Actualizing the Untapped Potential of the Innate Immune System - Affimed's Approach to Advancing Immuno-oncology
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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
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
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
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.
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
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
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
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
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 10Innate Cell Engagers in
CD16A
Hematologic Tumors
target
Treatment with AFM13
CD30
target
CONFIDENTIAL 11AFM13 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 lymphomaWe 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 diseaseCombination 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 15Innate 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 16Current 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 prednisoneAFM13 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 18Innate Cell Engagers
CD16A
in Solid Tumors
target
Treatment with AFM24
EGFR
target
CONFIDENTIAL 19We’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 20KOLs 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 21AFM24 (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 phagocytosisA 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 23AFM24, 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 24Key Milestones
CONFIDENTIAL 25Upcoming 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 26Thank you
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