ACTUALIZING THE UNTAPPED POTENTIAL OF THE INNATE IMMUNE SYSTEM - Affimed's Approach to Advancing Immuno-Oncology January 2023
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ACTUALIZING THE UNTAPPED POTENTIAL OF
THE INNATE IMMUNE SYSTEM
Affimed’s Approach to Advancing Immuno-Oncology
January 2023
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 (as well as
the fact that the current clinical data of AFM13 in combination with NK cell therapy is based on AFM13 precomplexed with allogeneic cord blood-derived NK cells from The
University of Texas MD Anderson Cancer Center, as opposed to Artiva’s AB-101), 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, 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, impacts of the COVID-19 pandemic, political events, war, terrorism, business interruptions and other geopolitical events and uncertainties, such as the Russia-Ukraine
conflict 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.
The information contained in this presentation is solely for the purpose of familiarizing potential investors with Affimed and should be considered in the context of Affimed’s SEC
filings (including its effective registration statement and related prospectus), Form 20-F and other documents Affimed had filed with the SEC) and other public announcements that
Affimed may make, by press release or otherwise from time to time. You should read these filings for more complete information about Affimed before making any investments in
Affimed. You may get these filings for free by visiting EDGAR or the SEC website at www.sec.gov. This presentation and information contained herein should not be construed as
a solicitation or an offer to buy or sell any securities and should not be treated as giving investment advice to recipients. It is not targeted to the specific investment objectives,
financial situation or particular needs of any recipient. It is not intended to provide the basis for any third-party evaluation of any securities or any offering of them and should not be
considered as a recommendation that any recipient should subscribe for or purchase any securities.
2
Driving the revolution in
cancer treatment
Inspired by the immense potential of
the innate immune system (NK cells and
macrophages), we are dedicated to
unlocking profound possibilities through
the development of our Innate Cell
Engagers (ICE®) and to bringing new hope
to those whose lives have been forever
changed by the impact of cancer
Our Approach for Delivering Transformative,
Indication-Specific Medicines Has Been Clinically Validated
Pioneer Powerful ICE® Monotherapies
In indications where the innate immune system is functional
Combine ICE® With NK Cells
Supplement patients with dysregulated innate
immune systems with targeted cellular therapy
Combine ICE® With Other I-O Therapies
Co-activation of innate and adaptive immune systems
Expand and Accelerate With Partnerships
Maximize potential of pipeline through partnership strategy
ICE® = innate cell engager
I-O = immuno-oncology
NK = natural killer
4
Affimed's ROCK® Platform
Triggering a Full Immune Response in the Fight Against Cancer
Key Features of Affimed’s Innate Cell Engagers (ICE ®)
Novel mode of action:
• ICE® activate the not yet leveraged anti-tumoral powers of innate immunity
• ICE® trigger ADCC and ADCP of NK cells and macrophages, respectively
• ICE® are active over a broad range of tumor antigen expression levels
• ICE® enable cross-talk with adaptive immunity
• Modular platform to build and develop ICE®
Clinical success story (based on AFM13, AFM24):
• Superior safety profile compared to other treatment options
• Utility across multiple indications
• Well suited for combinations:
• Synergy with NK cells
• Synergy with CPIs
5
Creating a New Dimension in Cancer Treatment Through
Innovation, Novel Products, Expertise and Partnerships
Proprietary ROCK® Platform
Broad Pipeline in Hematologic Value-Driving
Enables Customized, Tumor-
and Solid Tumor Indications Catalysts
Targeted Approach
ICE ® molecules with dual mode of Developing medicines in areas of high Several programs in clinical trials or
action, activating NK cells and unmet need and large opportunity advancing towards IND
macrophages
Pipeline with >10 wholly owned and Planned data releases from clinical
Efficient, predictable development of partnered ICE® molecules studies with ICE® as monotherapy and in
potent, CD16A-targeted ICE® molecules combinations
POC data supporting ICE ® development
Pre-clinical data demonstrating as monotherapy and in combinations Innovative platform enabling high-end
increased cytotoxicity vs. mAb platforms partnership deals
Strong Foundation of Experienced Leadership, Partnerships and Cash Position
Management team with depth and breadth of industry experience
Cash runway into 2025 with multiple value inflection points in 2023
CD = cluster of differentiation NK = natural killer
ICE® = innate cell engager POC = proof of concept
IND = investigational new drug ROCK® = Redirected Optimized Cell Killing
mAb = monoclonal antibody
6
A Growing Pipeline Poised to Advance the Treatment of Cancer
Broad Pipeline of Wholly Owned and Partnered Programs
Candidate Approach Indication Discovery Ph. 1 Ph. 2a Ph. 2b Status
Monotherapy Peripheral T-cell lymphoma (AFM13-202) Topline Data Reported December 2022
AFM13
+ Adoptive NK cells CD30-positive lymphomas (AFM13-104) Safety & POC, Data Reported at ASH22
(CD30)
+ Anti-PD-1 Hodgkin lymphoma (post BV) (AFM13-103) POC, Study Completed
Monotherapy Multiple solid tumors (AFM24-101) Safety & POC, Enrolling Expansion Cohorts
AFM24
+ Adoptive NK cells Multiple solid tumors (AFM24-103) Safety & POC, Enrolling Dose Escalation
(EGFR)
+ Anti-PD-L1 Multiple solid tumors (AFM24-102) Safety & POC, Enrolling Dose Escalation
Monotherapy Acute Myeloid Leukemia Initiation of phase 1 study expected H1 2023
AFM28
(CD123) + Adoptive NK cells Acute Myeloid Leukemia Pre-IND
AFM32
(AFVT-2101) Monotherapy Solid tumors Pre-IND, partnered with
A Roivant Sciences Company
(FRα)
Multiple indications (Not disclosed) Pre-IND, partnered with
Monotherapy
Novel ICE® Multiple indications (Not disclosed) Pre-IND, Affimed owned
+ Adoptive NK cells Multiple indications (Not disclosed) Pre-IND, Affimed owned
Monotherapy Combination With Adoptive NK Cells Combination With Other I-O Therapies
H1 = first half FRα = Folate receptor alpha PD-1 = programmed death protein1
BV = brentuximab vedotin ICE® = innate cell engager PD-L1 = programmed death ligand 1
CD = cluster of differentiation IND = investigational new drug POC = proof of concept
EGFR = epidermal growth factor receptor NK = natural killer 7
Our Experienced and Passionate Management Team is United by
a Bold Vision to Stop Cancer From Ever Derailing Patients’ Lives
Adi Hoess, MD, PhD Arndt Schottelius, MD, PhD
Chief Executive Officer Chief Scientific Officer
Wolfgang Fischer, PhD Andreas Harstrick, MD
Chief Operating Officer Chief Medical Officer
Denise Mueller Angus Smith
Chief Business Officer Chief Financial Officer
8
ICE® Molecule
Biology-Driven, Target-Specific
Strategy
Fit-For-Purpose ROCK® Platform
Targeted Combinations With I-O Therapies and NK Cells
Affimed’s ROCK® Platform Addresses Shortcomings of Other
Technologies and Mechanisms
Affimed pursues targets where
ROCK® platform designed to
traditional mAbs and/or ADCs As a consequence, clinical
succeed where others are
show little efficacy or limited success has been limited
limited
therapeutic window
CD16A binding HER2 (polymorphism, target expression) • Selective for CD16A
• mAbs may suffer from low affinity and specificity • mAb use restricted to high expressors • Binding unaffected by serum IgG competition
to CD16A and are subject to serum IgG (e.g. Herceptin)
• Binding not affected by CD16 V/F
competition for CD16A, inefficiently recruiting NK • ADCs with side effects leading to discontinuations polymorphism
cells/macrophages
(e.g. Kadcyla) • Efficacy maintained for low target expressors
CD16 polymorphism
CD30 (target expression)
• mAbs binding to CD16 affected by V/F
• mAbs discontinued due to low efficacy (e.g. MDX-
polymorphism leading to insufficient recruitment of 060)
a patient’s own NK cells/macrophages
• ADCs with best efficacy in high target expressors
Target expression (e.g. Adcetris)
• mAbs and ADCs require high target level CD123 (target expression, toxicity)
expression
• mAbs discontinued due to lack of meaningful
Safety/Toxicity
efficacy (e.g. talacotuzumab)
• ADCs show limited or no therapeutic windows
• ADCs with severe side effects (e.g. SGN-
CD123A)
ADC = antibody drug conjugate mAb = monoclonal antibody
CD = cluster of differentiation NK = natural killer
HER2 = human epidermal growth factor receptor 2 ROCK® = Redirected Optimized Cell Killing
IgG = immunoglobulin G V/F = valine/phenylalanine 10Unique Approach of Engaging NK Cells and Macrophages to
Kill Tumor Cells
Affimed’s Innate Cell Engagers (ICE®)
bind CD16A to a differentiated epitope ICE® Binding to CD16A
CD16A is sufficient to activate NK cells and
macrophages without a co-stimulatory signal à
Differentiated vs. platforms that can only engage NK cells
140 140 140
Highly selective for CD16A à Y H Y
No dilution and sink effect through neutrophils (CD16B+)
High affinity binding w/o serum IgG competition à
Superior to mAbs and Fc-enhanced mAbs
CD16A CD16B CD16A + IgG
ü binding × no binding ü binding
Binding not affected by V/F polymorphism à
Could be beneficial for outcomes
CD = cluster of differentiation mAb = monoclonal antibody
Fc-enhanced = fragment crystallizable NK = natural killer
ICE® = innate cell engager V/F = valine/phenylalanine
IgG = immunoglobulin G
11ICE® Molecules Show Superior Tumor Cell Killing
In vitro lysis of primary tumor cells* Affimed’s ICE® Molecules
(4h calcein release cytotoxicity assay; allogeneic HD NK cells,
E:T ratio 2.5:1)
Demonstrate:
120
ICE®
100 Higher cytotoxicity compared to
Specific lysis [%]
conventional and Fc-enhanced antibodies
80
60
Cytotoxicity against tumors with
40
low antigen expression without attenuated
Fc-enh. IgG1
20 potency
Neg. control
0
10 -1 10 0 10 1 10 2 10 3 10 4
Antibody concentration [pM]
*Source: Affimed data on file ICE® = innate cell engager
IgG = immunoglobulin G
E:T = effector to target NK = natural killer
12Transformative Treatment Opportunities Created by Efficient Targeting
of Adoptive NK Cells Through High Affinity Binding to CD16A
Two Options to Generate Targeted NK cells
ICE® co-administered with NK cells CAR-like NK cells
Prevalence of NK cells ICE® pre-complexed NK cell
is associated with
beneficial outcomes
Tumor targeting
of NK cells can
+ CD16A
improve responses receptor
Co-Administered Features Pre-Loaded Features
CD16A-specific High functionality ICE® retention on NK cells
High affinity Allogeneic or Simple manufacturing
Higher cytotoxicity autologous Higher cytotoxicity
CAR = chimeric antigen receptor
CD = cluster of differentiation
ICE® = innate cell engager
NK = natural killer
13CD16A
target
CD30
target
AFM13
ICE® for CD30+ LymphomasAFM13 Represents a Groundbreaking Immunotherapy
Approach for Patients with CD30+ Lymphomas
A new approach: activating the innate immune Unmet need and market opportunities
system in the fight against CD30+ lymphomas for CD30+ lymphomas
CD30+ lymphomas comprise different subtypes: HL, PTCL,
NK Cells CD30+ Tumor CTCL, DLBCL and FL
AFM13 Cell
Current treatment options largely chemo-based with
limitations on duration of response (DoR) and high toxicity
CD16A CD30 Despite limitations, there is a significant market opportunity:
brentuximab vedotin (B.V.) annual revenue > $1.3B in
Cytotoxic Granules 2021 and growing
Redirects NK cells and macrophages to tumor cells by binding Initial focus of AFM13 development in R/R patients with HL
to CD16A on innate immune cells and CD30 on cancer cells and TCL
Innate immune cells kill tumor cells via Antibody Dependent Opportunities in different CD30+ lymphomas of AFM13 in
Cell-mediated Cytotoxicity (ADCC) or Antibody-Dependent combination with NK cells
Cellular Phagocytosis (ADCP)
AFM13 could help restore NK cell function with the ability
to recognize CD30+ lymphomas
HL = Hodgkin lymphoma DLBCL = diffuse large B cell lymphoma
CTCL = cutaneous T cell lymphoma FL = follicular lymphoma
PTCL = peripheral T cell lymphoma CD = cluster of differentiation
R/R = relapsed/refractory NK = natural killer
TCL = T cell lymphoma 15AFM13 has Clinical Activity as Monotherapy and in Combination
with NK Cells in Certain Difficult-to-Treat CD30+ Lymphomas
10K patients in the R/R setting alone are eligible for treatment
with AFM13, with larger opportunities in earlier settings
Incident Cases Relapsed/Refractory Cases
50,000
46,373
45,000
Indicative CD30+ Patient Numbers ***
40,000 Cases of CD30+ Lymphomas in the 7 Major Markets (MM)**
35,000
30,000
1/3 of Lymphoma Patients Relapse or are
25,000 Refractory (R/R) to Initial Treatment
19,801
20,000
15,817
15,000 13,984
9,675
10,000
4,741 4,335 5,148
5,000 2,913
1,593
0
CTCL* PTCL* DLBCL* HL Total 7MM Market**
Data as of November 2022
*Data representative of CD30+ subsets only.
**7MM include US, EU5 (France, Germany, Italy, Spain, United Kingdom), and Japan.
***Source: Global Data; Kantar & the Leukemia and Lymphoma Society.
CD = cluster of differentiation DLBCL = diffuse large B-cell lymphoma
CTCL = cutaneous T-cell lymphoma HL= Hodgkin lymphoma
PTCL = peripheral T-cell lymphoma 16For AFM13, a Growing Body of Clinical Evidence Supports
Focus on Combination Therapy
More than 200 patients have received AFM13, which has consistently
demonstrated clinical activity and a differentiated safety profile
97%
88%
77%
In Hodgkin lymphoma, substantial synergy
46% ORR
observed in combination with CPI and NK cells; CR
18%
NK combo drives high rate of durable CRs 3%
Mono PD1 Combo NK Combo
In Non-Hodgkin lymphoma, monotherapy
32%
activity provides attractive opportunity to
provide durable efficacy by combining with 10%
N/A
TBD / Emerging
NK cells Mono PTCL PD1 Combo NK Combo AFM13-104
AFM13 is well positioned to be used in combination to treat CD30+ lymphomas
CD = cluster of differentiation NK = natural killer
CPI = checkpoint inhibitor ORR = objective response rate
CR = complete response PTCL = peripheral T cell lymphoma
17Combination Therapy of AFM13+cbNK Cells Maintains a 94%
ORR with 71% CR Rate (ASH 2022)2
Patient Case Study #2: CR of Multiple Disease Sites1
At Enrollment CR After Cycle 1
Patient Population2 Unprecedented Results2
R/R HL/ NHL Patients2 35 patients treated at
N=41 (36 HL/ 5 NHL) 1x108 per kg dose
7 prior lines therapy (median) (1-14) 94% ORR (1x10 per kg dose)
8
41 prior brentuximab vedotin
71% CR (25/35)
39 prior anti-PD-1
63% 6-month CR
32 prior SCT
96% 6-month OS
0% ORR to immediate prior therapy
17 of 25 CRs ongoing
cbNK = cord-blood derived natural killer cells; CR = complete response; DLT = dose-limiting toxicities; HL = Hodgkin lymphoma; ORR = objective response rate;
R/R = relapse/ refractory; T-NHL = T-cell non-Hodgkin lymphoma.
1. Nieto Y, Affimed Virtual Investor Event, December 2021
2. Nieto Y, ASH 2022 presentation, December10, 2022
18Artiva Partnership: Extensive Diligence Confirmed Artiva is the Ideal
Partner to Move the Combination of AFM13+cbNK Cells Forward
AFM13-mediated ADCC Inhibition of tumor growth
Lysis of Karpas-299 cells
80 E:T ratio of 5:1 AB-101
Vehicle AB-101 + AFM13
specific lysis [%] at 5:1
Key Criteria Check List 60
Strong preclinical data 40
Cleared IND & clinical data 20
Cryopreserved / off-the-shelf 0
01 13 13
AFM13
-1 FM xed M sed
B A le F
Consistent / high CD16 A o
A AFM13
01+ mp 01+ o-d
expression -1 c o c
-pre-complexed
B re - -1
A B
w/op A
GMP/ Manufacturing scale
Combining AFM13 with Co-dosing IV of Artiva’s AB-101 and
Viable COGS cryopreserved AB-101 AFM13 enables control of tumor
significantly enhanced cytotoxic outgrowth in a murine xenograft
activity towards CD30+ tumor cells model
ADCC = antibody-dependent cellular cytotoxicity GMP = good manufacturing practice
cbNK = cord-blood derived natural killer cells IND = investigational new drug
CD. = cluster of differentiation NK = natural killer
COGS = cost of goods sold 19Looking Forward: Goal Is to Expedite Clinical Development
2022 2023
Q3 Q4 Q1 Q2 Q3 Q4
Request for
pre-IND FDA feedback
meeting
submitted to
received in Goal: file IND in the first half of 2023
January 2023
FDA in Sep
Received FDA feedback on PIND requests in January 2023; based on feedback, on track
to submit IND in H1 2023 and, subject to IND clearance, to initiate clinical study
development in 2023 to evaluate the combination of AFM13 and AB-101 in r/r HL including
a cohort evaluating the combination in r/r CD30-positive PTCL
FDA = U.S. Food and Drug Administration PTCL = peripheral T cell lymphoma
CD = cluster of differentiation R/R = relapsed/refractory
HL = Hodgkin lymphoma
IND = investigational new drug
20Additional Near-Term Development Opportunities for AFM13 to
Provide Meaningful Benefit to Patients in Need
AFM13 has potential to benefit patients across many indications Market Potential
30,00 0
NK cell combo:
First Wave Second Wave Third Wave
• Addresses HL, PTCL, CTCL, and DLBCL
25,00 0 • Market research indicating premium above
CAR-T pricing
Indicative CD30+ Patient Numbers **
• Market potential of AFM13 + NK cell combo
20,00 0 18,816 stands to double when registered in EU and
other international markets
4,686
14,130
15,00 0
Value Inflection Points
6,534
10,00 0 7,596
7,436
160
5,889 NK cell combo:
1,547
5,000 3,783 2,106 • Updated data presented at ASH 2022
1,487 2,296
• FDA feedback received in Q1 2023
• IND filing expected in H1 2023
0
R/R R/R R/R 1L R/R 1L 1L
PTC L* HL DLBC L* PTC L* CT CL* HL DLBC L*
* Data representative of U.S. CD30+ subsets only CD = cluster of differentiation NK = natural killer
** Source: Global Data; Kantar & the Leukemia and DLBCL = diffuse large B-cell lymphoma PTCL = peripheral T-cell lymphoma
Lymphoma Society EU = European Union US = United States
FDA = US Food and Drug Administration
HL = Hodgkin lymphoma 21CD16A
target
• IND cleared
and initiation
of study
planned in 2H
2021
EGFR
target
AFM24
ICE® in EGFR+ Solid TumorsAFM24: Distinctive Approach to Targeting EGFR+ Tumors with
Potential to Bring Benefit to a Broad Range of Patients
EGFR is widely expressed in solid tumors: Colorectal, lung, ovarian, gastric, breast, pancreas, etc.
Incidence of >1,000,000 patients in EU and US with CRC, lung and gastric cancers
Current therapies rely on disruption Limitations of current
of the EGFR signaling cascade EGFR targeting therapies
Anti-EGFR
EGFR-ligands
Standard therapies (TKIs or mAbs) cannot address
mAbs
broad patient populations due to primary mechanism -
Cell membrane
signal inhibition
EGFR EGFR-mut
Resistance in the EGFR signaling cascade by
Tyrosine
Kinase Ras activation of alternate pathways or downstream
Inhibitors (TKI) PI3K
RAF
PI3K
inhibitors mutations limit use
TKI AKT Dose limiting side effects lead to treatment
MEK
TKI mTOR
discontinuation or non-optimal dosing
mTOR
MAPK inhibitors
TKI
Many indications with poor prognosis, e.g., mCRC:
14% 5-year survival rate
Cell growth and
proliferation
Nucleus
1. More Cancer Types – SEER Cancer Stat Facts. Acccessed January 5, 2021. https://seer.cancer.gov/statfacts/more.html.
2. LuCE Report on Lung Cancer. Accessed January 5, 2021. https://www.lungcancereurope.eu/wp-content/uploads/2017/10/LuCE-Report-final.pdf.
3. International Agency for Research on Cancer. Europe. Available from: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf.
4. ECIS – European Cancer Information System. Accessed January 5, 2021. https://ecis.jrc.ec.europa.eu/explorer.php?$0-0$1-All$2-All$4-1,2$3-0$6-0,85$5-2008,2008$7-
7$CEstByCountry$X0_8-3$X0_20-No$CEstBySexByCountry$X1_8-3$X1_19-AE27$X1_-1-1$CEstByIndiByCountry$X2_8-3$X2_19-AE27$X2_20-
No$CEstRelative$X3_8-3. 23With an MOA Independent of EGFR Signaling, AFM24 has Potential
to Disrupt the Treatment Paradigm and Overcoming Limitations
AFM24 activates NK cells and macrophages independent Preclinical data presented at AACR 20201 & 20212
of EGFR signaling and mutational status demonstrates key features of AFM24
MOA leverages the power of the innate immune system
and is distinctive from all current EGFR-targeting
Tumor cell killing therapies
AFM24 via ADCC / ADCP
Option to patients currently not eligible for approved
treatments due to resistance based on mutations in
EGFR EGFR-mut
EGFR pathway
Ras
ADCC even at low EGFR density and in the presence of
PI3K IgG1
Induces a prominent ADCP response against tumor cells
RAF
Not relevant
AKT
for AFM24
MEK mechanism with KRAS mutations and medium or high EGFR levels
of action
In combination with adoptive NK cells, leads to dose-
m TOR
MAPK
dependent tumor regression in a mouse xenograft model
Cell growth and
proliferation mAb = monoclonal antibody MOA = mechanism of action
E:T ratios = effector-to-target ratios ADCC = antibody-dependent cellular cytotoxicity
Nucleus KRAS = Kirsten rat sarcoma viral oncogene ADCP = antibody-dependent cellular phagocytosis
1. Reusch U. et al. AFM24, a bispecific EGFR/CD16A Innate Cell Engager with the potential to overcome resistance to current targeted treatments for EGFR-positive
malignancies (AACR Virtual Annual Meeting, June 2020)
2. Jens Pahl et. al. AFM24 is a novel, highly potent, tetravalent bispecific EGFR/CD16A-targeting Innate Cell Engager (ICE® ) designed for the treatment of EGFR-
positive malignancies (AACR Virtual Annual Meeting, April 2021)
24AFM24 Status: Safety, Pharmacodynamic Activity, and Correlative
Data Allowed RP2D Determination à P2 Expansions Initiated
Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Cohort 7
Status
14mg 40mg 80mg 160mg 320mg 480mg 720 mg
ü ü ü ü ü ü ü
• Safety profile continues to be good – no dose limiting toxicities observed at 480 mg or 720 mg
Deciding Factors
Safety
PK / Exposure • Proportionality of dose and exposure at 320 mg - 720 mg implies saturation of TM elimination
CD16A RO • Leveling off with 320 mg and 480 mg indicating sufficient saturation of CD16A on peripheral NK
cells for effective tumor cell killing; confirmed by data from 720 mg cohort
•
Supporting
Cytokines Consistent elevation of cytokines (e.g., TNF-α, IFN-ɣ) with doses ≥ 160 mg
NK Cell Activation
Marker
• Expression of NK cell activation markers with doses ≥ 160 mg
CD = cluster of differentiation P2 = phase 2 RP2D = recommended phase 2 dose
IFN = interferon PK = pharmacokinetic TM = target mediated
NK = natural killer RO = receptor occupancy TNF = tumor necrosis factor
25AFM24 Broad Early Development: Monotherapy & Combination
3 Trials Investigating 7 Different Indications
NSCLC EGFRmut Broad AFM24 development
AFM24-101 Exploring activity of
AFM24 monotherapy in aiming for high PoS to generate
Monotherapy Dose
CRC KRASwt, MSS
Dose escalation & expansion
tumors with favorable Expansion meaningful clinical data
immune status
study (AFMD)
RCC
Status / 2023 Milestones
• Data updates from all ongoing studies
NSCLC EGFRwt
are expected at scientific conferences in
AFM24-102 Exploring potential Q2 / Q3 2023
synergistic effect of co-
I-O combination activation of innate Dose
Gastric • Monotherapy: Expansion cohorts
Dose escalation & expansion and adaptive Escalation enrolling, from expansion cohorts
study (AFMD, Roche) immune systems expected in 2023
HCC, PanC
• Anti–PD-L1 combination: Initial data
presented at SITC 2022; dose
escalation enrolling at 480 mg; initiation
AFM24-103 Exploring potential of NSCLC EGFRwt of expansion cohorts expected in Q1
autologous NK cells to 2023
NK cell enhance AFM24 activity Dose CRC
combination in tumors with Escalation KRASwt / mut, MSS • NK cell combination: Dose
Dose escalation & expansion unfavorable immune escalation enrolling with completion
study (AFMD, NKGEN) status SCCHN in 2023
CRC = colorectal cancer MSS = Microsatellite Stable PanC = pancreatic cancer
EGFR = epidermal growth factor receptor mut = mutant RCC = renal cell carcinoma
HCC = hepatocellular carcinoma NSCLC = non-small cell lung cancer SCCHN = squamous cell carcinoma of head and neck
I-O = immuno-oncology KRAS = Kirsten rat sarcoma viral oncogene wt = wild type 26AFM24 SITC Update: Clinical Activity Was Observed in Two
Patients for the Combination of AFM24 with atezolizumab
Update Case study
Monotherapy An ongoing partial response was observed in a gastric cancer
• Changes of NK cells in peripheral blood suggest patient who had previously progressed on 4 lines of therapy,
that AFM24 activates and redirects NK cells including anti-PD-1 / chemotherapy combo
Late February 2022 14th March 2022 21st March 2022
from peripheral blood to EGFR-positive tissue
• T cells are activated within the periphery
• Gene expression profiling and IHC of biopsies
indicate an increase in cytotoxic cells within the
tumor
Combination with atezolizumab
2x doses AFM24 3x doses AFM24
• AFM24 at 160 mg in combination with Baseline
1x dose 1x dose
atezolizumab was adequately tolerated atezolizumab atezolizumab
• Clinical activity was observed in two patients
(one partial response / one stable disease) Cycle 1
• No DLTs were reported
The patient’s skin metastases did not respond to any prior treatment
• Dose escalation is proceeding at 480 mg
EGFR = Epidermal growth factor receptor Informed consent was obtained from patient for the
DLT = dose limiting toxicities publication of these images
IHC = Immunohistochemistry
27AFM24: Represents a Large Market Opportunity by Targeting
Multiple Solid Tumor Indications, Many with Poor Prognosis
Relapsed/Refractory Cases of EGFR+ Solid Tumors in the United States
2022 global therapeutics
500,000
468,688 market forecast for EGFR+
Incident Cases Relapsed/Refractory Cases
450,000 tumors estimated at
Indicative Patient Numbers*
400,000
350,000
>1.5 million patients
300,000
250,000
200,000 185,487
168,928
142,686
150,000
100,000 87,391
62,374
48,865 47,040
50,000 29,276
10,300 13,197 11,000
0
Gastric/ SCCHN* RCC* CRC* NSCLC* Total US Market*
Gastroesophageal* based on pursued indications
* Source: Global Data & internal research CRC = colorectal cancer SCCHN = squamous cell carcinoma of head and neck
EGFR = epidermal growth factor receptor
NSCLC = non-small cell lung cancer
RCC = renal cell carcinoma 28CD16A
target
• IND cleared
and initiation
of study
planned in 2H
2021
CD123
AFM28
ICE® in AML & MDSAFM28: Underserved AML Requires a Novel Product Concept
with a Strong Rationale and a Well Tolerated Tox Profile
Significant market Newly diagnosed AML: 42,000 annual incidence (7MM)
potential and high High relapse rate: 60% of patients are primary refractory or relapse within 1 year
unmet need R/R AML: 1-year OS: 29%, 5-year OS: 11%
Poor response to chemotherapy: Primary induction failures, early relapses
Lack of effective Measurable Residual Disease: High rates of relapse
treatments
Limited options for R/R AML
Primarily a disease of elderly, majority of patients cannot tolerate standard treatment
High toxicity
Treatment-related deaths and poor quality of life from treatment-related toxicity
ICE® increase NK cell and macrophage efficacy and have shown a benign safety profile
NK cells have shown a basal promising efficacy of 30-40%
Novel product concept
Combination of ICE ® (AFM13) with NK cells produces impressive ORRs and CRs
Targeting of CD123 enables elimination of both blasts and leukemic stem cells
AML = acute myeloid leukemia ORR = overall response rate
CR = complete response OS = overall survival
ICE® = innate cell engager R/R = relapsed refractory
NK = Natural Killer 30AFM28: Designed to Improve Efficacy and Safety in AML; to
Prevent or Delay Relapse, and Work in R/R Disease
AFM28 poster presentations at ASH 2021, NK2022 and ASH 20221,2
• Greater cell surface retention on NK cells than conventional monoclonal antibodies
• Efficiently directs allo NK cells to CD123-positive leukemic cells inducing depletion
AFM28 • Activated NK cells more potently than an Fc-enhanced anti-CD123
Shows differentiating preclinical • More active against primary AML blasts and against cells with low CD123
efficacy and safety data expression, when compared to Fc-enhanced anti-CD123
• Demonstrated low risk of CRS in preclinical toxicity studies
• Induced lysis of CD123-positive tumor cells when pre-complexed or co-
administered with cryopreserved NK cells
Monotherapy Outlook
Establish a dosing regimen and • Clinical trial applications approved in France and Spain; others pending
assess safety and preliminary
activity • Initiation of phase 1 study expected in H1 2023
Outlook
NK cell combinations • Study initiation planned as soon as feasible
H1, H2 = first and second half CRS = cytokine release syndrome R/R = relapsed refractory
AML = Acute Myeloid Leukemia IND = investigational new drug
CD = cluster of differentiation NK = natural killer
1. Jana-Julia Götz et al. AFM28, FM28, a Novel Bispecific Innate Cell Engager (ICE®), Designed to Selectively Re-direct NK Cell Lysis to CD123 + Leukemic Cells
in Acute Myeloid Leukemia and Myelodysplastic Syndrome (ASH – American Society for Hematology Annual Meeting, December 2021)
2. Jens Pahl et. al. Novel Bispecific Innate Cell Engager AFM28 in Combination with Allogeneic NK Cells for the Treatment of CD123+ Acute Myeloid Leukemia and
Myelodysplastic Syndrome (NK2022 – Society for Natural Immunity, May 2022) 31Preclinical Data Further Support the Development Rationale
for AFM28 in AML and MDS1
AFM28 inhibits tumor outgrowth in a
AFM28 induces efficient depletion of LSCs in murine model of AML
samples of patients with AML and HR-MDS
AML = Acute Myeloid Leukemia PBS = phosphate buffered saline
LSC = Leukemic stem cells
(HR)-MDS = (High Risk) Myelodysplastic Syndrome
Nanni Schmitt et al. Novel Bispecific Innate Cell Engager (ICE®) AFM28 Efficiently Directs Allogeneic NK Cells to CD123+ Leukemic Stem and Progenitor Cells in AML
– American Society for Hematology Annual Meeting, December 2022
32Multiple Potential Inflection Points in 2023
Strong Cash Position Enables Focused Execution
AFM13
• IND submission for combination of AFM13 + AB-101 planned in H1 2023
• Initiation of clinical development for AFM13 + AB-101 expected in 2023, subject to IND clearance
AFM24
• Data updates from the ongoing studies are expected at scientific conferences in Q2 / Q3 2023
• Monotherapy: Expansion cohorts enrolling; data from expansion cohorts expected in 2023
• Anti–PD-L1 combination: initiation of expansion cohorts expected in Q1 2023
• NK cell combination: Completion of dose escalation in 2023
AFM28
• Clinical trial applications approved in European countries; initiation of phase 1 study expected in Q2 2023
ROCK®, ICE® preclinical work/Genentech and Roivant Sciences collaborations
• Affivant Sciences (a Roivant Sciences company): AFM32 target (FRα) disclosed at SITC; initiation of clinical trial expected in 2023
• Novel Affimed-owned ICE® generation based on ROCK® platform underway
• Potential milestone payments from partnered programs
Cash runway into 2025
H1, H2 = first half, second half IND = investigational new drug ROCK® = Redirected Optimized Cell Killing
Q1, 2, 3 = first, second, third quarter MOA = mechanism of action RP2D = recommended phase 2 dose
FDA = US Food and Drug Administration NK = natural killer
ICE® = innate cell engager PD-L1 = programmed death ligand 1 33Activate Untapped Power: Our Blueprint for Delivering
Transformative Medicines
ICE® = innate cell engager
I-O = immuno-oncology
NK = natural killer
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