Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology

Page created by Debra Erickson
 
CONTINUE READING
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
Actualizing the Untapped
Potential of the Innate
Immune System
Affimed’s Approach to Advancing Immuno-oncology
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
Forward-Looking Statements / Cautionary Note

 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, the value of
 our ROCK® platform, the safety and efficacy of our product candidates, our ongoing and planned preclinical development and clinical trials, our
 collaborations and development of our products in combination with other therapies, the timing of and our ability to make regulatory filings and
 obtain and maintain regulatory approvals for our product candidates our intellectual property position, our collaboration activities, 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 heading “Risk Factors” in Affimed’s filings 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.

                                                                                                                                    CONFIDENTIAL        2
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
Every Patient Deserves More Options. Every Patient Deserves
Another Chance.

                                  The first patient to receive AFM13 to treat
                                  CD30+ lymphoma with cutaneous presentation

                                                                           CONFIDENTIAL   3
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
Our Innate Cell Engagers Fully Leverage the Innate Immune System

  Targeting both the innate and adaptive immune systems may provide more opportunities for durable
  responses and a cure for cancer

                   AFFIMED’S FOCUS                                              EXISTING IMMUNOTHERAPIES

            Innate Immunity, First Line of Defense                         Adaptive Immunity, Second Line of Defense

                                         NK cell
           Tumor cell                                                 Dendritic cell                     T cell
                                            CD16A
                                            receptor

                                                          Initiation of
                                                       adaptive response
                                           CD16A
                                           receptor

                                        Macrophage                                                     Tumor cell

                        Tumor killing                                                  Tumor killing

                                                                                                                       CONFIDENTIAL   4
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
A Team of Innate Immunity and Antibody Engineering Experts
Dedicated to Delivering Meaningful Therapeutics

   PRODUCTS                                                  PLATFORM
   • Versatile innate cell engagers                          • Fit-for-purpose ROCK® platform
     targeting hematologic and                                 generates customizable innate
     solid tumors                                              cell engagers with proprietary
   • First company with a clinical                             CD16A target
     stage innate cell engager

   PARTNERSHIPS                                              CORPORATE FACTS
   • Collaborations based on proprietary                     • Nasdaq listed since 2014
     CD16A engager capabilities and innate                     (NASDAQ: AFMD)
     immunity expertise                                      • ~90 employees in Heidelberg (HQ),
   • Genentech, Merck (MSD), MD Anderson                       Munich, New York
     Cancer Center, Columbia University,                     • Pro forma cash, cash equivalents, financial
     Leukemia & Lymphoma Society                               assets* of ~€106M/$116M** (September
                                                               30, 2019); cash runway at least into Q4
                                                               2021
      HQ, headquarters                        *"Pro forma" includes net proceeds from equity offering received in November 2019.
                                              “Financial assets” comprises short-term deposits.               CONFIDENTIAL         5
                                              **Based on an exchange rate of 1.1006 as of November 13, 2019.
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
Our Pipeline: Versatile Innate Cell Engagers Targeting Hematologic and
Solid Tumors
  AFM13 (Tumor Target CD30)                       Preclinical                Phase 1                               Phase 2
  CD30-positive T-cell lymphoma                                                                                   POC, Enrolling                         Affimed Programs

  Peripheral T-cell lymphoma                                                                            Registration Directed, FPFV 4Q/19                Partnered Programs

  Transformed mycosis fungoides                                                                                 POC, FPFV 4Q/19

  Hodgkin lymphoma (post BV and post anti-PD-1)                                                            POC, Enrollment Completed

  AFM13 + adoptive NK cells
  CD30-positive lymphoma                                                POC, IND Cleared

  AFM13 + anti-PD-1
  Hodgkin lymphoma (post BV)                                      POC, Enrollment Completed

  AFM24 (Tumor Target EGFR)
  Solid tumors                                    IND Cleared

  AFM26 (Tumor Target BCMA)
  Multiple Myeloma                                  Pre-IND

  AFM28 and AFM32 (Tumor Targets Undisclosed)
  Undisclosed                                       Pre-IND

  Genentech (Tumor Targets Undisclosed)
  Multiple Programs                                 Pre-IND

                                                                BV, brentuximab vedotin                  EGFR, epidermal growth factor receptor
                                                                PD-1, programmed cell death protein 1    BCMA, B-cell maturation antigen
                                                                                                                                                     CONFIDENTIAL       6
                                                                NK, natural killer                       IND, investigational new drug application
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
We Harness the Body’s First Line of Defense to Give Patients
More Options

                                         Engaging the
                                                                              We’re developing new
                                        innate immune                         treatment options for
                                         system holds                         patients in need
                                       promise for solid
                                            tumors

                             Activating the innate immune system
                               can trigger an adaptive immune
                                           response

                         Bringing adoptive NK cells to tumor cells can help
                         address the challenge of a dysfunctional immune
                                             system

   We activate the
   innate immune         Monotherapy shows engaging the innate immune
                          system has promise as a treatment in the fight
   system to fight                      against cancer
   cancer

                                                                                          CONFIDENTIAL   7
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
Our Innate Cell Engagers Power a Multitude of Opportunities

                                                                                     Adoptive NK & CAR-NK
                                                        Monotherapy                    Cell Combinations

     Innate cell engagers have the potential to
     enhance the magnitude and quality of
     innate immune cell responses through                                                      Adoptive NK &
     monotherapy or combinations.                                                               CAR-NK Cell
                                                                          Innate Cell Engagers Combinations
     Combinations with innate cell engagers also
     present promising therapeutic approaches
     when fortification or activation of the
     immune system is needed.

                                                                       Combinations w/
                                                                       Other I-O Agents
                                                   Next-gen Candidates to                 Combinations w/
                                                   Address Unmet Needs                    Other I-O Agents

                                                           I-O, immuno-oncology
                                                                                                               CONFIDENTIAL   8
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
A Fit-for-Purpose Platform & Unique Binding Domain Enable Us to
Build Patient-Specific Therapeutics

         The Fit-for-Purpose ROCK® Platform generates innate
         cell engagers customized to specific tumor targets.

         Our current engagers bind to innate immune cells                  Clinical                             Evidence of
         (natural killer cells and macrophages) via the             signs of efficacy &                          tolerable
         proprietary CD16A-binding domain, while binding                  ADCC*
                                                                                                                 safety profile*
         simultaneously to specific tumor cells.

                 CD16A                              Tumor
                                                    target           High affinity                              New epitope
                 target
                                                                      binding of                                 on CD16A
                                                                        CD16A
                                                                                                                Proprietary target

 *Based on AFM13 clinical studies.                             ADCC, antibody-dependent cellular cytotoxicity
                                                                                                                             CONFIDENTIAL   9
Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
Genentech Invested in Affimed's Innate Cell Engager Platform
Achieved two milestones and received payments in Q2 and Q4 2019

                                                                  Our strategic partnership was driven by
                                                                  our unique CD16A binding domain,
                                                                  expertise in innate immunity and depth
                                                                  of antibody engineering expertise

          $96M         Upfront, near term funding                  “This collaboration is based on Affimed’s
                                                                    innate immune cell drug discovery and
                                                                  development expertise and our team’s deep
                                                                                 understanding
           $5B        Potential milestones, plus royalties
                                                                            of cancer immunology.”

                                                                            James Sabry, M.D., Ph.D.,
                                                                           Global Head of Partnering, Roche
            $$        Received 2 milestone payments in 2019

                                                                                                              CONFIDENTIAL   10
Innate Cell Engagers in
CD16A
                  Hematologic Tumors
target
                  Treatment with AFM13

         CD30
         target

                                         CONFIDENTIAL   11
AFM13 Offers Unique Approach for Patients With CD30+ Lymphoma

                                                                                               Adoptive NK & CAR-NK
      Monotherapy                                                                              Cell Combinations
      First-in-class innate cell engager                                                       Preclinical data show promising
      that has shown promise as a novel                                                        signs of potential efficacy when
      treatment option for patients with                                                       used in combination with adoptive
      CD30+ lymphomas                                                                          NK cells*
                                                     Innate Cell Engager
                                                          AFM13
      Next-gen Candidates to Address
      Unmet Needs                                                                              Combinations w/ Other I-O Agents
      Offers a new option for hard-to-treat                                                    Shows promising signs of broad clinical
      patients with CTCL (TMF) and R/R PTCL                                                    development potential in augmenting other
                                                                                               I-O therapies, such as PD-1 inhibitors*

 *Based on AFM13 preclinical and clinical studies.               TMF, transformed mycosis fungoides
                                                                 R/R, relapsed/refractory                                 CONFIDENTIAL     12
                                                                 PTCL, peripheral T-cell lymphoma
We Are Focused on Accelerated Approval in Indications With High
Unmet Need
                                                                                                                                             PTCL
      We are strategically focusing on indications that have high
      unmet need and allow us to bring AFM13 to market as                                                 • Lack of standard of care in R/R – very high unmet
                                                                                                            need
      quickly as possible
                                                                                                          • Given lack of therapeutic options, AFM13 could
                                                                                                            establish a new standard of care for a large portion
                                                                                                            of R/R patients
                                                                                                                                             CTCL
                      Commercial Opportunity

                                                                                                          • Potential for small trial and accelerated timelines
                                                    HL                               PTCL                   for transformed mycosis fungoides
                                                   ~1600                            ~2600
                                                    eligible                        eligible              • The goal of the study is to position AFM13 as the
                                                    patients                        patients                preferred therapy for transformed mycosis
                                                                                                            fungoides
                                                                                               CTCL
                                                                                               ~200                                          HL
                                                                                               eligible
                                                                                               patients
                                                                                                          • Emerging vacuum of effective options in R/R as
                                                                                                            current therapies move to earlier lines

                                                                                                          • Expand into multiple settings with mono and
                                                         Unmet Need                                         combination approaches

HL: ~1,600 2L patients, R/R to 1L chemotherapy and/or radiotherapy                                         HL, Hodgkin lymphoma
PTCL: ~3,750 2L patients, R/R to 1L chemotherapy and/or radiotherapy, ~35% CD30+                           CTCL, cutaneous T-cell lymphoma          CONFIDENTIAL   13
CTCL: ~500 2L patients, R/R to 1L skin-directed and/or systemic therapies, ~35% CD30+
AFM13 Monotherapy Shows Promising Signs of Efficacy, Including the
Potential to Induce Complete Response

    AFM13 monotherapy in R/R CD30+ lymphoma                                                                               AFM13 followed by ASCT in TMF
                                             Results                                                                      Response: Lymph nodes (PET-CT)
   Cohort                  Disease                          Toxicity                     Response
     1                  S-ALCL, Alk (-)                      No AE                          PR
                            TMF                              No AE                         POD
                           C-ALCL                          Rash (G4)                        CR
                                                      Skin Infection (G3)
       2                      MF                            IRR (G1)                        SD
                              TMF                           IRR (G1)                        SD
                              TMF                     Skin Infection (G3)              Not assessed
                                                            IRR (G1)
       3                    TMF                              No AE                             PR
                        S-ALCL, Alk (-)                      No AE                             PR
                             MF                              No AE                            POD
       4                    TMF                              No AE                             PR

                                                                                                               Responses were observed in lymph nodes, skin and
                        50% ORR including 1 CR and 4 PRs                                                                       peripheral blood

 Principal Investigator: Ahmed Sawas, MD, Columbia University Medical Center, New York, NY.           ASCT, autologous stem cell transplant   POD, progression of disease
 A Sawas et al. ASH 2018 Abstract 2908.                                                               PR, partial response                    CR, complete response         CONFIDENTIAL   14
                                                                                                      ORR, objective response rate            SD, stable disease
Combination With Adoptive Transfer of Innate Immune Cells
Could Enhance Immune Response

      Studies across tumor indications
      suggest prevalence of NK cells is
         associated with beneficial                                                        Collaboration with MDACC aims to overcome hurdles posed by traditional NK cell
                 outcomes                                                                                                    therapies

        Adoptive NK cell transfer has
       demonstrated ability to induce                                                                                                                + AFM13
      remissions in patients with AML*

        Limitations of adoptive NK cell
           transfer include limited
           persistence and lack of
                  redirection

*Koehl et al. Oncoimmunology, 2015; Bachanova et al. Blood, 2014; Curti et al. Blood, 2014;                                        AML, Adult acute myeloid leukemia
Rubnitz et al. Journal of Clinical Oncology, 2010; Miller et al. Blood, 2005; Romee et al. Science Translational Medicine, 2016.                                       CONFIDENTIAL   15
Innate Cell Engagers With Adaptive Immunotherapies Produce High
Response Rates and May Bridge Patients to Other Lines of Therapy

                 R/R Hodgkin Lymphoma                                                          Efficacy Results

   Phase 1b Trial*:                                            Highest Dose (N=24): 88% ORR, 42%/46% CR rate (local/central read)
   • AFM13 in combination with Merck’s Keytruda®
     (pembrolizumab)
   • Total of 30 patients                                     Best Response, Tumor Volume
   • MTD not reached in Part 1; highest dose employed
     in Part 2/Extension
   • 24 patients evaluable in highest dose cohort

   Overview:
   • Combination was well tolerated, no new/worsening
     safety signals vs known safety profiles of each agent
     alone
   • Deepening of responses over time in multiple
     patients
   • Patients previously transplant ineligible transitioned
     to transplant after achieving an objective response
                                                              Change in tumor volume measured by CT-scan, efficacy (ITT) population (N=30)

 *Data cutoff date: 10 May 2019.                                               MTD, maximum-tolerated dose
 Ansell et al. 15-ICML 2019, Abstract 128.                                                                                                   CONFIDENTIAL   16
Current Development Informs Future Opportunities

                 Current Development Plans                         Future Opportunities (2021 – 2025)

                                                                       AFM13 + chemo in 1L PTCL (Ph 3)
        T-cell   AFM13 in R/R PTCL and TMF
      Lymphoma     (Ph 2 and Ph 2 registration                   AFM13 + aNK vs CHOP or CHP-BV in 1L PTCL
                           directed)                                                (Ph 3 confirmatory)

       CD30+          AFM13 + aNK                                                      AFM13 + aNK
     Lymphoma              (Ph 1b)                                             (Ph 2 registration directed)

                 AFM13 + pembro in post-BV/                               AFM13 + pembro in 2/3L (Ph 3)
      Hodgkin
     Lymphoma
                      anti-PD-1-naive                              AFM13 + aNK in post-BV/anti-PD-1 (Ph 2)
                             (Ph 1b)                                 AFM13 + aNK in peri-transplant (Ph 3)

                                         Pembro, pembrolizumab     CHOP, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone
                                                                   CHP-BV, brentuximab vedotin in combination with cyclophosphamide,   CONFIDENTIAL   17
                                                                   doxorubicin, and prednisone
AFM13 Shows Promise to Provide Meaningful Benefit to Patients as
Mono- and Combination Therapy

          Achievements                                            Upcoming Milestones and
                                                                  Opportunities
     ✓   Promising response rates as mono- and
                                                          •   Phase 1 trial with AFM13 + adoptive NK cells in
         combination therapy with anti-PD-1 in R/R
                                                              CD30+ lymphomas, sponsored by MDACC
         patients with CD30+ lymphomas
                                                          •   Development opportunities in earlier lines of
     ✓   Preclinical studies show synergistic effect in
                                                              therapy
         combination with adoptive NK cells
                                                          •   Business development strategy focused on
     ✓   Favorable emerging safety profile
                                                              securing a development and
     ✓   A total of 8 patients were bridged to                commercialization partner
         transplant
     ✓   Initiated Phase 2 trial with monotherapy in
         PTCL and TMF (potential for accelerated
         approval in PTCL)

                                                                                                         CONFIDENTIAL   18
Innate Cell Engagers
CD16A
                  in Solid Tumors
target
                  Treatment with AFM24

          EGFR
         target

                                         CONFIDENTIAL   19
We’re Leveraging the Role of CD16A Binding Affinity to Build New
Treatment Options in Solid Tumors
        High binding affinity to CD16A is associated with better        AFM24 is an EGFR-targeted innate cell engager with
                                outcomes                                         higher binding affinity to CD16A
                                    Trastuzumab in HER2+ mBC            • AFM24 has 5-fold higher affinity to CD16A than
                                                                          margetuximab, regardless of CD16A polymorphism

                                                                        • Enhanced binding properties could lead to enhanced
                                                                          outcomes in EGFR-expressing solid cancers

                                                                                               AFM24

                                                                           CD16A                                        EGFR
                                                                           target                                      target
    • Significantly higher ORR and PFS have been seen in HER2+
      metastatic breast cancer patients homozygous for CD16A 158V
      (V/V) treated with trastuzumab1

    • Recently, margetuximab, with 4-5x enhanced affinity to CD16A vs
      trastuzumab, also demonstrated 1.8 months’ improvement in PFS2

 1. Musolino et al. Journal of Clinical Oncology. 26, 1789-96 (2008).
 2. Rugo et al. ASCO 2019.                                                                                                 CONFIDENTIAL   20
KOLs Consider AFM24 to Be a Compelling I-O Agent That Has the
Potential to Address a Broad Set of EGFR-expressing Tumors
                                      16 Priority Indications Explored

 • Physicians expressed
   interest in the role of NK
   cells in tumors known to
   be immunogenic and
   responsive to I-O therapy

 • There is evidence
   supporting the
   importance of ADCC in
   multiple solid tumor
   types; KOLs cited the
   contrast between the
   success of HER2-targeted
   antibodies and failures of
   HER2 TKIs

 AFM24 Indication Triage Summary          PI, priority indication
 Source: ClearView Analysis.              KOL, key opinion leader        CONFIDENTIAL   21
AFM24 (CD16A/EGFR) Has the Potential to Disrupt the Treatment
Paradigm for Patients With EGFR-Expressing Tumors

                          AFM24 holds the promise of:                                         Based on preclinical data:

   ✓       Opportunity for improved outcomes                          ✓     Differentiated antibody profile
             • Efficacy of current therapies rely on mAb inhibition           • New MOA with preclinical data showing increased
               of EGFR signaling, which can be associated with side             activation of ADCC and ADCP vs cetuximab
               effects                                                        • Little IgG competition
                                                                              • High affinity binding to CD16A

   ✓       Opportunity for more tolerable side effect profile         ✓     Positive toxicity profile
            • Side effects of current EGFR-targeting mAbs can lead            • No toxicities observed in 2 independent cynomolgus
              to dose interruptions and discontinuations, resulting             toxicity studies (Potentially due to a much lower
              in potential lowered therapeutic efficacy                         inhibition of signaling)

  ✓       An effective therapy against EGFR-resistant tumors          ✓     Cytotoxicity regardless of mutation
           • Mutations in the EGFR pathway limit use and                      • Strong cytotoxic activity against EGFR-expressing
             effectiveness of EGFR mAbs                                         tumor cell lines, including wild type, KRAS or BRAF
                                                                                mutated
 Kluge et al. AACR 2019, Abstract 559                                 mAb, monoclonal antibody
                                                                      MOA, mechanism of action                             CONFIDENTIAL   22
                                                                      ADCP, antibody-dependent cellular phagocytosis
A Multipronged Clinical Development Strategy Designed to Deliver
AFM24 to Those Patients With Few Options

                                             Initial Opportunities                   Future Potential

                 Colorectal
                                               3L All-comers         2L All-comers, Wild Type and Those With Mutations
                  Cancer

                 Non-small
                 Cell Lung                     3L All-comers                2L Post-anti-PD-1 or 2L Post-TKI
                  Cancer

                  Priority                     3L All-comers                 2L Regardless of PD-1 Eligibility
                Indication 3

                  Priority
                                             2L Mutation Agnostic          1L Mutation Agnostic Opportunities
                Indication 4

 Physician Interviews; ClearView Analysis.
                                                                                                                         CONFIDENTIAL   23
AFM24, a New Mode of Action to Initiate Innate Immunity
in EGFR+ Solid Tumors, Such as CRC, NSCLC, and Others

         Achievements                                        Upcoming Milestones and Opportunities

     ✓ Demonstrated potent cell killing                •   Initiating Phase 1/2a study of AFM24
       capabilities (ADCC and ADCP) in                     monotherapy in H1 2020; preliminary safety
       preclinical studies                                 and efficacy data expected in 2020
         ✓   Potential for greater efficacy in tumor   •   Broad development opportunity as new
             types with EGFR mutations/resistance          MOA in addressing non-responsive patients,
     ✓ Differentiated safety profile in                    e.g., KRAS-mutant patients
       cynomolgus toxicity studies                     •   Potential for innate/adaptive I-O
     ✓ IND cleared in October 2019                         combinations enhancing efficacy in major
                                                           solid tumor types

                                                                                                CONFIDENTIAL   24
Key Milestones

                 CONFIDENTIAL   25
Upcoming Anticipated Milestones

                                     2019                         2020                               2021                               2022
                     Initiated registration-directed
                      Ph 2 study in PTCL and POC        POC data in PTCL and TMF        Progress update in PTCL and          LPI and top line data in PTCL
                           study in TMF in Q4                                                      TMF

    AFM13
                       Update on progress (study         Safety and initial efficacy     POC data for AFM13+aNK
                       initiation) of AFM13+aNK        update of AFM13+aNK cells*       cells*; if positive, initiate reg.
                                  cells*                                                              study

                                                        Phase 1 FPFV, preliminary        Initiate enrollment of dose         POC data in multiple EGFR+
    AFM24                     IND cleared in Q4
                                                       safety and first efficacy data   expansion cohorts; POC data                 indications

  AFM28 &
                         Preclinical development                                          AFM28 IND filing planned            AFM32 IND filing planned
   AFM32

                         Received two milestone             Pending program                   Pending program                     Pending program
      GNE                payments (Q2 and Q4);          progression, potential for        progression, potential for          progression, potential for
                          Final target selected            milestone payment                 milestone payment                   milestone payment

 *Investigator-sponsored trial conducted by MDACC.
                                                                                                                                                  CONFIDENTIAL   26
Thank you
You can also read