UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 OR 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): February 27, 2023
(Exact name of registrant as specified in its charter)
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
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Securities registered pursuant to Section 12(b) of the Act:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 2.02. Results of Operations and Financial Condition.
On February 27, 2023, Recursion Pharmaceuticals, Inc. (the “Company”) issued a press release announcing its results of operations and financial condition for the fourth quarter and fiscal year ended December 31, 2022. A copy of the press release is furnished as Exhibit 99.1 and is incorporated herein by reference.
Item 7.01. Regulation FD Disclosure.
On February 27, 2023, the Company released an updated investor presentation. The investor presentation will be used from time to time in meetings with investors. A copy of the presentation is attached hereto as Exhibit 99.2.
The Company announces material information to its investors using filings with the Securities and Exchange Commission (the “SEC”), the investor relations page on the Company’s website, at https://ir.recursion.com/, press releases, public conference calls and webcasts. The Company uses these channels, as well as social media, to communicate with investors and the public about the Company, its products and services and other matters. Therefore, the Company encourages investors, the media and others interested in the Company to review the information it makes public in these locations, as such information could be deemed to be material information.
The information furnished pursuant to Item 2.02 (including Exhibit 99.1) and 7.01 (including Exhibit 99.2) on this Form 8-K, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any other filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit Number | Description | ||||
| 99.1 | |||||
| 99.2 | |||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | ||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized on February 27, 2023.
| RECURSION PHARMACEUTICALS, INC. | ||||||||
| By: | /s/ Michael Secora | |||||||
Michael Secora | ||||||||
Chief Financial Officer | ||||||||
Exhibit 99.1
Recursion Provides Business Updates and Reports Fourth Quarter and Fiscal Year 2022 Financial Results
•Initiated five clinical trials in 2022, including three Phase 2 programs, and provided guidance on the timing of clinical data readouts
•Delivered against core elements of our Roche-Genentech collaboration (neuroscience and an indication in gastrointestinal oncology) and Bayer collaboration (fibrosis) in 2022
•Continued to build-out the Recursion OS with scaled transcriptomic technologies, industry-leading hiPSC-derived cell production, and additional in-house chemistry capabilities
•Released RXRX3 (largest public dataset of its kind) and MolRec™ (application to explore compound and gene relationships in RXRX3) - framing how proprietary biological and chemical data built fit-for-the purpose of training ML models can be a value driver
SALT LAKE CITY, February 27, 2023 — Recursion (Nasdaq : RXRX), a clinical stage TechBio company leading the space by decoding biology to industrialize drug discovery, today reported business updates and financial results for its fourth quarter and fiscal year ended December 31, 2022.
"2022 was a fantastic year for Recursion where we continued to deliver on the promise of our pipeline with five clinical trial initiations, continued execution of our Bayer and Roche-Genentech partnerships, and continued to grow our proprietary data moat through our scale and accelerating capabilities across transcriptomics, digital in vivo tolerability, and chemistry," said Chris Gibson, Ph.D., Co-Founder & CEO at Recursion. "I believe that the work we have done in 2022 is setting the stage for significant value-creation in the coming 12-24 months. What is most exciting to me is the rapid uptick in the world’s curiosity around ML and AI due to advances in other industries. I think it is important to reflect on the tremendous advancements taking place around us and I believe we are best positioned to deploy similar tools across the drug discovery and development process."
Summary of Business Highlights
•Internal Pipeline
◦Cerebral Cavernous Malformation (CCM) (REC-994): Our Phase 2 SYCAMORE clinical trial is a double-blind, placebo-controlled safety, tolerability and exploratory efficacy study of this drug candidate in 60 participants with CCM. At this time, we continue to actively enroll participants. We expect to share top-line data in 2H 2024.
◦Neurofibromatosis Type 2 (NF2) (REC-2282): Our Phase 2/3 POPLAR clinical trial is a parallel group, two stage, randomized, multicenter study of this drug candidate in approximately 90 participants with progressive NF2-mutated meningiomas. At this time, we continue to actively enroll participants. We expect to share a Phase 2 interim safety analysis in 2024.
◦Familial Adenomatous Polyposis (FAP) (REC-4881): Our Phase 2 TUPELO clinical trial is a multicenter, randomized, double-blind, placebo-controlled two-part clinical trial to evaluate efficacy, safety, and pharmacokinetics of this drug candidate in patients with FAP. Recent protocol amendments are aimed at accelerating the quality and pace of the trial.
◦AXIN1 or APC Mutant Cancers (REC-4881): In October 2022, we announced the nomination of REC-4881 for the potential treatment of AXIN1 or APC mutant cancers with an initial focus on hepatocellular carcinoma and ovarian cancer. We
expect to initiate a Phase 1b/2 biomarker enriched basket study across select AXIN1 or APC mutant tumors in early 2024.
◦Clostridioides difficile Colitis (REC-3964): Our Phase 1 clinical trial is a first-in-human protocol evaluating single and multiple doses of REC-3964 in healthy volunteers and will assess the safety, tolerability and pharmacokinetic profile of REC-3964. At this time, we continue to actively enroll participants. We expect to share safety and PK data in 2H 2023.
◦HR-Proficient Ovarian Cancer: In January 2023, we disclosed that RBM39 (previously identified as Target Gamma) is the novel CDK12-adjacent target identified by the Recursion OS. We believe that modulating RBM39 could lead to a potential treatment of HR-proficient ovarian cancer. We expect this program to reach IND-enabling studies in 2023.
◦Enhancing Anti-PD-(L)1 Response by Inhibiting Novel Targets (Target Alpha): This program is a potential first-in-class novel chemical entity with a novel polypharmacologic mechanism of action for which we have not yet disclosed the targets. We expect this program to reach IND-enabling studies in 2023.
•Transformational Collaborations
We continue to advance efforts to discover potential new therapeutics with our strategic partners in the areas of fibrotic disease (Bayer) as well as neuroscience and a single indication in gastrointestinal oncology (Roche-Genentech). In the near-term, there is the potential for option exercises associated with partnership programs, option exercises associated with map building initiatives or data sharing and additional partnerships in large, intractable areas of biology or technological innovation.
•Recursion OS
◦Cell and Tissue Culturing: In 2022, we industrialized stem cell production and produced over 500 billion hiPSC-derived cells in-house to enable neurology research. We believe that this volume of biological material could make Recursion one of the largest producers of neural hiPSC-derived cells in the world and could give Recursion flexibility around its consumables and collaboration activities.
◦Chemical Technology: We have begun configuring our automated drug metabolism and pharmacokinetics (DMPK) wet-lab module into the Recursion OS. Once fully onboarded, this module will enable scaled, automated processing and evaluation of compounds for plasma protein binding, microsomal stability, and cell permeability. With an operational capacity of up to 500 compounds per week, this module lays the foundation for us to generate additional proprietary data moats that enable the training of ML and AI algorithms.
◦Publicly Available Dataset and Application: In January 2023, Recursion released RxRx3, its largest open-source cellular imaging dataset to date, as well as MolRec™, an interactive application to explore compound and gene relationships. Both of these offerings are free to the public and can be found at www.rxrx.ai.
•Additional Corporate Updates
◦Letter to Shareholders: Recursion Co-Founder & CEO Chris Gibson, Ph.D. wrote an annual letter to shareholders which may be found in the 10-K report filed with the SEC, ahead of Part I.
◦Download Day: In January 2023, Recursion hosted Download Day, a R&D-focused event highlighting aspects of Recursion's platform, data, programs, partnerships and culture. Materials from this event can be found at www.Recursion.com/download-day.
◦Facilities: Recursion completed an expansion of its headquarters in Salt Lake City, making room for research and development activities related to expanding our human tissue culture and chemical compound handling capabilities, enabling new biological contexts for map building and scaling sequencing and automated DMPK assays.
◦ESG Reporting: In October 2022, Sustainalytics ranked Recursion in the top 100 of pharmaceutical companies with respect to its ESG efforts (approximately top 10%). In March 2023, Recursion plans to release an updated ESG report.
◦Annual Shareholder Meeting: The Recursion Annual Shareholder Meeting will be held on June 16, 2023 at 12:00 pm Mountain Time.
Fourth Quarter and Fiscal Year 2022 Financial Results
•Cash Position: Cash, cash equivalents and investments were $549.9 million as of December 31, 2022, compared to $516.6 million as of December 31, 2021.
•Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $13.7 million for the fourth quarter of 2022, compared to $2.5 million for the fourth quarter of 2021. Total revenue, consisting primarily of revenue from collaboration agreements, was $39.8 million for the year ended December 31, 2022, compared to $10.2 million for the year ended December 31, 2021. The increase in both periods in 2022 was due to revenue recognized from our Roche-Genentech collaboration.
•Research and Development Expenses: Research and development expenses were $44.0 million for the fourth quarter of 2022, compared to $48.3 million for the fourth quarter of 2021. Research and development expenses were $155.7 million for the year ended December 31, 2022, compared to $135.3 million for the year ended December 31, 2021. The increase in 2022 research and development expenses compared to the prior year was due to increased clinical costs as studies progressed.
•General and Administrative Expenses: General and administrative expenses were $19.8 million for the fourth quarter of 2022, compared to $19.2 million for the fourth quarter of 2021. General and administrative expenses were $81.6 million for the year ended December 31, 2022, compared to $57.7 million for the year ended December 31, 2021. The increase in 2022 general and administrative expenses compared to the prior year was due to the growth in size of the company's operations, including an increase in salaries and wages of $14.3 million, a fixed asset write-down of $2.8 million, increased rent expense of $2.4 million and increases in other administrative costs associated with operating a growing company.
•Net Loss: Net loss was $57.5 million for the fourth quarter of 2022, compared to a net loss of $64.9 million for the fourth quarter of 2021. Net loss was $239.5 million for the year ended December 31, 2022, compared to a net loss of $186.5 million for the year ended December 31, 2021.
About Recursion
Recursion 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 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, Montreal and the San Francisco Bay Area. Learn more at www.Recursion.com, or connect on Twitter and LinkedIn.
Media Contact
Media@Recursion.com
Investor Contact
Investor@Recursion.com
Recursion Pharmaceuticals, Inc.
Consolidated Statements of Operations (unaudited)
(in thousands, except share and per share amounts)
| Three months ended | Years ended | ||||||||||||||||
| December 31, | December 31, | ||||||||||||||||
| 2022 | 2021 | 2022 | 2021 | ||||||||||||||
| Revenue | |||||||||||||||||
| Operating revenue | 13,676 | 2,500 | $ | 39,681 | $ | 10,000 | |||||||||||
| Grant revenue | — | 33 | 162 | 178 | |||||||||||||
| Total revenue | 13,676 | 2,533 | 39,843 | 10,178 | |||||||||||||
| Operating costs and expenses | |||||||||||||||||
| Cost of revenue | 10,840 | — | 48,275 | — | |||||||||||||
| Research and development | 43,980 | 48,291 | 155,696 | 135,271 | |||||||||||||
| General and administrative | 19,838 | 19,202 | 81,599 | 57,682 | |||||||||||||
| Total operating costs and expenses | 74,658 | 67,493 | 285,570 | 192,953 | |||||||||||||
| Loss from operations | (60,982) | (64,960) | (245,727) | (182,775) | |||||||||||||
| Other income (loss), net | 3,490 | 27 | 6,251 | (3,704) | |||||||||||||
| Net loss | $ | (57,492) | $ | (64,933) | $ | (239,476) | $ | (186,479) | |||||||||
| Per share data | |||||||||||||||||
| Net loss per share of Class A and B common stock, basic and diluted | $ | (0.31) | $ | (0.38) | $ | (1.36) | $ | (1.49) | |||||||||
| Weighted-average shares (Class A and B) outstanding, basic and diluted | 185,669,683 | 169,368,999 | 175,537,487 | 125,348,110 | |||||||||||||
Recursion Pharmaceuticals, Inc.
Consolidated Balance Sheets (unaudited)
(in thousands)
| December 31, | ||||||||
| 2022 | 2021 | |||||||
| Assets | ||||||||
| Current assets | ||||||||
| Cash and cash equivalents | $ | 549,912 | $ | 285,116 | ||||
| Restricted cash | 1,280 | 1,552 | ||||||
| Accounts receivable | — | 34 | ||||||
| Other receivables | 2,753 | 9,056 | ||||||
| Investments | — | 231,446 | ||||||
| Other current assets | 15,869 | 7,514 | ||||||
| Total current assets | 569,814 | 534,718 | ||||||
| Restricted cash, non-current | 7,920 | 8,681 | ||||||
| Property and equipment, net | 88,192 | 64,725 | ||||||
| Operating lease right-of-use-assets | 33,255 | — | ||||||
| Intangible assets, net | 1,306 | 1,385 | ||||||
| Goodwill | 801 | 801 | ||||||
| Other non-current assets | — | 35 | ||||||
| Total assets | $ | 701,288 | $ | 610,345 | ||||
| Liabilities and stockholders’ equity | ||||||||
| Current liabilities | ||||||||
| Accounts payable | $ | 4,586 | $ | 2,819 | ||||
| Accrued expenses and other liabilities | 32,904 | 32,333 | ||||||
| Unearned revenue | 56,726 | 10,000 | ||||||
| Notes payable | 97 | 90 | ||||||
| Operating lease liabilities | 5,952 | — | ||||||
| Lease incentive obligation | — | 1,416 | ||||||
| Total current liabilities | 100,265 | 46,658 | ||||||
| Deferred rent | — | 4,110 | ||||||
| Unearned revenue, non-current | 70,261 | 6,667 | ||||||
| Notes payable, non-current | 536 | 633 | ||||||
| Operating lease liabilities, non-current | 44,420 | — | ||||||
| Lease incentive obligation, non-current | — | 9,339 | ||||||
| Total liabilities | 215,482 | 67,407 | ||||||
| Commitments and contingencies | ||||||||
| Stockholders’ equity | ||||||||
Common stock (Class A and B) | 2 | 2 | ||||||
| Additional paid-in capital | 1,125,360 | 943,142 | ||||||
| Accumulated deficit | (639,556) | (400,080) | ||||||
| Accumulated other comprehensive loss | — | (126) | ||||||
| Total stockholders’ equity | 485,806 | 542,938 | ||||||
| Total liabilities and stockholders’ equity | $ | 701,288 | $ | 610,345 | ||||
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 early and late stage discovery, preclinical, and clinical programs; the timing of data from our studies or initiating IND studies; licenses and collaborations, including whether additional partnerships are entered into, existing partner options are exercised and the timing of such exercises; prospective products and their potential future indications and market opportunities; Recursion OS and other technologies; business and financial plans and performance; the release of an updated ESG report; 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. 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, including our most recent Quarterly Report on Form 10-Q and our Annual Report on Form 10-K. 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.
End of Q4 2022
This presentation and any accompanying discussion and documents contain information that includes or is based upon "forward-looking statements" within the meaning of the Securities Litigation Reform Act of 1995. These forward-looking statements are based on our current expectations, estimates and projections about our industry and our company, management's beliefs and certain assumptions we have made. The words “plan,” “anticipate,” “believe,” “continue,” “estimate,” “expect,” “intend,” “may,” “will” and similar expressions are intended to identify forward-looking statements. Forward-looking statements made in this presentation include statements about Recursion's use of the proceeds from its private placement, the initiation, timing, progress, results, and cost of our research and development programs and our current and future preclinical and clinical studies, the potential size of the market opportunity for our drug candidates, our ability to identify viable new drug candidates for clinical development and the accelerating rate at which we expect to identify such candidates, our expectation that the assets that will drive the most value for us are those that we will identify in the future using our datasets and tools, and many others. Forward-looking statements made in this presentation are neither historical facts nor assurances of future performance, are subject to significant risks and uncertainties, and may not occur as actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. For a discussion of factors that could affect our business, please refer to the "Risk Factors" sections in our filings with the U.S. Securities and Exchange Commission, including our Annual Report on Form 10-K. This presentation does not purport to contain all the information that may be required to make a full analysis of the subject matter. We undertake no obligation to correct or update any forward-looking statements, whether as a result of new information, future events or otherwise. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the company’s own internal estimates and research. While the company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while the company believes its own internal research is reliable, such research has not been verified by any independent source. Any non-Recursion logos or trademarks included herein are the property of the owners thereof and are used for reference purposesonly. 2
3 Recursion’s value proposition 4 - 9 How we build maps of biology and chemistry to turn drug discovery into a search problem 10 - 15 How we create value using our maps of biology and chemistry 16 - 17 Pipeline 18 - 62 Partnerships 63 - 66 Data 67 - 68 Value driven by our team and our milestones 69 - 72 Additional scientific and business context 73 - 85
Novel oncology programs (RBM39, Target Alpha) nearing IND-enabling studies Advancing collaborations in Fibrosis (Bayer) and Neuroscience (Roche-Genentech) • $13B in potential milestones across 50+ possible programs plus royalties Initiated 5 clinical trials in 2022 (3 Ph2, 2 Ph1) and planning to initiate a 6th clinical trial (Ph1b/2) for AXIN1 or APC mutated oncology in early 2024 We believe that we have built one of the largest proprietary & relatable in-vitro biological and chemical datasets on Earth • >21 petabytes of data and >3 trillion searchable relationships 4 Expecting REC-3964 Ph1 readout in 2H 2023, REC-994 Ph2 top-line data in 2H 2024, and REC-2282 Ph2 interim analysis in 2024
5Adapted from Scannell, J et al (2012). Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov, 11, 191-200. 0.1 1 10 50B 100M 500K 1K 20201962 1970 1980 1990 2000 2010 Compute Power (Transistors per Microprocessor)NMEs per $B spent (inflation adjusted) Moore’s Law: Computing power becomes faster and less expensive over time Eroom’s Law: Drug discovery is becoming slower and more expensive over time Opportunity
Platforms drive discovery. Unbiased & target agnostic Literature drives discovery. Informs target-based hypotheses Data are our fuel. Shape our hypotheses Data are an exhaust. Limited to testing hypotheses Virtuous cycles of atoms & bits. Iterative feedback accelerates learning Linear process. Little cross-program learning or iteration Connected data across programs. Relatable high-dimensional data Disparate data generation. Siloed to individual programs and diseases Industrialized to scale. Automation & standardization Bespoke processes. Low-dimensional assays & biomarkers 6
7
Data shown is the average of all our programs since late 2017. All industry data adapted from Paul, et al. Nature Reviews Drug Discovery. (2010) 9, 203–214 8 Screen — Hit ID — Validated Lead — Advanced Candidate — Development Candidate — Industry Recursion Failing faster and earlier to › › spend less › C o st t o IN D ( $ M ) 25 — 20 — 15 — 10 — 5 — 0 — Industry 40 — 30 — 20 — 10 — 0 — › and go faster 100 80 60 51 80% 75% 85% 100 64 25 64% 39% 62% 12 50% St ag e Ti m e t o V al id at ed L e ad ( m o ) Recursion Industry Recursion 8 Industry Recursion
PreclinicalLate Discovery Oncology Rare & Other Therapeutic Area Indication AXIN1 or APC MUTANT CANCERS (AXIN1 or APC mutant cancers; est. 65K) MYC-DRIVEN ONCOLOGY (MYC; est. 54K4) HR-PROFICIENT OVARIAN CANCER, RBM39 (HR-proficient ovarian cancer; 13K) FAMILIAL ADENOMATOUS POLYPOSIS (APC; est. 50K) CANCER IMMUNOTHERAPY, TARGET DELTA (Multiple; 88K3) CEREBRAL CAVERNOUS MALFORMATION (CCM; est. 360K1) NEUROFIBROMATOSIS TYPE 2 (NF2; est. 33K2) CLOSTRIDIOIDES DIFFICILE INFECTION (est. 730K) CANCER IMMUNOTHERAPY, TARGET ALPHA (Multiple; 72K3) Phase 1 Phase 2 Phase 3 9 All populations defined above are US and EU5 incidence unless otherwise noted. EU5 is defined as France, Germany, Italy, Spain and UK. (1) Prevalence for hereditary and sporadic symptomatic population. (2) Annual US and EU5 incidence for all NF2-driven meningiomas. (3) Our program has the potential to address a number of indications in this space. (4) Our program has the potential to address a number of indications driven by MYC alterations, totaling 54,000 patients in the US and EU5 annually. We have not finalized a target product profile for a specific indication. More than a dozen early discovery and research programs in oncology, neuroscience, inflammation & immunology, and rare disease
11 Image adapted from D’Orazio, M., et al. Nature Scientific Reports 2022. RNA Level Transcriptomics DNA Level (Population-Scale) Genomics Protein Level Proteomics Metabolites Level Metabolomics Organism Level InVivomics Cell Level Phenotypes Phenomics Built and scaled AspirationalExploratory Like digital maps of Earth, connections within and between layers add useful context. Similarly, Recursion is mapping different multiomic layers of biology and identifying connections within and between layers to better understand biology at scale.
different human cell types small molecule library, we believe this scale is on par with some large pharma companies hiPSC-derived cells produced in 2022, we believe that we are one of the largest hiPSC- derived cell producers Diverse Biological and Chemical Inputs Robotic Automation at Scale Up to 2.2 Million wet-lab experiments per week profiling genes and compounds, we believe we are one of the largest phenomics (human cellular image-based) data producers Digitization of Biology and Chemistry >21 Petabytes of proprietary high- dimensional data, we believe this is one of the largest relatable in vitro biological and chemical datasets ML-Based Analysis Top 500 supercomputer across any industry (TOP500 List, Nov 2022), we leverage vast neural networks and multiomics approaches to extract features and drive insights relatable hypotheses across multiple biological and chemical contexts ML-Based RelationshipsHigh-Dimensional Validation Up to 12 Top 500 >21 Petabytes2.2 Million / Week near whole exomes per week, we believe we are one of the largest transcriptomics data producers >3 Trillion Novel Insights at Scale Enables quality, relatability and scale of data
This is a whole-genome arrayed CRISPR knock-out Map generated in primary human endothelial cells Every gene is represented in a pairwise way (each is present in columns and rows) Dark Red indicates phenotypic similarity according to our neural networks while Dark Blue indicates phenotypic anti- similarity (which in our experience often suggests negative regulation) We can add the phenotypes of hundreds of thousands of small molecules at multiple doses and query and interact with these maps using a web application Thousands of examples of known biology and chemistry 13 All Human Genes with Significant Effects in this Cellular Context → A ll H u m an G en es w it h S ig n if ic an t Ef fe ct s in t h is C el lu la r C o n te xt →
One such example – the JAK / STAT pathway clustered by strength of interaction, including both similar genes (red) and opposite genes (blue) Can wade into areas of novel biology and chemistry… 14 JAK1 TNKS1BP1 PPP1R9B PHF13 SOCS3 PRKCH MEGF8 ASB7 SLC39A1 DOCK9 ZMYM3 FAM49B STK24 YWHAB IL6ST IL6R STAT3 IL6 JA K 1 IL 6 ST A T3 IL 6 R IL 6 ST YW H A B ST K 2 4 FA M 4 9 B ZM YM 3 TN K S1 B P 1 P P P 1 R 9 B P H F1 3 SO C S3 P R K C H M EG F8 A SB 7 SL C 3 9 A 1 D O C K 9
Trademarks are the property of their respective owners and used for informational purposes only. 15 INTS9 INTS11 INTS4 INTS7 INTS2 INTS8 INTS1 INTS6 C7orf26 INTS10 INTS13 INTS14 IN TS 1 4 IN TS 1 3 IN TS 1 0 C 7 o rf 2 6 IN TS 6 IN TS 1 IN TS 8 IN TS 2 IN TS 7 IN TS 4 IN TS 1 1 IN TS 9 Phenomics TVN (below diagram) vs. Centerscale (above diagram) Similar Opposite • In 2022, new independent research identified a previously unknown gene, C7orf26, as part of the Integrator complex • Maps jointly developed by Recursion and Genentech replicated this same result • Demonstrates accuracy and consistency across different map building approaches
17 Pipeline Build internal pipeline in indications with potential for accelerated path to approval Pipeline Strategy Precision Oncology Rare Disease Partnerships Data Partnership Strategy Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capabilities License subsets of data Direct generation of new data internally to maximize pipeline and partnership value-drivers Data Strategy Fibrosis Other large, intractable areas of biology Neuroscience* Licensing Augment Recursion OS *Includes a single oncology indication from our Roche and Genentech collaboration.
18 Partnerships Pipeline Data Partnership Strategy Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capabilities Build internal pipeline in indications with potential for accelerated path to approval Pipeline Strategy License subsets of data Direct generation of new data internally to maximize pipeline and partnership value-drivers Data Strategy Precision Oncology Rare Disease Fibrosis Other large, intractable areas of biology Neuroscience* Licensing Augment Recursion OS *Includes a single oncology indication from our Roche and Genentech collaboration.
PreclinicalLate Discovery Oncology Rare & Other Therapeutic Area Indication AXIN1 or APC MUTANT CANCERS (AXIN1 or APC mutant cancers; est. 65K) MYC-DRIVEN ONCOLOGY (MYC; est. 54K4) HR-PROFICIENT OVARIAN CANCER, RBM39 (HR-proficient ovarian cancer; 13K) FAMILIAL ADENOMATOUS POLYPOSIS (APC; est. 50K) CANCER IMMUNOTHERAPY, TARGET DELTA (Multiple; 88K3) CEREBRAL CAVERNOUS MALFORMATION (CCM; est. 360K1) NEUROFIBROMATOSIS TYPE 2 (NF2; est. 33K2) CLOSTRIDIOIDES DIFFICILE INFECTION (est. 730K) CANCER IMMUNOTHERAPY, TARGET ALPHA (Multiple; 72K3) Phase 1 Phase 2 Phase 3 19 All populations defined above are US and EU5 incidence unless otherwise noted. EU5 is defined as France, Germany, Italy, Spain and UK. (1) Prevalence for hereditary and sporadic symptomatic population. (2) Annual US and EU5 incidence for all NF2-driven meningiomas. (3) Our program has the potential to address a number of indications in this space. (4) Our program has the potential to address a number of indications driven by MYC alterations, totaling 54,000 patients in the US and EU5 annually. We have not finalized a target product profile for a specific indication. More than a dozen early discovery and research programs in oncology, neuroscience, inflammation & immunology, and rare disease
REC-994 for the Treatment of Symptomatic Cerebral Cavernous Malformations (CCM) Target / MOA Superoxide Scavenger Molecule Type Small Molecule Lead Indication(s) Cerebral Cavernous Malformations Status Phase 2 Designation(s) US & EU Orphan Drug Source of Insight Recursion OS
21 • Large unmet need for a novel nonsurgical treatment • Vascular malformations (cavernomas) in the brain and spinal cord • High-risk for hemorrhage creates “ticking time bomb” • Progressive increase in CCM size and number over time in those with familial disease • Debilitating symptoms, including intractable seizure, intracerebral hemorrhage, focal neurological deficits Description “Historically, cavernomas have been managed primarily with observation, surgical resection, and occasionally radiotherapy. However, for a number of reasons, many patients with cavernomas must endure a life with neurologic symptoms” - Ryan Kellogg, MD, Investigator at the University of Virginia 21 Clinical: CCM
22 Sources: Angioma Alliance ; Flemming KD, et al . Population-Based Prevalence of Cerebral Cavernous Malformations in Older Adults: Mayo Clinic Study of Aging. JAMA Neurol. 2017 Jul 1;74(7):801-805. doi: 10.1001/jamaneurol.2017.0439. PMID: 28492932; PMCID: PMC5647645 ; Spiegler S, et al Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic Analyses, and Genetic Counselling. Mol Syndromol. 2018 Feb;9(2):60-69. doi: 10.1159/000486292. Epub 2018 Jan 25. PMID: 29593473; PMCID: PMC5836221. ~360,000 Patient Population – Large and Diagnosable No Approved Medical Therapy • >1 million patients worldwide live with these lesions today • Caused by loss of function mutation in one of three genes: CCM1 (60%), CCM2 (20%), and CCM3 (20%) • Inherited autosomal dominant mutation in 30-40%; or sporadic • US symptomatic population is more than 5 times larger than other rare diseases like Cystic Fibrosis (>31k patients) and Spinal Muscular Atrophy (>33k patients) • No approved drugs for CCM and no other potential therapeutic in industry-sponsored clinical development • Most patients receive no treatment or only symptomatic therapy • Surgical resection or stereotactic radiosurgery not always feasible because of location of lesion and is not curative Julia – living with CCM Clinical: CCM Symptomatic US + EU5 patients 22
23 Non-oncology Orphan Indication Product U.S. + EU5 Prevalence Cerebral cavernous malformation (CCM) REC-994 (Recursion) >1,800,000 (Symptomatic: ~360,000) Idiopathic pulmonary fibrosis (IPF) Esbriet (pirfenidone) >160,000 Cystic fibrosis (CF) VX-669/ VX-445 + Tezacaftor + Ivacaftor - Vertex >55,000 Spinal muscular atrophy (SMA) SPINRAZA (nusinersen) >65,000 Clinical: CCM Sources: Angioma Alliance ; Flemming KD, et al . Population-Based Prevalence of Cerebral Cavernous Malformations in Older Adults: Mayo Clinic Study of Aging. JAMA Neurol. 2017 Jul 1;74(7):801-805. doi: 10.1001/jamaneurol.2017.0439. PMID: 28492932; PMCID: PMC5647645 ; Spiegler S, et al Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic Analyses, and Genetic Counselling. Mol Syndromol. 2018 Feb;9(2):60-69. doi: 10.1159/000486292. Epub 2018 Jan 25. PMID: 29593473; PMCID: PMC5836221; Maher T, et al Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir Res. 2021 Jul 7;22(197). Doi: 10.1186/s12931-021-01791-z. PMID: 34233665. DRG 2022 Solutions, Report: Epidemiology, Cystic Fibrosis. CDC: SMA 23
24 • Symptoms associated with both increased size of lesions, but also inflammation or activation of lesions within the immunopriviledged environment of the brain • Lesions arise from the capillary bed and are not high-pressure (e.g., the lesion growth is unlikely to be primarily driven by the law of Laplace) • The Recursion Vascular Stability Hypothesis: • Eliminating the lesions may not be required for significant patient benefit • Slowing or halting the growth of the lesions while mitigating lesion leakiness and endothelial cell activation to halt the feed-forward inflammatory reaction may mitigate some symptoms and be beneficial to patients Novel therapeutic approach 24 Clinical: CCM
Clinical: CCM Gibson, et al. Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation, 2015 siCTRL siCCM2 siCCM2 + Simvastatin siCCM2 + Cholecalciferol siCCM2 + REC-994 Using an early version of our Recursion OS in an academic setting, we identified about 39 molecules out of 2,100 screened that according to a machine learning classifier rescued a complex unbiased phenotype associated with CCM2 loss of function. Through a set of follow-on confirmatory assays of increasing complexity, REC-994 stood out as one of two compounds we tested in a 5-month chronic CCM animal model where both compounds demonstrated significant benefit. 25
Healthy REC-994 ImpactCCM Clinical: CCM • Endothelial cell activation • Smooth muscle proliferation • Leukocyte adhesion • Platelet aggregation By regulating SOD2, CCM1 (KRIT1) & CCM2 suppress: CCM1 or CCM2 loss of function leads to activated endothelium: • Decreased cell-cell junctional integrity and increased monolayer permeability • Impaired vasodilation • Cavernous angioma formation Dosing of REC-994 restores normal function: • Normalized ROS balance • Restores quiescent endothelial cell state • Stabilizes endothelial barrier function Adapted from REC-994 Investigator Brochure 26
27 Source: Data above from Gibson, et al. Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation, 2015 or Recursion internal data (Ccm1 mouse model) Preclinical Studies: REC-994 reduces lesion burden and ameliorates vascular defects in genetic mouse models of CCM Vascular permeability is a clinically relevant feature of CCM lesions REC-994 stabilizes the integrity of vasculature against challenges to permeability Clinical: CCM Reduces lesion number and size in Ccm1 and Ccm2 LOF mouse models1 Completely rescues acetylcholine-induced vasodilation defect2 Rescues dermal permeability defect in CCM2 mice3 Lesion size (mm2) Ccm1 LOF Model ecKO + REC-994 WT ecKO % V as o d ila ti o n Acetylcholine [Log M] 27 Lesion size (mm2) Ccm2 LOF Model * * * DMSO control REC-994 Ccm2 WT Ccm2 ecKO D e rm al P e rm e ab ili ty (A b so rp ti o n , A U ) *
REC-994 Phase 1 Studies - well-tolerated with no dose-dependent adverse events in SAD and MAD Clinical: CCM MAD Study Placebo 50 mg 200 mg 400 mg 800 mg Total Number of TEAEs Total Subjects with ≥ one TEAE 5 4 0 0 10 3 4 3 15 4 Severity Mild Moderate Severe 3 1 0 0 0 0 3 0 0 3 0 0 3 1 0 Relationship to Study Drug None Unlikely Possibly Likely Definitely 3 1 0 0 0 0 0 0 0 0 0 1 0 2 0 2 1 0 0 0 1 2 0 1 0 Total Number of SAEs Total Subject with ≥ one TEAE Discontinued Study Drug Due to AE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Source: REC-994 for the Treatment of Symptomatic Cerebral Cavernous Malformation (CCM) Phase 1 SAD and MAD Study Results. Oral Presentation at Alliance to Cure Scientific Meeting. 2022 Nov 17 28
29 Phase 2 trial initiated in Q1 2022 Source: https://www.clinicaltrials.gov/ct2/show/NCT05130866?term=recursion&draw=2&rank=3; https://www.SycamoreCCM.com/ Screening & Randomization 1:1:1 Treatment Follow-up Enroll 60 400mg 200mg Placebo 12 Months Treatment Period Visits: Days 1 & 2 Months 1, 3, 6, 9 & 12 Extension study • Enrollment is progressing • Top-line data expected 2H 2024 Outcome Measures Enrollment Criteria • MRI-confirmed CCM lesion(s) • Familial or sporadic • Symptoms directly related to CCM • Primary: Safety and tolerability • Adverse events & symptoms • Secondary: Efficacy • Clinician-measured outcomes (CGI and PGI) • Imaging of CCM lesions – number, size & rate of change • Impact of acute stroke (mRS, NIHSS) • Patient reported outcomes (SMSS, PROMIS-29, CCM HI, symptom questionnaires) • Exploratory: Biomarkers Trial Update Clinical: CCM 29
REC-2282 for the Treatment of Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas Target / MOA HDAC Inhibitor Molecule Type Small Molecule Lead Indication(s) NF2 Mutated Meningiomas Status Phase 2/3 Designation(s) Fast Track; US and EU Orphan Drug Source of Insight Recursion OS
31 Source: https://rarediseases.org/rare-diseases/neurofibromatosis-2 Patient Population – Large and Diagnosable No Approved Medical Therapy • Rare autosomal dominant tumor syndrome resulting from biallelic inactivation of the NF2 gene which leads to deficiencies in the tumor suppressor protein merlin • NF2 can be inherited or spontaneous (>50% of patients represent new mutations); up to 1/3 are mosaic • CNS manifestations: meningiomas and vestibular schwannomas; mean age at presentation: ~20 years • No approved drugs for NF2 • Surgery is standard of care (when feasible) • Location may make complete resection untenable, leading to hearing loss, facial paralysis, poor balance and visual difficulty Ricki – living with NF2 Clinical: NF2 31
32 • Threatens mortality; if amenable, surgical excision is primary intervention • Many patients have multiple meningiomas that exhibit heterogenous behavior and asynchronous growth • Stasis or shrinkage of tumor could improve prognosis Clinical: NF2 ● Most tumors are benign and slow growing but location in CNS leads to serious morbidity or mortality ● Prognosis is adversely affected by early age at onset, a higher number of meningiomas and having a truncating mutation ~29,500 Patients who have Meningiomas that Harbor NF2 Mutations (Sporadic) ~3,500 NF2 Patients have Meningiomas (Familial) >66,000 Patients have Meningiomas Treatable US + EU5 patients ~33,000 Intracranial Meningioma Source: Pemov, et al. Comparative clinical and genomic analysis of neurofibromatosis type 2-associated cranial and spinal meningiomas. Nature. 2020 Jul 28;10(12563). Doi: https://doi.org/10.1038/s41598-020-69074-z; NORD 32
33 NF2 knockdown cells Healthy Cells REC-2282 REC-2282 identified as rescuing HUVEC cells treated with NF2 C o n tr o l N F2 s iR N A HUVEC, human umbilical vein endothelial cells; NF2, neurofibromatosis type 2; siRNA, small interfering RNA. Clinical: NF2 33
34 AKT, protein kinase B; eIF4F, eukaryotic initiation factor 4F; HDAC, histone deacetylase; mTor, mammalian target of rapamycin; mTORC1; mammalian target of rapamycin complex 1; NF2, neurofibromatosis type 2; PI3K, phosphoinositide 3-kinase; PP1, protein phosphate 1; Ras, reticular activating system. Clinical: NF2 Orally Bioavailable, CNS-penetrating, Small Molecule HDAC Inhibitor NF2 encodes for the protein Merlin and negatively regulates mTOR signaling 1 2 3 Loss of Merlin leads to increased signaling in the PI3K/AKT/mTOR pathway Oncogenic mTOR signaling arrested with HDAC inhibitors Cell proliferation and survival Normal cell proliferation and survival Cell proliferation and survival Constitutive activation is independent of extracellular factors and does not respond to biochemical signals that would normally regulate activity 34 1 2 3
35 REC-2282 preclinical studies demonstrated clear in-vivo efficacy in multiple NF2 tumor types Shrinks vestibular schwannoma xenografts in nude mice Prevents growth & regrowth of NF2- deficient meningioma model in mice Vehicle % Change tumor vol. REC-2282 % Change tumor vol. % c h an ge in t u m o r vo lu m e fr o m b as e lin e M R I % c h an ge in t u m o r vo lu m e fr o m b as e lin e M R I Clinical: NF2 https://link.springer.com/article/10.1007/s00280-020-04229-3 2 0% 10% 30% 60% -20% -40% 20% 40% 50% -10% -30% -50% 0% 10% -20% -40% -10% -30% -50% 35 1
• Evaluable Patients: CNS Solid Tumors: NF2 N=5; Non-CNS Solid Tumors: N=10 • PFS: CNS solid tumors = 9.1 months; Non-CNS solid tumors = 1.7 months • Best overall response = SD in 8/15 patients (53%; 95% CI 26.6–78.7) • Longest duration of follow-up without progression: > 27 months (N=1) • Most common AEs: cytopenia, fatigue, nausea 0 1 2 3 4 5 6 7 8 9 10 Overall Non-CNS solid tumors CNS solid tumors Months Progression-Free Survival 9.1m 1.7m 3.6m Clinical: NF2 Well understood clinical safety ... Multiple investigator-initiated studies in oncology indications Lengthy human clinical exposure in NF2 – multiple patients on drug for several years Well-characterized side effect profile … with a drug-like profile Established and scalable API manufacturing process Multiple cGMP batches of 10mg and 50mg tablets have been manufactured Excellent long-term stability 36
37 1 Sborov DW, et al. A phase 1 trial of the HDAC inhibitor AR-42 in patients with multiple myeloma and T- and B-cell lymphomas. Leuk Lymphoma. 2017 Oct;58(10):2310-2318. 2 Collier KA, et al. A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies. Cancer Chemother Pharmacol. 2021 May;87(5):599-611. 3 Prescribing Information of Vorinostat/Belinostat/Romidepsin respectively Clinical: NF2 REC-2282 Would be First-In-Class HDAC Inhibitor for Treatment of NF2 Meningiomas 37
Phase 2/3 trial initiated in Q2 2022 Outcome Measures Enrollment Criteria • MRI-confirmed progressive meningioma • Either of the below • Sporadic meningioma with confirmed NF2 mutation • Confirmed diagnosis of NF2 disease • Primary: Safety and tolerability • Progression-free survival • Time to progression • Duration of response • Overall response rate https://clinicaltrials.gov/ct2/show/NCT05130866 Clinical: NF2 Interim Analysis ▪ Go/No-go to Ph3 ▪ PFS ▪ Safety/Tolerability ▪ PK Enroll 20 40mg 60mg 6 Months Tx Period 20 Months Tx Period Extension Study Cohort A Final Data Screening & Randomization 1:1 Treatment Follow-up Agreement on Phase 3 registration plans FDA Mtg Phase 2 (Cohort A) Enroll 60 Phase 3 (Cohort B) 26 Months Tx Period Extension Study Interim Analysis ▪ At 50% of events ▪ For Sample size re-estimation (i.e., adaptive design) • Enrollment is progressing • Interim safety analysis expected 2024 Trial Update 38
REC-4881 for the Treatment of Familial Adenomatous Polyposis (FAP) Target / MOA MEK Inhibitor Molecule Type Small Molecule Lead Indication(s) Familial Adenomatous Polyposis Status Phase 2 Designation(s) Fast Track; US and EU Orphan Drug Source of Insight Recursion OS
40 Patient Population – Easily Identifiable Clinical: FAP ~50,000 Diagnosed US + EU5 patients • Autosomal dominant tumor predisposition syndrome caused by a mutation in the APC gene • Classic FAP (germline mutation) : • Hundreds to thousands of polyps in colon and upper GI tract • Extraintestinal manifestations (e.g., desmoid tumors) • 100% likelihood of developing colorectal cancer (CRC) before age 40, if untreated Polyps Found in Colon and Upper GI Tract 40 https://www.hopkinsmedicine.org/health/conditions-and-diseases/familial-adenomatous-polyposis
41 No Approved Medical Therapy • Standard of care: colectomy during adolescence (with or without removal of rectum) • Post-colectomy, patients still at significant risk of polyps progressing to GI cancer • Significant decrease in quality-of-life post-colectomy: continued endoscopies and surgical intervention Polyps on mucosal membrane of colon Cross section of colon and rectum Multiple polyps in the colon Sigmoidoscope Scope view Clinical: FAP “Despite progress with surgical management, the need for effective therapies for FAP remains high due to continued risk of tumors post-surgery” - Niloy Jewel Samadder, MD, Mayo Clinic https://www.hopkinsmedicine.org/health/conditions-and-diseases/familial-adenomatous-polyposis 41
42 REC-4881 rescued phenotypic defects of cells with APC knockdown 0.1 µM REC-4881 • Compared to thousands of other molecules tested, REC-4881 rescued phenotypic defects substantially better (including better rescue than other MEK inhibitors) for APC specific knockdown • Findings validated in tumor cell lines and spheroids grown from human epithelial tumor cells with APC mutation • 1,000x more selectivity in tumor cell lines with APC mutation • Inhibited growth and organization of spheroids APC knockdown cellsHealthy Cells Clinical: FAP 42
43 Jeon, WJ, et al. (2018). Interaction between Wnt/β-catenin and RAS-ERK pathways and an anti-cancer strategy via degradations of β-catenin and RAS by targeting the Wnt/β-catenin pathway. npj Precision Oncology, 2(5). 3 3 REC-4881 inhibits MEK 1/2 and recovers the destabilization of RAS by the β-Catenin destruction complex, restoring the cell back to a Wnt-off like state 2 1 Orally Bioavailable, Small Molecule MEK Inhibitor Disease State REC-4881 Impact Clinical: FAP 43
44 APC, adenomatosis polyposis coli; ERK, extracellular signal-regulated kinase; FAP, familial adenomatous polyposis. Clinical: FAP ↓ High-Grade Dysplasia 2• In-vivo efficacy in APCmin mouse model • Apcmin = FAP disease model • Mice treated once daily for 8 weeks After 8 weeks of treatment: ↓ Polyp Count1 1 2 To ta l P o ly p C o u n t (+ /- SE M ) H ig h G ra d e A d e n o m as ( % ) 44
45 Note: AE, adverse event; MEK, mitogen-activated protein kinase; NHV, normal healthy volunteer; pERK, phosphorylated extracellular signal-regulated kinase; SAE, serious adverse event. REC-4881-101: Single-center, double-blind, placebo- controlled, dose-escalation study in healthy volunteers • Group 1 (n=13): Food effect crossover (REC-4881 4 mg/PBO [fed/fasted]), followed by single dose REC-4881 8 mg/PBO [fed] • Group 2 (n=12): Matched single ascending dose (REC- 4881 4 mg/PBO; REC-4881 8 mg/PBO; REC-4881 12 mg/PBO) Accomplished Clinical: FAP Recursion formulation yields exposures comparable to Takeda’s formulation (molecule in-licensed from Takeda) No food effect Dose proportional increases in exposure Similar to C20001 study, observed pERK inhibition (i.e., target engagement) at 8 mg and 12 mg doses Acceptable safety profile 45
46 Clinical: FAP Phase 2 trial initiated in Q3 2022 Outcome Measures Enrollment Criteria • Confirmed APC mutation • Post-colectomy/proctocolectomy • No GI cancer present • Polyps in either duodenum (including ampulla of vater) or rectum/pouch • Primary: • Part 1: PK • Part 2: % change from baseline in polyp burden • Secondary: • Part 1: Safety & tolerability • Part 2: PK; PD; change from baseline in polyp number, histological grade, disease scoring • Exploratory: • Part 1: PD • Part 2: Time to first occurrence of FAP- related event; change from baseline in extent of desmoid disease https://clinicaltrials.gov/ct2/show/NCT05552755 46 • Recent protocol amendments aimed at accelerating quality and pace of the trial Trial Update Part 2 Screening & Randomization 1:1:1 Treatment Follow-up Enroll N = ~28/arm 8mg Placebo 6 Months Treatment Period Extension Study 12mg Part 1 Option to roll into Part 2… Multiple Dose (4mg or placebo) Single Dose (4mg or placebo) Safety, Tolerability, PK in up to 7 participants (5:2 active/placebo)
REC-4881 for the Treatment of Solid Tumors with AXIN1 or APC Mutant Cancers Target / MOA MEK Inhibitor Molecule Type Small Molecule Lead Indication(s) Solid Tumors with AXIN1 or APC Mutant Cancers Status Phase 1b/2 Source of Insight Recursion OS
48 • Sustained Wnt signaling is a frequent driver event found across a wide variety of solid tumors • Dysregulation of β-catenin destruction complex due to inactivating mutations in AXIN1 or APC leads to sustained Wnt signaling promoting cancer progression and survival1 • AXIN1 or APC mutant solid tumors are considered clinically aggressive and resistant to standard treatments 1 Bugter, J.M., et al. Nat Rev Cancer, 2021, 21, pp.5-21 Gross morphology of HCC tumor Clinical: AXIN1 or APC “Nothing in HCC has immediate therapeutic relevance and the most common mutations are TERT, TP53, and Wnt (CTNNB1/AXIN1/APC) and combined these alterations define almost 80% of patients and are not targetable” - KOL, Clinical Investigator, Texas 48
49 • AXIN1 and APC genes covered by commercially available NGS panels and liquid biopsy detection assays • FDA guidance supports utility of ctDNA as patient selection for the detection of alterations for eligibility criteria and as a stratification factor for trials enrolling marker-positive and marker-negative populations3 • Multiple tumor types will inform study design and patient selection Flexible Patient Selection Strategy and Study Design 1 Obtained from cbioportal.org. 2 Represents 2L treatable population estimates; obtained from DRG. 3 https://www.fda.gov/media/158072/download Tumor Type AXIN1 Mutation Frequency1 APC Mutation Frequency1 Treatable Population2 (US+EU5) CRC 3% 70% 27,450 LUAD 4% 11% 14,000 Prostate 2% 11% 6,700 Bladder 3% 8% 5,100 HCC 12% 5% 3,100 Endometrial 8% 12% 2,600 Esophageal 2% 7% 2,600 PDAC 1% 2% 1,500 Ovarian 1% 3% 1,400 TNBC 1% 2% 300 Preclinical data with REC-4881 at clinically relevant exposures in HCC and Ovarian PDX mouse models gives confidence to pursue other mutant cancer types Clinical: AXIN1 or APC 49 ~65,000
REC-4881 Dosage Hypothesis: Rescue of AXIN1 may impact tumor progression and/or restore checkpoint sensitivity in cancers driven by AXIN1 loss Recursion Differentiation: REC-4881 rescues tumor suppressor genes APC and AXIN1 • APC and AXIN1 are negative regulators of Wnt signaling • Both proteins form part of the B-catenin destruction complex. Strong clustering suggests map recapitulation of this biology Clinical: AXIN1 or APC Heat map from Recursion OS Similar Opposite 50
Efficacy found in In Vivo Mice Models … … Led to Significant Progression Free Survival Clinical: AXIN1 or APC -20 0 20 40 60 80 100 Tu m o r G ro w th In h ib it io n ( % ) AXIN1 or APC Mutant AXIN1 or APC Wildtype Average TGI: ~70% mutant vs ~49% wildtype Median TGI: ~72% mutant vs ~48% wildtype p = 0.0009 AXIN1 or APC mutant P ro b ab ili ty o f p ro gr es si o n -f re e (b y tu m o r d o u b lin g) Note: REC-4881 dosed at 3 mg/kg QD for up to 21 days. 3 mice per treatment per model (3 x 3 x 3) design p = 0.23 AXIN1 or APC wildtype P ro b ab ili ty o f p ro gr es si o n -f re e (b y tu m o r d o u b lin g) Next Steps ❑ Finalize design of a Phase 1b/2 biomarker-enriched trial ❑ Initiate Phase 1b/2 trial in select tumor types in early 2024 ❑ Identify suitable partners for genetic testing capabilities ❑ Evaluate REC-4881 in combination with targeted and/or immune modulating agents 51
REC-3964 for the Treatment of C. Difficile Infection Target / MOA Selective C. diff Toxin Inhibitor Molecule Type Small Molecule Lead Indication(s) C. Difficile Infection Status Phase 1 Source of Insight Recursion OS
53 Disruption of microbiota and colonization of C. diff Release of C. diff toxins Degradation of colon cell junction & toxin transit to bloodstream Clinical: C. Difficile Source: McCollum, D,, Rodriguez, JM . Detection, Treatment, and Prevention of Clostridium difficile Infection. Clinical Gastroenterology and Hepatology 2012 Mar 19. https://doi.org/10.1016/j.cgh.2012.03.008 53 1 2 3
Source, CDC *NAAT = Nucleic Acid Amplification Test; **rCDI = recurrent CDI • RCDI** occurs in 20-30% of patients treated with standard of care • 40% of those patients will continue to recur with 2+ episodes • >29,000 patients die in the US each year from CDI • Cost burden of up to $4.8bn annually 54 Patient Population – Large, Diagnosable and Easy to Identify Large, Unmet Need with Significant Cost Burden • Symptoms caused by clostridioides difficile tissue-damaging toxins released in the colon • Patients who experience >3 unformed stools are diagnosed via NAAT* for toxin gene or positive stool test for toxins • Patients who are at highest risk are those on antibiotics, and frequently visit hospitals or are living in a nursing home • More than 80% of cases occur among patients age 65 or older Clinical: C. Difficile ~730,000 Diagnosed US + EU5 patients Colleen – lived with rCDI 54
REC-3964 identified as a NCE that demonstrated strong rescue in HUVEC cells treated with C. diff toxin C. diff toxin B phenotype Healthy Control Disease State Healthy Cells REC-3964 0.1 µM Clinical: C. Difficile 55
Clinical: C. Difficile The glucosyltransferase locks Rho family GTPases in the inactive state C.diff toxins bind to cell surface receptors and trigger endocytic event 1 Autocatalytic cleavage event releases C.diff toxin's glucoyltransferase enzymatic domain into the cytosol of the infected cell 2 3 3 1 2 Inactivation of Rho GTPases alters cytoskeletal dynamics, induces apoptosis, and impairs barrier function which drives the pathological effects of C.diff infection 4 4 REC-3964 is Recursion’s 1st Small Molecule NCE to Reach the Clinic 56Adapted from Awad et al. 2014
Adapted from Awad, MM. et al. (2014). Clostridium difficile virulence factors: Insights into an anaerobic spore-forming pathogen. Gut Microbes. 5(5), 579-593. Clinical: C. Difficile 3 1 2 4 REC-3964 binds and blocks catalytic activity of the toxin’s innate glucosyltransferase, but not the host's 5 5 REC-3964 is Recursion’s 1st Small Molecule NCE to Reach the Clinic 57
✓ REC-3964 restores gut epithelial barrier integrity, which when disrupted causes inflammation and diarrhea REC-3964 rescues barrier integrity with increasing concentrations REC-3964 improved probability of survival in a hamster model of C. difficile infection ✓ Improved probability of survival beyond treatment completion Clinical: C. Difficile Healthy Monolayer (100%) Toxin-Damaged Monolayer (0%) REC-3964 Concentration (Log μM) R e si st an ce ( n o rm al iz e d % ) 58
59 Phase 1 FIH SAD/MAD Trial initiated in Q3 2022 • Enrollment is progressing • In several SAD cohorts and at least one MD cohort, REC-3964 has been extremely safe and well tolerated • Complete safety and PK data readout expected 2H 2023 Trial Design • Randomized, Double-blind Trial Population • Healthy Subjects • SAD (n = 56) • MAD (n = 50) Primary Objectives ✓ Assess the safety & tolerability of SAD and MAD of REC-3964 ✓ Evaluate the PK profile of REC-3964 after single and multiple doses Clinical: C. Difficile Trial Update 59
Preclinical Programs RBM39 : HR-Proficient Ovarian Cancer Target α : Immunotherapy
RBM39 CDK12 2.5μM 1.0μM REC-65029 0.1μM 0.25μM CDK13 REC-65029 Similar Opposite BRCA-proficient ovarian cancer PDX Preclinical: HR-Proficient Ovarian Cancer Identify potential first-in-class tumor-targeted precision therapeutic NCE with novel MOA capable of potentially treating HR-proficient ovarian cancer Inhibition of target RBM39 (previously referred to as Target γ) may mimic the inhibition of CDK12 while mitigating toxicity related to CDK13 inhibition A Recursion-generated NCE showed single agent efficacy that is enhanced in combination with Niraparib in a BRCA-proficient PDX model Program anticipates reaching IND-enabling studies in 2023 GOAL INSIGHT FROM OS FURTHER CONFIDENCE NEXT STEPS Vehicle Niraparib REC-204 100 mpk REC-204 100 mpk + Niraparib OV0273 (PDX) in-vivo efficacy Survival data Note: in the OV0273 PDX model, mice were treated with a representative lead molecule REC-1170204 (100 mg/kg, BID, PO) ± Niraparib (40 mg/kg, QD, PO) for 32 days. Single agent REC-1170204 or in combination with Niraparib resulted in a statistically significant response vs either Niraparib or vehicle arms. In addition, there was a statistically significant improvement in survival > 30 days post final dose. *p<0.05, ** p<0.01, **** p<0.0001 61
Gene B Gene B REC- 648918 REC-648918 BIRC2 Gene A Gene A BIRC2 Similar Opposite (A) CT26 in vivo efficacy Note: (A) Mice harboring CT26 tumors show 60% complete tumor regressions upon treatment with 100 mpk REC-1170035 in combination with 10 mpk anti-PD-1. (B) Flow cytometric analysis of the CT26 tumor microenvironment following 11 days of dosing. One-way ANOVA and Tukey’s post test, ***p<0.001, ****p<0.0001. (C) Blood levels of CXCL10 (left) and IFNγ (right) in CT26 tumor bearing mice following 10 days of dosing. Stat istical analysis performed using one-way ANOVA and Tukey’s post test against aPD1 alone, **p<0.01, ****p<0.0001 Preclinical: Target α GOAL INSIGHT FROM OS FURTHER CONFIDENCE NEXT STEPS Identify novel compounds capable of enhancing the therapeutic benefit of checkpoint therapy without concomitant inflammatory side effects Novel compound identified with similarity to knockout of potential immunotherapy resistance gene targets (Gene A, Gene B) A Recursion-generated NCE showed reduction in tumor growth vs. anti-PD- 1 alone in CT26 checkpoint resistance model - including 60% complete responses (B) Tumor Microenvironment Modulation (C) Suppressed Peripheral Inflammation Program anticipates reaching IND-enabling studies in 2023 62
63 Partnerships Partnership Strategy Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capabilities Fibrosis Other large, intractable areas of biology Neuroscience* Pipeline Build internal pipeline in indications with potential for accelerated path to approval Pipeline Strategy Precision Oncology Rare Disease Data License subsets of data Direct generation of new data internally to maximize pipeline and partnership value-drivers Data Strategy Licensing Augment Recursion OS *Includes a single oncology indication from our Roche and Genentech collaboration.
Fibrosis Neuroscience *and a single oncology indication • $30M upfront and $50M equity investment • Up to or exceeding $1.2B in milestones for up to or exceeding 12 programs • Mid single-digit royalties on net sales • Recursion owns all algorithmic improvements • $150M upfront and up to or exceeding $500M in research milestones and data usage options • Up to or exceeding $300M in possible milestones per program for up to 40 programs • Mid to high single-digit tiered royalties on net sales • Recursion owns or co-owns all algorithmic improvements (Announced Sep 2020; Expanded Dec 2021) (Announced Dec 2021) Trademarks are the property of their respective owners and used for informational purposes only. 64
Early DiscoveryScreening Brute Force (commenced 2020) Inferential Search (commenced 2022) Approach Late Discovery Transition to Inferential Search has accelerated new program initiation in 2022 Active Paused / Terminated Pre-programs 65
Fibrosis Neuroscience *and a single oncology indication • $30M upfront and $50M equity investment • Up to or exceeding $1.2B in milestones for up to or exceeding 12 programs • Mid single-digit royalties on net sales • Recursion owns all algorithmic improvements • $150M upfront and up to or exceeding $500M in research milestones and data usage options • Up to or exceeding $300M in possible milestones per program for up to 40 programs • Mid to high single-digit tiered royalties on net sales • Recursion owns or co-owns all algorithmic improvements (Announced Sep 2020; Expanded Dec 2021) (Announced Dec 2021) Trademarks are the property of their respective owners and used for informational purposes only. 66
67 Partnerships Partnership Strategy Partner in complex therapeutic areas requiring large financial commitment and competitive market dynamics Leverage partner knowledge and clinical development capabilities Fibrosis Other large, intractable areas of biology Neuroscience* Pipeline Build internal pipeline in indications with potential for accelerated path to approval Pipeline Strategy Precision Oncology Rare Disease Data License subsets of data Direct generation of new data internally to maximize pipeline and partnership value-drivers Data Strategy Licensing Augment Recursion OS *Includes a single oncology indication from our Roche and Genentech collaboration.
68 Recursion Data Universe: >21 PB of proprietary biological and chemical data, spanning phenomics, transcriptomics, invivomics, and more • We believe one of the largest biological and chemical datasets fit for the purpose of training large-scale ML models RXRX3: CRISPR knockouts of most of the human genome, 1,600 FDA approved / commercially available bioactive compounds • We believe the largest public dataset of its kind, <1% of Recursion Data Universe, what Recursion can generate in ~1 week MolRec™️: freemium web-based application to explore compound and gene relationships in RXRX3 Start working with RXRX3 and MolRec™️: www.rxrx.ai
Advanced degreesEmployees Team Members ~500 43% ESG Highlights ✓ Inaugural ESG report in 2022 – reporting on Healthcare and Technology Metrics ✓ 100% of electricity powering our Biohive-1 supercomputer comes from renewable sources 43% Female Male 55% 1% Non-Binary Parity Pledge Signer gender parity and people of color parity Life Sciences –biology, chemistry, development, etc. Technology –data science, software engineering, automation, etc. Strategic Operations Community Impact Committed to ESG Excellence Founding Partner, Life Science Accelerator Founding Member, Life Science Collective 70 Data shown reflective of Q4 2022 and Recursion’s 2022 ESG report
Strong Financials ~$550M in cash and cash equivalents at the end of 2022 with potential for increased revenue in the near term Near-Term • Potential option exercises for partnership programs • Potential option exercises for map building initiatives or data sharing • Potential for additional partnership(s) in large, intractable areas of biology and / or technological innovation • Ph1 clinical trial readout for C. difficile Infection program expected 2H 2023 • Potential for additional INDs and clinical starts, including Ph1b/2 trial initiation for AXIN1/APC program • Potential for consolidation of technologies, talent and assets to accelerate the Recursion OS Medium-Term • Multiple POC readout(s) for AI-discovered programs • NF2 interim safety analysis expected 2024 • CCM top-line data expected 2H 2024 • Potential for additional INDs and clinical starts • Potential option exercises for partnership programs • Potential option exercises for map building initiatives or data sharing • Potential additional partnership(s) in large, intractable areas of biology and / or technological innovation • Recursion OS moves towards autonomous map building and navigation with digital and micro-synthetic chemistry Upcoming Potential Milestones 71 Learn more about Recursion’s value proposition: www.recursion.com/download-day
Impact 72
Images adapted from Jayatunga, M., et al. Nature Reviews Drug Discovery 2022. 74 Top-20 Pharma Companies AI-Native Drug Discovery Companies 705 768 708 602 575 641 686 709 519 439 393 333 0 500 1,000 1,500 2,000 2,500 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 Discovery / Preclinical Phase I Phase II Phase III 6 2 4 6 10 18 23 28 56 121 119 158 0 50 100 150 200 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 N u m b er o f C lin ic al a n d P re cl in ic al A ss e ts N u m b er o f C lin ic al a n d P re cl in ic al A ss e ts
Well-known primary relationships between key members of five pathways: JAK/STAT | SWI/SNF | TGFβ | RAS | Proteasome All primary relationships found by the Recursion OS between key members of five pathways: JAK/STAT | SWI/SNF | TGFβ | RAS | Proteasome 75
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1 Includes approximately 500,000 compounds from Bayer’s proprietary library. 2 ‘Predicted Relationships’ refers to the number of Unique Perturbations that have been predicted using our maps. 78 Year 2018 2019 2020 2021 2022 Total Phenomics Experiments (Millions) 8 24 56 115 175 Total Transcriptomics Experiments (Thousands) NA NA 2 91 258 Data (PB) 1.8 4.3 6.8 12.9 21.2 Cell Types 12 25 36 38 48 Unique Compounds Physically Housed at Recursion1 (Millions) 0.02 0.1 0.7 1.0 1.7 In Silico Chemistry Library (Billions) NA 0.02 3 12 >1,000 Predicted Biological and Chemical Relationships2 (Trillions) NA NA 0.01 0.2 3.1
Drug Prediction Correct? Hydroxychloroquine x ✓ Lopinavir x ✓ Ritonavir x ✓ Remdesivir ✓ ✓ Baricitinib ✓ ✓ Tofacitinib ✓ ✓ Ivermectin x ✓ Fluvoxamine x ✓ Dexamethasone x x 79https://www.biorxiv.org/content/10.1101/2020.04.21.054387v1 • Recursion conducted several AI-enabled experiments in April 2020 to investigate therapeutic potential for COVID-19 - Included FDA-approved drugs, EMA-approved drugs, and compounds in late-stage clinical trials for the modulation of the effect of SARS-CoV-2 on human cells • Experiments were compiled into the RxRx19 dataset (860+ GB of data) and made publicly available to accelerate the development of methods and pandemic treatments. • Recursion OS correctly predicted 8 of 9 clinical trials associated with early and late-stage COVID-19
Program 1 Program 1 Program 1 Program 1 Program 1 Program 1 Program 1 Upfront Fee Programs 2 through N Programs 2 through N Programs 2 through N Programs 2 through N Programs 2 through N Collaboration Timeline Programs 2 through N Programs 2 through N Programs 2 through N Value Program 1 Program 1 Program 1 Program 1 Program 1 Program 1 Program 1 Programs 2 through N Programs 2 through N Technical and Map-Based Milestones Programs 2 through N Programs 2 through N Pre-Clinical Milestones Clinical and Approval Milestones Royalties & Commercial Milestones 80 Illustrative example of potential value inflection points
Julia – living with CCM 81 Clinical: CCM Symptomatic US + EU5, >1 million patients worldwide live with these lesions today PREVALENCE & STANDARD OF CARE CAUSE LOF mutations in genes CCM1, CCM2 & CCM3, key for maintaining the structural integrity of the vasculature due to unknown mechanisms PATHOPHYSIOLOGY & REASON TO BELIEVE Efficacy in Recursion OS as well as functional validation via scavenging of massive superoxide accumulation in cellular models; reduction in lesion number with chronic administration in mice KEY ELEMENTS • Targeting sporadic and familial symptomatic CCM patients with CCM1, CCM2, and CCM3 mutations • Superoxide scavenger, small molecule • Phase 2 trial initiated in Q1 2022 • US & EU Orphan Drug Designation • Oral dosing Vascular malformations of the CNS leading to focal neurological deficits, hemorrhage and other symptomsNo approved therapy • No other potential therapeutic in industry-sponsored clinical development • Most patients receive no treatment or only symptomatic therapy >5x larger US patient population than other rare diseases like Cystic Fibrosis (>31k patients) Vascular malformations (cavernomas)
82 Clinical: NF2 LOF mutations in NF2 tumor suppressor gene, leading to deficiencies in the tumor suppressor protein merlin PATHOPHYSIOLOGY & REASON TO BELIEVE Efficacy in Recursion OS, cellular, and animal models; suppression of aberrant ERK, AKT, and S6 pathway activation in a Phase 1 PD Study in NF2 patient tumors KEY ELEMENTS • Targeting familial and sporadic NF2 meningioma patients • HDAC inhibitor, small molecule • Oral dosing • Phase 2/3 trial initiated in Q2 2022 • Fast-Track and US & EU Orphan Drug Designation Inherited rare CNS tumor syndrome leading to loss of hearing and mobility, other focal neurologic deficits No approved therapy • There are no approved drugs for NF2 • Surgery is standard of care (when feasible) • Location may make complete resection untenable, leading to hearing loss, facial paralysis, poor balance and visual difficulty Treatable US + EU PREVALENCE & STANDARD OF CARE CAUSE Ricki – living with NF2 Intracranial meningiomas
83 Clinical: FAP Polyps Found in Colon and Upper GI Tract Inactivating mutations in the tumor suppressor gene APC PATHOPHYSIOLOGY & REASON TO BELIEVE KEY ELEMENTS • Targeting classical FAP patients (with APC mutation) • MEK inhibitor, small molecule • Oral dosing • Phase 2 trial initiated in Q3 2022 • Fast-Track and US & EU Orphan Drug Designation Polyps throughout the GI tract with extremely high risk of malignant transformation Efficacy in the Recursion OS showed specific MEK 1/2 inhibitors had an effect in context of APC LOF. Subsequent APCmin mouse model showed potent reduction in polyps and dysplastic adenomas No approved therapy • Colectomy during adolescence (with or without removal of rectum) is standard of care • Post-colectomy, patients still at significant risk of polyps progressing to GI cancer • Significant decrease in quality-of-life post-colectomy (continued endoscopies, surgical intervention) Diagnosed US + EU5 PREVALENCE & STANDARD OF CARE CAUSE
84 LOF mutations in AXIN1 or APC tumor suppressor genes PATHOPHYSIOLOGY & REASON TO BELIEVE Alterations in the WNT pathway are found in a wide variety of tumors and confer poor prognosis and resistance to standard of care Substantial need for developing therapeutics for patients harboring mutations in AXIN1 or APC, as these mutations are considered undruggable Treatable US + EU5 PREVALENCE & STANDARD OF CARE CAUSE Efficacy in the Recursion OS and favorable results in PDX models harboring AXIN1 or APC mutations vs wild-type leading to a significant PFS benefit in HCC and Ovarian tumors Gross morphology of HCC KEY ELEMENTS • Targeting solid tumors with AXIN1 or APC mutant cancers • MEK inhibitor, small molecule • Oral dosing • Finalize design of a Phase 1b/2 biomarker-enriched trial • Initiate Phase 1b/2 trial in select tumor types in early 2024 To our knowledge, REC-4881 is the only industry sponsored small molecule therapeutic designed to enroll solid tumor patients harboring mutations in AXIN1 or APC Clinical: AXIN1 or APC
85 Colleen – lived with rCDI C. difficile toxins from colonizing bacterium causes degradation of colon cell junction, toxin transit to bloodstream, and morbidity to host PATHOPHYSIOLOGY & REASON TO BELIEVE Highly recurrent infectious disease with severe diarrhea, colitis, and risk of toxic megacolon, sepsis, and death Diagnosed US + EU5 PREVALENCE & STANDARD OF CARE CAUSE Recursion OS identified a new chemical entity for recurrent C. difficile infection and potentially prophylaxis via glycosyl transferase inhibition with potential to be orally active KEY ELEMENTS • Enrollment is progressing • In several SAD cohorts and at least one MD cohort, REC-3964 has been extremely safe and well tolerated • Complete safety and PK data readout expected 2H 2023 • Selective C. diff toxin inhibitor, small molecule • Non-antibiotic approach with potential for combination with SOC and other therapies • Designed for selective antitoxin pharmacology to target infection • FIH Phase 1 trial initiated in Q3 2022 TRIAL UPDATE Standard of care includes antibiotic therapies which can further impair gut flora, and lead to relapse Clinical: C. Difficile