EX-99.2 3 atha-ex99_2.htm EX-99.2

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LIFT-AD Topline Readout September 3, 2024 Exhibit 99.2


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Disclaimer This presentation and the accompanying oral commentary contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to our management. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “could,” “expect,” “plan,” anticipate,” “believe,” “estimate,” “predict,” “intend,” “potential,” “would,” “continue,” “ongoing” or the negative of these terms or other comparable terminology. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our future financial performance, business plans and objectives, timing and success of our planned development activities, our ability to obtain regulatory approval, the potential therapeutic benefits and economic value of our product candidates as a potential treatment for Alzheimer’s disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases, the anticipated reporting of data, and the potential learnings from preclinical studies and other nonclinical data, the LIFT-AD trial and their ability to inform and improve future clinical development plans. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. These factors, together with those that are described in greater detail in our filings with the Securities and Exchange Commission (“SEC”) may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and although we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted a thorough inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and readers are cautioned not to unduly rely upon these statements. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. By attending or receiving this presentation you acknowledge that you will be solely responsible for your own assessment of the market and our market position and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of our business. This presentation contains estimates, projections and other information concerning market, industry and other data. We obtained this data from our own internal estimates and research and from academic and industry research, publications, surveys, and studies conducted by third parties, including governmental agencies. These data involve a number of assumptions and limitations, are subject to risks and uncertainties, and are subject to change based on various factors, including those discussed in our filings with the SEC. These and other factors could cause results to differ materially from those expressed in the estimates made by the independent parties and by us. While we believe such information is generally reliable, we have not independently verified any third-party information. This presentation concerns drug candidates that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. The drug candidates are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. We announce material information to the public through a variety of means, including filings with the SEC, press releases, public conference calls, our website (www.athira.com), our investor relations website (investors.athira.com), and our news site (investors.athira.com/news-and-events/press-releases). We use these channels, as well as social media, including our LinkedIn (https://www.linkedin.com/company/athirapharma), Facebook (https://www.facebook.com/athirapharmainc) and @athirapharma on X (formerly known as Twitter) and Instagram to communicate with investors and the public about Athira, our products, and other matters. Therefore, we encourage investors, the media, and others interested in Athira to review the information we make public in these locations, as such information could be deemed to be material information. © Athira Pharma, Inc.


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3 Therapeutic Potential of HGF Positive Modulation as a Neurotrophic Factor for Neurodegenerative Diseases HGF, hepatocyte growth factor. Potential first-in-class small molecule drug candidates Able to cross the blood-brain barrier Positively modulate HGF/MET Mechanism of action may Reduce inflammation Promote regeneration Provide neuroprotection Modify the course of disease ATH drug candidates increase HGF/MET activation © Athira Pharma, Inc.


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Randomized, Double-blind, Placebo-controlled, 26-week Trial LIFT-AD Study Design in Mild-to-Moderate Alzheimer’s Disease AChEI, acetylcholinesterase inhibitor; AD, Alzheimer’s disease; ADAS-Cog11, Alzheimer's Disease Assessment Scale–Cognitive Subscale; ADCS-ADL23, Alzheimer's Disease Cooperative Study–Activities of Daily Living; CDR, clinical dementia rating; GFAP, glial fibrillary acidic protein; MMSE, Mini Mental State Examination; NfL, neurofilament light chain; p-Tau, phosphorylated tau; Aβ, Amyloid-ß; SC, subcutaneous © Athira Pharma, Inc. PRIMARY Global Statistical Test - composite of ADAS-Cog11 and ADCS-ADL23 Safety SECONDARY ADAS-Cog11 ADCS-ADL23  Plasma NfL  EXPLORATORY PLASMA BIOMARKERS Aβ42/40, p-Tau181, p-Tau217, and GFAP ENDPOINTS 55-88 years of age Clinical diagnosis of probable AD Mild-to-moderate dementia MMSE score of 14-24 CDR global score of 1 or 2 POPULATION Fosgonimeton 40 mg SC Daily N=143 Placebo SC Daily N=144 Randomization (1:1) Primary analysis: 312 enrolled 287 evaluable participants without concomitant AChEI Safety analysis: 549 participants ANALYSIS SET Primary Analysis Set: without AChEI


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Baseline Characteristics and Demographics are Well Balanced © Athira Pharma, Inc. AChEI, acetylcholinesterase inhibitor; ADAS-Cog11, Alzheimer's Disease Assessment Scale–Cognitive Subscale; ADCS-ADL23, Alzheimer's Disease Cooperative Study–Activities of Daily Living; CDR, clinical dementia rating; MMSE, Mini Mental State Examination; NfL, neurofilament light chain; APOE, Apolipoprotein E; SD, standard deviation Characteristic Primary Analysis Population (No Concomitant AChEI) Placebo (N=144) Fosgonimeton 40 mg (N=143) Mean (SD) age, years 73.4 (7.1) 72.6 (6.9) Female, n (%) 82 (56.9) 76 (53.1) White, n (%) 118 (81.9) 116 (81.1) APOE4 carriers, n (%) 74 (51.4) 74 (51.7) Heterozygotes 59 (41.0) 59 (41.3) Homozygotes 15 (10.4) 15 (10.5) Concomitant AChEI, n (%) 0 (0) 0 (0) Mean (SD) MMSE Score 19.3 (3.4) 19.9 (3.5) MMSE ≥20 (mild), n (%) 74 (51.4) 81 (56.6) MMSE <20 (moderate), n (%) 70 (48.6) 61 (42.7) CDR Score, n (%) 0.5 1 (0.7) 1 (0.7) 1 123 (85.4) 122 (85.3) 2 19 (13.2) 20 (14.0) Mean (SD) ADAS-Cog 11 22.3 (7.6) 20.7 (7.8) Mean (SD) ADCS-ADL23 62.3 (10.0) 62.5 (9.9) Mean (SD) NfL, pg/mL 27.7 (16.4) 26.3 (25.5)


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Primary and secondary endpoints did not reach statistical significance Overview of Primary and Secondary Endpoints GST, global statistical test; ADAS-Cog11, Alzheimer's Disease Assessment Scale–Cognitive Subscale; ADCS-ADL23, Alzheimer's Disease Cooperative Study–Activities of Daily Living; NfL, neurofilament light chain; LS mean, least squares mean; SE, standard error *Weighted model p-value not reported due to lack of model convergence; Non-weighted analysis p-value shown © Athira Pharma, Inc. Measure (Direction of Improvement) LS Mean Change (SE) from Baseline at Week 26 (Primary Analysis Population) Placebo (N=144) Fosgonimeton 40 mg (N=143) Difference vs Placebo (N=287) GST -0.13 (0.07) -0.21 (0.07) -0.08 (0.10) p=0.70 ADAS-Cog11 -0.39 (0.54) -1.09 (0.56) -0.70 (0.77) p=0.35 ADCS-ADL23 -0.02 (0.65) 0.65 (0.67) 0.67 (0.92) p=0.61 NfL (pg/mL) 2.95 (2.49) -0.96 (2.48) -3.91 (3.46) (p=0.26)*


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Change in Cognition and Activities of Daily Living ADAS-Cog11, Alzheimer's Disease Assessment Scale–Cognitive Subscale; ADCS-ADL23, Alzheimer's Disease Cooperative Study–Activities of Daily Living; CFB, change from baseline; LS mean, least squares mean; SE, standard error; SD, standard deviation © Athira Pharma, Inc. 0.67 pts p=0.61 0 12 20 26 Study Visit (Week) -0.70 pts p=0.35 0 2 6 12 20 26 Study Visit (Week) ADAS-Cog11 ADCS-ADL23 Placebo (N=144) Fosgonimeton (N=143) Placebo (N=144) Fosgonimeton (N=143) Placebo (N=144) Fosgonimeton (N=143) Baseline, Mean (SD) 22.3 (7.6) 20.7 (7.8) CFB at Week 26, Mean (SE) -0.39 (0.54) -1.09 (0.56) Placebo (N=144) Fosgonimeton (N=143) Baseline, Mean (SD) 62.3 (10.0) 62.5 (9.9) CFB at Week 26, Mean (SE) -0.02 (0.65) 0.65 (0.67)


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Fosgonimeton Shows a Neuroprotective Effect Across Plasma Biomarkers of Neurodegeneration (NfL), Inflammation (GFAP), and Protein Pathology (Aβ42/40 and p-Tau 217) NfL, neurofilament light chain; GFAP, glial fibrillary acidic protein; Aβ, Amyloid-β; LS mean, least squares mean; SE, standard error *Weighted model p-value not reported due to lack of model convergence; Non-weighted analysis p-value = 0.26 © Athira Pharma, Inc. -3.91 pg/mL p=0.26* NfL LS Mean Change (SE) from Baseline at Week 26 Aβ42/40 p-Tau217 GFAP -21.8 pg/mL p=0.21 0.0020 p=0.20 -0.12 pg/mL p=0.0098 Placebo (N=144) Fosgonimeton (N=143)


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Change in Cognition in Mild and Moderate AD by MMSE © Athira Pharma, Inc. ADAS-Cog11, Alzheimer's Disease Assessment Scale–Cognitive Subscale; MMSE, Mini Mental State Examination; LS mean, least squares mean; SE, standard error Mild Baseline MMSE (20 – 24) Moderate Baseline MMSE (14 – 19) 0 2 6 12 20 26 Study Visit (Week) -1.16 pts p=0.39 -0.23 pts p=0.79 0 2 6 12 20 26 Study Visit (Week) Placebo (n=74) Fosgonimeton (n=81) Placebo (n=70) Fosgonimeton (n=61)


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Change in Cognition Assessed by ADAS-Cog11 in APOE4 Carriers © Athira Pharma, Inc. ADAS-Cog11, Alzheimer's Disease Assessment Scale–Cognitive Subscale; MMSE, Mini Mental State Examination; APOE, Apolipoprotein E; LS mean, least squares mean; SE, standard error APOE4 Non-Carrier APOE4 Carrier -1.07 pts p=0.33 -0.12 pts p=0.92 Placebo (n=70) Fosgonimeton (n=68) Placebo (n=74) Fosgonimeton (n=74) 0 2 6 12 20 26 Study Visit (Week) 0 2 6 12 20 26 Study Visit (Week)


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Change in Cognition in the Lowest and Highest ADAS-Cog11 Tertile Subsets at Baseline © Athira Pharma, Inc. ADAS-Cog11, Alzheimer's Disease Assessment Scale–Cognitive Subscale; MMSE, Mini Mental State Examination; LS mean, least squares mean; SE, standard error Lowest Tertile Highest Tertile -2.51 pts p=0.16 0.19 pts p=0.84 Placebo (n=46) Fosgonimeton (n=59) Placebo (n=52) Fosgonimeton (n=42) 0 2 6 12 20 26 Study Visit (Week) 0 2 6 12 20 26 Study Visit (Week)


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Change in Cognition in CDR Subgroups © Athira Pharma, Inc. ADAS-Cog11, Alzheimer's Disease Assessment Scale–Cognitive Subscale; MMSE, Mini Mental State Examination; CDR: Clinical Dementia Rating; LS mean, least squares mean; SE, standard error CDR 1 CDR 2 (moderate AD) -3.74 pts p=0.21 -0.33 pts p=0.67 Placebo (n=123) Fosgonimeton (n=122) Placebo (n=19) Fosgonimeton (n=20) 0 2 6 12 20 26 Study Visit (Week) 0 2 6 12 20 26 Study Visit (Week)


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Fosgonimeton was generally well tolerated, with a favorable safety profile Summary of Treatment-Emergent Adverse Events (Safety Analysis Population) AE, adverse event; TEAE, treatment-emergent adverse event Most TEAE discontinuations were due to injection site reactions © Athira Pharma, Inc. Subject Incidence, n (%) Placebo (N=218) Fosgonimeton 40 mg (N=224) Fosgonimeton 70 mg (N=107) Any AE 136 ( 62.4) 177 ( 79.0) 94 ( 87.9) TEAEs 132 ( 60.6) 175 ( 78.1) 94 ( 87.9) Treatment-related TEAEs 54 ( 24.8) 155 ( 69.2) 86 ( 80.4) Serious TEAEs 15 ( 6.9) 11 ( 4.9) 3 ( 2.8) Treatment-related serious TEAEs 0 3 ( 1.3) 2 ( 1.9) TEAEs leading to study drug withdrawal 9 ( 4.1) 24 ( 10.7) 23 ( 21.5) TEAEs leading to study drug interruption 9 ( 4.1) 29 ( 12.9) 11 ( 10.3) TEAEs leading to study withdrawal 10 (4.6) 24 (10.7) 23 (21.5) Deaths 0 0 0


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LIFT-AD trial did not meet primary endpoint of GST and key secondary endpoints; fosgonimeton compares favorably to placebo numerically despite the very small decline in the placebo group In subgroups1 of patients with moderate AD, or APOE4 carriers or those with greatest impairment in cognition by ADAS-Cog11 fosgonimeton showed a larger effect size Fosgonimeton treatment was associated with changes in biomarkers of Alzheimer’s disease pathology consistent with the broad neuroprotective mechanism of HGF modulation Fosgonimeton was generally well tolerated, with a favorable safety profile Summary and Interpretation 1. Prespecified Analysis – MMSE and APOE4; Post Hoc – ADAS-Cog11 Tertiles and CDR © Athira Pharma, Inc. Totality of the data suggests that positive modulation of HGF signaling may have potential beneficial effects in neurodegenerative diseases


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Thank You © Athira Pharma, Inc.