lung injury and providing a new underlying target for the treatment of lung injury.

News (Medical) associated with Tempol

20 Nov 2024

·www.globenewswire.com

Recursion and Exscientia, two leaders in the AI drug discovery space, have officially combined to advance the industrialization of drug discovery

Recursion unveils post-combination technology-enabled portfolio with more than 10 clinical and preclinical programs, 10 advanced discovery programs, and more than 10 partnered programsPlatform will focus on first and best-in-class drug discovery and development, demonstrating the ability to find novel insights and dramatically reduce the time and cost of discoveryRecursion will host an update call today, November 20, 2024 at 7:30 a.m. ET / 5:30 a.m. MT / 12:30 p.m. GMT on LinkedIn, X and Youtube SALT LAKE CITY, Nov. 20, 2024 (GLOBE NEWSWIRE) -- The business combination of two AI-powered drug discovery and development companies, Recursion (Nasdaq: RXRX) and Exscientia has been completed, with Exscientia becoming a wholly owned subsidiary of Recursion creating a vertically-integrated and technology-enabled drug discovery platform. Exscientia ADSs (Nasdaq: EXAI) ceased trading and will be delisted from Nasdaq. “I believe the combination of the incredible teams and platforms at Exscientia and Recursion position us as the leader of the AI-enabled drug discovery and development space,” said Chris Gibson, Ph.D., Co-Founder and CEO of Recursion. “With more than 10 clinical and preclinical programs in the internal pipeline, more than 10 partnered programs and over $450M in upfront and realized milestone payments received from partners to date out of more than $20B possible, we are advancing a flywheel of discovery and creating value in our pipeline through technology.” “The combination of our platforms and people make us the company to beat,” said David Hallett, Ph.D., former CSO and Interim CEO of Exscientia and newly appointed Chief Scientific Officer at Recursion. “With our combined strength of real-world proprietary data and the models we’ve created – hypothesizing, testing and learning in a continuous loop – we're redefining the space by shrinking timelines and costs, identifying and optimizing lead candidates faster than traditional methods.” The Company is pleased to share updates on the combined entity’s pipeline, partnerships, and platform below: Pipeline The combined pipeline represents more than 10 clinical and preclinical programs. In addition there are approximately 10 advanced discovery programs in the current pipeline. Updated guidance is bulleted below as well as a snapshot of our pipeline: REC-617 (CDK7 inhibitor; Advanced Solid Tumors): Initial Phase 1 monotherapy safety and PK/PD data expected at the AACR Special Conference on December 9th 2024, and a webinar to follow on December 10th 2024.REV102 (ENPP1 inhibitor; Hypophosphatasia): Development candidate nomination expected in Q4 2024REC-4881 (MEK1/2 inhibitor, Familial Adenomatous Polyposis): Phase 1b/2 safety and early efficacy data expected in H1 2025REC-2282 (pan-HDAC inhibitor; Neurofibromatosis Type 2): PFS6 futility analysis expected by H1 2025REC-3565 (MALT1 inhibitor, B-Cell Malignancies): Phase 1 first patient dosed (FPD) expected in Q1 2025REC-4539 (LSD1 inhibitor, Small-Cell Lung Cancer): Phase 1 first patient dosed (FPD) expected in H1 2025REC-994 (Superoxide scavenger, Cerebral Cavernous Malformation): Further data to be shared at an upcoming medical conference / publication / webinar in H1 2025; regulatory update expected by H2 2025REC-394 (C. difficile Toxin B selective inhibitor, C. difficile): Phase 2 update expected in Q1 2026REC-1245 (RBM39 degrader; Solid Tumors and Lymphoma): Phase 1 dose-escalation data update expected in H1 2026REC-4209 (undisclosed target; Idiopathic Pulmonary Fibrosis): IND-enabling studies are ongoingREC-4881 in APC/AXIN1 indications have been deprioritized as part of a disciplined strategic prioritization of the portfolio. Study status will be updated on clinicaltrials.gov Partnerships The combined company’s therapeutic partnerships represent more than 10 partnered programs in areas such as oncology and immunology. The combined company has received approximately $450M in upfront and milestone payments from partnerships to date. Through these partnerships, we have the potential to receive more than approximately $20B in additional milestone payments before royalties. Platform With chemical design and synthesis methods from Exscientia and over 60 petabytes of proprietary data generated in house or licensed from partners like Helix and Tempus, the combined entity will strengthen the Recursion OS to be a first-in-class and best-in-class drug discovery and development platform. The platform will continue to drive iterative loops of hypotheses and active learning all the way from research to development, with the goal of eventually creating virtual cells that will allow the company to execute clinical trials at scale. Company, Board, and Leadership Updates The combined company will have approximately 800 employees with the headquarters remaining in Salt Lake City, and primary offices in Toronto, Montreal, Milpitas, New York, the Oxford area, and London. Individual board and executive leadership changes of Recursion, effective as of November 20, 2024, are summarized below: Franziska Michor, a former member of the Board of Directors of Exscientia, was appointed as a Class II Director of the Board of Directors of Recursion, with her initial term to extend until the 2026 Annual Meeting of Stockholders of Recursion.Ben Taylor, former Chief Financial and Strategy Officer of Exscientia, was appointed as the Chief Financial Officer of the Company and President of Recursion UK.Dave Hallett, former Interim Chief Executive Officer of Exscientia, was appointed as Chief Scientific Officer of the Company.Kristen Rushton, Chief Business Operations Officer of the Company, was promoted to Chief Operating Officer of the Company.Matthew Kinn, Senior Vice President, Business Development and Corporate Initiatives of the Company was promoted to serve as Chief Business Officer of the Company.Lina Nilsson, Senior Vice President, Emerging Technologies of the Company, was promoted to serve on the executive team as Senior Vice President, Head of Platform of the Company.Michael Secora, Tina Marriott, and Laura Schaevitz will transition from their executive roles into advisor roles for the combined company. All three have provided many years of dedicated service to the Company and we wish to express our heartfelt gratitude for each of them. Recursion would not be where it is today without their dedication and efforts. Update Call Information Recursion will host an update call today at 7:30 a.m. ET / 5:30 a.m. MT / 12:30 p.m. GMT. The Company will broadcast the live stream from Recursion’s X (formerly Twitter), LinkedIn and YouTube accounts, and on Exscientia’s LinkedIn account. Questions can be submitted via this link ahead of time or during the livestream. About Recursion Recursion is a leading, clinical-stage TechBio company decoding biology to industrialize drug discovery. Central to its mission is the Recursion Operating System (OS), a platform built across diverse technologies that continuously expands one of the world’s largest proprietary biological, chemical and patient-centric 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, chemistry and patient-centric data 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 other primary offices in Toronto, Montreal, the San Francisco Bay Area, New York, the Oxford area, and London. Recursion Investor Relationsinvestor@recursion.com Recursion Mediamedia@recursion.com Forward Looking Statements Statements contained herein which are not historical facts may be considered forward-looking statements under federal securities laws and may be identified by words such as “anticipates,” “believes,” “estimates,” “expects,” “intends,” “plans,” “potential,” “predicts,” “projects,” “seeks,” “should,” “will,” or words of similar meaning and include, but are not limited to, statements regarding the leadership position of the combined company and its impact on the industry; the ability for the combined business to accelerate the discovery of better solutions for patients; the timing of IND submissions and IND enabling studies; the potential to receive upfront, milestone, and royalty payments and work on over 60 therapeutic programs; the strengthening of the Recursion OS through the combined company; the continued learning of Recursion’s platform and the creation of virtual cells to enable execution of clinical trials at scale; Recursion’s achievement of efficiencies; the continuous expansion of the Recursion OS datasets; and advancing the future of medicine; the outlook for Recursion’s future business and financial performance; and others. Such forward-looking statements are based on the current beliefs of Recursion’s management as well as assumptions made by and information currently available to them, which are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. Actual outcomes and results may vary materially from these forward-looking statements based on a variety of risks and uncertainties including: the ability of the combined company to retain key personnel; the ability to realize the benefits of the combination, including cost synergies; the ability to successfully integrate Exscientia's business with Recursion’s business, at all or in a timely manner; the amount of the costs, fees, expenses and charges related to the combination; the effect of economic, market or business conditions, including competition, regulatory approvals and commercializing drug candidates, or changes in such conditions, have on the combined company’s operations, revenue, cash flow, operating expenses, employee hiring and retention, relationships with business partners, the development or launch of technology enabled drug discovery, and commercializing drug candidates; the risks of conducting business internationally; the impact of changes in interest rates by the Federal Reserve and other central banks; the impact of potential inflation, volatility in foreign currency exchange rates and supply chain disruptions; the ability to maintain technology-enabled drug discovery in the biopharma industry; and risks relating to the market value of Recursion’s Class A common stock. Other important factors and information are contained in Recursion’s most recent Annual Report on Form 10-K, including the risks summarized in the section entitled “Risk Factors,” Recursion’s subsequent Quarterly Reports on Form 10-Q, the joint definitive proxy statement filed by Recursion and Exscientia on October 10, 2024, as amended by the supplemental disclosures filed by Recursion on November 6, 2024, and each of Recursion’s other filings with the U.S. Securities and Exchange Commission (the “SEC”), which can be accessed at https://ir.recursion.com, or www.sec.gov. All forward-looking statements are qualified by these cautionary statements and apply only as of the date they are made. Recursion undertakes no obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Photos accompanying this announcement are available athttps://www.globenewswire.com/NewsRoom/AttachmentNg/359d7cd4-0ccf-4210-938d-f585a9b073eehttps://www.globenewswire.com/NewsRoom/AttachmentNg/a94dc301-518d-48a8-b8d3-430cd726d651https://www.globenewswire.com/NewsRoom/AttachmentNg/57cb9454-a7a7-4abf-a76f-82356a3682ac

Phase 1Executive Change

06 Nov 2024

·www.globenewswire.com

Recursion Provides Business Updates and Reports Third Quarter 2024 Financial Results

Multiple clinical trial milestones were achieved, including encouraging topline data for a Phase 2 trial in CCM, the first patient dosed for a Phase 2 trial in recurrent C. difficile infection, and IND clearance for a Phase 1/2 trial in biomarker-enriched solid tumors and lymphoma (Target RBM39), which highlight a growing number of potential clinical program catalystsOur first neuroscience phenomap was optioned by Roche-Genentech for $30 million as part of a fee structure that could exceed a total of $500 million across multiple maps before program-specific milestones or royaltiesEntered into an expanded collaboration with Google Cloud to leverage technologies to support our drug discovery platform, which continues to highlight Recursion’s close partnership with leading technology companies like Google, NVIDIA, Tempus, and othersThe potential business combination with Exscientia continues to advance towards close with a special shareholder meeting to be held on November 12, 2024 and an expected date for the scheme of arrangement to be November 20, 2024 SALT LAKE CITY, Nov. 06, 2024 (GLOBE NEWSWIRE) -- Recursion (Nasdaq: RXRX), a leading clinical stage TechBio company decoding biology to industrialize drug discovery, today reported business updates and financial results for its third quarter ending September 30, 2024. “We are excited to continue to drive rapidly towards the closure of our proposed business combination with Exscientia in a matter of weeks, ahead of the original guidance,” said Chris Gibson, Ph.D., Co-founder and CEO of Recursion. "We believe the combination with Exscientia will help to build a robust and diverse portfolio of tech-enabled clinical and near-clinical programs, significant value-creation opportunities through multiple transformational partnerships with both biopharma and technology companies, and the industry’s first full-stack technology-enabled small molecule discovery platform. Ultimately, we have never been more confident in our ability to translate our work into potential medicines for patients. These developments will drive additional value beyond the clinical trial catalysts we’ve seen in the last few months, including encouraging data from our Phase 2 trial in CCM, the first patient dosed in our Phase 2 trial in C. difficile infection, and our IND clearance for a Phase 1/2 trial in biomarker-enriched solid tumors and lymphoma (Target RBM39)." Summary of Business Highlights Pipeline Cerebral Cavernous Malformation (CCM) (REC-994): In September, we announced that our Phase 2 SYCAMORE clinical trial, which is a randomized, double-blind, placebo-controlled, study of two doses of REC-994 in participants with CCM, met its primary endpoint of safety and demonstrated encouraging trends in objective MRI-based exploratory efficacy measures at the highest dose, seeing reductions in lesion volume and hemosiderin ring size. We plan to meet with the FDA and advance the development of REC-994 for the potential treatment of symptomatic CCM in subsequent studies. We also plan to present the Phase 2 data at a medical conference and publish results in a peer reviewed scientific journal.Neurofibromatosis Type 2 (NF2) (REC-2282): Our adaptive Phase 2/3 POPLAR clinical trial is an open label, two part study of REC-2282 in participants with progressive NF2-mutated meningiomas. Part 1 of the study explores two doses of REC-2282 in adult and pediatric participants. Enrollment of adult patients in Part 1 of the study is complete (n=24). We expect to share an update in Q4 2024.Familial Adenomatous Polyposis (FAP) (REC-4881): Our Phase 1b/2 TUPELO clinical trial is an open label, multicenter, two part study of REC-4881 in participants with FAP. Part 1 is complete and enrollment in Part 2 has commenced. We expect to share Phase 2 safety and preliminary efficacy data in H1 2025.APC or AXIN1 Mutant Cancers (REC-4881): Our Phase 2 LILAC clinical trial is an open label, multicenter study of REC-4881 in participants with unresectable, locally advanced or metastatic cancer with AXIN1 or APC mutations. We expect to share Phase 2 safety and preliminary efficacy data in H1 2025.Clostridioides difficile Infection (REC-3964): In October, we announced the first patient dosed in our Phase 2 clinical study of REC-3964, a potential first-in-class, oral, non-antibiotic small molecule for recurrent Clostridioides difficile infection. Our Phase 2 ALDER clinical trial is an open-label, multicenter randomized study designed to evaluate rates of recurrence with REC-3964 at two doses compared with an observational cohort after patients have achieved initial cure with vancomycin. We expect a preliminary readout by the end of 2025.Biomarker-Enriched Solid Tumors and Lymphoma, Target RBM39 (REC-1245): In October, we announced FDA clearance of an IND for REC-1245, a potential first-in-class RBM39 degrader for biomarker-enriched solid tumors and lymphoma. RBM39 is a novel CDK12-adjacent target identified by the Recursion OS. We plan to initiate dosing of Phase 1/2 in Q4 2024 to evaluate REC-1245. Phase 1 data from the dose-escalation portion of the study is expected by the end of 2025.Undisclosed Indication in Fibrosis, Target Epsilon: We are advancing our lead candidate and expect an IND submission in early 2025. Partnerships Transformational Collaborations: We continue to advance efforts to discover potential new therapeutics with our strategic partners in the areas of undruggable oncology (Bayer) as well as neuroscience and a single indication in gastrointestinal oncology (Roche-Genentech). In August, our first neuroscience phenomap was optioned by Roche-Genentech for $30 million as part of a fee structure that could exceed a total of $500 million across multiple maps. In the near-term, there is the potential for option exercises associated with partnership programs and map building initiatives or data sharing. Platform Google Cloud Collaboration: We entered into an expanded collaboration with Google Cloud in order to leverage Google Cloud's technologies to support our drug discovery platform. This strategic partnership includes exploring generative AI capabilities, including Gemini models, to support the RecursionOS, drive improved search and access with BigQuery, and help scale compute resources. In addition, we will also explore making some of our AI models available on Google Cloud. Additional Corporate Updates Combination with Exscientia: A special shareholder meeting will be held on Nov 12, 2024 at 5:00 pm Eastern Time / 3:00 pm Mountain Time in order to vote on Recursion’s proposed combination with Exscientia. Shareholders may vote in advance of this meeting by telephone, mail, or online at www.virtualshareholdermeeting.com/RXRX2024SM. Following this shareholder meeting, we expect the date of the scheme of arrangement to be Nov 20, 2024.L(earnings) Call: We will not host a L(earnings) Call in relation to the business updates and financials for the third quarter. Instead, we expect to host an Update Call around the date of the scheme of arrangement which is expected to be Nov 20, 2024. We will broadcast the live stream from Recursion’s X (formerly Twitter), LinkedIn, and YouTube accounts and there will be opportunities to ask questions of the company.Chief People & Impact Officer: In October, Erica Fox joined Recursion as its Chief People & Impact Officer. Ms. Fox has over 20 years experience as a people and systems strategist having previously led various human resource functions at technology companies Primer.ai and Google. Third Quarter 2024 Financial Results Cash Position: Cash and cash equivalents were $427.6 million as of September 30, 2024.Revenue: Total revenue was $26.1 million for the third quarter of 2024, compared to $10.5 million for the third quarter of 2023. The increase was due to revenue recognized from our partnership with Roche & Genentech and the $30.0 million acceptance fee for the completion of a neuroscience phenomap.Research and Development Expenses: Research and development expenses were $74.6 million for the third quarter of 2024, compared to $70.0 million for the third quarter of 2023. The increase in research and development expenses was driven by our platform and personnel costs as we continue to expand and upgrade our platform, including our chemical technology, machine learning, and transcriptomics platform.General and Administrative Expenses: General and administrative expenses were $37.8 million for the third quarter of 2024, compared to $29.2 million for the third quarter of 2023. The increase in general and administrative expenses compared to prior period was primarily driven by an increase in software and lease expense.Net Loss: Net loss was $95.8 million for the third quarter of 2024, compared to a net loss of $93.0 million for the third quarter of 2023.Net Cash: Net cash used in operating activities was $59.2 million for the third quarter of 2024, compared to $72.9 million for the third quarter of 2023. The change in net cash used in operating activities compared to the same period last year was the net result of the $30.0 million acceptance fee received during the third quarter of 2024, partially offset by the higher operating costs incurred for research and development and general and administrative activities. About RecursionRecursion is a clinical stage TechBio company leading the space by decoding biology to industrialize drug discovery. Enabling its mission is the Recursion OS, a platform built across diverse technologies that continuously expands one of the world’s largest proprietary biological, chemical and patient-centric 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, chemistry and patient-centric data 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, Montreal, the San Francisco Bay Area, and London, UK. Learn more at www.Recursion.com, or connect on X (formerly Twitter) and LinkedIn. Media ContactMedia@Recursion.com Investor ContactInvestor@Recursion.com Recursion Pharmaceuticals, Inc.Condensed Consolidated Statements of Operations and Comprehensive Loss (unaudited)(in thousands, except share and per share amounts) Three months ended Nine months ended September 30, September 30,Revenue 2024 2023 2024 2023 Operating revenue$26,082 $10,102 $53,977 $33,252 Grant revenue - 431 316 432 Total revenue 26,082 10,533 54,293 33,684 Operating costs and expenses Cost of revenue 12,079 10,877 32,444 32,706 Research and development 74,600 70,007 216,087 171,744 General and administrative 37,757 29,199 100,998 80,364 Total operating costs and expenses 124,436 110,083 349,529 284,814 Loss from operations (98,354) (99,550) (295,236) (251,130) Other income, net 2,679 6,533 9,347 16,060 Loss before income tax benefit (95,675) (93,017) (285,889) (235,070) Income tax benefit (167) - 1,134 - Net loss and comprehensive loss$(95,842)$(93,017) $(284,755)$(235,070) Per share data Net loss per share of Class A, B and Exchangeable common stock, basic and diluted$(0.34)$(0.43) $(1.12)$(1.16)Weighted-average shares (Class A, B and Exchangeable) outstanding, basic and diluted 282,583,048 214,327,186 253,447,099 203,090,637 Recursion Pharmaceuticals, Inc.Condensed Consolidated Balance Sheets (unaudited)(in thousands) September 30,December 31, 2024 2023 Assets Current assets Cash and cash equivalents$427,647 $391,565 Restricted cash 1,555 3,231 Other receivables 2,255 3,094 Other current assets 42,715 40,247 Total current assets 474,172 438,137 Restricted cash, non-current 6,629 6,629 Property and equipment, net 84,410 86,510 Operating lease right-of-use assets 47,882 33,663 Financing lease right-of-use assets 26,897 - Intangible assets, net 34,093 36,443 Goodwill 52,056 52,056 Other assets, non-current 360 261 Total assets$726,499 $653,699 Liabilities and stockholders’ equity Current liabilities Accounts payable$2,260 $3,953 Accrued expenses and other liabilities 40,597 46,635 Unearned revenue 49,579 36,426 Operating lease liabilities 8,233 6,116 Notes payable and financing lease liabilities 8,219 41 Total current liabilities 108,888 93,171 Unearned revenue, non-current 15,712 51,238 Operating lease liabilities, non-current 53,663 43,414 Notes payable and financing lease liabilities, non-current 20,510 1,101 Deferred tax liabilities 168 1,339 Other liabilities, non-current 2,999 - Total liabilities 201,940 190,263 Commitments and contingencies Stockholders’ equity Common stock (Class A, B and Exchangeable) 3 2 Additional paid-in capital 1,776,933 1,431,056 Accumulated deficit (1,252,377) (967,622) Total stockholder's equity 524,559 463,436 Total liabilities and stockholders’ equity$726,499 $653,699 Forward-Looking StatementsThis 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 expectations related to early and late stage discovery, preclinical, and clinical programs, including timelines for enrollment in studies, data readouts, and progression toward IND-enabling studies; the timing and likelihood of completing the proposed business transaction with Exscientia plc; the impact of the Google Cloud agreement on our drug discovery platform; the option exercise by Roche-Genentech and the potential future revenue related to the potential creation, delivery, and option of future maps; the completion and uses of additional maps being built; our anticipated meeting with the FDA regarding REC-994; plans to present SYCAMORE trial data at a medical conference and submit the data for publication; developments with Recursion OS and other technologies, including construction of foundation models and augmentation of our dataset; developments of our transcriptomics technology, including the timing of development of a whole-genome knockout transcripts map; expectations and developments with respect to licenses and collaborations, including option exercises by partners and additional partnerships; prospective products and their potential future indications and market opportunities; expectations for business and financial plans and performance, including cash runway; Recursion’s plan to maintain a leadership position in data generation and aggregation and advancing the future of medicine; 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,” “could,” “continue,” and similar terms. These statements are subject to known or unknown risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements, including but not limited to: challenges inherent in pharmaceutical research and development, including the timing and results of preclinical and clinical programs, where the risk of failure is high and failure can occur at any stage prior to or after regulatory approval due to lack of sufficient efficacy, safety considerations, or other factors; our ability to leverage and enhance our drug discovery platform; our ability to obtain financing for development activities and other corporate purposes; the success of our collaboration activities; our ability to obtain regulatory approval of, and ultimately commercialize, drug candidates; our ability to obtain, maintain, and enforce intellectual property protections; cyberattacks or other disruptions to our technology systems; our ability to attract, motivate, and retain key employees and manage our growth; inflation and other macroeconomic issues; and other risks and uncertainties such as those described under the heading “Risk Factors” in our filings with the U.S. Securities and Exchange Commission (the “SEC”), including in the definitive joint proxy statement related to the proposed business combination filed with the SEC on October 10, 2024, our most recent Annual Report on Form 10-K, and our subsequent Quarterly Reports on Form 10-Q. All forward-looking statements are based on management’s current estimates, projections, and assumptions, and Recursion undertakes no obligation to correct or update any such statements, whether as a result of new information, future developments, or otherwise, except to the extent required by applicable law. Additional Information and Where to Find ItThis communication relates to the proposed business combination by and between Recursion and Exscientia plc. Recursion and Exscientia have delivered a definitive joint proxy statement related to the proposed business combination to Recursion’s stockholders and Exscientia’s shareholders, which was also filed with the SEC on October 10, 2024. The definitive joint proxy statement provides full details of the proposed business combination and the attendant benefits and risks, including the terms and conditions of the Scheme of Arrangement and the other information required to be provided to Exscientia’s shareholders under the applicable provisions of the United Kingdom Companies Act 2006. This communication is not a substitute for the definitive joint proxy statement or any other document that Recursion or Exscientia may file with the SEC or send to their respective security holders in connection with the proposed business combination. Security holders are urged to read the definitive joint proxy statement and all other relevant documents filed with the SEC or sent to Recursion’s stockholders or Exscientia’s shareholders as they become available because they will contain important information about the proposed business combination. All documents, when filed, will be available free of charge at the SEC’s website (www.sec.gov). You may also obtain these documents by contacting Recursion’s Investor Relations department at investor@recursion.com; or by contacting Exscientia’s Investor Relations department at investors@exscientia.ai. This communication does not constitute an offer to sell or the solicitation of an offer to buy any securities or a solicitation of any vote or approval. INVESTORS AND SECURITY HOLDERS ARE URGED TO READ THE DEFINITIVE PROXY STATEMENT (WHICH INCLUDES AN EXPLANATORY STATEMENT IN RESPECT OF THE SCHEME OF ARRANGEMENT OF EXSCIENTIA, IN ACCORDANCE WITH THE REQUIREMENTS OF THE UNITED KINGDOM COMPANIES ACT 2006) AND ANY OTHER RELEVANT DOCUMENTS THAT MAY BE FILED WITH THE SEC, AS WELL AS ANY AMENDMENTS OR SUPPLEMENTS TO THESE DOCUMENTS, CAREFULLY AND IN THEIR ENTIRETY IF AND WHEN THEY BECOME AVAILABLE BECAUSE THEY CONTAIN OR WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION. Participants in the SolicitationThe Company, Exscientia and their respective directors and executive officers may be deemed to be participants in any solicitation of proxies in connection with the proposed business combination. Information about Recursion’s directors and executive officers is available in Recursion’s proxy statement dated April 23, 2024 for its 2024 Annual Meeting of Stockholders. Information about Exscientia’s directors and executive officers is available in Exscientia’s Annual Report on Form 20-F dated March 21, 2024. Other information regarding the participants in the proxy solicitation and a description of their direct and indirect interests, by security holdings or otherwise, is contained in the definitive joint proxy statement. Investors are urged to read the definitive joint proxy statement and any other relevant materials to be filed with the SEC regarding the proposed business combination when they become available, carefully before making any voting or investment decisions. No Offer or SolicitationThis communication is not intended to and shall not constitute an offer to buy or sell or the solicitation of an offer to buy or sell any securities, or a solicitation of any vote or approval, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. The Company securities issued in the proposed business combination are anticipated to be issued in reliance upon an available exemption from such registration requirements pursuant to Section 3(a)(10) of the Securities Act of 1933, as amended. A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/3213e888-501b-4736-adad-9672e8e8792a

Phase 2Phase 1Clinical ResultFinancial StatementIND

18 Sep 2024

·endpts.com

With few efficacy details, Insilico claims a Phase 2a win in latest AI readout

Insilico Medicine reported Phase 2a results for its lead program, saying the study achieved its primary endpoint of safety and tolerability. But the efficacy data it released were much more vague. In a 71-patient trial testing ISM001-055 in idiopathic pulmonary fibrosis (IPF), Insilico said Wednesday that the drug improved a measurement of breathing called forced vital capacity compared to placebo after 12 weeks, and the responses were dose-dependent. However, Insilico did not report the absolute scores of each trial arm and whether the difference was statistically significant. In an interview Tuesday morning, Insilico CEO Alex Zhavoronkov declined to comment on the program’s statistical significance, saying he was not legally cleared to do so. He instead pointed to a trend identified by Insilico’s researchers across dosing arms as evidence the program works. “It depends on what kind of statistics you use,” Zhavoronkov said of ISM001-055’s statistical significance. “Currently, we don’t have enough patients to claim that it is statistically significant for approval, for example. But if you look at the data, it becomes very clear that there is a trend and there is a response.” If Insilico had run a longer trial specifically looking for efficacy, he said the dose response would have continued to increase. There’s no timeline yet for the program’s next steps, though Zhavoronkov said the company’s most immediate tasks are to submit the results to a medical journal and talk to regulators. ISM001-055 is a small molecule targeting TNIK, short for Traf2- and Nck-interacting kinase. Insilico said it discovered TNIK through its AI software and that inhibiting the target can halt or reverse fibrotic processes. Insilico is one of several biotechs aiming to speed up drug development through the use of artificial intelligence, and the readout comes a few weeks after Recursion — another AI player — also unveiled its first Phase 2 data. Some investors and VCs had framed the Recursion data drop as a “ moment of truth ” for the company and, by extension, the field after the first wave of AI-designed drugs fell short in the clinic . But Recursion’s data were too short on specifics for the public markets, and the startup’s stock price closed 16% lower the day it announced the data. In a rare neurological disease called cerebral cavernous malformations (CCM), Recursion’s drug, REC-994, succeeded on safety and tolerability endpoints but provided mixed results on efficacy. Recursion plans to advance the program, though it’s not yet clear if it will run a Phase 3 study or another Phase 2 trial. Zhavoronkov resisted comparing Insilico’s results to Recursion’s, citing both the differences in program design and diseases. He said IPF is a much more heterogeneous disease than CCM. While he said he respects Recursion and its CEO Chris Gibson, Zhavoronkov said people he spoke to were surprised the company didn’t terminate REC-994. “I don’t want to even compare with Recursion because it’s a different story,” Zhavoronkov said. “It’s not apples to apples. It’s like apples to seeds.”

Phase 2Clinical Result

100 Deals associated with Tempol

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KEGG	Wiki	ATC	Drug Bank
-	Tempol	-	DB12449

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Radiodermatitis	Phase 3	US	Matrix Biomed, Inc.	30 Jan 2022
COVID-19	Phase 3	US	DMK Pharmaceuticals Corp.	01 Sep 2021
Central Nervous System Cavernous Hemangioma	Phase 2	US	Recursion Pharmaceuticals, Inc.	17 Mar 2022
radiation oral mucositis	Phase 2	US	Matrix Biomed, Inc.	30 Jan 2022
Ataxia Telangiectasia	Phase 2	US	Matrix Biomed, Inc.	01 Jul 2021
Glioblastoma Multiforme	Phase 2	US	Matrix Biomed, Inc.	01 Jun 2021
Non-metastatic prostate cancer	Phase 2	US	Matrix Biomed, Inc.	30 May 2021
Recurrent Prostate Carcinoma	Phase 2	US	Matrix Biomed, Inc.	30 May 2021
Head and Neck Neoplasms	Phase 2	US	Matrix Biomed, Inc.	13 May 2019
Mucositis	Phase 2	US	Matrix Biomed, Inc.	13 May 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2014	Not Applicable	interleukin-1 beta \| tumor necrosis factor alpha \| IL-6	-	Tempol	zjefkmmfjr(uatxyrhqqi) = bvxlgyrewk lcszimhnew (anzkjerwsk )	Positive	11 Nov 2014
				Tempol	zjefkmmfjr(uatxyrhqqi) = jzdjcarpqe lcszimhnew (anzkjerwsk )
ARVO2013	Not Applicable	Toxicity superoxide dismutase \| oxidative stress	-	50 mM tempol	vqvicxmcil(gnjwasoxlp) = nxybzmrjkc vmmctkzufu (pxuwsfilnt )	Positive	01 Jun 2013
ARVO2008	Not Applicable	-	11	TEMPOL at 100mg/kg	bmmyucappt(stmhjuvrmn) = avmxglqatu yrxocdnrvk (jodctelqws, 29) View more	Positive	01 May 2008
				Saline	bmmyucappt(stmhjuvrmn) = naihxogfhs yrxocdnrvk (jodctelqws, 10) View more

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