Breakthrough Cancer Therapies: Directing the Immune System to Eliminate Tumor Cells. Corporate Presentation May 2015

Transcription

1 Breakthrough Cancer Therapies: Directing the Immune System to Eliminate Tumor Cells Corporate Presentation May 2015

2 Forward-looking statements / safe harbor This presentation and the accompanying oral commentary contain forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation and the accompanying oral commentary, including statements regarding our future financial condition, business strategy and plans and objectives of management for future operations, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as believe, will, may, estimate, continue, anticipate, intend, should, plan, might, approximately, expect, predict, could, potentially or the negative of these terms or other similar expressions. Forward-looking statements appear in a number of places throughout this presentation and the accompanying oral commentary and include statements regarding our intentions, beliefs, projections, outlook, analyses and current expectations concerning, among other things, our ongoing and planned preclinical development and clinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates AFM13, AFM11 and AFM21, our intellectual property position, our ability to develop commercial functions, expectations regarding clinical trial data, our results of operations, cash needs, financial condition, liquidity, prospects, future transactions, growth and strategies, the industry in which we operate, the trends that may affect the industry or us and the risks uncertainties and other factors described under the leading Risk Factors in Affimed sfilings with the Securities and Exchange Commission. Forward-looking statements involve known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Forward-looking statements represent our management s beliefs and assumptions only as of the date of this presentation. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. 2

3 Corporate facts Nasdaq: AFMD Affimed is a serious player in immuno-oncology developing immune cell engagers Leading edge technology platforms that Direct the immune system to eliminate tumor cells Target NK-cells or T-cells Clinical stage product candidates are unencumbered Leader in NK-cell-based approach Validation through partnerships with Amphivena/Janssen (JnJ) and support from The Leukemia & Lymphoma Society (LLS) Raised $97 million in IPO on Nasdaq and follow-on Cash and cash equivalents as of March 31, 2015: EUR 37.0 million (not including EUR ~33.2 million net proceeds from follow-on on May 12, 2015) 3

4 Current pipeline and programs Global rights retained with 3 candidates Compound Disease Target Immune Cell Target Indication Discovery Preclinical Phase 1 Phase 2 Phase 3 Hodgkin Lymphoma AFM13 CD30 CD16A / NK-cell AFM11 CD19 CD3 / T-cell AFM21 EGFRvIII CD3/T-cell CD16A/NK-cell CD30+ Lymphoma Hodgkin Lymphoma Combination with CPIs* Hodgkin Lymphoma Combination with Lenalidomide Non-Hodgkin Lymphoma Acute Lymphocytic Leukemia Solid Tumors TandAb CD33 CD3 / T-cell Acute Myeloid Leukemia Trispecific Abs Undisclosed undisclosed Multiple Myeloma *CPI = Checkpoint inhibitor Worldwide rights with Affimed Partnered program 4

5 Highlights H1-15 In May 2015, raised $41 million in follow-on offering to enhance AFM13 and AFM11 programs and to generate further NK-cell engagers Performed pre-clinical studies of AFM13 in combination with checkpoint inhibitors (Stanford) and lenalidomide (Mayo Clinic); CPI data to be presented at ASCO 2015 (1 poster, Abstract #3050) Selected CD33/CD3 candidate for IND-enabling studies in collaboration with Amphivena/Janssen; received milestone; 3 posters to be presented at ASCO Published three papers: AFM13 phase 1 (BLOOD), AFM11 preclinical data (mabs) and TandAb generation (Eur. Pharm. Rev.) Received BMBF grant to support dual tumor targeting platform and development of multi-specific antibodies for multiple myeloma 5

6 Engaging NK-cells to Fight Cancer: AFM13 Credit: Joshua Stokes, St. Jude Children's Research Hospital 6

7 NK-cells: Important cells for innate immunity Significant interest by industry Lirilumab Innate/BMS IgGs TandAbs KIR2 Other cytokines AFM13 CD16A TandAbs Affimed CD16A (FcγRIIIA) TNFα IFNγ Stimulation of T-cell response MK-4166 Merck GITR Urelumab PF BMS, Pfizer CD137 (4-1BB) CD319 (CS1) Elotuzumab BMS/Abbvie PD-1 NKG2a IPH2201 Innate/AZ Nivolumab Pembrolizumab BMS, Merck PD-L1 MEDI4736 MPDL3280A MSB C AZ, Roche MerckSerono/Pfizer 7

8 NK-cell engagement: Targeted single cell apoptosis induction via immune cell engagement Stage 1 Stage 2 Stage 3 Stage 4 NK-cell with CD16A receptors and tumor cell with CD30 receptors NK-cell TandAb locks NK-cell and tumor cell in close proximity and activates NK-cell NK-cell releases perforin, creating pores in tumor cell membrane through which granzyme enters, triggering caspase cascade Granzyme and caspase action trigger apoptosis of tumor cell 8

9 AFM13 Multiple near term milestones in 15 and 16 AFM13 Clinically most advanced NK-cell engager validating platform Potential as drug in CD30-positive lymphoma Demonstrated clinical and PD activity in heavily pretreated HL patients Maximize effect by optimized regimen and longer treatment period Monotherapy phase 2a study in HL with first data expected end of 2015 (ASH) Very good safety, well suited for combination with wide range of other drugs CPIs and lenalidomide in preclinical investigations (Stanford University and Mayo Clinic) CPI data to be presented ASCO 2015 and updates expected end of 2015 (ASH) Study role of NK-cells in tumor environment NK-cells may influence T-cell tumor infiltration Clinical study in CD30+ lymphoma to confirm role of NK-cells in tumor environment data expected in H1/2016 9

10 AFM13: CD137 co-stimulation and blocking PD-1 enhances NK cell-mediated target cell lysis Potential synergy of AFM13 and checkpoint inhibitors was evaluated Efficacy was assessed by in vitro cytotoxicity and patient-derived xenograft (PDX) in vivo models with AFM13, αctla4, αpd-1, and αcd137 antibodies In vitro, the addition of αpd-1 or αcd137 to AFM13 strongly enhanced specific lysis of CD30-positive cell line In vivo, synergy of AFM13 and CPI combination was observed AFM13 + αpd1 (regression in 9/10 tumors) AFM13 + αctla-4 (regression in 3/10 tumors) AFM13 + αcd137 mab (regression in 3/10 tumors) This was influenced by presence of regulatory T-cells, NK-cells, and Th1 cytokines AFMD plans to initiate combination trials to investigate the efficacy of AFM13 and CPIs in early

11 AFM13 Clinical development strategy Study initiated Phase 2, PoC r/r HL GHSG; n=40 Data on PoC Studies in planning Phase 1b/2a, TR CD30+ lymphoma Columbia; n=24 Data on dose End of Ph2 Meeting FDA Registration Study Phase 1b, + CPI r/r HL n=t.b.d. Data on combo 11

12 AFM13 Summary Encouraging phase 1 data (published in BLOOD) Clinical strategy to validate AFM13 and NK-cell platform The Leukemia & Lymphoma Society provides major financial contribution Opportunity for mono- and combination therapies Multiple near-term milestones AFM13 ASCO ASH ASCO ASH ASCO Ph2a HL Monotherapy Preclin. AFM13+CPI Ph1b/2a CD30+ lymph. Funded activities Planned milestones, news releases, posters/ presentations Preclin. AFM13+Len. Ph1b HL AFM13+CPI Follow-on Manufacturing Broadening of NK-cell engager pipeline in NHL, colon/h&n, MM or GBM 12

13 Engaging T-cells to Fight Cancer: AFM11 STEVE GSCHMEISSNER/SCIENCE SOURCE 13

14 AFM11 Differentiation from BiTE Blincyto (blinatumomab) is first T-cell engager approved by FDA for treatment of ALL (12/14) AFM11 (CD19/CD3 TandAb) preclinical data (published in mabs) ~100-fold higher affinity to CD3 as compared to BiTE Low pm cytotoxicity maintained at low effector to target (E:T) ratio Prolonged t½ allows regular i.v. infusion Blincyto AFM11 MW ~55 kda ~104 kda Binding sites 1 for each, CD3 & CD19 2 for each, CD3 & CD19 Affinityto CD3 + cells 100 nm 1 nm Phase 1 dose escalation in NHL/ALL patients ongoing 14

15 AFM11 Clinical development strategy Study initiated Phase 1, Safety r/r NHL/ALL AFMD; n=30-36 Data Studies in planning Phase 1, Safety NHL (new regimen) AFMD; n=t.b.d. Data Scientific Advice Meeting FDA/EMA POC studies in NHL and/or ALL Phase 1, Safety ALL (new regimen) AFMD; n=t.b.d. Data 15

16 AFM11 Summary Phase 1 dose escalation in NHL/ALL patients initiated Endpoints: safety, activity, efficacy Drug administered by regular i.v. infusion Multiple options for differentiation from competition Indication, convenience ( CAR-T in a vial ) Multiple near term milestones ASCO ASH ASCO ASH ASCO AFM11 Ph1 NHL/ALL Ph1 NHL (new dose regimen) Funded activities Planned milestones, news releases, posters/ presentations Ph1 ALL (new dose regimen) Follow-on Strong market potential 16

17 AFM21 Summary of preclinical program EGFRvIII is a highly tumor-specific receptor variant EGFRvIII is expressed e.g. in glioma/glioblastoma, prostate, H&N, breast, lung Data update at AACR 2015 (poster presentation) 2 molecules at discovery stage EGFRvIII/CD3 TandAb TandAb candidates are potent and show efficacy in animal tumors model EGFRvIII/CD16A TandAb Molecule generation has been advanced Milestone and news flow AFM21 (T- or NK-cell) AACR ASH ASCO ASH ASCO Preclinical Development Planned milestones, news releases, posters/ presentations 17

18 Partnership with Amphivena/Janssen Achieved milestone ahead of schedule Development of a CD33/CD3 TandAb for AML Program further validates robustness of Affimed s TandAb platform Rapid identification of preclinical candidate (< 18 months) Molecules are stable, highly expressed, and display significant in vitro and in vivo cytotoxicity 2 nd milestone achieved in March 2015 triggering payment of EUR 7.5 million Corroborative evidence of direct correlation between binding affinity and potency Confirmed in translational studies (primary AML specimens) To be presented at ASCO (3 posters Abstracts 3057, 7067 & 7071) Amphivena/Janssen ASCO ASH ASCO ASH ASCO Preclinical Development Planned milestones, news releases, posters/ presentations

19 Platform development Trispecific Abs Based on tetravalent platform Results in high affinity and, importantly, in increased selectivity for malignant tissues compared to healthy tissues CD19 CD30 Healthy cell Healthy cell Cytotoxic effector cell Tumor cell Platform offers an expansion of target space Program for the therapy of multiple myeloma initiated Supported by EUR 2.4 million ($3 million) German government research grant 19

20 Use of proceeds and milestones Strong news flow in 2015 and 2016 AFM13 ASCO ASH ASCO ASH ASCO Ph2a HL Monotherapy Ph1b/2a CD30+ lymph. Preclin. AFM13+CPI Preclin. AFM13+Len. Ph1b HL AFM13+CPI Funded activities IPO Follow-on AFM11 AFM21 (T- or NK-cell) Janssen/Amphivena Discovery/ Preclin. Development Manufacturing Ph1 NHL/ALL Ph1 NHL (new dose regimen) Ph1 ALL (new dose regimen) Preclinical Development Preclinical Development Novel NK-cell engagers Trispecific Program Planned milestones, new releases, posters/ presentations

21 Q1/2015 Cash flow statement in thousands of For the three months ended March 31, 2015 Cash and Cash equivalents at the beginning of the period 39,725 FX related changes to Cash and Cash equivalents 1,269 Net cash used in operating activities (3,924) Cash Flow from investing activities (37) Cash Flow from financing activities 0 Cash and Cash equivalents as of March 31, ,033 Net proceeds of May 2015 follow-on ~33,166 Cash reach projected through H2/2017 (including this financing and additional use of proceeds of this financing) 21

22 Our strategy Maximize value from pipeline and technologies Leverage first product to establish market in key indication Develop AFM13 through approval in salvage settings in multiple CD30-positive indications and detail product through own U.S. and/or EU sales forces Salvage settings enable fast development path and cost-efficient M&S structure Scientific leadership in NK-cell engagement Position AFM13 as combination drug with CPIs and other anti-cancer agents Use pipeline and technologies to create value through both next-generation products and deal opportunities Develop AFM11 through phase 2 POC studies Advance EGFRvIII TandAbs (AFM21) in solid tumors Enhance CD16A/NK-cell TandAb pipeline Add high-value technology platform partnership 22