Slide 1: Decoding Biology To Radically Improve Lives
Decoding Biology To Radically Improve Lives i) Recursion
Slide 2: Forward-looking statements
This presentation and any accompanying discussion or documents may 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 an
Slide 3: Recursion is a clinical stage Pharmatech company
Recursion is a clinical stage Pharmatech company Mapping and Navigating biology with the goal of bringing better medicines to patients faster and at lower cost via an Internal Pipeline and Partnerships 3 The Leading Pharmatech Mission is to decode biology to radically improve lives >150 biologists,
Slide 4: Top-20 Pharma vs AI-native drug discovery companies assets
Images adapted from Jayatunga, M., et al. Nature Reviews Drug Discovery 2022. 4 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
Slide 5: Primary relationships found by the Recursion OS across five pathways
Well-known primary relationships found by the Recursion OS 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 5
Slide 6: Technology has reshuffled major industries
Technology has reshuffled major industries by bringing order and prediction to complex systems
Slide 7: Real (atoms) to digital (bits)
1 3 Real (atoms) Digital (bits) 1 Profile real systems Capture high-dimensional data to create a digital record of reality (things, places, behaviors, preferences, etc) Aggregate and analyze Aggregate data to create digital maps of reality Algorithmic Inference Navigate digital maps to predict or su
Slide 8: How we build maps of biology
How we build maps of biology
Slide 9: How we build maps of biology
How we build maps of biology Enables quality, reliability, repeatability and scale Novel Efficacy and Insights At Scale Human cell types Small Molecules Arrayed CRISPR guides Cytokines & soluble factors Biological and Chemical Diversity Automated Execution at Scale Experiments per week Up to Digitiz
Slide 10: How we navigate our maps of biology
How we navigate our maps of biology to rapidly identify novel insights that can drive better programs faster 10
Slide 11: Whole-genome CRISPR KO map and chemical map
To the left is a whole-genome arrayed CRISPR KO Map generated in primary human endothelial cells Recursion visualizes its Maps in different ways. Below is a Map of thousands of new chemical entities, clustered by chemical similarity and colored by potency, which demonstrated a strong anti-inflammato
Slide 12: Mitochondrial-related genes cluster together
Many known mitochondrial-related genes cluster together along with a few less well-known genes 12
Slide 13: JAK/STAT genes cluster together
JAK1 Many known JAK / STAT genes cluster together along with a few less well-known genes 13
Slide 14: JAK/STAT pathway clustered by strength of interaction
JAK1 JAK1 The JAK / STAT pathway now clustered by strength of interaction, including both similar genes (red) and ‘opposite’ genes (blue) – note that both expected and less well-known genes can serve as novel hypotheses 14
Slide 15: Proteasome clusters give confidence in the map
20S Subunit 26S Subunit The 20S and 26S proteosomes are another of hundreds of expected clusters that give confidence in this Map, one of many we have built – however, the most exciting elements of each map are the tens of thousands of unknown and unexplored high-confidence relationships 15
Slide 16: Traditional approach versus map of biology approach
World’s literature reviewed People generate hypotheses Hypotheses validated in low dimensional assays 1. Millions of disparate journal articles and publications 2. Many data cannot be independently replicated 3. Human-selected low dimensional assays prone to confirmation bias 4. Humans prone to conf
Slide 17: Program efficiency versus industry averages
Data shown are the averages of all our programs from 2017 through 2021. All industry data adapted from Paul, et al. Nature Reviews Drug Discovery. (2010) 9, 203–214 17
Slide 18: Mapping and Navigating Biology has demonstrated leading indicators of efficiency
Mapping and Navigating Biology has demonstrated leading indicators of efficiency including scale ‘Stage of Development CLINICAL PRECLINICAL LATE DISCOVERY EARLY DISCOVERY ‘O. NEURAL OR SYSTEMIC INFLAMMATION (Bestneceng 20) 20000 5 PROGRAMS, Neuroscience (© FAMILIAL ADENOMATOUS POLYPoSiS (APC: et. 50
Slide 19: Partnership strategy
Internal Pipeline - Rare Genetic Diseases Asset Sales / Licenses / Commercialization Partnership strategy • Partner in large, difficult and/or competitive therapeutic areas • Add knowledge to and improve our growing atlas of biology Internal Pipeline Discovery Partnerships Commercialization, licensi
Slide 20: Evolution of Recursion OS program generations
The earliest iterations of the Recursion OS leveraged brute-force search (where small molecules were tested directly in the context of each disease model we built) and used a small molecule library restricted primarily to known chemical entities. Programs arising from this iteration of the Recursion
Slide 21: REC-994 for Cerebral Cavernous Malformation
US + EU5 PREVALENCE CAUSE LOF mutations in genes CCM1, CCM2 & CCM3, key for maintaining the structural integrity of the vasculature due to unknown mechanisms PATHOPHYSIOLOGY Vascular malformations of the CNS leading to focal neurological deficits, hemorrhage and other symptoms OUR REASON TO BELIEVE
Slide 22: REC-2282 for NF2 meningioma
US + EU5 INCIDENCE CAUSE LOF mutations in NF2 tumor suppressor gene PATHOPHYSIOLOGY OUR REASON TO BELIEVE Efficacy in Recursion OS, cellular, & 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
Slide 23: REC-4881 for Familial Adenomatous Polyposis
US + EU5 PREVALENCE CAUSE Inactivating mutations in the tumor suppressor gene APC PATHOPHYSIOLOGY Polyps throughout the GI tract with extremely high risk of malignant transformation OUR REASON TO BELIEVE Efficacy in the Recursion OS shows that specific MEK 1/2 inhibitors had an effect in context of
Slide 24: C. difficile colitis program
US + EU5 INCIDENCE CAUSE Release of C. difficile toxins by colonizing bacterium causes degradation of colon cell junction, toxin transit to bloodstream, and morbidity to host PATHOPHYSIOLOGY Highly recurrent infectious disease with severe diarrhea, colitis, and risk of toxic megacolon, sepsis, and d
Slide 25: REC-65029 in HRD-negative ovarian cancer
Gene A CDK12 2.5μM 1.0μM REC-65029 0.1μM 0.25μM REC-65029 • Goal: Identify potential first-in-class NCE with novel MOA capable of potentially treating HRD-negative ovarian cancer • Phenomap insight: Inhibition of target Gene A (for example, with REC-65029) may mimic inhibition of CDK12 while mitigat
Slide 26: REC-648918 checkpoint resistance efficacy
Efficacy demonstrated in CT26 checkpoint resistance (left) mouse model; complete response (CR) mice show minimal tumor growth when rechallenged (middle left). Peripheral IL-6 remain unchanged (middle right) while intertumoral IFNg increases EMT6 Gene B Gene B REC- 648918 REC-648918 BIRC2 Gene A Gene
Slide 27: REC-64151 in STK11 mutant cancers
• Goal: Identify novel compounds capable of re-sensitizing tumors to checkpoint therapy in STK11 mutant cancers • Phenomap insight: Novel class of compounds (REC-64151) inferred to rescue loss of STK11 • Result: REC-64151 restores anti-PD1 (aPD1) response of STK11 mutant CT26 tumors (Fig. A, B) and
Slide 28: MYC program proliferation inhibition data
-2 -1 0 1 2 0 50 100 % P ro li fe ra ti o n I n h ib it io n PC-12 MSTO-211H MV-4-11 HL-60 REC-142221 Conc. (Log, uM) -2 -1 0 1 2 0 50 100 % P ro li fe ra ti o n I n h ib it io n REC-136467 Conc. (Log, uM) -2 -1 0 1 2 0 50 100 % P ro li fe ra ti o n I n h ib it io n PC-12 MSTO-211H MV-4-11 HL-60 MYC
Slide 29: Team members
Life Sciences - biology, chemistry, development, etc. Technology - data science, software engineering, automation, etc. Strategic Operations Advanced degrees Employees today Team Members 450+ 46% All employees VP and above Gender: % Women 43% 44%
Slide 30: Recursion OS build and clinical predictions
Enables quality, reliability, repeatability and scale Recursion OS Continued digital chemistry and predictive ADMET OS build Clinical Predictions Near-TermToday Intermediate-Term 30
Slide 31: Recent milestones and upcoming catalysts
• Expanded Bayer collaboration to use mapping and navigating techniques to explore fibrotic diseases • Announced transformational collaboration with Roche-Genentech focused predominantly in neuroscience • Enrolled and dosed multiple participants in Ph2 clinical trial evaluating REC-994 for the poten
Slide 32: Impact
IMPACT 32
Slide 33: Executive team and Board of Directors
Board of Directors TINA LARSON President & COO MASON VICTORS Chief Product Officer Executive Team CHRIS GIBSON, PHD Co-Founder & CEO DEAN LI, MD/PHD Recursion Co-founder, President of Merck Research Labs ZAVAIN DAR Partner, Lux Capital ZACHARY BOGUE, JD Partner, Data Collective ROBERT HERSHBERG, MD/
Slide 34: Biotechnology company scaling like a technology company
• Growth in capabilities, proprietary data, programs, and partnerships • Increasing business opportunities • Reducing binary risks We are a biotechnology company scaling more like a technology company, as demonstrated by our growth in inputs (experiments) and growth in outputs (data, biological and
Slide 35: Appendix: Recursion is a leading pharmatech company
Appendix: Recursion is a leading pharmatech company Computational focused, known biology Felease Date: March 3,2022 Recursion engaged Frost & Sullvan to perform ths ancysis Mature internal pipeline, large strategic partnerships, advanced computational resources Schrodinger @ tale @ Valo Health es ee
Slide 36: Appendix: Highlights from our approach
Appendix: Highlights from our Approach ESG Highlights Our ESG Commitments ton JQGOO 44% 54% 41% 59% 44%) NX <j ©) Parity Pledge 100% Scene altitude » lab The Recursion : Foundation