Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (2006)
34 slides from Acumen Pharmaceuticals's investor presentation, 2006
Slide 1: Acumen Pharmaceuticals
Acumen Pharmaceuticals Developing disease-modifying drugs that block and reverse memory loss in Alzheimer’s disease
Slide 2: Why Acumen and Why Now?
Why Acumen and Why Now? z z Why Acumen? –– World-class ADDL expertise World-class –– Established IP estate (vetted by Merck) –– Proven partner –– Driven to develop first in class disease disease-- modifying drugs for Alzheimer ’s disease (in it for Alzheimer’s the long haul) z z Why Now? –– Programs
Slide 3: Acumen's Partnering Objectives
Acumen’s Partnering Objectives z z Advance leads to IND z z Parallel screen large, proprietary libraries to expand IP and diversify leads z z Cash to fund lead development z z Access development capabilities and expertise
Slide 4: Agenda
Agenda z z Acumen overview z z Recent advances in ADDL SAR z z Acumen IP summary z z Blocking ADDL assembly and/or binding z z Identification of the ADDL receptor z z Conclusions and next steps
Slide 5: Acumen's History
Acumen’s History Founded, IP from Opened R&D facility Northwestern & USC in SSF Virtual Company, strengthened IP Small molecule portfolio, solidified the scientific story programs initiated 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 $1.5M convertible note seed round Notes converted to co
Slide 6: Acumen's Management Team
Acumen’s Management Team z z David W. Summa - CEO and Director –– Former CEO - Mendel Biotechnology; VP - Monsanto; Partner - McKinsey & Co. z z Grant A. Krafft, PhD - Chairman & CSO –– Former CTO - Tibotec Tibotec,, Inc.; Professor Professor -- Northwestern Northwestern University; Sr. Scientist -
Slide 7: Acumen's Goal, Advantage & Strategy
Acumen’s Goal, Advantage & Strategy z z Our goal: Develop first -in-class disease first-in-class -modifying drugs disease-modifying that block and reverse memory loss in Alzheimer ’s Alzheimer’s disease z z Our advantage: World -class scientific expertise and key World-class enabling IP on the valid
Slide 8: Agenda
Agenda ; ;Acumen Acumen overview z z Recent advances in ADDL SAR z z Acumen IP summary z z Blocking ADDL assembly and/or binding z z Identification of the ADDL receptor z z Conclusions and next steps
Slide 9: ADDLs ... soluble Aβ oligomers (1996)
“ADDLs” … soluble Aβ oligomers (1996) 12-mer Low- n-mer 4oC 37oC •Form at < 10 nM Aβ 1-42 •Globular molecules, metastable •Heterogeneous sizes, certain preferred forms Chromy Chromy et et al, al, 2003 2003
Slide 10: Structure of ADDLs: AD extracts (2003)
Structure of ADDLs: AD extracts (2003) Dot blot of soluble brain extracts with ADDL-specific Age Matched Controls AD Brain Samples polyclonal Ab Brain & synthetic ADDLs equal in size, pI pI,, conformation PROMINENT SPECIES -- 12 mers Gong Gong et et al, al, 2003 2003
Slide 11: Confirmation: 12-mers toxic in tg-mice
Confirmation: 12-mers toxic in tg-mice Nature, 2006
Slide 12: ADDLs initiate AD-type hyperphosphorylation of tau
ADDLs initiate AD-type hyper- phosphorylation of tau Vehicle ADDLs Synthetic ADDLs AD brain P231 P404 P231 Integrated Fluorescence 4 Intensity (R.U.) 3 2 1 0 A D le AD AD n A D le s s DL DL ai c c hi hi br n- ve ve No • 4 AD tau-P sites • Signaling pathway: Src family kinase • Blocked by ADDL antibo
Slide 13: Agenda
Agenda ; ;Acumen Acumen primer ; ;Recent Recent advances in ADDL SAR z z Acumen IP summary z z Blocking ADDL assembly and/or binding z z Identification of the ADDL receptor z z Conclusions
Slide 14: ADDL IP: Background
ADDL IP: Background z z Amyloid fibril staining described in 1907 (Alzheimer). z z Fibril structure described from late ‘‘70s 70s to present; no claims issued. z z Amyloid β peptide characterized in ‘‘84 84 ((Glenner); Glenner); no claims for Aβ monomer. Aβ z z ADDLs discovered in latelate ‘‘95 95 a
Slide 15: Acumen Intellectual Property
Acumen Intellectual Property Amyloid β-Derived Diffusible Ligands ADDLS “soluble non-fibrillar amyloid β protein assembly comprising at least from 3-24 amyloid β proteins and which exhibits neurotoxic activity” z Issued US and Foreign Patent Claims: – ADDL composition, methods and uses for therapeut
Slide 16: Acumen ADDL IP: Issued Claims
Acumen ADDL IP: Issued Claims z z Composition: –– Oligomers Oligomers comprised comprised of of 33-24 -24 monomers monomers of of A β1-42 Aβ1-42 z z Methods: –– Assaying Assaying ADDL ADDL activity activity –– Preventing/reversing Preventing/reversing learning learning and and memory memory deficits
Slide 17: Acumen ADDL IP: Pending Claims
Acumen ADDL IP: Pending Claims z z Composition: –– Oligomers comprised comprised of of 25 -48 A 25-48 β1-42 monomers Aβ1-42 –– Oligomers comprised of 3-12 A 3-12 β1-42 monomer surrogates Aβ1-42 –– Stabilized oligomers comprised of 3 -12 A 3-12 β1-42 monomers Aβ1-42 or surrogates –– ADDL-specific ant
Slide 18: Acumen ADDL IP: Pending Claims
Acumen ADDL IP: Pending Claims z z Methods: –– Methods for detecting ADDLs using ADDL -specific ADDL-specific antibodies –– Methods of treatment (prevention) of ADDL-related ADDL-related diseases involving administration of compounds that interfere with ADDL formation or ADDL activity –– Methods of
Slide 19: Agenda
Agenda ; ;Acumen Acumen overview ; ;Recent Recent advances in ADDL SAR ; ;Acumen Acumen IP summary z z Blocking ADDL assembly and/or binding z z Identification of the ADDL receptor z z Conclusions and next steps
Slide 20: 3-pronged approach to block ADDLs
3-pronged approach to block ADDLs Reverse Receptor Antagonist Antagonist Aβ-monomer Aβ-Low-n-mers Aβ-dodecamer ADDLs MAP2 DAPI Block Assembly
Slide 21: First lead series
First lead series z z 3 scaffold variants z z Sub µµM Kiiapp M potency ((K app ~ 150 nM) z z Common pharmacophore z z Non -aggregating Non-aggregating z z Good solubility z z No apparent neuronal toxicity z z Chemically tractable z z Novel structures z z Dose dependent, reversible binding to Aβ Aβ
Slide 22: Lead series blocks assembly
Lead series blocks assembly Low-n-mer to Dodecamer Inhibition Correlation 1.75 1.75 M) 1.50 ((µµM) 1.50 1.25 1.25 app K IIapp 1.00 1.00 Low-n-mer K Low-n-mer 0.75 0.75 0.50 0.50 0.25 0.25 0.00 0.00 0.00 0.00 0.25 0.25 0.50 0.50 0.75 0.75 1.00 1.00 1.25 1.25 app µ app Dodecamer Dodecamer K KII (( µM)
Slide 23: Lead series shows dose dependent blocking of ADDL binding to neurons
Lead series shows dose dependent blocking of ADDL binding to neurons! 20uM cmpd 10uM cmpd 20µm 20µm no cmpd Punctuate binding of ADDLs to dentrites 20µm
Slide 24: Antagonist screening strategy
Antagonist screening strategy z z Primary screen identifies two MOAs –– Reverse antagonists:bind ADDLs and prevent receptor binding –– Receptor antagonists: bind receptor and prevent ADDL binding z z Assay is ““physiologically physiologically relevant relevant”” –– Low nM ADDL concentrations –– Prim
Slide 25: Dose dependent inhibition of ADDL binding in antagonist screening assay
Dose dependent inhibition of ADDL binding in antagonist screening assay Average Total Intensity 135000 115000 95000 75000 55000 35000 15000 -5000 0.0001 0.001 0.01 0.1 1 ADDL mAb [uM]
Slide 26: Small Molecule Programs: May '06
Small Molecule Programs: May ‘06 Assembly Blocker 1o Screens 2o Screens Validated Hits Hit-2-Lead Potency & POC 5 Series in Development 3 Series 1 Series 1 Lead Series Reverse & Receptor Antagonist 1o Screens 2o Screens Validated Hits Hit-2-Lead Potency & POC HTS Started Complete In Progress
Slide 27: ADDL inhibition of LTP – ventricular injection
ADDL inhibition of LTP – ventricular injection March 2006 Two-injection paradigm Vehicle Vehicle (0.1% glycerol PBS) 3 Differences significant at all time 50nM CADDLs points (regression analysis) 12-mer 2.5 2 Feild EPSP slope 1.5 1 0.5 0 -40.00 -20.00 0.00 20.00 40.00 60.00 80.00 100.00 minute s
Slide 28: Agenda
Agenda ; ;Acumen Acumen primer ; ;Recent Recent advances in ADDL SAR ; ;Acumen Acumen IP summary ; ;Blocking Blocking ADDL assembly and/or binding z z Identification of the ADDL receptor z z Conclusions
Slide 29: Receptor antagonist inhibition of ADDL binding
Receptor antagonist inhibition of ADDL binding (+) control 100% inhibition LS-2a 50% inhibition LS-2a
Slide 30: ADDL receptor ID
ADDL receptor ID z z Receptor characterization data and know know-- how to be provided following receipt of acceptable term sheet. z z Due caution essential to avoid enablement of competition
Slide 31: Agenda
Agenda ; ;Acumen Acumen overview ; ;Recent Recent advances in ADDL SAR ; ;Acumen Acumen IP summary ; ;Blocking Blocking ADDL assembly and/or binding ; ;Identification Identification of the ADDL receptor z z Conclusions and next steps
Slide 32: Conclusions
Conclusions z z ADDLs are widely recognized as central to AD z z Acumen has deep understanding of ADDL MOA and SAR z z Acumen has fully operational anti-ADDL therapeutic anti-ADDL discovery and development capabilities z z Blocking ADDL binding is a tractable therapeutic target z z Blocking ADDL ass
Slide 33: Next Steps:
Next Steps: z z To obtain additional information or arrange a confidential meeting, contact: William Goure Vice President, Business Development Acumen Pharmaceuticals, Inc. 385 Oyster Point Blvd., Suite 9A South San Francisco, CA 94080 Phone: 650 -875-7700 ext. 204 650-875-7700 Fax: 650 -875-7772 65
Slide 34: Acumen Pharmaceuticals
Acumen Pharmaceuticals Developing disease-modifying drugs that block and reverse memory loss in Alzheimer’s disease
Acumen Pharmaceuticals — Investor Presentation (2006) on 6ix