Slides
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December 20, 2024Strategic Update
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Forward-Looking Statements 2 Certain statements contained in this presentation regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities and Exchange Act of 1934, as amended, and the Private Securities Litigation Act of 1995, known as the PSLRA. These include statements regarding management’s intention, plans, beliefs, expectations or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. Forward-looking statements may include, without limitation, express or implied statements regarding: the timing and completion of the proposed sale of FYARRO to Kaken Pharmaceuticals and the anticipated timing of the closing of the transaction; expectations regarding the timing, closing and completion of a concurrent private financing, including investment amounts from investors, timing of closing, expected proceeds and impact on ownership structure; Aadi’s expected cash position at the closing and cash runway of the company following the sale of FYARRO and private financing; the future operations of Aadi; the development and potential benefits of any of Aadi’s product candidates; anticipated preclinical and clinical development activities and related timelines, including the expected timing for announcement of data and other preclinical and clinical results and potential submission of IND filings for one or more product candidates; and other statements that are not historical fact. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Aadi uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “opportunity,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions of the PSLRA.Such forward-looking statements are based on our expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, (i) the risk that the conditions to the closing of the proposed sale of FYARRO and concurrent private financing are not satisfied, including the failure to timely obtain stockholder approval for the transactions, if at all; (ii) uncertainties as to the timing of the consummation of the proposed transactions and the ability of each of Kaken and Aadi to consummate the proposed sale of FYARRO; (iii) risks related to Aadi’s ability to manage its operating expenses and its expenses associated with the proposed transactions pending the closing; (iv) risks related to the failure or delay in obtaining required approvals from any governmental or quasi-governmental entity necessary to consummate the proposed transactions; (v) unexpected costs, charges or expenses resulting from the transactions; (vii) potential adverse reactions or changes to business relationships resulting from the announcement or completion of the proposed sale of FYARRO, concurrent private financing and in-license of the ADC portfolio; (vii) the uncertainties associated with Aadi’s product candidates, as well as risks associated with the preclinical and clinical development and regulatory approval of product candidates, including potential delays in the completion of preclinical studies and clinical trials; (viii) risks related to the inability of Aadi to obtain sufficient additional capital to continue to advance these product candidates; (ix) uncertainties in obtaining successful preclinical and clinical results for product candidates and unexpected costs that may result therefrom; (x) risks related to the failure to realize any value from product candidates being developed and anticipated to be developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; (xi) risks associated with the possible failure to realize certain anticipated benefits of the proposed sale of FYARRO, concurrent private financing and in-license of the ADC portfolio, including with respect to future financial and operating results; (xii) the risk that the private financing is not consummated upon the closing.These risks are described in detail under the caption “Risk Factors” in Aadi’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including under the caption "Item 1A. Risk Factors," and in Aadi's subsequent Quarterly Reports on Form 10-Q, and other documents filed from time to time with the SEC. Forward-looking statements included in this presentation are based on information available to Aadi as of the date of this presentation. Except as required by law, Aadi undertakes no obligation to revise or update any forward-looking statement, whether as a result of new information, future events or otherwise.
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Participants 3 Dave Lennon, PhDPresident & Chief Executive OfficerScott Giacobello, CPAChief Financial Officer
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Overview of Proposed Transactions
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Transformative Transactions Rooted in Aadi Long-Term VisionPipeline of three ADC portfolio targeting common, high-potential indication cancersLeveraging next wave ADC linker-payload architecture5 Kaken Pharmaceuticals to purchase FYARRO and associated infrastructure for $100MIn-licensing 3 ADC assets from WuXi Biologics leveraging advanced linker-payload technology from Hangzhou DACPrivate financing of $100M at 3.4% premium to the closing price on December 19, 2024 FYARRO SaleADC PortfolioPIPE Financing
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Kaken to Purchase FYARRO for $100M to Continue Providing This Important Treatment for Patients with Malignant PEComa 6 Kaken will pay Aadi $100 million in cash at closing, a 4X multiple over the trailing 12 months of salesKaken to retain associated infrastructure, including the Aadi brand and the majority of Aadi employees who support the FYARRO businessExpected to close 1H’25, subject to Aadi stockholder approval and certain closing conditions
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FYARRO Expands US Business for Kaken Pharmaceutical, an R&D Driven Pharmaceutical Company Based in Japan 7•The only FDA-approved treatment for advanced malignant PEComa•Cumulative sales of $58.3m since launch1•Net sales of $7.2m in Q3 2024•Consistent strong demand across major oncology centers in the US, with a ~90% reorder rate year-to-date•R&D driven pharmaceutical company in Japan building sales structure in the U.S. market•Acquisition positions Aadi at the center of Kaken’s sales structure in the U.S. market•Greatly accelerates the building of a foundation to meet global medical needs•Earnings forecast of 88,500 million yen for fiscal year 20242 1. Commercial launch on Feb 22, 2022. Sales as of close of 3Q 2024.2.Kaken, “Consolidated Financial Results for the Six-Months Period of Fiscal 2024 (Six-Months Period ended September 30, 2024.”
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Aadi In-Licensing Portfolio from WuXi Biologics in Dynamic ADC Space 8 Licensing 3 ADC assets from WuXi Biologics utilizing advanced linker-payload from Hangzhou DAC$44M in upfront payments, cumulative development milestone payments of up to $265 million, cumulative commercial milestone payments of up to $540 million, single-digit royaltiesADCs directed at promising cancer targets with broad tumor expression and precedent clinical data in high-potential indicationsIND filings expected in 12-24 months for all three assets
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PIPE Financing of $100M Projected to Extend Runway into Late 2028 9 Expected to result in gross proceeds of approximately $100 millionSelling common stock at $2.4 per shareCumulative cash position projected to extend runway into late 2028, enabling anticipated key clinical data readoutsExpected close 1H’25, subject to stockholder approval and certain closing conditions Ally Bridge Group KalehuaCapital Management
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Baiteng Zhao Brings Significant ADC Expertise to Board 10 •Co-founder and former CEO and Chairman of ProfoundBio, a clinical stage next-gen ADC developer•Profound was acquired by Genmab for $1.8 billion in May 2024•Formerly at Seagen (now part of Pfizer), responsible for the modeling and simulation strategies for the ADC development pipeline •Formerly a clinical PK/PD scientist at Merck Baiteng Zhao, PhD Director
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Aadi 2.0Advancing Next Wave ADCs
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PTK7-CPT113PTK7 is an oncofetal pseudokinase w/ broad tumor overexpression mMUC16-CPT113MUC16 is a glycoprotein overexpressed in cancers of female originbiSEZ6-CPT113SEZ6 is a CNS protein upregulated in tumors of neuroendocrine originLicensing 3 Preclinical ADC Assets From WuXi Biologics Utilizing Advanced Linker-Payload From Hangzhou DAC 12CPT113 PlatformAdvanced ADC architecture based on a novel TOPO1 payload and highly stable linker design Protein Tyrosine Kinase 7 (PTK7) Mucin 16 (MUC16) Seizure Protein 6 (SEZ6)CPT113 Platform [X][X][X][X]
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ADC Portfolio Expected to Enter Clinic in Next 12-24 Months with Broad Opportunities Across Tumor Types 13 Other target positive tumorsTumors with precedent data (US incidence of metastatic cases)IND / Phase I*IND-enabling*Candidate selectionADC Programs•GI cancers•Prostate•Head & Neck•Endometrial•Cervical•NSCLC (~63K)1•Ovarian (~4K)2•Breast (~13K)22H’25PTK7-CPT113•Endometrial•Cervical•Breast•Pancreatic•Ovarian (~4K)2YE’25YE’24mMUC16-CPT113•CNS tumors•Head & Neck•SCLC (~18K)3•Neuroendocrine (~5K)4Mid’26YE’24biSEZ6-CPT113*Anticipated timing, subject to IND approval, as applicable. 1. JAMA Oncol. 2021;7(12):1824-1832. 2. SEER data 3. https://www.ncbi.nlm.nih.gov/books/NBK482458/. 4. JAMA Oncol. 2017;3(10):1335-1342.
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Hangzhou DAC CPT113 ADC Platform Designed to Enable Next Wave ADC Capabilities 14Data on file. *Programs in clinical development are not part of in-licensing. Presented data at AACR 2024, Abstract numbers 5819 and 1884. Clinical trial information available at ClinicalTrials.gov(https://clinicaltrials.gov/study/NCT06224855?term=DXC006&rank=1) and ChicTr.org (https://www.chictr.org.cn/showprojEN.html?proj=216486) Proprietary TOPO1 inhibitor payloadHighly stable linker with low free payload release in circulation Proprietary carbon-bridge technologyCleavable linkerOptimized PK profileDXC006 and DXC1002, using same platform, are in Phase 1 clinical development in China* [X][X][X][X]
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CPT113 Platform Has Highly Competitive Stability Profile 15 In-Licensed Platform Stability Compared to First- andNext-Generation Platforms Based on Free Payload Release11st-gen approved ADCs typically show 1-20% free payload release in circulationNext-gen platforms generate lower free payload release in non-clinical pK modelsCPT113 is on par with or better than the latest platforms051015202530Free Payload/ADC2, %CmaxAUC1st-Generation (Approved)Next-Generation (In Development)CPT1131. Based on highest species reported in publications on file; note that stability is largely consistent (~1-5X differences) between species for an individual ADC. 2. Calculated based on molar concentration of free payload and ADC in representative pK studies..01 .02.01 .06.02 N/A.04 .06.06.32.07 .10.80.63.58 .491.1.611.1 1.13.6133.1191727
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PTK7 Is an Oncofetal Pseudokinase Upregulated Across a Broad Spectrum of Cancers 16 No approved PTK7 ADCsOncofetal pseudokinase withbroad tumor overexpression Clinical validation from Pfizer 1stGeneration ADC, Cofetuzumab Pelidotin (Cofe-P)2PTK7 expression across solid tumors1(Annual US Incidence)0% 20% 40% 60% 80% 100%Moderate/highAny(26,890)(19,680)(234,580) (22,370)(152,810)(310,720)(71,000)(13,820)(299,010)(67,880)EndometrialProstateCervicalHead and NeckBreastColorectalEsophagealLungOvarianGastric Protein Tyrosine Kinase 7 (PTK7) Schematic 1. Aadi analysis based on Human Protein Atlas, Gepia, and literature review. 2. Maitland et al. Clin Cancer Research, 2021: 27:4511–20.
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PTK7 Tumor Target Clinically Validated by Pfizer 1stGeneration ADC 17 STRICTLY CONFIDENTIAL*Mod-high ORR reflects Aadi analysis of the PTK7 protein expression and best overall response data for Q3W cohorts in Figure 2 of Maitland et al. Clin Cancer Research, 2021: 27:4511–20. There were 13, 16, and 13 patients with mod-high PTK 7 expressions in PROC, NSCLC, and TNBC, respectively. Cofe-P, Cofetuzumab pelidotin; FIH, First-in-Human; G3, Grade 3; NSCLC, Non-small cell lung cancer; PROC, Platinum resistant ovarian cancer; Q3W, every 3 weeks; TNBC, Triple negative breast cancer; ORR, objective response rate; TRAE, treatment-related adverse eventORR Range in Q3W Cohorts:• 16-27% in all patients• 23-46% in PTK7 moderate-high subgroup27%16%21%46%25%23%PROC (n=44) NSCLC (n=25) TNBC (n=29)Cofe-P ORR from FIH Q3W Cohorts1ORR (all evaluable)ORR PTK7 mod-highToxicities in Q3W dosing cohorts were consistent with MMAE class effects• Dose-limiting toxicities included G3 headache and G3 fatigue• Most common G≥3 TRAE was neutropenia (25%) in Q3W cohorts (N=112)• Common TRAEs in Q3W cohorts included nausea, alopecia, fatigue, headache, neutropenia and vomiting
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PTK7-CPT113 Is a Differentiated Next Wave PTK7-Directed ADC Targeting NSCLC and Ovarian Cancer 18Targeting superior outcomes vs 1stgen ADCs due to optimized linker with TOPO1 payload switchPhase 1 planned in NSCLC & PROC – potential to expand into novel indications (e.g. gastrointestinal, gynecological)Anticipated to be among the first in next wave ADCs to enter the clinicSuperior tumor reduction vs first-generation ADC in in vitro and in vivo preclinical models Tumor growth inhibition in NCI-H446 Xenograft model Data on file. NSCLC, non small cell lung cancer; PROC, platinum resistant ovarian cancerPBSPTK7 -CPT113 (4mg/kg)Cofe-P (4mg/kg)PTK7 -CPT113 (0.25mg/kg)Cofe-P (0.25mg/kg)Cofe-P (1mg/kg)Isotype-CPT113 (4 mg/kg)PTK7 -CPT113 (1mg/kg)Tumor volume (mm3)Days after 1sttreatment007 14 21 28 35100030002000IV
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MUC16 is a Cleaved Glycoprotein Expressed in Cancers Affecting Women and Contributes to Cancer Pathogenesis 19 1. Aadi analysis based on Human Protein Atlas, Gepia, and literature review. 2. Liu J, et al. Gynecol Oncol. 2021;163(3):473-480. Clinical validation from Genentech 1st-Gen ADC, DMUC4064A2Glycoprotein overexpressed in cancers affecting women, as well as lung and pancreaticShed MUC16 (or CA125) is a widely utilized biomarker for ovarian cancerMUC16 expression across tumor types1(Annual US Incidence) Mucin 16 (MUC16) Protein Schematic0% 20% 40% 60% 80% 100%Moderate-high expressionOvarian(19,680)Cervical(13,820)Endometrial(67,880)Pancreatic(57,600)Lung(234,580)Breast(45,424)Gastric(26,890)
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Genentech 1stGeneration ADC Discontinued Due to Limited Therapeutic Index Driven by Tubulin Inhibitor Payload Toxicity and Circulating CA125 Antigen 20DMUC4064A showed toxicities consistent with MMAE class effects•Ocular toxicities arose in 40% of patients, with G3 events in 9% of patients•G≥3 TRAEs occurred in 25% of patients•Common AEs included fatigue, nausea, abdominal pain, constipation, blurred vision, diarrhea, anemia and peripheral neuropathy42% ORR at RP2DBinding to circulating CA125 may have hindered DMUC4064A effectivenessDMUC4064A ORR by dose cohortN= 3 3 8 7 6 7 261 1.8 2.4 3.2 4.0 4.8 5.20%17%29%42%Saturated levels of circulating CA1250%0% 0%mg/kgSources: Liu J, et al. Gynecol Oncol.2021;163(3):473-480; Liu J, et al. Ann Oncol. 2016;27(11):2124-2130; Chen Y, et al. Cancer Res. 2007;67(10):4924-4932. MMAE. monomethyl auristatin E. ORR, objective response rate.
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21 Cleaved CA125MUC16Tumor cell surfaceTumor1)Tumor progression leads to upregulationof MUC16CirculationCA125 shedding and antigen sink effect in MUC16-positive cancers1stGen MUC16 ADCs(Genentech)2)MUC16 is cleaved and shedsextracellular CA1253)CA125 crosses into blood circulation4)CA125 binds 1stGen MUC16 ADCs promoting clearance and blocking ADC reaching tumorMUC16 Inadequately Targeted by 1stGen ADCs Due To Antigen Sink SheddingAntigensinkSources: Aadi analysis of literature; Liu J, et al. Gynecol Oncol. 2021;163(3):473-480; Liu J, et al. Ann Oncol. 2016;27(11):2124-2130; Chen Y, et al. Cancer Res. 2007;67(10):4924-4932.
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mMUC16-CPT113 is a Novel ADC Directly Targeting Non-Shed MUC16 with Significant Potential in Cancers Affecting Women 22 Membrane-bound targeting avoids CA125 antigen sink issue of 1stgen ADCs Phase 1 planned in ovarian cancer – potential to expand into additional cancers affecting women (e.g. endometrial, cervical)Potentially the first-and-only ADC targeting membrane-bound MUC16In vitro and in vivo data suggest improved efficacy vs 1stgen predecessor in ovarian cancerData on file. Tumor growth inhibition in OVCAR-3 xenograft modelmMUC16-MMAEmMUC16-CPT113 DMUC-MMAE PBSIsotype control-MMAEDays post treatment2000150010005000Tumor volume (mm3)0 7 14 21 28 35
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SEZ6 is a CNS-Limited Protein Overexpressed in SCLC, Other Neuroendocrine Neoplasms and CNS Tumors 23 Clinical validation from AbbVie Next Wave ADC, ABBV-7062Limited clinical-stage class competitionCNS protein upregulated in tumors of neuroendocrine originSeizure Protein 6 (SEZ6) Protein Schematic SEZ6 expression across tumor types1(SEER 2024 Annual US Incidence) 1. Aadi analysis based on Human Protein Atlas, Gepia, and literature review. 2. Morgensztern D, et al. ASCO 2023. Abstract 3002 (oral presentation); Chandana SR, et al. ASCO 2024. Abstract 3001 (oral presentation). 0% 20% 40% 60% 80% 100%CNS(25,400)NETs(31,000)SCLC(35,000)Any expression
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AbbVie Next-Wave ADC ABBV-706 Demonstrated Improved Efficacy Compared to 1stGeneration in an Ongoing Early Ph1 Study 24ABBV-706 dose1.3 mg/kg 1.8 mg/kg 2.5 mg/kg 3 mg/kg 3.5 mg/kg60.9% ORR in SCLC (14/23) 200-30-60-80-100PatientsPD SD SDSD SDSD*PR* PR*SDPR SD* PR* PR*PR PR*PRPDPRPR PR PRPRPR*Best Percent Change in Target Lesions, %* : OngoingConfirmed Best Response:AbbVie ABBV-706 reported ORR of 44% across SCLC and NET cohorts (excludes 5 pts with GBM)1. Morgensztern D, et al. ASCO 2023. Abstract 3002 (oral presentation); Chandana SR, et al. ASCO 2024. Abstract 3001 (oral presentation). 2. Wiedemeyer WR, et al. Mol Cancer Ther. 2022:21:986-998. ORR, objective response rate; SCLC, small cell lung cancer; NET, neuroendocrine tumor; GBM, glioblastoma.
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Source: Weisser et al. Nat Commun. 2023;14(1):1394. Despite Improvements Seen With Next Wave SCLC ADCs, a BiparatopicApproach May Provide Path to Greater Gains 25 CapTransBinding Enables Better Binding and ClusteringLeading to Improved Target Specificity, Binding & ADC Internalization at the Tumor Site Concentration of surface receptorsFormation of large receptor clusters and cell surface capsRapid, pronounced receptor internalizationIncreased payload release and localized concentration
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biSEZ6-CPT113 Is a Biparatopic SEZ6-Directed ADC Aimed at Improving Binding & Internalization 26 Source: Data on file. MFI, Mean Florescence Intensity FACS Binding on HEK293.SEZ6ABBV-706 mAbbiSEZ6 mAbIsotypeInternalization on HEK293.SEZ6Concentration (nM)MFI10-44000300020001000010-2100102104MFIConcentration (nM)10-25000400030002000010-11001011031000102Ab used in biSEZ6-CPT113 shows improved binding & internalization compared to Ab used in ABBV-706biSEZ6-CPT113 is the only biparatopicADC in development for SCLCPhase 1 planned in SCLC and NENs, where there are limited treatment optionsDespite gains with next wave SCLC ADC, a biparatopic approach may provide greater benefitsbiSEZ6 Ab shows superior binding and internalization compared to single epitope SEZ6 Abs
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Clinically validated, broadly overexpressed tumor targets combined with next wave ADC linker-payload architecture High-potential indications with anticipated ability to competeTargeting 3 US IND submissions in 12 to 24 months, including lead asset in 2H'25 Experienced team and partners with ability to execute against development goals Post-closing cash expected to fund operations into late 2028, including anticipated key clinical dataTransformative Opportunity for Aadi 27 Value-driving potentialPatient opportunityMomentum to IND submissionExecution-focusedCapitalized to clinical data Filing proxy statement and then convening stockholder meeting and distributing proxy materials; closing of transactions expected in the first half of 2025Next Steps
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Questions